WO2020215297A1 - 基于聚氨酯的喷射型光固化水凝胶敷料前驱液及制备方法 - Google Patents

基于聚氨酯的喷射型光固化水凝胶敷料前驱液及制备方法 Download PDF

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WO2020215297A1
WO2020215297A1 PCT/CN2019/084460 CN2019084460W WO2020215297A1 WO 2020215297 A1 WO2020215297 A1 WO 2020215297A1 CN 2019084460 W CN2019084460 W CN 2019084460W WO 2020215297 A1 WO2020215297 A1 WO 2020215297A1
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polyurethane
precursor liquid
hydrogel dressing
hydrogel
precursor
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English (en)
French (fr)
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张利
侯毅
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四川大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2/00—Processes of polymerisation
    • C08F2/46—Polymerisation initiated by wave energy or particle radiation
    • C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52

Definitions

  • the invention belongs to the field of medical materials, and specifically relates to a polyurethane-based spray type light-curing hydrogel dressing precursor liquid and a preparation method of the precursor liquid.
  • the skin is a tissue located on the surface of the body and wrapped outside the muscles. It is an important organ that keeps the body's internal environment stable and resists foreign invasions. It has physical, chemical and biological barrier functions. As the outermost barrier of the human body, the skin is often damaged due to various external environmental factors. Burns, scalds, and large-scale ulcers caused by trauma are serious threats to human health. In China, there are as many as 5-10 million burn victims every year, and about 5% of them require hospitalization. In addition, according to the latest data released by the World Health Organization, it is estimated that in the future, 265,000 people will die from burn infection every year worldwide.
  • Wound injuries are often accompanied by increased metabolism, excessive loss of water and protein, endocrine and immune system disorders, etc., which in turn lead to various types of injuries, such as non-healing wounds and pressure ulcers. Therefore, the development of a suitable wound dressing can instantly and effectively control wound infection and promote wound healing, which is very important for clinical wound care and rehabilitation.
  • the advantage of the spray film type dressing is that it can form a protective film suitable for its size and fit on the wound surface by spraying to form a film according to the actual situation of the wound, so as to resist bacterial invasion and prevent infection.
  • this type of dressing has limited liquid absorption capacity and the film is brittle, resulting in a short action time.
  • Hydrogel is a polymer network material that contains a lot of water. It is soft in nature. As a wound dressing, it can effectively absorb wound exudate and keep the wound surface moist. It can effectively prevent dehydration and drying of the wound surface, and can effectively relieve the discomfort of the patient. And pain.
  • the ideal wound dressing should have the following functions: (1) resist the invasion of exogenous substances and prevent further infection; (2) absorb tissue exudate and keep the wound environment clean and moist; (3) have a good fit with the wound surface And adaptability; (4) It has certain mechanical properties; (5) It can adhere well to the surrounding normal tissues.
  • Patent CN107106724A discloses a composition containing a polymer, a conversion initiator and a hydrocolloid.
  • the composition can present two forms: the liquid state before conversion and the adhesive state after conversion.
  • the liquid is used to apply to the stoma
  • the skin surface is converted into an adhesive state and the skin is bonded to the ostomy appliance.
  • this composition does not use water as a solvent, but uses organic solvents such as ethyl acetate, toluene, tetrahydrofuran, etc. to dissolve the polymer. Dry at high temperature.
  • Patent CN107106724A provides a feasible case for manufacturing application materials with two states, but the material is suitable for use on non-traumatic skin surface, has the function of bonding and keeping dry, and cannot be used as a wound skin surface dressing. Residual organic solvents pose a very large safety risk, leading to limited clinical use.
  • the present invention designs a polyurethane-based spray type light-curing forming hydrogel dressing precursor.
  • the precursor liquid can realize rapid solidification during the spraying process, forming a layer of wound-adaptive adhesive hydrogel dressing on the surface of the skin wound, moisturizing, breathable, strong liquid absorption, excellent mechanical properties, easy to use, and can be significant Promote the healing of wounds.
  • the first aspect of the present invention provides a polyurethane-based spray type photocurable hydrogel dressing precursor liquid, the precursor liquid containing polyurethane, photocurable polymer monomer, photoinitiator and water, wherein the mass content of the photoinitiator 0.5 to 5%, the mass content of water is 50 to 80%, the mass ratio of photocurable polymer monomer to polyurethane is 1.5:1 to 4:1, the complex viscosity of the precursor liquid is 0.2-0.8mPa ⁇ s, the precursor The liquid is sprayed in liquid form and cured by light to form a hydrogel dressing.
  • the hydrogel dressing is stored in the form of a hydrogel precursor before use. It is sprayed on the wound surface by a jet method to form a liquid film. Under certain wavelengths of light, the liquid film quickly solidifies to form an adherent hydrogel layer. The gel does not need to introduce any adhesive, and the presence of polyurethane gives the gel layer self-adhesive characteristics.
  • the polyurethane is introduced into the precursor liquid as an aqueous polyurethane emulsion.
  • Light-curing polymer monomers refer to monomers that can undergo addition polymerization under the action of light, including but not limited to acrylic acid, gelatin-methacrylamide (gelMA), PEG-diacrylate (PEGDA), acrylamide (PAAm), etc.
  • gelMA gelatin-methacrylamide
  • PEGDA PEG-diacrylate
  • PAAm acrylamide
  • the dressing cures to form a hydrogel at a slower speed (more than 300s), which is extremely important for patients who need to treat the wound as soon as possible.
  • Adverse After research by the inventor, it is found that adding an appropriate amount of polyurethane can significantly shorten the curing time to 10-250s, the preferred curing time is 30-200s, and the more preferred curing time is 50-120s.
  • the inventors also surprisingly found that the mechanical properties of the hydrogel, especially the tensile properties, are greatly improved after proper polyurethane is introduced.
  • the mass ratio of the photocurable polymer monomer to the polyurethane is set to be 1.5:1 to 4:1, preferably 3:1.
  • the complex viscosity of the precursor liquid determines whether the precursor liquid can be smoothly ejected from the container, and whether the precursor liquid sprayed to the skin can maintain the shape when it is attached and solidify. When the viscosity is too low, the precursor fluid will flow away quickly after spraying onto the skin surface, and it will not be able to form a hydrogel that matches the shape and size of the wound. When the viscosity is too high, the precursor liquid cannot be sprayed from the container onto the wound surface smoothly.
  • the suitable complex viscosity of the precursor fluid is 0.2-0.8 mPa ⁇ s, and the more preferred complex viscosity is 0.3-0.6 mPa ⁇ s.
  • the viscosity of the precursor liquid can be adjusted by the content of the photocurable polymer monomer and the polyurethane, but the two still need to be kept within the aforementioned ratio range to take into account reasonable curing time, mechanical properties and transparency.
  • Pharmaceutically acceptable viscosity modifiers can also be used for adjustment. Normally, a modifier with a large molecular weight can increase the viscosity, and conversely, a modifier with a small molecular weight can reduce the viscosity.
  • Polyurethane can be obtained by reacting molecules containing alcoholic hydroxyl groups with isocyanates.
  • isocyanates include but are not limited to isophorone diisocyanate, toluene diisocyanate, 4,4'-diphenylmethyl diisocyanate, 1,6-hexane diisocyanate and the like.
  • isophorone diisocyanate is used.
  • Molecules containing alcoholic hydroxyl groups include polyester/polyether glycols or polyols and chain extenders.
  • the diol or polyol polyol of the polyester/polyether is selected from polyoxyethylene diol, polytetrahydrofuran ether glycol, polyoxypropylene diol, polylactic acid diol/polyol, polycaprolene One or more of ester diol/polyol and polyglycolide diol/polyol.
  • the chain extender is selected from one or more of 1,4-butanediol, dimethylolpropionic acid, triethanolamine, and methyldiethanolamine.
  • the precursor of the present invention will be converted into a hydrogel after use, and the emulsified and dispersed state of the polyurethane molecular chain in the dispersion medium-water will affect the uniformity of the polyurethane emulsion and the state of the hydrogel.
  • the R value the molar ratio of the group NCO to OH
  • the polyurethane molecular chain will agglomerate in water. Curl and form microsphere particles instead of milk droplets.
  • the R value of the isocyanate and the alcoholic hydroxyl-containing molecule for preparing the polyurethane is greater than 1 and 2.5 or less.
  • the polyurethane is derived from an aqueous polyurethane emulsion prepared by a water emulsion method.
  • the precursor liquid preferably contains a pH regulator that neutralizes the acid and alkali.
  • the pH regulator neutralization of the precursor liquid is also beneficial to the formation of the emulsion.
  • the pH adjuster can be an inorganic acid/base or an organic acid/base.
  • the invention uses water as the dispersion medium to achieve multiple effects.
  • most of the water and polymer materials in the cured hydrogel exist in the form of combined water, with a boiling point> 120°C, and will not volatilize in a short time. It can keep the environment around the wound surface moist and help wound healing;
  • the hydrogel obtained by curing the polyurethane-photocurable polymer monomer with a proper amount of water has a special three-dimensional network structure, which makes the skin and the outside world The establishment of small molecule exchange channels is helpful for air circulation and drug application.
  • the dressing of the present invention uses water with a content greater than or equal to 50% by weight as the dispersion medium.
  • the experimental results of some examples show that the greater the water content, the lower the swelling performance, and the relatively longer curing time. Therefore, the dressing water of the present invention The content is less than or equal to 80wt%.
  • the hydrogel dressing precursor liquid also contains a drug, and the drug includes but is not limited to one or more of antibacterial drugs, anti-inflammatory drugs, growth factors and the like. Because the hydrogel dressing after solidification of the precursor liquid of the present invention has a porous network structure, drugs filled in these structures can be continuously delivered to the wound to achieve a lasting therapeutic effect.
  • the precursor liquid of the present invention preferably has a light absorption range of the photoinitiator in the ultraviolet region (250-420 nm) or visible region (400-800 nm).
  • Photoinitiators that meet these absorption ranges include but are not limited to 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-acetone, 2,4,6-trimethyl Benzoyl-diphenylphosphine oxide, methyl benzoylformate, 2-dimethylamino-2-benzyl-1-[4-(4-morpholinyl)phenyl]-1-butanone, Fluorinated diphenyl titanocene, bis(pentafluorophenyl) titanocene, etc.
  • the second aspect of the present invention provides a method for preparing the aforementioned polyurethane-based spray-type photocurable hydrogel precursor, and the method includes the following steps:
  • the third aspect of the present invention provides a method for using the aforementioned precursor liquid, which includes spraying the precursor liquid on the wound surface, and exposing to a certain wavelength of light to form a hydrogel dressing with a certain thickness.
  • the beneficial effects of the present invention are as follows: (1) Before use, the hydrogel precursor is stored in liquid form, and sprayed on the wound surface to form a liquid film by spraying. The liquid film quickly solidifies to form a hydrogel under a specific wavelength of light. , The use process is convenient; (2) the formed hydrogel can effectively cover the wound, and it fits perfectly with the wound shape, thereby preventing bacterial invasion, breeding or infection; (3) the hydrogel material contains a lot of water, which can be Keep the environment around the wound moist; (4) The hydrogel can absorb a large amount of tissue fluid to ensure the self-cleaning of the wound; (5) After use, the hydrogel can be directly removed from the skin surface non-invasively without secondary damage.
  • Figure 1 is a diagram of the particle size distribution of emulsion droplets of the aqueous polyurethane emulsion of Example 1 of the present invention
  • FIG. 2 is a diagram of the particle size distribution of emulsion droplets of the precursor solution of the hydrogel dressing of Example 1 of the present invention
  • Figures 3-5 are SEM photos of PP-50, P-50 and PP-42 hydrogel dressings prepared in Example 3, Comparative Example 1 and Comparative Example 3 of the present invention;
  • Fig. 7 is a diagram showing the curing state of PP-50, PP-70, P-50, P-70 prepared in Examples 3 and 4 and Comparative Examples 1 and 2 of the present invention over time;
  • Fig. 8 is a volume and mass swelling curve diagram of the hydrogel cured by the precursor liquid of Examples 3 and 4 of the present invention.
  • FIG. 9 is a drawing curve diagram of the hydrogel cured by the precursor liquid of Examples 3 and 4 of the present invention.
  • Fig. 10 is a diagram of adhesion and peeling of PP-70 hydrogel on the skin surface of Example 4 of the present invention.
  • the water content of the polyurethane-polyacrylamide hydrogel precursor liquid is 80 wt%, the R value is 2, the photocurable polymer monomer: polyurethane is 3, and the complex viscosity is 0.2 mPa ⁇ s.
  • the water content of the polyurethane-polyacrylamide hydrogel precursor liquid is 53 wt%, the R value is 2, the photocurable polymer monomer: polyurethane is 1.5, and the emulsion viscosity is 0.3 mPa ⁇ s.
  • the water content of the polyurethane-polyacrylamide hydrogel precursor liquid is 50% by weight, the R value is 2, the photocurable polymer monomer: polyurethane is 3, and the emulsion viscosity is 0.46 mPa ⁇ s. (Denoted as PP-50).
  • the obtained precursor liquid was sprayed out, and cured after being irradiated at 365 nm for 90 s to obtain a hydrogel dressing.
  • the SEM photo of the dressing is shown in Figure 3, which has a porous three-dimensional network structure with good moisture retention, air permeability, self-adhesion and mechanical properties.
  • the water content of the polyurethane-polyacrylamide hydrogel precursor liquid is 70% by weight, the R value is 2, the photocurable polymer monomer: polyurethane is 3, and the emulsion viscosity is 0.32 mPa ⁇ s. (Denoted as PP-70).
  • the hydrogel dressing obtained after solidification of the precursor liquid has a three-dimensional network structure similar to that of Example 3.
  • Antibacterial drugs, anti-inflammatory drugs, growth factors and other drugs were added to the precursor solutions of Examples 1-5 to prepare a hydrogel dressing capable of carrying and slowly releasing active drugs.
  • the obtained precursor solution was sprayed out, and cured after exposure to 365 nm light for 300 s to obtain a hydrogel dressing.
  • the SEM photo of the dressing is shown in Figure 4.
  • the gel structure is dense, the surface is wrinkled, and holes without communication appear, which is not conducive to material exchange.
  • the hydrogel dressing obtained after solidification of the precursor liquid has a dense structure similar to that of Comparative Example 1.
  • the obtained precursor liquid was sprayed out, and cured after being illuminated at 365 nm for 100 s to obtain a hydrogel dressing.
  • the SEM photo of the dressing is shown in Figure 5.
  • the material has a dense structure and a rough surface, which is not conducive to substance exchange.
  • the precursor liquid cannot form an emulsion with good dispersibility.
  • the polyurethane molecular chains are entangled and solidified to form microsphere particles.
  • the SEM photo is shown in Figure 6.
  • mPa ⁇ s dressing liquid the complex viscosity is adjusted by the total amount of light-curing polymer monomer and polyurethane, and the same amount of dressing liquid is filled into the same spray can (15ml vacuum spray bottle, commercially available), Surface spray, 0.1mPa ⁇ s excipients are sprayed on the skin and flow away quickly.
  • the shape of the cured hydrogel is poorly matched to the wound, and the required thickness cannot be stably achieved.
  • the dressing liquid with a complex viscosity of 1.0 mPa ⁇ s needs a large pressing force when spraying, and the extrusion is not smooth.
  • the dressing liquid with a complex viscosity of 0.2-0.8mPa ⁇ s has good spraying and curing effects, especially 0.4 and 0.6mPa ⁇ s.
  • the dressings of Examples 3 and 4 were subjected to a one-month swelling performance test.
  • the cylinder is immersed in the PBS solution, and the cylinder is weighed for a fixed period of time to calculate the mass swelling ratio; at the same time, the diameter and height of the cylinder are measured with a vernier caliper, and the volume swelling ratio is calculated.
  • the test results are shown in Figure 8.
  • the left figure is the volume swelling curve
  • the right figure is the mass swelling curve.
  • the swelling mass ratio reached 6 times the original mass, and the volume swelling ratio was close to 8 times the original volume. This is conducive to the absorption of exudate from the wound surface and keeps the wound surface self-cleaning.
  • Test method for tensile properties Use a universal material testing machine (model: AGIC 50KN, Japan Shimadzu company) to test the tensile properties of the hydrogel material. First, make the test gel into a dumbbell-shaped spline with a length of 75mm, a width of 4mm, and a thickness of 2mm; secondly, set up a tensile experiment with a tensile rate of 50mm/min and a tensile load of 10N; finally, fix the spline in the fixture , Start to stretch the spline until the spline breaks from the middle.
  • a universal material testing machine model: AGIC 50KN, Japan Shimadzu company
  • the elastic modulus of the hydrogel ranges from 10 3 to 10 5 Pa.
  • the stability of the material was tested in the frequency sweep mode. It was found that when the frequency was increased to 100Hz, the elastic modulus and viscous modulus of these gel materials did not change significantly, indicating that the material is structurally stable under external force stimulation.
  • the tensile elongation of the material can reach 800-3000% of the original length.
  • the elongation rate of PP-50 hydrogel can reach 900%.
  • the elongation of the PAAm hydrogel with the same elastic modulus is only 300%. It can be seen that PU also has a greater impact on the mechanical properties of the gel.
  • the hydrogel can be detached from the skin without residue and no damage to the skin, such as the PP-70 hydrogel peeling diagram shown in Figure 10.
  • the experiment used adult New Zealand white rabbits weighing about 2000g.
  • the white rabbits were anesthetized with urethane (25wt%, 5ml/kg) intravenous ear source injection, and all their backs were depilated. Then, a round full-thickness skin notch model with a diameter of 1.5 cm was made on its back.
  • the polyurethane-polyacrylamide hydrogel precursor solution (experimental group, PP-70) in Example 4 was sprayed on the wound surface, and cured under ultraviolet light for a short time to form a gel film; the control group did not do any treatment.
  • the white rabbits were injected with penicillin subcutaneously every day 3 days after the operation. Observe the wound healing on 0, 3, 9, and 17 days respectively.
  • the experimental phenomenon can be observed at 3 days, the surface of the wound with hydrogel material (experimental group, PP-70) is clean, no blood crust appears, and a large amount of granulation tissue grows; while the control group has obvious blood crust on the surface of the wound cover. It shows that the hydrogel material can effectively absorb the tissue fluid exuded from the wound and promote the self-cleaning of the wound surface.
  • the control group the growth of connective tissue in the dermis was blocked due to blood scab coverage, resulting in slower wound healing; while the wound (experimental group, PP-70) applied with hydrogel material healed in a large area with obvious healing area Higher than the blank group.
  • the wound (experimental group, PP-70) applied with the hydrogel material had basically healed, and the scar was relatively shallow; while the wound surface of the control material was long, but the scar was deeper. It shows that the use of hydrogel materials can effectively promote the healing of skin wounds.

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Abstract

一种基于聚氨酯的喷射型光固化水凝胶敷料前驱液，含有聚氨酯、光固化聚合物单体、光引发剂和水，其中，光引发剂的质量含量为0.5～5％，水的质量含量为50～80％，光固化聚合物单体与聚氨酯的质量比为1.5:1～4:1，前驱液的复数粘度为0.2-0.8mPa·s，前驱液以液体形态喷涂，经光照固化在皮肤创伤表面形成一层具有伤口适应性的黏附水凝胶敷料，保湿、透气、吸液能力强、力学性能佳，移除无损，使用方便，能够促进创伤面的愈合。

Description

基于聚氨酯的喷射型光固化水凝胶敷料前驱液及制备方法 技术领域
本发明属于医用材料领域，具体涉及一种基于聚氨酯的喷射型光固化水凝胶敷料前驱液，以及该前驱液的制备方法。
背景技术
皮肤是位于体表、包在肌肉外面的组织，是保持机体内部环境稳定、抵御外来入侵的重要器官，具有物理、化学和生物屏障功能。作为人体最外层的屏障，皮肤往往由于外界各种环境因素受到损伤。烧烫伤、刮擦伤以及外伤引起的大面积溃烂等都严重威胁着人体健康。在中国，每年有高达500～1000万的烧烫伤受害者，其中约5％的病患需要住院治疗。另外，世界卫生组织最新发布的数据称，预计未来在全世界范围内，每年还将有265,000人死于烧伤感染。
创面损伤往往伴随着新陈代谢加剧、水分和蛋白质过度流失、内分泌和免疫系统失调等现象，进而引发各类损伤，如伤口不愈合、压力性溃疡等。因此，研制一种适宜的创面敷料能够即时、有效地控制伤口感染并促进伤口愈合，对于临床伤口护理与康复治疗至关重要。
传统敷料如棉垫、纱布、软麻布等有较强的吸收创面渗液的能力，从而对伤口有一定的保护作用。受限于其材料特性，传统敷料在治疗过程中容易粘连伤口、需要多次更换，且无保湿性，导致其治疗周期长，还往往引起伤口的二次损伤。随着人们对敷料的进一步研究，多种新型敷料逐渐被开发并得以应用。
目前，用于临床治疗的创面敷料主要有以下几种：液体类、喷膜类和水凝胶类等。其中，喷膜型敷料的优点在于其能根据伤口实际情况，通过喷涂成膜在创伤表面形成与其大小尺寸适应并贴合的保护膜，用以抵御细菌的入侵，防止感染。但这类敷料的吸液能力有限，且薄膜易脆，导致其作用时间短。水凝胶是一种含有大量水分的高分子网络材料，其性质柔软，作为创面敷料能够有效吸收伤口渗出液并且保持创面湿润，有效防止伤口表面的脱水和干燥，可以有效缓解病患的不适和疼痛感。但由于皮肤创伤部位形状不规则，预制成型的水凝胶敷料往往难以满足创面的实际需求，较差的组织贴合性直接导致材料与创口表面分离，导致细菌滋生或者感染，进一步带来更大的损伤。理想的创面敷料应该具有如下功能(1)抵御外源性物质的入侵，防止进一步感染；(2)吸收组织渗出液并保持创面环境清洁湿润；(3)与创口表面具有良好的贴合性和适应性；(4)具有一定的机械性能；(5)能与周围正常组织良好粘连。
专利CN107106724A公开了一种包含聚合物、转换引发剂和水状胶体的组合物，该组合物能呈现转换前的液体状态和转换后的粘合剂状态两种形态，液体用于涂在造口皮肤表面，转换成粘合剂状态后将皮肤与造口术器具粘接。但是出于对造口皮肤的健康和粘合剂的形成考虑，这种组合物并不以水为溶剂，而是采用如乙酸乙酯、甲苯、四氢呋喃等有机溶剂溶解聚合物，然后再在一定高温下干燥。专利CN107106724A为制造具有两种状态的施用材料提供了一种可行的案例，但是其材料适合用在无创伤的皮肤表面，起到粘合和保持干燥的功能，无法作为创伤皮肤表面敷料使用，而且有机溶剂残留存在非常大的安全风险，导致临床使用受限。
发明内容
针对现有技术存在的不足，本发明设计了一种基于聚氨酯的喷射型光固化成形的水凝胶敷料前驱液。该前驱液可在喷射过程中实现快速固化，在皮肤创伤表面形成一层具有伤口适应性的黏附水凝胶敷料，保湿、透气、吸液能力强、力学性能极佳，使用方便，而且能够显著促进创伤面的愈合。
本发明的第一方面提供一种基于聚氨酯的喷射型光固化水凝胶敷料前驱液，该前驱液含有聚氨酯、光固化聚合物单体、光引发剂和水，其中，光引发剂的质量含量为0.5～5％，水的质量含量为50～80％，光固化聚合物单体与聚氨酯的质量比为1.5:1～4:1，前驱液的复数粘度为0.2-0.8mPa·s，前驱液以液体形态喷涂，经光照固化形成水凝胶敷料。
水凝胶敷料在使用前以水凝胶前驱液形式保存，通过喷射的方法喷涂于伤口表面形成液膜，在某些波段的光照下，液膜快速固化形成可黏附的水凝胶层。该凝胶无需引入任何粘接剂，聚氨酯的存在赋予了凝胶层自黏附的特性。
在一些实施例中，聚氨酯以水性聚氨酯乳液引入前驱液中。
光固化聚合物单体是指在光引发作用下能发生加成聚合的单体物，包括但不限于丙烯酸、明胶-甲基丙烯酰胺(gelMA)、PEG-二丙烯酸酯(PEGDA)、丙烯酰胺(PAAm)等中的一种或多种。当仅采用这些单体光固化后的聚合物作为敷料的交联材料骨架时，敷料固化形成水凝胶的速度较慢(大于300s以上)，这对需要尽快处理创面的患者而言，是极为不利的。经过发明人研究后发现，加入适量的聚氨酯，可以显著缩短固化时间至10-250s，优选的固化时间为30-200s，更优选的固化时间为50-120s。在一些实施例中，发明人还惊奇地发现，引入适当的聚氨酯后，水凝胶的力学性能大为改善，特别是拉伸性能。但是大量的聚氨酯又会影响水凝胶的透明度。因此，将光固化聚合物单体与聚氨酯的质量比设置为1.5:1～4:1，优选为3:1。
前驱液的复数粘度决定着前驱液能否顺利从容器中喷射出去，以及喷射到皮肤的前驱液能否保持附着时的形状进行固化。当粘度过低时，前驱液喷射到皮肤表面后迅速流走，不能形成与创伤的形状和大小匹配的水凝胶。而当粘度过高时，前驱液不能顺利地从容器中喷涂到伤口表面。经过发明人的研究，前驱液的适宜的复数粘度为0.2-0.8mPa·s，更优选的复数粘度为0.3-0.6mPa·s。
前驱液的粘度可以通过光固化聚合物单体与聚氨酯的含量进行调节，但是二者仍需保持在前述的比例范围内，以兼顾合理的固化时间、力学性能和透明度。也可以采用医药上可接受的粘度调节剂进行调节，通常情况下，分子量大的调节剂能够增大粘度，反之，分子量小者降低粘度。
聚氨酯可以通过将含有醇羟基的分子与异氰酸酯反应获得。这些异氰酸酯包括但不限于异佛尔酮二异氰酸酯、甲苯二异氰酸酯、4,4’-二苯基甲基二异氰酸酯、1,6-己烷二异氰酸酯等等。在一些实施例中，采用异佛尔酮二异氰酸酯。含有醇羟基的分子包括聚酯/聚醚的二元醇或多元醇和扩链剂。所述聚酯/聚醚的二元醇或多元醇多元醇选自聚氧化乙烯二元醇、聚四氢呋喃醚二醇、聚氧化丙烯二元醇、聚乳酸二元醇/多元醇、聚己内酯二元醇/多元醇、聚乙交酯二元醇/多元醇中的一种或多种。扩链剂选自1,4-丁二醇、二羟甲基丙酸、三乙醇胺、甲基二乙醇胺中的一种或多种。因为本发明的前驱液使用后将转换为水凝胶，而聚氨酯分子链在分散介质-水中的乳化分散状态将影响聚氨酯乳液的均匀性以及水凝胶的状态。发明人在研究过程中发现，异氰酸酯与含有醇羟基的分子的R值(基团NCO与OH的摩尔比)与聚氨酯乳液的分散状态相关，当R值大于2.5时，聚氨酯分子链在水中大量团聚卷曲并形成微球颗粒，而非乳滴。但是当R值小于1时，固化后的水凝胶弹性模量极低，力学性能差。因此，优选制备聚氨酯的异氰酸酯与含有醇羟基的分子的R值为大于1且小于等于2.5。
在一些实施例中，聚氨酯来源于水乳法制备的水性聚氨酯乳液。本领域的技术人员知晓，当原料或反应物存在一定的酸碱性时，可能对皮肤产生一定的刺激，对这种情况的前驱液，优选其中还含有中和酸碱的pH调节剂，用pH调节剂中和前驱液对乳液的形成也是有利的。pH调节剂可以是无机酸/碱，或者有机酸/碱。
本发明选用水作为分散介质能够实现多重效果，其一，在固化后的水凝胶中大部分水与聚合物材料以结合水的形式存在，沸点＞120℃，不会在短时间内挥发，能够保持创伤面周围环境湿润，有助于伤口愈合；其二，含适量水的聚氨酯-光固化聚合物单体固化得到的水凝胶具有特殊的三维网络立体结构，这种结构使皮肤与外界建立小分子交换通道，有助于空 气的流通和药物的施用，具有较好的生物相容性，且皮肤湿润但不过度水合；其三，未完全反应的具有生物毒性的异氰酸根(-NCO)能够与水反应生成无毒产物，同时避免有机溶剂存在的安全隐患。因此，本发明的敷料选用含量大于等于50wt％的水为分散介质，但是一些实施例的实验结果表明，水含量越大，溶胀性能降低，而且固化时间也相对延长，因此，本发明的敷料水含量小于等于80wt％。
作为一种优选的实施方式，水凝胶敷料前驱液中还含有药物，所述药物包括但不限于抗菌药、抗炎药、生长因子等中的一种或多种。因为本发明的前驱液固化后的水凝胶敷料具有多孔网络结构，药物填充在这些结构中能够持续地向创伤输送，达到持久的治疗作用。
本发明的前驱液优选光引发剂的吸光范围在紫外光区(250-420nm)或可见光区(400～800nm)。符合这些吸光范围的光引发剂包括但不限于2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮，2,4,6-三甲基苯甲酰基-二苯基氧化膦，苯甲酰甲酸甲酯，2-二甲氨基-2-苄基-1-[4-(4-吗啉基)苯基]-1-丁酮，氟化二苯基钛茂，双(五氟苯基)钛茂等。
本发明的第二方面提供了前述基于聚氨酯的喷射型光固化水凝胶前驱液的制备方法，该方法包括以下步骤：
(1)用水乳法制备含水量为50～80wt％的水性聚氨酯乳液；
(2)按光固化聚合物单体：聚氨酯＝1.5:1～4:1的质量比，加入光固化聚合物单体，搅拌均匀后形成混合乳液；
(3)向上述乳液中加入光引发剂，调整前驱液的含水量保持为50～80wt％，复数粘度为0.2-0.8mPa·s，均匀混合后形成水凝胶前驱液。
本发明的第三个方面提供了前述前驱液的使用方法，包括将前驱液喷涂于创伤表面，暴露在一定波长的光照下形成具有一定厚度的水凝胶敷料。
本发明的有益效果在于：(1)使用前，水凝胶前驱液以液体形式保存，通过喷射的方法喷涂于伤口表面形成液膜，在特定波段的光照下，液膜快速固化形成水凝胶，使用过程便捷；(2)所形成的水凝胶能够有效覆盖创口，与创口形貌完全贴合，进而防止细菌入侵、滋生或感染；(3)水凝胶材料内部含有大量的水分，可保持创伤周围环境湿润；(4)水凝胶可吸收大量的组织液，保证伤口的自清洁；(5)使用完后，水凝胶可直接从皮肤表面无创去除，无二次损伤。
附图说明
图1是本发明实施例1的水性聚氨酯乳液的乳滴粒径分布图；
图2是本发明实施例1的水凝胶敷料前驱液的乳滴粒径分布图；
图3-5是本发明实施例3、对比例1和对比例3制备的PP-50、P-50、PP-42水凝胶敷料的SEM照片；
图6是本发明对比例4制备的R值为3的水凝胶敷料前驱液中微球颗粒的SEM图；
图7是本发明实施例3、4和对比例1、2制备的PP-50、PP-70、P-50、P-70随时间固化状态图；
图8是本发明实施例3、4的前驱液固化的水凝胶的体积和质量溶胀曲线图；
图9是本发明实施例3、4的前驱液固化的水凝胶的拉伸曲线图；
图10是本发明实施例4的PP-70水凝胶在皮肤表面的黏附和剥离图。
具体实施方式
以下通过具体实施例对本发明的发明内容做进一步的阐释，但不应理解为本发明的范围仅限于以下的实例，根据本发明的发明思路和全文内容，可以将以下实例中的各个技术特征做适当的组合/替换/调整/修改等，这对于本领域技术人员而言是显而易见的，仍属于本发明保护的范畴。
实施例1
将13.34g异佛尔酮二异氰酸酯与24g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至50℃，分别将2.4g的2,2-二羟甲基丙酸加入上述反应体系中，保持温度搅拌2h。之后，降温至57℃后继续搅拌0.5～1h，得到聚氨酯预聚体。最后，将2.02g三乙胺加入到97.44g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体加入到中和液中，剪切乳化仪高速搅拌2h左右，得到含水量为70wt％的阴离子聚氨酯乳液。乳滴粒径分布15-100nm，如图1所示。
取上述聚氨酯乳液20g，加入90g去离子水和18g丙烯酰胺单体，磁力搅拌1h使其混合均匀。之后，向其中加入2.0g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮，搅拌30min后，装瓶储存于室温中待用。乳滴粒径分布90％集中于26-300nm，如图2所示。
上述聚氨酯-聚丙烯酰胺水凝胶前驱液的含水量为80wt％，R值为2，光固化聚合物单体：聚氨酯为3，复数粘度为0.2mPa·s。
实施例2
将13.34g异佛尔酮二异氰酸酯与24g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至60℃，分别将一定2.14g的甲基二乙醇胺加入上述反应体系中， 保持温度搅拌2h。之后，加入适量丙酮(5-20mL)调节反应体系粘度，降温至57℃后继续搅拌0.5～1h，得到PU预聚体。最后，将2.3g乙酸加入到97.44g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体加入到中和液中，剪切乳化仪高速搅拌2h左右，得到含水量为70wt％的阳离子聚氨酯乳液。乳滴粒径分布集中于15-100nm之间。。
取上述聚氨酯乳液30g，加入5g去离子水和13.5g丙烯酸单体，磁力搅拌1h使其混合均匀。之后，向其中加入1g 2,4,6-三甲基苯甲酰基-二苯基氧化膦，搅拌30min后，装瓶储存于室温中待用。乳滴粒径分布50～1000nm。
上述聚氨酯-聚丙烯酰胺水凝胶前驱液的含水量为53wt％，R值为2，光固化聚合物单体：聚氨酯为1.5，乳液粘度为0.3mPa·s。
实施例3
将13.34g异佛尔酮二异氰酸酯与24g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至50℃，分别将2.4g的2,2-二羟甲基丙酸加入上述反应体系中，保持温度搅拌2h。之后，降温至57℃后继续搅拌0.5～1h，得到聚氨酯预聚体。最后，将2.02g三乙胺加入到97.44g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体加入到中和液中，剪切乳化仪高速搅拌2h左右，得到含水量为70wt％的阴离子聚氨酯乳液。
取上述聚氨酯乳液20g，向其中加入12.4g水，称取18g丙烯酰胺单体分2次加入上述乳液中，室温下磁力搅拌1h。随后加入2.4g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮继续搅拌1h，装瓶储存于室温中待用。乳滴粒径15-500nm。
上述聚氨酯-聚丙烯酰胺水凝胶前驱液的含水量为50wt％，R值为2，光固化聚合物单体：聚氨酯为3，乳液粘度为0.46mPa·s。(记作PP-50)。
将所得前驱液喷出，经365nm光照90s时间后固化得到水凝胶敷料，敷料的SEM照片如图3所示，呈多孔的三维网络立体结构，保湿、透气、自黏附和力学性能好。
实施例4
将13.34g异佛尔酮二异氰酸酯与24g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至50℃，分别将2.4g的2,2-二羟甲基丙酸加入上述反应体系中，保持温度搅拌2h。之后，降温至57℃后继续搅拌0.5～1h，得到聚氨酯预聚体。最后，将2.02g三乙胺加入到97.44g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体 加入到中和液中，剪切乳化仪高速搅拌2h左右，得到含水量为70wt％的阴离子聚氨酯乳液。
取上述聚氨酯乳液20g，向其中加入47.6g水，称取18g丙烯酰胺单体分2次加入上述乳液中，室温下磁力搅拌1h。随后加入2.4g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮继续搅拌1h，装瓶储存于室温中待用。乳滴粒径集中分布在15-500nm。
上述聚氨酯-聚丙烯酰胺水凝胶前驱液的含水量为70wt％，R值为2，光固化聚合物单体：聚氨酯为3，乳液粘度为0.32mPa·s。(记作PP-70)。
该前驱液固化后得到的水凝胶敷料具有与实施例3类似的三维网络立体结构。
实施例5
在实施例1-5的前驱液中加入抗菌药、抗炎药、生长因子等药物，制得能够携载并缓释活性药物的水凝胶敷料。
对比例1
取24g丙烯酰胺单体在26.4g水中磁力搅拌1h(室温下)，随后加入2.4g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮继续搅拌1h，直至其完全溶解并与丙烯酰胺均匀混合形成含水量为50wt％聚丙烯酰胺水凝胶的前驱液(记作P-50)。
将所得前驱液喷出，经365nm光照300s时间后固化得到水凝胶敷料，敷料的SEM照片如图4所示，凝胶结构致密，表面褶皱，无联通的孔洞出现，不利于物质交换。
对比例2
取24g丙烯酰胺单体在61.6g水中磁力搅拌40min(室温下)，随后加入2.4g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮继续搅拌1h，直至其完全溶解并与丙烯酰胺均匀混合形成含水量为70wt％聚丙烯酰胺水凝胶的前驱液(记作P-70)。
该前驱液固化后得到的水凝胶敷料具有与对比例1类似的致密结构。
对比例3
将13.34g异佛尔酮二异氰酸酯与24g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至50℃，分别将2.4g的2,2-二羟甲基丙酸加入上述反应体系中，保持温度搅拌2h。之后，降温至57℃后继续搅拌0.5～1h，得到聚氨酯预聚体。最后，将2.02g三乙胺加入到97.44g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体加入到中和液中，剪切乳化仪高速搅拌2h左右，得到含水量为70wt％的阴离子聚氨酯乳液。
取上述聚氨酯乳液15g，向其中加入6.8g水，称取18g丙烯酰胺单体分2次加入上述乳液中，室温下磁力搅拌1h。随后加入0.9g 2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮继续搅拌1h，待其完全溶解并均匀混合后形成含水量为42wt％聚氨酯-聚丙烯酰胺水凝胶前驱液(PP-42)。
将所得前驱液喷出，经365nm光照100s时间后固化得到水凝胶敷料，敷料的SEM照片如图5所示，材料结构致密，表面粗糙，不利于物质的交换。
对比例4
将26.67g异佛尔酮二异氰酸酯与28g聚四氢呋喃二醇-2000加入装有温度计、回流冷凝管和搅拌器的三口烧瓶(100mL)中，滴加2-3滴辛酸亚锡，在80℃的条件下通氮气混合搅拌3h。然后，降温至50℃，分别将3.49g的2,2-二羟甲基丙酸加入上述反应体系中，保持温度搅拌2h。之后，降温至57℃后继续搅拌0.5～1h，得到聚氨酯预聚体。最后，将3.93g三乙胺加入到134.75g的去离子水中配制乳化中和液。室温下，缓慢将制得的聚氨酯预聚体加入到中和液中，剪切乳化仪高速搅拌2h。得到R值为3的前驱液。
该前驱液不能形成分散性好的乳液，在乳化过程中聚氨酯分子链缠结固化形成微球颗粒，其SEM照片如图6所述。
试验例1
按照前述实施例1方法制备含水量为70％，光固化聚合物单体：聚氨酯＝3:1，光交联剂含量为5wt％，复数粘度分别为0.1，0.2，0.4，0.6，0.8，1.0mPa·s的敷料液体，复数粘度通过光固化聚合物单体和聚氨酯的总量进行调节，将等量的敷料液装入相同的喷壶(15ml真空型喷雾瓶，商购获得)中，对皮肤表面喷涂，0.1mPa·s的辅料喷涂到皮肤上后迅速流走，固化后的水凝胶形状与伤口匹配度差，也不能稳定地达到需求的厚度。复数黏度为1.0mPa·s的敷料液体喷出时需要较大的按压力，挤出不顺畅。复数黏度为0.2-0.8mPa·s的敷料液体喷涂和固化效果好，特别是0.4，0.6mPa·s效果较佳。
试验例2
将实施例3、对比例1和对比例3的敷料前驱液分别固化后，观察水凝胶的微观形貌。其SEM照片分别如图3、4、5所示，含水量、含PU均会影响水凝胶三维网络立体结构的形成。在水含量50-80％，光固化聚合物单体：聚氨酯质量比为1.5-4:1情况下，水凝胶形成具有贯通孔隙的三维网络立体结构，有利于材料对水分的吸收，以及皮肤与外界小分子(空气、分子药物等)进行交换。
试验例3
用实施例3、4和对比例1、2的水凝胶敷料前驱液做光固化特性研究，考察含水量和聚氨酯对前驱液固化时间的影响。结果如图7所示，其中，P表示只含有丙烯酰胺单体(PAAM)，PP表示同时含有丙烯酰胺单体(PAAM)和聚氨酯(PU)，后面的数字表示含水量。由图中可以看出，当不含有聚氨酯时，含水量50％和70％的敷料在300s内都无法固化。加入聚氨酯后，敷料在30s可以肉眼观察到固化，完全固化的时间分别是PP-50为62s，PP-70为75s。聚氨酯的加入显著促进了敷料的固化，此外，含水量更高的PP-70所需的固化时间也更长。
试验例4
将实施例3和4的敷料进行一个月的溶胀性能试验，具体实验过程如下：将凝胶前驱液放于固定模具中，光照固化成为尺寸为底面直径(Φ)×高(h)＝5×5mm的圆柱体。将上述圆柱体浸泡于PBS溶液中，固定时间称量圆柱体的重量，计算质量溶胀比；同时用游标卡尺测量圆柱体的直径和高度，并计算体积溶胀比。试验结果如图8所示，左图为体积溶胀曲线，右图为质量溶胀曲线。一个月内，溶胀质量比达到原质量的6倍，体积溶胀比接近原体积的8倍，这有利于对创口表面渗出液的吸收，保持伤口表面的自清洁。
试验例5
测试实施例3和4的PU-PAAm前驱液固化后的凝胶材料的弹性模量和拉伸性能。
拉伸性能的测试方法：用万能材料试验机(型号：AGIC 50KN，日本Shimadzu公司)对水凝胶材料拉伸性能进行测试。首先将测试凝胶制成长75mm、宽4mm、厚2mm的哑铃状样条；其次，设置拉伸实验，其中拉伸速率为50mm/min，拉伸载荷10N；最后，将样条固定于夹具中，开始拉伸样条直至样条从中部断裂。
弹性模量的测试方法：使用流变仪(型号:Discovery DHR-2，美国TA公司)对水凝胶的弹性模量进行测试。首先，选择直径20mm的平底不锈钢圆盘为实验夹具，夹具与样品台间距1000μm，将测试凝胶平铺与样品台上；其次，选择时间扫描模式，设置参数应力＝1Pa，应变＝1％，频率＝1Hz，时间＝300s。设置好相关参数后，即可开始对材料弹性模量的测试。
测得，该水凝胶的弹性模量范围在10 3～10 5Pa。同时用频率扫描模式对材料的稳定性进行测试，发现当频率加到100Hz时，这些凝胶材料的弹性模量和粘性模量并没有发生明显的变化，说明材料在受到外力刺激下结构稳定。
材料的拉伸伸长率可达到原始长度的800～3000％。其中，PP-50水凝胶的伸长率可达 900％。而同样弹性模量的PAAm水凝胶的伸长率却只有300％。可见PU还对凝胶的力学性能构成较大影响。
试验例6
测试实施例3和4的固化水凝胶的黏附性能。
以猪皮为基材，测量水凝胶的黏附强度。首先，将猪皮剪切成长(l)×宽(w)＝75mm×25mm的长方形样条，将面积为25mm×20mm的水凝胶材料粘在两块待测基底(猪皮)之间。再通过万能材料试验机(型号：AGIC 50KN，日本Shimadzu公司)以5mm/min的速率拉伸样品直至破坏。拉伸曲线如图9所示，两种水凝胶材料与组织均具有良好的黏附性能，其最大黏附强度能达到0.008～0.016MPa。同时可以看出，水含量的增加有利于提高水凝胶的黏附性能。
同时，使用结束后，水凝胶可以无残留地从皮肤上脱离，对皮肤无损伤，例如图10所示的PP-70的水凝胶剥离图。
试验例7
在新西兰大白兔的背部区域构建一个全层皮肤损伤模型(直径Φ＝1.5cm)，用实施例4中的聚氨酯-聚丙烯酰胺水凝胶对伤口进行处理；没有水凝胶填充的空白伤口作为对照组。具体步骤如下：
实验使用体重约为2000g的成年新西兰大白兔。先用乌拉坦(25wt％，5ml/kg)静脉耳源注射对白兔进行麻醉，并将其背部全部脱毛。然后，在其背部制造直径为1.5cm的圆形全层皮肤缺损伤口模型。其后，将实施例4中的聚氨酯-聚丙烯酰胺水凝胶前驱液(实验组，PP-70)喷洒于伤口表面，紫外灯下短时间固化形成凝胶膜；对照组不做任何处理。术后3天每天给白兔皮下注射青霉素。分别观察0，3，9，17天伤口的愈合情况。
实验现象可观察到3天时，敷了水凝胶材料的伤口(实验组，PP-70)表面干净，无血痂出现，同时有大量肉芽组织长出；而对照组伤口表面有明显的血痂覆盖。说明，水凝胶材料可以有效吸收创口处渗出的组织液，促进创口表面的自清洁。另外，9天时，对照组由于血痂覆盖，使得真皮层结缔组织生长受阻，导致伤口愈合较慢；而敷过水凝胶材料的伤口(实验组，PP-70)大面积愈合，愈合面积明显高于空白组。17天时，敷过水凝胶材料的伤口(实验组，PP-70)已基本愈合，且伤口的疤痕相对较浅；而对照组材料伤口表面长合，但疤痕较深。说明，水凝胶材料的使用能够有效促进皮肤创口的愈合。

Claims (10)

  1. 一种基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，该前驱液含有聚氨酯、光固化聚合物单体、光引发剂和水，其中，光引发剂的质量含量为0.5～5％，水的质量含量为50～80％，光固化聚合物单体与聚氨酯的质量比为1.5:1～4:1，前驱液的复数粘度为0.2-0.8mPa·s，前驱液以液体形态喷涂，经光照固化形成水凝胶敷料。
  2. 根据权利要求1所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，光固化聚合物单体与聚氨酯的质量比为3:1，前驱液的复数粘度为0.3-0.6mPa·s。
  3. 根据权利要求1所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，所述聚氨酯以水性聚氨酯乳液引入前驱液中。
  4. 根据权利要求3所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，所述水性聚氨酯乳液通过含有醇羟基的分子与异氰酸酯用水乳法制备。
  5. 根据权利要求4所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，所述异氰酸酯与含有醇羟基的分子的R值大于1且小于等于2.5。
  6. 根据权利要求4所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，所述异氰酸酯为异佛尔酮二异氰酸酯、甲苯二异氰酸酯、4,4’-二苯基甲基二异氰酸酯、1,6-己烷二异氰酸酯、六亚甲基二异氰酸酯、萘二异氰酸酯、对苯二异氰酸酯中的至少一种，所述光固化聚合物单体选自丙烯酸、明胶-甲基丙烯酰胺、PEG-二丙烯酸酯、丙烯酰胺中的至少一种。
  7. 根据权利要求4所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，所述含有醇羟基的分子包括聚酯/聚醚的二元醇或多元醇和扩链剂，所述聚酯/聚醚的二元醇或多元醇为聚氧化乙烯二元醇、聚四氢呋喃醚二醇、聚氧化丙烯二元醇、聚乳酸二元醇/多元醇、聚己内酯二元醇/多元醇、聚乙交酯二元醇/多元醇中的一种或多种，所述扩链剂为1,4-丁二醇、2,2-二羟甲基丙酸、三乙醇胺、甲基二乙醇胺中的一种或多种。
  8. 根据权利要求1所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液，其特征在于，该前驱液中还含有药物，所述药物包括抗炎药物、抗菌药物、生长因子类药物中的一种或多种。
  9. 如权利要求1-8任意一项所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液的制备方法，该方法包括以下步骤：
    (1)用水乳法制备含水量为50～80wt％的水性聚氨酯乳液；
    (2)按光固化聚合物单体：聚氨酯＝1.5:1～4:1的质量比，加入光固化聚合物单体，搅拌均匀后形成混合乳液；
    (3)向上述乳液中加入光引发剂，调整前驱液的含水量保持为50～80wt％，复数粘度为0.2-0.8mPa·s，均匀混合后形成水凝胶敷料前驱液。
  10. 如权利要求1-8任意一项所述的基于聚氨酯的喷射型光固化水凝胶敷料前驱液的使用方法，包括将前驱液喷涂于创伤表面，暴露在一定波长的光照下形成具有一定厚度的水凝胶敷料。
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