A degradable disulfide-bonded carboxybetaine zwitterionic polymer and preparation method thereof

Abstract

The present invention discloses a degradable carboxy betaine zwitterionic polymer containing disulfide bonds and a preparation method thereof. First, a zwitterionic carboxylic betaine monomer is prepared. Specifically, a tertiary amine monomer containing disulfide bonds is prepared by reacting a terminal amino group of lipoic acid with a tertiary amine containing active hydrogen, and then zwitterionicization is achieved by ring opening of β-propiolactone. Then, a degradable zwitterionic polymer containing disulfide bonds is prepared by combining solvent concentration or melt heat driven ring opening polymerization with compression molding. The polymer preparation method is simple, does not require a chemical crosslinking agent, and has the properties of degradability and self-healing at the same time.

Description

Technical Field

[0001] The invention belongs to the field of polymers, and more specifically, relates to a method for preparing a degradable disulfide-bond-containing carboxybetaine zwitterionic monomer and a polymer thereof. Background Art

[0002] The strong hydration between the surface charge of zwitterionic polymers and water molecules forms an ordered hydration layer on the polymer surface, which can effectively inhibit the adsorption of nonspecific proteins, thereby reducing biological contamination and avoiding foreign body reactions in biomedical processes. Zwitterionic polymers are widely used in wound dressings due to their good hydrophilicity, antifouling properties and biocompatibility. Usually, the preparation of zwitterionic polymers requires the addition of crosslinkers under the action of thermal initiation or photoinitiator, and is prepared by free radical polymerization. Due to the presence of chemical crosslinking, its polymer skeleton is non-degradable and difficult to achieve on-demand degradation, which also brings inconvenience in its application. Non-degradable zwitterionic polymers need to be removed or replaced regularly to avoid hypoxia of the wound surface, which increases the inconvenience of patients and brings a certain risk of infection. Regular replacement of dressings will also increase the burden on medical resources. Secondly, non-degradable zwitterionic polymers may accumulate as foreign matter at the wound site and lead to the formation of pathological tissue. This may hinder the healing and regeneration of normal cells, thereby prolonging the healing time of the wound. Compared with non-degradable zwitterionic polymers, biodegradable zwitterionic polymers have good biocompatibility and biomechanical properties. They are degraded into safe and non-toxic small molecules by enzymes or non-enzymatic pathways in the body and excreted from the body through the urinary system, causing minimal harm to the human body. The degradation products are also biocompatible, and this type of material better meets the requirements of medical materials. Summary of the invention

[0003] The object of the present invention is to overcome the deficiencies of the prior art, and provide a degradable carboxybetaine zwitterionic polymer containing disulfide bonds and a preparation method thereof. The present invention introduces an amide group by reacting the carboxyl group at the end of the lipoic acid chain with a tertiary amine containing active hydrogen, obtains a tertiary amine monomer containing a disulfide bond, further undergoes a ring-opening reaction with β-propiolactone, obtains a carboxybetaine zwitterionic monomer containing multiple hydrogen bonds, and performs physical crosslinking through the action of multiple hydrogen bonds between polymer molecules, and achieves thermally initiated ring-opening polymerization by solution concentration-induced ring-opening polymerization or thermally driven dynamic covalent disulfide bonds, thereby solving the problem that traditional zwitterionic polymers are difficult to degrade. And because the polymer is physically crosslinked, the polymer of the present invention also has good self-healing properties.

[0004] The technical purpose of the present invention is achieved through the following technical solutions.

[0005] A degradable disulfide-bonded carboxybetaine zwitterionic polymer, the chemical formula of which is shown below:

[0006]

[0007] R is CH2 or -NHCO, m is an integer of 1-5, preferably 1 or 2; n is the degree of polymerization of the zwitterionic polymer, which is 20-6000, preferably 800-3000, and the number average molecular weight is 10000-1000000, preferably 100000-600000.

[0008] The preparation method of a degradable disulfide bond-containing carboxybetaine zwitterionic polymer of the present invention is carried out according to the following steps:

[0009] Step 1, dispersing lipoic acid uniformly in a solvent for activation, then mixing and dispersing it with a tertiary amine containing active hydrogen, and drying and concentrating to obtain a tertiary amine monomer containing a disulfide bond;

[0010] In step 1, the structure of lipoic acid is shown in the following chemical formula:

[0011]

[0012] In step 1, the structure of the tertiary amine containing active hydrogen is shown in the following chemical formula:

[0013] (N,N-dimethylaminohydrazide, prepared by reference https: / / doi.org / 10.1016 / j.colsurfa.2022.130243 , Multifunctional quaternaryammonium surfactants with controlled release of carbonyl perfumes, Colloids and Surfaces A:Physicochemical and Engineering Aspects Volume 655,20December2022,130243)

[0014] In step 1, the tertiary amine monomer containing a disulfide bond is shown in the following molecular formula:

[0015]

[0016] R is CH2 or -NHCO, and m is an integer of 1-5, preferably 1 or 2.

[0017] In step 1, the solvent used is anhydrous methanol, anhydrous ethanol, anhydrous dichloromethane, preferably anhydrous dichloromethane. In step 1, the molar ratio of lipoic acid to the active hydrogen-containing tertiary amine is 1:(1-1.5), preferably 1:1.1, and the reaction time at room temperature is 6-24h, preferably 12-15h.

[0018] In step 1, after the reaction is completed, the mixture is washed with a saturated salt solvent and then dried, and concentrated using a rotary evaporator. The saturated salt solvent is selected to be a saturated sodium chloride aqueous solution, a saturated sodium carbonate aqueous solution, a saturated sodium bicarbonate aqueous solution, a mixture of a saturated sodium chloride aqueous solution and a saturated sodium carbonate aqueous solution, preferably a mixture of a saturated sodium chloride aqueous solution and a saturated sodium carbonate aqueous solution; the heating temperature of the rotary evaporator is 20-40° C., preferably 25-30° C.

[0019] In step 1, lipoic acid and CDI are mixed for activation, the activation time of lipoic acid is 1-6 hours, preferably 4 hours; the molar ratio of lipoic acid to CDI is 1:(1-1.5), preferably 1:1.1.

[0020] Step 2, reacting the disulfide bond-containing tertiary amine monomer prepared in step 1 with β-propiolactone to obtain a degradable disulfide bond-containing carboxybetaine zwitterionic monomer, as shown in the following molecular formula:

[0021]

[0022] R is CH2 or -NHCO, m is an integer of 1-5, preferably 1, 2; the added amount (i.e., molar ratio) of β-propiolactone and disulfide bond-containing tertiary amine monomer is (1-2): 1 equivalent

[0023] In step 2, the solvent used in the reaction is anhydrous dichloromethane, anhydrous methanol, anhydrous tetrahydrofuran, anhydrous ethanol, preferably anhydrous tetrahydrofuran.

[0024] In step 2, the added amount of β-propiolactone and the disulfide bond-containing tertiary amine monomer is 1.1:1.

[0025] In step 2, the reaction temperature is room temperature 20-30 degrees Celsius, and the reaction time is 60-80 hours, preferably 70-80 hours.

[0026] In step 2, after the reaction is completed, a crude product is obtained, which is washed with anhydrous ether and acetone and dried in a vacuum drying oven to obtain a degradable carboxybetaine zwitterionic monomer containing a disulfide bond.

[0027] Step 3, subjecting the degradable carboxybetaine zwitterionic monomer containing disulfide bonds prepared in step 2 to induced ring-opening polymerization to obtain a degradable carboxybetaine zwitterionic polymer containing disulfide bonds, the chemical formula of which is as follows:

[0028]

[0029] R is CH2 or -NHCO, m is an integer of 1-5, preferably 1 or 2; n is the degree of polymerization of the zwitterionic polymer, which is 20-6000, preferably 800-3000, and the number average molecular weight is 10000-1000000, preferably 100000-600000.

[0030] In step 3, solution concentration is used to induce ring-opening polymerization, or melt method heat-driven induced ring-opening polymerization is used, and finally compression molding is used to shape the zwitterionic polymer.

[0031] In step 3, a mixed solvent of water and ethanol is used to dissolve the degradable carboxybetaine zwitterionic monomer containing disulfide bonds, and then the monomer is placed in a constant temperature and humidity chamber to volatilize the solvent to prepare a degradable carboxybetaine zwitterionic polymer containing disulfide bonds.

[0032] In a mixed solvent of water and ethanol, the volume percentage of ethanol is 20-80%, preferably 50-60%; the molar concentration of the degradable disulfide-bond-containing carboxybetaine zwitterionic monomer is 0.5-3 mol / L, preferably 1-1.5 mol / L; the temperature and humidity of the constant temperature and humidity chamber are set to 25-45° C. and 30-80%, preferably 30-35° C. and 55-60%, respectively; the solvent volatilization time is 1-14 days, preferably 5-7 days, and one day is 24 hours.

[0033] In step 3, the dynamic disulfide bonds of the degradable carboxybetaine zwitterionic monomer containing disulfide bonds are thermally driven by a melt method to achieve ring-opening polymerization to prepare a degradable carboxybetaine zwitterionic polymer containing disulfide bonds.

[0034] The degradable disulfide bond-containing carboxy betaine zwitterionic monomer is melted at high temperature, the polymerization temperature is 90-150° C., preferably 110-120° C., and the polymerization time is 1-10 hours, preferably 5-8 hours.

[0035] The present invention introduces an amide group by reacting the thioctic acid chain end carboxyl group with a tertiary amine containing active hydrogen, obtains a tertiary amine monomer containing a disulfide bond, further undergoes a ring-opening reaction with β-propiolactone, obtains a carboxybetaine zwitterionic monomer containing multiple hydrogen bonds, and is physically cross-linked by the action of multiple hydrogen bonds between polymer molecules, and is induced to open the ring by solution concentration or heat-driven dynamic covalent disulfide bonds to achieve thermally initiated ring-opening polymerization, which not only solves the problem of the difficulty in degrading traditional zwitterionic polymers, but also degradable zwitterionic polymers with good biocompatibility and function help to improve the effect of wound dressings, and reduce the patient's discomfort and complication risks. In the present invention, raw materials are easily available, and the synthesis and preparation methods are simple, the prepared zwitterionic polymer can be gelled without adding any cross-linking agent, and the prepared zwitterionic polymer has a degradable property. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is the tertiary amine monomer containing a disulfide bond in Example 1 of the present invention 1 HNMR spectrum.

[0037] Figure 2 is the disulfide bond-containing carboxybetaine zwitterionic monomer CBDS in Example 1 of the present invention 1 HNMR spectrum.

[0038] Figure 3 It is a DSC curve diagram of the zwitterionic polymer pCBDS prepared by solution concentration polymerization in Example 1 of the present invention.

[0039] Figure 4 is a DSC curve diagram of pCBDS through heat-driven ring-opening polymerization in Example 2 of the present invention.

[0040] Figure 5 is the tertiary amine monomer containing a disulfide bond in Example 3 of the present invention 1 H NMR spectrum.

[0041] Figure 6 It is the disulfide bond-containing carboxybetaine zwitterionic monomer (CBDHS) in Example 3 of the present invention. 1 H NMR spectrum.

[0042] Figure 7 It is a DSC curve diagram of the zwitterionic polymer pCBDHS prepared by solution concentration polymerization in Example 3 of the present invention.

[0043] Figure 8 3 is a DSC curve diagram of the zwitterionic polymer pCBDHS prepared by heat-driven ring-opening polymerization in Example 4 of the present invention.

[0044] Fig. 9 These are actual photographs of the zwitterionic polymers pCBDS and pCBDHS prepared by thermal ring-opening polymerization in the present invention.

[0045] Fig.10 These are actual photographs of zwitterionic polymers pCBDS and pCBDHS prepared by solution concentration polymerization in the present invention.

[0046] Fig.11 It is a schematic photo of the degradation of zwitterionic polymers pCBDS and pCBDHS prepared by solution concentration polymerization in the present invention. DETAILED DESCRIPTION

[0047] The following is a further description of the present invention, but does not limit the scope of the present invention.

[0048] The nuclear magnetic resonance spectrometer (AVANCEⅢ, 400MHz, Bruker) was used to perform H NMR spectrum test ( 1 H NMR), D2O and CDCl3 were used as solvents, MestRenova software was used for analysis, and Origin was used for mapping. The NMR test results showed the successful preparation of degradable carboxybetaine zwitterionic monomers containing disulfide bonds.

[0049] DSC analysis was performed using a DSC instrument (DSC 3, METTLER TOLEDO, Switzerland) within a specified temperature range of -50 to 220°C, with a heating rate of 10°C / min, using STARe thermal analysis software, combined with origin software for analysis and plotting. DSC testing showed that the polymer had good thermal properties and that the zwitterionic polymer was successfully prepared.

[0050] Example 1

[0051] Step 1, dissolving 10.316g thioctic acid (50mmol) in 30mL anhydrous dichloromethane to form a thioctic acid solution, dissolving 8.9183g CDI (55mmol, N,N'-carbonyldiimidazole, CAS No. 530-62-1) in 110mL anhydrous dichloromethane, and slowly adding the thioctic acid solution dropwise to the above solution; after the addition is completed, continuing the reaction activation at room temperature (20-30°C) for 4h; then adding 8.815g N,N-dimethylethylenediamine (55mmol) dropwise, after the reaction is completed, washing with saturated sodium bicarbonate and saturated brine, drying, and rotary evaporation to obtain a tertiary amine monomer containing a disulfide bond.

[0052] The obtained tertiary amine monomer containing disulfide bonds 1 H NMR spectrum Figure 1 As shown, 1 HNMR (CDCl3): δ = 3.31 (H a ,-SS-CH2-);1.95,2.78(Hb,-S-CH2-CH2-);3.13(H c ,-CH2-CH-S-); 1.65(H d ,-CH-CH2-CH2-); 1.45(He,-CH-CH2-CH2-); 1.65(H f ,-CH2-CH2-); 2.19(H g ,-CH2-CONH-NH-); 2.40(H h ,-CONH-CH2-N-(CH3)2-); 3.59(H i ,-CONH-CH2-CH-N-(CH3)2-); 2.24(Hj,k ,-CH-N-(CH3)2-); ppm. This proves that the tertiary amine monomer containing a disulfide bond (CBDS intermediate monomer) was successfully synthesized.

[0053] Step 2, 3.9633 g of β-propiolactone (55 mmol) was dissolved in 30 mL of tetrahydrofuran, and the solution was added dropwise to the intermediate monomer solution dissolved in tetrahydrofuran at 0° C. under nitrogen protection. After the addition was completed, the reaction was placed at 25° C. for 72 hours. The crude product was a light yellow precipitate, which was washed with anhydrous ether and acetone, and the obtained product was dried in a vacuum drying oven to obtain a disulfide-bonded carboxybetaine zwitterionic monomer CBDS, whose structural formula is shown below:

[0054]

[0055] The 1H NMR spectrum of the obtained disulfide bond-containing tertiary amine monomer is as follows: Figure 2 As shown, 1 HNMR (CDCl3): δ = 3.19 (H a ,-SS-CH2-); 1.93,2.48(H b ,-S-CH2-CH2-); 3.58(H c ,-CH2-CH-S-); 1.72(H d ,-CH-CH2-CH2-); 1.52(H e ,-CH-CH2-CH2-); 1.72(H f ,-CH2-CH2-); 2.31(H g ,-CH2-CONH-NH-); 3.11(H h ,-CONH-CH2-N-(CH3)2-); 2.38(H i,j ,-CH2-N-(CH3)2-); ppm. This proves that the tertiary amine monomer CBDS containing a disulfide bond was successfully synthesized.

[0056] Step 3, weigh 0.3 g of CBDS with a balance, dissolve it in 0.7 mL of 50% ethanol aqueous solution, place it in a constant temperature and humidity chamber at 37° C. and 55% humidity for 7 days, evaporate the solution and concentrate it for ring-opening polymerization, place it in a model for compression molding, and obtain a degradable carboxybetaine zwitterionic polymer pCBDS containing disulfide bonds, the polymer structure of which is shown below:

[0057]

[0058] The thermodynamic properties of solution-concentrated polymerized pCBDS were characterized by DSC. Figure 3 shown.

[0059] Example 2

[0060] Step 1, dissolving 10.316g thioctic acid (50mmol) in 30mL anhydrous dichloromethane, dissolving 8.9183g CDI (55mmol) in 110mL anhydrous dichloromethane, slowly adding the thioctic acid solution dropwise to the above solution; after the addition is completed, continuing the reaction activation at room temperature (20-30°C) for 4h; then adding 8.815g N,N-dimethylethylenediamine (55mmol) dropwise, after the reaction is completed, fully washing with saturated sodium bicarbonate and saturated brine, drying, and rotary evaporation to obtain a tertiary amine monomer containing a disulfide bond.

[0061] Step 2, 3.9633 g of β-propiolactone (55 mmol) was dissolved in 30 mL of tetrahydrofuran, and the mixture was added dropwise to the intermediate monomer solution dissolved in tetrahydrofuran at 0°C under nitrogen protection. After the addition was completed, the reaction was placed at 25°C for 72 hours. The crude product was a light yellow precipitate, which was washed with anhydrous ether and acetone, and the obtained product was dried in a vacuum drying oven.

[0062] Step 3: Weigh an appropriate amount of CBDS monomer using a balance, and use the melt method to achieve heat-driven ring-opening polymerization, stirring and heating at 110°C for 5 hours. Then place it in a mold for compression molding, and characterize the thermal properties of pCBDS after heat-driven ring-opening polymerization by DSC, such as Figure 4 shown.

[0063] Example 3

[0064] Step 1, dissolving 10.316g thioctic acid (50mmol) in 30mL anhydrous dichloromethane, dissolving 8.9183g CDI (55mmol) in 110mL anhydrous dichloromethane, slowly adding the thioctic acid solution dropwise to the above solution; after the addition is completed, continuing the reaction activation at room temperature 25°C for 4h; then adding 6.435g N,N-dimethylaminohydrazide (55mmol) dropwise, after the reaction is completed, fully washing with saturated sodium bicarbonate and saturated brine, drying, and rotary evaporation to obtain a tertiary amine monomer containing a disulfide bond.

[0065] The obtained tertiary amine monomer containing disulfide bonds 1 H NMR spectrum Figure 5 As shown, 1 H NMR (D2O): δ = 2.15; (H a ,-SS-CH2-); 1.39,1.59,(H b ,-S-CH2-CH2-); 1.99(H c ,-CH2-CH-S-); 1.30(H d ,-CH-CH2-); 1.13(H e ,-CH-CH2-CH2-); 1.30(Hf ,-CH2-CH2-); 1.83(H g ,-CH2-CONH-); 2.94(H h ,-CONH-CH2); 2.88(H i ,-CH2-N-(CH3)2-); 2.50(H j,k ,-CH2-N-(CH3)2-); 2.76(H l ,-N-(CH3)2-CH2-); 2.55(Hm,-CH2-COO)ppm, which proves that the tertiary amine monomer containing disulfide bonds was successfully synthesized.

[0066] Step 2, 3.9633 g of β-propiolactone (55 mmol) was dissolved in 30 mL of tetrahydrofuran, and the solution was added dropwise to the intermediate monomer solution dissolved in tetrahydrofuran at 0° C. under nitrogen protection. After the addition was completed, the reaction was placed at 25° C. for 72 hours. The crude product was a light yellow precipitate, which was washed with anhydrous ether and acetone. The obtained product was dried in a vacuum drying oven, i.e., a disulfide bond-containing carboxybetaine zwitterionic monomer (CBDHS) as shown below:

[0067]

[0068] The obtained degradable disulfide-bonded carboxybetaine zwitterionic monomer (CBDHS) 1 H NMR spectrum Figure 6 As shown, 1 HNMR (D2O): δ = 2.65 (H a ,-SS-CH2-);1.93,3,13(H b ,-S-CH2-CH2-); 2.89(H c ,-CH2-CH-S-); 1.70(Hd,-CH-CH2-CH2-); 1.41(H e ,-CH-CH2-CH2-); 1.59(H f ,-CH2-CH2-); 2.28(H g ,-CH2-CONH-NH-); 4.12(H h ,-CONH-CH2-N-(CH3)2-); 3.22(H i,j ,-CH2-N-(CH3)2-); 3.73(H k ,-N-(CH3)2-CH2-)ppm. This proves that the degradable carboxybetaine zwitterionic monomer containing disulfide bonds (CBDHS) was successfully synthesized.

[0069] Step 3, weigh 0.3 g of CBDHS with a balance, dissolve it in 0.7 mL of 50% ethanol solution, place it in a constant temperature and humidity chamber at 37° C. and 55% humidity for 7 days, evaporate the solution and concentrate it for ring-opening polymerization, place it in a model for compression molding, and obtain a degradable disulfide-bonded carboxybetaine zwitterionic polymer pCBDHS, whose polymer structure is shown below.

[0070]

[0071] The thermal properties of solution-concentrated polymerized pCBDHS were characterized by DSC. Figure 7 shown.

[0072] Example 4

[0073] Step 1, dissolving 10.316g thioctic acid (50mmol) in 30mL anhydrous dichloromethane, dissolving 8.9183g CDI (55mmol) in 110mL anhydrous dichloromethane, slowly adding the thioctic acid solution dropwise to the above solution; after the addition is completed, continuing the reaction activation at room temperature 25°C for 4h; then adding 6.435g N,N-dimethylaminohydrazide (55mmol) dropwise, after the reaction is completed, fully washing with saturated sodium bicarbonate and saturated brine, drying, and rotary evaporation to obtain a tertiary amine monomer containing a disulfide bond.

[0074] Step 2, 3.9633 g of β-propiolactone (55 mmol) was dissolved in 30 mL of tetrahydrofuran, and the mixture was added dropwise to the intermediate monomer solution dissolved in tetrahydrofuran at 0°C under nitrogen protection. After the addition was completed, the reaction was placed at 25°C for 72 hours. The crude product was a light yellow precipitate, which was washed with anhydrous ether and acetone, and the obtained product was dried in a vacuum drying oven.

[0075] Step 3: Weigh an appropriate amount of CBDHS monomer on a balance, use the melt method to achieve thermally driven ring-opening polymerization, and stir and heat at 110°C for 5 hours. Then place it in a mold for compression molding. The thermodynamic properties of pCBHDS in thermally driven ring-opening polymerization were characterized by DSC, such as Figure 8 shown.

[0076] DSC analysis was performed using a DSC instrument (DSC 3, METTLER TOLEDO, Switzerland) in the specified temperature range of −50 to 220 °C with a heating rate of 10 °C min -1, using STARe thermal analysis software for analysis, combined with origin software for analysis and drawing. From the DSC test, it can be seen that the Tg of pCBDS and pCBDHS obtained by thermal ring-opening polymerization are -33.3 and 7.3°C, respectively, and the melting limits of pCBDS obtained by solution concentration and thermal ring-opening polymerization are 127-130°C and 90-125°C, respectively, and the melting limits of pCBDHS obtained by solution concentration and thermal ring-opening polymerization are 116-129°C and 90-110°C, respectively. The DSC test shows that the degradable disulfide-bonded carboxybetaine zwitterionic polymer can show good flexibility above the glass transition temperature, and the maximum use temperature can reach 90°C, and the polymer has good thermal stability.

[0077] like Fig. 9 —10 It can be seen that the carboxybetaine zwitterionic polymer containing disulfide bonds of the present invention has a complete morphology. The zwitterionic polymers pCBDS and pCBDHS prepared by solution concentration polymerization were placed in ultrapure water and degraded within one hour. After testing, the zwitterionic polymers prepared by thermal ring-opening polymerization also showed the same properties, such as Fig.11 shown.

[0078] According to the present invention, the process parameters can be adjusted to achieve the preparation of carboxybetaine zwitterionic polymers, and after testing, the performance is basically consistent with the present invention. The above is an exemplary description of the present invention. It should be noted that, without departing from the core of the present invention, any simple deformation, modification or equivalent replacement that can be made by other technicians in this field without spending creative labor falls within the protection scope of the present invention.

Claims

1. A degradable disulfide-bonded carboxybetaine zwitterionic polymer, characterized in that: Its chemical formula structure is shown below: R is CH2 or -NHCO, m is an integer of 1-5; n is the degree of polymerization of the zwitterionic polymer, which is 20-6000, and the number average molecular weight is 10000-1000000.

2. A degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 1, characterized in that: m is 1, 2; n is 800-3000, and the number average molecular weight is 100000-600000.

3. A method for preparing a degradable disulfide-bonded carboxybetaine zwitterionic polymer, characterized in that: Follow the steps below: Step 1, dispersing lipoic acid uniformly in a solvent for activation, then mixing and dispersing it with a tertiary amine containing active hydrogen, and drying and concentrating to obtain a tertiary amine monomer containing a disulfide bond; The structure of lipoic acid is shown in the following chemical formula: The structure of tertiary amine containing active hydrogen is shown in the following chemical formula: In step 1, the tertiary amine monomer containing a disulfide bond is shown in the following molecular formula: R is CH2 or -NHCO, and m is an integer from 1 to 5; The molar ratio of lipoic acid to the tertiary amine containing active hydrogen is 1:(1-1.5), and the reaction time is 6-24 hours at room temperature of 20-30 degrees Celsius; lipoic acid and CDI are mixed for activation, and the activation time of lipoic acid is 1-6 hours; the molar ratio of lipoic acid to CDI is 1:(1-1.5); Step 2, reacting the disulfide bond-containing tertiary amine monomer prepared in step 1 with β-propiolactone to obtain a degradable disulfide bond-containing carboxybetaine zwitterionic monomer, as shown in the following molecular formula: R is CH2 or -NHCO, m is an integer of 1-5; the molar ratio of β-propiolactone to the disulfide bond-containing tertiary amine monomer is (1-2):1 equivalent; the reaction temperature is room temperature 20-30 degrees Celsius, and the reaction time is 60-80 hours; Step 3, subjecting the degradable carboxybetaine zwitterionic monomer containing disulfide bonds prepared in step 2 to induced ring-opening polymerization to obtain a degradable carboxybetaine zwitterionic polymer containing disulfide bonds, the chemical formula of which is as follows: R is CH2 or -NHCO, m is an integer of 1-5; n is the degree of polymerization of the zwitterionic polymer, which is 20-6000, and the number average molecular weight is 10000-1000000; In step 3, solution concentration is used to induce ring-opening polymerization, or melt method heat-driven induced ring-opening polymerization is used.

4. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 1, the solvent used is anhydrous methanol, anhydrous ethanol, and anhydrous dichloromethane.

5. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 1, the molar ratio of lipoic acid to the tertiary amine containing active hydrogen is 1:1.1, and the reaction time is 12-15 hours at room temperature of 20-30 degrees Celsius.

6. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 1, lipoic acid and CDI are mixed for activation, the activation time of lipoic acid is 4 hours; the molar ratio of lipoic acid to CDI is 1:1.

1.

7. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 2, the solvent used in the reaction is anhydrous dichloromethane, anhydrous methanol, anhydrous tetrahydrofuran, and anhydrous ethanol; the added amount of β-propiolactone and the disulfide bond-containing tertiary amine monomer is 1.1:1, and the reaction time is 70-80 hours.

8. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: n is 800-3000, and the number average molecular weight is 100000-600000.

9. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 3, a mixed solvent of water and ethanol is used to dissolve a degradable carboxybetaine zwitterionic monomer containing a disulfide bond, and then the mixed solvent is placed in a constant temperature and humidity chamber to volatilize the solvent to prepare a degradable carboxybetaine zwitterionic polymer containing a disulfide bond; in the mixed solvent of water and ethanol, the volume percentage of ethanol is 20-80%; the molar concentration of the degradable carboxybetaine zwitterionic monomer containing a disulfide bond is 0.5-3 mol / L; the temperature and humidity of the constant temperature and humidity chamber are set to 25-45° C. and 30-80% respectively, and the solvent volatilization time is 1-14 days, and one day is 24 hours.

10. The method for preparing a degradable disulfide bond-containing carboxybetaine zwitterionic polymer according to claim 3, characterized in that: In step 3, the dynamic disulfide bonds of the degradable carboxybetaine zwitterionic monomer containing disulfide bonds are thermally driven by a melting method to achieve ring-opening polymerization to prepare a degradable carboxybetaine zwitterionic polymer containing disulfide bonds; the degradable carboxybetaine zwitterionic monomer containing disulfide bonds is melted at a high temperature, the polymerization temperature is 90-150° C., and the polymerization time is 1-10 hours.

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