WO2023125758A1

WO2023125758A1 - Multifunctional layer structure, preparation method therefor and product thereof

Info

Publication number: WO2023125758A1
Application number: PCT/CN2022/143199
Authority: WO
Inventors: 唐增超; 杜慧
Original assignee: 江苏百赛飞生物科技有限公司
Priority date: 2021-12-31
Filing date: 2022-12-29
Publication date: 2023-07-06
Also published as: CN116410503A

Abstract

The present invention relates to a multifunctional layer structure, a preparation method therefor and a product thereof. The multifunctional layer structure comprises a polyelectrolyte multilayer film and a functional layer located on one side of the polyelectrolyte multilayer film. The polyelectrolyte multilayer film contains a first host unit or a first guest unit, and the functional layer contains a second guest unit or a second host unit, corresponding to the first host unit or the first guest unit. The functional layer is linked to the polyelectrolyte multilayer film by means of host-guest interaction. The polyelectrolyte multilayer film contains at least one first functional group and the functional layer contains at least one second functional group, the first functional group and the second functional group being different in functions. The multifunctional layer structure has multiple functions; and the first functional group and the second functional group are located inside the polyelectrolyte multilayer film and the functional layer respectively, so that even if functional groups on the surface fall off under external force, the functional groups inside the structure can still perform corresponding functions, and the durability of the corresponding functions is thereby kept.

Description

Multifunctional layer structure and its preparation method and product

technical field

The invention relates to the technical field of biomedical functional polymer materials, in particular to a multifunctional layer structure and its preparation method and product.

Background technique

It is of great significance to construct a multifunctional layer structure on the surface of the substrate. The traditional method of building a layer structure on the surface of a substrate is the layer-by-layer assembly technology. Specifically, the layer-by-layer assembly technology is mainly based on electrostatic interactions to adsorb alternate layers of polymers with different charges on the surface of the substrate. In the process of layer-by-layer assembly, adamantane unit (Ada) is introduced. After complete assembly, it is soaked in the solution of biofunctional molecules grafted with cyclodextrin (β-CD) in the last step, and adamantane and cyclodextrin pass through The host-guest interaction realizes the process of surface functionalization. In addition, cyclodextrin derivatives with different functions can also be post-modified to achieve functionalization of the layer structure. However, in the traditional preparation method of layer structure, on the one hand, the electrostatic assembly only plays the role of assembly, and cannot maximize the function of the layer structure; on the other hand, the layer structure obtained by the traditional preparation method is The functional groups located on the surface are easily affected by external forces and fall off, resulting in poor use of the layer structure.

Contents of the invention

Based on this, it is necessary to provide a multi-functional layer structure and its preparation method and product for the problem of how to realize the multi-function of the layer structure and maintain the persistence of the function.

A multifunctional layer structure, the multifunctional layer structure includes a polyelectrolyte multilayer film and a functional layer located on one side of the polyelectrolyte multilayer film, the polyelectrolyte multilayer film contains a first main body unit or a first A guest unit, the functional layer contains a second guest unit or a second host unit corresponding to the first host unit or the first guest unit, and the functional layer and the polyelectrolyte multilayer film pass through the host-guest unit role connection;

The polyelectrolyte multilayer film contains at least one first functional group, the functional layer contains at least one second functional group, and the first functional group and the second functional group The functions are different.

In the above multifunctional layer structure, on the one hand, because it contains at least one first functional group and at least one second functional group, and the functions of the first functional group and the second functional group are different, the multifunctional layer The structure has multiple functions; on the other hand, the first functional group and the second functional group are respectively located in the polyelectrolyte multilayer film and the functional layer. The group can still exert its corresponding function, thereby maintaining the persistence of the corresponding function.

In a feasible implementation manner, the first functional group and the second functional group are independently selected from at least one of biologically active groups, antibacterial groups and antifouling groups.

In a feasible implementation, the bioactive group is obtained based on a bioactive molecule selected from the group consisting of heparin, hirudin, lysine, polylysine, lysine derivatives, heparins, at least one of antiplatelet agents, plasminogen activators, plasminogen, biotin, and avidin;

The antibacterial group is selected from at least one of quaternary ammonium salt group, bisquat group, imidazole group and phenolic group;

The antifouling group is at least one selected from polyethylene glycol groups, polyvinyl alcohol groups, polyvinylpyrrolidone groups and zwitterionic groups.

In a feasible implementation, the polyelectrolyte multilayer film includes at least one cationic polyelectrolyte layer and at least one anionic polyelectrolyte layer alternately stacked;

The cationic polyelectrolyte layer includes a cationic polyelectrolyte obtained by participating in the polymerization of at least one cationic electrolyte monomer; the anionic polyelectrolyte layer includes an anionic polyelectrolyte obtained by participating in the polymerization of at least one anionic electrolyte monomer;

The main chain or branch of the cationic polyelectrolyte contains the first host unit or the first guest unit; or the main chain or branch of the anionic polyelectrolyte contains the first host unit or the first guest unit;

The first functional group is located on the main chain or branch chain of the cationic polyelectrolyte, or on the main chain or branch chain of the anionic polyelectrolyte.

In a feasible implementation, the cationic electrolyte monomer is selected from at least one of lysine, lysine derivatives, polyethyleneimine and chitosan;

The anion electrolyte monomer is at least A sort of.

In a feasible implementation manner, the second functional group is grafted on the second guest unit or the second host unit.

In a feasible implementation manner, the first host unit and the second host unit are respectively obtained based on a first host molecule and a second host molecule, and the first host molecule and the second host molecule are independently selected from β-cyclodextrin, β-cyclodextrin derivatives, α-cyclodextrin, α-cyclodextrin derivatives, γ-cyclodextrin, γ-cyclodextrin derivatives, cucurbituril, cucurbituril derivatives, At least one of crown ether, crown ether derivative, calixarene, calixarene derivative, pillar arene and pillar arene derivative;

The first guest unit and the second guest unit are obtained based on the first guest molecule and the second guest molecule respectively, and the first guest molecule and the second guest molecule are independently selected from adamantane, adamantane derivatives, At least one of azobenzene, azobenzene derivatives, ferrocene, ferrocene derivatives, cholesterol and cholesterol derivatives.

The present invention also provides a preparation method of a multifunctional layer structure, comprising the steps of:

A polyelectrolyte multilayer film is formed on the surface of the substrate, and the polyelectrolyte multilayer film contains a first host unit or a first guest unit; and

A functional layer is formed on the surface of the polyelectrolyte multilayer film, the functional layer contains a second guest unit or a second host unit corresponding to the first host unit or the first guest unit, the functional layer Connecting with the polyelectrolyte multilayer film through host-guest interaction to obtain a multifunctional layer structure;

Wherein, the polyelectrolyte multilayer film contains at least one first functional group, the functional layer contains at least one second functional group, and the first functional group and the second functional group Groups have different functions.

The preparation method of the above-mentioned multi-functional layer structure of the present invention has a simple process, and the prepared layer structure not only has multi-functions, but also can maintain the persistence of functions.

In a feasible implementation, the operation of forming a polyelectrolyte multilayer film on the surface of the substrate is as follows: at least one cationic polyelectrolyte layer and at least one anionic polyelectrolyte layer are alternately formed on the surface of the substrate by layer-by-layer assembly. On the surface, a polyelectrolyte multilayer film was obtained.

In a feasible implementation, the operation of forming a polyelectrolyte multilayer film on the surface of the substrate is:

copolymerizing the first guest molecule with a cationic electrolyte monomer to obtain a cationic polyelectrolyte; copolymerizing an anionic electrolyte monomer with a hydrophilic monomer to obtain an anionic polyelectrolyte; and

The cationic polyelectrolyte and the anionic polyelectrolyte are respectively formulated into a cationic polyelectrolyte solution and an anionic polyelectrolyte solution, and then the cationic polyelectrolyte solution and the anionic polyelectrolyte solution are alternately applied to the surface of the substrate to obtain a layer The cationic polyelectrolyte layer and the anionic polyelectrolyte layer assembled in layers, namely the polyelectrolyte multilayer membrane.

In addition, the present invention also provides a product, which is characterized in that it includes a substrate and any of the above-mentioned multifunctional layer structures, and the multifunctional layer structure is provided on the substrate.

The above-mentioned article of the present invention has multiple functions and can maintain the durability of the functions.

In a feasible implementation manner, the substrate is a medical device.

Description of drawings

Fig. 1 (a) is the proton nuclear magnetic spectrum (1HNMR) figure of monomer 1-Adama prepared in embodiment 3;

Fig. 1 (b) is the proton nuclear magnetic spectrum (1HNMR) figure of the monomer Lys (P) prepared in embodiment 3;

Fig. 2 is the infrared spectrogram of the β-CD-PEI that embodiment 3 prepares;

Fig. 3 is the polyelectrolyte multilayer membrane that step S4 step 1) makes in embodiment 3 and the multifunctional layer structure that step 2) makes, and the PVC sheet of comparative example 1, the PVC sheet after surface hydroxylation Water contact angle test results;

Fig. 4 is the toluidine blue dyeing result of the multifunctional layer structure that embodiment 3 makes and the PVC sheet of comparative example 1;

Fig. 5 is the protein adsorption test result of the multifunctional layered junction that embodiment 3 makes and the PVC sheet of comparative example 1;

Fig. 6 is the fibrinolytic performance test result of the multifunctional layer structure that embodiment 5 makes and the PVC sheet of comparative example 1;

Fig. 7 is the function durability test result of the multifunctional layer structure prepared in Example 4 and the multifunctional layer structure prepared in Comparative Example 2.

Detailed ways

In order to make the above objects, features and advantages of the present invention more comprehensible, specific implementations of the present invention will be described in detail below in conjunction with the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, the present invention can be implemented in many other ways different from those described here, and those skilled in the art can make similar improvements without departing from the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field of the invention. The terms used herein in the description of the present invention are for the purpose of describing specific embodiments only, and are not intended to limit the present invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

The term "polyelectrolyte multilayer membrane" in the present invention refers to a membrane having at least one "bilayer" of deposited anionic and cationic polyelectrolyte layers. For example, there may be one, two, three, four, five or more.

The term "host-guest interaction" in the present invention refers to the process in which a host and a guest selectively combine through non-covalent interactions to form supramolecules with certain specific functions under the conditions of structural complementarity and energy matching.

The term "monomer" in the present invention means any chemical substance that can be represented by a chemical formula having a polymerizable group that can be polymerized into oligomers or polymers to increase molecular weight.

In the present invention, the term "structural unit" refers to the residue of a monomer after polymerization, that is, a polymerized monomer or a monomer in a polymerized form, also referred to as a "polymerized unit".

In the present invention, the term "polymer" refers to a molecule containing two or more repeating units. Specifically, a polymer can be formed from two or more identical or different monomers. When used in the present invention, the The term also includes oligomers or prepolymers.

The term "salt" in the present invention refers to any and all salts, including pharmaceutically acceptable salts.

The multifunctional layer structure in one embodiment of the present invention comprises a polyelectrolyte multilayer film and a functional layer located on one side of the polyelectrolyte multilayer film, the polyelectrolyte multilayer film contains a first host unit or a first guest unit, and the functional layer contains The second guest unit or the second host unit corresponding to the first host unit or the first guest unit, the functional layer and the polyelectrolyte multilayer film are connected through host-guest interaction. The polyelectrolyte multilayer film contains at least one first functional group, and the functional layer contains at least one second functional group, and the functions of the first functional group and the second functional group are different.

In the above embodiment, when the polyelectrolyte multilayer film contains the first host unit, the functional layer contains the second guest unit corresponding to the first host unit; correspondingly, when the polyelectrolyte multilayer film contains the first guest unit , the functional layer contains a second host unit corresponding to the first guest unit. Therefore, the functional layer and the polyelectrolyte multilayer film can be connected through host-guest interaction.

In the above embodiment, the different functions of the first functional group and the second functional group refer to that the respective functions of the first functional group and the second functional group are different, for example, the first functional group has anti- One of the functions of coagulation, antibacterial, anti-fouling, lubrication, etc., and the second functional group has another of the functions of anti-coagulation, antibacterial, anti-fouling, and lubrication. In some cases, two groups are different but have the same function, for example, a heparin group and a hirudin group, both of which are anticoagulant, should not be classified as the first functional group and the second functional group of the present invention. functional group.

In addition, it should be noted that when the polyelectrolyte multilayer film contains two or more first functional groups, the functions of the two or more first functional groups may be the same, or may be different. Similarly, when the functional layer contains two or more second functional groups, the functions of the two or more second functional groups may be the same or different.

In the above embodiment, the first functional group and the second functional group make the multifunctional layer structure have multiple functions, and since the first functional group and the second functional group are located in the polyelectrolyte multilayer film and the functional layer respectively , even if the functional groups on the surface fall off due to external force, the functional groups on the inside can still perform their corresponding functions, thus maintaining the persistence of the corresponding functions.

In a feasible implementation manner, the first functional group and the second functional group are independently selected from at least one of biologically active groups, antibacterial groups and antifouling groups. Wherein, the biologically active group refers to a group with biological activity, and the biologically active group further includes a biological recognition group, an anticoagulant group and a fibrinolytic group. The biorecognition group refers to a group with a biorecognition function, the anticoagulant group refers to a group with an anticoagulant function, and the fibrinolytic group refers to a group with a fibrinolytic function. Wherein, the antibacterial group refers to a group with antibacterial function. The antifouling group refers to a group having an antifouling function.

In a feasible implementation, the bioactive group is obtained based on a bioactive molecule selected from the group consisting of heparin, hirudin, lysine, polylysine, lysine derivatives, heparinoids, antiplatelet agents, At least one of plasminogen activator, plasminogen, biotin and avidin; the antibacterial group is selected from quaternary ammonium salt group, bisquat group, imidazole group and phenolic group At least one of them; the antifouling group is selected from at least one of polyethylene glycol groups, polyvinyl alcohol groups, polyvinylpyrrolidone groups and zwitterionic groups. Among the bioactive molecules mentioned above, heparin, hirudin, lysine, polylysine, lysine derivatives, heparinoids, and antiplatelet agents are anticoagulant molecules, and lysine, polylysine, The lysine derivative can also serve as a fibrinolytic molecule, and the fibrinolytic molecule can also be a plasminogen activator or plasminogen. In addition, biotin and avidin are biorecognition molecules. It should be noted that the biologically active group can also be other proteins or polypeptides with biological functions.

In a feasible implementation, the polyelectrolyte multilayer film includes at least one cationic polyelectrolyte layer and at least one anionic polyelectrolyte layer alternately stacked; the cationic polyelectrolyte layer includes at least one cationic electrolyte monomer that participates in the polymerization Cationic polyelectrolyte; the anionic polyelectrolyte layer includes an anionic polyelectrolyte obtained by participating in the polymerization of at least one anionic electrolyte monomer; the main chain or branch of the cationic polyelectrolyte contains the first host unit or the first guest unit; or an anionic polyelectrolyte The main chain or branched chain contains the first subject unit or the first guest unit; the first functional group is located on the main chain or branched chain of the cationic polyelectrolyte, or located on the main chain or branched chain of the anionic polyelectrolyte.

In the above implementation mode, when the main chain of the cationic polyelectrolyte contains the first host unit or the first guest unit, the cationic polyelectrolyte includes at least one cationic electrolyte monomer and the monomer constituting the first host unit or the first guest unit. A copolymer of the monomer of the guest unit; when the branched chain of the cationic polyelectrolyte contains the first host unit or the first guest unit, then the first host unit or the first guest unit is grafted to any of the main chains of the cationic electrolyte on the structural unit. Similarly, when the main chain of the anionic polyelectrolyte contains the first host unit or the first guest unit, the anionic polyelectrolyte includes at least one anion electrolyte monomer and the monomer that constitutes the first host unit or the first guest unit A copolymer of monomers; when the branched chain of the anionic polyelectrolyte contains the first host unit or the first guest unit, the first host unit or the first guest unit is grafted to any structural unit in the main chain of the anionic electrolyte superior.

In a feasible implementation, the cationic electrolyte monomer is selected from at least one of lysine, lysine derivatives, polyethyleneimine and chitosan; the anionic electrolyte monomer is selected from acrylic acid, acrylate, formazan At least one of acrylic acid, methacrylate, styrenesulfonic acid, styrenesulfonate, acrylamide, methylpropanesulfonic acid and sodium alkenylsulfonate.

In a feasible implementation, the second functional group is grafted on the second guest unit or the second host unit. In this implementation manner, the second functional group is located on the outer surface of the layer structure, so it can directly play the role of the second functional group.

In a feasible implementation, the first host unit and the second host unit are respectively obtained based on the first host molecule and the second host molecule, and the first host molecule and the second host molecule are independently selected from β-cyclodextrin, β- Cyclodextrin derivatives, α-cyclodextrin, α-cyclodextrin derivatives, γ-cyclodextrin, γ-cyclodextrin derivatives, cucurbituril, cucurbituril derivatives, crown ether, crown ether derivatives, At least one of calixarene, calixarene derivatives, pillar arenes and pillar arene derivatives; the first guest unit and the second guest unit are obtained based on the first guest molecule and the second guest molecule respectively, the first guest molecule and the second The guest molecule is independently selected from at least one of adamantane, adamantane derivatives, azobenzene, azobenzene derivatives, ferrocene, ferrocene derivatives, cholesterol and cholesterol derivatives.

The preparation method of the multifunctional layer structure of one embodiment, comprises the following steps:

S10, forming a polyelectrolyte multilayer film on the surface of the substrate, where the polyelectrolyte multilayer film contains a first host unit or a first guest unit.

S11. Copolymerize the first guest molecule with a cationic electrolyte monomer to obtain a cationic polyelectrolyte; copolymerize an anionic electrolyte monomer with a hydrophilic monomer to obtain an anionic polyelectrolyte.

In a feasible implementation manner, the first guest molecule is selected from at least one of adamantane, azobenzene, ferrocene and cholesterol, and the cationic electrolyte monomer is lysine. Lysine has a fibrinolytic function and biological activity, and can decompose and liquefy the fibrin formed in the blood coagulation process, thereby endowing the multifunctional layer structure in this implementation with a good fibrinolytic function.

In one possible implementation, the anionic electrolyte monomer is acrylic acid or sodium styrene sulfonate.

In a feasible implementation, the hydrophilic monomer is oligoethylene glycol methyl ether methacrylate. Oligoethylene glycol methyl ether methacrylate is a hydrophilic substance with good antifouling effect, thus endowing the multifunctional layer structure in this implementation with good antifouling function.

S12. Prepare cationic polyelectrolyte and anionic polyelectrolyte into cationic polyelectrolyte solution and anionic polyelectrolyte solution, respectively, and then alternately apply cationic polyelectrolyte solution and anionic polyelectrolyte solution to the surface of substrate to obtain cationic polyelectrolyte assembled layer by layer layer and anionic polyelectrolyte layer to obtain a polyelectrolyte multilayer membrane.

In step S12, the cationic polyelectrolyte solution and the anionic polyelectrolyte solution can be alternately applied to the surface of the substrate by soaking, spraying or spin coating. In the multifunctional layer structure of the present invention, the number of cationic polyelectrolyte layers and anionic polyelectrolyte layers in the polyelectrolyte multilayer film is not limited.

S20, forming a functional layer on the surface of the polyelectrolyte multilayer film, the functional layer contains a second guest unit or a second host unit corresponding to the first host unit or the first guest unit, and the functional layer and the polyelectrolyte multilayer film pass through the host unit The guest interacts and connects to obtain a multifunctional layer structure; wherein, the polyelectrolyte multilayer film contains at least one first functional group, and the functional layer contains at least one second functional group, and the first functional group and the second Functional groups have different functions.

In a feasible implementation, the second functional group is grafted on the second guest unit or the second host unit. At this time, the second functional group can be grafted on the second guest unit or the second host unit first, and then jointly formed on the surface of the polyelectrolyte multilayer film; The unit solution is applied on the surface of the polyelectrolyte multilayer membrane, and then the second functional group is grafted.

In a feasible implementation, the operation of forming a functional layer on the surface of the polyelectrolyte multilayer film is:

S21. Copolymerize the second host molecule with polyethyleneimine to obtain a copolymer of the second host molecule and polyethyleneimine.

In a feasible implementation, the second host molecule in step S21 is selected from β-cyclodextrin, β-cyclodextrin derivatives, α-cyclodextrin, α-cyclodextrin derivatives, γ-cyclodextrin At least one of quinine, γ-cyclodextrin derivatives, cucurbituril, cucurbituril derivatives, crown ethers, crown ether derivatives, calixarene, calixarene derivatives, pillararene and pillararene derivatives.

S22. Polymerizing the copolymer of the second host molecule and polyethyleneimine with anticoagulant molecules to obtain a polymer grafted with anticoagulant molecules, and then preparing the polymer grafted with anticoagulant molecules into a polymer solution, and The polymer solution is applied to the surface of the polyelectrolyte multilayer membrane to obtain a functional layer.

In a feasible implementation manner, the anticoagulant molecule in step S22 is selected from at least one of heparin, hirudin, lysine, polylysine, lysine derivatives, heparinoids and antiplatelet agents.

In step S22, the polymer solution may be applied to the surface of the polyelectrolyte multilayer film by soaking, spraying or spin coating.

In another feasible implementation, the operation of forming a functional layer on the surface of the polyelectrolyte multilayer film is:

S23. Copolymerize the second host molecule with polyethyleneimine to obtain a copolymer of the second host molecule and polyethyleneimine.

In a feasible implementation, the second host molecule in step S23 is selected from β-cyclodextrin, β-cyclodextrin derivatives, α-cyclodextrin, α-cyclodextrin derivatives, γ-cyclodextrin At least one of quinine, γ-cyclodextrin derivatives, cucurbituril, cucurbituril derivatives, crown ethers, crown ether derivatives, calixarene, calixarene derivatives, pillararene and pillararene derivatives.

S24. Prepare the copolymer of the second host molecule and polyethyleneimine into a polymer solution, and then apply the polymer solution and the aqueous solution containing anticoagulant molecules to the surface of the polyelectrolyte multilayer film in sequence, and obtain a functional layer after sufficient reaction .

In a feasible implementation manner, the anticoagulant molecule in step S24 is selected from at least one of heparin, hirudin, lysine, polylysine, lysine derivatives, heparinoids and antiplatelet agents.

In step S24, the polymer solution and the aqueous solution containing anticoagulation molecules can be sequentially applied to the surface of the polyelectrolyte multilayer membrane by soaking, spraying or spin coating.

In step S24, the polymer solution and the aqueous solution containing anticoagulant molecules react on the surface of the polyelectrolyte multilayer membrane. After sufficient reaction, the anticoagulant molecules are grafted on the second host group, and the obtained functional layer contains anticoagulant group, thus endowing the multifunctional layer structure in this implementation with good anticoagulant function.

A product according to one embodiment includes a substrate and the aforementioned multifunctional layer structure, and the multifunctional layer structure is disposed on the substrate. Specifically, the multifunctional layer structure is located on the surface of the substrate.

Wherein, the material and shape of the substrate are not limited, the material can be organic material or inorganic material, and the shape can be film, sheet, rod, tube, molded part, fiber, fabric or particle.

In one embodiment, the substrate is a medical device. "Medical device" in the present invention should be interpreted broadly. A medical device can be an implantable device or an extracorporeal device. The device can be used temporarily for short term or permanently implanted for long term. Examples of suitable medical devices are catheters, guide wires, endoscopes, laryngoscopes, feeding tubes, drainage tubes, medical leads, condoms, barrier structures such as for gloves, stents, stent grafts, anastomotic connectors, in vitro Blood catheters, membranes such as those used in dialysis, blood filters, circulatory aids, wound dressings, urine collection bags, ear tubes, intraocular lenses and any tubes used in minimally invasive procedures, etc. Typically, the medical device is selected from catheters, guide wires, endoscopes, laryngoscopes, feeding tubes, drainage tubes, medical leads. Articles particularly suitable for use in the present invention include catheters (e.g., intermittent catheters, balloon catheters, PTCP catheters, stent delivery catheters), guidewires, guide wires, syringes, contact lenses, medical tubing and stents, and other metal or polymeric Implants in the matrix. In particular, the present invention is applicable to catheters/guidewires made of various materials, including polyvinyl chloride, polyethylene, polypropylene, silicone rubber, latex, polytetrafluoroethylene, polyperfluoroethylene propylene, and the like.

With reference to the above implementation content, in order to make the technical solution of the present application clearer and easier to understand, the technical solution of the present application is now given as an example, but it should be noted that the content to be protected in the present application is not limited to the following examples.

Example 1

S1, synthesizing poly(lysine-co-adamantane) (poly(Lys-co-Adama)), the process is as follows:

1) Synthesis of 1-Adamantyl methacrylate (1-Adama, full name 1-Adamantyl methacrylate)

1-Adamantane methanol (5 g, 30 mmol, English name 1-Adamantane methanol) and purified triethylamine (7 mL) were dissolved in 100 mL of anhydrous dichloromethane. The reaction system was cooled to 0° C., and methacryloyl chloride (4.36 mL, 45 mmol) was slowly added dropwise under N ₂ atmosphere. After the dropwise addition, the reaction system was kept at 0°C for 30 minutes, and then returned to room temperature for 24 hours. After the reaction, extract with saturated _NaHCO3 solution, 0.1M HCl solution and saturated brine successively, collect the organic phase, dry and filter the organic phase with anhydrous magnesium sulfate, and obtain the crude product by rotary evaporation of the obtained filtrate; Prepare eluent with n-hexane (1/10), and separate by column chromatography to obtain white crystals, which is the final product 1-Adama. The reaction equation is as follows:

2) Synthesis of vinyl lysine monomer (Lys(P))

Add lysine raw material (H-Lys-(Boc)-OtBu·HCl) (2.71g, 8.0mmol) and 35mL of anhydrous dichloromethane into the flask, and after it is completely dissolved, add purified triethyl Amine (2.25 mL, 16.2 mmol). The flask was placed in an ice-water bath, and methacryloyl chloride (0.8 mL, 8.1 mmol) was slowly added dropwise to the reaction solution using a constant-pressure dropping funnel under nitrogen protection. After reacting for 1 h under ice-bath conditions, the flask was placed at room temperature to continue the reaction for 18 h. After the reaction, the reaction solution was washed three times with saturated brine, 0.1M hydrochloric acid and 0.1M sodium bicarbonate solution successively. The organic phase was collected and dried with anhydrous magnesium sulfate, and a colorless viscous crude product was obtained after spin-drying the solvent. It was separated and purified by silica gel column chromatography, and the eluent was ethyl acetate/n-hexane (1/2). The product was collected and dried to obtain a white solid, which was stored in a refrigerator at 4°C. The reaction equation is as follows:

3) Synthesis of adamantane-lysine copolymer

Lys(P) (1 g, 6.84 mmol), 1-Adama (0.153 g, 0.69 mmol) and AIBN (0.2 mg, 1.2 μmol) were dissolved in 10 mL of N,N dimethylformamide (DMF). The solution was purged with nitrogen for 30 min to remove oxygen and then transferred to a glove box purified with dry nitrogen. The reaction mixture was stirred at 65 °C for 24 hours. Polymerization was quenched by exposure to air under an ice-water bath. To obtain poly(Lys(P)-co-Adama), add 10 ml of concentrated hydrochloric acid for deprotection for 3 hours to obtain poly(Lys-co-Adama). Then the polymer solution was dialyzed for 48 hours with a 3500Da dialysis bag, and the product was freeze-dried and separated to obtain the product. The reaction equation is as follows:

S2, synthesizing poly(acrylic acid-co-oligoethylene glycol methyl ether methacrylate) (poly(AAc-co-OEGMA)), the process is as follows:

Acrylic acid (1g, 13.9mmol, English name is Acrylic acid), oligoethylene glycol methyl ether methacrylate (0.6662g, 1.39mmol, English name is poly(ethylene glycol) methyl ether methacrylate) and AIBN (0.2mg , 1.2 μmol) was dissolved in 10 mL N,N dimethylformamide (DMF). The solution was purged with nitrogen for 30 min to remove oxygen and then transferred to a glove box purified with dry nitrogen. The reaction mixture was stirred at 65 °C for 24 hours. Polymerization was quenched by exposure to air under an ice-water bath. Then the polymer solution was dialyzed for 48 hours with a 3500Da dialysis bag, and the product was freeze-dried and separated to obtain the product. The reaction equation is as follows:

S3. Synthesis of heparin-modified cyclodextrin (β-CD-PEI-Hep), the process is as follows:

1) Synthesis of β-CD-PEI

Dissolve 2.1g β-CD and 4.0g CDI in 25mL DMF and place under nitrogen protection at 20-30°C for 1.0h, then place it in ether at -4.0°C for 1.0h, filter Obtain N,N'-carbonyldiimidazole-β-cyclodextrin (β-CD-CDI); dry β-CD-CDI and dissolve in 25mL DMSO to obtain mixed solution 1; dissolve 7.5g PEI in 15mL Mixed solution 2 was obtained in DMSO; mixed solution 1 and 1.5mL Et3N were added dropwise to mixed solution 2 at a rate of 30 drops/min, and stirred for 5.0h. After the reaction was completed, it was dialyzed with deionized water for 3 days, and then frozen Dry to obtain β-CD-PEI.

2) Reduced heparin

Heparin (1 g) was dissolved in pure water (300 ml) at 0°C. Add sodium nitrite (NaNO ₂ , 10 mg), add hydrochloric acid (HCl, 0.1 M) to adjust the pH to 2.7, and react at 0° C. for 2 hours. The reaction product was adjusted to pH 7.0 with 0.1M NaOH, dialyzed and freeze-dried.

3) Synthesis of β-CD-PEI-Hep

β-CD-PEI was reacted with a pH 3.5 aqueous solution containing partially degraded heparin (0.2 mg/mL), sodium cyanoborohydride (0.01 mg/mL) and sodium chloride (0.15 M) at 50 °C. After two hours of reaction, the polymer solution was dialyzed with a 3500Da dialysis bag for 48 hours, and the product was freeze-dried and separated to obtain the product. The reaction equation is as follows:

S4, preparing a multifunctional layer structure, the method is as follows:

1) First prepare the polyelectrolyte multilayer film, the method is as follows:

Preparation of solution: Prepare 30ml of 2mg/ml poly(AAc-co-OEGMA) solution, add 2.631g of sodium chloride, use 1M hydrochloric acid solution to adjust pH=3; prepare 30ml of 2mg/ml poly(Lys-co-Adama) solution, use Adjust the pH to 9 with 1M sodium hydroxide solution; prepare a 2 mg/ml β-CD-PEI-Hep solution.

Cut the PVC sheet into a square piece with a side length of 1cm×1cm, ultrasonically clean it for 10 minutes, and dry it with lens cleaning paper. Plasma treatment for 10 minutes, immediately take solution A (2mg/ml PEI solution, Mn=70000) dropwise on the surface, soak for 10 minutes. Wash with pure water for 3 times, add the above poly(AAc-co-OEGMA) solution dropwise and soak for 5 minutes. Wash with pure water 3 times. Add the above poly(Lys-co-Adama) solution dropwise and soak for 5 minutes. Repeat the above operations to modify the eight-layer membrane (including eight cationic polyelectrolyte layers and eight anionic polyelectrolyte layers) to obtain a polyelectrolyte multilayer membrane.

2) Form a functional layer on the surface of the above-mentioned polyelectrolyte multilayer film, the method is as follows:

Soak the above polyelectrolyte multilayer membrane in β-CD-PEI-Hep solution for 10 minutes, rinse the surface with deionized water to remove unbound heparin-modified β-cyclodextrin, and then dry it under nitrogen flow to obtain Example 1 multifunctional layer structure.

Example 2

S1. Synthesis of poly(lysine-co-adamantane) (poly(Lys-co-Adama)), the method is the same as step S1 in Example 1.

S2, synthesizing poly(sodium styrene sulfonate-co-oligoethylene glycol methyl ether methacrylate) (poly(SSNa-co-OEGMA)), the process is as follows:

Dissolve SSNa (1.0088g, English full name 4-Vinylbenzenesulfonic Acid Sodium Salt Hydrate), oligoethylene glycol methyl ether methacrylate (232.4mg) and AIBN (0.2mg) in 10mL N, N dimethylformamide (DMF). The solution was purged with nitrogen for 30 min to remove oxygen and then transferred to a glove box purified with dry nitrogen. The reaction mixture was stirred at 65 °C for 24 hours. Polymerization was quenched by exposure to air under an ice-water bath. Then the polymer solution was dialyzed with water for 72 hours, and the product was freeze-dried and separated to obtain the obtained product.

S3. Synthesis of heparin-modified cyclodextrin (β-CD-PEI-Hep), the method is the same as step S3 in Example 1.

S4, preparing a multifunctional layer structure, the method is as follows:

1) First prepare the polyelectrolyte multilayer film, the method is as follows:

Preparation of solution: Prepare 30ml of 2mg/ml poly(SSNa-co-OEGMA) solution, add 2.631g of sodium chloride, use 1M hydrochloric acid solution to adjust pH=3; prepare 30ml of 2mg/ml poly(Lys-co-Adama) solution, use Adjust the pH to 9 with 1M sodium hydroxide solution; prepare a 2 mg/ml β-CD-PEI-Hep solution.

Cut the PVC sheet into a square piece with a side length of 1cm×1cm, ultrasonically clean it for 10 minutes, and dry it with lens cleaning paper. Plasma treatment for 10 minutes, immediately take solution A (2mg/ml PEI solution, Mn=70000) dropwise on the surface, soak for 10 minutes. Wash with pure water for 3 times, add the above poly(SSNa-co-OEGMA) solution dropwise and soak for 5 minutes. Wash with pure water 3 times. Add the above poly(Lys-co-Adama) solution dropwise and soak for 5 minutes. Repeat the above operations to modify the eight-layer membrane (including eight cationic polyelectrolyte layers and eight anionic polyelectrolyte layers) to obtain a polyelectrolyte multilayer membrane.

The above-mentioned multilayer film was soaked in β-CD-PEI-Hep solution for 10 min, and the surface was rinsed with deionized water to remove unbound heparin-modified β-cyclodextrin, and then dried under nitrogen flow to obtain the β-cyclodextrin of Example 2. Multifunctional layer structure.

Example 3

S2. Synthesis of poly(sodium styrene sulfonate-co-oligoethylene glycol methyl ether methacrylate) (poly(SSNa-co-OEGMA)), the method is the same as step S2 in Example 2.

S3, synthesizing β-CD-PEI, the method is the same as step 1) of step S3 in embodiment 1.

S4, preparing a multifunctional layer structure, the method is as follows:

1) First prepare the polyelectrolyte multilayer film, the method is as follows:

Preparation of solution: Prepare 30ml of 2mg/ml poly(SSNa-co-OEGMA) solution, add 2.631g of sodium chloride, use 1M hydrochloric acid solution to adjust pH=3; prepare 30ml of 2mg/ml poly(Lys-co-Adama) solution, use Adjust pH=9 with 1M sodium hydroxide solution;

Soak the above-mentioned multilayer film in the aqueous solution of 2mg/ml β-CD-PEI, soak for 10min, wash three times with deionized water, then wash with partially degraded heparin (0.2mg/mL), sodium cyanoborohydride (0.01 mg/mL) and sodium chloride (0.15 M), pH 3.5 in water at 50 °C to react with the above multilayer film. After two hours of reaction, the surface was rinsed with deionized water to remove unbound heparin, and then dried under nitrogen flow.

Example 4

S1, synthetic poly (dimethyl diallyl ammonium chloride-co-adamantane), method: weigh dimethyl diallyl ammonium chloride (1g), Adama (0.153g), 4-cyano Valeric dithiobenzoic acid (CPTP) (0.64 mg) and AIBN (0.2 mg) were dissolved in 10 ml of anhydrous DMF. After purging the reaction system with nitrogen gas to remove oxygen, the reaction solution was transferred to a glove box and placed at 65° C. for 24 h. After the reaction, the reaction solution was transferred to a dialysis bag with a MWCO of 3500 for dialysis for three days; flocculent powder was obtained after freeze-drying.

S3. Synthesis of heparin-modified cyclodextrin (β-CD-PEI-Hep), the method is the same as step S3 in Example 1

S4. Prepare a multifunctional layer structure, the method is the same as step S4 in Example 1.

Example 5

S1, synthesis of poly (dimethyl diallyl ammonium chloride-co-adamantane), method: take dimethyl diallyl ammonium chloride alkanone (1g), Adama (0.153g), 4- Cyanovaleric dithiobenzoic acid (CPTP) (0.64 mg) and AIBN (0.2 mg) were dissolved in 10 ml of anhydrous DMF. After purging the reaction system with nitrogen to remove oxygen, the reaction solution was transferred to a glove box and placed at 65°C for 24 hours. After the reaction, the reaction solution was transferred to a dialysis bag with a MWCO of 3500 for dialysis for three days; flocculent powder was obtained after freeze-drying.

S3, synthesizing heparin-modified cyclodextrin (β-CD-Lys), the method is as follows:

H-Lys(Boc)-OtBu.HCl (1.02g) and TEA (0.25ml) were dissolved in 20ml of dry dichloromethane. Weigh acetylenic anhydride (0.79 g) and dissolve it in 5 ml of dichloromethane, and slowly add it dropwise to the above solution under ice-bath conditions. After the dropwise addition, the reaction system was returned to room temperature to continue the reaction for 24 h. After the reaction was completed, it was post-treated with saturated NaHCO ₃ solution, 0.1M HCl solution and saturated saline in sequence, dried and purified through a column to obtain the product Lys(P)-alkynyl. Lys(P)-alkynyl (704.8 mg) and CD-(N3)7 (262.0 mg) were dissolved in 5 ml dry DMSO. In an oxygen-free environment, PMDETA (20.9 μl) and CuBr (14.5 mg) were added, and the temperature was raised to 50° C. for 24 h. After the reaction, the precipitate was purified and freeze-dried. Then the freeze-dried product was dissolved in 6 ml of anhydrous dichloromethane, and 2 ml of TFA was added dropwise under ice-bath conditions. After the dropwise addition, the mixture was placed in an ice bath to continue the reaction for 1 h, and then rose to room temperature for 4 h. After the reaction, precipitate with glacial ether, collect the precipitate and transfer it to a dialysis bag with a MWCO of 1000 for dialysis and freeze-dry to obtain a white powder, which is the final product.

Comparative example 1

Cut the PVC sheet into a square piece with a side length of 1cm×1cm without any modification.

Comparative example 2

S1, synthesis of poly(acrylic acid-co-adamantane) P(AA-Ada), method: take AA (1.080g), Adama (0.153g), 4-cyanopentanoic acid dithiobenzoic acid (CPTP) ( 0.64mg) and AIBN (0.2mg), dissolved in 10ml of anhydrous DMF. After purging the reaction system with nitrogen gas to remove oxygen, the reaction solution was transferred to a glove box and placed at 65° C. for 24 h. After the reaction, the reaction solution was transferred to a dialysis bag with a MWCO of 3500 for dialysis for three days; flocculent powder was obtained after freeze-drying.

S2, synthesis of poly(sodium styrene sulfonate) (PSS): SSNa (1.0088g, English full name 4-Vinylbenzenesulfonic Acid Sodium Salt Hydrate) and AIBN (0.2mg) were dissolved in 10mL N, N dimethylformamide ( DMF). The solution was purged with nitrogen for 30 min to remove oxygen and then transferred to a glove box purified with dry nitrogen. The reaction mixture was stirred at 65 °C for 24 hours. Polymerization was quenched by exposure to air under an ice-water bath. Then the polymer solution was dialyzed with water for 72 hours, and the product was freeze-dried and separated to obtain the product.

S3. The steps for synthesizing β-CD-Lys are the same as step S3 in Example 4; the steps for synthesizing β-CD-PEI-Hep are the same as step S3 in Example 1.

S4, preparing a multifunctional layer structure, the method is as follows:

Soak the aminated substrate in the solution of the copolymer P(AA-Ada) of acrylic acid monomer and 1-adamantyl acrylate monomer for a period of time, then soak in the PSS solution for a period of time, and repeat the soaking several times , that is, to obtain a polyelectrolyte multilayer membrane modified surface with several layers of P(AA-Ada)/PSS bilayers; -The reaction is carried out in the solution of PEI-Hep, and the multifunctional layer structure with lysine and heparin molecules immobilized on the surface can be obtained.

Performance Testing:

(1) The monomer 1-Adama synthesized in step S1 step 1) and the monomer Lys (P) synthesized in step S1 step 2) in embodiment 3 are carried out by nuclear magnetic spectrum (1HNMR), and the obtained Fig. 1 (a) and Figure 1(b): D ₂ O was used to dissolve the polymer, and CDCl ₃ was used to dissolve the monomer. Analyzing Fig. 1(a), it can be obtained that the substance synthesized in step S1, step 1) in Example 3 is 1-Adama. Analyzing Fig. 1(b), it can be obtained that the substance synthesized in step S1, step 2) of Example 3 is Lys(P).

(2) Infrared test was carried out on the β-CD-PEI synthesized in the step 1) of step S3 in Example 3, and FIG. 2 was obtained. It can be seen from Figure 2 that the infrared spectrum of β-CD-PEI has a characteristic peak belonging to secondary amines at 3300-3500 cm ^-1 , indicating that the synthesized substance is β-CD-PEI.

(3) to the polyelectrolyte multilayer membrane that step S4 step 1) makes in embodiment 3 and the multifunctional layer structure that step 2) makes, and the PVC sheet of comparative example 1, the PVC sheet after surface hydroxylation (obtained by plasma treatment of PVC sheet for 10min) to test the water contact angle respectively, the test method is as follows: the static water contact angle of the surface of the material is tested by the stop-drop method, and the sample is placed on the stage during the test, and the micro-sampler is used 2 μL of deionized water was dropped on the surface of the sample, and 6 data were tested in parallel for each sample, and the average value and standard deviation were calculated to obtain Figure 3.

As can be seen from Fig. 3, the water contact angle of the PVC sheet (marked as control) of comparative example 1 is 96.06 °, PVC-OH is the PVC sheet after surface hydroxylation, and the surface water contact angle is 59.69 °, in embodiment 3 Step S4 step 1), after surface modification of two layers of polyelectrolyte (marked as PVC-Lys (2)) or eight layers of polyelectrolyte (marked as PVC-Lys (8)), compared with the untreated PVC sheet, its water contact angle obviously drops, and the water contact angle of the polyelectrolyte multilayer film that makes after surface modification eight-layer polyelectrolyte is 67.05 °, the surface (marked as SOLAND) water of the multifunctional layer structure that obtains after modifying heparin The contact angle was 59.30°, indicating that the successful modification of heparin further improved the hydrophilicity of the surface, indicating that the multifunctional layer structure prepared in Example 3 had better hydrophilicity.

(4) Carry out toluidine blue dyeing test respectively to the multifunctional layer structure that embodiment 3 makes and the PVC sheet of comparative example 1: drop toluidine blue solution room temperature and place 1min, rear deionized water washes three times, takes pictures, obtains the picture 4. It can be seen from FIG. 4 that the surface of the multifunctional layer structure prepared in Example 3 is purple, and the heparin modification is successful.

(5) Carry out protein adsorption test respectively to the multifunctional layer structure that embodiment 3 makes and the PVC sheet of comparative example 1, test method is as follows: In order to study the situation that material surface adsorbs fibrinogen (Fg) from buffer solution and blood plasma First, Fg and ¹²⁵ I-labeled Fg are mixed with PBS and plasma respectively, wherein the amount of radioactive protein accounts for 10% of the protein content in plasma. The sample was first soaked in phosphate buffer solution (PBS, pH=7.4) overnight, and then immersed in plasma containing radioactive protein. After adsorption at room temperature for 3 hours, the sample was taken out of the well plate, washed with PBS for 3 times, each time for 10 minutes, and filtered with filter paper. Transfer to a clean centrifuge tube after drying. The γ-counter was used to test the radiation dose on the surface of the material, and the adsorption amount of the surface protein was obtained through conversion, and Figure 5 was obtained. Fg protein is the main protein in coagulation reaction and can mediate the adhesion of platelets on the surface of materials. The degree of adsorption of Fg on the surface of the material can reflect the ability of the material to resist non-specific protein adsorption, and can also evaluate the anticoagulant performance of the material to a certain extent.

As can be seen from Figure 5, compared with the PVC sheet of Comparative Example 1 (marked as Control), the multifunctional layer structure (marked as SOLAND) made in Example 3 reduces 58.57% of Fg adsorption in PBS, and Plasma (plasma) The Fg adsorption in the medium was reduced by 82.16%, which indicated that the multifunctional layer structure prepared in Example 3 had excellent anticoagulant effect.

(6) Antibacterial performance test: Escherichia coli was planted on the surface of the sample and cultured for 3 hours, then the sample was taken out, immersed in a centrifuge tube containing 1 mL of phosphate buffer (pH=7.4), and centrifuged at 5000 rpm for 5 minutes to collect bacteria on the surface of the substrate. Take 500 μL of the collected bacterial solution and spread it on the agar culture plate by the plate coating method, place it in a 37°C incubator and cultivate it for 18 hours, take it out, and take pictures.

(7) Fibrinolytic performance test: Soak the multifunctional layer structure prepared in Example 5 and the PVC sheet of Comparative Example 1 in Tris buffer solution (pH=7.4) for 1 hour, take it out and then soak it in ordinary After being immersed in human plasma for 3 hours, the substrate was taken out and rinsed three times with Tris buffer. Soak the sample in t-PA for 10min. Rinse the slice with tris buffer solution for 3 times, take out the substrate, blot dry with filter paper, add 100 μL of plasma, and then add 100 μL of 0.025M calcium chloride solution. All the above immersions were carried out in a constant temperature incubator at 37°C, and the added plasma and t-PA should be preheated in the incubator at 37°C. Measure the absorbance at 405nm with a microplate reader, the time interval is set at 30s, and the total test time shall not be less than 1h. The test results are shown in Figure 6. When a primary thrombus (i.e., a fibrin clot) occurs in blood, the exposed carboxy-terminal lysine residues on its surface selectively bind Plg and its physiological activator t-PA from plasma to form a ternary complex . This complex will accelerate the activation of Plg by t-PA, thereby producing a large amount of plasmin and degrading the formed fibrin. The above test simulates this process and can be used to evaluate the thrombolytic ability of the material surface.

It can be seen from Figure 6 that the surface of the PVC sheet in Comparative Example 1 does not contain functional lysine, thus showing a typical thrombus formation curve: as time goes on, the light absorption value gradually increases, and a platform is formed after reaching the highest value, indicating that Stabilizes the formation of fibrin clots. In contrast, since the surface of the sample in Example 5 contains lysine in the outermost functional layer, the corresponding absorbance value rises to a certain extent and then drops to the baseline rapidly, indicating that the fibrin is completely dissolved after being produced.

(8) Functional durability test: the multifunctional layer structure made in embodiment 4 and the multifunctional layer structure made in comparative example 2 are soaked in the solution of surfactant sodium dodecyl sulfate (SDS) (concentration is 10 %), ultrasonically cleaned for 10 min. Then take it out and soak it with deionized water to remove the surface residue, and carry out the antibacterial performance test according to (6). The test results are shown in Figure 7. SDS and ultrasonic cleaning will destroy the host-guest interaction. Through this relatively harsh and harsh destruction experiment process, the outermost functional layer can be destroyed to make it fall off as much as possible, so as to explore the stability of the inner structure.

As can be seen from Figure 7, compared with Comparative Example 2, the bacteria collected from the sample with a multifunctional layer structure prepared in Example 4 have died substantially, without forming any obvious colonies, which proves that after a period of more than normal Under the damage of dozens of times the external force of the environment, the outermost functional layer partly falls off, while the functionality in the inner layer structure can maintain and exert its biological functions. However, after the outermost functional layer of Comparative Example 2 fell off, since there were no functional groups in the inner layer structure, it had no antibacterial effect, and a large number of colonies were formed.

The technical features of the above-mentioned embodiments can be combined arbitrarily. To make the description concise, all possible combinations of the technical features in the above-mentioned embodiments are not described. However, as long as there is no contradiction in the combination of these technical features, should be considered as within the scope of this specification.

The above-mentioned embodiments only express several implementation modes of the present invention, and the descriptions thereof are relatively specific and detailed, but should not be construed as limiting the patent scope of the invention. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention should be based on the appended claims.

Claims

A multifunctional layer structure, characterized in that the multifunctional layer structure includes a polyelectrolyte multilayer film and a functional layer located on one side of the polyelectrolyte multilayer film, and the polyelectrolyte multilayer film contains a first body unit or a first guest unit, the functional layer contains a second guest unit or a second host unit corresponding to the first host unit or the first guest unit, the functional layer and the polyelectrolyte multilayer The membrane is connected by host-guest interaction;

The polyelectrolyte multilayer film contains at least one first functional group, the functional layer contains at least one second functional group, and the first functional group and the second functional group The functions are different.
The multifunctional layer structure according to claim 1, wherein the first functional group and the second functional group are independently selected from at least one of biologically active groups, antibacterial groups and antifouling groups. A sort of.
The multifunctional layer structure according to claim 2, wherein the bioactive group is obtained based on bioactive molecules selected from the group consisting of heparin, hirudin, lysine, polylysine, lysine At least one of amino acid derivatives, heparinoids, antiplatelet agents, plasminogen activators, plasminogen, biotin and avidin;

The antibacterial group is selected from at least one of quaternary ammonium salt group, bisquat group, monoguanidine group, imidazole group and phenolic group;

The antifouling group is at least one selected from polyethylene glycol groups, polyvinyl alcohol groups, polyvinylpyrrolidone groups and zwitterionic groups.
The multifunctional layer structure according to claim 1, wherein the polyelectrolyte multilayer film comprises at least one cationic polyelectrolyte layer and at least one anionic polyelectrolyte layer alternately stacked;

The cationic polyelectrolyte layer includes a cationic polyelectrolyte obtained by participating in the polymerization of at least one cationic electrolyte monomer; the anionic polyelectrolyte layer includes an anionic polyelectrolyte obtained by participating in the polymerization of at least one anionic electrolyte monomer;

The main chain or branch of the cationic polyelectrolyte contains the first host unit or the first guest unit; or the main chain or branch of the anionic polyelectrolyte contains the first host unit or the first guest unit;

The first functional group is located on the main chain or branch chain of the cationic polyelectrolyte, or on the main chain or branch chain of the anionic polyelectrolyte.
The multifunctional layer structure according to claim 4, wherein the cationic electrolyte monomer is selected from at least one of lysine, lysine derivatives, polyethyleneimine and chitosan;

The anion electrolyte monomer is at least A sort of.
The multifunctional layer structure according to claim 1, wherein the second functional group is grafted on the second guest unit or the second host unit.
The multifunctional layer structure according to any one of claims 1, 4 and 6, wherein the first host unit and the second host unit are obtained based on the first host molecule and the second host molecule respectively, The first host molecule and the second host molecule are independently selected from β-cyclodextrin, β-cyclodextrin derivatives, α-cyclodextrin, α-cyclodextrin derivatives, γ-cyclodextrin, At least one of γ-cyclodextrin derivatives, cucurbituril, cucurbituril derivatives, crown ethers, crown ether derivatives, calixarene, calixarene derivatives, columnarene and columnarene derivatives;

The first guest unit and the second guest unit are obtained based on the first guest molecule and the second guest molecule respectively, and the first guest molecule and the second guest molecule are independently selected from adamantane, adamantane derivatives, At least one of azobenzene, azobenzene derivatives, ferrocene, ferrocene derivatives, cholesterol and cholesterol derivatives.
A method for preparing a multifunctional layer structure, comprising the steps of:

A polyelectrolyte multilayer film is formed on the surface of the substrate, and the polyelectrolyte multilayer film contains a first host unit or a first guest unit; and

A functional layer is formed on the surface of the polyelectrolyte multilayer film, the functional layer contains a second guest unit or a second host unit corresponding to the first host unit or the first guest unit, the functional layer Connecting with the polyelectrolyte multilayer film through host-guest interaction to obtain a multifunctional layer structure;

Wherein, the polyelectrolyte multilayer film contains at least one first functional group, the functional layer contains at least one second functional group, and the first functional group and the second functional group Groups have different functions.
The preparation method of the multifunctional layer structure according to claim 8, characterized in that, the operation of forming a polyelectrolyte multilayer film on the surface of the substrate is: passing at least one cationic polyelectrolyte layer and at least one anionic polyelectrolyte layer through The method of layer-by-layer assembly is alternately formed on the surface of the substrate to obtain a polyelectrolyte multilayer film.
According to the preparation method of claim 8 or 9 described multifunctional layer structure, it is characterized in that, the operation of forming polyelectrolyte multilayer film on the substrate surface is:

copolymerizing the first guest molecule with a cationic electrolyte monomer to obtain a cationic polyelectrolyte; copolymerizing an anionic electrolyte monomer with a hydrophilic monomer to obtain an anionic polyelectrolyte; and

The cationic polyelectrolyte and the anionic polyelectrolyte are respectively formulated into a cationic polyelectrolyte solution and an anionic polyelectrolyte solution, and then the cationic polyelectrolyte solution and the anionic polyelectrolyte solution are alternately applied to the surface of the substrate to obtain a layer The cationic polyelectrolyte layer and the anionic polyelectrolyte layer assembled in layers, namely the polyelectrolyte multilayer membrane.
A product, characterized in that it comprises a substrate and the multifunctional layer structure according to any one of claims 1 to 7, the multifunctional layer structure is provided on the substrate.
The article of claim 11, wherein the substrate is a medical device.