An iron-based polymer composite fiber, its preparation method and application

Abstract

The present invention discloses an iron-based polymer composite fiber, a preparation method thereof and an application thereof. The iron-based polymer composite fiber provided by the present invention is obtained by uniformly mixing a polymer, a ferric salt and a solvent to obtain a spinning solution, and preparing a uniform polymer / FeCl3 composite fiber from the spinning solution by means of electrospinning technology; soaking the prepared polymer / FeCl3 composite fiber in an aqueous solution of NaOH, washing and drying to obtain a polymer / hydroxy iron oxide composite fiber. The iron-based polymer composite fiber has MRI imaging (visualization) performance, can achieve the function of positive contrast within a preferred iron concentration range, has good biocompatibility, a simple preparation process, and can enable the composite film to be used in most polymer-based implantable medical devices by means of methods such as solvent annealing, interfacial adhesion, heat treatment or soluble template layer, etc., providing an additional MRI imaging (visualization) function for implantable medical devices, and having good application prospects.

Description

Technical Field

[0001] The present invention relates to the fields of functional fiber materials and biomedical materials, and particularly relates to an iron-based polymer composite fiber, a preparation method thereof, and an application thereof. Background Art

[0002] MRI (Magnetic Resonance Imaging) is a non-invasive imaging technique that obtains detailed internal structure and tissue information of the human body by emitting signals using a strong magnetic field and harmless radio waves. However, MRI imaging of polymer-based implantable medical devices such as heart valves and vascular stents poses certain challenges because polymers are similar to human tissue components and it is difficult to produce good contrast in images. Therefore, to prepare MRI-visualizable implantable medical devices, some magnetic susceptibility contrast agents need to be added to the polymers to improve the imaging contrast of the implantable medical devices in MRI. The imaging principle of contrast agent-doped polymer MRI is that the contrast agent changes the magnetic moment of protons in the water around the polymer, increasing or decreasing the imaging contrast between the polymer and the surrounding tissue, making the stent brighter than its original state as positive contrast, and vice versa as negative contrast. The contrast agents mainly include metal chelates or compounds. The influencing factors of positive contrast mainly include the size, geometric shape, surface structure, and surface modification of the contrast particles; the influencing factors of negative contrast mainly include the size, geometric shape, crystal structure, and aggregated state structure of the particles. Clinically, positive contrast stents or tissues are more favored by doctors in some cases due to their clearer and sharper boundaries. Gadolinium has the strongest paramagnetism because there are 7 lone electrons in the outermost layer of its atomic nucleus, so it has the strongest positive contrast effect. However, free gadolinium is nephrotoxic in the human body. In contrast, iron ions are more biocompatible. Therefore, the iron-based MRI positive contrast imaging of polymer-based implantable medical devices has great research value and potential application strength. Summary of the Invention

[0003] The primary object of the present invention is to overcome the disadvantages and deficiencies of the prior art, improve the problem that traditional iron-based polymer composite fibers cannot achieve positive contrast, and provide a preparation method for polymer / hydroxy iron oxide composite fibers with nuclear magnetic imaging function and positive contrast function.

[0004] Another object of the present invention is to provide the polymer / hydroxy iron oxide composite fiber prepared by the above method.

[0005] A further object of the present invention is to provide the application of the above polymer / hydroxy iron oxide composite fiber.

[0006] The object of the present invention is achieved by the following technical solutions:

[0007] A preparation method for a polymer / hydroxy iron oxide composite fiber with nuclear magnetic imaging function, comprising the following steps:

[0008] (1) Mix the polymer, ferric salt, and solvent evenly to obtain a spinning solution, and use electrospinning technology to prepare uniform polymer / FeCl3 composite fibers from the spinning solution.

[0009] (2) Immerse the polymer / FeCl3 composite fibers prepared in step (1) into an aqueous solution of NaOH, then wash until the pH = 7, and dry to obtain polymer / iron oxyhydroxide composite fibers.

[0010] Preferably, the polymer described in step (1) includes at least one of polylactic acid, polycaprolactone, polyglycolide, poly(lactide), poly(glycolic acid), hyaluronic acid, fibrin, silk fibroin, polyethylene glycol, chitosan, collagen, gelatin, polyethylene, polypropylene, polyvinyl chloride, polystyrene, polymethyl methacrylate, polyamide, polycarbonate, polyoxymethylene, polybutylene terephthalate, polyethylene terephthalate, cellulose acetate, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, cyanoethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl starch, carboxymethyl starch, polyvinyl pyrrolidone, polyvinyl alcohol, polyacrylonitrile, polyethylene glycol-polylactic acid block copolymer, polyethylene glycol-polycaprolactone block copolymer, polyethylene glycol-polyvinyl pyrrolidone block copolymer, polystyrene-polybutadiene block copolymer, styrene-butadiene-styrene triblock copolymer, polystyrene-poly(ethylene-butylene)-polystyrene block copolymer, styrene-isoprene / butadiene-styrene block copolymer, polystyrene-polybutadiene-polystyrene block copolymer; more preferably, it includes at least one of polyamide, polylactic acid, polymethyl methacrylate, and polystyrene.

[0011] Preferably, the ferric salt described in step (1) includes ferric chloride and ferric chloride hydrate, and more preferably FeCl3·6H2O.

[0012] Preferably, the solvent described in step (1) includes at least one of water, dichloromethane, chloroform, dichloroethane, tetrachloroethane, methyl acrylate, tetrahydrofuran, methyltetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, ether, petroleum ether, acetone, formic acid, acetic acid, trifluoroacetic acid, carbon tetrachloride, xylene, toluene, phenol, chlorobenzene, nitrobenzene, pentane, n-hexane, methylcyclohexane, N-methylpyrrolidone, anisole, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, pentanol, N-methylmorpholine-N-oxide, methylimidazolium chloride, and cresol.

[0013] Preferably, the mass fraction of the polymer in the spinning solution described in step (1) is 5-50%.

[0014] Preferably, Fe in the spinning solution described in step (1)3+ The quality is 0.1-10% of the quality of the polymer.

[0015] Preferably, the conditions of the electrospinning in step (1) are as follows: positive pressure 5-50 kV; the distance between the needle and the collector is 5-30 cm; the injection speed is 0.1-10 mL / h; the collector is a flat plate, a roller or a cage collector; when the collector is a roller collector, the rotation speed of the roller collector is 0-3000 r / min, and the diameter is 10-15 cm. More preferably, the conditions of the electrospinning in step (1) are as follows: positive pressure 15-30 kV; the distance between the needle and the collector is 10-30 cm; the injection speed is 0.1-1 mL / h; when the collector is a roller collector, the rotation speed of the roller collector is 1000-3000 r / min, and the diameter is 10-15 cm.

[0016] Preferably, the pH value of the aqueous solution of NaOH in step (2) is 8-14.

[0017] Preferably, the washing in step (2) is washing with deionized water.

[0018] Preferably, the drying in step (2) is drying at a temperature below 40°C.

[0019] A polymer / hydroxy iron oxide composite fiber with nuclear magnetic imaging function is prepared by the above method.

[0020] Application of the above polymer / hydroxy iron oxide composite fiber in the preparation of nuclear magnetic imaging materials.

[0021] Application of the above polymer / hydroxy iron oxide composite fiber in the preparation of positive contrast materials. Preferably, in the preparation method of the above polymer / hydroxy iron oxide composite fiber, the mass of Fe 3+ is 0.1-4% of the mass of the polymer.

[0022] Application of the above polymer / hydroxy iron oxide composite fiber in the preparation of medical devices; the medical device has a nuclear magnetic imaging function.

[0023] Preferably, the nuclear magnetic imaging function includes a positive contrast function.

[0024] Preferably, the medical devices include artificial joints, heart valves, vascular stents, cranial pads, hernia patches and nerve stimulators.

[0025] Preferably, the application of the above polymer / hydroxy iron oxide composite fiber in the preparation of medical devices includes the following steps:

[0026] Cover and fix the polymer / hydroxy iron oxide composite fiber on the surface of the medical device; the covering and fixing on the surface of the medical device can be achieved by methods such as solvent annealing, interfacial adhesion, heat treatment, or soluble template layer.

[0027] More preferably, the solvent annealing method includes the following steps:

[0028] A1. Plasma-treat the surface of the polyamide implantable medical device;

[0029] A2. Using the surface of the polyamide implantable medical device as the coating substrate, cover the polymer / hydroxy iron oxide composite fiber on the surface of the polyamide implantable medical device pretreated in S1, compact it to make it closely combine with the treated surface, and anneal it under the atmosphere of the common solvent of the polymer / hydroxy iron oxide composite fiber and the substrate to further improve the bonding force.

[0030] Further preferably, the plasma treatment atmosphere in step A1 is oxygen, the gas flow rate is 1 - 100 sccm, the power is 10 - 200 W, and the time is 0.5 - 10 min.

[0031] Further preferably, the annealing solvent in step A2 is at least one of water, dichloromethane, chloroform, dichloroethane, tetrachloroethane, methyl acrylate, tetrahydrofuran, methyltetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, ether, petroleum ether, acetone, formic acid, acetic acid, trifluoroacetic acid, carbon tetrachloride, xylene, toluene, phenol, chlorobenzene, nitrobenzene, pentane, n-hexane, methylcyclohexane, N-methylpyrrolidone, anisole, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, pentanol, N-methylmorpholine-N-oxide, chloromethylimidazolium salt, and cresol.

[0032] Further preferably, the annealing conditions in step A2 are: the annealing temperature is 30 - 80 °C, and the annealing time is 5 - 300 min.

[0033] More preferably, the interfacial adhesion method specifically includes the following steps:

[0034] B1. Uniformly coat the solution containing the interfacial adhesive on the surface of the polymer implantable medical device by spin coating, dip coating, or spraying methods to ensure complete coverage.

[0035] B2. Cover the polymer / hydroxy iron oxide composite fiber on the surface of the polymer implantable medical device treated in step B1 and dry and cure it.

[0036] Further preferably, the interfacial adhesive in step B1 includes at least one of an aqueous polymer emulsion, an organic solvent-based adhesive, a silane coupling agent, a polymer mixture, and a hot melt adhesive; most preferably, the aqueous polymer emulsion includes a polylactic acid (PLA) emulsion and a polyacrylic acid (polyamide A) emulsion; the organic solvent-based adhesive includes a methyl methacrylate / methyl acrylate adhesive and a chlorinated polybutadiene (CSBR) adhesive; the silane coupling agent includes 3-aminopropyltrimethoxysilane and 3-aminopropyltrimethoxysilane; the polymer mixture includes a polylactic acid / polycaprolactam mixture; the hot melt adhesive includes a hot melt ethylene-vinyl acetate (EVA) adhesive and a hot melt polyamide adhesive.

[0037] Further preferably, the concentration of the interfacial adhesive described in step B1 is 0.5 to 50 wt%.

[0038] More preferably, the heat treatment method includes the following steps:

[0039] Cover the polymer / hydroxy iron oxide composite fiber on the surface of the polymer-based implantable medical device and perform hot pressing to make the two combine tightly and form a good bond at the interface.

[0040] The conditions for the hot pressing are: the temperature is 150 to 180 °C, and the pressure is 10 to 20 MPa.

[0041] More preferably, the soluble template layer method includes the following steps:

[0042] C1. Uniformly coat a layer of compatible soluble template layer material on the surface of the polymer-based implantable medical device.

[0043] C2. Cover the polymer / hydroxy iron oxide composite fiber on the surface of the polymer-based implantable medical device treated in step C1 to ensure good fitting between the two; perform heat treatment on the coated implantable medical device to melt the soluble template layer and make the polymer / hydroxy iron oxide composite fiber penetrate into the polymer body of the polymer-based implantable medical device.

[0044] Further preferably, the component of the soluble template layer in step C1 is at least one of methyl acrylate, polymethyl methacrylate, gelatin, cellulose, polyvinyl alcohol, polyethylene glycol, a waxy polymer, and wax acid.

[0045] Further preferably, the temperature of the heat treatment in step C2 is 40 to 90 °C.

[0046] The present invention has the following advantages and effects compared with the prior art:

[0047] 1) The present invention utilizes electrospinning technology to achieve good dispersion of FeCl3 in fibers, and through in-situ conversion to iron hydroxide, good dispersion of iron hydroxide in fibers is achieved, thereby achieving the effect of positive nuclear magnetic resonance imaging of iron-based tissue engineering scaffolds. There are many polymer varieties to choose from, the preparation process is relatively simple, the controllability is strong, and the size can be adjusted.

[0048] 2) The nuclear magnetic resonance imaging effect of the polymer / iron hydroxide composite fiber film prepared by the present invention has a concentration dependence on iron hydroxide. When the concentration of iron hydroxide is low, it shows a positive effect, and when the concentration of iron hydroxide is high, it shows a negative nuclear magnetic resonance imaging effect, which is suitable for different in-vivo usage scenarios.

[0049] 3) The adhesion between the polymer / iron hydroxide composite fiber film prepared by the present invention and a medical device can be adjusted as needed. By changing process parameters or adjusting material combinations, the adaptation between different medical devices and the fiber film can be achieved, and the best adhesion effect can be ensured.

[0050] 4) The present invention's patented technology adopts a special process and material combination, enabling a high adhesion strength to be formed between the polymer / iron hydroxide composite fiber film and the medical device. This high-strength adhesion can effectively fix and maintain the connection between the fiber film and the medical device, reducing the risk of loosening or falling off during long-term use. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 is the in-vitro nuclear magnetic resonance imaging obtained in Example 9.

[0052] Figure 2 is the in-vitro relaxation rate performance obtained in Example 9. DETAILED DESCRIPTION OF THE INVENTION

[0053] The present invention will be further described in detail below in conjunction with the examples and the drawings, but the implementation manners of the present invention are not limited thereto.

[0054] Example 1

[0055] 1) Take 3 g of polyamide and dissolve it in 6.94 mL of formic acid (the mass fraction of polyamide is 25 wt%), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe 3+ in the solution is 0.1% of the polymer), and stir for 24 h to form a uniform spinning solution.

[0056] 2) Add the spinning solution into a syringe, fix it to an injection pump. The distance from the needle to the roller is 10 cm, the flow rate is 0.1 mL / h, the receiving method is a flat receiver, the spinning voltage is 30 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm. Prepare a polyamide / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0057] 3) Immerse the polyamide / FeCl3 composite fiber membrane into an aqueous NaOH solution with pH = 10. After reacting for 12 h, take it out, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0058] 4) Select a polyamide implantable medical device as the film covering substrate, put the surface to be treated into a plasma reaction chamber, ensure the sample is exposed to the plasma, turn on the plasma equipment, and process it according to an oxygen gas flow rate of 100 sccm and a power of 200 W for a duration of 10 minutes.

[0059] 5) Cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly, and anneal it at 80 °C for 5 minutes under a formic acid atmosphere.

[0060] Example 2

[0061] 1) Take 3 g of polylactic acid and dissolve it in a mixed solvent with a volume ratio of formic acid: chloroform: acetone of 9:7:7 (the mass fraction of polylactic acid is 10 wt%). Add 1.014 g of FeCl3·6H2O (so that the mass of Fe in the solution is 7% of the polymer), and stir for 24 h to form a uniform spinning solution. 3+ in the solution is 7% of the polymer), stir for 24 h to form a uniform spinning solution.

[0062] 2) Add the spinning solution into a syringe, fix it to an injection pump. The distance from the needle to the roller is 10 cm, the flow rate is 0.1 mL / h, the receiving method is a flat receiver, the spinning voltage is 30 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm. Prepare a polylactic acid / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0063] 3) Immerse the polylactic acid / FeCl3 composite fiber membrane into an aqueous NaOH solution with pH = 14. After reacting for 12 h, take it out, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0064] 4) Select a polylactic acid implantable medical device as the film covering substrate. After cleaning the surface, dip-coat it in a 0.5 wt% 3-aminopropyltrimethoxysilane solution for 2 hours, cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly, and place it under a ventilation device to volatilize naturally until the solvent completely evaporates.

[0065] Example 3

[0066] 1) Dissolve 3 g of polymethyl methacrylate in 17 g of ethyl acetate (EA), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), stir for 24 h to form a uniform spinning solution. 3+ The quality of is 0.1% of the polymer, stir for 24 h to form a uniform spinning solution.

[0067] 2) Add the spinning solution into a syringe, fix it to an injection pump. The distance from the needle to the drum is 15 cm, the flow rate is 1 mL / h, the receiving method is a drum receiver, the drum rotation speed is 3000 rpm, the diameter is 15 cm, the spinning voltage is 15 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polymethyl methacrylate / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0068] 3) Immerse the polymethyl methacrylate / FeCl3 composite fiber membrane in an aqueous NaOH solution with pH = 10, take it out after reacting for 12 h, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0069] 4) Select a polymethyl methacrylate implantable medical device as the film-covered substrate. After cleaning the surface, dip-coat it in a 50 wt% hot-melt polyvinyl alcohol solution for 2 hours, cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly, and place it under a ventilation device to volatilize naturally until the solvent completely evaporates.

[0070] Example 4

[0071] 1) Dissolve 3 g of polystyrene in 15 g of N,N-dimethylformamide (DMF), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), stir for 24 h to form a uniform spinning solution. 3+ The quality of is 0.1% of the polymer, stir for 24 h to form a uniform spinning solution.

[0072] 2) Add the spinning solution into a syringe, fix it to an injection pump. The distance from the needle to the drum is 30 cm, the flow rate is 1 mL / h, the receiving method is a drum receiver, the drum rotation speed is 1000 rpm, the diameter is 10 cm, the spinning voltage is 10 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polystyrene / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0073] 3) Immerse the polystyrene / FeCl3 composite fiber membrane in an aqueous NaOH solution with pH = 14, take it out after reacting for 12 h, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0074] 4) Select a polystyrene implantable medical device as the film - covering substrate. After cleaning the surface, place the prepared polystyrene / hydroxy - iron oxide composite fiber membrane on the surface of the polystyrene implantable medical device to ensure good adhesion between the two.

[0075] 5) Place the polystyrene implantable medical device covered with the electrospun fiber membrane in a hot press. Control the temperature of the hot press at 180 °C and the pressure at 10 MPa, and maintain a certain pressure and temperature for a period of time to promote the adhesion between the electrospun fiber membrane and the surface of the implantable medical device.

[0076] Example 5

[0077] 1) Take 3 g of polyamide and dissolve it in 10 g of formic acid (the mass fraction of polyamide is 30 wt%), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), and stir for 24 h to form a uniform spinning solution. 3+ The mass of Fe in the solution is 0.1% of the polymer, stir for 24 h to form a uniform spinning solution.

[0078] 2) Add the spinning solution into a syringe, fix it on an injection pump. The distance from the needle to the roller is 10 cm, the flow rate is 0.1 mL / h, the receiving method is a flat receiver, the electrospinning voltage is 30 kV, the inner diameter of the flat - mouth needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polyamide / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0079] 3) Immerse the polyamide / FeCl3 composite fiber membrane in an aqueous NaOH solution with pH = 10. After reacting for 12 h, take it out, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0080] 4) Select a polypropylene implantable medical device as the film - covering substrate, clean the surface of the polypropylene, and use an aqueous solution of 5 wt% polyvinyl alcohol as the soluble template layer solution, and uniformly coat it on the surface of the polypropylene substrate.

[0081] 5) Cover the polyamide / hydroxy - iron oxide composite fiber film and bond it tightly, then place it in an oven at 90 °C and dry it for a period of time to remove the soluble template layer.

[0082] Example 6

[0083] 1) Take 3 g of polyamide and dissolve it in 6.94 mL of formic acid (the mass fraction of polyamide is 25 wt%), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), and stir for 24 h to form a uniform spinning solution. 3+ The mass of Fe in the solution is 0.1% of the polymer, stir for 24 h to form a uniform spinning solution.

[0084] 2) Add the spinning solution into a syringe, fix it onto an injection pump. The distance from the needle to the flat receiver is 10 cm, the flow rate is 0.1 mL / h, the receiving method is the flat receiver, the spinning voltage is 30 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polyamide / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0085] 3) Immerse the polyamide / FeCl3 composite fiber membrane into an aqueous NaOH solution with pH = 10. After reacting for 12 h, take it out, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0086] 4) Select a polyamide implantable medical device as the film covering substrate. Put the surface to be treated into the plasma reaction chamber to ensure that the sample is exposed to the plasma. Turn on the plasma equipment and process it according to an oxygen gas flow rate of 1 sccm and a power of 10 W for a duration of 0.5 minutes.

[0087] 5) Cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly. Anneal it at 30 °C for 300 minutes under a formic acid atmosphere.

[0088] Example 7

[0089] 1) Take 3 g of polystyrene and dissolve it in 15 g of DMF. Add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), and stir for 24 h to form a uniform spinning solution. 3+ in the polymer), stir for 24 h to form a uniform spinning solution.

[0090] 2) Add the spinning solution into a syringe, fix it onto an injection pump. The distance from the needle to the drum receiver is 30 cm, the flow rate is 1 mL / h, the receiving method is the drum receiver, the drum rotation speed is 1000 rpm, the diameter is 10 cm, the spinning voltage is 10 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polystyrene / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0091] 3) Immerse the polystyrene / FeCl3 composite fiber membrane into an aqueous NaOH solution with pH = 14. After reacting for 12 h, take it out, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0092] 4) Select a polystyrene implantable medical device as the film covering substrate. After cleaning the surface, place the prepared polystyrene / hydroxy iron oxide composite fiber membrane on the surface of the polystyrene implantable medical device to ensure good adhesion between the two.

[0093] 5) Place the polystyrene implantable medical device covered with the electrospun fiber membrane in a hot press, control the temperature of the hot press at 150 °C and the pressure at 20 MPa, and maintain a certain pressure and temperature for a period of time to promote the adhesion between the electrospun fiber membrane and the surface of the implantable medical device.

[0094] Example 8

[0095] 1) Dissolve 3 g of polyamide in 10 g of formic acid (the mass fraction of polyamide is 30 wt%), add 0.1448 g of FeCl3·6H2O (so that the mass of Fe in the solution is 0.1% of the polymer), and stir for 24 h to form a uniform spinning solution. 3+ 2) Add the spinning solution into a syringe, fix it to an injection pump, the distance from the needle to the flat receiver is 10 cm, the flow rate is 0.1 mL / h, the receiving method is a flat receiver, the electrospinning voltage is 30 kV, the inner diameter of the flat-tip needle is 0.61 mm, and the outer diameter is 0.91 mm to prepare a polyamide / FeCl3 composite fiber membrane. Tear the fiber membrane off the aluminum foil of the receiver.

[0096] 3) Immerse the polyamide / FeCl3 composite fiber membrane in an aqueous NaOH solution with pH = 10, take it out after reacting for 12 h, wash it with deionized water until pH = 7, and dry it at 40 °C for standby.

[0097] 4) Select a polypropylene implantable medical device as the film coating substrate, clean the surface of the polypropylene, and use an aqueous solution of 20 wt% polyethylene glycol as the soluble template layer solution, and uniformly coat it on the surface of the polypropylene substrate.

[0098] 5) Cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly, and place it in an oven at 40 °C for a period of time to remove the soluble template layer.

[0099] 5) Cover the polyamide / hydroxy iron oxide composite fiber film and bond it tightly, and place it in an oven at 40 °C for a period of time to remove the soluble template layer.

[0100] Example 9

[0101] Prepare polyamide / hydroxy iron oxide composite fibers (PA6 / FeOOH) according to the method of Example 1, prepare poly(methyl methacrylate) / hydroxy iron oxide composite fibers (PMMA / FeOOH) according to the method of Example 3, and prepare polystyrene / hydroxy iron oxide composite fibers (PS / FeOOH) according to the method of Example 4. Adjust the addition amount of FeCl3·6H2O so that the mass of Fe in the spinning solution is 0 - 7% of PA6, 0 - 4% of PMMA, and 0 - 4% of PS, and the specific percentages are as 3+ 28) 0 - 7% of PA6, 0 - 4% of PMMA, and 0 - 4% of PS, and the specific percentages are as Figure 1As shown in each group. In vitro nuclear magnetic resonance imaging tests were performed, and the specific imaging parameters were as follows: In T1-weighted images, TE = 20 ms, TR = 2045 ms, TI = 800 ms, voxel 0.65 mm × 0.81 mm, slice thickness 4 mm; in T2-weighted images, TE = 105 ms, TR = 3000 ms, TSEes / SHOT = 7.8 / 171 ms, voxel 0.3 mm × 0.3 mm, slice thickness 1 mm. The in vitro nuclear magnetic resonance imaging diagram is as Figure 1 shown. The imaging effect of iron oxyhydroxide has a concentration-dependent characteristic. When the concentration is low, it shows a positive contrast effect, and when the concentration is high, it shows a negative contrast effect.

[0102] According to the method of Example 1, the addition amount of FeCl3·6H2O was adjusted to prepare polyamide / iron oxyhydroxide composite fibers (PA6 / FeOOH) so that the mass of Fe 3+ in the spinning solution was 0.16, 0.33, 0.67, 0.93, 1.38, 3.11, 4.61% of PA6 (corresponding to Figure 2 0.0286, 0.0589, 0.120, 0.166, 0.246, 0.555, 0.823 mmol Fe 3+ / g PA6), respectively), and the prepared polyamide / iron oxyhydroxide composite fibers were subjected to low-field nuclear magnetic tests. The test parameters were as follows: For the measurement of the T1 value, the inversion recovery pulse sequence was used, recycledelay = 20 s, gain = 53 dB, scan times = 4, first separation = 0.5 ms, final separation = 4000 ms, fitting number of points = 10; for the measurement of the T2 value, the Carr Purcell Meiboom Gill sequence was used, recycledelay = 20 s, scantimes = 8, gain = 56 dB. R1 = 1 / T1, R2 = 1 / T2. Taking R1 and R2 as the vertical coordinates and the amount of substance of Fe 3+ in 1 g PA6 as the horizontal coordinate (unit mmol Fe 3+ / g PA), and linearly fitting the scatter points to draw Figure 2 , and the slopes of the obtained curves were r1 and r2, respectively. The results are as Figure 2 shown. The imaging effect of iron oxyhydroxide has a concentration-dependent characteristic. When the concentration is low, it shows a positive contrast effect (r2 / r1 < 5), and when the concentration is high, it shows a negative contrast effect.

[0103] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. Use of polymer / hydroxy iron oxide composite fiber in preparing magnetic resonance imaging material, characterized in that: The preparation of the polymer / hydroxy iron oxide composite fiber includes the following steps: (1) Mix a polymer, a ferric salt, and a solvent evenly to obtain a spinning solution, and use electrospinning technology to obtain uniform polymer / FeCl3 composite fiber from the spinning solution; (2) Immerse the polymer / FeCl3 composite fiber prepared in step (1) into an aqueous solution of NaOH, then wash until the pH = 7, and dry to obtain the polymer / hydroxy iron oxide composite fiber; The polymer described in step (1) includes at least one of polyamide, polylactic acid, polymethyl methacrylate, and polystyrene; The ferric salt described in step (1) includes at least one of ferric chloride and ferric chloride hydrate; The mass of Fe in the spinning solution described in step (1) 3+ is 0.1 - 7% of the mass of the polymer.

2. The application according to claim 1, characterized in that: The solvent described in step (1) includes at least one of water, dichloromethane, chloroform, dichloroethane, tetrachloroethane, methyl acrylate, tetrahydrofuran, methyltetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, ether, petroleum ether, acetone, formic acid, acetic acid, trifluoroacetic acid, carbon tetrachloride, xylene, toluene, phenol, chlorobenzene, nitrobenzene, pentane, n-hexane, methylcyclohexane, N-methylpyrrolidone, anisole, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, pentanol, N-methylmorpholine-N-oxide, methylimidazolium chloride, and cresol; The mass fraction of the polymer in the spinning solution described in step (1) is 5-50%; The conditions of the electrospinning described in step (1) are: positive pressure 5-50 kV; the distance between the needle and the collector is 5-30 cm; the injection speed is 0.1-10 mL / h; the collector is a flat plate, a roller or a cage collector; The pH value of the aqueous solution of NaOH described in step (2) is 8-14.

3. The application according to claim 1 or 2, characterized in that: The magnetic resonance imaging material is a positive contrast agent; In the preparation method of the polymer / hydroxy iron oxide composite fiber, in step (1), the mass of Fe 3+ in the spinning solution is 0.1-4% of the mass of the polymer.

4. The polymer / hydroxy iron oxide composite fiber described in any one of claims 1 or 2.

5. Use of the polymer / hydroxy iron oxide composite fiber according to claim 4 in the preparation of a medical device with nuclear magnetic imaging function, characterized in that, Includes the following steps: Cover and fix the polymer / hydroxy iron oxide composite fiber on the surface of a medical device.

6. The application according to claim 5, wherein The covering and fixing of the polymer / hydroxy iron oxide composite fiber on the surface of a medical device specifically includes the following steps: A1. Plasma-treat the surface of a polyamide implantable medical device; A2. Using the surface of the polyamide implantable medical device as a film covering substrate, cover the polymer / hydroxy iron oxide composite fiber on the surface of the pre-treated polyamide implantable medical device in step S1, compact it, and anneal it in an atmosphere of a common solvent of the polymer / hydroxy iron oxide composite fiber and the substrate.

7. The application according to claim 5, wherein The covering and fixing of the polymer / hydroxy iron oxide composite fiber on the surface of a medical device specifically includes the following steps: B1. Uniformly coat a solution containing an interfacial adhesive on the surface of a polymer implantable medical device by spin coating, dip coating, or spraying; B2. Cover the surface of the polymer-based implantable medical device treated in step B1 with polymer / hydroxy iron oxide composite fibers, and dry and cure.

8. The application according to claim 5, characterized in that, The specific steps of covering and fixing the polymer / hydroxy iron oxide composite fibers on the surface of the medical device are as follows: Cover the surface of the polymer-based implantable medical device with polymer / hydroxy iron oxide composite fibers and perform hot pressing to form, so that the two are combined.

9. The application according to claim 5, wherein The specific steps of covering and fixing the polymer / hydroxy iron oxide composite fibers on the surface of the medical device are as follows: C1. Uniformly coat a layer of compatible soluble template layer material on the surface of the polymer-based implantable medical device; C2. Cover the surface of the polymer-based implantable medical device treated in step C1 with polymer / hydroxy iron oxide composite fibers; perform heat treatment to melt the soluble template layer and make the polymer / hydroxy iron oxide composite fibers and the polymer body of the polymer-based implantable medical device penetrate each other.

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