Double-layer waterborne polyurethane coating for sustained release of riboflavin and anticoagulants and its application

Abstract

The present invention relates to a double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants and its application. The double-layer aqueous polyurethane coating comprises an inner and outer two-layer structure, wherein the inner layer is a cationic aqueous polyurethane layer, and the outer layer is an anionic aqueous polyurethane layer. Riboflavin is added to the raw materials of the cationic aqueous polyurethane layer, and riboflavin and anticoagulants are added to the raw materials of the anionic aqueous polyurethane layer. The double-layer aqueous polyurethane coating is applied to the inner wall surface of the blood channel in the photodynamic therapy device for extracorporeal blood circulation. When the present invention is used for extracorporeal blood circulation therapy, the double-layer aqueous polyurethane coating can stably and continuously release riboflavin and anticoagulants into the blood after contacting the blood, thereby improving the durability and stability of riboflavin and anticoagulants in photodynamic therapy. Riboflavin generates reactive oxygen species (ROS) after light irradiation, which can rapidly inactivate tumor cells in the blood.

Description

Technical Field

[0001] The invention relates to a double-layer waterborne polyurethane coating for continuously releasing riboflavin and anticoagulants and application of the coating in extracorporeal blood circulation photodynamic therapy, belonging to the technical field of biomedicine. Background Art

[0002] Riboflavin RF, also known as vitamin B2, is a type of B vitamin. As a component of the flavonoids cofactor, it is an indispensable component in the body. However, due to its short half-life and relatively low bioavailability, riboflavin is not easy to accumulate in the human body for a long time. At the same time, if it is taken in excessive amounts, it will be excreted from the body through urine.

[0003] As a photosensitizer, riboflavin is an important biological redox cofactor. It will be activated under the irradiation of a certain wavelength of light (ultraviolet or blue light) to produce reactive oxygen species (ROS) with strong oxidative effects, thereby inactivating malignant tumor cells and pathogenic microorganisms. In the prior art, when adding riboflavin to participate in phototherapy to inactivate tumor cells, the riboflavin solution is often directly injected into the phototherapy system. This method makes the process of accurately controlling the amount of riboflavin added complicated, requires more manpower and material resources, and the effect of riboflavin accumulation around tumor cells is not good. Summary of the invention

[0004] In order to overcome the above-mentioned defects of the prior art, the present invention provides a double-layer aqueous polyurethane coating for continuously releasing riboflavin and anticoagulants and the application of the coating in extracorporeal blood circulation photodynamic therapy, which can stably and continuously release riboflavin and anticoagulants into the blood, thereby improving the durability and stability of riboflavin and anticoagulants participating in photodynamic therapy.

[0005] The technical solution for achieving the above-mentioned purpose is as follows: a double-layer water-based polyurethane coating for continuously releasing riboflavin and anticoagulants comprises an inner and outer two-layer structure, wherein the inner layer is a cationic water-based polyurethane layer and the outer layer is an anionic water-based polyurethane layer, riboflavin is added to the raw material of the cationic water-based polyurethane layer, and riboflavin and anticoagulants are added to the raw material of the anionic water-based polyurethane layer.

[0006] Preferably, the coating for forming the cationic waterborne polyurethane layer is prepared by the following method: adding polyether polyol, cationic hydrophilic chain extender and polydimethylsiloxane into a reaction kettle, introducing nitrogen under stirring, heating to 35-100° C., sequentially adding diisocyanate, catalyst and crosslinking agent, diamino compound containing triazine and photosensitizer to react, cooling to 20-40° C., adding a neutralizer for neutralization, cooling to 0-30° C., adding deionized water for stirring and emulsification, removing the solvent, and obtaining a cationic waterborne polyurethane emulsion, wherein the photosensitizer is riboflavin.

[0007] Preferably, the polyether polyol is any one of polytetramethylene glycol, polyethylene glycol and polypropylene glycol or any combination of any multiple thereof (including all); the cationic hydrophilic chain extender is any one of N-methyldiethanolamine and N-ethyldiethanolamine or any combination of the two; the polydimethylsiloxane is any one of polydimethylsiloxane with hydroxyl groups at both ends and polydimethylsiloxane with amino groups at both ends or any combination of the two; the diisocyanate is toluene diisocyanate, dicyclohexylmethane diisocyanate, diphenylmethane diisocyanate or diisocyanate. Any one of isocyanate, isophorone diisocyanate and hexamethylene diisocyanate or any combination of any two; the catalyst is any one of stannous octoate and dibutyltin dilaurate or any combination of these two; the cross-linking agent is any one of castor oil and trimethylolpropane or any combination of these two; the diamino compound containing triazine is 2,4-diamino-6-undecyl-1,3,5-triazine; the neutralizing agent is any one of acetic acid and hydrochloric acid or any combination of these two; the solvent is acetone or butanone.

[0008] Furthermore, the 2,4-diamino-6-undecyl-1,3,5-triazine (a diamine compound containing triazine) is prepared by the following method: dicyandiamide, dodecanitrile, n-butanol and potassium hydroxide are added to a single-mouth container, nitrogen is introduced, and the reaction is stirred at 118° C. The crude reaction mixture obtained after the reaction is filtered, cooled and crystallized, and filtered again to obtain white crystals. The white crystals are washed and purified with n-heptane and distilled water, and vacuum dried to obtain 2,4-diamino-6-undecyl-1,3,5-triazine in the form of a white powder.

[0009] Preferably, the coating for forming the anionic waterborne polyurethane layer is prepared by the following method: polyester polyol and anionic hydrophilic chain extender are added to a reaction kettle, nitrogen is introduced under stirring, and after heating to 35-100° C., diisocyanate, catalyst, photosensitizer, and anticoagulant are added in sequence for reaction, the temperature is lowered to 20-40° C., a neutralizer is added for neutralization, the temperature is lowered to 0-30° C., deionized water is added for stirring and emulsification, and the solvent is removed to obtain an anionic waterborne polyurethane emulsion, wherein the photosensitizer is riboflavin.

[0010] Preferably, the polyester polyol is any one of polycarbonate polyol, polycaprolactone polyol and 1,6-hexyl-1,2-ethyl carbonate diol or any combination of any two; the anionic hydrophilic chain extender is any one of 2,2-dihydroxymethylbutyric acid and 2,2-dihydroxymethylpropionic acid or any combination of these two; the diisocyanate is any one of dimethylene diisocyanate and hexamethylene diisocyanate or any combination of these two; the catalyst is any one of stannous octoate and dibutyltin dilaurate or any combination of these two; the anticoagulant is argatroban; the neutralizer is triethylamine; and the solvent is acetone or butanone.

[0011] Furthermore, the diisocyanate is prepared by the following method: adding dimethyl sulfoxide to a container, then adding amine and carbon disulfide and stirring to mix, then adding tetrabutylammonium iodide and mixing, continuing to stir and slowly adding iodine until the flavin element S appears, washing the reaction mixture with a 10% sodium thiosulfate aqueous solution, then washing with distilled water to remove sulfur in the mixture, separating the organic layer, drying with anhydrous sodium sulfate, filtering, concentrating, and finally purifying with a chromatography column to obtain the diisocyanate.

[0012] Application of any double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants disclosed in the present invention in extracorporeal blood circulation photodynamic therapy.

[0013] Preferably, the double-layer aqueous polyurethane coating is coated on the inner wall surface of the blood channel in the photodynamic therapy device.

[0014] Furthermore, the cationic water-based polyurethane is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and after curing, a cationic water-based polyurethane layer is formed. Then, the anionic water-based polyurethane is coated on the surface of the cationic water-based polyurethane layer, and after curing, an anionic water-based polyurethane layer is formed. When blood flows through the blood channel, the coating on the inner surface of the blood channel continuously releases (slowly releases) riboflavin used as a photosensitizer into the blood.

[0015] Preferably, the photodynamic therapy device is provided with a blood delivery device, the blood delivery device is provided with a shell, the shell is provided with a blood inlet and a blood outlet, a blood channel is provided in the shell, and both ends of the blood channel are respectively connected to the blood inlet and the blood outlet.

[0016] Preferably, the blood channels are tubular, and there are multiple of them, which are regularly arranged in parallel.

[0017] Preferably, the plurality of blood channels constitute a blood channel unit, the blood channel unit and the shell adopt a detachable structure, and an installation space conforming to the blood channel unit is provided in the shell for embedding the blood channel unit.

[0018] Preferably, the photodynamic therapy device is provided with a lighting device for irradiating light to the blood channel.

[0019] A device for extracorporeal blood storage and / or transportation is provided with one or more blood channels, wherein the inner wall (inner surface) of the blood channel is provided with any double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants disclosed in the present invention.

[0020] Preferably, the blood channel is a regular hexagonal channel (a regular hexagonal channel or a honeycomb channel in cross section), and there are multiple of them, and the multiple blood channels are closely arranged in a honeycomb shape.

[0021] A device housing may be provided to place a plurality of closely arranged blood channels within the device housing.

[0022] A photodynamic therapy device is provided with a blood channel, and at least a portion of the inner wall (inner surface) of the blood channel is provided with any double-layer aqueous polyurethane coating disclosed in the present invention that continuously releases riboflavin and anticoagulants. When extracorporeal blood passes through these blood channels provided with the coating, the coating on the surface of the channel continuously releases riboflavin used as a photosensitizer into the blood.

[0023] For example, the blood delivery device in the photodynamic therapy equipment includes or adopts any device for extracorporeal blood storage and / or transportation disclosed in the present invention, that is, at least a part of the blood delivery device is any device for extracorporeal blood storage and / or transportation disclosed in the present invention, thereby forming a blood channel in the photodynamic therapy equipment provided with the above-mentioned coating.

[0024] The beneficial effects of the present invention are:

[0025] (1) When extracorporeal blood circulation therapy is performed, the double-layer water-based polyurethane coating contacts the blood. The biological enzymes (such as cholesterol esterase, etc.) contained in the blood biodegrade the anionic water-based polyurethane of the outer layer (or the first layer). The riboflavin and anticoagulant drugs obtained by degradation are free in the blood. Riboflavin accumulates in large quantities around tumor cells. After the start of light irradiation, the riboflavin contained in the inner layer (or the second layer) of cationic water-based polyurethane, the undegraded riboflavin in the outer layer, and the free riboflavin obtained by degradation, after light irradiation, produce reactive oxygen species (ROS) that can rapidly inactivate tumor cells in the plasma.

[0026] (2) Due to multiple blood circulation treatments, a small amount of riboflavin will be degraded and separated from the coating. In addition, during each blood circulation, a part of the degradation products of the biological enzyme (the degradation products of the outer layer of anionic waterborne polyurethane) will be returned to the patient's body with the blood. The riboflavin and anticoagulant drugs will continue to decrease. However, due to the riboflavin contained in the difficult-to-biodegrade chain segments of the inner layer of cationic waterborne polyurethane and the slow degradation rate of the outer layer, it can be ensured that before the end of the treatment, the riboflavin carried by the double-layer waterborne polyurethane coating is sufficient for the extracorporeal blood circulation photodynamic therapy. In addition, the high hydrophobicity formed on the inner layer surface and the slow degradation rate of the outer layer also provide a continuous anticoagulant function for the treatment.

[0027] (3) The anionic waterborne polyurethane layer and the cationic waterborne polyurethane layer are connected by electrostatic and anionic-cationic bonding, which can regulate the biodegradation rate of the outer layer of anionic waterborne polyurethane, utilize the biodegradability of the anionic waterborne polyurethane layer to achieve the sustained release of riboflavin and anticoagulant drugs, utilize the high hydrophobicity and self-repairing properties of the cationic waterborne polyurethane layer to meet the requirements of long-term and stable anticoagulant performance in the blood treatment process, and utilize the low surface energy and surface roughness of the polydimethylsiloxane polymer to increase the high hydrophobicity of the inner layer to achieve the anticoagulant purpose of this layer. The combination of anionic and cationic waterborne polyurethanes significantly improves the durability and stability of riboflavin in phototherapy. After the outer layer of anionic waterborne polyurethane is degraded, the basic anticoagulant and phototherapy effects of the inner layer of cationic waterborne polyurethane are maintained by the quadruple hydrogen bonding in the structure.

[0028] (4) During the treatment process, the coating releases riboflavin to inactivate tumor cells, and at the same time, it also releases isothiocyanate compounds. The isothiocyanate compounds are free in the blood and can further inactivate tumor cells, enhance the treatment effect, shorten the treatment time, and reduce the treatment risk. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 It is a structural unit (first half) of the cationic waterborne polyurethane contained in the polymer molecular chain of the double-layer waterborne polyurethane of the present invention;

[0030] Figure 2 It is a structural unit (latter half) of the cationic waterborne polyurethane contained in the polymer molecular chain of the double-layer waterborne polyurethane of the present invention;

[0031] Figure 3 It is a structural unit of anionic waterborne polyurethane contained in the polymer molecular chain of the double-layer waterborne polyurethane of the present invention;

[0032] Figure 4 yes Figure 1 and Figure 2 The structural formula of α1 in;

[0033] Figure 5 yes Figure 3 The structural formula of α2 in ;

[0034] Figure 6 It is a schematic structural diagram of the anionic waterborne polyurethane of the present invention;

[0035] Figure 7 It is a schematic structural diagram of the cationic waterborne polyurethane of the present invention;

[0036] Figure 8 It is a schematic diagram of the process of preparing the double-layer waterborne polyurethane coating of the present invention and its degradation in blood;

[0037] Fig. 9 is a schematic longitudinal section view of an embodiment of a device for extracorporeal blood storage and / or transportation of the present invention;

[0038] Fig.10 yes Fig. 9 Schematic cross-section of the illustrated embodiment. DETAILED DESCRIPTION

[0039] See also Figure 1-Figure 8 The present invention discloses a double-layer waterborne polyurethane coating for sustained release of riboflavin and anticoagulants, comprising an inner and outer layer structure, wherein the inner layer (or the second layer) is a cationic waterborne polyurethane layer, and the outer layer (or the first layer) is an anionic waterborne polyurethane layer. Riboflavin is added to the raw materials of the cationic waterborne polyurethane layer, and riboflavin and anticoagulants are added to the raw materials of the anionic waterborne polyurethane layer.

[0040] The polymer molecular chain of the double-layer waterborne polyurethane contains Figure 1 , Figure 2 and Figure 3 The structural unit shown, wherein n, n1, n2, and n3 are all positive integers greater than 0, α1 is a residue of toluene diisocyanate (TDI), dicyclohexylmethane diisocyanate (HMDI), diphenylmethane diisocyanate (MDI), isophorone diisocyanate (IPDI), or hexamethylene diisocyanate (HDI) without the diisocyanate group, and the structure of α1 is Figure 4 One of the structures shown in FIG. 1 , when α1 is a, it is one of 2,4-TDI, 2,6-TDI or a mixture of the two. α2 is a residue of dicyclohexylmethane diisocyanate (HMDI), isophorone diisocyanate (IPDI) or lysine-diisocyanate (LDI) without the diisocyanate group. The structure of α2 is Figure 5One of the structures shown. Pr1 is the residue structure of polytetramethylene glycol (PTMG), polyethylene glycol (PEG) or polypropylene glycol (PPG) after removing the hydroxyl group. Pr2 is the residue structure of polycarbonate polyol (PCDL), polycaprolactone diol (PCL) or 1,6-hexyl-1,2-ethyl carbonate diol (PCN) after removing the hydroxyl group. β is the residue structure of crosslinking agent castor oil (CO) or trimethylolpropane (TMP) after removing the hydroxyl group.

[0041] The material preparation method of the cationic waterborne polyurethane layer is preferably as follows: adding polyether polyol, cationic hydrophilic chain extender and polydimethylsiloxane into a reaction kettle, introducing nitrogen under stirring, heating to 35-100° C., adding diisocyanate to react for 0.5-15 h, then adding a catalyst and a crosslinking agent to react for 0.5-8 h, then adding a triazine-containing diamine compound and a photosensitizer to react for 0.5-8 h, cooling to 20-40° C., adding a neutralizer to neutralize for 0.5-1 h, cooling to 0-30° C., adding deionized water to rapidly stir and emulsify, removing the solvent, and obtaining a cationic waterborne polyurethane emulsion.

[0042] The polyether polyol is one or a mixture of two or more of polytetramethylene glycol (PTMG), polyethylene glycol (PEG), and polypropylene glycol (PPG), and the molecular weight of the polyol is 1000-3000 g / mol; the cationic hydrophilic chain extender is one or a mixture of N-methyldiethanolamine (MDEA) and N-ethyldiethanolamine (N-EDEA), and the mass content of the hydrophilic chain extender in all the reaction raw materials is 1.5-15wt%; the polydimethylsiloxane is one or a mixture of polydimethylsiloxane with hydroxyl groups at both ends and polydimethylsiloxane with amino groups at both ends, and the molar number is the same as the molar number of the polyether polyol; the diisocyanate is one or a mixture of two or more of toluene diisocyanate (TDI), dicyclohexylmethane diisocyanate (HMDI), diphenylmethane diisocyanate (MDI), isophorone diisocyanate (IPDI), and hexamethylene diisocyanate (HDI). The molar ratio of isocyanate to polyol / chain extender is 1.1-2.0, and the amount of diisocyanate can be flexibly set by the operator; the catalyst is one of stannous octoate and dibutyltin dilaurate or a mixture of two, and the mass ratio of the catalyst to the polyol is 0.1-10wt%; the crosslinking agent is one of castor oil (CO) and trimethylolpropane (TMP) or a mixture of two, and its molar number accounts for 0.5-5% of the molar number of all isocyanate groups; the diamino compound containing triazine is 2,4-diamino-6-undecyl-1,3,5-triazine (DAUTA), Its molar number accounts for 1-30% of the molar number of all isocyanate groups; the photosensitizer is riboflavin (RF), and its molar number is the same as the molar number of isocyanate groups remaining after all raw materials react; the neutralizer is one of acetic acid and hydrochloric acid or a mixture of the two, and its molar number is the same as the molar number of the cationic hydrophilic chain extender; the solvent is acetone or butanone, and the amount used is 1-8 times the total mass of all reaction raw materials. If the solution is relatively viscous, a small amount of solvent can be added; the amount of deionized water used depends on the dispersion of the emulsion and is 1-5 times the total mass of all reaction raw materials.

[0043] The preparation method of the 2,4-diamino-6-undecyl-1,3,5-triazine (a diamine compound containing triazine) is preferably as follows: dicyandiamide (0.15 mol, 12.6 g), dodecanitrile (0.158 mol, 28.65 g), n-butanol (120 mol) and potassium hydroxide (2.66 g) are added into a single-mouth container, nitrogen is introduced (in a nitrogen atmosphere), and the reaction is stirred at 118° C. for 15 hours. After the reaction is completed, a crude reaction mixture is obtained, the crude reaction mixture is filtered, cooled and crystallized, and filtered again to obtain white crystals, the white crystals are washed and purified with n-heptane and distilled water, and a white powdery diamine compound containing triazine, 2,4-diamino-6-undecyl-1,3,5-triazine (DAUTA), is obtained after vacuum drying.

[0044] The single-necked container is preferably a single-necked flask provided with a condenser and a magnetic stirrer.

[0045] The molar amounts of the raw materials of the cationic waterborne polyurethane layer are preferably: 18-28 parts of polyether polyol, 30-38 parts of diisocyanate, 9-13 parts of cationic hydrophilic chain extender, 2-4 parts of riboflavin, 12.9-14.9 parts of polydimethylsiloxane, 0.1 parts of catalyst, 1-2 parts of crosslinking agent, 2-8 parts of diamino compound containing triazine, and 9-13 parts of neutralizer.

[0046] The material preparation method of the anionic waterborne polyurethane layer is preferably as follows: polyester polyol and anionic hydrophilic chain extender are added into a reaction kettle, nitrogen is introduced under stirring, and after heating to 35-100° C., diisothiocyanate is added to react for 0.5-15 h, a catalyst and a photosensitizer are added to react for 0.5-12 h, and then an anticoagulant is added to react for 0.5-8 h, the temperature is lowered to 20-40° C., a neutralizer is added to neutralize for 0.5-1 h, the temperature is lowered to 0-30° C., deionized water is added to rapidly stir and emulsify, and the solvent is removed to obtain an anionic waterborne polyurethane emulsion.

[0047] The polyester polyol is one or a mixture of two or more of polycarbonate polyol (PCDL), polycaprolactone polyol (PCL), and 1,6-hexyl-1,2-ethyl carbonate diol (PCN), and the molecular weight of the polyol is 1000-3000 g / mol; the anionic hydrophilic chain extender is one or a mixture of 2,2-dihydroxymethylbutyric acid (DMBA) and 2,2-dihydroxymethylpropionic acid (DMPA), The hydrophilic chain extender accounts for 1.5-15wt% of the mass content of all the reaction raw materials; the diisocyanate is one of dimethylene diisocyanate and hexamethylene diisocyanate or a mixture of two, and the molar number of the diisocyanate is the same as the molar number of the remaining hydroxyl groups after all the raw materials react; the catalyst is one of stannous octoate and dibutyltin dilaurate or a mixture of two, and the mass ratio of the catalyst to the polyol is 0.1-10wt%; the photosensitizer is riboflavin (RF), and the molar number of the RF is 1-30% of the molar number of all isocyanate groups; the anticoagulant drug is argatroban, and the molar number of the RF is 1-15% of the molar number of all isocyanate groups; the neutralizer is triethylamine; the solvent is acetone or butanone, and the amount used is 1-8 times the total mass of all the reaction raw materials. If the solution is relatively viscous, a small amount of solvent can be added; the amount of deionized water used depends on the dispersion of the emulsion and is 1-5 times the total mass of all the reaction raw materials.

[0048] The preparation method of the diisocyanate is preferably as follows: 10 ml of dimethyl sulfoxide (DMSO) is added to a container (e.g., a clean and dry round-bottom flask), 1 mmol of amine and 1 mmol of carbon disulfide are added and stirred and mixed, 1 mmol of tetrabutylammonium iodide (TBAI) is added and mixed for ten minutes, and then 1 mmol of iodine is slowly added while stirring continuously within ten minutes until the flavin element S appears, the reaction mixture is washed with 2 ml of a 10% sodium thiosulfate aqueous solution, and then washed with 5 ml of distilled water to remove sulfur in the mixture, the organic layer is separated, dried with anhydrous sodium sulfate, filtered, concentrated, and finally purified with a chromatography column (silica gel, ethyl acetate / hexane = 1 / 10) to obtain the diisocyanate.

[0049] The reactor is preferably a reactor equipped with a stirrer and a condenser.

[0050] The raw materials of the anionic waterborne polyurethane layer are preferably used in molar amounts as follows: 36.9-43 parts of polyester polyol, 15-20 parts of diisothiocyanate, 9-13 parts of anionic hydrophilic chain extender, 2-8 parts of riboflavin, 0.1 parts of catalyst, 2-10 parts of argatroban, and 9-13 parts of neutralizer.

[0051] Application of any double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants disclosed in the present invention in extracorporeal blood circulation photodynamic therapy.

[0052] The double-layer water-based polyurethane coating is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and the coating method is preferably: using the different ionic groups contained in the anionic and cationic water-based polyurethane layers, the cationic water-based polyurethane and the anionic water-based polyurethane are sequentially coated on the inner wall surface of the blood channel in the photodynamic therapy device by electrostatic deposition. Specifically, the cationic water-based polyurethane (emulsion) is first coated on the inner wall surface of the blood channel in the photodynamic therapy device, and a cationic water-based polyurethane layer is formed after curing, and then the anionic water-based polyurethane is coated on the surface of the cationic water-based polyurethane layer, and an anionic water-based polyurethane layer is formed after curing. The coating method can be a traditional brush coating method or a dip coating method.

[0053] See also Fig. 9 and Fig.10As an application mode, the above coating can be set in a device for extracorporeal blood storage and / or transportation (referred to as a blood delivery device) for photodynamic therapy equipment or other suitable equipment. The blood delivery device is provided with a housing 1, which is preferably columnar, and is provided with a blood inlet 2 and a blood outlet 3. The blood inlet and the blood outlet are preferably respectively arranged at the axial ends of the housing, and a blood channel 4 is provided in the housing for blood circulation, and the two ends of the blood channel are respectively connected to the blood inlet and the blood outlet.

[0054] The blood channels are preferably tubular in shape and there are multiple of them. The multiple blood channels are regularly arranged in parallel, and adjacent blood channels are tightly attached or fixedly connected. In order to save space and avoid gaps between adjacent blood channels after being tightly attached or fixedly connected, the cross-section of the blood channel can be a regular hexagon.

[0055] The plurality of blood channels constitute a blood channel unit, and the blood channel unit and the housing can be detachable, and the housing is provided with an installation space conforming to the blood channel unit for embedding the blood channel unit. In this arrangement, the blood channel unit can be prepared by using a mold, and after the inner wall surface of each blood channel of the blood channel unit is coated with the double-layer waterborne polyurethane coating, the blood circulation unit can be embedded in the housing.

[0056] The housing may be provided with an openable cover, which is convenient for embedding the blood circulation unit in the housing after opening.

[0057] The photodynamic therapy device is also provided with a lighting device for irradiating light to the blood channel.

[0058] The double-layer aqueous polyurethane coating can also be coated on the wall surface of the blood storage space of an extracorporeal blood storage (short-term storage) device, wherein the extracorporeal blood storage device is provided with an illumination device for illuminating the blood storage space for photodynamic therapy.

[0059] The anionic waterborne polyurethane is used as the outer layer (first layer) of the double-layer waterborne polyurethane coating, and can perform the following functions after coating: a small amount of nitrogen and oxygen atoms contained in the molecular chain are combined with the cationic waterborne polyurethane of the inner layer (second layer) through hydrogen bonding, which is conducive to the adhesion of the first layer to the surface of the second layer.

[0060] The anionic waterborne polyurethane synthetic monomer does not contain a crosslinking agent and is a linear long-chain polymer. The linear structure contains a large number of carbamate bonds, which are easily degraded by biological enzymes, and the degradation products are non-toxic and easily excreted from the body. The anionic waterborne polyurethane synthetic monomer contains rich riboflavin. After the carbamate bonds are degraded by biological enzymes, a part of the riboflavin is free in the blood environment as a molecular monomer. Under the irradiation of light of a certain wavelength, the riboflavin in the coating and the riboflavin free in the blood are transformed from the ground state to the excited state, and reactive oxygen ROS are formed through type I and type II photosensitive reaction mechanisms, thereby achieving an anti-tumor effect. The anticoagulant drug contained in the anionic waterborne polyurethane synthetic monomer is argatroban, which is a direct thrombin inhibitor with the advantages of fast time effect, short action time, low bleeding tendency, and no immunogenicity. After the carbamate bonds of the coating are degraded by biological enzymes, argatroban is dispersed and free in the blood, providing a stable anticoagulant release for the in vitro treatment system. The anionic waterborne polyurethane synthetic monomer also contains isothiocyanate, which is hexamethylene diisothiocyanate. Isothiocyanate belongs to plant-derived isocyanate. On the one hand, it participates in the synthesis process of the coating and provides degradation sites for biological enzymes. On the other hand, isothiocyanate has the function of sterilizing and inactivating tumor cells through various mechanisms, including inducing oxidative stress, inhibiting tumor angiogenesis, inducing cell cycle arrest and apoptosis, etc. When the ester bond of the coating is degraded by biological enzymes, the isothiocyanate group is free in the blood, and its sterilization and tumor inactivation performance enhances the therapeutic effect of extracorporeal blood circulation. The polyester polyol contained in the anionic waterborne polyurethane synthetic monomer is polycaprolactone diol PCL, which contains rich ester bonds and provides a large number of degradation sites for the degradation of biological enzymes, thereby improving the degradation rate of the coating during blood treatment to ensure the release of functional drug monomers such as riboflavin in the molecular chain. The anionic hydrophilic chain extender contained in the anionic waterborne polyurethane synthetic monomer is 2,2-dihydroxymethylbutyric acid, which provides stability for the emulsification process of the waterborne polyurethane prepolymer by increasing the hydrophilicity of the molecular chain, and at the same time provides some anionic groups for the preparation of the subsequent double-layer waterborne polyurethane coating, forming a small amount of ionic bonds with the inner cationic groups, thereby enhancing the adhesion of the coating and ensuring the continuous degradation of the coating during the treatment process.

[0061] Cationic waterborne polyurethane is the inner layer (second layer) of the double-layer waterborne polyurethane coating. After being coated, it can perform the following functions: using the abundant nitrogen, oxygen, and hydrogen atoms in the molecular chain, it forms a large number of hydrogen bonds with the ester bonds on the surface of the blood channel material (preferably polymethyl methacrylate PMMA) of the extracorporeal blood circulation photodynamic therapy device, and closely adheres to the surface of the blood channel. The cationic waterborne polyurethane synthetic monomer contains polydimethylsiloxane, which is hydroxyl-terminated polydimethylsiloxane. When forming a film, the PDMS segment migrates to the surface of the coating. Since the segment contains a large number of Si-O-Si groups, it has low surface energy. At the same time, the migrated PDMS segment also increases the roughness of the coating surface, so it has high hydrophobicity and can resist the nonspecific adhesion of proteins and platelets to prevent the phenomenon of blood coagulation blocking the pipeline during the blood circulation process. The crosslinking agent used in the cationic waterborne polyurethane synthetic monomer is castor oil, which gives the system a certain degree of crosslinking density, thereby preventing the destruction of the carbamate group by biological enzymes during the treatment process. Cationic waterborne polyurethane synthetic monomers contain a small amount of riboflavin. Since the riboflavin contained in the outer layer is continuously consumed during extracorporeal blood therapy, the coating is used to protect the loss of the outer layer. When the coating is exposed to the blood, the riboflavin in the coating continues to provide active oxygen for treatment to inactivate tumor cells. The triazine-containing diamine compound contained in the cationic waterborne polyurethane synthetic monomer is 2,4-diamino-6-undecyl-1,3,5-triazine, which provides a large number of hydrogen bonds for the molecular structure of the polymer. The strong hydrogen bonding increases the crosslinking density of the waterborne polyurethane, further preventing the biological enzymes in the blood from destroying the carbamate groups. At the same time, the dynamic crosslinking system formed by hydrogen bonding gives the coating a self-repairing function. When the coating is damaged due to various reasons, it will self-repair to ensure the integrity of the coating surface. In addition, a large amount of nitrogen and hydrogen in the system form stable hydrogen bonds with the ester groups on the surface of the PMMA material, enhancing the adhesion of the coating to the substrate. The -C in the monomer structure of this layer 11 H 23 The groups migrate to the coating surface when the coating dries and forms a film, and the hydrophobicity of the long carbon chain is used to further enhance the surface anticoagulant effect of the coating. The cationic waterborne polyurethane synthetic monomer contains a polyether polyol, polyethylene glycol PEG, which is used as the soft segment of the waterborne polyurethane to reduce the interaction between the device and blood components, effectively reduce the adhesion of plasma proteins and platelets, thereby reducing blood activation and thrombosis, and enhancing the biocompatibility and surface anticoagulation of the coating. The cationic hydrophilic chain extender contained in the cationic waterborne polyurethane synthetic monomer is N-methyldiethanolamine MDEA, which provides stability for the prepolymer emulsification process of the waterborne polyurethane by increasing the hydrophilicity of the molecular chain, and at the same time provides some cationic groups for the subsequent preparation of a double-layer waterborne polyurethane coating.

[0062] The biodegradable principle of anionic waterborne polyurethane is:

[0063] "Biodegradation" of a material can be defined as the chemical breakdown of a material into smaller components or low molecular weight products mediated by any component of the physiological environment, which are then processed, absorbed or eliminated by the body. In vivo, polyurethane coatings come into contact with body fluids in the biological environment and are degraded by enzymes.

[0064] The principles of biodegradation include hydrolytic degradation and oxidative degradation.

[0065] The rate of hydrolysis of biodegradation is affected by its chemical structure and the biological environment in which it is located, and can be catalyzed by acid, base or enzyme. In general, heterochain polymers, especially those containing O and N in the main chain, are easily hydrolyzed, for example, esters, thioesters, carbonates, carbamates, anhydrides, amides, etc. The hydrolyzable groups usually contain C=O bonds connected to heteroatoms such as oxygen, nitrogen or sulfur. These groups provide cleavage sites on the polymer backbone, which makes the coating susceptible to hydrolysis and subsequent biodegradation. At the same time, the abundant hydrolases (such as phosphatases, esterases, and proteases) contained in the physiological environment contribute greatly to the hydrolysis of the coating, which has an accelerating effect on the degradation of polyesters and polyamides.

[0066] Oxidative degradation is a biologically relevant process that directly induces the degradation of polymers through free radicals generated by chemical and enzymatic action. The oxidative degradation process involves free radical reaction mechanisms that target bonds substituted by aliphatic chains and aromatic cycles, such as ethers, phenols, alcohols, aldehydes, amines or carbons. Oxidative degradation is always triggered by immune responses in the body, where activated macrophages initiate oxidation of the coating surface by releasing reactive oxygen species (ROS) around the coating, which are converted into hydroxyl radicals in the presence of transition metal catalysts such as iron.

[0067] The degradation mechanism of the anionic waterborne polyurethane layer is mainly hydrolysis, supplemented by oxidation.

[0068] It is important to point out that all of the above-mentioned degradation phenomena in vivo are closely related to the surface organization of the polyurethane coating. In polyurethane-based materials, the microphase separation process leads to the formation of a dual microphase structure with regions rich in soft and hard segments. Due to the mobility of the soft segments, the surface composition of the segmented polyurethanes changes. When the environment is polar (such as water or blood), the polyurethane will have a higher proportion of polar hard segments at the interface, while when the environment is non-polar (such as air or vacuum), there will be more non-polar soft segments on the surface. This special behavior of polyurethane is of great significance, so the degradation reaction is largely determined by the surface composition of the material.

[0069] Existing studies have shown that enzymes such as cholesterol esterase prefer to degrade ester bonds adjacent to the hard segment rather than catalyzing the hydrolysis of carbamates in the hard segment to produce diamine small molecules.

[0070] Degradable polyurethanes are often made from diisocyanates, such as lysine-diisocyanate (LDI), hexamethylene diisocyanate (HMDI) and 1,4-diisocyanatobutane, and their final degradation products are non-toxic. Polyurethane soft segments are usually used to change the degradation rate, including polylactide or polyglycolic acid, polycaprolactone (PCL) and polyethylene oxide (PEO).

[0071] The following examples further illustrate the preparation method and application of the double-layer waterborne polyurethane coating of the present invention, but are not intended to limit the scope of protection of the present invention. Unless otherwise specified, the polyols, hydrophilic chain extenders, and crosslinking agents involved are vacuum dried before use. The R value is the molar ratio of cyanate groups (-NCO) to hydroxyl groups (-OH), i.e., the isocyanate index.

[0072] Embodiment 1:

[0073] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 50°C, add isophorone diisocyanate IPDI and stir and mix for 30 minutes; add 1wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 10 hours; add a crosslinker to react for 4 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 4 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 6 days to obtain a cationic waterborne polyurethane coating. Among them, the R value is 1.1.

[0074] The mass content of MDEA is 3wt%; the molar ratio of hydroxyl groups of PEG2000 and PDMS is 1:1; the crosslinking agent is castor oil, and its mass content is 5wt%; the mass fraction of DAUTA is 10wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 5 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0075] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 50°C, add hexamethylene diisocyanate and stir and mix for 30 minutes; add 1wt% DBTDL and acetone to react for 10 hours; add riboflavin to react for 4 hours; add argatroban to react for 4 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 6 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.1.

[0076] The mass content of DMBA is 3wt%; the mass content of argatroban is 10wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 5 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0077] Embodiment 2:

[0078] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 5 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 2 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a cationic waterborne polyurethane coating. Among them, the R value is 1.2.

[0079] The mass content of MDEA is 3wt%; the molar ratio of hydroxyl groups of PEG2000 and PDMS is 1:2; the crosslinking agent is castor oil, and its mass content is 5wt%; the mass fraction of DAUTA is 10wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 5 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0080] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 3wt% DBTDL and acetone to react for 5 hours; add riboflavin to react for 2 hours; add argatroban to react for 2 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.2.

[0081] The mass content of DMBA is 3wt%; the mass content of argatroban is 8wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 5 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0082] Embodiment 3:

[0083] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0084] The mass content of MDEA is 4wt%; the molar ratio of hydroxyl groups of PEG2000 and PDMS is 1:3; the crosslinking agent is castor oil, and its mass content is 5wt%; the mass fraction of DAUTA is 12wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0085] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 3wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0086] The mass content of DMBA is 4wt%; the mass content of argatroban is 10wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0087] Embodiment 4:

[0088] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PTMG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0089] The mass content of MDEA is 1.5wt%; the molar ratio of hydroxyl groups of PTMG2000 and PDMS is 1:1; the crosslinking agent is castor oil, and its mass content is 0.5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0090] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCDL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 3wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0091] The mass content of DMBA is 1.5wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0092] Embodiment 5:

[0093] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PTMG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0094] The mass content of MDEA is 8wt%; the molar ratio of hydroxyl groups of PTMG2000 and PDMS is 1:2; the crosslinking agent is castor oil, and its mass content is 5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0095] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCDL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 3wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0096] The mass content of DMBA is 8wt%; the mass content of argatroban is 1wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0097] Embodiment 6:

[0098] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PTMG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0099] The mass content of MDEA is 15wt%; the molar ratio of hydroxyl groups of PTMG1000 and PDMS is 1:3; the crosslinking agent is castor oil, and its mass content is 2.5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0100] In a four-mouth reactor equipped with stirring and condenser, add polyester polyol PCDL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisothiocyanate and stir and mix for 10 minutes; add 5wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0101] The mass content of DMBA is 8wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0102] Embodiment 7:

[0103] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PPG2000, cationic hydrophilic chain extender N-DEDA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0104] The mass content of N-DEDA is 8wt%; the molar ratio of hydroxyl groups of PPG1000 and PDMS is 1:1; the crosslinking agent is castor oil, and its mass content is 2.5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of residual isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0105] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCN1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 10wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.1.

[0106] The mass content of DMPA is 1.5wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0107] Embodiment 8:

[0108] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PPG2000, cationic hydrophilic chain extender N-DEDA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add diisocyanate HMDI and stir and mix for 10 minutes; add 5wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.5.

[0109] The mass content of N-DEDA is 1.5wt%; the molar ratio of hydroxyl groups of PPG2000 and PDMS is 1:2; the crosslinking agent is castor oil, and its mass content is 2.5wt%; the mass fraction of DAUTA is 30wt%; the molar number of riboflavin is the molar number of residual isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0110] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCN1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisothiocyanate and stir and mix for 10 minutes; add 10wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.5.

[0111] The mass content of DMPA is 1.5wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0112] Embodiment 9:

[0113] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PPG2000, cationic hydrophilic chain extender N-DEDA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 10wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 2.0.

[0114] The mass content of N-DEDA is 8wt%; the molar ratio of hydroxyl groups of PEG1000 and PDMS is 1:3; the crosslinking agent is castor oil, and its mass content is 5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of residual isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0115] In a four-mouth reactor equipped with stirring and condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 1wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 2.0.

[0116] The mass content of DMPA is 15wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0117] Embodiment 10:

[0118] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG1000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add diisocyanate HMDI and stir and mix for 10 minutes; add 1wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinker TMP to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.1.

[0119] The mass content of MDEA is 8wt%; the molar ratio of hydroxyl groups of PEG1000 and PDMS is 1:1; the crosslinking agent is TMP, and its mass content is 2.5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0120] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCL2000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 5wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.1.

[0121] The mass content of DMPA is 1.5wt%; the mass content of argatroban is 1wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0122] Embodiment 11:

[0123] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG1000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add diisocyanate MDI and stir and mix for 10 minutes; add 5wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinker TMP to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.5.

[0124] The mass content of MDEA is 8wt%; the molar ratio of hydroxyl groups of PEG1000 and PDMS is 1:2; the crosslinking agent is TMP, and its mass content is 2.5wt%; the mass fraction of DAUTA is 15wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0125] In a four-mouth reactor equipped with stirring and condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisothiocyanate and stir and mix for 10 minutes; add 5wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.5.

[0126] The mass content of DMPA is 8wt%; the mass content of argatroban is 7.5wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0127] Embodiment 12:

[0128] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG1000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add diisocyanate HMDI and stir and mix for 10 minutes; add 15wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinker TMP to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 2.0.

[0129] The mass content of MDEA is 15wt%; the molar ratio of hydroxyl groups of PEG1000 and PDMS is 1:3; the crosslinking agent is TMP, and its mass content is 5wt%; the mass fraction of DAUTA is 30wt%; the molar number of riboflavin is the molar number of the remaining isocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0130] In a four-mouth reactor equipped with stirring and condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 15wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0131] The mass content of DMPA is 15wt%; the mass content of argatroban is 15wt%; the molar number of riboflavin is the molar number of the remaining isothiocyanate groups; the amount of acetone used is 6 times the total mass of all reaction raw materials, and the amount of deionized water used depends on the dispersion of the emulsion.

[0132] Embodiment 13:

[0133] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PEG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 50°C, add isophorone diisocyanate IPDI and stir and mix for 30 minutes; add 1wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 10 hours; add a crosslinker to react for 4 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 4 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 6 days to obtain a cationic waterborne polyurethane coating. Among them, the R value is 1.1.

[0134] In terms of molar parts, 18 parts of polyether polyol, 34 parts of isophorone diisocyanate, 13 parts of cationic hydrophilic chain extender, 2 parts of riboflavin, 13.9 parts of polydimethylsiloxane, 0.1 parts of catalyst, 2 parts of crosslinking agent, 2 parts of 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA, 11 parts of acetic acid, and the amount of deionized water depends on the dispersion of the emulsion.

[0135] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 50°C, add hexamethylene diisocyanate and stir and mix for 30 minutes; add 1wt% DBTDL and acetone to react for 10 hours; add riboflavin to react for 4 hours; add argatroban to react for 4 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 6 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.1.

[0136] In terms of molar parts, the polyester polyol is 36.9 parts, the hexamethylene diisocyanate is 18 parts, the anionic hydrophilic chain extender is 13 parts, the riboflavin is 2 parts, the catalyst is 0.1 parts, the argatroban is 6 parts, the triethylamine is 13 parts, and the amount of deionized water used depends on the dispersion of the emulsion.

[0137] Embodiment 14:

[0138] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PTMG2000, cationic hydrophilic chain extender MDEA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0139] In terms of molar parts, there are 23 parts of polyether polyol, 38 parts of isophorone diisocyanate, 9 parts of cationic hydrophilic chain extender, 3 parts of riboflavin, 14.9 parts of polydimethylsiloxane, 0.1 parts of catalyst, 1 part of crosslinking agent, 5 parts of 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA, 13 parts of acetic acid, and the amount of deionized water depends on the dispersion of the emulsion.

[0140] In a four-mouth reactor equipped with stirring and condenser, add polyester polyol PCDL1000 and anionic hydrophilic chain extender DMBA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisothiocyanate and stir and mix for 10 minutes; add 5wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.3.

[0141] In terms of molar proportions, the polyester polyol is 40 parts, the hexamethylene diisocyanate is 20 parts, the anionic hydrophilic chain extender is 9 parts, the riboflavin is 5 parts, the catalyst is 0.1 parts, the argatroban is 10 parts, the triethylamine is 9 parts, and the amount of deionized water used depends on the dispersion of the emulsion.

[0142] Embodiment 15:

[0143] In a four-mouth reactor equipped with a stirrer and a condenser, add polyether polyol PPG2000, cationic hydrophilic chain extender N-DEDA, and polydimethylsiloxane PDMS, start stirring and introduce N2. Heat to 70°C, add isophorone diisocyanate IPDI and stir and mix for 10 minutes; add 3wt% dibutyltin dilaurate DBTAL (mass ratio to polyol) and acetone to react for 7 hours; add crosslinking agent castor oil to react for 2 hours; add 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA and riboflavin to react for 3 hours. Cool down to room temperature, add acetic acid to neutralize; cool down and add deionized water to quickly stir and emulsify, evaporate and remove the solvent to obtain a cationic waterborne polyurethane emulsion or dispersion. The cationic waterborne polyurethane emulsion or dispersion is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and cured at room temperature for 5 days to obtain a polyurethane coating. Among them, the R value is 1.3.

[0144] In terms of molar parts, there are 28 parts of polyether polyol, 30 parts of isophorone diisocyanate, 11 parts of cationic hydrophilic chain extender, 4 parts of riboflavin, 12.9 parts of polydimethylsiloxane, 0.1 parts of catalyst, 1.5 parts of crosslinking agent, 8 parts of 2,4-diamino-6-undecyl-1,3,5-triazine DAUTA, 9 parts of acetic acid, and the amount of deionized water depends on the dispersion of the emulsion.

[0145] In a four-mouth reactor equipped with a stirrer and a condenser, add polyester polyol PCN1000 and anionic hydrophilic chain extender DMPA, start stirring and introduce N2. Heat to 70°C, add hexamethylene diisocyanate and stir and mix for 10 minutes; add 10wt% DBTDL and acetone to react for 7 hours; add riboflavin to react for 3 hours; add argatroban to react for 3 hours. Cool down to room temperature, add triethylamine to neutralize; cool down and add deionized water to stir and emulsify quickly, evaporate and remove the solvent to obtain anionic waterborne polyurethane emulsion or dispersion. Coat the anionic waterborne polyurethane emulsion or dispersion on the surface of the prepared cationic waterborne polyurethane layer, and cure at room temperature for 5 days to obtain a double-layer waterborne polyurethane coating. The R value is 1.1.

[0146] In terms of molar proportions, the polyester polyol is 43 parts, the hexamethylene diisocyanate is 15 parts, the anionic hydrophilic chain extender is 11 parts, the riboflavin is 8 parts, the catalyst is 0.1 parts, the argatroban is 2 parts, the triethylamine is 11 parts, and the amount of deionized water used depends on the dispersion of the emulsion.

[0147] Unless otherwise specified or one preferred or optional technical means is a further limitation of another technical means, all preferred and optional technical means disclosed in the present invention can be arbitrarily combined to form several different technical solutions.

Claims

1. A double-layer waterborne polyurethane coating for sustained release of riboflavin and anticoagulants, characterized in that The invention comprises an inner and outer two-layer structure, wherein the inner layer is a cationic waterborne polyurethane layer, and the outer layer is an anionic waterborne polyurethane layer. Riboflavin is added to the raw materials of the cationic waterborne polyurethane layer, and riboflavin and anticoagulant drugs are added to the raw materials of the anionic waterborne polyurethane layer. The coating for forming the cationic waterborne polyurethane layer is prepared by the following method: polyether polyol, cationic hydrophilic chain extender and polydimethylsiloxane are added to a reaction kettle, nitrogen is introduced under stirring, and after heating to 35-100° C., diisocyanate, catalyst and crosslinking agent, diamino compound containing triazine and photosensitizer are added in sequence for reaction, the temperature is lowered to 20-40° C., and a neutralizing agent is added. Neutralization, cooling to 0-30°C, adding deionized water for stirring and emulsification, removing the solvent to obtain a cationic waterborne polyurethane emulsion, wherein the photosensitizer is riboflavin. The coating for forming the anionic waterborne polyurethane layer is prepared by the following method: adding polyester polyol and anionic hydrophilic chain extender into a reaction kettle, introducing nitrogen under stirring, heating to 35-100°C, adding diisothiocyanate, catalyst, photosensitizer and anticoagulant in sequence for reaction, cooling to 20-40°C, adding a neutralizer for neutralization, cooling to 0-30°C, adding deionized water for stirring and emulsification, removing the solvent to obtain anionic waterborne polyurethane emulsion, wherein the photosensitizer is riboflavin.

2. The double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as claimed in claim 1, characterized in that The polyether polyol is any one of polytetramethylene glycol, polyethylene glycol and polypropylene glycol or any combination of any two; the cationic hydrophilic chain extender is any one of N-methyldiethanolamine and N-ethyldiethanolamine or any combination of the two; the polydimethylsiloxane is any one of polydimethylsiloxane with hydroxyl groups at both ends and polydimethylsiloxane with amino groups at both ends or any combination of the two; the diisocyanate is toluene diisocyanate, dicyclohexylmethane diisocyanate, diphenylmethane diisocyanate, Any one of isophorone diisocyanate and hexamethylene diisocyanate or any combination of any two; the catalyst is any one of stannous octoate and dibutyltin dilaurate or any combination of these two; the cross-linking agent is any one of castor oil and trimethylolpropane or any combination of these two; the diamino compound containing triazine is 2,4-diamino-6-undecyl-1,3,5-triazine; the neutralizing agent is any one of acetic acid and hydrochloric acid or any combination of these two; the solvent is acetone or butanone.

3. The double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as claimed in claim 1, characterized in that The polyester polyol is any one of polycarbonate polyol, polycaprolactone polyol and 1,6-hexyl-1,2-ethyl carbonate diol or any combination of any two; the anionic hydrophilic chain extender is any one of 2,2-dihydroxymethylbutyric acid and 2,2-dihydroxymethylpropionic acid or any combination of these two; the diisocyanate is any one of dimethylene diisocyanate and hexamethylene diisocyanate or any combination of these two; the catalyst is any one of stannous octoate and dibutyltin dilaurate or any combination of these two; the anticoagulant drug is argatroban; the neutralizer is triethylamine; and the solvent is acetone or butanone.

4. Use of the double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants according to any one of claims 1 to 3 in an extracorporeal blood circulation photodynamic therapy device.

5. Use of the double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as claimed in claim 4 in an extracorporeal blood circulation photodynamic therapy device, characterized in that A double-layer waterborne polyurethane coating is coated on the inner wall surface of a blood channel in a photodynamic therapy device.

6. Use of the double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as claimed in claim 5 in an extracorporeal blood circulation photodynamic therapy device, characterized in that Cationic waterborne polyurethane is coated on the inner wall surface of the blood channel in the photodynamic therapy device, and a cationic waterborne polyurethane layer is formed after curing. Anionic waterborne polyurethane is then coated on the surface of the cationic waterborne polyurethane layer, and anionic waterborne polyurethane is formed after curing.

7. A device for extracorporeal blood storage and / or transport, provided with one or more blood channels, characterized in that The inner wall of the blood channel is provided with a double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as claimed in any one of claims 1 to 3.

8. Photodynamic therapy device, provided with a blood channel, characterized in that At least part of the inner wall of the blood channel is provided with a double-layer aqueous polyurethane coating for sustained release of riboflavin and anticoagulants as described in any one of claims 1 to 3.

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