Medical material for releasing amino acid and its derivative drugs and its application method

Abstract

The application discloses a medical material for releasing amino acid and derivative drugs and an application method thereof, wherein the medical material for releasing drugs comprises bistrichloromethyl carbonate dissolved in tetrahydrofuran. The application method of the medical material comprises the following steps: S1, putting the drugs into the medical material, and obtaining N-carboxyanhydride monomers of the drugs after reaction; and S2, polymerizing the N-carboxyanhydride monomers of the drugs to obtain a high polymer material containing the drugs. The amino acid and derivative drugs are prepared into N-carboxyanhydride monomers of the drugs, and the high polymer material containing amino acid drug units is obtained through polymerization, the material can slowly degrade and release drug monomers in the body, so that the effect of long-term treatment through one-time administration is achieved.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to a medical material that releases amino acid and its derivative drugs and its application method. Background Technology

[0002] Amino acids and their derivatives are widely used in clinical practice. For example, 1-methyl-D / L-tryptophan, as an inhibitor of indoleamine 2,3-dioxygenase (IDO), is used in clinical research on cancer immunotherapy; azoserine and diazooxyleucine are used to treat acute leukemia; arginine hydrochloride can be used to lower blood ammonia and as an adjunct treatment for acute liver dysfunction; calcium glutamate, γ-tyrosine, and serotonin are used to treat neurological diseases; and iodoalanine is used in tumor radiotherapy. Amino acid molecules are also frequently used as nutritional supplements.

[0003] Amino acid and its derivative drugs are currently usually administered orally or intravenously. Because these drugs participate in human metabolism and are eliminated from the body relatively quickly, they are typically administered in larger doses and more frequently. For example, in a phase II clinical trial (NCT01042535) of 1-methyl-D / L-tryptophan for the treatment of recurrent breast cancer, patients were required to take 100 mg to 1600 mg of the drug orally twice daily. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a medical material for releasing amino acid and its derivative drugs and the application method thereof, so as to reduce the frequency of administration of amino acid drugs in clinical practice and maintain long-term blood drug concentration balance.

[0005] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows:

[0006] A medical material for releasing drugs includes bis(trichloromethyl) carbonate dissolved in tetrahydrofuran.

[0007] Furthermore, the drug refers to amino acid and its derivative drugs.

[0008] Furthermore, the amino acid and its derivative drugs refer to amino acid drugs.

[0009] Furthermore, the amino acid and its derivative drugs include 1-methyl-D / L-tryptophan.

[0010] A method for applying the above-mentioned medical material includes the following steps:

[0011] S1. The drug is added to the medical material, and after the reaction, the N-carboxylic acid ring anhydride monomer of the drug is obtained;

[0012] S2. The N-carboxylic acid anhydride monomer of the drug is polymerized to obtain a polymeric material containing the drug.

[0013] Furthermore, it also includes the following steps:

[0014] S11. Lysine is added to the medical material, and after reaction, an N-carboxylic acid ring anhydride monomer of lysine is obtained; in step S2, the N-carboxylic acid ring anhydride monomer of lysine is mixed with the N-carboxylic acid ring anhydride monomer of the drug and then polymerized to obtain a polymer material containing the drug.

[0015] Furthermore, the mass ratio of the N-carboxylic acid anhydride monomer of the lysine to the N-carboxylic acid anhydride monomer of the drug is 1:1 to 1:9.

[0016] Furthermore, in step S11, the free amino group of lysine is first protected with a tert-butoxycarbonyl protecting group, and then the protection is removed after polymerization to obtain the N-carboxylic acid anhydride monomer of lysine.

[0017] Furthermore, it also includes the following steps:

[0018] S11. Lysine and / or arginine are respectively added to the medical material, and after reaction, N-carboxylic acid ring anhydride monomers of lysine and arginine are obtained; in step S2, the N-carboxylic acid ring anhydride monomers of lysine and arginine are mixed with the N-carboxylic acid ring anhydride monomer of the drug and then polymerized to obtain a polymer material containing the drug.

[0019] Further, S1 specifically involves adding the drug pretreated with toluene and tetrahydrofuran to a dry reaction flask, stirring and heating in an oil bath to 45-55°C, and slowly dripping the solution into the medical material after the reaction solution has stabilized. The reaction is stopped when the solution becomes a clear, slightly yellow solution, and the reaction solution is concentrated by rotary evaporation. The solution is then poured into n-hexane to precipitate, and vacuum filtered to obtain the N-carboxylic acid anhydride monomer of the drug. S2 specifically involves weighing the N-carboxylic acid anhydride monomer of the drug under a dry protective atmosphere, adding it to tetrahydrofuran to fully dissolve it, then adding benzylamine and potassium carbonate powder to obtain a reaction solution. The reaction solution is placed in an oil bath at 35-45°C for reaction. After the reaction is complete, the solution is concentrated, centrifuged, and dried to obtain the polymer material containing the drug.

[0020] The beneficial effects of this invention are:

[0021] This invention prepares N-carboxylic acid ring anhydride monomers of amino acids and their derivatives into drugs, and polymerizes them to obtain a polymer material containing amino acid drug units. This material can slowly degrade and release drug monomers in vivo to achieve the effect of long-term treatment with a single dose. Attached Figure Description

[0022] Figure 1 The N-carboxylic acid ring anhydride monomer of 1-methyl-D / L-tryptophan of the present invention has a 1H NMR spectrum (1H 500MHz, DMSO-d6).

[0023] Figure 2 The polymeric material of the present invention having an N-carboxylic acid ring anhydride monomer content of 100% (1H 500MHz, D2O:DMSO-D6 = 1:2);

[0024] Figure 3 The N-carboxylic acid ring anhydride monomer of lysine protected by the tert-butoxycarbonyl protecting group of the present invention has a 1H NMR spectrum (1H 500MHz, DMSO-d6).

[0025] Figure 4 The polymer material (1H 500MHz, D2O) in Example 2 of the present invention has an N-carboxylic acid ring anhydride monomer content of 10%.

[0026] Figure 5 The polymer material (1H 500MHz, D2O:DMSO-D6 = 1:1) with an N-carboxylic acid ring anhydride monomer content of 50% is used in Example 3 of the present invention.

[0027] Figure 6 This is a schematic diagram illustrating the IDO inhibition effect in HeLa cells according to the present invention. Detailed Implementation

[0028] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0029] This invention prepares N-carboxylic acid ring anhydride monomers of amino acids and their derivatives into drugs, and polymerizes them to obtain a polymer material containing amino acid drug units. This material can slowly degrade and release drug monomers in vivo to achieve the effect of long-term treatment with a single dose.

[0030] For non-amino acid drugs, they can first be bonded to amino acids through chemical reactions, and then similar sustained-release polymer materials can be prepared using this invention.

[0031] By using amino acid and derivative drugs to copolysaturate lysine, arginine, and other amino acid monomers, different numbers of protease cleavage sites are provided for the material, making the biodegradation of the material somewhat controllable. This eliminates the need for repeated oral or injectable administration, while still meeting treatment needs, providing convenience for both doctors and patients.

[0032] Example 1

[0033] The following experiments must be conducted under strictly anhydrous conditions. All solvents should be refluxed with sodium potassium hydroxide or calcium hydride and then freshly distilled before use. Amino acids and their derivatives should be refluxed with toluene under reduced pressure, the water removed using a water separator, and the toluene removed by further distillation under reduced pressure before use. Experimental operations must be conducted under a dry protective atmosphere (nitrogen, argon, or compressed air), and glassware must be strictly dried before use. Intermediate products must be stored in a desiccator. The drugs mentioned in this embodiment refer to amino acids and their derivatives. This embodiment uses 1-methyl-D / L-tryptophan as an example for a detailed description of the protocol.

[0034] S1. The drug is added to the medical material, and the reaction yields the N-carboxylic acid ring anhydride monomer (NCA) of the drug. Specifically, this includes the following steps:

[0035] Add toluene-pretreated 1-methyl-D / L-tryptophan (1-MT, 2.18 g, 10 mmol) and 50 mL of dry tetrahydrofuran to a dry reaction flask. Heat to 50 °C in an oil bath with stirring. After the reaction solution temperature stabilizes, slowly add the medical material for drug release (2 g of 6.67 mmol of methyl bis(trichloromethyl) carbonate dissolved in 10 mL of tetrahydrofuran) dropwise through a constant-pressure dropping funnel. The reaction solution should initially thicken to a gel-like consistency, then slowly dissolve and become clear. After the reaction solution has completely become a clear, slightly yellow solution (usually about 3 hours), continue the reaction for another 30 minutes to ensure complete reaction and remove excess byproducts such as carbonyl chloride and hydrogen chloride. After stopping the reaction, concentrate the reaction solution to about 10 mL by rotary evaporation, then pour it into 100 mL of n-hexane to precipitate. Vacuum filter to obtain a solid white crude product. Recrystallize the crude product twice in the tetrahydrofuran / n-hexane reaction solution and dry under vacuum at room temperature for 24 hours. Figure 1 As shown, 1.44 g of the N-carboxylic acid ring anhydride monomer (denoted as 1-MT NCA monomer), which appeared white, was obtained with a yield of 45%.

[0036] S2. The N-carboxylic acid anhydride monomer of the drug is polymerized to obtain a polymeric material containing the drug.

[0037] Weigh 0.5 g of the N-carboxylic acid ring anhydride monomer of the drug prepared in step S1 under a dry protective atmosphere, place it in a reaction flask, and add 5 ml of tetrahydrofuran to dissolve it completely. Add 5 μl of benzylamine as an initiator and 20 mg of potassium carbonate powder to balance the pH in the reaction flask, then seal the flask and place the reaction solution in an oil bath at 40 °C for 72 hours. After the reaction is complete, concentrate the solution to 1 ml and add it dropwise to 20 ml of diethyl ether to precipitate the product. Then centrifuge to collect the precipitate, redissolve the precipitate in 1 ml of tetrahydrofuran, and add it dropwise to 20 ml of diethyl ether again to precipitate the product. Repeat this process twice, collect the final product, and vacuum dry for 4 hours. Figure 2 As shown, a polymer material with 100% N-carboxylic acid ring anhydride monomer content (P-MT100%) can be obtained for subsequent use.

[0038] This polymer material can slowly degrade in the body, releasing drug monomers (1-methyl-D / L-tryptophan) to achieve the effect of long-term treatment with a single dose.

[0039] Example 2

[0040] S1. The drug is added to the medical material, and the reaction yields the N-carboxylic acid ring anhydride monomer of the drug. Specifically, this includes the following steps:

[0041] Add toluene-pretreated 1-methyl-D / L-tryptophan (1-MT, 2.18 g, 10 mmol) and 50 mL of dry tetrahydrofuran to a dry reaction flask. Heat to 45 °C in an oil bath with stirring. After the reaction solution temperature stabilizes, slowly add the medical material for drug release (2 g of 6.67 mmol of bis(trichloromethyl) carbonate dissolved in 10 mL of tetrahydrofuran) dropwise through a constant pressure dropping funnel. Observe that the reaction solution first thickens to a gel-like state, then slowly dissolves and becomes clear. After the reaction solution has completely become a clear, slightly yellow solution (usually about 3 hours), continue the reaction for another 30 minutes to ensure complete reaction and remove excess byproducts such as carbonyl chloride and hydrogen chloride. After stopping the reaction, concentrate the reaction solution to about 10 mL by rotary evaporation, then pour it into 100 mL of n-hexane to precipitate, and then filter under vacuum to obtain a solid white crude product. The crude product was recrystallized twice in a tetrahydrofuran / n-hexane reaction solution and dried under vacuum at room temperature for 24 h to obtain 1.44 g of the white-looking N-carboxylic acid ring anhydride monomer (1-MT NCA monomer), with a yield of 50%.

[0042] S11. Lysine is added to the medical material, and after the reaction, an N-carboxylic acid ring anhydride monomer of lysine (Lys NCA monomer) and / or an N-carboxylic acid ring anhydride monomer of arginine (denoted as Arg NCA monomer) are obtained.

[0043] The preparation of the N-carboxylic acid ring anhydride monomer of lysine is similar to that of the N-carboxylic acid ring anhydride monomer of the drug. The difference lies in that lysine has a free amino group, requiring initial protection with a tert-butyloxycarbonyl protecting group. Deprotection is then performed after polymerization to obtain the final product. Specifically, 10 g (33.56 mmol) of lysine protected by a tert-butyloxycarbonyl protecting group and 100 mL of tetrahydrofuran are added to a reaction flask. The mixture is heated to 45°C under stirring in an oil bath. After the reaction solution temperature stabilizes, the medical material used for drug release (4.6 g, 15.4 mmol of bis(trichloromethyl) carbonate dissolved in 20 mL of tetrahydrofuran) is slowly added dropwise through a constant-pressure dropping funnel. After the reaction, the reaction solution is concentrated to approximately 20 mL by rotary evaporation. The concentrated reaction solution is then poured into 200 mL of n-hexane to precipitate. The crude product is recrystallized twice from tetrahydrofuran / n-hexane to obtain a white, flaky crystalline product. Figure 3 As shown, 8.05 g of the N-carboxylic acid anhydride monomer of lysine protected by the tert-butyloxycarbonyl protecting group was obtained, with a yield of 73.8%.

[0044] S2. The N-carboxylic acid anhydride monomer of the drug is polymerized to obtain a polymeric material containing the drug.

[0045] Weigh out 0.5 g of the N-carboxylic acid anhydride monomer and the N-carboxylic acid anhydride monomer of lysine prepared in step S1 under a dry protective atmosphere, wherein the N-carboxylic acid anhydride monomer of lysine is 0.45 g and the N-carboxylic acid anhydride monomer of the drug is 0.05 g. Place the N-carboxylic acid anhydride monomer of the drug and the N-carboxylic acid anhydride monomer of lysine in a reaction flask, and add 5 ml of tetrahydrofuran to dissolve them completely. Add 5 μl of benzylamine as an initiator and 20 mg of potassium carbonate powder to balance the pH in the reaction flask, then seal the flask and place the reaction solution in an oil bath at 45°C for 72 hours. After the reaction is complete, open the flask cap, add 0.5 ml of trifluoroacetic acid, and continue the reaction at room temperature for 2 hours to remove the tert-butyloxycarbonyl protecting group. Then concentrate the solution to 1 ml and precipitate the product by adding it dropwise to 20 ml of diethyl ether. The precipitate was then collected by centrifugation and redissolved in 1 ml of tetrahydrofuran. This precipitate was then added dropwise to 20 ml of diethyl ether. This process was repeated twice, and the final product was collected and vacuum dried for 4 hours to obtain a polymeric material with a 10% N-carboxylic acid ring anhydride monomer content (P-MT-Lys 10%). Figure 4 As shown, this is for subsequent use.

[0046] Example 3

[0047] S1. The drug is added to the medical material, and the reaction yields the N-carboxylic acid ring anhydride monomer of the drug. Specifically, this includes the following steps:

[0048] Add toluene-pretreated 1-methyl-D / L-tryptophan (2.18 g, 10 mmol) and 50 mL of dry tetrahydrofuran to a dry reaction flask. Heat to 45 °C in an oil bath with stirring. After the reaction solution temperature stabilizes, slowly add the medical material for drug release (2 g of 6.67 mmol of bis(trichloromethyl) carbonate dissolved in 10 mL of tetrahydrofuran) dropwise through a constant pressure dropping funnel. Observe that the reaction solution first thickens to a gel-like state, then slowly dissolves and becomes clear. After the reaction solution has completely become a clear, slightly yellow solution (usually about 3 hours), continue the reaction for another 30 minutes to ensure complete reaction and remove excess byproducts such as carbonyl chloride and hydrogen chloride. After stopping the reaction, concentrate the reaction solution to about 10 mL by rotary evaporation, then pour it into 100 mL of n-hexane to precipitate, and then filter under vacuum to obtain a solid white crude product. The crude product was recrystallized twice in a tetrahydrofuran / n-hexane reaction solution and dried under vacuum at room temperature for 24 h to obtain 1.44 g of the N-carboxylic acid ring anhydride monomer of the drug, which appeared white, with a yield of 50%.

[0049] S11. Lysine is added to the medical material, and after the reaction, N-carboxylic acid ring anhydride monomers of lysine and / or N-carboxylic acid ring anhydride monomers of arginine are obtained.

[0050] The preparation of the N-carboxylic acid ring anhydride monomer of lysine is similar to that of the N-carboxylic acid ring anhydride monomer of the drug. The difference is that lysine has a free amino group, which needs to be protected with a tert-butyloxycarbonyl protecting group first, and then deprotected after polymerization to obtain the final product. Specifically, lysine protected by benzyl formate (10 g, 33.56 mmol) and 100 mL of tetrahydrofuran were added to a reaction flask, and the mixture was stirred and heated to 45 °C in an oil bath. After the reaction solution temperature stabilized, the medical material for drug release (4.6 g, 15.4 mmol of bis(trichloromethyl) carbonate dissolved in 20 mL of tetrahydrofuran) was slowly added dropwise through a constant pressure dropping funnel. After the reaction was completed, the reaction solution was concentrated to about 20 mL by rotary evaporation, and the concentrated reaction solution was poured into 200 mL of n-hexane to precipitate. The crude product was recrystallized twice with tetrahydrofuran / n-hexane to obtain 8.05 g of N-carboxylic acid ring anhydride monomer of lysine, which is a white flaky crystalline product, with a yield of 73.8%.

[0051] S2. The N-carboxylic acid anhydride monomer of the drug is polymerized to obtain a polymeric material containing the drug.

[0052] Weigh out 0.5 g of the N-carboxylic acid anhydride monomer and the N-carboxylic acid anhydride monomer of lysine prepared in step S1 under a dry protective atmosphere, wherein 0.25 g of the N-carboxylic acid anhydride monomer of lysine and 0.25 g of the N-carboxylic acid anhydride monomer of the drug are respectively weighed out. Place the N-carboxylic acid anhydride monomer of the drug and the N-carboxylic acid anhydride monomer of lysine in a reaction flask, and add 5 ml of tetrahydrofuran to dissolve them completely. Add 5 μl of benzylamine as an initiator and 20 mg of potassium carbonate powder to balance the pH in the reaction flask, then seal the flask and place the reaction solution in an oil bath at 45°C for 72 hours. After the reaction is completed, open the cap, add 0.5 ml of trifluoroacetic acid, and continue the reaction at room temperature for 2 hours to remove the tert-butyloxycarbonyl protecting group. Then concentrate the solution to 1 ml and precipitate the product by adding it dropwise to 20 ml of diethyl ether. The precipitate was then collected by centrifugation and redissolved in 1 ml of tetrahydrofuran. This precipitate was then added dropwise to 20 ml of diethyl ether. This process was repeated twice, and the final product was collected and dried under vacuum for 4 hours. Figure 5 As shown, a polymer material with an N-carboxylic acid ring anhydride monomer content of 50% (P-MT-Lys50%) can be obtained for subsequent use.

[0053] This invention yields polymer materials containing N-carboxylic acid ring anhydride monomers with different proportions of drugs (the content of N-carboxylic acid ring anhydride monomers of drugs is 100%, 10%, and 50%, corresponding to Examples 1, 2, and 3, respectively).

[0054] Comparative test

[0055] HeLa cells were resuspended at a density of 2.5 x 10⁵ cells / mL in complete DMEM medium and seeded into 96-well plates at a density of 200 μL (5 x 10⁴ cells / well). The cells were incubated overnight at 37°C and 5% CO₂ to allow for adherence. After removing the supernatant, 200 μL of fresh complete DMEM medium containing different concentrations of human interferon-γ (IFN-γ), 1-methyl-D / L-tryptophan, or equivalent concentrations of the polymeric material from Examples 1, 2, and 3 were added to each well. Complete DMEM medium refers to DMEM medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution (PS). The role of human interferon-γ (IFN-γ) is to activate HeLa cells, causing them to highly express IDO1.

[0056] 1. Negative control wells (3 wells): only complete DMEM medium was added.

[0057] 2. Positive control wells (3 wells): Add complete DMEM medium containing 10 ng / ml human interferon (IFN-γ).

[0058] 3.1-MT group (five concentrations, 3 wells per concentration): Add complete DMEM medium containing 10 ng / ml human interferon (IFN-γ) and 200 μg / ml, 100 μg / ml, 20 μg / ml, 2 μg / ml and 0.2 μg / ml 1-MT.

[0059] 4. P-MT 100% group (five concentrations, 3 wells per concentration): add complete DMEM medium containing 10 ng / ml human interferon (IFN-γ) and P-MT-Lys 10% polymer material at concentrations of 200 μg / ml, 100 μg / ml, 20 μg / ml, 2 μg / ml, and 0.2 μg / ml (Example 1);

[0060] 5. P-MT-Lys 10% group (five concentrations, 3 wells per concentration): Add complete DMEM medium containing 10 ng / ml human interferon (IFN-γ) and 2000 μg / ml, 1000 μg / ml, 200 μg / ml, 20 μg / ml, and 2 μg / ml P-MT-Lys 10% polymer material (Example 2);

[0061] 6. P-MT-Lys 50% group (five concentrations, 3 wells per concentration): add complete DMEM medium containing 10 ng / ml human interferon (IFN-γ) and 400 μg / ml, 200 μg / ml, 40 μg / ml, 4 μg / ml, and 0.4 μg / ml of P-MT-Lys 50% polymer material (Example 3).

[0062] After co-culturing HeLa cells with the aforementioned culture media containing different components for 24 hours, 150 μL of supernatant was aspirated from each well and transferred to a new 96-well plate. 50 μL of 30% (v / v) trichloroacetic acid in glacial acetic acid solution was added to each well of the new 96-well plate, mixed well, and incubated in a 50°C water bath for 30 minutes. After the reaction, the plate was centrifuged at 10000 x g for 10 minutes, and 100 μL of the reaction supernatant was transferred from each well to another new 96-well plate. Then, 100 μL of 20% dimethylaminobenzaldehyde in glacial acetic acid solution was added to each well, and the plate was incubated at room temperature for 10 minutes. The absorbance at 492 nm was measured, and the absorbance of the negative control wells was subtracted from the background and normalized to 1 (positive control wells were considered as 1) to compare the differences in IDO activity among different groups. Figure 6 As shown.

[0063] Experiments showed that the polymers obtained in Example 1 (P-MT 100%), Example 2 (P-MT-Lys 10%), and Example 3 (P-MT-Lys 50%) were similar to those of free 1-methyl-D / L-tryptophan (1-MT) and could inhibit the function of IDO. The inhibitory effects of polymers containing different proportions of the drug within the N-carboxylic acid ring anhydride monomer were significantly different. Specifically, the IDO1 enzyme inhibitory effect of the polymer obtained in Example 3 was essentially the same as that of free 1-methyl-D / L-tryptophan. Polymers with a high proportion of N-carboxylic acid anhydride monomers in the drug ring (such as the polymer with 100% N-carboxylic acid anhydride monomer content in Example 1) showed lower inhibitory effects than polymers with a low proportion of N-carboxylic acid anhydride monomers in the drug ring (such as the polymer with 50% N-carboxylic acid anhydride monomer content in Example 3 and the polymer with 10% N-carboxylic acid anhydride monomer content in Example 2). This difference in inhibitory effect can be explained by the different degradation rates of the polymers. The experimental results demonstrate that polymerized amino acid and derivative drugs can retain their original functions, and that copolymerizing different proportions of lysine can regulate the function of the polymer.

[0064] The medical material of the present invention releases amino acids and their derivatives, the release rate of which can be controlled, and can be prepared into a subcutaneous implantable drug, avoiding the inconvenience of frequent administration and avoiding missed doses due to poor patient compliance.

[0065] The above content is only a preferred embodiment of the present invention. For those skilled in the art, many changes can be made in the specific implementation and application scope based on the concept of the present invention. As long as these changes do not depart from the concept of the present invention, they all fall within the protection scope of the present invention.

Claims

1. The application of a medical material in the preparation of a drug, said medical material comprising bis(trichloromethyl) carbonate dissolved in tetrahydrofuran, characterized in that, The medical material is used to release a drug, which refers to an amino acid and its derivatives, specifically 1-methyl-D / L-tryptophan. Includes the following steps: S1. The drug is added to the medical material, and after the reaction, the N-carboxylic acid ring anhydride monomer of the drug is obtained; S2. The N-carboxylic acid ring anhydride monomer of the drug is polymerized to obtain a polymer material containing the drug; It also includes the following steps: S11. Lysine is added to the medical material, and after reaction, an N-carboxylic acid ring anhydride monomer of lysine is obtained; in step S2, the N-carboxylic acid ring anhydride monomer of lysine is mixed with the N-carboxylic acid ring anhydride monomer of the drug and then polymerized to obtain a polymer material containing the drug; the mass ratio of the N-carboxylic acid ring anhydride monomer of lysine to the N-carboxylic acid ring anhydride monomer of the drug is 1:1 to 1:9; In step S11, the free amino group of lysine is first protected with a tert-butoxycarbonyl protecting group, and then the protection is removed after polymerization to obtain the N-carboxylic acid anhydride monomer of lysine.

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