A selenium-containing block polymer, a preparation method and application thereof
By precisely designing block structures, selenium-containing block polymers were prepared, overcoming the shortcomings of polyesteramide materials in terms of mechanical properties, hydrophilicity/hydrophobicity, and biodegradability. This enabled the material to achieve multifunctionality and large-scale production, making it suitable for medical devices such as covered stents and artificial blood vessels.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SUZHOU UNIV
- Filing Date
- 2026-02-27
- Publication Date
- 2026-06-05
AI Technical Summary
Existing polyesteramide materials cannot simultaneously meet the requirements of mechanical properties and hydrophilicity/hydrophobicity. Rigid materials are prone to breakage, elastic materials lack sufficient support, and they do not have adequate biodegradability. The synthesis process uses expensive or toxic raw materials and catalysts, making it difficult to achieve multifunctionality and large-scale production of the materials.
Selenium-containing block polymers were prepared by precise block structure design, comprising diselenyl ether polymer block chains and polyesteramide backbones, enabling controllable adjustment of the material's mechanical properties and hydrophilic/hydrophobic properties, and endowing the material with NO catalytic release capability. The synthesis was carried out under mild reaction conditions.
It achieves controllable adjustment of the material's mechanical properties and hydrophilic/hydrophobic properties, ensuring the long-term effectiveness of NO catalytic release function and avoiding the dissolution or shedding of functional components in the human body environment. It is suitable for medical devices such as covered stents and artificial blood vessels.
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Figure CN122145812A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, specifically to a selenium-containing block polymer and its preparation method and application. Background Technology
[0002] Polyesteramides are synthetic polymers with alternating or block-distributed ester and amide bonds in their main chain, belonging to typical segmented block copolymers. Their structural characteristics endow materials with both the mechanical strength and abrasion resistance of polyamides, as well as the good processability and biocompatibility of polyesters. Despite these advantages, polyesteramide materials still face some problems and challenges in practical applications. For example, traditional polyesteramide materials cannot simultaneously meet the requirements of mechanical properties and hydrophobicity / hydrophilicity; rigid materials are prone to fracture, elastic materials lack sufficient support, and they lack adequate biodegradability or have difficult-to-control degradation rates. Furthermore, the synthesis of polyesteramides may require expensive or toxic raw materials and catalysts, which limits their application in the biomedical field.
[0003] With the upgrading of demand, materials research and development is gradually focusing on multifunctional performance. Selenium-containing polymers have become a research hotspot due to their unique advantages such as redox response and catalytic activity. The application of derivative materials such as nano-selenium and selenium-doped polymers in antibacterial and antioxidant scenarios is constantly expanding. However, selenium-containing polymers mostly adopt simple homopolymer or random copolymer designs, lacking precise block structure control, making it difficult to achieve controllable transformation of mechanical properties (rigidity-elasticity). At the same time, functions such as hydrophilicity optimization and NO catalytic release are difficult to organically integrate in the same system, and some designs rely on complex monomer synthesis or harsh polymerization conditions, resulting in poor material performance stability, difficulty in large-scale production, and inability to meet the multi-dimensional needs of high-end medical materials.
[0004] Currently, medical materials have entered a new stage of "precise performance regulation + bioactivity integration". The key breakthroughs are in adapting the mechanical properties of materials, adjusting hydrophilicity and hydrophobicity, and integrating specific biological functions. At the same time, the large-scale production of high-end medical materials is being promoted to meet the high-end clinical needs of interventional medical devices. Summary of the Invention
[0005] This invention addresses the shortcomings of existing technologies by providing a selenium-containing block polymer, its preparation method, and its application. Through precise block structure design, a selenium-containing block polymer is prepared, resulting in a selenium-containing block polymer formula comprising a diselenyl ether polymer block chain A and a polyesteramide backbone B. This allows for controllable adjustment of the material's mechanical properties and hydrophilic / hydrophobic properties, while also endowing the material with NO catalytic release capability, thus filling the gaps in existing material design.
[0006] To address the aforementioned technical problems, the first aspect of this invention provides a method for preparing a selenium-containing block polymer, comprising the following steps:
[0007] S1 and Formula 1 compounds react under oxygen-induced conditions to obtain the polymer of Formula I;
[0008] S2. Under a protective atmosphere, the compound of formula 1 reacts with the compound of formula 2 to obtain the polymer of formula II.
[0009] S3. Under a protective atmosphere, polymer of formula I and dithreothiol undergo a reduction reaction, and then are mixed with polymer of formula II for a block reaction to obtain selenium-containing block polymer of formula III, which includes diselenyl ether polymer block chain A and polyester amide backbone B.
[0010] ;
[0011] Wherein, R is selected from (CH2CH2O). y Alkyl groups with 2-20 carbon atoms or carbon ring-containing groups with 6-20 carbon atoms, where y is an integer between 2 and 10; R 1 Selected from (CH2CH2O) x Or an alkyl group with 2-20 carbon atoms, where x is an integer between 2-10; p is an integer between 1-5; and m and n are independently selected from positive integers.
[0012] This invention prepares a selenium-containing block polymer with a "rigid backbone-hydrophilic block" composite structure through precise block structure design. The selenium-containing block polymer consists of diselenyl ether polymer block chain A (weight-average molecular weight 1-5 kg / mol) and polyesteramide backbone B (weight-average molecular weight 10-16 kg / mol), wherein the mass fraction of the block chain is strictly controlled at 5%~25%. It combines the excellent mechanical properties of polyesteramide with the good hydrophilicity of diselenyl ether polymer, solving the pain points of poor hydrophilicity and insufficient mechanical properties of single selenium-containing polymers. The selenium-containing block polymer with this composite structure enables controllable adjustment of the material's mechanical properties and hydrophilic / hydrophobic properties.
[0013] This invention utilizes precise reactions such as selenool-alkynyl click polymerization and reductive block polymerization to achieve a stable bond between selenium-containing functional segments and the matrix polymer. This avoids the risk of dissolution or shedding of functional components in the human physiological environment, ensuring the long-term effectiveness of NO catalytic generation. The preparation process of this invention is excellent, the reaction conditions are mild, and it does not require harsh extreme environments, making it easy to promote and apply.
[0014] Furthermore, in S3, the amount of polymer of formula I added is 5-25% of the total mass of polymer of formula I and polymer of formula II.
[0015] Furthermore, in S3, the molar ratio of the polymer of formula I to dithreothiol is 1:(0.8-1.2).
[0016] Furthermore, in S1, the compound of formula 1 is obtained by reacting the compound of formula 4 with a selenolactone under a protective atmosphere;
[0017] .
[0018] Furthermore, the molar ratio of the compound of formula 4 to the selenolactone is 1:(2-3).
[0019] Furthermore, the selenolactone is selected from... , , One or more of them.
[0020] Furthermore, in S2, the molar ratio of the compound of formula 1 to the compound of formula 2 is 1:(1-1.5).
[0021] Furthermore, in S2 and S3, the protective atmosphere is nitrogen and / or argon.
[0022] The synthetic route for the selenium-containing block polymer of this invention is as follows:
[0023] .
[0024] The second aspect of the present invention provides a selenium-containing block polymer prepared by the preparation method described in the first aspect.
[0025] The third aspect of this invention provides the application of the selenium-containing block polymer described in the second aspect in the fabrication of covered stents and artificial blood vessels.
[0026] The beneficial effects of this invention are:
[0027] This invention prepares a selenium-containing block polymer with a "rigid main chain-hydrophilic block" composite structure through precise block structure design, resulting in a selenium-containing block polymer formula consisting of diselenyl ether polymer block chain A and polyesteramide main chain B. The mass fraction of the block chain is strictly controlled to be 5%~25%, and the precise grafting of the main chain and block chain is achieved through selenium-carbon covalent bonds.
[0028] This invention comprises a selenium-containing block polymer with a "rigid main chain-hydrophilic block" composite structure, which enables controllable adjustment of the material's mechanical properties and hydrophilic / hydrophobic properties, while also endowing the material with NO catalytic release capability, filling the gaps in existing material designs, and can be widely used in medical devices such as covered stents and artificial blood vessels. Attached Figure Description
[0029] To more clearly illustrate the technical solution of the present invention, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0030] Figure 1This is the NMR spectrum of the selenium-containing block polymer obtained in Example 1 of the present invention;
[0031] Figure 2 These are GPC diagrams of the polymers obtained in Examples 1-5 and Comparative Example 1 of the present invention;
[0032] Figure 3 These are the polymer thermal analysis diagrams obtained from Examples 1-5 and Comparative Example 1 of the present invention;
[0033] Figure 4 These are mechanical property test diagrams of the polymer films obtained in Examples 1-5 and Comparative Example 1 of the present invention;
[0034] Figure 5 These are water contact angle test diagrams of the polymer films obtained in Examples 1-5 and Comparative Example 1 of the present invention;
[0035] Figure 6 These are NO release rate test graphs of the polymer films obtained in Examples 1-5 and Comparative Example 1 of the present invention. Detailed Implementation
[0036] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0037] This embodiment relates to a method for preparing a selenium-containing block polymer, comprising the following steps:
[0038] S1 and Formula 1 compounds react under oxygen-induced conditions to obtain the polymer of Formula I;
[0039] S2. Under a protective atmosphere, the compound of formula 1 reacts with the compound of formula 2 to obtain the polymer of formula II.
[0040] S3. Under a protective atmosphere, polymer of formula I and dithreothiol undergo a reduction reaction, and then are mixed with polymer of formula II for a block reaction to obtain selenium-containing block polymer of formula III, which includes diselenyl ether polymer block chain A and polyester amide backbone B.
[0041] ;
[0042] Wherein, R is selected from (CH2CH2O). y Alkyl groups with 2-20 carbon atoms or carbon ring-containing groups with 6-20 carbon atoms, where y is an integer between 2 and 10; R 1 Selected from (CH2CH2O) xOr an alkyl group with 2-20 carbon atoms, where x is an integer between 2-10; p is an integer between 1-5; and m and n are independently selected from positive integers.
[0043] This embodiment utilizes a precise block structure design to prepare a selenium-containing block polymer with a "rigid backbone-hydrophilic block" composite structure. The selenium-containing block polymer consists of diselenyl ether polymer block chain A (weight-average molecular weight 1-5 kg / mol) and polyesteramide backbone B (weight-average molecular weight 10-16 kg / mol), with the block chain mass fraction strictly controlled at 5%~25%. This composite structure combines the excellent mechanical properties of polyesteramide with the good hydrophilicity of diselenyl ether polymers, overcoming the shortcomings of poor hydrophilicity and insufficient mechanical properties of single selenium-containing polymers. The selenium-containing block polymer with this composite structure allows for controllable adjustment of the material's mechanical and hydrophilic / hydrophobic properties. By employing precise reactions such as selenool-alkynyl click polymerization and reductive block polymerization, a stable bond between the selenium-containing functional segments and the matrix polymer is achieved, avoiding the risk of dissolution or shedding of functional components in the human physiological environment and ensuring the long-term effectiveness of NO catalytic generation. The preparation process of this invention is excellent, the reaction conditions are mild, and it does not require harsh extreme environments, making it easy to promote and apply.
[0044] In a preferred embodiment, in S3, the amount of polymer I added is 5-25% of the total mass of polymer I and polymer II, and the molar ratio of polymer I to dithreothiol is 1:(0.8-1.2); in S2, the molar ratio of compound I to compound II is 1:(1-1.5); in S2 and S3, the protective atmosphere is nitrogen and / or argon.
[0045] In a preferred embodiment, in S1, the compound of formula 1 is obtained by reacting the compound of formula 4 and selenolactone under a protective atmosphere. The molar ratio of the compound of formula 4 and the selenolactone is 1:(2-3); the selenolactone is selected from... , , One or more of them.
[0046] The synthetic route for the selenium-containing block polymer in this embodiment is as follows:
[0047] .
[0048] Another embodiment provides a selenium-containing block polymer prepared by the preparation method described in the above embodiments.
[0049] Another embodiment provides the application of the selenium-containing block polymer described in the above embodiments in the fabrication of covered stents and artificial blood vessels.
[0050] Example 1
[0051] This embodiment relates to a method for preparing a selenium-containing block polymer, comprising the following steps:
[0052] (1) Preparation of alkynyl-terminated polyesteramide: In a glove box, 3.7 mol of 4,4'-diaminodicyclohexylmethane and 7.77 mol of selenobutyrolactone were added to a 50 ml flask and mixed evenly by magnetic stirring (300 rpm). The ring-opening reaction was carried out in 2.44 ml of hexafluoroisopropanol solution for 12 h under nitrogen atmosphere and room temperature to generate bis-terminated selenool. Then, 4.44 mol of butanediol dipropynate and 2 ml of hexafluoroisopropanol solution were added to the reaction system and the reaction was continued by stirring to complete the selenool alkynyl click polymerization to obtain alkynyl-terminated polyesteramide.
[0053] (2) Preparation of hydrophilic diselenide polymer: First, in a glove box, add 2 mol of amino-polyethylene glycol-amino and 4.4 mol of selenobutyrolactone to a 50 mL single-necked flask. Under a nitrogen atmosphere, stir magnetically (300 rpm) to mix evenly and carry out the ring-opening reaction at room temperature for 12 h. Then, introduce oxygen and continue stirring to carry out the oxidative coupling polymerization reaction for 12 h. After the reaction is completed, purify by low-temperature precipitation of diethyl ether: slowly drop the reaction solution into 10 times the volume of diethyl ether, place it in a -8℃ environment to stand and precipitate, filter and collect the precipitate, and place the precipitate in a vacuum drying oven (40℃) to dry for 12 h to obtain the hydrophilic diselenide polymer.
[0054] (3) Preparation of selenium-containing block polymer: Weigh 0.058 mol (5% by mass, based on the total mass of the final block polymer) of the hydrophilic diselenide polymer prepared in step (2), add 0.058 mol of dithreothiol, dissolve in 1 mL of hexafluoroisopropanol, and perform a reduction reaction at room temperature with magnetic stirring (300 rpm) for 3 h to obtain a hydrophilic polymer containing selenol groups; add it to a 1 mol / L polyesteramide-hexafluoroisopropanol solution, stir to complete the block reaction, and obtain the selenium-containing block polymer. The NMR spectrum is shown in [reference needed]. Figure 1 .
[0055] Example 2
[0056] The difference between this embodiment and Example 1 is that the amount of hydrophilic diselenyl ether polymer and dithreothiol added in step (3) is 0.121 mol, and the mass fraction of hydrophilic diselenyl ether polymer is 10% based on the total mass of the final block polymer. Other steps and parameters remain unchanged.
[0057] Example 3
[0058] The difference between this embodiment and Example 1 is that the amount of hydrophilic diselenyl ether polymer and dithreothiol added in step (3) is 0.221 mol, and the mass fraction of hydrophilic diselenyl ether polymer is 15% based on the total mass of the final block polymer. Other steps and parameters remain unchanged.
[0059] Example 4
[0060] The difference between this embodiment and Example 1 is that the amount of hydrophilic diselenyl ether polymer and dithreothiol added in step (3) is 0.313 mol, and the mass fraction of hydrophilic diselenyl ether polymer is 20% based on the total mass of the final block polymer. Other steps and parameters remain unchanged.
[0061] Example 5
[0062] The difference between this embodiment and Example 1 is that the amount of hydrophilic diselenyl ether polymer and dithreothiol added in step (3) is 0.417 mol, and the mass fraction of hydrophilic diselenyl ether polymer is 25% based on the total mass of the final block polymer. Other steps and parameters remain unchanged.
[0063] Comparative Example 1
[0064] The difference between this comparative example and Example 1 is that it only includes step (1) to obtain an alkyne-terminated polyesteramide.
[0065] Figure 2 and Figure 3 The GPC diagrams and thermal analysis diagrams of the polymers obtained in Examples 1-5 and Comparative Example 1 are shown respectively. The change in glass transition temperature proves that the polymers are connected by chemical covalent bonds, rather than by simple physical mixing.
[0066] Application examples
[0067] The polymers obtained in Examples 1-5 and Comparative Example 1 were used to prepare films by solution casting, and their mechanical properties, water contact angle, and NO release rate were tested.
[0068] Figure 4-6 The mechanical properties, water contact angle, and NO release rate of the polymer films from Examples 1-5 and Comparative Example 1 are presented respectively. It can be seen that the polyesteramide in Comparative Example 1 is a rigid body. In Examples 1-5, as the mass fraction of hydrophilic diselenide increased from 5% to 25%, the material changed from a rigid body to an elastomer, resulting in a corresponding increase in elongation at break and a change in water contact angle. At a mass fraction of 20%, the elongation at break was 150% and the water contact angle was 72°. Simultaneously, the increase in the hydrophilic diselenide content allows for adjustment of the initial burst amount as needed, while ensuring a continuous NO supply for more than two weeks, providing a direct basis for subsequent antibacterial or healing-promoting dosage design.
[0069] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.
Claims
1. A method for preparing a selenium-containing block polymer, characterized in that, Includes the following steps: S1 and Formula 1 compounds react under oxygen-induced conditions to obtain the polymer of Formula I; S2. Under a protective atmosphere, the compound of formula 1 reacts with the compound of formula 2 to obtain the polymer of formula II. S3. Under a protective atmosphere, polymer of formula I and dithreothiol undergo a reduction reaction, and then are mixed with polymer of formula II for a block reaction to obtain selenium-containing block polymer of formula III, which includes diselenyl ether polymer block chain A and polyesteramide chain B. ； Wherein, R is selected from (CH2CH2O). y Alkyl groups with 2-20 carbon atoms or carbon ring-containing groups with 6-20 carbon atoms, where y is an integer between 2 and 10; R 1 Selected from (CH2CH2O) x Or an alkyl group with 2-20 carbon atoms, where x is an integer between 2-10; p is an integer between 1-5; and m and n are independently selected from positive integers.
2. The method for preparing the selenium-containing block polymer as described in claim 1, characterized in that, In S3, the amount of polymer of formula I added is 5-25% of the total mass of polymer of formula I and polymer of formula II.
3. The method for preparing the selenium-containing block polymer as described in claim 1, characterized in that, In S3, the molar ratio of polymer of formula I to dithreothiol is 1:(0.8-1.2).
4. The method for preparing the selenium-containing block polymer as described in claim 1, characterized in that, In S1, the compound of formula 1 is obtained by reacting the compound of formula 4 and selenolactone under a protective atmosphere; 。 5. The method for preparing the selenium-containing block polymer as described in claim 4, characterized in that, The molar ratio of the compound of formula 4 to the selenolactone is 1:(2-3).
6. The method for preparing selenium-containing unsaturated polyesteramide as described in claim 5, characterized in that, The selenolactone is selected from , , One or more of them.
7. The method for preparing the selenium-containing block polymer according to claim 1, characterized in that, In S2, the molar ratio of the compound of Formula 1 to the compound of Formula 2 is 1:(1-1.5).
8. The method for preparing the selenium-containing block polymer according to claim 1, characterized in that, In S2 and S3, the protective atmosphere is nitrogen and / or argon.
9. A selenium-containing block polymer prepared by the preparation method according to any one of claims 1-8.
10. The application of the selenium-containing block polymer of claim 9 in the fabrication of covered stents and artificial blood vessels.