Polyimide short-cut fiber adsorbent and application thereof

Abstract

The application discloses a kind of polyimide short-cut fiber adsorbents, the adsorbent carrier is polyimide short-cut fiber, the preparation steps of the polyimide short-cut fiber are as follows: diamine and dianhydride are carried out polycondensation in strong polar solution to obtain polyamide acid solution, then water-soluble porogen is added, then dry spinning or wet spinning is carried out, the polyamide acid hollow fiber prepared is drawn and cut into 1-10mm short-cut fiber, washing and drying, soak in ligand solution, and the polyimide short-cut fiber adsorbent is obtained by reaction.The polyimide short-cut fiber in the application is partially imidized, a large number of carboxyl groups are reserved on the surface and inside of the fiber, the carrier does not need to be pre-activated to couple ligand, the preparation process is simple, the hydrophilicity of short-cut fiber is significantly improved, the biocompatibility of adsorbent is improved, so as to be better applied in biological related materials.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of blood purification materials, in particular to a polyimide short-cut fiber adsorbent and application thereof. BACKGROUND

[0002] Blood purification is a new clinical treatment method in recent years, which mainly realizes the purpose of treatment by removing pathogenic substances and metabolic toxins existing in blood. The immunoadsorption therapy is an important method of blood purification, which is characterized by establishing a human blood circulation branch in vitro to make blood pass through a special adsorbent to adsorb and remove pathogenic substances in blood, so as to purify the body environment and treat diseases. The key of immunoadsorption therapy lies in the immunoadsorbent.

[0003] The adsorbent includes a carrier part, a ligand part and a linking mode between them. The adsorbent carrier serves as the support skeleton of the ligand. The materials that can be used generally include multifunctional carbon materials (activated carbon), synthetic resin materials (polystyrene resin, silica gel material, polyvinyl alcohol resin, polyurethane resin) and polysaccharide materials (chitosan, cellulose, agarose, etc.).

[0004] In order to couple more ligands, the commonly used adsorbent carriers currently adopt a spherical structure to increase the contact area with the ligand, and generally do not consider the fiber structure. The fiber inside is not easy to couple with the ligand, and the adsorption effect is poor during adsorption. The existing short-cut fibers are mostly used as reinforcing materials. From the perspective of surface adsorption, the amount of coupled ligands of the short-cut fibers is obviously less than that of the spherical resin carriers due to the different surface areas, thereby leading to a decrease in adsorption effect.

[0005] At the same time, the commonly used adsorbent carrier materials have certain defects on the one hand, for example, the polystyrene resin carrier has high mechanical strength, stable physical / chemical properties and controllable structure, but the resin has strong hydrophobicity and poor blood compatibility, and needs to be coated with a hydrophilic material or modified to be hydrophilic. The agarose carrier has good biocompatibility, but has poor mechanical stability and poor acid and alkali resistance. On the other hand, the above-mentioned carriers need to be pre-activated to form specific coupling groups during use, so as to successfully couple with the ligand. The coupling mode is complex and the coupling effect is poor. The above-mentioned problems limit the preparation and application of the immunoadsorbent.

[0006] Polyimide is a kind of aromatic heterocyclic polymer material containing imide chain segments, which has outstanding heat resistance and excellent mechanical properties, and has wide application prospect. The fiber film or microspheres prepared from polyimide can be used in microelectronic field and catalysis, packaging, controlled release and filler, etc. The precursor of polyimide prepared from polyamide acid contains rich carboxyl groups, which can be grafted with various different functional adsorption ligands, and has good mechanical properties and biocompatibility, and can be considered as a carrier of blood purification adsorbent. However, there are some problems in the preparation of polyimide resin microspheres, such as difficult to control the morphology and easy to collapse, large solvent consumption, etc., which limits its application as an adsorbent carrier. SUMMARY

[0007] The purpose of the present application is to overcome at least one deficiency of the prior art, and to provide a polyimide chopped fiber adsorbent and its application.

[0008] The technical solution adopted by the present application is:

[0009] The present application provides a polyimide chopped fiber adsorbent, and the adsorbent carrier is polyimide chopped fiber, and the preparation method comprises:

[0010] 1) diamine and dianhydride are subjected to polycondensation reaction in a strong polar solution to obtain a polyamide acid solution, and then a water-soluble porogen is added to obtain a polyamide acid precursor solution;

[0011] 2) the polyamide acid precursor solution is subjected to dry spinning or wet spinning to prepare a polyamide acid hollow fiber;

[0012] 3) the polyamide acid hollow fiber is drawn to obtain a fiber preform;

[0013] 4) the fiber preform is cut into 1-10 mm chopped fibers, and then washed and dried to obtain polyimide chopped fibers;

[0014] 5) the polyimide chopped fibers are soaked in a ligand solution to obtain a polyimide chopped fiber adsorbent.

[0015] In some examples, the dianhydride of step 1) is selected from any one of 3,3',4,4'-benzophenone tetracarboxylic dianhydride, 4,4'-hexafluoroisopropyl- phthalic anhydride, 3,3',4,4'-biphenyl tetracarboxylic dianhydride, 1,2',4,5'-benzophenone tetracarboxylic anhydride, 3,3',4,4'-diphenyl sulfone tetracarboxylic dianhydride.

[0016] In some examples, the diamine of step 1) is selected from any one of 3,3'-dimethyl-4,4'-diphenylmethane diamine, 4,4'-diamino diphenyl methane, 4,4'-diphenyl methane diisocyanate or 4,4'-diamino diphenyl ether, p-phenylene diamine.

[0017] In some examples, the molar ratio of the dianhydride to the diamine is (1-1.05):1.

[0018] In some examples, the drying temperature of step 4) is 60-150℃.

[0019] In some examples, the components of the polyamic acid precursor solution are allocated in a ratio of 10-50 parts of polyamic acid, 0.1-10 parts of water-soluble porogen, and 100-300 parts of strong polar solution.

[0020] In some examples, the strong polar solution is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0021] In some examples, the water-soluble porogen is selected from one or more of polyethyleneimine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60, and Tween-80.

[0022] In some examples, the ligand is selected from one or more of protein A, phenylalanine, tryptophan, polymyxin B, and antibody.

[0023] In a second aspect, the application provides use of the polyimide short-cut fiber adsorbent of the first aspect in the preparation of a blood purification material.

[0024] The application has the following advantages:

[0025] The polyimide short-cut fiber in the application is partially imidized, and a large number of carboxyl groups are retained on the surface and inside of the fiber. The carrier does not need to be pre-activated to couple the ligand, and the preparation process of the adsorbent is simple. The carboxyl groups that are not coupled with the ligand can significantly increase the hydrophilicity of the polyimide short-cut fiber and improve the biocompatibility of the adsorbent.

[0026] The application uses short-cut fibers as the carrier, which can be prepared by using ordinary wet spinning, and the processing technology is simple. The carrier structure is stable and is not easy to collapse.

[0027] The carrier in the application is made into short-cut fibers, the drawing requirement in the spinning process is low, and the cleaning and drying in the post-processing process are simple and sufficient, thereby reducing the use of solvents.

[0028] The carrier in the application is made into short-cut fibers, and the carboxyl groups inside the hollow fibers can participate in coupling at the same time. The contact with the ligand is easy in the subsequent coupling step, the coupling effect is good, and the prepared adsorbent has good adsorption effect. DETAILED DESCRIPTION

[0029] A polyimide short fiber adsorbent, the adsorbent carrier is polyimide short fiber, the preparation method comprises the following steps:

[0030] 1) diamine and dianhydride are subjected to polycondensation reaction in strong polar solution to obtain polyamide acid solution, and then water-soluble pore-forming agent is added to obtain polyamide acid precursor solution;

[0031] 2) the polyamide acid precursor solution is subjected to dry spinning or wet spinning to prepare polyamide acid hollow fiber;

[0032] 3) the polyamide acid hollow fiber is drawn to obtain fiber preform;

[0033] 4) the fiber preform is cut into 1-10mm short fibers, and then washed and dried to obtain polyimide short fibers;

[0034] 5) the polyimide short fibers are soaked in ligand solution to obtain polyimide short fiber adsorbent.

[0035] In some examples, the dianhydride of step 1) is selected from any one of 3,3',4,4'-benzophenone tetracarboxylic dianhydride, 4,4'-hexafluoroisopropylidene-phthalic anhydride, 3,3',4,4'-biphenyl tetracarboxylic dianhydride, 1,2',4,5'-benzophenone tetracarboxylic anhydride, 3,3',4,4'-diphenyl sulfone tetracarboxylic dianhydride.

[0036] In some examples, the diamine of step 1) is selected from any one of 3,3'-dimethyl-4,4'-diphenylmethane diamine, 4,4'-diamino diphenyl methane, 4,4'-diphenyl methane diisocyanate or 4,4'-diamino diphenyl ether, p-phenylene diamine.

[0037] The above-mentioned dianhydride and diamine are common raw materials for polycondensation reaction to obtain polyamide acid, and are safe.

[0038] In some examples, the molar ratio of the dianhydride to the diamine is (1-1.05):1.

[0039] In some examples, the drying temperature of step 4) is 60-150℃. At this drying temperature, it is beneficial to partially imidize the polyimide short fibers, and a large number of carboxyl groups are retained on the surface and inside of the fibers. The presence of these carboxyl groups makes it possible to directly and covalently couple with ligands without activating the polyimide short fibers.

[0040] In some examples, the component ratio of the polyamide acid precursor solution is: polyamide acid 10-50 parts, water-soluble pore-forming agent 0.1-10 parts, and strong polar solution 100-300 parts.

[0041] In some examples, the strong polar solution is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0042] In some examples, the water-soluble porogen is selected from one or more of polyethyleneimine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60, Tween-80. The specific porogen can be adjusted according to the porogenic effect to obtain satisfactory performance.

[0043] The ligand is a ligand that can be coupled with the carboxyl group, or the ligand can be activated so that the activated ligand can be coupled with the carboxyl group. In some examples, the ligand is selected from one or more of protein A, phenylalanine, tryptophan, polymyxin B, and antibodies. These ligands are commonly used in blood purification.

[0044] The following disclosure provides many different embodiments or examples for implementing different aspects of the present application.

[0045] The materials and proportions used in the preparation processes of embodiments 1-3 of the present application are shown in Table 1 below.

[0046] Table 1

[0047] Example Solvent Diamine Dianhydride Molar ratio (diamine:dianhydride) Porogen Mass ratio of solution components (polyamic acid:porogen:solvent) 1 DMF 4,4'-oxydianiline 1,2',4,5'-benzenetetracarboxylic anhydride 1:1 Polyethyleneimine 20：5：150 2 NMP p-phenylenediamine 3,3',4,4'-diphenyltetracarboxylic dianhydride 1:1.05 Tween-60 10：1：100 3 DMSO 3,3'-dimethyl-4,4'-diphenylmethane diamine 3,3',4,4'-benzophenonetetracarboxylic dianhydride 1:1.03 Polyethylene glycol 800 50：10：300

[0048] The preparation method of the polyimide short fibers of embodiments 1-3 of the present application is as follows:

[0049] 1) Preparation of polyamide acid precursor solution:

[0050] A certain amount of strong polar solvent is measured, and diamine is gradually added under nitrogen protection, stirred for 2h to completely dissolve, and then dianhydride is gradually added, and the polycondensation reaction is carried out by stirring to obtain a polyamide acid solution. An appropriate amount of water-soluble porogen is added and dissolved to obtain a polyamide acid precursor solution.

[0051] 2) Preparation of polyimide short fibers:

[0052] The polyamide acid precursor solution is extruded from the spinneret at an extrusion speed of 3-15ml / min using a spinning device, and is introduced into a coagulation bath at 20-50℃ to be coagulated and formed into a polyamide acid hollow fiber;

[0053] The prepared polyamide acid hollow fiber is drawn to obtain a fiber preform, and the drawing temperature is 20-50℃;

[0054] The fiber preform is cut into 1-10mm short fibers and ultrasonically cleaned to remove the spinning core liquid;

[0055] The obtained short-cut fibers are air-dried at 30°C and heated at 60-150°C to obtain partially imidized polyimide short-cut fibers.

[0056] Comparative Example 1

[0057] A polyimide hollow fiber membrane is prepared according to the material ratio used in Example 1, and the specific steps are as follows:

[0058] 1) Preparation of polyamide acid precursor solution:

[0059] A certain amount of strong polar solvent is measured, and diamine is gradually added under nitrogen protection, stirred for 2 h until completely dissolved, and then dianhydride is gradually added, and the polycondensation reaction is carried out by stirring to obtain a polyamide acid solution. An appropriate amount of water-soluble pore-forming agent is added and dissolved to obtain a polyamide acid precursor solution.

[0060] 2) Preparation of polyimide hollow fiber membrane:

[0061] The polyamide acid precursor solution is extruded from the spinneret at an extrusion speed of 3-15 ml / min, enters the coagulation bath at 20-50°C, and is coagulated and formed at a speed of 5-50 m / min. The formed fiber is immersed in water to remove residual solvents and unreacted raw materials, and is heated to obtain a partially imidized polyimide hollow fiber membrane.

[0062] Example 4

[0063] In a 500 mL reaction vessel, 10 g of polyimide short-cut fibers prepared in Example 1, 150 mL of 0.1 mol / L borate buffer solution, and 14 g of genetically engineered recombinant protein A are added. The pH value of the system is controlled at 7.5 to 8.5, and the reaction is carried out at 37°C for 20 h. After stopping the reaction, the filler is washed with about 10 times the volume of water for injection. After washing, 200 mL of 0.2 M ethanolamine solution is added to block the unreacted carboxyl groups, and the reaction is carried out at 20°C for 10 h. After the reaction is completed, a large amount of water for injection is used for washing, and finally it is stored in a solution containing a preservative.

[0064] Take 1 g of adsorbent and add it to the thawed plasma according to the ratio of adsorbent:plasma=1:4. Place the sample in a 37°C water bath constant temperature oscillator and oscillate at a speed of 60 rpm for 2 h. After adsorption is completed, the upper layer of plasma is taken out and sent for testing. The measured adsorption capacity of the prepared protein A immunoadsorbent for IgG is 52 mg / g.

[0065] Example 5

[0066] The polyimide short-cut fiber of Example 2 was soaked with anhydrous tetrahydrofuran for 3-5 times, 10 g of the polyimide short-cut fiber was added into a 500 mL reaction container, then 0.2 g of tryptophan and 100 mL of anhydrous pyridine were added, and the reaction was carried out at 30°C for 10 h. The adsorbent was washed with water and stored at 4°C.

[0067] 1 g of the adsorbent was added into thawed plasma at an adsorbent:plasma ratio of 1:4. The sample was placed in a water bath constant temperature oscillator at 37°C and oscillated at a speed of 60 rpm for 2 h. After the adsorption was completed, the upper plasma was taken out and sent for testing. The adsorption amount of the prepared tryptophan adsorbent for IgG was 37 mg / g.

[0068] As can be seen from the adsorption amounts of IgG in Examples 4 and 5, the blood purification adsorbent prepared by using the polyimide short-cut fiber as the carrier has an adsorption amount of pathogenic factors that meets the requirements of clinical application.

[0069] Comparative Example 2

[0070] The polyimide hollow fiber membrane prepared in Comparative Example 1 was cut into fiber segments of about 20 cm, 10 g of the polyimide fiber membrane prepared in Comparative Example 1 was added into a 500 mL reaction container, 150 mL of 0.1 mol / L borate buffer was added, the pH value of the system was controlled to be 7.5 to 8.5, 14 g of genetically engineered recombinant protein A was added, and the reaction was carried out at 37°C for 20 h. After the reaction was stopped, the filler was washed with about 10 times the volume of water for injection, after the washing was completed, 200 mL of 0.2 M ethanolamine solution was added to block the unreacted carboxyl groups, and the reaction was carried out at 20°C for 10 h. After the reaction was completed, the product was washed with a large amount of water for injection, and finally stored in a solution containing a preservative.

[0071] 1 g of the adsorbent was added into thawed plasma at an adsorbent:plasma ratio of 1:4. The sample was placed in a water bath constant temperature oscillator at 37°C and oscillated at a speed of 60 rpm for 2 h. After the adsorption was completed, the upper plasma was taken out and sent for testing. The adsorption amount of the prepared protein A immunoadsorbent for IgG was 28 mg / g.

[0072] As can be seen from Comparative Example 1, the polyimide hollow fiber membrane as the adsorption carrier has a certain adsorption effect on pathogenic factors, but the adsorption amount is significantly lower than that of the short-cut fiber form.

[0073] Comparison of resin carrier performance

[0074] The polyimide short-cut fiber carriers of Examples 1-3 were subjected to performance testing, and were compared with common agarose microspheres and polystyrene resins, and the results are shown in Table 2.

[0075] Table 2

[0076] Sample Water contact angle (°) Hemolysis rate (%) Example 1 56.5 0.28 Example 2 60.3 0.35 Example 3 62.5 0.39 Agarose microspheres 47.5 0.12 Polystyrene resin 85.2 4.78

[0077] It can be seen that the prepared polyimide short-cut fiber has water contact angle and hemolysis rate data comparable to agarose microspheres, significantly better than polystyrene resin, and the mechanical strength of the short-cut fiber is higher than that of agarose microspheres, having excellent performance.

[0078] The above is a further detailed description of the present application, which cannot be considered as a limitation of the specific implementation of the present application. For ordinary skilled persons in the technical field to which the present application belongs, simple deduction or replacement without departing from the concept of the present application is within the protection scope of the present application.

Claims

1. A polyimide short-cut fiber adsorbent for blood purification material, characterized by, The adsorbent carrier is polyimide short-cut fiber, and the preparation method comprises the following steps: 1) performing polycondensation reaction on diamine and dianhydride in a strong polar solution to obtain a polyamide acid solution, and then adding a water-soluble pore-forming agent to obtain a polyamide acid precursor solution, wherein the molar ratio of the dianhydride to the diamine is (1-1.05):1, and the polyamide acid precursor solution is prepared by mixing 10-50 parts of polyamide acid, 0.1-10 parts of water-soluble pore-forming agent and 100-300 parts of strong polar solution, wherein the strong polar solution is at least one selected from dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide and N,N-dimethylacetamide; 2) performing dry spinning or wet spinning on the polyamide acid precursor solution to obtain polyamide acid hollow fibers; 3) drawing the polyamide acid hollow fibers to obtain a fiber preform; 4) cutting the fiber preform into short-cut fibers with a length of 1-10 mm, and then cleaning and drying to obtain polyimide short-cut fibers; 5) soaking the polyimide short-cut fibers in a ligand solution to obtain polyimide short-cut fiber adsorbents.

2. The polyimide chopped fiber adsorbent of claim 1, wherein The dianhydride in step 1) is any one selected from 3,3',4,4'-benzophenone tetracarboxylic dianhydride, 4,4'-hexafluoroisopropyl-phthalic anhydride, 3,3',4,4'-biphenyl tetracarboxylic dianhydride, 1,2',4,5'-pyromellitic anhydride and 3,3',4,4'-diphenyl sulfone tetracarboxylic dianhydride.

3. The polyimide chopped fiber adsorbent of claim 1, wherein, The diamine in step 1) is any one selected from 3,3'-dimethyl-4,4'-diphenylmethane diamine, 4,4'-diamino diphenyl methane, 4,4'-diphenyl methane diisocyanate and p-phenylenediamine.

4. The polyimide chopped fiber adsorbent of claim 1, wherein The drying temperature in step 4) is 60-150 DEG C.

5. The polyimide chopped fiber adsorbent of claim 1, wherein The water-soluble pore-forming agent is one or more selected from polyethyleneimine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinyl pyrrolidone, polyacrylic acid, polyvinyl alcohol, Tween-20, Tween-60 and Tween-80.

6. The polyimide chopped fiber adsorbent of claim 1, wherein The ligand is one or more selected from protein A, phenylalanine, tryptophan, polymyxin B and antibodies.

7. Use of the polyimide short-cut fiber adsorbent in any one of claims 1-6 in the preparation of a blood purification material.