A production process of PEEK material with antibacterial function

Abstract

The present invention relates to the technical field of polyetheretherketone modification, and in particular to a process for preparing a PEEK material with antibacterial function. The process comprises the following steps: (1) plasma treating a PEEK substrate; (2) immersing the plasma-treated PEEK substrate in a grafting solution containing a photoinitiator and an antibacterial monomer, and initiating a grafting reaction by ultraviolet irradiation; (3) after the grafting of the antibacterial monomer is completed, placing the PEEK substrate as a cathode in the antibacterial agent solution, and applying a voltage to start the electrophoretic deposition process; (4) placing the PEEK substrate after electrophoretic deposition under ultraviolet light irradiation for photocuring treatment; (5) alternately depositing a positively charged antibacterial polymer layer and a negatively charged hyaluronic acid layer or an antibacterial nanoparticle layer on the photocured PEEK substrate. The PEEK material prepared by the present invention has good antibacterial properties, and has good antibacterial persistence, sustained release performance and biocompatibility.

Description

Technical Field

[0001] The invention relates to the technical field of polyetheretherketone modification, and in particular to a process for preparing a PEEK material with antibacterial function. Background Art

[0002] As a special engineering plastic, PEEK has attracted extensive attention due to its good biocompatibility, chemical stability and mechanical properties similar to human cancellous bone, especially showing great potential in hard tissue repair materials. However, PEEK itself is biologically inert, resulting in a lack of interaction between it and tissues, limiting its clinical application as an implant. In addition, PEEK lacks antibacterial properties, and its surface is prone to bacterial adhesion and biofilm formation, increasing the risk of implant-related infection.

[0003] 1. Insufficient antibacterial properties: PEEK surface is easily adhered by bacteria, forming biofilm, which increases the risk of infection. Direct use of antibiotics for treatment is prone to produce drug-resistant bacteria and may cause irreversible damage to certain organs.

[0004] 2. Limitations of antimicrobial agents: It is often difficult to achieve long-lasting and reproducible antimicrobial effects by modifying the PEEK surface with endogenous antimicrobial agents (such as antibiotics, precious metal nanoparticles, antimicrobial polymers, etc.).

[0005] 3. Single antimicrobial mechanism: Existing antimicrobial modification methods often rely on a single antimicrobial mechanism, such as reactive oxygen species production and contact killing, which may not be able to fully inhibit bacterial growth.

[0006] 4. The antibacterial effect of metal ions is limited: Although antibacterial metal ions can improve the antibacterial properties of PEEK, their effect is far from the ideal antibacterial level and there may be toxicity issues. Summary of the invention

[0007] In order to solve the problem of insufficient antibacterial performance of PEEK in the prior art, a process for manufacturing a PEEK material with antibacterial function is provided.

[0008] A process for producing a PEEK material with antibacterial function comprises the following steps:

[0009] (1) Plasma treatment: Plasma treatment of the PEEK matrix;

[0010] (2) Grafting antibacterial monomers: The plasma-treated PEEK substrate is immersed in a grafting solution containing a photoinitiator and an antibacterial monomer, and the grafting reaction is initiated by ultraviolet irradiation;

[0011] (3) Electrophoretic deposition: After the grafting of antimicrobial monomers is completed, the PEEK substrate is placed in the antimicrobial solution as a cathode, and a voltage is applied to start the electrophoretic deposition process;

[0012] (4) Photocuring: The PEEK substrate after electrophoretic deposition is placed under irradiation of an ultraviolet light source for photocuring;

[0013] (5) Component sustained-release layer: A positively charged antibacterial polymer layer and a negatively charged hyaluronic acid layer or antibacterial nanoparticle layer are alternately deposited on the photocured PEEK substrate.

[0014] Furthermore, before the plasma treatment in step (1), a surface pretreatment step of increasing the surface roughness of the PEEK substrate is also included.

[0015] Preferably, the surface pretreatment adopts laser sandblasting process. Laser sandblasting can increase the surface roughness, improve the specific surface area, and provide better mechanical anchoring for subsequent coatings. At the same time, plasma treatment introduces polar functional groups at the chemical level. The combination of the two makes the surface have both physical anchoring points and chemical active sites, which is more conducive to the adhesion and fixation of the antibacterial coating. This synergistic effect may lead to a more durable coating that can remain stable even in harsh environments.

[0016] Furthermore, during the plasma treatment in step (1), oxygen gas is introduced, the power is adjusted to 100 W, and the pressure is controlled at 50 Pa for 3 to 10 minutes.

[0017] Preferably, the antibacterial monomer in step (2) includes one or more of a quaternary ammonium salt monomer or a polylactic acid derivative. Under the action of a photoinitiator, a grafting reaction is initiated by ultraviolet irradiation. The sample is placed under an ultraviolet irradiation device and irradiated for about 30 minutes. In this process, the photoinitiator absorbs ultraviolet energy and decomposes to produce free radicals. The free radicals further induce the antibacterial monomer to undergo a polymerization reaction on the surface of PEEK, which is grafted onto the surface of PEEK to form a coating with antibacterial function. Among them, the quaternary ammonium salt monomer can be selected from one or more of benzalkonium chloride, phenoxy ammonium chloride, and dimethyl ammonium chloride; the polylactic acid (PLA) derivative can be selected from polylactic acid, polylactic acid copolymers (for example, polylactic acid copolymerized with glycolic acid (PLGA) or glycolide (PGA)), and polylactic acid-based block copolymers (for example, PLA-b-PEG (polylactic acid-polyethylene glycol block copolymer)).

[0018] Preferably, the grafting solution also includes N-acetylcysteine. N-acetylcysteine ​​(NAC) has a mitigating effect on the cytotoxicity caused by quaternary ammonium salt antibacterial monomers, but has no significant effect on the cell differentiation inhibition caused by them, thereby improving the biosafety of antibacterial materials containing quaternary ammonium salt antibacterial monomers.

[0019] Furthermore, the antibacterial agent solution in step (3) is a gentamicin sulfate aqueous solution, the applied voltage is 10 V, and the electrophoretic deposition is performed for 5 minutes. After the deposition is completed, the undeposited components are removed through the steps of washing and drying to ensure the uniformity and stability of the coating.

[0020] Preferably, the light curing conditions in step (4) are 365nm or 405nm ultraviolet light with a light intensity of 100mW / cm 2 Irradiate for 2 minutes.

[0021] Specifically, the step (5) of forming a sustained-release layer is as follows: ① adjusting the pH of a poly-lysine solution having a concentration of 0.01 to 0.1 wt % to a value higher than the isoelectric point of poly-lysine, immersing the photocured PEEK substrate therein for 1 to 10 minutes, taking it out and rinsing it, and obtaining a PEEK substrate having an antibacterial polymer layer with a positive charge after heat treatment;

[0022] ② Adjusting the pH of the hyaluronic acid or nanoparticle solution with a concentration of 0.05-0.5wt% to 4-6, immersing the PEEK substrate with the positively charged antibacterial polymer layer therein for 1-10 minutes, taking it out and rinsing it, and subjecting it to heat treatment to obtain a PEEK substrate with negatively charged hyaluronic acid or antibacterial nanoparticles;

[0023] Repeat the above steps ① and ② 2 to 10 times.

[0024] The nanoparticles may be one or more of silver nanoparticles, ZnO nanoparticles or TiO2 nanoparticles.

[0025] Preferably, the heat treatment temperature is 50-70°C.

[0026] Beneficial technical effects: The PEEK material with antibacterial function prepared by the present invention has good antibacterial performance, and has good antibacterial persistence, sustained release performance and biocompatibility. DETAILED DESCRIPTION

[0027] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Unless otherwise specifically stated, the numerical value set forth in these embodiments does not limit the scope of the present invention. The technology and method known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the technology and method should be considered as a part of the specification. In all examples shown and discussed here, any specific value should be interpreted as being merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments may have different values.

[0029] In addition, it should be noted that the use of terms such as "first" and "second" to limit the added catalyst and the filtrate after the reaction is only to facilitate the distinction between the catalyst used in each reaction step and the filtrate produced. Unless otherwise stated, the above terms have no special meaning and therefore cannot be understood as limiting the scope of protection of the present invention.

[0030] The experimental methods in the following examples without specifying specific conditions are usually measured in accordance with national standards; if there is no corresponding national standard, they are carried out in accordance with general standard requirements or general methods.

[0031] Example 1

[0032] A process for producing a PEEK material with antibacterial function comprises the following steps:

[0033] (1) Surface pretreatment: The surface of the PEEK substrate is treated by laser sandblasting; laser sandblasting can increase the surface roughness, increase the specific surface area, and provide better mechanical anchoring for subsequent coatings, etc.

[0034] (2) Plasma treatment: Plasma treatment of the PEEK substrate for 5 minutes with oxygen flowing in, power adjusted to 100W, and pressure controlled at 50Pa; plasma treatment introduces polar functional groups at the chemical level, and combined with laser sandblasting, the surface has both physical anchor points and chemically active sites, which is more conducive to the adhesion and fixation of the antibacterial coating. This synergistic effect may result in a more durable coating that remains stable even in harsh environments.

[0035] (3) Grafting antibacterial monomers: The plasma-treated PEEK substrate is immersed in a grafting solution containing a photoinitiator benzophenone (specifically 3,3',4,4'-benzophenone tetracarboxylic acid), an antibacterial monomer-quaternary ammonium salt monomer benzalkonium chloride and N-acetylcysteine ​​(NAC), wherein the mass concentration of the photoinitiator is 0.5%, the mass concentration of the antibacterial monomer is 6%, and the mass concentration of N-acetylcysteine ​​(NAC) is 0.02%. The grafting reaction is initiated by ultraviolet irradiation for 30 minutes. During this process, the photoinitiator absorbs ultraviolet energy and decomposes to produce free radicals. The free radicals further induce the polymerization reaction of the antibacterial monomer on the surface of PEEK, which is grafted onto the surface of PEEK to form a coating with antibacterial function;

[0036] (4) Electrophoretic deposition: After the grafting of the antibacterial monomer is completed, the PEEK substrate is placed in the antibacterial solution as the cathode, and a voltage is applied to start the electrophoretic deposition process; the antibacterial solution is a 5 μg / mL gentamicin sulfate aqueous solution, the applied voltage is 10 V, and the electrophoretic deposition is performed for 5 minutes. After the deposition is completed, the undeposited components are removed through the steps of washing and drying to ensure the uniformity and stability of the coating.

[0037] (5) Photocuring: The PEEK substrate after electrophoretic deposition is placed under ultraviolet light for photocuring. The photocuring conditions are 365 nm ultraviolet light and a light intensity of 100 mW / cm 2 Irradiate for 2 minutes;

[0038] (6) Component sustained-release layer: A positively charged antibacterial polymer layer and a negatively charged hyaluronic acid layer are alternately deposited on the photocured PEEK substrate.

[0039] The steps of forming a sustained-release layer of the component are as follows: ① adjusting the pH of a poly-lysine solution having a concentration of 0.05 wt % to a value higher than the isoelectric point of poly-lysine, immersing the photocured PEEK substrate therein for 5 minutes, taking it out and rinsing it, and obtaining a PEEK substrate having an antibacterial polymer layer with a positive charge after heat treatment at 60° C.;

[0040] ② The pH of the hyaluronic acid with a concentration of 0.2wt% was adjusted to 5, and the PEEK substrate with the positively charged antibacterial polymer layer was immersed therein for 5 minutes, taken out and rinsed, and subjected to heat treatment at 60°C to obtain a PEEK substrate with negatively charged hyaluronic acid;

[0041] Repeat the above steps ① and ② 6 times to obtain the PEEK material with antibacterial function.

[0042] Example 2

[0043] A process for producing a PEEK material with antibacterial function comprises the following steps:

[0044] (1) Surface pretreatment: The surface of the PEEK substrate is treated by laser sandblasting; laser sandblasting can increase the surface roughness, increase the specific surface area, and provide better mechanical anchoring for subsequent coatings, etc.

[0045] (2) Plasma treatment: The PEEK substrate was subjected to plasma treatment for 10 minutes under the condition of oxygen flow, adjusting the power to 100 W, and controlling the gas pressure to 50 Pa;

[0046] (3) Grafting antibacterial monomer: The plasma-treated PEEK substrate is immersed in a grafting solution containing a photoinitiator benzophenone (3,3',4,4'-benzophenonetetracarboxylic acid), an antibacterial monomer-quaternary ammonium salt monomer (phenoxyammonium chloride) and N-acetylcysteine ​​(NAC), wherein the mass concentration of the photoinitiator is 1%, the mass concentration of the antibacterial monomer is 8%, and the mass concentration of N-acetylcysteine ​​(NAC) is 0.05%. The grafting reaction is initiated by ultraviolet irradiation for 30 minutes;

[0047] (4) Electrophoretic deposition: After the grafting of the antibacterial monomer is completed, the PEEK substrate is placed in the antibacterial solution as the cathode, and a voltage is applied to start the electrophoretic deposition process; the antibacterial solution is a 5 μg / mL gentamicin sulfate aqueous solution, the applied voltage is 10 V, and the electrophoretic deposition is performed for 5 minutes. After the deposition is completed, the undeposited components are removed through the steps of washing and drying to ensure the uniformity and stability of the coating.

[0048] (5) Photocuring: The PEEK substrate after electrophoretic deposition is placed under ultraviolet light for photocuring. The photocuring conditions are 405 nm ultraviolet light and a light intensity of 100 mW / cm 2 Irradiate for 2 minutes;

[0049] (6) Component sustained-release layer: A positively charged antibacterial polymer layer and a negatively charged hyaluronic acid layer are alternately deposited on the photocured PEEK substrate.

[0050] The steps of forming a sustained-release layer of the component are as follows: ① adjusting the pH of a poly-lysine solution having a concentration of 0.01 wt % to a value higher than the isoelectric point of poly-lysine, immersing the photocured PEEK substrate therein for 10 minutes, taking it out and rinsing it, and obtaining a PEEK substrate having an antibacterial polymer layer with a positive charge after heat treatment at 70° C.;

[0051] ② The pH of the 0.5wt% hyaluronic acid solution was adjusted to 6, and the PEEK substrate with the positively charged antibacterial polymer layer was immersed therein for 1 minute, taken out and rinsed, and subjected to a heat treatment at 50° C. to obtain a PEEK substrate with negatively charged hyaluronic acid;

[0052] Repeat the above steps ① and ② twice to obtain the PEEK material with antibacterial function.

[0053] Example 3

[0054] A process for producing a PEEK material with antibacterial function comprises the following steps:

[0055] (1) Surface pretreatment: The surface of the PEEK substrate is treated by laser sandblasting; laser sandblasting can increase the surface roughness, increase the specific surface area, and provide better mechanical anchoring for subsequent coatings, etc.

[0056] (2) Plasma treatment: The PEEK substrate was subjected to plasma treatment for 10 minutes under the condition of oxygen flow, adjusting the power to 100 W, and controlling the gas pressure to 50 Pa;

[0057] (3) Grafting antibacterial monomer: The plasma-treated PEEK substrate is immersed in a grafting solution containing a photoinitiator benzophenone (selected as 3,3',4,4'-benzophenone tetracarboxylic acid), an antibacterial monomer-quaternary ammonium salt monomer dimethyl ammonium chloride and N-acetylcysteine ​​(NAC), wherein the mass concentration of the photoinitiator is 0.1%, the mass concentration of the antibacterial monomer is 5%, and the mass concentration of N-acetylcysteine ​​(NAC) is 0.01%. The grafting reaction is initiated by ultraviolet irradiation for 30 minutes;

[0058] (4) Electrophoretic deposition: After the grafting of the antibacterial monomer is completed, the PEEK substrate is placed in the antibacterial solution as a cathode, and a voltage is applied to start the electrophoretic deposition process; the antibacterial solution is a 5 μg / mL gentamicin sulfate aqueous solution, the applied voltage is 10 V, and the electrophoretic deposition is performed for 5 minutes. After the deposition is completed, the undeposited components are removed through the steps of washing and drying to ensure the uniformity and stability of the coating.

[0059] (5) Photocuring: The PEEK substrate after electrophoretic deposition is placed under ultraviolet light for photocuring. The photocuring conditions are 365 nm and a light intensity of 100 mW / cm 2 Irradiate for 2 minutes;

[0060] (6) Component sustained-release layer: A positively charged antibacterial polymer layer and a negatively charged antibacterial nanoparticle layer are alternately deposited on the photocured PEEK substrate.

[0061] The steps of forming a sustained-release layer of the component are as follows: ① adjusting the pH of a poly-lysine solution having a concentration of 0.1 wt% to a value higher than the isoelectric point of poly-lysine, immersing the photocured PEEK substrate therein for 1 minute, taking it out and rinsing it, and obtaining a PEEK substrate having an antibacterial polymer layer with a positive charge after heat treatment at 50° C.;

[0062] ② The pH of the 0.05wt% ZnO nanoparticle solution was adjusted to 4, and the PEEK substrate with the positively charged antibacterial polymer layer was immersed therein for 10 minutes, taken out and rinsed, and subjected to a heat treatment at 70°C to obtain a PEEK substrate with negatively charged hyaluronic acid;

[0063] Repeat the above steps ① and ② 10 times to obtain the PEEK material with antibacterial function.

[0064] Performance Testing

[0065] Sustained release and antibacterial properties

[0066] Release medium selection:

[0067] Phosphate buffered saline (PBS, pH 7.4) was used to simulate the physiological environment because it provides a chemical and pH condition close to the internal environment of the human body.

[0068] Sample preparation:

[0069] The PEEK material with antibacterial function prepared above was cut into uniform sizes of 1x1 cm as samples.

[0070] Test container preparation:

[0071] Select containers of appropriate size, ensuring that each container can accommodate one piece of PEEK sample and 5 mL of release medium.

[0072] Constant temperature conditions:

[0073] A constant temperature shaker was used, the temperature was set to 37 °C to simulate human body temperature, and a constant stirring speed of 100 rpm was maintained to ensure the homogeneity of the release medium.

[0074] Time point setting:

[0075] Sampling was performed at multiple time points, such as 0 hour (initial state), 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and once a day thereafter until a significant decrease in the release effect was observed.

[0076] Sampling and changing media:

[0077] At each time point, 0.5 mL of the release medium was removed for analysis and an equal amount of fresh PBS solution was added to maintain a constant volume.

[0078] Antimicrobial activity assay:

[0079] The released medium was mixed with LB liquid culture medium containing 106 CFU / mL of Staphylococcus aureus, and the formation of the antibacterial zone was observed.

[0080] result:

[0081] Rapid Release Period:

[0082] In the initial stage (1-2 hours), a higher release of antimicrobial agents may be observed, forming a larger antimicrobial zone.

[0083] Sustained release plateau:

[0084] Then it enters the sustained-release plateau phase (4-24 hours), the release rate decreases, and the change in the size of the antibacterial zone slows down.

[0085] Lasting Effect:

[0086] In the next few days to a week, a certain degree of antibacterial effect can still be observed, indicating excellent sustained-release performance. As the sustained-release layer gradually dissolves, the antibacterial substances are continuously released.

[0087] Biocompatibility

[0088] The PEEK material with antibacterial function prepared above was cut into discs with a diameter of 10 mm and a thickness of 1 mm. Osteoblasts were selected as test cells. Cell suspension was prepared with a cell concentration of 1x10 4 cells / mL. Place the PEEK material sheets in a 24-well culture plate, one sheet in each well. Add 200 μL of cell suspension to each well to ensure that the cells are evenly distributed on the surface of the PEEK material. Place the culture plate in a cell culture incubator at 37°C and 5% CO2 for 24 hours, 48 ​​hours, and 72 hours.

[0089] Control group setting:

[0090] Cell culture wells without PEEK material were set up as the control group, and the culture conditions were the same as those of the experimental group.

[0091] The results showed that after 72 hours, the cell survival rate exceeded 90%, indicating that the material was non-toxic to cells and had good biocompatibility.

[0092] Cell proliferation test: The proliferation rate of cells in the presence of the material was measured by Cell Counting Kit-8 (CCK-8). The CCK-8 test showed that cell proliferation was not significantly affected within 1-3 days, indicating that the material supported cell growth well.

[0093] Cell differentiation test: evaluates the differentiation ability of osteoblasts on the surface of the material by measuring alkaline phosphatase (ALP) activity and the formation of mineralized nodules. The evaluation of ALP activity and mineralized nodules showed that the differentiation ability of cells on the surface of the material was not inhibited and was even enhanced under certain conditions.

[0094] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A process for producing a PEEK material with antibacterial function, characterized in that: The following steps are involved: (1) Plasma treatment: Plasma treatment of PEEK matrix; (2) Grafting antibacterial monomers: immersing the plasma-treated PEEK substrate in a grafting solution containing a photoinitiator and an antibacterial monomer, and initiating the grafting reaction by ultraviolet irradiation; the antibacterial monomers include one or more of quaternary ammonium salt monomers or polylactic acid derivatives, and the grafting solution also includes N-acetylcysteine; (3) Electrophoretic deposition: After the grafting of the antimicrobial monomer is completed, the PEEK substrate is placed as a cathode in an antimicrobial solution, and a voltage is applied to start the electrophoretic deposition process. The antimicrobial solution contains gentamicin sulfate. (4) Photocuring: The PEEK substrate after electrophoretic deposition is placed under ultraviolet light for photocuring; (5) Constructing a sustained-release layer: alternately depositing a positively charged antibacterial polymer layer and a negatively charged hyaluronic acid layer or an antibacterial nanoparticle layer on a photocured PEEK substrate; the positively charged antibacterial polymer includes polylysine.

2. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: Before the plasma treatment in step (1), a surface pretreatment step of increasing the surface roughness of the PEEK substrate is also included.

3. The process for producing a PEEK material with antibacterial function according to claim 2, characterized in that: The surface pretreatment adopts laser sandblasting technology.

4. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: In step (1), the plasma treatment is carried out for 3 to 10 minutes under the condition of introducing oxygen, adjusting the power to 100 W, and controlling the gas pressure to 50 Pa.

5. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: In step (2), the mass concentration of the antibacterial monomer in the grafting solution is 5% to 8%, and the mass concentration of the photoinitiator is 0.1% to 1%.

6. The process for producing a PEEK material with antibacterial function according to claim 5, characterized in that: The mass concentration of N-acetylcysteine ​​is 0.01-0.05%.

7. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: The antibacterial agent solution in step (3) is a gentamicin sulfate aqueous solution, the concentration of the gentamicin sulfate aqueous solution is 5 µg / mL, the applied voltage is 10 V, and the electrophoretic deposition is performed for 5 minutes.

8. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: Step (4) The light curing conditions are 365nm or 405nm ultraviolet light and a light intensity of 100mW / cm 2 Irradiate for 2 minutes.

9. The process for producing a PEEK material with antibacterial function according to claim 1, characterized in that: Step (5) constructing a sustained-release layer comprises: ① adjusting the pH of a poly-lysine solution having a concentration of 0.01-0.1 wt % to a value higher than the isoelectric point of poly-lysine, immersing the photocured PEEK substrate therein for 1-10 minutes, taking it out and rinsing it, and obtaining a PEEK substrate having an antibacterial polymer layer with a positive charge after heat treatment; ② Adjust the pH of the hyaluronic acid or nanoparticle solution with a concentration of 0.05-0.5wt% to 4-6, immerse the PEEK substrate of the positively charged antibacterial polymer therein for 1-10 minutes, take it out and rinse it, and heat-treat it to obtain the PEEK substrate of the negatively charged hyaluronic acid or antibacterial nanoparticles; Repeat the above steps ① and ② 2 to 10 times.

10. The process for producing a PEEK material with antibacterial function according to claim 9, characterized in that: The heat treatment temperature is 50-70°C.