Thermoresponsive slip-ring grafted polyrotaxane block topological copolymer and its synthesis method, and application thereof in high-strength tough injectable hydrogel

Abstract

The application belongs to the technical field of high polymer functional materials, and particularly relates to a temperature-sensitive sliding ring grafted polyrotaxane block topological copolymer, a synthesis method thereof, and application of the copolymer in high-strength tough injectable hydrogel. The structural characteristics of the copolymer are as follows: the block copolymer composed of a middle polyether segment and two temperature-sensitive segments at the ends is used as a main chain, and the cyclic molecules grafted on the side chains can freely slide along the middle polyether segment of the main chain; the sliding behavior is constrained by the two temperature-sensitive segments at the ends of the main chain, forming a mechanical interlocking topological structure; the two ends of the block copolymer main chain and the cyclic molecules grafted on the side chains are temperature-sensitive segments with the same structure. The preparation process comprises the following steps: synthesizing PEG and cyclic molecules with ATRP initiation activity, one-pot step-by-step assembly and polymerization, and obtaining the target product. Compared with traditional hydrogels, the high-strength tough injectable hydrogel provided by the application has both sol-gel injectability and structural strength in the gel state, and excellent creep resistance, and can be used in medical scenarios such as external wound repair and in-vivo tissue engineering.

Description

Technical Field

[0001] This invention belongs to the field of polymer functional materials technology, specifically relating to a temperature-sensitive slip ring grafted polyrotaxane block topological copolymer, its synthesis method, and its application in high-strength and tough injectable hydrogels. Background Technology

[0002] Injectable thermo-responsive hydrogels are materials that exist in a sol state at room temperature and transform into a mechanically supportive gel state upon triggering at a specific temperature. Therefore, they exhibit significant application value in biomedicine, clinical intervention, and in-situ tissue filling. The sol state's fluidity is determined by its viscosity, typically controlled within the range of approximately 0.01-50 Pa·s to ensure smooth injection under manual conditions (injection pressure less than 12 N) using conventional medical syringes (20G-26G). Simultaneously, after gel formation near body temperature, they must possess tissue-matched mechanical strength and structural stability, requiring a storage modulus (G') of approximately 10. 2 -10 5 The stress should be 5-50 times the loss modulus (G'') to achieve effective tissue support and shape retention. In addition, in practical applications of tissue engineering, the condensed state of the material must also have good creep resistance, that is, it should be able to maintain a high strain recovery capacity (usually ≥70%) after multiple cycles of loading under a certain stress (such as 10-50 Pa) to suppress irreversible deformation and maintain long-term structural stability.

[0003] However, currently reported injectable thermosensitive hydrogels typically only meet some of the aforementioned properties due to the mutually exclusive properties of their sol viscosity and gel modulus. More importantly, they exhibit almost no creep resistance or stretchability. This is because in the traditional structural design of thermosensitive polymers, the ratio of hydrophilic, hydrophobic, and thermosensitive segments, as well as their distribution in the main chain or side chains, is crucial in determining whether their aqueous solutions can achieve a sol-gel phase transition. The length of the thermosensitive segment and its proportion in the copolymer directly determine the sensitivity of the phase transition. Linear block or low graft density structures are beneficial for forming intermolecular hydrogen bonds, retaining water, and forming an intermolecular physical entanglement network. However, simply increasing the overall molecular weight has limited effect on improving the strength of the condensed state, and increasing the molecular weight increases the sol viscosity index and induces a hysteresis in temperature response, thus limiting their application in injectable hydrogels. Furthermore, as the overall proportion of thermosensitive segments or the distribution of grafted side chains increases, intramolecular hydrogen bonds are easily formed during the phase transition, causing the collapse of intramolecular hydrophobic aggregates, leading to the precipitation of non-gel transitions and making it difficult to construct a stable gel network. Currently, no thermosensitive hydrogel exhibiting a sol-gel phase transition can maintain a low viscosity in a 10wt% low-concentration sol state while still exhibiting a shear strength exceeding 1 kPa and a creep resistance with a recovery rate of approximately 80% after 5 cycles following a rapid thermosensitive phase transition at body temperature. Therefore, developing a structure that facilitates intermolecular hydrogen bonding while reducing sol viscosity and enhancing reversible response is crucial for constructing high-performance thermosensitive phase transition hydrogels. Slip-ring grafted polyrotaxane block copolymers, relying on their mechanically interlocked, sliding thermosensitive side-chain structure, hold promise for achieving a synergistic improvement in the mechanical properties and creep resistance of the gel state after a thermosensitive phase transition, while maintaining the low viscosity and injectability of the sol state. This would effectively suppress irreversible deformation and maintain structural stability, overcoming a performance bottleneck that urgently needs to be addressed in this field. Summary of the Invention

[0004] To address the aforementioned challenges, this invention proposes a thermo-responsive slip-ring grafted polyrotaxane block topological copolymer, its synthesis method, and its application in high-strength and tough injectable hydrogels. The thermo-responsive slip-ring grafted polyrotaxane block topological copolymer prepared by this invention is a core component of high-strength and tough injectable hydrogels. The structural features of this thermo-responsive slip-ring grafted polyrotaxane block topological copolymer are: a block copolymer with a central polyether segment and thermo-sensitive segments at both ends as the main chain; cyclic molecules of the grafted side chains can slide freely along the central polyether segment of the main chain; this sliding behavior is constrained by the thermo-sensitive segments at both ends of the main chain, thus forming a mechanically interlocked topological structure; the side chains grafted to the two ends of the block copolymer main chain and the cyclic molecules are thermo-sensitive segments with the same structure. Unlike traditional thermosensitive polymers that rely on covalent bonds for fixed connections and are prone to intramolecular collapse, the core of this invention lies in the simultaneous introduction of thermosensitive polymer segments into both the cyclic molecules and the block copolymer backbone, based on the structural framework of polyrotaxane. This allows for the simultaneous initiation of end-capping and the grafting of sliding thermosensitive polymer segments. This strategy achieves both stable end-capping of the polyrotaxane structure and simultaneous grafting of thermosensitive polymer segments onto the cyclic molecules, forming a sliding network structure with mechanical interlocking characteristics. During the thermosensitive phase transition, the sliding cyclic molecules grafted with thermosensitive polymer segments undergo cooperative rearrangement and stress dissipation under topological constraints. This maintains the low viscosity and injectability of the sol state while improving the mechanical properties and structural stability of the gel state, overcoming the technical bottleneck of traditional thermosensitive hydrogels that struggle to balance injectability and mechanical properties.

[0005] The thermo-responsive slip-ring grafted polyrotaxane block topological copolymer provided by this invention completes assembly and polymerization via a "one-pot" method, that is, the pseudorotaxane assembly and precise polymerization of thermo-sensitive polymer segments are completed sequentially in the same reaction system. Specifically: First, functionalized polyether and functionalized cyclodextrin are assembled to form a pseudorotaxane topological core using host-guest interactions; second, using this core as a macromolecular initiator, thermo-sensitive polymer segments are constructed at both ends of the main chain through atom transfer radical polymerization (ATRP) and physical end-capping is completed simultaneously; at the same time, highly dense thermo-sensitive polymer segments are constructed using the active sites on the cyclodextrin ring as initiation centers. These highly branched thermo-sensitive polymer segments can effectively reduce the entanglement resistance between segments in the sol state, ensuring that the material can be smoothly injected through a 20 G or finer medical needle.

[0006] This invention utilizes this strategy to achieve precise control over the microscopic topology and macroscopic injection performance of hydrogels: the total length of the thermosensitive polymer segments determines the thermosensitive phase transition response sensitivity of the hydrogel; while the length and density of the thermosensitive polymer segments on the restricted sliding ring molecules determine the water retention and final achievable modulus of the network after the phase transition. Compared to traditional random grafting or single-block systems, this dual thermosensitive synergistic design has significant structural advantages: upon entering a high-temperature environment, the intermolecular hydrogen bonds between the hydrophilic groups at the ends of the main chain and in the thermosensitive polymer segments on the ring molecules are disrupted, and the alkyl chain structure simultaneously generates hydrophobic interactions. The sliding nature of the rings makes the thermosensitive polymer segments more inclined to form intermolecular hydrogen bonds, forming an intermolecular physical cross-linked network, rapidly constructing a topological network with a certain degree of toughness at the injection site. The resulting topological thermosensitive hydrogel not only suppresses volume shrinkage caused by hydrophobic drainage but also possesses stretchability and creep resistance.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of the present invention is to provide a thermo-responsive slip-ring grafted polyrotaxane block topological copolymer, comprising a block copolymer backbone and restricted slip-ring thermosensitive brush-like side chains; the block copolymer backbone comprises polyether blocks and thermosensitive polymer segments connected to both ends of the polyether blocks and forming end caps, the thermosensitive polymer segments undergoing hydrophobic collapse above the lowest critical solution temperature (LCST), acting as steric hindrance groups to prevent the detachment of cyclic molecules, and participating in network construction as a first thermosensitive response source; the thermosensitive brush-like side chains comprise a plurality of cyclic molecules capable of sliding on the polyether blocks and thermosensitive... Polymer segments; cyclic molecules are cyclodextrins or cyclodextrin derivatives; thermosensitive polymer segments grafted onto cyclic molecules are distributed at a high grafting density on the outer edge of cyclic molecules to form a thermosensitive polymer brush structure, which acts as a second thermosensitive response source and produces a synergistic effect with the thermosensitive polymer segments connected to both ends of the main chain; the topological copolymer provided by this invention has a LCST of more than 100 μL, and through the co-association of thermosensitive polymer segments connected to both ends of the block copolymer main chain and connected to the cyclic molecules, a dynamic topological network with stress self-regulation function is constructed, so that the thermosensitive hydrogel configured by this polymer has both injectability and high toughness.

[0008] The chemical structural formula of the slip ring-grafted polyrotaxane block topological copolymer is as follows: ; in: It is a segmented copolymer main chain; It is a polyether block; The cyclic molecule is represented by m, which represents the number of cyclic molecules, ranging from 1 to 50. The cyclic molecule can slide along the polyether block in the block copolymer backbone, and this sliding behavior is constrained by the thermosensitive polymer segments at both ends of the block copolymer backbone. The ends of the polyether block and the cyclic molecule are grafted with structurally identical thermosensitive polymer segments, which are obtained by polymerization of thermosensitive monomers. n represents the molecular weight of the thermosensitive polymer segment, ranging from 0.5k to 5000k. The thermosensitive monomer is an unsaturated monomer with double bonds, and its molecular structure contains a hydrophobic alkyl chain structure and a hydrophilic group. R3 is -Cl or -Br; R4 is obtained by polymerization of the thermosensitive monomer; R5 is -H or -CH3; R6 is -CH3 or -CH2CH3; the average number of thermosensitive polymer segments grafted onto each cyclic molecule ranges from 1 to 12.

[0009] As a preferred technical solution, the polyether block is a polyethylene glycol segment; the cyclic molecule is α-cyclodextrin, hydroxypropyl α-cyclodextrin, carboxymethyl α-cyclodextrin, amino α-cyclodextrin, or vinyl α-cyclodextrin; the thermosensitive monomer is an unsaturated monomer with double bonds, and its molecular structure contains a hydrophobic alkyl chain structure and a hydrophilic group; the hydrophilic group is an amide bond or a quaternary ammonium bond structure, specifically, at least one of acrylamide monomers, caprolactam monomers, or ester monomers containing quaternary ammonium groups can be selected; specifically, the acrylamide monomer is N-isopropylacrylamide (abbreviated as NIPAM, structural formula is...). ), or N,N-diethylacrylamide (abbreviated as DEAM, structural formula is ); the caprolactam monomer is poly(N-vinylcaprolactam) (abbreviated as PNVCL, structural formula is ). The ester monomer containing a quaternary ammonium group is dimethylaminoethyl methacrylate (abbreviated as DMAEMA, structural formula is...). The temperature-sensitive monomers used in this invention are all hydrophilic. Hydrophobic amphiphilic molecular structure: This molecule simultaneously contains hydrophilic groups (such as amide bonds and quaternary ammonium groups) that can participate in hydrogen bonding interactions, and alkyl chains that can induce hydrophobic association. Based on this structure, the resulting polymer segments exhibit typical low critical solution temperature (LCST) behavior in aqueous solutions: below the phase transition temperature, the hydrophilic groups form hydrogen bonds with water, and the chain segments extend and dissolve; above the phase transition temperature, the intermolecular hydrogen bonds are broken, and the hydrophobic alkyl chains dominate rapid, reversible chain aggregation and physical cross-linking. This structural characteristic is the basis for achieving temperature-sensitive phase transition response and for further adjustment of phase transition temperature, hydrophobicity, and response speed through molecular design.

[0010] The unified naming rule for the temperature-sensitive slip ring-grafted polyrotaxane block topological copolymers provided by this invention is as follows: M n -b PEG y (R-α-CD g-[M n ] z ) m bM n Where: M represents the thermosensitive polymer segments grafted onto both ends of the polyether block (e.g., PNIPAM is polyisopropylacrylamide, PNIPAM is polyn-propylacrylamide), and the subscript n represents its molecular weight, ranging from 0.5k to 5000k; "-b " indicates a block; PEG" y R-α-CD indicates a polyether block (polyethylene glycol segment), with the subscript y indicating its molecular weight, ranging from 1k to 35k; R-α-CD indicates a cyclic molecule (α-... Cyclodextrin or its derivatives), for example, HP-α-CD represents hydroxypropyl-α-CD; m represents the number of cyclic molecules that cross the ring, ranging from 1 to 50; the subscript z represents the degree of substitution of its acyl halide group, ranging from 1 to 4; g "" indicates a grafting relationship. The parameter values ​​corresponding to m, y, z, and n can be easily adjusted by controlling the relative amounts of reactants during the reaction process. Those skilled in the art can design accordingly based on actual needs.

[0011] Example: PNIPAM 10k -b-PEG 35k -(HP α CD g [PNIPAM 10k ]2)8-b-PNIPAM 10k The structure of the slip-ring grafted polyrotaxane block topological copolymer is as follows: it has a polyethylene glycol backbone with a molecular weight of 35k and grafted with 8 hydroxypropyl groups. α The cyclodextrin cyclic molecule has two thermosensitive polymer segments grafted onto each cyclic molecule; the thermosensitive polymer segments grafted to both ends of the polyethylene glycol backbone and the thermosensitive polymer segments grafted onto the cyclic molecule are both polyisopropylacrylamide with a molecular weight of 10k.

[0012] A second aspect of the present invention is to provide a method for preparing a thermo-responsive slip ring-grafted polyrotaxane block topological copolymer as described in the first aspect, specifically comprising the following steps: Step 1: Construction of functionalized polyethers with terminal modification of atom transfer radical polymerization initiating groups: Polyethylene glycol is dissolved in a solvent (such as dichloromethane) and reacted with an acyl halide reagent to obtain functionalized polyethers with terminal modification of atom transfer radical polymerization (ATRP) initiating groups; Step 2: Construction of functionalized cyclodextrins with terminal modification of atom transfer radical polymerization initiating groups: α-cyclodextrin or its derivatives were reacted with acyl halide reagents in a solvent and stirred for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin or its derivatives with terminal modification of atom transfer radical polymerization initiating groups. After precipitation, washing and drying, the α-cyclodextrin was ready for use.

[0013] Step 3: Assemble the functionalized polyether with the functionalized cyclodextrin to obtain a pseudorotaxane topological core; disperse the pseudorotaxane topological core, thermosensitive monomer, catalyst, and ligand in a solvent and carry out an atom transfer radical polymerization reaction under a protective atmosphere to obtain the target product; specifically, use the functionalized polyether with ATRP initiating groups from Step 1 as a macromolecular initiator, and at least one solvent selected from N,N-dimethylformamide, water, acetone, methanol, and ethanol as the assembly and reaction solvent. After assembling with the functionalized α-cyclodextrin or its derivative obtained in Step 2, add the thermosensitive monomer and the catalyst and ligand required for the atom transfer radical polymerization system to carry out an atom transfer radical polymerization reaction, thereby forming thermosensitive polymer segments at both ends of the functionalized polyethylene glycol and on the macrocyclic cyclodextrin molecules in the pseudorotaxane topological core. After the reaction is completed, remove excess copper ions with a neutral Al2O3 flash column and freeze-dry to finally obtain the target product, thus obtaining the thermosensitive responsive slip ring grafted polyrotaxane block topological copolymer.

[0014] In the above steps, on the one hand, the main chain length and side chain length can be precisely controlled by the feeding ratio of functionalized polyether, functionalized cyclodextrin and temperature-sensitive monomer; on the other hand, the grafting density can be precisely controlled by changing the feeding ratio of functionalized polyether, functionalized cyclodextrin and the degree of substitution of acyl halide groups on the macrocyclic cyclodextrin molecule, which greatly improves the synthesis efficiency and structural controllability.

[0015] Further, in step 1, the functionalized polyethylene glycol with an atom transfer radical polymerization (ATRP) initiator group at the end is prepared by the following method: the polyethylene glycol is reacted with at least one acyl halide reagent selected from 2-bromoisobutyryl bromide, 2-bromopropionyl bromide, 2-bromobutyryl bromide, 2-chloroisobutyryl chloride, 2-chloropropionyl chloride and 2-chlorobutyryl chloride in at least one solvent selected from N-methylpyrrolidone, N,N-dimethylformamide, and dichloromethane, wherein the molar ratio of the polyether to the acyl halide reagent is 1 to 1:20.

[0016] Furthermore, in step 3, the assembly reaction temperature is 0~50℃ and the reaction time is 0.5~5 days.

[0017] Further, in step 3, the temperature-sensitive monomer and the functionalized polyether are fed at a mass ratio of 1 to 100:1; the catalyst is at least one of ferrous chloride, ferric chloride, cuprous chloride, cuprous chloride, cuprous bromide, and cuprous bromide; and the ligand is at least one of triethylamine, 4-dimethylaminopyridine, tris(2-dimethylaminoethyl)amine, 2,2'-bipyridine, and 4,4'-bipyridine.

[0018] This invention utilizes a one-pot polymerization method for assembly and stepwise polymerization, using functionalized polyethers and cyclodextrins or their derivatives as starting materials. The product transformation is completed in only two steps within the same reaction system: first, a pseudo-rotaxane topological core is constructed through host-guest interactions; then, using this core as an initiator, a sliding ring-grafted polyrotaxane block topological copolymer is formed via atom transfer radical polymerization. Through step integration and precise control, this method ultimately yields a sliding ring-grafted polyrotaxane block topological copolymer with a precisely tunable structure and temperature-sensitive phase transition sensitivity. The aqueous solution of this material exhibits low viscosity in its sol state and high strength and toughness in its condensed state.

[0019] This invention further provides the application of the above-mentioned temperature-responsive slip ring-grafted polyrotaxane block topological copolymer in high-strength and tough injectable hydrogels, specifically as follows: A sol of 10wt%-20wt% is prepared using a slip-ring grafted polyrotaxane block topological copolymer. This system has low viscosity in the sol state, making it easy to apply to wounds via syringe or spray. Under body temperature, it rapidly transforms into a gel state, forming a covering layer with good mechanical stability, thus effectively adapting to wounds with complex shapes. Compared with existing technologies, the hydrogel of this invention significantly reduces sol viscosity and weakens thermal hysteresis while maintaining high gel strength, resulting in better controllability and responsiveness in practical applications. Furthermore, its network structure possesses certain dynamic characteristics, which help alleviate external stress and improve the fit and comfort of the dressing.

[0020] The thermosensitive injectable tough hydrogel solution prepared in this invention has good stretchability and cyclic tensile stability in the gel state. It can maintain structural integrity and mechanical properties under repeated deformation conditions, thus adapting to the dynamic mechanical environment of soft tissue and having the potential to be used as a tissue engineering scaffold material.

[0021] Compared with existing technologies, the beneficial effects of this invention are reflected in: 1. Compared with the multi-step sequential polymerization of traditional block copolymers, the present invention uses a "one-pot" method to complete assembly and polymerization, and completes the construction of topological core, simultaneous main chain extension and end capping and side linking in a single reaction system in sequence, which significantly simplifies the synthesis steps.

[0022] 2. Compared with traditional thermosensitive block copolymer hydrogels, the hydrogel of the present invention maintains low viscosity in the sol state and is easy to inject, while achieving high strength and high toughness mechanical properties in the gel state. It also has good ease of operation and structural stability, thus significantly expanding its application potential in medical materials such as wound dressings.

[0023] 3. The modulus and toughness of the hydrogel described in this invention can be flexibly customized by adjusting the molecular weight and the ring density, so that its mechanical strength (such as Young's modulus, fracture energy, etc.) can highly simulate the mechanical behavior of natural soft tissues such as muscles and skin. This high mechanical matching not only effectively solves the problem of limited application of traditional injectable thermosensitive hydrogels due to insufficient mechanical strength or high brittleness, but its excellent cyclic tensile recovery also endows the material with excellent fatigue resistance, significantly broadening its application range in tissue engineering. Attached Figure Description

[0024] Figure 1 This invention relates to the reaction steps and related chemical reaction formulas involved in the preparation of the thermosensitive slip ring grafted polyrotaxane block topological copolymer. Figure 2 PEG prepared in Example 1 20K -2MeBr 1H NMR spectrum; Figure 3 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K The hydrogen nuclear magnetic spectrum (¹H NMR); Figure 4 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Gel permeation chromatogram (GPC); Figure 5 PEG prepared in Example 2 35K -MeBr 1H NMR spectrum; Figure 6 The 1H NMR spectrum (¹H NMR) of the cyclodextrin derivative CM-α-CD-(MeBr)2 with a degree of substitution of 2 prepared in Example 2; Figure 7 The PNIPAM prepared in Example 2 of this paper 110K -b-PEG35K -(CM-α-CD-g-[PNIPAM 110K ]2)5-b-PNIPAM 110K The hydrogen nuclear magnetic spectrum (¹H NMR); Figure 8 The PNIPAM prepared in Example 2 of this paper 110K -b-PEG 35K -(CM-α-CD-g-[PNIPAM 110K ]2)5-b-PNIPAM 110K Gel permeation chromatogram (GPC); Figure 9 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K A schematic diagram illustrating the injectability of a 10wt% sol at 25°C; Figure 10 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Shear rate-viscosity curve; Figure 11 PNIPAM prepared for Comparative Example 1 50K - b -PEG 20K - b -PNIPAM 50K A schematic diagram showing the failure of the sol to gel at 40°C and demold. Figure 12 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K A schematic diagram of the gelation and demolding of a 10wt% sol at 40℃ and its stretchability; Figure 13 The PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Temperature-modulus curve; Figure 14 PNIPAM prepared for Comparative Example 1 50K - b -PEG 20K - b -PNIPAM 50K Temperature-modulus curve; Figure 15 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Shear stress-strain curves of 10 wt% sol in the gelled state at 40 °C; Figure 16 PNIPAM prepared in Example 3 40K - b -PEG 20K -( CM-α-CD- g -PNIPAM 40K ) 15 - b -PNIPAM 40K Shear stress-strain curves of 10 wt% sol in the gelled state at 40 °C; Figure 17 PNIPAM prepared for Comparative Example 1 50K - b -PEG 20K - b -PNIPAM 50K Shear stress-strain curves of 10 wt% sol in the gelled state at 40 °C; Figure 18 PNIPAM prepared in Example 1 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Cyclic creep-strain recovery curves of 10 wt% sol in the gelled state at 40 °C. Detailed Implementation

[0025] The present invention will be further described below with reference to the accompanying drawings and embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments are not intended to limit the present invention. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the experimental materials and reagents used in the embodiments are commercially available unless otherwise specified.

[0026] refer to Figure 1 , Figure 1 The main reaction steps and related chemical reaction formulas involved in the preparation of the thermosensitive slip ring grafted polyrotaxane block topological copolymer of the present invention are described below with reference to specific examples.

[0027] Example 1 PNIPAM 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 24 -b-PNIPAM 50K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 20K -2MeBr, its structural formula is (where l is the number of polyethylene glycol monomer units), after precipitation, washing, and drying, it is ready for use. Its ¹H NMR spectrum is shown below. Figure 2 As shown, from Figure 2 It can be seen that the aliphatic hydrogen signal around 2.0 ppm corresponds to the methyl hydrogen of 2-bromoisobutyryl bromide, and the hydrogen signal between 3.5 and 4.0 ppm corresponds to the hydrogen on the methylene group in PEG. Integration proves that the degree of substitution of the 2-bromoisobutyryl bromide initiating group is fully substituted.

[0028] Step 2: Dissolve α-cyclodextrin and 2-bromoisobutyryl bromide in DMF at a molar ratio of hydroxyl to acyl bromide group of 1:1.1. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin with a monosubstituted 2-bromoisobutyryl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named α-CD-2MeBr.

[0029] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol prepared in Step 1 in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.12g of α-CD-2MeBr prepared in Step 2 in 3mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solution A and solution B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core; the reaction process is described in [reference needed]. Figure 1 The reaction shown in step 1 of the process.

[0030] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation; separately, 6.5 g of NIPAM was dissolved in 65 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the above deoxygenated pseudorotaxane topological core water / DMF mixed solution and temperature-sensitive monomer solution were transferred together to a reaction flask containing 1 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. The reaction was stirred at 45 °C for 8 h, and the reaction proceeded. Figure 1 The reaction proceeds in step 2. Excess copper ions are removed by a neutral Al₂O₃ flash column, followed by freeze-drying to finally obtain the target product.

[0031] The molecular formula of the target product obtained in Example 1 is PNIPAM. 50K -b-PEG 20K -(α-CD-g-PNIPAM 50K ) 30 -b-PNIPAM 50K Its 1H NMR spectrum is as follows: Figure 3 As shown in the spectrum, aliphatic hydrogen signals can be observed in the range of approximately 1.0–2.5 ppm, corresponding to the aliphatic structure of NIPAM; obvious ether-related hydrogen signals can be observed in the range of approximately 3.3–4.5 ppm, corresponding to the polyethylene glycol (PEG) segment; and a hydrogen signal at 5.0 ppm corresponds to α-CD. The simultaneous presence of these characteristic signals indicates that the substance is composed of multiple structural units, including poly(N-isopropylacrylamide), polyethylene glycol, and α-cyclodextrin, and its structure is consistent with that of the molecule described above. The final polymer molecular weight and the number of rings were calculated from the above NMR data.

[0032] Its gel permeation chromatography (GPC) chromatogram is as follows: Figure 4 As shown. The number-average molecular weight (M) of this polymer was calculated. n The molecular weight is 1612 kDa, the weight-average molecular weight (Mw) is 2112 kDa, and the polydispersity index (PDI) is... = Mw / M n The result is 1.31. The results show that the polymer prepared by the "one-pot method" of this invention, which completes assembly and polymerization, has a controllable molecular weight and a narrow molecular weight distribution. <1.5, demonstrating that this method has good controllability in synthesizing complex slip ring-grafted polyrotaxane block topological copolymers.

[0033] Example 2 PNIPAM 110K -b-PEG 35K -(CM-α-CD-g-[PNIPAM 110K ]2)5-b-PNIPAM 110K Step 1: Polyethylene glycol with a molecular weight of 35,000 and 2-bromopropionyl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol with 2-bromopropionyl bromide initiating groups at the end, abbreviated as PEG. 35K -MeBr, after precipitation, washing and drying, is ready for use. Its ¹H NMR spectrum is as follows: Figure 5 As shown. The aliphatic hydrogen signal around 1.75 ppm corresponds to the methyl hydrogen of 2-bromopropionyl bromide, the aliphatic hydrogen signal around 4.5 ppm corresponds to the bromomethyl hydrogen of 2-bromopropionyl bromide, and the hydrogen signal between 3.5 and 4.0 ppm corresponds to the hydrogen on the methylene group in PEG. Integration proves that the degree of substitution of the 2-bromopropionyl bromide initiating group is fully substituted.

[0034] Step 2: Dissolve CM-α-cyclodextrin and 2-bromopropionyl bromide in DMAc at a molar ratio of hydroxyl to acyl bromide group of 1:2.2. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized CM-α-cyclodextrin with 2-substituted 2-bromopropionyl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named CM-α-CD-(MeBr)2. Figure 6 The ¹H NMR spectrum of this substance shows an aliphatic hydrogen signal around 2.0 ppm, corresponding to the methyl hydrogen of 2-bromopropionyl bromide, and hydrogen signals between 4.9 and 5.2 ppm, corresponding to the hydrogen on the α-CD glucose unit in CM-α-CD. Integration proves that the degree of substitution of the initiating group of 2-bromopropionyl bromide is 2-substituted.

[0035] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.02g of CM-α-CD-(MeBr)2 in 0.2mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0036] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 3.8 g of NIPAM was dissolved in 38 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixture and the monomer solution were transferred together to a pre-deoxygenated reaction flask containing 10 mg of cuprous bromide and 60 µL of tris(2-dimethylaminoethyl)amine. The mixture was stirred at 45 °C for 8 h. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the final target product.

[0037] The molecular formula of this substance is PNIPAM. 110K -b-PEG 35K -(CM-α-CD-g-[PNIPAM 110K ]2)5-b-PNIPAM 110K Its 1H NMR spectrum is as follows: Figure 7 The NMR data show that aliphatic hydrogen signals in the range of approximately 1.0–2.5 ppm correspond to the aliphatic structure of NIPAM; distinct ether-related hydrogen signals are observed in the range of approximately 3.3–4.5 ppm, corresponding to related structures and carboxymethyl substituents in the polyethylene glycol (PEG) chain and α-cyclodextrin backbone; and hydrogen signals in the range of 4.9–5.2 ppm correspond to hydrogens on the α-CD glucose units in CM-α-CD. The simultaneous presence of these characteristic signals indicates that the substance is composed of multiple structural units, including poly(N-isopropylacrylamide), polyethylene glycol, and CM-α-cyclodextrin, and its structure is consistent with the described molecule. The final polymer molecular weight and number of rings were calculated from the above NMR data.

[0038] Its gel permeation chromatography (GPC) chromatogram is as follows: Figure 8 As shown. The number-average molecular weight (M) of this polymer was calculated. n ) 1362kDa, weight-average molecular weight (Mw) is 1743kDa, polydispersity index ( = Mw / M n The result is 1.28. The results show that the polymer prepared by the "one-pot method" of this invention, which completes assembly and polymerization, has a controllable molecular weight and a narrow molecular weight distribution. <1.5, demonstrating that this method has good controllability in synthesizing complex slip ring-grafted polyrotaxane block topological copolymers.

[0039] Example 3 PNIPAM 40K - b -PEG 20K -( CM-α-CD- g -PNIPAM 40K ) 15 - b -PNIPAM 40K Step 1: Polyethylene glycol with a molecular weight of 20,000 and bromobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromobutyryl bromide initiating groups at the end. 20K -EtBr, after precipitation, washing and drying, is ready for use.

[0040] Step 2: Dissolve CM-α-cyclodextrin and bromobutyryl bromide in NMP at a molar ratio of hydroxyl to acyl bromide group of 1:1.2. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized CM-α-cyclodextrin with a monosubstituted bromobutyryl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named CM-α-CD-EtBr.

[0041] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.075g of CM-α-CD-EtBr in 2mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0042] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 3.4 g of NIPAM was dissolved in 34 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixture and the temperature-sensitive monomer solution were transferred together to a reaction flask containing 1 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. The mixture was stirred at 45 °C for 8 h. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the final target product.

[0043] The molecular formula of this substance is PNIPAM. 40K - b -PEG 20K -( CM-α-CD- g -PNIPAM 40K ) 15 - b -PNIPAM 40K The peak positions of the NMR spectrum and the calculation method of molecular weight are the same as in Example 2.

[0044] Example 4 PNIPAM 50K - b -PEG 20K -(NH2-α-CD- g -PNIPAM 50K ) 10 - b -PNIPAM 50K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 20K -2MeBr was precipitated, washed, and dried for later use.

[0045] Step 2: Dissolve NH2-α-cyclodextrin and 2-bromoisobutyryl bromide in DMAc at a molar ratio of hydroxyl to acyl bromide group of 1:1.1. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized NH2-α-cyclodextrin with 2-substituted 2-bromoisobutyryl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named NH2-α-CD-2MeBr.

[0046] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.05g of NH2-α-CD-2MeBr in 0.5mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0047] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation; separately, 3g of NIPAM was dissolved in 30mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the above deoxygenated pseudorotaxane topological core water / DMF mixed solution and temperature-sensitive monomer solution were transferred together to a reaction flask containing 1mg of cuprous bromide and 20µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated, and the reaction was stirred at 45°C for 8h. Excess copper ions were removed by a neutral Al₂O₃ flash column, and the product was freeze-dried to finally obtain the target product.

[0048] Example 5 PNIPAM 3K - b -PEG 20K -(α-CD- g -[PNIPAM 3K ]3)8- b -PNIPAM 3K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 20K-2MeBr was precipitated, washed, and dried for later use.

[0049] Step 2: Dissolve α-cyclodextrin and 2-bromoisobutyryl bromide in pyridine at a molar ratio of hydroxyl to acyl bromide group of 1:3.3. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin with 3-substituted 2-bromoisobutyryl bromide initiating group at the end. After precipitation, washing and drying, it is used for later use and named α-CD-(2MeBr)3.

[0050] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.04g of α-CD-(2MeBr)3 in 0.5mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0051] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 0.39 g of NIPAM was dissolved in 4 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixture and the temperature-sensitive monomer solution were transferred together to a reaction flask containing 1 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. The mixture was stirred at 45 °C for 8 h. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the target product.

[0052] Example 6 PDEAM 20K -co-PNIPAM 20K - b -PEG 10k -(NH2-α-CD- g -PNIPAM 20K -co-PDEAM 20K )8- b -PDEAM 20k -co-PNIPAM 20K (Where -co- indicates concatenation of multiple segments) Step 1: Polyethylene glycol with a molecular weight of 10000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 10K -2MeBr was precipitated, washed, and dried for later use.

[0053] Step 2: Dissolve NH2-α-cyclodextrin and 2-bromoisobutyryl bromide in DMF at a molar ratio of hydroxyl to acyl bromide group of 1:1.1. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin with a monosubstituted 2-bromoisobutyryl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named NH2-α-CD-2MeBr.

[0054] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.08g of NH2-α-CD-2MeBr in 1mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0055] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 2 g of NIPAM was dissolved in 20 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixed solution and the temperature-sensitive monomer solution were transferred together to a reaction flask containing 2 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. After stirring at 45 °C for 6 h, 2 g of PDEAM was dissolved in a mixed solution of 5 mL of DMF and 5 mL of water to prepare a monomer solution. This solution was further deoxygenated and then added to the mixed solution for another 6 h of reaction. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the final target product. The use of a multi-block monomer allows for the utilization of the temperature differences in the thermosensitive response of the polymers corresponding to the monomers to achieve multi-order responses.

[0056] Example 7 PDMAEMA 30K -co-PNIPAM 30K - b -PEG 20k -(CM-α-CD- g -PNIPAM 30K -co-PDMAEMA 30K ) 15 - b -PDMAEMA 30K -co-PNIPAM 30K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end.20K -2MeBr was precipitated, washed, and dried for later use.

[0057] Step 2: Dissolve CM-α-cyclodextrin and 2-bromoisobutyryl bromide in DMF at a molar ratio of hydroxyl to acyl bromide group of 1:1.1. Stir and react for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin with a monosubstituted 2-bromoisobutyryl bromide initiator group at the end. After precipitation, washing and drying, it is used for later use and named CM-α-CD-2MeBr.

[0058] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.08g of CM-α-CD-2MeBr in 1mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0059] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 2.6 g of NIPAM was dissolved in 25 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixed solution and the temperature-sensitive monomer solution were transferred together to a reaction flask containing 2 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. After stirring at 45 °C for 6 h, 2.6 g of DMAEMA was dissolved in a mixed solution of 5 mL of DMF and 5 mL of water to prepare a monomer solution. After further deoxygenation, this solution was added to the mixed solution and reacted for another 6 h. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the target product.

[0060] Example 8 PNVCL 10K -co-PNIPAM 20K - b -PEG 40k -(Hp-α-CD- g -PNIPAM 20K -co-PNVCL 10K ) 30 - b -PNIPAM 20K -co-PNVCL 10K Step 1: Polyethylene glycol with a molecular weight of 40,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 40K -2MeBr was precipitated, washed, and dried for later use.

[0061] Step 2: HP-α-cyclodextrin and 2-bromoisobutyryl bromide were dissolved in DMF at a molar ratio of hydroxyl to acyl bromide group of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized α-cyclodextrin with a monosubstituted 2-bromoisobutyryl bromide initiator group at the end. After precipitation, washing and drying, it was used for later use and named HP-α-CD-2MeBr.

[0062] Step 3: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.08g of HP-α-CD-2MeBr in 1mL of water to prepare solution B. Under the conditions of pH=7 and temperature of 20℃, mix solution A and solution B and stir for 12h to complete the host-guest ring-connection assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0063] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation. Separately, 1.6 g of NIPAM was dissolved in 16 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the deoxygenated pseudorotaxane topological core water / DMF mixed solution and the temperature-sensitive monomer solution were transferred together to a reaction flask containing 2 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. After stirring at 45 °C for 6 h, 0.8 g of NVCL was dissolved in 8 mL of water to prepare a monomer solution, which was further deoxygenated and then added to the mixed solution for another 6 h of reaction. Excess copper ions were removed using a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the target product.

[0064] Comparative Example 1 PNIPAM 50K - b -PEG 20K - b -PNIPAM 50K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromopropionyl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromopropionyl bromide initiating groups at the end. 20K-MeBr, after precipitation, washing and drying, is ready for use.

[0065] Step 2: Dissolve 0.1 g of the functionalized polyethylene glycol in 2 mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; separately dissolve 0.5 g of NIPAM in 5 mL of water to prepare temperature-sensitive monomer solution B. Perform three freeze-drain-thaw cycles on solutions A and B respectively to thoroughly deoxygenate them. Under nitrogen protection, transfer the deoxygenated pseudorotaxane solution and the temperature-sensitive monomer solution together to a reaction flask containing 1 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which has been pre-deoxygenated. Stir the reaction at 45 °C for 8 h. Remove excess copper ions using a neutral Al₂O₃ flash column and freeze-dry to finally obtain the target product.

[0066] Comparative Example 2 PNIPAM 50K - b -PEG 20K -(α-CD) 24 - b -PNIPAM 50K Step 1: Polyethylene glycol with a molecular weight of 20,000 and 2-bromoisobutyryl bromide were dissolved in dichloromethane at a molar ratio of hydroxyl to acyl bromide groups of 1:1.1. The mixture was stirred and reacted for 24 hours under ice bath and nitrogen protection to prepare functionalized polyethylene glycol (PEG) with 2-bromoisobutyryl bromide initiating groups at the end. 35K -2MeBr was precipitated, washed, and dried for later use.

[0067] Step 2: Dissolve 0.1g of the functionalized polyethylene glycol in 2mL of a mixed solvent of water and DMF (volume ratio 1:1) to prepare solution A; dissolve 0.12g of α-CD in 1.2mL of water to prepare solution B. Under conditions of pH=7 and temperature of 20℃, mix solutions A and B and stir for 12h to complete host-guest circumferential assembly, obtaining a water / DMF mixed solution containing a pseudorotaxane topological core.

[0068] Step 4: The obtained pseudorotaxane topological core solution was subjected to three freeze-drain-thaw cycles for thorough deoxygenation; separately, 0.5 g of NIPAM was dissolved in 5 mL of water to prepare a temperature-sensitive monomer solution. Under nitrogen protection, the above deoxygenated pseudorotaxane topological core water / DMF mixed solution and temperature-sensitive monomer solution were transferred together to a reaction flask containing 1 mg of cuprous bromide and 20 µL of tris(2-dimethylaminoethyl)amine, which had been pre-deoxygenated. The reaction was stirred at 45 °C for 8 h. Excess copper ions were removed by a neutral Al₂O₃ flash column, and the product was freeze-dried to obtain the target product.

[0069] Application Example 1 Application testing of slip ring-grafted polyrotaxane block topological copolymers in the preparation of injectable, tough hydrogels This embodiment illustrates how the slip-ring grafted polyrotaxane block topological copolymer prepared in Example 1 was configured into a 10 wt% thermosensitive hydrosol solution for the preparation of an injectable hydrogel. The specific steps are as follows: The hydrogel prepared by diluting Example 1 to a 10 wt% aqueous solution was loaded into a 1 mL medical syringe, fitted with a 25G medical injection needle, and tested after equilibration at room temperature for 30 min. Under conditions of 23±2℃, the syringe plunger was advanced at a constant speed of 30 mm / min, and the change in pushing force was recorded.

[0070] The results showed that the hydrogel extrusion process was continuous, uniform, and smooth, without clogging, flow interruption, or stringing. The average extrusion force was 3.2 N, the maximum extrusion force did not exceed 4.0 N, the extrusion resistance was moderate, and it had good medical injectability, making it suitable for minimally invasive injection and in-situ molding applications.

[0071] Reference for corresponding hydrogel extrusion states (see attached) Figure 9 .

[0072] Viscosity tests were performed on the sol-gel thermosensitive hydrogel of Example 1 at temperatures of 20°C and 5°C. The results are as follows: Figure 10 As shown, the viscosity is only 3.9 Pa·s at 5℃ and even lower at 20℃, only 2.2 Pa·s, which also indicates that the 10wt% sol of this slip ring grafted polyrotaxane block topological copolymer has a viscosity that is easy to inject.

[0073] Application Example 2 Rheological properties testing of slip ring-grafted polyrotaxane block topological copolymer sol phase transition gel The solutions of Comparative Example 1 and Example 1 were respectively cast onto silicone rubber molds using syringes and preheated in a hot water bath for 2 minutes to obtain gel-state thermosensitive hydrogel strips with a thickness of about 0.5 mm.

[0074] The thermosensitive hydrogel sample formed in Comparative Example 1 was brittle and weak, and crumbled easily upon demolding; the thermosensitive hydrogel formed in Example 1 was flexible and could be easily demolded as shown in the attached figure. Figure 11 , 12 As shown.

[0075] Temperature-modulus testing was performed on the gel-state thermosensitive hydrogel of Example 1, with a test temperature range of 0-50℃. The results are as follows: Figure 13 As shown, the maximum G' reaches 366.9 Pa, and the condensed state G' / G” ratio reaches 10.3, indicating that the 10wt% sol-phase transition gel of this slip ring-grafted polyrotaxane block topological copolymer is an elastically dominant, self-supporting gel. The temperature-modulus test curve corresponding to Comparative Example 1 is shown below. Figure 14The G' / G” shown is only 2.6, which is typical of a weak gel.

[0076] The performance of the prepared gel-state thermosensitive hydrogel was tested under the following conditions: temperature-modulus curve: heating rate of 2 degrees / minute, frequency of 1 Hz, stress of 1 Pa; shear stress-strain curve test: frequency of 1 Hz, stress of 1-10000 Pa; creep cycle test: frequency of 1 Hz, stress of 50 Pa.

[0077] The shear stress-strain test results of the thermosensitive hydrogel formed by the copolymer prepared in Example 1 are as follows: Figure 15 As shown, the maximum shear stress it can withstand can reach 1595 Pa. The shear stress-strain curve of the gel-state thermosensitive hydrogel in Example 3 is shown below. Figure 16 As shown, the maximum shear stress is 800.1 Pa. The shear stress-strain curve for Comparative Example 1 is shown below. Figure 17 The corresponding shear stress is only 97.8 Pa. This indicates that the strength and toughness of the 10 wt% sol-phase transition gel of the slip ring-grafted polyrotaxane block topological copolymer are significantly improved.

[0078] Cyclic creep tests were conducted on the gel-state thermosensitive hydrogel of Example 1 at a temperature of 38°C and an applied stress of 50 Pa. The results are as follows: Figure 18 As shown, the maximum strain was 25% when stress was first applied, and the recovery rate remained at around 80% after 5 creep cycles, indicating that the strength and toughness of the 10wt% sol phase transition gel of the slip ring grafted polyrotaxane block topological copolymer were significantly improved.

[0079] The products prepared in Examples 2 to 8 were formulated into 10 wt% sols for rheological testing. The results are shown in Table 1. As can be seen from Table 1, when the total molecular weight and the number of rings are at a high level, this slip-ring grafted polyrotaxane block topological copolymer can maintain a low viscosity and low loss modulus in the sol state, while exhibiting a high loss modulus / storage modulus ratio in the phase transition gel state, as well as relatively excellent shear stress resistance and creep resistance. This is because, compared with traditional random grafting or single-block systems, this dual thermosensitive synergistic design of the main chain and sliding side chains has significant structural advantages: when entering a high-temperature environment (above LCST), the ends of the main chain and the sliding brushes of the side chains simultaneously generate hydrophobic interactions. The sliding nature of the slip rings makes the thermosensitive segments more inclined to form intermolecular hydrogen bonds, forming an intermolecular physical cross-linking network, that is, when the temperature rises above LCST, a topological network with a certain degree of toughness is rapidly constructed.

[0080] Table 1. Rheological and mechanical test results of sols and phase transition gels prepared in different embodiments.

[0081] Note: The product prepared in Example 7 has a structural characteristic that raises the temperature-sensitive phase transition temperature to 45°C. Therefore, the gel performance test results corresponding to Example 7 were tested under the condition of 45°C. The shear stress test and creep recovery rate test of Comparative Example 1 were brittle at the beginning and could not be used to obtain effective data.

[0082] Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. A slip-ring grafted polyrotaxane block topological copolymer characterized in that, Its chemical structural formula is ; wherein: is a block co-polymer main chain; is a polyether block; represents a cyclic molecule, m represents the number of cyclic molecules, and m has a value of 1-50; the cyclic molecule is capable of sliding along the polyether block in the block copolymer main chain, and the sliding behavior is constrained by the temperature-sensitive polymer segments at both ends of the block copolymer main chain; The polyether block has identical thermosensitive polymer segments grafted to both ends and the cyclic molecule. The thermosensitive polymer segments are obtained by polymerization of thermosensitive monomers. n represents the molecular weight of the thermosensitive polymer segments, with a value ranging from 0.5k to 5000k. The thermosensitive monomer is an unsaturated monomer with double bonds, and its molecular structure contains hydrophobic alkyl chain structures and hydrophilic groups. R3 is either -Cl or -Br; R4 is obtained by polymerization of temperature-sensitive monomers; R5 is -H or -CH3; R6 is either -CH3 or -CH2CH3.

2. The sliding-ring grafted polyrotaxane block-topology copolymer according to claim 1, characterized in that, The temperature-sensitive monomer is at least one of acrylamide monomers, caprolactam monomers, or ester monomers containing quaternary ammonium groups.

3. The slip ring-grafted polyrotaxane block topological copolymer according to claim 2, characterized in that, The acrylamide monomer is N-isopropylacrylamide or N,N-diethylacrylamide; the caprolactam monomer is N-vinylcaprolactam; and the ester monomer containing a quaternary ammonium group is dimethylaminoethyl methacrylate.

4. The slip ring-grafted polyrotaxane block topological copolymer according to any one of claims 1 to 3, characterized in that, The polyether block is a polyethylene glycol segment.

5. The slip ring-grafted polyrotaxane block topological copolymer according to any one of claims 1 to 3, characterized in that, The cyclic molecule is α-cyclodextrin, hydroxypropyl α-cyclodextrin, carboxymethyl α-cyclodextrin, amino α-cyclodextrin, or vinyl α-cyclodextrin.

6. The method for preparing the slip ring-grafted polyrotaxane block topological copolymer according to any one of claims 1 to 5, characterized in that, Includes the following steps: The polyether was reacted with an acyl halide reagent to obtain a functionalized polyether with terminally modified atom transfer radical polymerization initiator groups; Cyclodextrin or cyclodextrin derivatives are reacted with acyl halide reagents to obtain functionalized cyclodextrins with terminally modified atom transfer radical polymerization initiator groups; Functionalized polyethers and functionalized cyclodextrins were assembled to obtain pseudorotaxane topological cores; The pseudorotaxane topological core, temperature-sensitive monomer, catalyst, and ligand are co-dispersed in a solvent and subjected to atom transfer radical polymerization in a protective atmosphere to obtain the target product.

7. The preparation method according to claim 6, characterized in that, The polyethylene glycol has a molecular weight of 1k to 35k; the acyl halide reagent is at least one of 2-bromoisobutyryl bromide, 2-bromopropionyl bromide, 2-bromobutyryl bromide, 2-chloroisobutyryl chloride, 2-chloropropionyl chloride, and 2-chlorobutyryl chloride.

8. The preparation method according to claim 6, characterized in that, The method for assembling functionalized polyether and functionalized cyclodextrin is as follows: the functionalized polyether and functionalized cyclodextrin are dissolved in an assembly solvent and mixed and reacted at a temperature of 0~40℃ for 0.5~5 days.

9. A high-strength, tough, injectable, toughened hydrogel, characterized in that, Its raw material composition includes the slip ring grafted polyrotaxane block topological copolymer as described in any one of claims 1 to 5 and water; its formation method is as follows: The slip ring grafted polyrotaxane block topological copolymer as described in any one of claims 1 to 5 is mixed with water to form a sol, and the sol is heated to gel it, thereby obtaining a high-strength and tough injectable strong hydrogel.

10. The high-strength and tough injectable hydrogel according to claim 9, characterized in that, The sol contains 10wt%-20wt% of slip ring-grafted polyrotaxane block topologic copolymer; the heating temperature is 40℃~50℃.

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