Selenium-containing polymer as well as preparation method and application thereof

Abstract

The invention discloses a selenium-containing polymer as well as a preparation method and application thereof, and belongs to the technical field of medical polymer materials. The structure of the selenium-containing polymer is shown as a formula 1, a formula 2 or a formula 3. The selenium-containing polymer has excellent antibacterial and anti-inflammatory capabilities, oxidation resistance and blood compatibility, and has excellent antibacterial properties on gram-negative bacteria escherichia coli, pseudomonas aeruginosa, acinetobacter baumannii and gram-positive bacteria staphylococcus aureus; the compound has good scavenging capacity on DPPH free radicals based on electron transfer and ABTS free radicals based on hydrogen atom transfer, and red blood cells cannot be hemolyzed basically even under the high concentration (16 mg / mL). # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of medical polymer materials, and particularly relates to a selenium-containing polymer, a preparation method thereof and an application thereof. Background Art

[0002] Bacterial resistance is a serious global health problem that affects the effectiveness of modern medicine and human lifespan. Cationic polymers have shown significant potential in sterilization, especially against drug-resistant bacteria and biofilms. Bacteria are usually one of the infection sources that cause immune imbalance in the human body, and immune function imbalance is likely to lead to severe infections and disease outcomes. Therefore, in addition to paying attention to pathogenic bacteria, more attention should be paid to the immune imbalance secondary to inflammatory reactions.

[0003] At present, most cationic polymers can only achieve a single sterilization function, and have limitations in the treatment of inflammation-related diseases. Selenium (Se) is a semi-metal element located in Group VI of the periodic table and has chemical properties similar to sulfur. Compared with sulfur atoms, selenium atoms have lower electronegativity and larger atomic radii. These characteristics endow selenium with high chemical activity. Selenium-containing polymers are a kind of functional materials and have various potential applications in the fields of responsive and biomedical materials.

[0004] Therefore, the research and development of a new type of selenium-containing cationic antibacterial polymer is of great significance for sterilization and anti-inflammation. Summary of the Invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide a selenium-containing polymer, a preparation method thereof and an application thereof. The selenium-containing polymer has excellent antibacterial and anti-inflammatory abilities, antioxidant ability and good blood compatibility.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] The present invention provides a selenium-containing polymer, the structure of which is shown in Formula 1, Formula 2 or Formula 3:

[0008]

[0009] Wherein, m, n, and q are degrees of polymerization, m and n independently selected from 20 - 100, and q is selected from 5 - 100;

[0010] R1, R4, R5, R6 and R 11 are independently selected from C1-C6 alkylene groups;

[0011] The C1-C6 alkylene groups include but are not limited to methylene, ethylene, propylene, butylene, pentylene, hexylene, etc.

[0012] R2, R8 and R 12Independently selected from one or more of C1-C4 alkyl, C3-C6 cycloalkyl, and C6-C 12 aryl;

[0013] The C1-C4 alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, etc.

[0014] The C3-C6 cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0015] The C6-C 12 aryl includes, but is not limited to, phenyl, naphthyl, anthryl, phenanthryl, etc.

[0016] R3, R9, and R 13 are independently selected from one or more of halide ions, trifluoroacetate, tetrafluoroborate, trifluoromethanesulfonate;

[0017] R7 is selected from C1-C6 alkyl or C6-C 12 aryl;

[0018] The C1-C6 alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, etc.

[0019] R 10 is selected from hydrogen, C3-C6 alkyl, C6-C 12 aryl or trimethylsilyl;

[0020] The C6-C 12 aryl has the same value range as above and will not be repeated here.

[0021] R 14 is selected from hydroxyl or benzylamine.

[0022] The above selenium-containing polymer has excellent antibacterial and anti-inflammatory abilities, antioxidant ability, and good blood compatibility due to its characteristics of high bactericidal activity, low hemolytic property, high selectivity, and no drug resistance.

[0023] Preferably, m and n are independently selected from 30-90; more preferably, m and n are independently selected from 40-60; further preferably, m and n are independently selected from 30-50.

[0024] Preferably, q is selected from 45-80; more preferably 48-60.

[0025] Preferably, R1, R4, R5, R6, and R 11 are independently selected from C1-C3 alkylene;

[0026] The C1-C3 alkylene groups include, but are not limited to, methylene, ethylene, propylene, etc.

[0027] Preferably, the R2, R8, and R 12 are independently selected from C1-C4 alkyl groups;

[0028] Preferably, the R3, R9, and R 13 are independently selected from one or more of halide ions, trifluoroacetate, tetrafluoroborate, and trifluoromethanesulfonate;

[0029] Preferably, the R7 is selected from C1-C6 alkyl groups;

[0030] Preferably, the R 10 is selected from hydrogen or C3-C6 alkyl groups;

[0031] Preferably, the R 14 is selected from a hydroxyl group or a benzylamino group.

[0032] Preferably, in the present invention, the structure of the selenium-containing polymer is as shown in any of the following:

[0033]

[0034] The present invention also provides a method for preparing the selenium-containing polymer with the structure as shown in Formula 1 above, comprising the following steps:

[0035] (1) Mix and react the monomer shown in Formula 4 and an initiator to obtain a polymer with a selenium-containing side chain shown in Formula a;

[0036] (2) Mix the polymer with a selenium-containing side chain shown in Formula a with a halogenated hydrocarbon, or mix it with a halogenated hydrocarbon and a precipitating agent, and carry out a cationization reaction to obtain a selenium-containing polymer with the structure as shown in Formula 1;

[0037] The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate, or silver trifluoroacetate;

[0038]

[0039]

[0040] Preferably, in the present invention, the molar ratio of selenium to the halogenated hydrocarbon in the polymer with a selenium-containing side chain shown in Formula a is 1:(0.5 - 5); more preferably 1:(2 - 5).

[0041] The molar ratio of the halogenated hydrocarbon to the precipitating agent is preferably 1:(1 - 1.5); more preferably 1:1.

[0042] The halogenated hydrocarbon is selected from saturated halogenated hydrocarbons or aromatic halogenated hydrocarbons.

[0043] The saturated halogenated hydrocarbon is selected from alkyl halogenated hydrocarbons having 1 to 4 carbon atoms or cycloalkyl halogenated hydrocarbons having 3 to 6 carbon atoms.

[0044] The aromatic halogenated hydrocarbon is selected from aryl halogenated hydrocarbons having 6 to 12 carbon atoms.

[0045] The halogen in the saturated halogenated hydrocarbon or aromatic halogenated hydrocarbon includes fluorine, chlorine, bromine, and iodine. In the present invention, iodine is preferred.

[0046] The solvent for the cationization reaction is a mixed solution of N,N-dimethylformamide and water.

[0047] The volume ratio of N,N-dimethylformamide to water in the mixed solution is preferably 1:1.

[0048] The time for the cationization reaction is preferably 48 - 60 h.

[0049] Preferably, the initiator is selected from benzoyl peroxide (BPO), azobisisobutyronitrile (AIBN), or persulfate.

[0050] In the preparation method of the selenium-containing polymer having the above structure shown in Formula 1, the reaction temperature in step (1) is preferably 10°C - 50°C;

[0051] The reaction time is preferably 12 - 48 h;

[0052] The solvent for the reaction in step (1) is selected from one or more of dimethyl sulfoxide, tetrahydrofuran, acetonitrile, and N,N-dimethylformamide.

[0053] The present invention also provides a preparation method of the selenium-containing polymer having the above structure shown in Formula 2, comprising the following steps:

[0054] (1) Reacting a dihydroxy monomer having a selenium-containing side chain shown in Formula 5 with a diisocyanate to obtain a polymer having a selenium-containing side chain shown in Formula b;

[0055] (2) Mixing the polymer having a selenium-containing side chain shown in Formula b with a halogenated hydrocarbon, or with a halogenated hydrocarbon and a precipitating agent, and subjecting to a cationization reaction to obtain a selenium-containing polymer having the structure shown in Formula 2;

[0056] The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate, or silver trifluoroacetate;

[0057]

[0058] Preferably, the diisocyanate is selected from hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), diphenylmethane diisocyanate (MDI), or toluene diisocyanate (TDI);

[0059] Preferably, the molar ratio of the dihydroxy monomer with a selenium-containing side chain to the diisocyanate is 1:(1 - 2);

[0060] Preferably, the molar ratio of selenium in the polymer with a selenium-containing side chain represented by Formula b to the halogenated hydrocarbon is 1:(0.5 - 5); more preferably 1:(2 - 5).

[0061] Preferably, the molar ratio of the halogenated hydrocarbon to the precipitating agent is 1:(1 - 1.5).

[0062] The solvent for the cationization reaction is a mixed solution of N,N-dimethylformamide and water.

[0063] Preferably, the volume ratio of N,N-dimethylformamide to water in the mixed solution is 1:1.

[0064] Preferably, the time for the cationization reaction is 48 - 60 h.

[0065] In the preparation method of the selenium-containing polymer with the above structure shown in Formula 2, the reaction temperature in step (1) is 20°C - 60°C;

[0066] The reaction time is 4 - 12 h;

[0067] The solvent for the reaction is selected from one or more of dichloromethane, dimethyl sulfoxide, tetrahydrofuran, and N,N-dimethylformamide.

[0068] The present invention also provides a preparation method of the selenium-containing polymer with the above structure shown in Formula 3, including the following steps:

[0069] (1) Mix the anhydride monomer with a selenium-containing side chain shown in Formula 6 with an initiator and carry out a ring-opening polymerization reaction to obtain a polymer with a selenium-containing side chain shown in Formula c;

[0070] (2) Mix the polymer with a selenium-containing side chain shown in Formula c with a halogenated hydrocarbon, or mix it with a halogenated hydrocarbon and a precipitating agent, and carry out a cationization reaction to obtain a selenium-containing polymer with the structure shown in Formula 3;

[0071] The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate, or silver trifluoroacetate;

[0072]

[0073] Preferably, the initiator in step (1) is selected from benzylamine, lithium trimethylsilylamide, or lithium chloride;

[0074] Preferably, the molar ratio of the anhydride monomer with a selenium-containing side chain shown in Formula 6 to the initiator is 1:(10 - 100);

[0075] Preferably, the molar ratio of selenium to halogenated hydrocarbon in the polymer with a selenium-containing side chain represented by Formula c is 1:(0.5 - 5); more preferably 1:(3 - 5).

[0076] Preferably, the molar ratio of the halogenated hydrocarbon to the precipitating agent is 1:(1 - 1.5).

[0077] The solvent for the cationization reaction is preferably a mixed solution of N,N-dimethylformamide and water.

[0078] The volume ratio of N,N-dimethylformamide to water in the mixed solution is preferably 1:1.

[0079] The time for the cationization reaction is preferably 48 - 60 h.

[0080] In the preparation method of the selenium-containing polymer with the above structure shown in Formula 3, the reaction temperature in step (1) is preferably 10°C - 40°C;

[0081] The reaction time is preferably 12 - 24 h;

[0082] The reaction solvent in step (1) is selected from one or more of dichloromethane, tetrahydrofuran, and N,N-dimethylformamide.

[0083] The biological activity of the selenium-containing polymer obtained by the above preparation method can be regulated in multiple aspects, including but not limited to the selection of monomers, initiators, alkylating agents, reaction conditions, and the molecular weight of the product, etc.

[0084] The present invention also provides the use of the above selenium-containing polymer or the selenium-containing polymer prepared by the above preparation method in the preparation of antibacterial and anti-inflammatory materials or drugs.

[0085] The selenium-containing polymer described in the present invention can be directly used as an antibacterial and anti-inflammatory medical material, or used in combination with other substances to prepare antibacterial and anti-inflammatory medical materials.

[0086] Compared with the prior art, the selenium-containing polymer provided by the present invention has a structure shown in Formula 1, Formula 2 or Formula 3, wherein m, n, and q are degrees of polymerization, m and n independently selected from 20 - 100, q selected from 5 - 100; R1, R4, R5, R6 and R 11 independently selected from C1-C6 alkylene groups; R2, R8 and R 12 independently selected from one or more of C1-C4 alkyl groups, C3-C6 cycloalkyl groups, and C6-C 12 aryl groups; R3, R9 and R 13 independently selected from one or more of halide ions, trifluoroacetate ions, tetrafluoroborate ions, and trifluoromethanesulfonate ions; R7 is selected from C1-C6 alkyl groups or C6-C 12aryl; R 10 selected from hydrogen, C3-C6 alkyl, C6-C 12 aryl or trimethylsilyl; R 14 selected from hydroxyl or benzylamino. The selenium-containing polymer has excellent antibacterial and anti-inflammatory capabilities, antioxidant capacity, and good blood compatibility. It has excellent antibacterial properties against Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Gram-positive bacteria Staphylococcus aureus, has good scavenging ability for DPPH radicals based on electron transfer and ABTS radicals based on hydrogen atom transfer, and basically does not cause hemolysis of red blood cells even at a high concentration (16 mg / mL). BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 Test chart of the bactericidal efficiency of the selenium-containing polymer prepared in Example 3 against Gram-negative bacterium Escherichia coli (E. coli);

[0088] Figure 2 Test chart of the scavenging ability of the selenium-containing polymer prepared in Example 3 for DPPH radicals;

[0089] Figure 3 Test chart of the scavenging ability of the selenium-containing polymer prepared in Example 3 for ABTS radicals. DETAILED DESCRIPTION OF THE INVENTION

[0090] To further illustrate the present invention, the selenium-containing polymer provided by the present invention, its preparation method and applications will be described in detail below in conjunction with examples.

[0091] Example 1

[0092] 1. Synthesis of polyolefin

[0093] Azobisisobutyronitrile (0.01 mol) was dissolved in 10 mL of anhydrous dimethyl sulfoxide, denoted as solution A. Allyl methyl selenide (0.3 mol) was dissolved in 100 mL of anhydrous dimethyl sulfoxide, and an inert gas nitrogen was introduced for 30 min, denoted as solution B. Solution A was quickly added to solution B, and the reaction was carried out at 50 °C for 12 h. The product was precipitated with ether 3 times and then dried under vacuum at room temperature for 4 h to obtain a white solid product, the structure of which is shown below:

[0094]

[0095] 2. Synthesis of cationic selenium-containing polyolefin

[0096] Disperse the polyolefin prepared in Step 1 in an anhydrous and oxygen-free acetonitrile solution, purge with the inert gas nitrogen for 30 minutes, add iodomethane with 3 times the selenium content and silver tetrafluoroborate dissolved in anhydrous and oxygen-free acetonitrile. After the reaction is completed, centrifuge to remove the yellow precipitate. Take the solution and dialyze it with a dialysis bag with a molecular weight cut-off of 3500 for 24 h, and then freeze-dry to obtain the final product, whose structure is shown below:

[0097]

[0098] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 4 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 4 μg / mL.

[0099] Example 2

[0100] 1. Synthesis of polyurethane

[0101] 3-(Methylseleno)propane-1,2-diol and hexamethylene diisocyanate are fed in a molar ratio of 1:1. The solvent is tetrahydrofuran. After reacting at 30 °C for 12 h, the product is obtained by precipitation with ether, and its structure is shown below:

[0102]

[0103] 2. Preparation of cationic polyurethane

[0104] Disperse the polyurethane prepared in Step 1 in an anhydrous and oxygen-free DMF solution, purge with the inert gas nitrogen for 30 minutes, add iodomethane with 3 times the selenium content and silver tetrafluoroborate dissolved in anhydrous and oxygen-free DMF, and react at 50 °C for 48 h under nitrogen protection. After the reaction is completed, centrifuge to remove the yellow precipitate. Take the solution and dialyze it with a dialysis bag with a molecular weight cut-off of 3500 for 24 h, and then freeze-dry to obtain the final product, whose structure is shown below:

[0105]

[0106] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 8 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 8 μg / mL.

[0107] Example 3

[0108] 1. Synthesis of selenomethionine anhydride

[0109] Weigh 2 g of selenomethionine and disperse it in an anhydrous and anaerobic tetrahydrofuran solvent. Introduce nitrogen gas into the system for 15 min. Dissolve 1.5 g of triphosgene in anhydrous and anaerobic tetrahydrofuran and add it to the system. React at room temperature for 2 h under nitrogen protection. Remove most of the solvent by rotary evaporation at 37 °C, extract and separate with n-hexane once, extract and separate with saturated brine twice, and recrystallize with ethyl acetate / n-hexane in a cold room at -80 °C to obtain a white solid, the structure of which is shown below:

[0110]

[0111] 2. Polyamide synthesis

[0112] The benzylamine initiator and the selenomethionine anhydride prepared in step 1 are subjected to ring-opening polymerization in anhydrous tetrahydrofuran at a molar ratio of 1:50 and react at 30 °C for 18 h. After treatment, precipitate three times with diethyl ether and then dry at room temperature under vacuum. The structure is shown below:

[0113]

[0114] 3. Preparation of cationic polyamide

[0115] Disperse the polyamide prepared in step 2 in a mixed solution of DMF and water (1:1 (v / v)), add methyl iodide with 3 times the selenium content, and react at 37 °C for 48 h. The product is dialyzed with a dialysis bag with a molecular weight cut-off of 3500 for 24 h and then freeze-dried to obtain the final product, the structure of which is shown below:.

[0116]

[0117] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 16 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 8 μg / mL.

[0118] Figure 1 This is a test chart of the bactericidal efficiency of the selenium-containing polymer prepared in Example 3 against the Gram-negative bacterium Escherichia coli (E. coli). The results show that the selenium-containing polymer prepared in Example 3 has a bactericidal rate greater than 99% in only 2 hours at a concentration of 4 MIC against the Gram-negative bacterium Escherichia coli.

[0119] Figure 2 This is a test chart of the scavenging ability of the selenium-containing polymer prepared in Example 3 against DPPH radicals. The results show that the selenium-containing polymer prepared in Example 3 has a DPPH radical scavenging rate of 58.4% at a concentration of 1000 μg / mL.

[0120] Figure 3Test chart of the scavenging ability of the selenium-containing polymer prepared in Example 3 against ABTS radicals. The results show that the selenium-containing polymer prepared in Example 3 has a scavenging rate of 86.42% against ABTS radicals at a concentration of 100 μg / mL.

[0121] Table 1 shows the minimum inhibitory concentration (MIC) and hemolysis rate of the selenium-containing polymers prepared in Examples 1-3 against Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Gram-positive bacteria Staphylococcus aureus.

[0122] Table 1 MIC and hemolysis rate of the selenium-containing polymers prepared in Examples 1-3

[0123] Sample Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa Acinetobacter baumannii 10% Hemolysis rate Example 1 4 μg / mL 4 μg / mL 8 pg / mL 8 μg / mL 16000 μg / mL Example 2 8 μg / mL 8 μg / mL 16 μg / mL 16 μg / mL 16000 μg / mL Example 3 8 μg / mL 16 μg / mL 32 pg / mL 32 μg / mL 16000 μg / mL

[0124] The results show that the selenium-containing polymers prepared in the present invention all have broad-spectrum bactericidal properties and good biosafety, and basically do not cause hemolysis of red blood cells at a concentration of 16,000 μg / mL.

[0125] Example 4

[0126] 1. Polyurethane synthesis

[0127] 3-(Methylseleno)butane-1,2-diol and isophorone diisocyanate were fed in a molar ratio of 1:1. The solvent was anhydrous dimethyl sulfoxide, and the reaction was carried out at 50 °C for 8 h. The product was precipitated three times with ether and dried in vacuo to obtain a product, the structure of which is shown below:

[0128]

[0129] 2. Preparation of cationic polyurethane

[0130] The polyurethane polymer prepared in step 1 was dispersed in an anhydrous and anaerobic acetonitrile solution, nitrogen was passed for 30 minutes, methyl iodide with 0.7 times the selenium content and silver trifluoroacetate dissolved in anhydrous and anaerobic acetonitrile were added, and the reaction was carried out at 37 °C for 48 h. After the reaction was completed, the yellow precipitate was removed by centrifugation, and the solution was dialyzed for 24 h using a dialysis bag with a cut-off molecular weight of 3500 and then freeze-dried to obtain the final product, the structure of which is shown below:

[0131]

[0132] Through the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli was 4 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus was 8 μg / mL.

[0133] Example 5

[0134] 1. Synthesis of selenomethionine propionic anhydride

[0135] Weigh 2 g of selenomethionine and disperse it in anhydrous and anaerobic tetrahydrofuran solvent. Pass nitrogen into the system for 15 min. Dissolve 1.5 g of triphosgene in anhydrous and anaerobic tetrahydrofuran and add it to the system. React at room temperature for 2 h under nitrogen protection. Remove most of the solvent by rotary evaporation at 37 °C, extract and separate with n-hexane once, extract and separate with saturated brine twice, and recrystallize with ethyl acetate / n-hexane in a cold room at -80 °C to obtain a white solid, the structure of which is shown below:

[0136]

[0137] 2. Polyamide synthesis

[0138] Carry out ring-opening polymerization of lithium trimethylsilylamide initiator and selenomethionine anhydride in a molar ratio of 1:50 in anhydrous N,N-dimethylformamide at 37 °C for 24 h. After treatment, precipitate three times with diethyl ether and then dry under vacuum at room temperature. Hydrolyze both ends of the polymer chain to obtain the final product, the structure of which is shown below:

[0139]

[0140] 3. Preparation of cationic polyamide

[0141] Disperse the polyurethane polymer prepared in step 1 in anhydrous and anaerobic acetonitrile solution, pass nitrogen for 30 minutes, add iodomethane with 0.7 times the selenium content and silver trifluoroacetate dissolved in anhydrous and anaerobic acetonitrile, and react at 37 °C for 48 h. After the reaction is completed, centrifuge to remove the yellow precipitate, take the solution, dialyze with a dialysis bag with a molecular weight cut-off of 3500 for 24 h, and then freeze-dry to obtain the final product, the structure of which is shown below:

[0142]

[0143] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 8 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 16 μg / mL.

[0144] Comparative Example 1

[0145] 1. Selenomethionine anhydride synthesis

[0146] Weigh 2 g of selenomethionine and disperse it in anhydrous and anaerobic tetrahydrofuran solvent. Pass nitrogen into the system for 15 min. Dissolve 1.5 g of triphosgene in anhydrous and anaerobic tetrahydrofuran and add it to the system. React at room temperature for 2 h under nitrogen protection. Remove most of the solvent by rotary evaporation at 37 °C, extract and separate with n-hexane once, extract and separate with saturated brine twice, and recrystallize with ethyl acetate / n-hexane in a cold room at -80 °C to obtain a white solid, the structure of which is shown below:

[0147]

[0148] 2. Polyamide synthesis

[0149] The benzylamine initiator and the selenomethionine anhydride prepared in Step 1 are subjected to ring-opening polymerization in anhydrous tetrahydrofuran at a molar ratio of 1:25 and reacted at 30 °C for 18 h. After treatment, it is precipitated three times with ether and then dried under vacuum at room temperature to obtain the product, the structure of which is shown below:

[0150]

[0151] 3. Preparation of cationic polyamide

[0152] The polyamide prepared in Step 2 is dispersed in a mixed solution of DMF and water (1:1 (v / v)), and methyl iodide with 3 times the selenium content is added, and the reaction is carried out at 37 °C for 48 h. The product is dialyzed for 24 h using a dialysis bag with a molecular weight cut-off of 1000 and then freeze-dried to obtain the final product, the structure of which is shown below:

[0153]

[0154] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 32 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 32 μg / mL.

[0155] Comparative Example 2

[0156] 1. Synthesis of selenomethionine anhydride

[0157] Weigh 2 g of selenomethionine and disperse it in an anhydrous and anaerobic tetrahydrofuran solvent, and pass nitrogen into the system for 15 min. Dissolve 1.5 g of triphosgene in anhydrous and anaerobic tetrahydrofuran and add it to the system, and react at room temperature for 2 h under nitrogen protection. Most of the solvent is removed by rotary evaporation at 37 °C, extracted and separated once with n-hexane, extracted and separated twice with saturated brine, and recrystallized with ethyl acetate / n-hexane in a cold room at -80 °C to obtain a white solid, the structure of which is shown below:

[0158]

[0159] 2. Polyamide synthesis

[0160] The benzylamine initiator and the selenomethionine anhydride prepared in Step 1 are subjected to ring-opening polymerization in anhydrous tetrahydrofuran at a molar ratio of 1:10 and reacted at 30 °C for 18 h. After treatment, it is precipitated three times with ether and then dried under vacuum at room temperature to obtain the product, the structure of which is shown below:

[0161]

[0162] 3. Preparation of cationic polyamide

[0163] Disperse the polyamide prepared in Step 2 in a mixed solution of DMF and water (1:1 (v / v)), add methyl iodide with a selenium content three times that of the polyamide, and react at 37 °C for 48 h. The product is dialyzed using a dialysis bag with a molecular weight cut-off of 1000 for 24 h and then freeze-dried to obtain the final product, whose structure is shown below:

[0164]

[0165] After the minimum inhibitory concentration test, the minimum inhibitory concentration of the polymer against Escherichia coli is 512 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 64 μg / mL.

[0166] By comparing Example 3 with Comparative Examples 1 and 2, the results show that as the degree of polymerization of the selenium-containing polymer decreases, the antibacterial activity also decreases.

[0167] The description of the above examples is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. A selenium-containing polymer, characterized in that, The structure is as shown in Formula 1, Formula 2 or Formula 3: Wherein, m, n, and q are degrees of polymerization, m and n are independently selected from 20 - 100, and q is selected from 5 - 100; R1, R4, R5, R6 and R 11 independently selected from C1-C6 alkylene groups; R2, R8, and R 12 independently selected from one or more of C1-C4 alkyl, C3-C6 cycloalkyl, and C6-C 12 aryl; R3, R9, and R 13 are independently selected from one or more of halide ions, trifluoroacetate, tetrafluoroborate, and trifluoromethanesulfonate; R7 is selected from C1-C6 alkyl or aryl of C6-C 12 aryl; R 10 selected from hydrogen, C3-C6 alkyl, C6-C 12 aryl or trimethylsilyl; R 14 Selected from a hydroxyl group or a benzylamino group.

2. The selenium-containing polymer according to claim 1, wherein Said m and n are independently selected from 30 - 90, and q is selected from 45 - 80; The R1, R4, R5, R6 and R 11 are independently selected from C1-C3 alkylene groups; The R2, R8 and R 12 independently selected from C1-C4 alkyl; R3, R9, and R 13 independently selected from one or more of halide ions, trifluoroacetate, tetrafluoroborate, and trifluoromethanesulfonate; R7 is selected from C1 - C6 alkyl; R 10 selected from hydrogen or C3-C6 alkyl; R 14 Selected from a hydroxyl group or a benzylamino group.

3. The selenium-containing polymer according to claim 1, wherein The structure of the selenium - containing polymer is as shown in any of the following:

4. The preparation method of the selenium-containing polymer with the structure shown in Formula 1 as described in Claim 1, characterized in that, Comprising the following steps: (1) Mix and react the monomer shown in Formula 4 and an initiator to obtain a polymer with a selenium - containing side chain shown in Formula a; (2) Mix the polymer with a selenium - containing side chain shown in Formula a with a halogenated hydrocarbon, or mix it with a halogenated hydrocarbon and a precipitating agent, and carry out a cationization reaction to obtain a selenium - containing polymer with a structure shown in Formula 1; The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate or silver trifluoroacetate; 5. The preparation method according to claim 4, characterized in that, The molar ratio of selenium in the polymer with a selenium - containing side chain shown in Formula a to the halogenated hydrocarbon is 1:(0.5 - 5); The molar ratio of the halogenated hydrocarbon to the precipitating agent is 1:(1 - 1.5); The initiator is selected from benzoyl peroxide, azobisisobutyronitrile or persulfate.

6. The preparation method of the selenium-containing polymer with the structure shown in Formula 2 as described in Claim 1, characterized in that, Comprising the following steps: (1) React the dihydroxy monomer with a selenium - containing side chain shown in Formula 5 with a diisocyanate to obtain a polymer with a selenium - containing side chain shown in Formula b; (2) Mix the polymer with a selenium - containing side chain shown in Formula b with a halogenated hydrocarbon, or mix it with a halogenated hydrocarbon and a precipitating agent, and carry out a cationization reaction to obtain a selenium - containing polymer with a structure shown in Formula 2; The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate or silver trifluoroacetate; 7. The preparation method according to claim 6, characterized in that, The diisocyanate is selected from hexamethylene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate or toluene diisocyanate; The molar ratio of the dihydroxy monomer with a selenium - containing side chain to the diisocyanate is 1:(1 - 2); The molar ratio of selenium in the polymer with a selenium - containing side chain shown in Formula b to the halogenated hydrocarbon is 1:(0.5 - 5); The molar ratio of the halogenated hydrocarbon to the precipitating agent is 1:(1 - 1.5).

8. The preparation method of the selenium-containing polymer with the structure shown in Formula 3 according to Claim 1, characterized in that, Comprising the following steps: (1) Mix the cyclic anhydride monomer with a selenium - containing side chain shown in Formula 6 and an initiator, and carry out a ring - opening polymerization reaction to obtain a polymer with a selenium - containing side chain shown in Formula c; (2) Mix the polymer with a selenium - containing side chain shown in Formula c with a halogenated hydrocarbon, or mix it with a halogenated hydrocarbon and a precipitating agent, and carry out a cationization reaction to obtain a selenium - containing polymer with a structure shown in Formula 3; The precipitating agent is selected from silver tetrafluoroborate, silver trifluoromethanesulfonate or silver trifluoroacetate; 9. The preparation method according to claim 8, characterized in that, The initiator in step (1) is selected from benzylamine, lithium trimethylsilylamide or lithium chloride; The molar ratio of the cyclic anhydride monomer with a selenium - containing side chain shown in Formula 6 to the initiator is 1:(10 - 100); the molar ratio of selenium in the polymer with a selenium - containing side chain shown in Formula c to the halogenated hydrocarbon is 1:(0.5 - 5); The molar ratio of the halogenated hydrocarbon to the precipitating agent is 1:(1 - 1.5).

10. Use of the selenium - containing polymer according to any one of claims 1 - 3 or the selenium - containing polymer prepared by the preparation method according to any one of claims 4 - 9 in the preparation of antibacterial and anti - inflammatory medical materials.

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