Preparation method and application of modified polytetrafluoroethylene

Abstract

The invention discloses a preparation method and application of modified polytetrafluoroethylene, and relates to the technical field of high polymer materials, and the preparation method comprises the following steps: providing photosensitive nitrobenzyloxycarbonyl protected perfluoroaniline and perfluorooctyl polyoxyethylene ether; dissolving in ethyl acetate, and performing ultrasonic dispersion treatment to obtain penetrating fluid; putting the polytetrafluoroethylene film and penetrating fluid into a supercritical fluid reaction kettle, introducing carbon dioxide, raising temperature and pressure, keeping constant temperature and constant pressure, reducing pressure and emptying to obtain the gradient functionalized inert polytetrafluoroethylene intermediate. According to the method, controllable functionalization of high density and high strength of the surface of the polytetrafluoroethylene material is realized, the long-term stability of a modified layer is improved through a post-treatment process, high consistency of large-scale production is ensured by utilizing an online feedback control system, and the problem that performance and stability are difficult to consider in a traditional modification technology is solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of high polymer materials, and particularly relates to a preparation method and application of modified polytetrafluoroethylene. BACKGROUND

[0002] Polytetrafluoroethylene has extremely high chemical inertness, extremely low surface energy, excellent heat resistance and biocompatibility due to the existence of carbon-fluorine bond with extremely high bond energy in its molecular structure. These unique physical and chemical properties make it a key high-performance polymer material, which is widely used in aerospace, semiconductor industry and biomedical engineering, especially in implantable medical devices such as artificial blood vessels, heart valves and high-end neural interface electronic devices, because it can resist the long-term corrosion of body fluids and is considered as an ideal substrate or packaging material. However, it is also this extreme chemical inertness that makes the surface of polytetrafluoroethylene difficult to be effectively modified. For bioelectronic devices that need to establish stable physical connection and efficient signal transmission with biological tissues (such as nerve cells, endothelial cells, etc.), the material surface must have a certain number of active functional groups to achieve covalent bonding or specific adsorption with biological molecules, so as to guide the adhesion, proliferation and differentiation of cells and build functional biological-material interface. Therefore, how to perform controllable functional modification on the surface of polytetrafluoroethylene without damaging its excellent performance is a key technical bottleneck for its application to higher-end biomedical fields.

[0003] In order to solve the contradiction between the surface inertness and functionalization of polytetrafluoroethylene, the existing technology has carried out a series of explorations, mainly focusing on high-energy physical or strong chemical methods such as plasma treatment, high-energy ray irradiation and chemical etching. The core logic of these methods is to break the carbon-fluorine bond on the surface by external energy, thereby introducing active groups containing oxygen or nitrogen. However, these technologies generally face a fundamental internal contradiction and performance compromise dilemma. On the one hand, if the treatment conditions are relatively mild, only a very low density of active sites can be formed on the surface of the material, which is far from enough to build a stable, uniform and powerful biological functional interface, resulting in low efficiency of biological molecule fixation and weak interface bonding. On the other hand, if deep or strong treatment is used, although more active groups can be introduced, the cost is the irreversible large-scale destruction of the surface layer structure of polytetrafluoroethylene. This destruction not only weakens the physical strength of the material itself, but more importantly, the damaged surface layer is very fragile in the dynamic environment of physiological fluids and is prone to hydrolysis, degradation or physical peeling, which usually fails in a very short time, thereby losing the core advantage of polytetrafluoroethylene as a long-term implant material. Therefore, the existing technology has always been unable to meet the stringent requirements of high-end bioelectronic devices that require both absolute chemical inertness to isolate corrosion and high-density active functional groups to achieve stable biological bonding. SUMMARY

[0004] The present application aims to provide a preparation method and application of modified polytetrafluoroethylene, and solve the problems in the background art.

[0005] To solve the above technical problems, the present application provides a preparation method of modified polytetrafluoroethylene, comprising the following steps:

[0006] Step A: providing photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline and perfluorooctyl polyoxyethylene ether;

[0007] Step B: dissolving the photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline and perfluorooctyl polyoxyethylene ether in ethyl acetate, and treating by ultrasonic dispersion to obtain a permeate;

[0008] Step C: placing the polytetrafluoroethylene film and the permeate in a supercritical fluid reaction kettle, introducing carbon dioxide into the reaction kettle, starting from the initial temperature and the initial pressure, and performing gradient temperature rise at a preset temperature rise rate, while performing gradient pressure rise at a preset pressure rise rate, after reaching the permeation temperature and the permeation pressure, keeping constant temperature and constant pressure for a preset permeation time, and then depressurizing and emptying to obtain a gradient functionalized inert polytetrafluoroethylene intermediate;

[0009] Step D: placing the gradient functionalized inert polytetrafluoroethylene intermediate in a photoetching machine, and using a specific wavelength of ultraviolet light source to selectively irradiate through a quartz chrome plate photomask with a preset pattern, so that the nitrobenzyloxycarbonyl protecting group in the irradiated area is removed, exposing the active amino group, to obtain a patterned active polytetrafluoroethylene film;

[0010] In step A, the steps for preparing the photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline include: under low temperature of-15℃ to-5℃ and nitrogen protection, slowly adding triethylamine into a three-necked flask containing pentafluoroaniline and dry dichloromethane, then uniformly adding 2-nitrobenzyl chloroformate dissolved in dry dichloromethane, after the addition is completed, continuing the reaction at room temperature for 10-14 hours, removing the solvent by rotary evaporation after the reaction is completed, and purifying by silica gel column chromatography to obtain the photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline;

[0011] In step A, the steps for preparing the perfluorooctyl polyoxyethylene ether include: first, adding p-toluenesulfonyl chloride into the anhydrous pyridine solution of octaethylene glycol monomethyl ether at 0℃ in batches, and preparing the octaethylene glycol monomethyl ether p-toluenesulfonic acid ester intermediate after reacting for 10-14 hours; then, under nitrogen protection, adding the solution of perfluorooctyl alcohol into the suspension of sodium hydride in anhydrous tetrahydrofuran, and then uniformly adding the solution of the intermediate, after the addition is completed, heating to 55-65℃ for reflux reaction for 20-28 hours, and purifying by extraction, water washing and column chromatography after the reaction is completed to obtain the perfluorooctyl polyoxyethylene ether.

[0012] Preferably, in step C, the mass fraction of polytetrafluoroethylene film, photosensitive nitrobenzyloxy carbonyl protected perfluoroaniline, perfluoro octyl polyoxyethylene ether is 100:(1.5-2.5):(0.4-0.6).

[0013] Preferably, in step C, the initial temperature is 45-55℃, and the initial pressure is 15-25MPa; the terminal penetration temperature of gradient heating is 75-85℃, and the terminal penetration pressure of gradient pressure increase is 30-40MPa; the penetration time is 3-5 hours.

[0014] Preferably, the rate of gradient heating is 0.5-1.5℃ / min, and the rate of gradient pressure increase is 0.5-1.5MPa / min.

[0015] Preferably, in step D, the wavelength of the ultraviolet light source is 360-370nm, the power density is 15-25mW / cm 2 , and the irradiation time is 80-100 seconds.

[0016] Preferably, after step C and before step D, there is also a step of programmed annealing of the gradient functionalized inert polytetrafluoroethylene intermediate: heating the intermediate to 125-135℃ and keeping it for 1-3 hours to enhance the physical anchoring of the photosensitive nitrobenzyloxy carbonyl protected perfluoroaniline on the surface layer of polytetrafluoroethylene.

[0017] Preferably, in step C, the intensity of the specific infrared absorption peak on the surface layer of the polytetrafluoroethylene film is monitored in real time by an online attenuated total reflection Fourier transform infrared spectroscopy probe integrated in the supercritical fluid reaction kettle, and the real-time signal is compared with the preset target gradient curve, and the PID control algorithm is used to automatically adjust the replenishment rate of carbon dioxide and the heating power in real time to feedback control the penetration process.

[0018] Preferably, in the step of preparing photosensitive nitrobenzyloxy carbonyl protected perfluoroaniline, the molar ratio of pentafluoroaniline, 2-nitrobenzyl chloroformate and triethylamine is 1:(0.9-1.1):(0.9-1.1).

[0019] Also provided is a modified polytetrafluoroethylene prepared by the above-mentioned method for preparing a modified polytetrafluoroethylene.

[0020] Also provided is the use of a modified polytetrafluoroethylene in the preparation of a biocompatible coating of a neural interface, a cochlear implant or other high-end bioelectronic device.

[0021] Compared with the prior art, the present application has the following beneficial effects:

[0022] By constructing a brand-new gradient permeation and light-activated system, high-density active functional groups are controllably introduced into the surface layer of polytetrafluoroethylene while the chemical inertness and physical properties of the polytetrafluoroethylene substrate are completely maintained, avoiding the damage to the material surface caused by traditional high-energy treatment. The active interface formed by the covalent bond with subsequent biomolecules has extremely high interface bonding strength, can accurately guide the adhesion and growth of cells, and construct a stable and powerful bio-material interface, fully meeting the stringent requirements of high-end bio-electronic devices for interface signal transmission efficiency and stability.

[0023] By introducing a unique programmed annealing treatment step after the core process, the long-term service stability of the modified functional layer is significantly improved. The thermal energy induces the micro rearrangement of the polytetrafluoroethylene surface layer molecular chain, effectively physically anchors and locks the permeated functional molecules, greatly inhibits their thermal motion and exudation trend in the long-term physiological environment, and even after long-term immersion in simulated body fluid, the surface activity and interface bonding strength can still be maintained at a very high level, effectively solving the problem of performance decay over time after implantation of traditional modified layers, and ensuring the reliability of medical devices throughout their life cycle.

[0024] By integrating an online monitoring and intelligent feedback control system in the key supercritical permeation process, the batch consistency problem in large-scale production is fundamentally solved. The permeation state of functional molecules in the material surface layer can be tracked in real time and accurately, and the key process parameters can be automatically adjusted according to the preset target curve to compensate for minor fluctuations in equipment or environment, transforming the previous experience-dependent open process into data-driven precision manufacturing, ensuring that different batches, even different positions in the same batch, have highly consistent gradient distribution profiles and final performance, providing a solid technical guarantee for the industrialization and high-yield production of this high-performance modified material. DETAILED DESCRIPTION

[0025] Example 1

[0026] The present embodiment discloses a specific preparation method of modified polytetrafluoroethylene;

[0027] First, a photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline (Nvoc-PFA) is prepared. The raw materials used are pentafluoroaniline (purity > 99%), 2-nitrobenzyl chloroformate (purity > 98%), triethylamine (analytical pure), and dichloromethane (analytical pure). In the preparation step, the molar ratio of pentafluoroaniline, 2-nitrobenzyl chloroformate, and triethylamine is 1:0.9:0.9.

[0028] Secondly, perfluorooctyl polyoxyethylene ether (F-PEG-8) was prepared; the raw materials used were perfluorooctyl alcohol (purity > 99%), octaethylene glycol monomethyl ether (purity > 98%), p-toluenesulfonyl chloride (purity > 99%) and sodium hydride (60% oil dispersion);

[0029] In the main process steps of the preparation method, the commercial PTFE film (thickness 50 μm); in step C, the mass fractions of polytetrafluoroethylene film, photosensitive nitrobenzyloxy carbonyl-protected perfluoroaniline and perfluorooctyl polyoxyethylene ether were 100:1.5:0.4; the process parameters of step C were: initial temperature 45 °C, initial pressure 15 MPa; gradient heating rate 0.5 °C / min, gradient pressure rate 0.5 MPa / min; end point penetration temperature 75 °C, end point penetration pressure 30 MPa, penetration time 3 hours; in step D, the wavelength of the ultraviolet light source was 360 nm, the power density was 15 mW / cm 2 , and the irradiation time was 100 seconds;

[0030] The patterned active polytetrafluoroethylene film prepared in this example was tested for performance, and the interfacial bonding strength was 12.5 MPa, and the cell adhesion density reached 8.5 x 10 4 / cm 2 ; when this modified polytetrafluoroethylene was used as a biocompatible coating for a cochlear implant, the activated area could effectively guide the directional growth of nerve cells, and initially met the basic requirements of bioelectronic devices for interfacial stability.

[0031] Example 2

[0032] This example discloses a specific preparation method of modified polytetrafluoroethylene, and the sources and preparation methods of the raw materials and self-made functional components are the same as in Example 1;

[0033] In step C of the method, the mass fractions of polytetrafluoroethylene film, photosensitive nitrobenzyloxy carbonyl-protected perfluoroaniline and perfluorooctyl polyoxyethylene ether were 100:2.0:0.5; the process parameters of step C were: initial temperature 50 °C, initial pressure 20 MPa; gradient heating rate 1.0 °C / min, gradient pressure rate 1.0 MPa / min; end point penetration temperature 80 °C, end point penetration pressure 35 MPa, penetration time 4 hours; in step D, the wavelength of the ultraviolet light source was 365 nm, the power density was 20 mW / cm 2 , and the irradiation time was 90 seconds;

[0034] The patterned active polytetrafluoroethylene film prepared in this example was tested for performance, and the interfacial bonding strength reached 15.2 MPa, and the cell adhesion density exceeded 1.0 x 10 5 / cm 2The modified polytetrafluoroethylene has high-density active sites and excellent bonding strength, so that when the modified polytetrafluoroethylene is applied to preparation of a neural interface, a stable and reliable covalent bonding interface between the device and nerve tissue is formed after implantation of the device, and impedance of signal transmission is reduced.

[0035] Embodiment 3

[0036] The embodiment discloses a specific preparation method of modified polytetrafluoroethylene, and the raw materials and the source and preparation method of the self-prepared functional components are the same as those in embodiment 1.

[0037] In step C of the method, the mass fractions of the polytetrafluoroethylene film, the photosensitive nitrobenzyloxy carbonyl-protected perfluoroaniline and the perfluorooctyl polyoxyethylene ether are 100:2.5:0.6; the process parameters of step C are as follows: the initial temperature is 55 DEG C, the initial pressure is 25 MPa; the gradient heating rate is 1.5 DEG C / min, the gradient pressure increasing rate is 1.5 MPa / min; the terminal penetration temperature is 85 DEG C, the terminal penetration pressure is 40 MPa, and the penetration time is 5 hours; in step D, the wavelength of the ultraviolet light source is 370 nm, the power density is 25 mW / cm 2 , and the irradiation time is 80 seconds.

[0038] The patterned active polytetrafluoroethylene film prepared in the embodiment has the following performances: the interfacial bonding strength is 15.8 MPa, and the cell adhesion density reaches 1.2 x 10 5 / cm 2 ; when the modified polytetrafluoroethylene is used as a coating of a high-end bioelectronic device, the higher penetration concentration and time length make the surface have a higher active functional group density, and the modified polytetrafluoroethylene is suitable for application scenarios with more stringent requirements for cell adhesion and interfacial stability.

[0039] Embodiment 4

[0040] The embodiment discloses a preparation method of modified polytetrafluoroethylene comprising a programmed annealing step; the specific parameter selection of the embodiment is basically the same as that in embodiment 2, and the difference lies in that the embodiment adds a step of programmed annealing of the gradient functionalized inert polytetrafluoroethylene intermediate after step C and before step D; the step heats the intermediate to 130 DEG C and keeps the temperature for 2 hours, so as to enhance physical anchoring of the photosensitive functional molecule on the surface layer of the polytetrafluoroethylene and improve long-term stability of the modified layer.

[0041] The modified polytetrafluoroethylene prepared by introducing a programmed annealing step in this example has an initial interfacial bonding strength of 15.1 MPa, similar to that of Example 2, but its long-term stability is significantly improved; after immersion in a simulated body fluid for 6 months, the interfacial strength attenuation rate is only 4%, much lower than that of the sample without annealing treatment (about 15%); this method is particularly suitable for artificial cochlea or neural interface that needs to be implanted in the body for a long time, and can effectively deal with the problem of active molecule exudation caused by body temperature fluctuations and tissue micro-movement.

[0042] Example 5

[0043] This example discloses a method for preparing modified polytetrafluoroethylene comprising an online feedback control and a programmed annealing step; the specific parameter selection of this example is basically the same as that of Example 4, the difference is that in step C, this example additionally introduces a step of feedback control of the penetration process through an online attenuated total reflection Fourier transform infrared spectroscopy probe integrated in the supercritical fluid reaction kettle; the system monitors the nitro absorption peak intensity of Nvoc-PFA in real time, and through the PID control algorithm, automatically adjusts the replenishment rate of carbon dioxide and the heating power in real time, so that the error between the penetration gradient profile and the preset target gradient curve is controlled within ±2%;

[0044] By introducing an online feedback control system, the modified polytetrafluoroethylene prepared in this example shows high consistency in performance; the fluctuation range of the interfacial bonding strength and cell adhesion density of the sample is extremely small, and the product yield reaches more than 98% after continuous production of 100 batches; the implementation of this method solves the problem of batch difference caused by the sensitivity of the supercritical fluid penetration process to temperature and pressure, and provides a reliable technical guarantee for the large-scale and high-quality production of high-end bioelectronic device coatings.

[0045] Comparative Example 1

[0046] This comparative example uses the conventional physical adsorption method in the prior art to modify the PTFE film; the commercial PTFE film is immersed in a fibronectin solution with a concentration of 1 mg / mL and incubated at 37°C for 24 hours; then it is taken out, washed with phosphate buffered saline (PBS) to remove the unadsorbed protein, and dried; this method corresponds to the traditional modification method in the prior art.

[0047] Performance test and comparison

[0048] The modified PTFE films prepared in Examples 1-5 and Comparative Example 1 are tested for performance, and the results are shown in the following table:

[0049]

[0050] From the data in the above table, it can be seen that the interfacial bonding strength and cell adhesion density of the modified polytetrafluoroethylene prepared in Examples 1-5 are significantly better than that of the physical adsorption method of Comparative Example 1; compared with Examples 1 and 3, Example 2 achieves a good balance in material consumption and process parameters; by introducing a programmed annealing step, Example 4 greatly improves the long-term stability of the coating without sacrificing the initial performance, and the strength decay rate is reduced from 15% to 4%; based on Example 4, Example 5 further introduces an online feedback control system, so that the batch consistency of the product is improved from 85% to more than 98%, showing its great advantage in stable industrial production; in summary, the disclosed preparation method, especially the technical solution combining programmed annealing and online process control, can prepare modified polytetrafluoroethylene with excellent performance, long-term stability and uniform quality, meeting the stringent requirements of high-end bioelectronic devices such as neural interfaces and cochlear implants for biocompatible coatings in applications.

[0051] The above is only a preferred embodiment of the present application, and does not limit the present application in other forms. Any skilled person in the art can modify or change the above disclosed technical content to equivalent embodiments applied to other fields, but any simple modification, equivalent change and modification made to the above embodiments without departing from the technical solution content of the present application, and in accordance with the technical essence of the present application, still belong to the protection scope of the technical solution of the present application.

Claims

1. A method for preparing modified polytetrafluoroethylene, characterized in that, Includes the following steps: Step A: Provide photosensitive nitrobenzyloxycarbonyl protected perfluoroaniline and perfluorooctyl polyoxyethylene ether; Step B: Photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline and perfluorooctyl polyoxyethylene ether are dissolved in ethyl acetate and then ultrasonically dispersed to obtain a permeate; Step C: Place the polytetrafluoroethylene film and the permeate in a supercritical fluid reactor, introduce carbon dioxide into the reactor, and start from the initial temperature and initial pressure, perform gradient heating at a preset heating rate, and simultaneously perform gradient pressurization at a preset pressurization rate. After reaching the permeation temperature and permeation pressure, maintain the preset temperature and pressure for the permeation time, and then reduce the pressure and discharge the air to obtain a gradient functionalized inert polytetrafluoroethylene intermediate. Step D: The gradient functionalized inert polytetrafluoroethylene intermediate is placed in a photolithography machine and selectively irradiated with a specific wavelength of ultraviolet light through a quartz chromium photomask with a preset pattern, so that the nitrobenzyloxycarbonyl protecting groups in the irradiated area are removed, exposing the active amino groups, and a patterned active polytetrafluoroethylene film is obtained. The step A in preparing photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline includes: under low temperature of -15℃ to -5℃ and nitrogen protection, triethylamine is slowly added dropwise to a three-necked flask containing pentafluoroaniline and dry dichloromethane, followed by uniform dropwise addition of 2-nitrobenzyl chloroformate dissolved in dry dichloromethane. After the addition is complete, the mixture is brought back to room temperature and the reaction continues for 10-14 hours. After the reaction is complete, the solvent is removed by rotary evaporation, and the mixture is purified by silica gel column chromatography to obtain photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline. The step A in preparing perfluorooctyl polyoxyethylene ether includes: first, adding p-toluenesulfonyl chloride in batches to an anhydrous pyridine solution of octaethylene glycol monomethyl ether at 0°C, and reacting for 10-14 hours to obtain an intermediate of octaethylene glycol monomethyl ether p-toluenesulfonate; then, under nitrogen protection, adding a solution of perfluorooctyl ethanol dropwise to an anhydrous tetrahydrofuran suspension of sodium hydride, followed by adding the intermediate solution dropwise at a uniform rate, and then heating to 55-65°C for reflux reaction for 20-28 hours. After the reaction is completed, the perfluorooctyl polyoxyethylene ether is obtained by extraction, washing with water and column chromatography purification.

2. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, In step C, the mass fractions of polytetrafluoroethylene film, photosensitive nitrobenzyloxycarbonyl protected perfluoroaniline, and perfluorooctyl polyoxyethylene ether are 100:(1.5-2.5):(0.4-0.6).

3. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, In step C, the initial temperature is 45-55℃ and the initial pressure is 15-25MPa; the final permeation temperature of the gradient heating is 75-85℃ and the final permeation pressure of the gradient pressurization is 30-40MPa; the permeation time is 3-5 hours.

4. The method for preparing modified polytetrafluoroethylene according to claim 3, characterized in that, The rate of gradient heating is 0.5-1.5℃ / min, and the rate of gradient pressure is 0.5-1.5MPa / min.

5. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, In step D, the wavelength of the ultraviolet light source is 360-370 nm, and the power density is 15-25 mW / cm². 2 The irradiation time is 80-100 seconds.

6. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, After step C and before step D, a programmed annealing step is also included for the gradient functionalized inert polytetrafluoroethylene intermediate: the intermediate is heated to 125-135°C and held for 1-3 hours to enhance the physical anchoring of photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline on the polytetrafluoroethylene surface.

7. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, In step C, the intensity of a specific infrared absorption peak on the surface of the polytetrafluoroethylene film is monitored in real time by an online attenuated total reflection Fourier transform infrared spectroscopy probe integrated in the supercritical fluid reactor. This real-time signal is compared with a preset target gradient curve, and the carbon dioxide replenishment rate and heating power are automatically adjusted in real time through a PID control algorithm to provide feedback control for the permeation process.

8. The method for preparing modified polytetrafluoroethylene according to claim 1, characterized in that, In the step of preparing photosensitive nitrobenzyloxycarbonyl-protected perfluoroaniline, the molar ratio of pentafluoroaniline, 2-nitrobenzyl chloroformate and triethylamine is 1:(0.9-1.1):(0.9-1.1).

9. A modified polytetrafluoroethylene, characterized in that, It is prepared by the method for preparing modified polytetrafluoroethylene as described in any one of claims 1-8.

10. An application of the modified polytetrafluoroethylene as described in claim 9 in the preparation of a biocompatible coating for neural interfaces, cochlear implants, or other high-end bioelectronic devices.

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