Block copolymer as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of chemical material engineering, and particularly relates to a block copolymer as well as a preparation method and application thereof. The segmented copolymer PPDO-PEG-COOH-PCL provided by the invention is of a triblock structure, combines the advantages of PPDO, PEG and carboxylated PCL, and can improve the biocompatibility and biodegradability of the material, so that the segmented copolymer is more suitable for implants and drug delivery systems in human bodies. Particularly, the block compound provided by the invention contains carboxylated PCL (COOH-PCL), and the introduction of the carboxylated PCL and the interaction between PPDO-PEG significantly enhance the biocompatibility and biodegradability of the material, thereby broadening the application of the block compound in the field of biomedicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical material engineering, and in particular relates to a block copolymer and a preparation method and application thereof. Background Art

[0002] Block copolymers, also known as mosaic copolymers, are a special type of polymer prepared by linking two or more polymer segments with different properties. Block polymers with specific structures exhibit properties different from simple linear polymers, many random copolymers, and even mixtures of homopolymers. They can be used as thermoplastic elastomers, blending compatibilizers, interfacial modifiers, etc. They are widely used in various fields such as biomedicine, construction, and chemical industry. Among existing polymer materials, block copolymers have attracted widespread attention due to their unique structure and properties. PPDO (polydioxanone), PEG (polyethylene glycol), and PCL (polycaprolactone) are three commonly used biodegradable polymer materials, each of which has different physical and chemical properties and biocompatibility. However, existing block copolymers often cannot combine the advantages of these materials well, which limits their application in biomedicine and other fields.

[0003] Some literatures mentioned the synthesis, characterization and gel-sol transition behavior of a water-soluble PPDO / PEG alternating multi-block copolymer. This study mainly focused on the alternating multi-block copolymer of PPDO and PEG, and the structure was alternating rather than block. Some literatures reviewed the synthesis, physical and mechanical properties of amphiphilic hydrogels based on polycaprolactone (PCL) and polyethylene glycol (PEG). It was mentioned that the combination of PEG and PCL can improve the biodegradability of PEG hydrogels, but the combination of PPDO was also not involved, and the structure was amphiphilic rather than block. Some literatures mentioned PPDO-PEG-PPDO triblock copolymers. This literature mentioned that PPDO-PEG-PPDO triblock copolymers were synthesized for the first time by suspension ring-opening polymerization (PDO) in supercritical carbon dioxide.

[0004] In summary, existing block copolymers have limitations in biocompatibility due to their structural limitations and cannot be widely used in various biomedical fields. Summary of the Invention

[0005] (1) Technical issues to be resolved

[0006] In view of the above-mentioned shortcomings and deficiencies of the prior art, the present invention provides a block copolymer having a PPDO-PEG-COOH-PCL structure, which can significantly improve the biocompatibility and biodegradability of the material, making it more suitable for use in implants and drug delivery systems inside the human body;

[0007] Correspondingly, the present invention also provides a preparation method and application of the block copolymer.

[0008] (2) In order to achieve the above-mentioned objectives, the main technical solutions adopted by the present invention include:

[0009] In a first aspect, the present invention provides a block copolymer having a block structure of PPDO-PEG-COOH-PCL.

[0010] The block copolymer PPDO-PEG-COOH-PCL of the present invention has a triblock structure that combines the advantages of PPDO, PEG, and carboxylated PCL. This improves the biocompatibility and biodegradability of the material, making it more suitable for use in implants and drug delivery systems within the human body. In particular, the block compound of the present invention contains carboxylated PCL (COOH-PCL). The interaction between the introduction of carboxylated PCL and PPDO-PEG significantly enhances the biocompatibility and biodegradability of the material, broadening its applications in the biomedical field.

[0011] More specifically, PPDO provides high mechanical strength and a suitable degradation rate, which is suitable for the strength requirements of medical implants. The introduction of PEG increases the hydrophilicity and anti-protein adsorption properties of the material, significantly improving biocompatibility. COOH-PCL gives the material acid-base responsiveness through carboxylation, and the degradation behavior of the material can be dynamically regulated by the environmental pH value. This structure is significantly superior to traditional linear block copolymers, and there is no public literature recording a triblock design that is exactly the same as the present invention. The introduction of carboxylated PCL significantly improves the cell adhesion and tissue compatibility of the material through the interaction between the surface carboxyl group and the tissue environment. The carboxyl group of COOH-PCL exhibits protonation and deprotonation behavior at different pH values, which slows down the degradation of the material in an acidic environment and accelerates degradation under neutral conditions. This responsive degradation behavior meets the needs of different stages after surgery (such as pancreatic drainage). Through block design, the material of the present invention can be applied to multiple fields such as drug delivery systems, tissue engineering scaffolds and medical drainage tubes, while traditional copolymers can usually only be optimized for a single function.

[0012] In a second aspect, the present invention provides a method for preparing a block copolymer, comprising the following steps:

[0013] The block copolymer is prepared by coupling reaction of PPDO, COOH-PCL and PEG.

[0014] The present invention uses a coupling reaction to effectively combine PPDO, PEG and COOH-PCL. COOH-PCL is directly prepared by introducing a carboxylation step during the polymerization process. Compared with late chemical modification, this avoids complex post-processing methods, can achieve high-purity, high-performance triblock copolymer products, and reduce the difficulty of industrialization.

[0015] Optionally, the coupling agent includes one or a combination of two or more of the following components: diisocyanate, epoxy group.

[0016] Optionally, a solvent is used to dissolve PPDO, COOH-PCL, PEG and a coupling agent, and the solvent is one or a combination of two or more of the following components: dimethylformamide and tetrahydrofuran.

[0017] Optionally, the method for preparing COOH-PCL comprises the following steps: preparing COOH-PCL by introducing a carboxylation step during the polymerization process of ε-caprolactone (ε-CL).

[0018] Optionally, the preparation method of COOH-PCL uses stannous octoate as a catalyst, the reaction temperature is 130-150° C., and the reaction time is 20-32 hours.

[0019] In a third aspect, the present invention provides use of the block copolymer described in any of the above solutions in medical devices.

[0020] Optionally, the medical device includes: a pancreatic juice or bile drainage tube, and a medical engineering stent.

[0021] Among them, after pancreatic cancer surgery, patients often face the problem of poor drainage of pancreatic juice and bile. Existing drainage methods and drainage tubes cannot intelligently adapt to changes in the tissue environment after surgery, resulting in poor drainage effect and slow tissue repair. The present invention can use a drainage tube made of a main material of PPDO-PEG-COOH-PCL block copolymer and a developer barium sulfate. In the early stage of tissue injury, the environmental pH value is acidic. At this time, the polymer containing COOH can be protonated, slowing the hydrolysis rate. In the later stage of tissue repair, the environment returns to a neutral pH value. At this time, COOH is deprotonated, which can increase the hydrolysis rate.

[0022] The block copolymer of this invention, through the synergistic effect of carboxyl groups and PPDO-PEG, has broad application prospects in the medical field. When used in drainage tubes, the material can remain stable in the early postoperative period, preventing premature degradation of the tubes; it can also rapidly degrade in the later stages of repair, reducing the risk of secondary tube removal.

[0023] (3) Beneficial effects

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

[0025] The present invention combines the advantages of PPDO, PEG and carboxylated PCL to prepare a block copolymer with a PPDO-PEG-COOH-PCL structure, thereby improving the biocompatibility and biodegradability of the material, making it more suitable for use in implants and drug delivery systems inside the human body, and can widely expand its application in tissue engineering, wound healing, drug delivery and other fields.

[0026] The block copolymers of the present invention can improve drug release characteristics. In drug delivery systems, controlling drug release rate and pattern is a key technical challenge. In particular, the present invention gives the material pH-responsive degradation behavior by introducing COOH-PCL blocks, solving the key problem that existing drainage tubes cannot dynamically adapt to changes in the pH of the tissue environment after surgery. In the process of overcoming the technical difficulties of carboxylation, the present invention effectively solves the two core problems of uneven control of carboxyl density (such as easy decomposition of carboxylation reagents during high-temperature ring-opening polymerization) and interference of carboxyl active sites in block coupling (easy to induce cross-linking or too wide molecular weight distribution) in traditional methods through the innovative design of in-situ polymerization and step-by-step coupling process, and successfully achieves precise control of carboxyl density (0.2-0.8 mmol / g) and stable construction of linear triblock structure; this breakthrough gives the material a unique pH-responsive degradation behavior: in an acidic environment (pH≈5.0), carboxyl protonation inhibits It can inhibit hydrolysis and maintain the structural integrity of the device (for example, the mass loss of the drainage tube after surgery is less than 20% in 28 days). In a neutral environment (pH≈7.4), the carboxyl group is deprotonated to activate nucleophilic attack and accelerate degradation (the molecular weight retention rate drops to 5.4% after 45 days), thereby dynamically adapting to the postoperative tissue repair process. At the same time, the hydrophilic-hydrophobic balance of the drug carrier is regulated by the ionization state of the carboxyl group, achieving sustained release of anticancer drugs in the acidic tumor microenvironment and reduced release in normal tissues, significantly improving the clinical adaptability and therapeutic precision of medical devices, and completely different from the existing block copolymer technology without carboxyl group functionality.

[0027] The block copolymer of the present invention can improve biocompatibility and biodegradability and enhance the mechanical properties of the material:

[0028] The block copolymer of the present invention can expand the scope of application: existing block copolymers may not be widely used in different biomedical fields due to their structural limitations.

[0029] The present invention aims to expand the application scope of the block copolymer in the fields of tissue engineering, wound healing, drug delivery, etc. through innovative block copolymer design.

[0030] The block copolymers of the present invention improve production efficiency and reduce costs: Traditional block copolymer synthesis processes can be inefficient and costly. By optimizing the synthesis method, the present invention aims to improve production efficiency and reduce costs, making the novel block copolymers more economical and practical.

[0031] The block copolymer of the present invention can enhance environmental adaptability: Taking into account the influence of environmental factors on material properties, the present invention aims to improve the stability and adaptability of the material under different environmental conditions through the design of a new block copolymer.

[0032] The present invention can prepare a block copolymer with the required corresponding biocompatibility or mechanical strength properties by adjusting the content of each group in the structure according to different application scenarios. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is the ATR-FTIR spectrum of PPDO;

[0034] Figure 2 is the ATR-FTIR spectrum of PPDO-PEG;

[0035] Figure 3 is the ATR-FTIR spectrum of PPDO-PEG-COOH-PCL;

[0036] Figure 4 is the H NMR spectrum of PPDO;

[0037] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of PPDO-PEGPPDO;

[0038] Figure 6 This is the H NMR spectrum of PPDO-PEG-COOH-PCLPPDO;

[0039] Figure 7 The degradation trend diagram of each substance;

[0040] Figure 8 This is a graph showing the molecular weight changes of various substances. DETAILED DESCRIPTION

[0041] In order to explain in detail the possible application scenarios, technical principles, specific solutions that can be implemented, and the purpose and effects achieved by this application, the following is a detailed description of the specific embodiments listed. The embodiments described herein are only used to more clearly illustrate the technical solutions of this application and are therefore only examples and are not intended to limit the scope of protection of this application.

[0042] References to "embodiments" herein mean that the specific features, structures, or characteristics described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the word "embodiment" in various places in the specification does not necessarily refer to the same embodiment, nor does it particularly limit its independence or relevance to other embodiments. In principle, in this application, as long as there are no technical contradictions or conflicts, the various technical features mentioned in the embodiments can be combined in any manner to form a corresponding implementable technical solution.

[0043] Unless otherwise defined, the technical terms used herein have the same meanings as those generally understood by those skilled in the art to which this application belongs; the use of relevant terms herein is only for describing specific embodiments and is not intended to limit this application.

[0044] In the description of this application, the term "and / or" is used to describe a logical relationship between objects, indicating that three relationships can exist. For example, A and / or B means: A exists, B exists, and both A and B exist. In addition, the character " / " in this document generally indicates that the objects before and after are in a logical "or" relationship.

[0045] In this application, terms such as "first" and "second" are merely used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual quantity, priority or sequence relationship between these entities or operations.

[0046] Without further limitations, in this application, the words "include", "comprise", "have" or other similar expressions used in the sentences are intended to cover non-exclusive inclusion. These expressions do not exclude the presence of additional elements in the process, method or product including the elements, so that the process, method or product including a series of elements may include not only those defined elements, but also other elements not explicitly listed, or elements inherent to such process, method or product.

[0047] Consistent with the understanding in the Examination Guidelines, in this application, expressions such as "greater than," "less than," and "exceed" are understood to exclude the number itself; expressions such as "above," "below," and "within" are understood to include the number itself. Furthermore, in the description of the embodiments of this application, "multiple" means more than two (including two), and similar expressions related to "multiple" are also understood in this manner, such as "multiple groups," "multiple times," etc., unless otherwise specifically defined.

[0048] In the description of the embodiments of the present application, the space-related expressions used, such as "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "vertical", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., indicate the orientation or position relationship based on the orientation or position relationship shown in the specific embodiments or drawings, and are only for the convenience of describing the specific embodiments of the present application or facilitating the reader's understanding, and do not indicate or imply that the device or component referred to must have a specific position, a specific orientation, or be constructed or operated in a specific orientation. Therefore, it should not be understood as a limitation on the embodiments of the present application.

[0049] Unless otherwise expressly specified or limited, in the description of the embodiments of the present application, the terms "installed", "connected", "connected", "fixed", "set", etc. used should be understood in a broad sense. For example, the "connection" can be a fixed connection, a detachable connection, or an integrated setting; it can be a mechanical connection, an electrical connection, or a communication connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be the internal connection of two elements or the interaction relationship between two elements. For those skilled in the art of the present application, the specific meanings of the above terms in the embodiments of the present application can be understood according to the specific circumstances.

[0050] Example 1

[0051] This embodiment provides a block copolymer having a block structure of PPDO-PEG-COOH-PCL.

[0052] Example 2

[0053] This embodiment provides a block copolymer having a block structure of PPDO-PEG-COOH-PCL, wherein the PPDO portion accounts for 20%-50% of the total mass of the block copolymer and provides strength and degradation performance.

[0054] PEG part: accounts for 5%-30%, provides hydrophilicity and regulates the hydrolysis rate, with a molecular weight range of 1000-6000Da. COOH-PCL part: accounts for 20%-50%, and the density of carboxyl groups affects the hydrolysis rate and acid-base responsiveness of the material.

[0055] In this embodiment, the surface hydrophilicity can be adjusted by the carboxyl content, and the typical carboxyl density is 0.2-0.8 mmol / g.

[0056] Example 3

[0057] This embodiment provides a high carboxyl content block copolymer having a PPDO-PEG-COOH-PCL block structure, wherein the PPDO portion has a molecular weight of 20,000 Da; the PEG portion has a molecular weight of 2,000 Da; and the COOH-PCL portion has a carboxyl group density of 0.6 mmol / g.

[0058] The preparation method is as follows: PPDO and PEG are coupled through diisocyanate, followed by the addition of COOH-PCL with a high carboxyl density; the solvent is dimethylformamide (DMF), the reaction temperature is 100°C, and the time is 6 hours; after precipitation in water, the product is washed with ethanol and dried in vacuo.

[0059] The high-carboxyl group-content block copolymer obtained in this embodiment has a short degradation time under neutral conditions; is suitable for drainage tubes after pancreatic cancer surgery, and has an acid-base responsive regulation function.

[0060] Example 4

[0061] This embodiment provides an application of a block copolymer in a drug carrier, wherein: PPDO-PEG-COOH-PCL: PPDO content 40%, PEG content 20%, COOH-PCL content 40%;

[0062] Drug loading: incorporation of hydrophilic drugs (such as the anticancer drug doxorubicin);

[0063] The preparation method comprises the following steps: dissolving the block copolymer in an organic solvent (THF), adding a drug solution and mixing; preparing nanoparticles by emulsification and solvent volatilization; washing and freeze-drying the nanoparticles to obtain a drug carrier.

[0064] The drug carrier obtained in this example is sustained-released in an acidic environment, and the drug release rate is regulated by changes in pH value; it can be applied to local chemotherapy of pancreatic cancer to reduce systemic toxicity.

[0065] Example 5

[0066] This embodiment provides a method for preparing a block copolymer, the steps of which are:

[0067] S1 PEG purification: Dissolve 10 g of PEG in 50 mL of dichloromethane to form a homogeneous solution. Slowly add 100 mL of ether while stirring to precipitate the PEG. Centrifuge at 5000 rpm for 10 minutes to collect the precipitate. Wash twice with ether, transfer the precipitate to a vacuum oven, and dry at 25°C for 12 hours to obtain purified PEG.

[0068] S2 synthesis and purification of PPDO:

[0069] 20 g of paradioxanone (PDO) and 0.1 wt % of stannous octoate were added to a dry reactor; the reactor was sealed and stirred at 120° C. for 72 hours to carry out a polymerization reaction; after cooling to room temperature, methanol was added to terminate the reaction; the precipitate was collected by centrifugation (4000 rpm, 10 minutes) and washed three times with methanol; the resulting precipitate was dried in a vacuum oven at 40° C. for 24 hours to obtain purified PPDO.

[0070] S3 Synthesis and purification of COOH-PCL

[0071] 30 g of ε-caprolactone (ε-CL) and 0.1 wt% stannous octoate were added to a dry reactor; a carboxylating agent was added during the reaction, and the reaction temperature was set at 140°C for 24 hours. After cooling to room temperature, 100 mL of methanol was added to terminate the reaction; the precipitate was collected by centrifugation (5000 rpm, 10 minutes) and washed twice with methanol; and dried in a vacuum oven at 45°C for 24 hours to obtain purified COOH-PCL.

[0072] COOH-PCL was synthesized by polymerization of ε-caprolactone (ε-CL), and carboxyl groups were introduced during the polymerization process. S4 Synthesis and Purification of PPDO-PEG-COOH-PCL

[0073] 2 g of purified PPDO, 1 g of PEG, and 2 g of COOH-PCL were dissolved in 30 mL of dimethylformamide (DMF); 0.5 g of diisocyanate was added as a coupling agent, and the mixture was stirred at 80°C for 6 hours. The reaction mixture was poured into 500 mL of deionized water to precipitate the polymer. The precipitate was collected by centrifugation (4000 rpm, 10 minutes) and washed once with water and once with methanol. The product was dried in a vacuum oven at 40°C to obtain the final PPDO-PEG-COOH-PCL block copolymer.

[0074] Example 6

[0075] This embodiment provides a method for preparing a PPDO-PEG-COOH-PCL block copolymer, the steps of which are:

[0076] S1 Material preparation: PPDO (molecular weight 30,000 Da); PEG (molecular weight 4,000 Da); COOH-PCL (carboxyl group density 0.4 mmol / g); diisocyanate (coupling agent); solvent: dimethylformamide (DMF);

[0077] S2 Preparation of COOH-PCL: ε-caprolactone (ε-CL) and stannous octoate catalyst were added to the reactor;

[0078] The reaction was carried out at 140°C for 24 hours while a carboxylating agent (such as maleic anhydride) was added dropwise. After cooling to room temperature, methanol was added to terminate the reaction. The precipitate was collected and dried to obtain COOH-PCL.

[0079] Coupling reaction of the S3 block copolymer: PPDO, PEG, and COOH-PCL were dissolved in DMF and mixed evenly; diisocyanate was added and reacted at 80°C for 8 hours; the reaction solution was poured into a large amount of deionized water to form a precipitate; the precipitate was centrifuged, washed, and vacuum-dried to obtain the target block copolymer.

[0080] Example 7

[0081] This embodiment provides a preparation and application of a PPDO-PEG-COOH-PCL block copolymer drainage tube, the steps of which are:

[0082] The materials used are:

[0083] PPDO-PEG-COOH-PCL block copolymers in Examples 1-4;

[0084] Barium sulfate (BaSO4): developer, medical grade;

[0085] Polymer molding equipment: used for extrusion molding.

[0086] 90 g of PPDO-PEG-COOH-PCL block copolymer and 10 g of barium sulfate were mixed uniformly at room temperature. The mixture was placed in an extruder and heated and extruded at 180°C to form a drainage tube with an outer diameter of 5 mm and an inner diameter of 3 mm. After cooling and cutting, the drainage tube was obtained to the desired length. The surface of the drainage tube was sterilized by ultraviolet light.

[0087] The method for verifying the application effect of the PPDO-PEG-COOH-PCL block copolymer drainage tube obtained in this example is: the drainage tube is used for internal drainage and support of pancreatic juice or bile in patients undergoing digestive tract surgery;

[0088] In the early stage, the environmental pH is acidic, and the protonation of the COOH group reduces the hydrolysis rate of the material, thereby maintaining the structural integrity of the drainage tube. As the tissue repairs, the pH returns to neutral, the deprotonation of the COOH group causes the hydrolysis rate of the material to accelerate, and the drainage tube gradually degrades, avoiding a second surgical removal of the tube.

[0089] Clinical observations have shown that the drainage effect is stable and the tissue repair time is shortened by 15% compared with traditional drainage tubes.

[0090] Example 8

[0091] This embodiment provides a preparation and application of a PPDO-PEG-COOH-PCL block copolymer drainage tube, the steps of which are:

[0092] Machines used: Extruder brand and model: Davis-Standard, USA, screw diameter: 25.4 mm, length-to-diameter ratio (L / D=25:1), screw type: barrier screw with spiral Maddock mixer;

[0093] S1 Drying and Dehumidification: The block copolymer particles were dried in hot air at 60°C for 4 hours; the dried block copolymer particles were mixed with 0.003 w / w barium sulfate and poured into an extruder, heated and extruded to form a drainage tube with an outer diameter of 5 mm and an inner diameter of 3 mm; the drainage tube was cooled and cut to obtain the desired length;

[0094] The extruder parameters were as follows: the temperature of different sections was set between 180°C and 195°C;

[0095] Extrusion speed (screw speed): 4-11rpm;

[0096] Traction speed: 5.3-9.3m / min;

[0097] The method for verifying the application effect of the PPDO-PEG-COOH-PCL block copolymer drainage tube obtained in this example is: internal drainage and support of pancreatic juice or bile in patients after digestive tract surgery;

[0098] In the early stage, the environmental pH is acidic, and the protonation of the COOH group reduces the hydrolysis rate of the material, thereby maintaining the structural integrity of the drainage tube. As the tissue repairs, the pH returns to neutral, the deprotonation of the COOH group causes the hydrolysis rate of the material to accelerate, and the drainage tube gradually degrades, avoiding a second surgical removal of the tube.

[0099] Clinical observations have shown that the drainage effect is stable and the tissue repair time is shortened by 15% compared with traditional drainage tubes.

[0100] Example 9

[0101] This embodiment provides an application of a block copolymer in a medical engineering stent.

[0102] Medical scaffold preparation: 3D printing was used to prepare scaffold models using PPDO-PEG-COOH-PCL block copolymers. The scaffolds had a porosity of 80% and a pore size of 100-200 μm to promote cell adhesion and tissue ingrowth.

[0103] The medical engineering stent prepared in this embodiment exhibits a lower degradation rate in an acidic environment, thereby extending the support time; in a neutral environment, the stent degradation is accelerated and eventually completely absorbed, thereby avoiding postoperative residues.

[0104] In order to prove that the block copolymer of the present invention is creative, the following experiments were performed:

[0105] The preparation method of a PPDO-PEG diblock copolymer comprises, by weight, 50-80 parts of p-dioxanone monomer, 10-30 parts of a hydroxyl-terminated PEG initiator, and 0.005-0.05 parts of a stannous octoate catalyst. The specific preparation process involves first dehydrating a PEG initiator with a molecular weight of 1000-5000 Da at 110°C and 0.1 mmHg under vacuum for 6 hours. The dehydrated PEG initiator, p-dioxanone monomer, and catalyst are then added to a reactor in the aforementioned proportions and reacted at 80-120°C under nitrogen for 6-24 hours, maintaining a vacuum of <0.1 kPa. After the reaction, 0.1-0.3 parts of glacial acetic acid are added to quench the catalyst. The product is dissolved in chloroform and purified by methanol precipitation. This purification is repeated three times before vacuum drying to obtain a PPDO-PEG diblock copolymer with a PDI ≤ 1.4, wherein the PPDO block number average molecular weight is 10k-50kDa.

[0106] Preparation of COOH-PCL: ε-caprolactone monomer, a carboxyl-containing initiator (such as malic acid or citric acid), and a stannous octoate catalyst are mixed in a molar ratio of 100:(1-5):(0.01-0.05). The mixture is reacted at 110°C under a vacuum of <0.5 kPa for 6-12 hours. By precisely controlling the initiator dosage and reaction conditions, COOH-PCL with a carboxyl content of 0.2-0.8 mmol / g, a molecular weight of 5k-20 kDa, and a PDI of <1.5 is obtained.

[0107] Experiment 1: Fourier transform infrared spectroscopy test

[0108] Sample preparation

[0109] Drying treatment: PPDO-PEG diblock copolymer, PPDO, and PPDO-PEG-COOH-PCL triblock copolymer were placed in a freeze dryer (SCIENTZ-10N / C (manifold type, cold trap temperature -85°C)) at -50°C for 48 h to remove moisture and avoid water peak interference.

[0110] Sample preparation method: The freeze-dried sample was ground into powder and mixed with potassium bromide (KBr, Sinopharm Group (GB / T 649-2023, moisture ≤ 0.3%)) at a ratio of 1:200, and pressed into transparent sheets.

[0111] 1.2. Test steps

[0112] Instrument parameter settings: infrared spectrometer (Thermo Fisher Nicolet 6700), scanning range 4000-500 cm-1; resolution set to 4 cm -1The number of scans was 32, and signal accumulation was used to improve the signal-to-noise ratio. Background correction was performed by collecting blank KBr or air background spectra under the same conditions to eliminate environmental interference.

[0113] Sample Scanning: Place the prepared sample in the sample chamber, start the scanning process, record the interference pattern, and perform a Fast Fourier Transform (FFT) to generate an infrared absorption spectrum. At least three parallel samples should be tested for each sample group to ensure data reproducibility.

[0114] In this experiment,

[0115] PPDO-PEG-COOH-PCL: carboxylic acid C=O (1700 cm -1 ) and PCL ester peak (1725cm -1 ), and the PEG ether bond peak shifts, proving the formation of triblocks and the effect of carboxyl-PEG hydrogen bonding. The coupling efficiency can also be judged by the residual hydroxyl peak to ensure the synthesis quality.

[0116] For PPDO, Figure 1 In the middle, pure PPDO is at 1720cm -1 and 1090cm -1 The characteristic peaks of ester group C=O and ether bond COC are respectively presented at the positions, and their narrow peak shape (σ=15) is related to the regular segment arrangement.

[0117] For PPDO-PEG, Figure 2 After the introduction of PEG into PPDO, the ether bond vibration peak in the PPDO-PEG diblock copolymer splits to 1090 cm -1 (PPDO) and 1100cm -1 The double peak structure of (PEG) (Δν=10cm -1 ), and the CH2 stretching vibration peak (2940 / 2860cm -1 ) intensity superposition, indicating that the two blocks are chemically bonded; and 1720 cm -1 The ester peak at 3400 cm -1 The presence of weak OH peaks further verified the covalent connection between blocks and the residual hydroxyl groups of PEG end groups.

[0118] For PPDO-PEG-COOH-PCL, Figure 3 Medium triblock copolymer, 3000cm -1 The broad peak at the center is derived from the stretching vibration of the OH group of the COOH-PCL segment carboxylic acid. Its broadening characteristics (half-peak width > 100 cm -1 ) is caused by hydrogen bonding, while 1720cm -1 The significant enhancement of the ester peak intensity at 1090 / 1100 cm is attributed to the superposition of the ester vibrations of PPDO and PCL.-1 ) and a broadened peak suggest microdomain heterogeneity caused by restricted segmental motion within the triblock copolymer. Mechanistically, a stepwise ring-opening polymerization strategy sequentially initiates the growth of PEG and COOH-PCL segments via the terminal active sites of PPDO. No characteristic peak shifts or new peaks are observed in the spectrum, ruling out the possibility of physical blending. Infrared spectroscopy confirmed the successful synthesis of the PPDO-PEG-COOH-PCL triblock copolymer.

[0119] Experiment 2: Nuclear Magnetic Proton Spectrum Test ( 1 H NMR)

[0120] Sample preparation

[0121] Solvent of choice: deuterated DMSO (DMSO-d6) (Sigma-Aldrich, 99.9%).

[0122] Sample concentration: 5-10 mg / mL. Ultrasonicate for 10 minutes after dissolution to ensure uniformity.

[0123] Instrument parameters

[0124] Instrument model: Bruker Avance III 400 MHz NMR instrument.

[0125] Scan parameters: pulse sequence was single pulse (zg30), spectral width was 20 ppm, number of scans was 64, relaxation delay was 1 s, and temperature was 25°C.

[0126] Quantitative analysis: The ratio of each block was calculated by integrating the peak areas.

[0127] Experimental groups were divided into groups to analyze block composition and coupling efficiency by chemical shift and integrated area:

[0128] For PPDO, Figure 4 It shows that the characteristic peaks of pure PPDO are highly consistent with the literature: the intracyclic methylene (1.90 ppm, multiple peaks), ether oxygen ortho position (3.72 ppm, singlet) and ether oxygen methylene (4.32 ppm, sharp singlet) correspond to the -CH2-, -O-CH2- and -O-CH2-O- groups in its repeating unit, respectively.

[0129] For PPDO-PEG, Figure 5 It shows that in the PPDO-PEG diblock copolymer, a typical single peak (-O-CH2-CH2-) of the PEG main chain appears at 3.64-3.66ppm, which is clearly distinguished from the ether oxygen ortho-peak of PPDO (3.69-3.71ppm); the newly appeared weak peak at 4.08-4.12ppm may originate from the -O-CH2-O- group at the connection between the two blocks, confirming the formation of chemical bonds between the blocks.

[0130] For PPDO-PEG-COOH-PCL, H NMR spectrum ( 1 H NMR) analysis confirmed the sequence structure of the PPDO-PEG-COOH-PCL triblock copolymer. Figure 6 In the experiment, the characteristic peaks of the PCL segment (-(CH2)3- at 1.3ppm, -CH2-C=O at 2.3ppm, and -O-CH2- at 4.0ppm) coexist with the characteristic peaks of PPDO and PEG (1.9, 3.7, and 4.3ppm), and the broad peak of the carboxylic acid proton at 12.0ppm confirms the successful introduction of the COOH-PCL end. The deviation of the peak area ratio of each component from the theoretical feed ratio is less than 5%, indicating that the step-by-step ring-opening polymerization strategy effectively realizes the sequential growth of PEG and COOH-PCL chain segments initiated by the active site at the end of PPDO. It is worth noting that no free monomer or homopolymer residual peaks were detected in the triblock copolymer (such as the 4.32ppm single peak of PPDO did not shift), which ruled out the possibility of physical blending. This NMR data corroborates the previous infrared spectroscopy analysis, providing dual evidence for the precise construction of the block copolymer. Its structural characteristics lay the foundation for subsequent research on material degradation behavior and functional applications.

[0131] Experiment 3: In vitro degradation experiment

[0132] Sample preparation

[0133] Form: thin film (thickness 0.1~0.2mm).

[0134] Size: 5×5mm 2 , mass is about 20 mg / tablet, weigh accurately.

[0135] For pH 5.0, use citric acid-sodium citrate buffer by dissolving 2.10 g of citric acid and 2.94 g of sodium citrate in 100 mL of deionized water. For pH 7.4, use phosphate buffered saline (PBS) by adding 1.36 g of potassium dihydrogen phosphate and 11.50 g of sodium dihydrogen phosphate to 1000 mL of water. For pH 8.0, use phosphate buffer (0.2 M Na₂HPO₄ and 0.2 M Na₂HPO₄ in a volume ratio of 94.7:5.3). After preparation, test with a pH meter (Mettler Toledo SevenMulti).

[0136] Degradation medium:

[0137] Acidic conditions: 0.1 M phosphate buffer (pH 5.0), neutral conditions: 0.1 M PBS buffer (pH 7.4).

[0138] Volume: 10 mL / sample, constant temperature shaking at 37°C (constant temperature shaker (New Brunswick Innova 44, rotation speed 100 rpm, 100 rpm).

[0139] Experimental procedures

[0140] Time points: 0, 7, 14, 21, 28 days.

[0141] Periodic sampling: Take out the sample, rinse with ultrapure water three times, and vacuum dry to constant weight (W1).

[0142] Buffer replacement: Change every 3 days to maintain pH stability.

[0143] 3.3. Detection indicators

[0144] Mass loss rate:

[0145] Molecular weight change: GPC analysis. The degraded sample was dissolved in DMF (Sigma-Aldrich, HPLC) containing 0.05M LiBr (2 mg / mL) and sonicated for 30 minutes. The sample was filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane. A Waters 1515 GPC system and a PLgel Mixed-D column were used with DMF as the mobile phase (flow rate 1.0 mL / min, column temperature 35°C). The number average molecular weight (M) was calculated using Waters Empower software. n ), weight average molecular weight (M w ) and dispersion

[0146] Experimental groups:

[0147] PPDO: As a basic control, the degradation rate of unmodified PPDO (mainly ester bond hydrolysis) was clarified and a benchmark degradation curve was provided;

[0148] COOH-PCL: The pH responsiveness of carboxylated PCL was tested separately to demonstrate the regulatory ability of the carboxyl group on degradation kinetics;

[0149] PEG: demonstrated rapid erosion of the highly hydrophilic segments (complete dissolution in 7 days), explaining the accelerating effect of PEG in the copolymer on medium-term water penetration;

[0150] PPDO-PEG-COOH-PCL: By comparing the first three groups, it was verified that: multi-stage degradation: PPDO maintains the initial strength, PEG accelerates the hydrolysis in the middle stage, and COOH-PCL triggers rapid disintegration in the later stage (after pH rises).

[0151] In the 45-day in vitro degradation experiment, the materials in each group showed significant differences in degradation behavior.

[0152] Figure 7 The results showed that carboxylated polycaprolactone (COOH-PCL) homopolymer exhibited a progressive mass loss (71.3±5.9% in 45 days) due to the hydrolysis resistance of the ester bonds in the molecular chain and the decrease in crystallinity caused by carboxylation.

[0153] Figure 8 The results showed that the molecular weight retention of carboxylated polycaprolactone (COOH-PCL) decreased simultaneously to 10.2±1.2% (p<0.01 vs. initial value).

[0154] In contrast, PPDO homopolymer, due to its more susceptible ester bonds to hydrolysis, degraded significantly faster, with a mass loss of 82.3±5.2% at 28 days and near-complete degradation at 45 days (96.2±6.8%). Molecular weight retention decreased to 1.5±0.2% (p<0.001), indicating that backbone cleavage dominated the degradation process. PEG's high hydrophilicity led to rapid initial swelling and enzymatic attack (45.6±3.5% mass loss at 7 days), but this slowed down due to structural disintegration (99.0±6.9% at 45 days). The degradation behavior of the block copolymer (COOH-PCL-PPDO-PEG) exhibited a synergistic effect: the PEG segments accelerated the formation of a hydrophilic microenvironment, promoting PPDO chain hydrolysis, while the COOH-PCL delayed overall disintegration. Its mass loss (88.5±6.1%) and molecular weight retention (5.4±0.8%) were intermediate between those of the homopolymers (p<0.05). The solution pH decreased from 7.4 to 6.2 ± 0.3 (day 45) during the degradation process, which was associated with the release of acidic products (such as glycolic acid and adipic acid) from PPDO and COOH-PCL.

[0155] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A block copolymer, characterized in that: It has a block structure of PPDO-PEG-COOH-PCL.

2. The block copolymer according to claim 1, wherein: The molecular weight of PPDO is 20,000 to 50,000 Da; PEG is polyethylene glycol, with a molecular weight of 1,000 to 6,000 Da; COOH-PCL is carboxylated polycaprolactone with a carboxyl group density of 0.2 to 0.8 mmol / g.

3. A method for preparing the block copolymer according to claim 1, characterized in that: It includes the following steps: The block copolymer is prepared by coupling reaction of PPDO, COOH-PCL and PEG through a coupling agent.

4. The method for preparing a block copolymer according to claim 3, wherein The coupling agent includes one or a combination of two or more of the following components: diisocyanate and epoxy group.

5. The method for preparing a block copolymer according to claim 3, wherein: PPDO, COOH-PCL and PEG are dissolved in a solvent and subjected to a coupling reaction under the action of a coupling agent; the solvent is one or a combination of two or more of the following components: dimethylformamide and tetrahydrofuran.

6. The method for preparing a block copolymer according to claim 3, wherein: The preparation method of COOH-PCL comprises the following steps: performing a ring-opening polymerization reaction of ε-caprolactone under the action of a catalyst; and adding and introducing a carboxylation reagent during the polymerization process to complete carboxylation.

7. The method for preparing a block copolymer according to claim 6, wherein: The catalyst is stannous octoate, the reaction temperature is 130-150° C., and the reaction time is 20-32 hours.

8. Use of the block copolymer according to claim 1 in medical devices.

9. Use of the block copolymer according to claim 8 in medical devices, characterized in that: The medical devices include: pancreatic juice or bile drainage tubes, and medical engineering stents.

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