A medical polycarbonate and its preparation method

Abstract

The present invention belongs to the field of medical engineering plastics, and specifically relates to a medical polycarbonate and a preparation method thereof. A medical polycarbonate, by mass, comprises 100-120 parts of polycarbonate, 10-20 parts of 4-nitro-2-(2-propynyloxy)aniline, 15-20 parts of 1,3,5-tri(p-formylphenyl)benzene, 0.5-2 parts of heparin, and 0.1-0.2 parts of a cross-linking agent. The present invention uses a framework material with a topological structure as an intermediate carrier, and the framework material forms a stable combination with the polycarbonate, so that the heparin forms a stable combination with the polycarbonate with the help of the framework material, avoids the shedding of the heparin, and improves the anticoagulant stability of the polycarbonate.

Description

Technical Field

[0001] The invention belongs to the field of medical engineering plastics, and in particular relates to medical polycarbonate and a preparation method thereof. Background Art

[0002] Polycarbonate is a common medical engineering plastic with good biocompatibility, mechanical properties and light transmittance, which are more compatible with the requirements of medical polymer materials. However, polycarbonate will stimulate the coagulation mechanism when it comes into contact with blood. Therefore, medical devices such as hemodialysis machines cannot be directly manufactured with polycarbonate, and the anti-coagulation properties of polycarbonate need to be modified.

[0003] At present, in order to improve the anticoagulant performance of polycarbonate, heparin is usually used to modify polycarbonate. Heparin is an effective anticoagulant. The common method of combining heparin and polycarbonate is to directly coat heparin on the surface of polycarbonate. However, the combination between heparin and polycarbonate using this method is not stable. After being stored for a long time, the heparin on the surface of polycarbonate may fall off. Summary of the invention

[0004] In order to solve the problems existing in the above-mentioned prior art, the present invention provides a medical polycarbonate and a preparation method thereof, which adopts a framework material with a topological structure as an intermediate carrier. The framework material can form a stable combination with the polycarbonate, so that heparin can form a stable combination with the polycarbonate with the help of the framework material, thereby avoiding the shedding of heparin and improving the anti-coagulation stability of the polycarbonate.

[0005] The specific technical solution adopted by the present invention is:

[0006] A medical polycarbonate comprises, by weight, 100-120 parts of polycarbonate, 10-20 parts of 4-nitro-2-(2-propynyloxy)aniline, 15-20 parts of 1,3,5-tri(p-formylphenyl)benzene, 0.5-2 parts of heparin, and 0.1-0.2 parts of a cross-linking agent.

[0007] The cross-linking agent includes any one of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and dicyclohexylcarbodiimide.

[0008] A method for preparing medical polycarbonate comprises the following steps:

[0009] S1, adding 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tri(p-formylphenyl)benzene and a reaction solvent into a reaction kettle, and heating the reaction to generate a framework material;

[0010] S2, then adding heparin and the framework material into an organic solvent, and then adding a cross-linking agent to react to generate an anticoagulant framework material;

[0011] S3. Dissolve tris(hydroxymethyl)aminomethane in water and sonicate to completely dissolve it. Then, add dilute hydrochloric acid solution dropwise to adjust the pH value to the range of 8 - 9 to prepare a buffer solution.

[0012] S4. Add the anticoagulant frame material to the buffer solution, stir evenly to form a loading solution, then put the polycarbonate into the loading solution, react at room temperature for 8 - 12 h, and obtain medical polycarbonate after drying.

[0013] The reaction solvent includes any one of anhydrous tetrahydrofuran, ethanol, methanol, and toluene, and the mass ratio of the reaction solvent to 4 - nitro - 2 - (2 - propynyloxy)aniline is 15 - 20:1.

[0014] In step S1, the heating temperature is 90 - 120 °C and the reaction time is 8 - 12 h.

[0015] In step S2, the organic solvent includes any one of methanol, ethanol, benzene, toluene, cyclohexane, and methylcyclohexane.

[0016] The molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.03 - 0.06 mol / L.

[0017] Before the polycarbonate is put into the loading solution, an antioxidant treatment is carried out, and the antioxidant treatment includes the following steps:

[0018] A. Dissolve the polycarbonate in acetone to form a polycarbonate solution.

[0019] B. Put the nano - zinc oxide into acetone, then add an antioxidant, stir evenly at a rate of 2000 - 3000 r / min, and complete the antioxidant treatment of the polycarbonate after drying.

[0020] The mass ratio of the polycarbonate, nano - zinc oxide, and antioxidant is 100:1 - 2:1 - 2.

[0021] The antioxidant includes a hindered phenol antioxidant and a phosphite antioxidant with a mass ratio of 10:1 - 3.

[0022] The beneficial effects of the present invention are:

[0023] 1. In the present invention, in order to improve the binding stability between heparin and polycarbonate, a frame material with a topological structure is used as an intermediate carrier. First, the hydroxyl group of heparin and the amino group of the frame material are cross - linked and combined through a chemical reaction to form a stable cross - link between the two. Then, the frame material is coated on the surface of the polycarbonate. Since the frame material has a hexahedron - like solid structure, the frame material will form a stable complex with the polycarbonate, so that heparin forms a stable complex with the polycarbonate with the help of the frame material, avoiding the shedding of heparin and improving the anticoagulant stability of the polycarbonate.

[0024] 2. In the present invention, antioxidant treatment is also carried out on polycarbonate. Generally, the antioxidant treatment of traditional polycarbonate is to stir the polycarbonate powder and antioxidant powder evenly and then use an extruder to reform polycarbonate. However, this method will cause the antioxidant to be unevenly distributed in the polycarbonate, resulting in the problem of local yellowing. In the present invention, the polycarbonate is first dissolved into a liquid. During the process of dissolving polycarbonate in acetone, the surface of polycarbonate molecules will become rough, so that nano-zinc oxide can be embedded in the polycarbonate. On the one hand, nano-zinc oxide can jointly produce a compound synergistic effect with hindered phenol antioxidants and phosphite antioxidants, improving the anti-yellowing performance of polycarbonate and making it not easy to change color. In addition, the porous structure of nano-zinc oxide will cooperate more stably with the cage-like framework material, further improving the binding stability between the framework material and polycarbonate, thus avoiding the shedding of heparin. Detailed implementation manners

[0025] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention. I. Specific embodiments

[0027] Embodiment 1

[0028] S0. Weigh 110 parts of polycarbonate, 15 parts of 4-nitro-2-(2-propynyloxy)aniline, 18 parts of 1,3,5-tris(p-formylphenyl)benzene, 1 part of heparin, and 0.15 part of 1-ethyl-(3-dimethylaminopropyl)carbodiimide;

[0029] S1. Add 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tris(p-formylphenyl)benzene, and anhydrous tetrahydrofuran into a reaction kettle, and react at 100 °C for 10 h to generate a framework material;

[0030] S2. Then add heparin and the framework material into methanol, and then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide to react to generate an anticoagulant framework material;

[0031] S3. Dissolve tris(hydroxymethyl)aminomethane in water, and ultrasonically dissolve it completely. Then add a dilute hydrochloric acid solution to adjust the pH to 8.5 to prepare a buffer solution. The molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.05 mol / L;

[0032] S4. Dissolve polycarbonate in acetone to form a polycarbonate solution. Put nano-zinc oxide into acetone, and then add an antioxidant, and stir evenly at a rate of 2500 r / min. After drying, the antioxidant treatment of polycarbonate is completed;

[0033] Among them, the mass ratio of polycarbonate, nano-zinc oxide and antioxidant is 100:1.5:1.5. The antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:2;

[0034] S5. Add the anticoagulant frame material into the buffer solution, stir evenly to form a loading solution, then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 10 h, and obtain medical polycarbonate after drying.

[0035] Example 2

[0036] S0. Weigh 100 parts of polycarbonate, 10 parts of 4-nitro-2-(2-propynyloxy)aniline, 15 parts of 1,3,5-tris(4-formylphenyl)benzene, 0.5 part of heparin, and 0.1 part of dicyclohexylcarbodiimide;

[0037] S1. Add 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tris(4-formylphenyl)benzene and anhydrous tetrahydrofuran into the reaction kettle, and react at 90 °C for 12 h to generate the frame material;

[0038] S2. Then add heparin and the frame material into methanol, and then add dicyclohexylcarbodiimide to react to generate the anticoagulant frame material;

[0039] S3. Dissolve tris(hydroxymethyl)aminomethane in water, ultrasonically dissolve it completely, then add dilute hydrochloric acid solution dropwise to adjust the pH to 8.0 to prepare a buffer solution. The molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.03 mol / L;

[0040] S4. Dissolve polycarbonate in acetone to form a polycarbonate solution, put nano-zinc oxide into acetone, then add the antioxidant, stir evenly at a rate of 2000 r / min, and complete the antioxidant treatment of polycarbonate after drying;

[0041] Among them, the mass ratio of polycarbonate, nano-zinc oxide and antioxidant is 100:1:1. The antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:1;

[0042] S5. Add the anticoagulant frame material into the buffer solution, stir evenly to form a loading solution, then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 8 h, and obtain medical polycarbonate after drying.

[0043] Example 3

[0044] S0. Weigh 120 parts of polycarbonate, 20 parts of 4-nitro-2-(2-propynyloxy)aniline, 20 parts of 1,3,5-tris(4-formylphenyl)benzene, 2 parts of heparin, and 0.2 part of 1-ethyl-(3-dimethylaminopropyl)carbodiimide;

[0045] S1. Add 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tris(4-formylphenyl)benzene, and anhydrous tetrahydrofuran into a reaction kettle, and react at 120 °C for 8 h to generate a framework material;

[0046] S2. Then add heparin and the framework material into methanol, and then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide to react to generate an anticoagulant framework material;

[0047] S3. Dissolve tris(hydroxymethyl)aminomethane in water, and ultrasonically dissolve it completely. Then add a dilute hydrochloric acid solution dropwise to adjust the pH to 9.0 to prepare a buffer solution. The molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.06 mol / L;

[0048] S4. Dissolve polycarbonate in acetone to form a polycarbonate solution. Put nano-zinc oxide into acetone, and then add an antioxidant, and stir evenly at a rate of 3000 r / min. After drying, the antioxidant treatment of polycarbonate is completed;

[0049] Among them, the mass ratio of polycarbonate, nano-zinc oxide, and antioxidant is 100:2:2. The antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:3;

[0050] S5. Add the anticoagulant framework material into the buffer solution, stir evenly to form a loading solution, and then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 12 h, and obtain medical polycarbonate after drying.

[0051] Example 4

[0052] S0. Weigh 105 parts of polycarbonate, 12 parts of 4-nitro-2-(2-propynyloxy)aniline, 16 parts of 1,3,5-tris(4-formylphenyl)benzene, 0.8 part of heparin, and 0.12 part of 1-ethyl-(3-dimethylaminopropyl)carbodiimide;

[0053] S1. Add 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tris(4-formylphenyl)benzene, and anhydrous tetrahydrofuran into a reaction kettle, and react at 95 °C for 11 h to generate a framework material;

[0054] S2. Then add heparin and the framework material into methanol, and then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide to react to generate an anticoagulant framework material;

[0055] S3. Dissolve tris(hydroxymethyl)aminomethane in water, and ultrasonically dissolve it completely. Then, add dilute hydrochloric acid solution to adjust the pH to 8.0 to prepare a buffer solution, where the molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.04 mol / L;

[0056] S4. Dissolve polycarbonate in acetone to form a polycarbonate solution. Put nano-zinc oxide into acetone, then add an antioxidant, and stir evenly at a rate of 2500 r / min. After drying, the antioxidant treatment of polycarbonate is completed;

[0057] Wherein the mass ratio of polycarbonate, nano-zinc oxide and antioxidant is 100:1.2:1.2, and the antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:1.5;

[0058] S5. Add the anticoagulant frame material to the buffer solution, stir evenly to form a loading solution, then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 10 h, and obtain medical polycarbonate after drying.

[0059] Example 5

[0060] S0. Weigh 115 parts of polycarbonate, 18 parts of 4-nitro-2-(2-propynyloxy)aniline, 18 parts of 1,3,5-tris(p-formylphenyl)benzene, 1.8 parts of heparin, and 0.18 part of 1-ethyl-(3-dimethylaminopropyl)carbodiimide;

[0061] S1. Add 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tris(p-formylphenyl)benzene and anhydrous tetrahydrofuran to a reaction kettle, and react at 110 °C for 9 h to generate a frame material;

[0062] S2. Then add heparin and the frame material to methanol, and then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide to react to generate an anticoagulant frame material;

[0063] S3. Dissolve tris(hydroxymethyl)aminomethane in water, and ultrasonically dissolve it completely. Then, add dilute hydrochloric acid solution to adjust the pH to 9.0 to prepare a buffer solution, where the molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.06 mol / L;

[0064] S4. Dissolve polycarbonate in acetone to form a polycarbonate solution. Put nano-zinc oxide into acetone, then add an antioxidant, and stir evenly at a rate of 3000 r / min. After drying, the antioxidant treatment of polycarbonate is completed;

[0065] Among them, the mass ratio of polycarbonate, nano-zinc oxide and antioxidant is 100:1.8:1.8, and the antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:2.5;

[0066] S5. Add the anticoagulant frame material to the buffer solution, stir evenly to form a loading solution, then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 10 h, and obtain medical polycarbonate after drying.

[0067] Comparative Example 1

[0068] The difference between Comparative Example 1 and Example 1 is only that the frame material is not used as an intermediate carrier in Comparative Example 1. The specific steps of Comparative Example 1 are as follows:

[0069] S0. Weigh 110 parts of polycarbonate and 1 part of heparin;

[0070] S1. Dissolve tris(hydroxymethyl)aminomethane in water, sonicate to completely dissolve it, then add dilute hydrochloric acid solution to adjust the pH to 8.5 to prepare a buffer solution, and the molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.05 mol / L;

[0071] S2. Dissolve polycarbonate in acetone to form a polycarbonate solution, put nano-zinc oxide into acetone, then add an antioxidant, stir evenly at a rate of 2500 r / min, and complete the antioxidant treatment of polycarbonate after drying;

[0072] Among them, the mass ratio of polycarbonate, nano-zinc oxide and antioxidant is 100:1.5:1.5, and the antioxidant includes hindered phenol antioxidant 1010 and phosphite antioxidant 168 with a mass ratio of 10:2;

[0073] S3. Add heparin to the buffer solution, stir evenly to form a loading solution, then put the antioxidant-treated polycarbonate into the loading solution for impregnation, react at room temperature for 10 h, and obtain medical polycarbonate after drying.

[0074] Comparative Example 2

[0075] The difference between Comparative Example 2 and Example 1 is only that nano-zinc oxide is not added in the oxidation treatment process of Comparative Example 2.

[0076] Comparative Example 3

[0077] The difference between Comparative Example 3 and Example 1 is only that the antioxidant is not added in the oxidation treatment process of Comparative Example 3.

[0078] II. Performance Test

[0079] Measure the surface heparin weight a1 of the medical polycarbonate prepared in the measurement examples and comparative examples. Then, place the medical polycarbonate in an ultrasonic cleaner and process it for 60 minutes, and measure the surface heparin weight a2 again. The heparin residue rate is a2 / a1, and the heparin content is determined by the toluidine blue colorimetric method; for the antioxidant performance test, prepare the medical polycarbonate prepared in the examples and comparative examples into test pieces with a thickness of 3 mm. After irradiation with Co-60 γ-rays at a dose of 30 kGy, place them under natural light conditions for 15 days, and determine the yellowness index before and after irradiation according to the method of HG / T 3862-2006. The results are shown in Table 1.

[0080] Table 1

[0081]

[0082] As can be seen from Table 1, in Examples 1-5 and Comparative Examples 2-3, the framework material was used as the intermediate carrier, which can effectively increase the binding stability between heparin and polycarbonate. At the same time, it can be seen from Example 1 and Comparative Example 2 that the porous structure of nano-zinc oxide can cooperate more stably with the cage-like framework material, further improving the binding stability between the framework material and polycarbonate.

[0083] By comparing Example 1 with Comparative Examples 2-3, it can be seen that nano-zinc oxide, hindered phenol antioxidant, and phosphite antioxidant jointly produce a compound synergistic effect, and they jointly produce an unexpected antioxidant effect, far exceeding the antioxidant effect of binary compounding.

Claims

1. A medical polycarbonate, characterized in that: The composition comprises, by weight, 100-120 parts of polycarbonate, 10-20 parts of 4-nitro-2-(2-propynyloxy)aniline, 15-20 parts of 1,3,5-tri(p-formylphenyl)benzene, 0.5-2 parts of heparin, and 0.1-0.2 parts of a cross-linking agent; The preparation method of medical polycarbonate comprises the following steps: S1, adding 4-nitro-2-(2-propynyloxy)aniline, 1,3,5-tri(p-formylphenyl)benzene and a reaction solvent into a reaction kettle to react and generate a framework material; S2, then adding heparin and the framework material into an organic solvent, and then adding a cross-linking agent to react to generate an anticoagulant framework material; S3, dissolving tris(hydroxymethyl)aminomethane in water, sonicating to completely dissolve it, and then dropping dilute hydrochloric acid solution to adjust the pH value to 8-9 to prepare a buffer solution; S4. Add the anticoagulant framework material into the buffer solution, stir evenly to form a loading liquid, then immerse the polycarbonate in the loading liquid, react at room temperature for 8-12 hours, and obtain the medical polycarbonate after drying.

2. A medical polycarbonate according to claim 1, characterized in that: The cross-linking agent includes any one of 1-ethyl-(3-dimethylaminopropyl)carbodiimide and dicyclohexylcarbodiimide.

3. The medical polycarbonate according to claim 1, characterized in that: The reaction solvent includes any one of anhydrous tetrahydrofuran, ethanol, methanol and toluene, and the mass ratio of the reaction solvent to 4-nitro-2-(2-propynyloxy)aniline is 15-20:

1.

4. The medical polycarbonate according to claim 1, characterized in that: The heating temperature of the reaction in step S1 is 90-120° C., and the reaction time is 8-12 hours.

5. The medical polycarbonate according to claim 1, characterized in that: The organic solvent in step S2 includes any one of methanol, ethanol, benzene, toluene, cyclohexane, and methylcyclohexane.

6. The medical polycarbonate according to claim 1, characterized in that: The molar concentration of tris(hydroxymethyl)aminomethane in the buffer solution is 0.03-0.06 mol / L.

7. The medical polycarbonate according to claim 1, characterized in that: The polycarbonate is subjected to an antioxidant treatment before being placed in the loading liquid, and the antioxidant treatment comprises the following steps: A. dissolving polycarbonate in acetone to form a polycarbonate solution; B. Put nano zinc oxide into acetone, then add antioxidant, stir evenly at a rate of 2000-3000r / min, and complete the antioxidant treatment of polycarbonate after drying.

8. The medical polycarbonate according to claim 7, characterized in that: The mass ratio of the polycarbonate, nano zinc oxide and antioxidant is 100:1-2:1-2.

9. The medical polycarbonate according to claim 7, characterized in that: The antioxidant comprises a hindered phenol antioxidant and a phosphite antioxidant in a mass ratio of 10:1-3.

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