Antibacterial coating based on modified parylene and preparation method

Abstract

The invention belongs to the technical field of medical interventional catheters, and particularly relates to a modified parylene-based antibacterial coating and a preparation method thereof, and is characterized in that a monomer molecular structure of a high-molecular compound is formed by carboxyl-containing parylene and parylene N through a gas deposition process together to form a parylene polymer with the surface containing carboxyl, and the modified parylene-based antibacterial coating is prepared from the modified parylene-based antibacterial coating and the preparation method of the modified parylene-based antibacterial coating. Then guanidine salt or antibacterial peptide reacts with carboxyl and is grafted on the parylene polymer coating. The composite material can be applied to the related aspects of biological medicine, has excellent antibacterial and anti-adhesion properties, and also has the beneficial effects of water resistance, moisture resistance, solid lubrication, small friction force, relatively low interface constant and the like; the preparation method is simple and low in cost.

Description

Technical Field

[0001] The invention belongs to the technical field of medical interventional catheters, and in particular relates to an antibacterial coating based on modified parylene and a preparation method thereof. Background Art

[0002] Paracyclophane is an organic compound with the chemical formula C16H16. It is also known as di-paraxylene, paraxylene dimer and parylene N. Its structural formula is The Parylene produced by it is the general name of polyparaxylene polymer system, a polymer with paraxylene as the skeleton. The benzene ring or methylene group can be all hydrogen or contain various substituted groups. It is prepared by a unique vacuum vapor deposition process and is a protective polymer material with a completely linear and highly crystalline structure. It can be vapor deposited under vacuum to form a new type of conformal coating at the molecular level.

[0003] The widely used parylene materials can be divided into parylene N (p-xylene ring dimer), parylene C (monochloro p-xylene ring dimer), parylene D (dichloro p-xylene ring dimer), parylene HF (octafluoro p-xylene dimer), F type (tetrafluoro p-xylene ring dimer) according to different molecular structures, such as Figure 1 As shown. Their main difference lies in the different types or numbers of substituents on the molecules, which determines the differences in thermal stability and insulation properties. The commonly used method for preparing parylene is chemical vapor deposition (CVD), in which the reactants undergo a spatial gas-phase chemical reaction under gaseous conditions to directly generate solid substances on the surface of a solid substrate, and then form a coating on the surface of the substrate. In the preparation process of parylene film, the two connected carbon-carbon bonds of the cyclic dimer are broken at high temperature to generate an active para-xylene benzene monomer. When it enters the deposition chamber at room temperature from a high temperature environment, the unstable monomer will polymerize into a film, such as Figure 2 The preparation process is shown in FIG.

[0004] Parylene is a polymer film coating that is "grown" from active small molecules on the surface of the substrate. Its penetrating power enables it to form a high-quality protective layer without pinholes inside, at the bottom, and around the components. It can be used in the fields of microelectronics, semiconductors, printed circuit board biosensors, and cultural relics protection to prevent moisture, mildew, corrosion, and salt spray. Because of its biocompatibility and biostability, it can be used in biomedicine and can be implanted in the body for a long time.

[0005] In medical devices, parylene can be used in a variety of applications, such as bone screws, disposable surgical instruments, replacement devices, catheters, brakes, etc. For example, it is used on blood pressure sensors, where a small amount of coating will not significantly change the operation of these devices, and on the housing of heart assist devices to prevent them from being corroded by biological fluids. Parylene deposition can prevent complex appearance mounting and mixed electronic circuits from being corroded by water and chemicals and provide excellent dielectric properties; and on ultrasonic transducers, it is used to observe micro sensors on the inner wall of blood vessels to avoid corrosion and insulation breakdown, etc. These are all using the smooth, non-porous and anti-electronic barrier properties of parylene, thereby waterproofing, corrosion-resistant and insulating.

[0006] Currently, there are relatively few reports on the use of parylene in biomedicine. Most of them have few biological functions, and parylene coatings do not have antibacterial properties. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides an antibacterial coating based on modified parylene and a preparation method, which is applied to biomedicine-related aspects, has excellent antibacterial and anti-adhesive properties, and also has the beneficial effects of water blocking, moisture resistance, solid lubrication, low friction, relatively low interface constant, etc.; the preparation method is simple and low in cost.

[0008] The present invention solves the above technical problems by providing an antibacterial coating based on modified parylene, characterized in that the antibacterial coating contains a monomer molecular structure as follows: , Wherein, R is an amino-containing antimicrobial peptide or guanidine salt, and m and n>1.

[0009] The role of introducing carboxyl groups: to allow chemically active functional groups to appear in the main chain molecular structure, to facilitate subsequent chemical grafting, and to connect the side chains with antibacterial functions to the main chain molecules. Compared with chemical groups such as amino and NCO, the method of introducing carboxyl groups to complete subsequent grafting is more feasible.

[0010] In the optimized scheme, R is an antimicrobial peptide containing an amino group.

[0011] The guanidine salt is polyhexamethylene biguanidine salt.

[0012] In a further optimized solution, the antimicrobial peptide is one or two of AMPs (WR (sequence: WRWRWR-NH2) and Bac2A (sequence: RLARIVVIRVAR-NH2)).

[0013] The coating is formed by gas deposition of carboxyl parylene and parylene N to form a parylene polymer with carboxyl groups on the surface, and then guanidine salt or antimicrobial peptide reacts with the carboxyl groups and is grafted onto the parylene polymer, thus having antimicrobial function.

[0014] The present invention provides a method for preparing an antibacterial coating based on modified parylene, comprising the following steps: (1) Gasification: Parylene N and carboxyl-modified parylene are sublimated into gaseous state by decompression and heating under vacuum conditions of 0.9-1.1 torr and temperature of 120℃-180℃; (2) Thermal cracking: When the temperature rises to 600-750°C in a vacuum of 0.4-0.6 torr, the two dimers undergo thermal cracking to generate intermediate monomers, namely p-xylene and 2,4-dimethylbenzoic acid; (3) Deposition polymerization: The intermediate monomer enters the deposition chamber in the form of gas phase for deposition polymerization. The deposition temperature is room temperature and the vacuum degree is 0.4-0.6 torr to obtain a carboxyl-containing parylene coating. (4) Grafting antimicrobial peptides or guanidine salts to obtain the product.

[0015] The grafting of guanidine salt or antimicrobial peptide is carried out under normal pressure.

[0016] The temperature in step (1) described in the optimization scheme is 150-170°C.

[0017] The vacuum in step (1) is 1.0 torr.

[0018] The temperature in step (2) is 680°C.

[0019] The vacuum in step (2) and step (3) is 0.5 torr.

[0020] The room temperature is 23-26°C, and the room temperature in the optimized solution is 25°C.

[0021] The structural formula of carboxyl-modified parylene is as follows: .

[0022] The overall reaction process is as follows: , (Reaction process I), , (Reaction process II).

[0023] In the present invention, chemical vapor deposition and grafting of antimicrobial peptides or guanidine salts are performed. In the vapor deposition step, two dimers are sublimated and free radicals are cleaved, and two connected carbon-carbon bonds are broken to generate active p-xylene and 2,4-dimethylbenzoic acid, which are then deposited and polymerized under room temperature conditions. Grafting is performed by reacting the antimicrobial peptide or guanidine salt with the carboxyl group of the polymer monomer to form an amide bond.

[0024] The step (4) of grafting an antimicrobial peptide-modified antimicrobial coating using an EDC / NHS chemical method comprises the following steps: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS. The EDC concentration is 5-10 mg / ml, the Sulfo-NHS concentration is 0.5-5 mg / ml, the pH of the solution is 3-6, the reaction time is 1-12 hours, and the reaction temperature is 2-10°C; B. washing the obtained substrate with MES solution three times and drying with nitrogen flow to obtain a substrate after activation of carboxyl groups; C. Treat the activated substrate with a PBS solution containing 0.5-10 mg / ml of antimicrobial peptide, wherein the pH of the solution is 7-10, the reaction time is 12-48 hours, and the reaction temperature is 2-10°C; D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0025] Alternatively, the grafting in step (4) using EDC / NHS chemical method to prepare the guanidine salt-modified antibacterial coating comprises the following steps: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS; wherein the EDC concentration is 5-10 mg / ml, the Sulfo-NHS concentration is 0.5-5 mg / ml, the pH of the solution is 3-6, the reaction time is 1-12 hours, and the reaction temperature is 2-10°C; B. washing the obtained substrate with MES solution three times and drying with nitrogen flow to obtain a substrate after activation of carboxyl groups; C. Treating the activated substrate with a PBS solution having a guanidine salt concentration of 2-20 mg / ml; wherein the pH of the solution is 7.5-10, the reaction time is 6-48 hours, and the reaction temperature is 2-25°C; in the optimized solution, the pH is 9-10, the reaction time is 12-48 hours, and the reaction temperature is 2-10°C; D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0026] The thickness of the coating formed in the present invention is 1-3 micrometers.

[0027] The present invention introduces carboxyl groups, and the bio-coating formed by the polymer has beneficial effects such as antibacterial and anti-adhesive properties, and also has water-blocking and moisture-proof effects. It is also slippery due to its low friction and relatively low interface constant. The antibacterial compound is hydrophobic, and no bacteria can grow therein, so it has a bactericidal function. It also has good electrical and protective properties, and good biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 11 is a structural diagram of different monomers of parylene in the present invention (wherein N, C, D, F, and HF are structural codes).

[0029] Figure 2 and Figure 3 Schematic diagram of the preparation of the antibacterial coating in the present invention.

[0030] Figure 4 This is the result diagram of sample 3 in the present invention.

[0031] Figure 5 This is the result diagram of sample 1 in the present invention.

[0032] Figure 6 This is the result diagram of sample 2 in the present invention. DETAILED DESCRIPTION

[0033] The following is further described by specific examples: The vapor deposition adopts Parylene vacuum coating machine, and the materials and reagents are: N-hydroxysulfosuccinimide (Sulfo-NHS), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC); the antimicrobial peptide is one or two of AMPss (WR (sequence: WRWRWR-NH2) and Bac2A (sequence: RLARIVVIRVAR-NH2)).

[0034] Implementation 1: The monomer structure is as follows: , R is an antimicrobial peptide containing an amino group, and m, n>1.

[0035] The antimicrobial peptides are AMPs (WR (sequence: WRWRWR-NH2).

[0036] The preparation method of the antibacterial coating is as follows: (1) In a vacuum environment of 1.0 torr at 120℃-180℃, the two solid dimers are decompressed and heated to sublime into gas.

[0037] (2) In a vacuum environment of 0.5 torr, when the temperature reaches 600-750°C (optimal 680°C), the two dimers will undergo thermal cracking to generate active intermediate monomers with free radicals (p-xylene and 2,4-dimethylbenzoic acid).

[0038] (3) Then it enters the deposition chamber in the form of gas phase, the temperature is about room temperature 25℃, and the vacuum degree is 0.5 torr. After that, as the temperature decreases, the free radical intermediates approaching each other come into contact, and at room temperature, they are polymerized on the surface of the object through vapor deposition to form a carboxyl-containing parylene coating.

[0039] (4) Grafting antimicrobial peptides to obtain.

[0040] The grafting in step (4) adopts EDC / NHS chemical method: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 8 mg / ml, the Sulfo-NHS concentration is 2 mg / ml, the pH of the solution is ~5.5, the reaction time is 6 hours, and the reaction temperature is 4°C.

[0041] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0042] C. Treat the activated substrate with a PBS solution containing 5 mg / ml of antimicrobial peptide, wherein the pH of the solution is 7.4, the reaction time is 24 hours, and the reaction temperature is 4°C.

[0043] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0044] In the present invention, the polymer compound, polyparaxylene, is pyrolyzed to split its dimer into single free radical paraxylene. In the deposition chamber (25° C.), the monomers are aggregated on all exposed surfaces and polymerized into polyparaxylene at a rate of about 5 μm / h. Polyparaxylene is obtained by the free radical polymerization reaction of paraxylene, and the monomer molecules are connected by chemical bonds to form a source-relin modified polymer compound.

[0045] The reaction process is as follows: .

[0046] Embodiment 2: The other contents are as in Example 1, wherein the antimicrobial peptide is Bac2A (sequence: RLARIVVIRVAR-NH2)), the vacuum in step (1) is 0.9 torr and the temperature is 120°C; the vacuum in step (2) is 0.4 torr and the temperature is 600°C; the vacuum in step (3) is 0.4 torr and the temperature is 26°C.

[0047] Grafting using EDC / NHS chemistry: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 5 mg / ml, the Sulfo-NHS concentration is 0.5 mg / ml, the pH of the solution is ~3, the reaction time is 12 hours, and the reaction temperature is 2°C.

[0048] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0049] C. Treat the activated substrate with a PBS solution containing 0.5 mg / ml of antimicrobial peptide, wherein the pH of the solution is 7, the reaction time is 12 hours, and the reaction temperature is 10°C.

[0050] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0051] The specific cracking and grafting reactions in the above Examples 1 and 2 are as follows: Figure 2 and Figure 3 shown.

[0052] Embodiment 3: The other contents are the same as those in Example 1, wherein in step (1), the vacuum is 1.1 torr and the temperature is 180°C; in step (2), the vacuum is 0.6 torr and the temperature is 750°C; and in step (3), the vacuum is 0.6 torr and the temperature is 23°C.

[0053] Grafting using EDC / NHS chemistry: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 10 mg / ml, the NHS concentration is 5 mg / ml, the pH of the solution is ~6, the reaction time is 1 hour, and the reaction temperature is 10°C.

[0054] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0055] C. Treat the activated substrate with a PBS solution containing 10 mg / ml of antimicrobial peptide, wherein the pH of the solution is 10, the reaction time is 48 hours, and the reaction temperature is 2°C.

[0056] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0057] Embodiment 4: The other contents are the same as those in Example 1, wherein in step (1), the vacuum is 0.9 torr and the temperature is 150°C; in step (2), the vacuum is 0.5 torr and the temperature is 650°C; and in step (3), the vacuum is 0.6 torr and the temperature is 25°C.

[0058] Grafting using EDC / NHS chemistry: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 6 mg / ml, the NHS concentration is 3 mg / ml, the pH of the solution is ~4, the reaction time is 8 hours, and the reaction temperature is 6°C.

[0059] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0060] C. Treat the activated substrate with a PBS solution containing 7 mg / ml of antimicrobial peptide, wherein the pH of the solution is 9, the reaction time is 18 hours, and the reaction temperature is 6°C.

[0061] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0062] Embodiment 5: The other contents are the same as those in Example 1, wherein in step (1), the vacuum is 1.0 torr and the temperature is 170°C; in step (2), the vacuum is 0.5 torr and the temperature is 700°C; and in step (3), the vacuum is 0.5 torr and the temperature is 24°C.

[0063] Grafting using EDC / NHS chemistry: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 7 mg / ml, the NHS concentration is 4 mg / ml, the pH of the solution is ~4.5, the reaction time is 4 hours, and the reaction temperature is 8°C.

[0064] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0065] C. Treat the activated substrate with a PBS solution containing 2 mg / ml of antimicrobial peptide, wherein the pH of the solution is 8, the reaction time is 36 hours, and the reaction temperature is 8°C.

[0066] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0067] Embodiment 6: The antibacterial layer monomer structure is as follows: , R is guanidine salt, m, n>1.

[0068] The preparation method of the antibacterial coating is as follows: (1) In a vacuum environment of 1.0 torr at 160°C, the two solid dimers are decompressed and heated to sublime into gas.

[0069] (2) In a vacuum environment of 0.5 torr, when the temperature reaches 680°C, the two dimers will undergo thermal decomposition to generate active intermediate monomers with free radicals (p-xylene and 2,4-dimethylbenzoic acid).

[0070] (3) Then it enters the deposition chamber in the form of gas phase, the temperature is about room temperature 25℃, and the vacuum degree is 0.5 torr. After that, as the temperature decreases, the free radical intermediates approaching each other come into contact, and at room temperature, they are polymerized on the surface of the object through vapor deposition to form a carboxyl-containing parylene coating.

[0071] (4) Grafting guanidine salt to obtain.

[0072] The grafting in step (4) adopts EDC / NHS chemical method: A. The carboxyl-containing substrate was activated in a MES solution containing EDC and Sulfo-NHS, wherein the EDC concentration was 5 mg / ml, the NHS concentration was 4 mg / ml, the pH of the solution was 5.5, the reaction time was 48 hours, and the reaction temperature was 9°C.

[0073] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0074] C. The substrate was treated with a PBS solution containing 10 mg / ml guanidine salt, wherein the pH of the solution was 10, the reaction time was 6 hours, and the reaction temperature was 25°C.

[0075] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0076] Embodiment 7: The antibacterial layer monomer structure is as follows: , R is polyhexamethylene biguanide salt, m, n>1.

[0077] The preparation method of the antibacterial coating is as follows: (1) In a vacuum environment of 1.0 torr at 160°C, the two solid dimers are decompressed and heated to sublime into gas.

[0078] (2) In a vacuum environment of 0.5 torr, when the temperature reaches 680°C, the two dimers will undergo thermal decomposition to generate active intermediate monomers with free radicals (p-xylene and 2,4-dimethylbenzoic acid); (3) Then it enters the deposition chamber in the form of gas phase, the temperature is about room temperature 25℃, and the vacuum degree is 0.5 torr. After that, as the temperature decreases, the free radical intermediates approaching each other come into contact, and at room temperature, they are polymerized on the surface of the object through vapor deposition to form a carboxyl-containing parylene coating.

[0079] (4) Grafting polyhexamethylene biguanidine salt to obtain. From the perspective of practicality, grafted guanidine salt is more practical.

[0080] The grafting in step (4) adopts EDC / NHS chemical method: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 8 mg / ml, the Sulfo-NHS concentration is 2 mg / ml, the pH of the solution is 5.5, the reaction time is 6 hours, and the reaction temperature is 4°C.

[0081] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0082] C. Treat the activated substrate with a PBS solution containing 10 mg / ml polyhexamethylene biguanide, wherein the pH of the solution is 7.4, the reaction time is 24 hours, and the reaction temperature is 4°C.

[0083] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0084] Embodiment 8: The antibacterial layer monomer structure is as follows: , R is polyhexamethylene biguanide salt, m, n>1.

[0085] The preparation method of the antibacterial coating is as follows: (1) In a vacuum environment of 1.0 torr at 160°C, the two solid dimers are decompressed and heated to sublime into gas.

[0086] (2) In a vacuum environment of 0.5 torr, when the temperature reaches 680°C, the two dimers will undergo thermal decomposition to generate active intermediate monomers with free radicals (p-xylene and 2,4-dimethylbenzoic acid); (3) Then it enters the deposition chamber in the form of gas phase, the temperature is about room temperature 25℃, and the vacuum degree is 0.5 torr. After that, as the temperature decreases, the free radical intermediates approaching each other come into contact, and at room temperature, they are polymerized on the surface of the object through vapor deposition to form a carboxyl-containing parylene coating.

[0087] (4) Grafting polyhexamethylene biguanidine salt to obtain. From the perspective of practicality, grafted guanidine salt is more practical.

[0088] The grafting in step (4) adopts EDC / NHS chemical method: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS, where the EDC concentration is 6 mg / ml, the Sulfo-NHS concentration is 3 mg / ml, the pH of the solution is ~5, the reaction time is 5 hours, and the reaction temperature is 8°C.

[0089] B. The obtained substrate was rinsed with MES solution three times and dried with nitrogen flow to obtain a substrate with activated carboxyl groups.

[0090] C. The substrate was treated and activated with a PBS solution containing 8 mg / ml polyhexamethylene biguanide, wherein the pH of the solution was 9, the reaction time was 30 hours, and the reaction temperature was 18°C.

[0091] D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

[0092] Test 1 Surface contact sterilization test Material preparation: Coating 1 and coating 2 grafted with antimicrobial peptides, and control sample 3 without antimicrobial peptides were cut into samples of 1*1 cm, and the samples were sterilized by moist heat sterilization.

[0093] Bactericidal test: 10 μl of concentration 10 5 cfu / mL of Staphylococcus aureus were evenly inoculated on the surface of the sample, and then a layer of polyethylene plastic film was covered on the surface of the sample. Incubate in a humid incubator at 37°C for 6 hours. Samples 1-3 were placed in different sterile test tubes together with polyethylene plastic films, and 3 ml of PBS was added to each test tube. Ultrasonication was performed for 3-5 minutes to shake the bacteria off. Then 100 microliters of the above PBS liquid was inoculated on the agar medium, cultured overnight, and the bacterial growth was observed. Figure 4-Figure 6 shown.

[0094] Result analysis: From the results, Figure 4 Sample 3 was covered with bacteria, indicating that the sample without grafted antimicrobial peptides had no bactericidal function. Figure 5 Sample 1 and Figure 6 No bacterial growth was found in sample 2, indicating that the grafted antimicrobial peptide killed all bacteria and the sample had excellent antibacterial properties.

[0095] Experimental Di-grafted Guanidine Salt Surface Contact Bactericidal Test Material preparation: The coating sample 4 grafted with polyhexamethylene biguanide salt and the control sample 5 not grafted with polyhexamethylene biguanide salt were cut into samples of 1*1 cm, and the samples were sterilized by wet heat sterilization method.

[0096] Sterilization test: 10 microliters of 105 cfu / mL Staphylococcus aureus are evenly inoculated on the surface of the sample, and then a layer of polyethylene plastic film is covered on the surface of the sample. Incubate in a humid incubator at 37°C for 6 hours. Place samples 1-3 and polyethylene plastic films in different sterile test tubes, add 3 ml of PBS to each test tube, and ultrasonicate for 3-5 minutes to shake the bacteria down. Then take 100 microliters of the above PBS liquid and inoculate it on the agar medium, incubate overnight, and observe the bacterial growth.

[0097] Result analysis: Sample 5 was covered with bacteria, indicating that the sample without grafted guanidine salt had no bactericidal function. No bacteria growth was found in Sample 4, indicating that the grafted polyhexamethylene biguanide salt killed all bacteria and the sample had excellent antibacterial properties. Guanidine salt is a polymer, not easy to inactivate, insensitive to sterilization process, product shelf life aging process, etc., and guanidine salt is durable.

[0098] The above implementation / test examples are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. An antibacterial coating based on modified parylene, characterized in that: The monomer molecular structure of the antibacterial coating is as follows: ； Wherein, R is an amino-containing antimicrobial peptide or guanidine salt, and m and n>1.

2. The antibacterial coating based on modified parylene according to claim 1, characterized in that: R is an antimicrobial peptide containing an amino group.

3. An antimicrobial coating based on modified parylene according to claim 2, characterized in that: The antimicrobial peptides are AMPs, namely one or both of WR and Bac2A, wherein the sequence of WR is: WRWRWR-NH2, and the sequence of Bac2A is: RLARIVVIRVAR-NH2.

4. The antibacterial coating based on modified parylene according to claim 1, characterized in that: The guanidine salt is polyhexamethylene biguanidine salt.

5. The method for preparing an antibacterial coating based on modified parylene according to claim 1, characterized in that: The following steps are involved: (1) Gasification: Parylene N and carboxyl-modified parylene are sublimated into gaseous state by decompression and heating under vacuum conditions of 0.9-1.1 torr and temperature of 120℃-180℃; (2) Thermal cracking: When the temperature rises to 600-750°C in a vacuum of 0.4-0.6 torr, the two dimers undergo thermal cracking to generate intermediate monomers, namely p-xylene and 2,4-dimethylbenzoic acid; (3) Deposition polymerization: The intermediate monomer enters the deposition chamber in the form of gas phase for deposition polymerization. The deposition temperature is room temperature and the vacuum degree is 0.4-0.6 torr to obtain a carboxyl-containing parylene coating. (4) Grafting antimicrobial peptides or guanidine salts to obtain the product.

6. The method for preparing an antibacterial coating based on modified parylene according to claim 5, characterized in that: The temperature in step (1) is 150-170° C. and the vacuum is 1.0 torr.

7. The method for preparing an antibacterial coating based on modified parylene according to claim 5, characterized in that: The temperature in step (2) is 680° C.; the vacuum in steps (2) and (3) is 0.5 torr.

8. The method for preparing an antibacterial coating based on modified parylene according to claim 5, characterized in that: The grafting of antimicrobial peptides in step (4) comprises the following steps: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS; wherein the EDC concentration is 5-10 mg / ml, the Sulfo-NHS concentration is 0.5-5 mg / ml, the pH of the solution is 3-6, the reaction time is 1-12 hours, and the reaction temperature is 2-10°C; B. washing the obtained substrate with MES solution three times and drying with nitrogen flow to obtain a substrate after activation of carboxyl groups; C. treating the activated substrate with a PBS solution having an antimicrobial peptide concentration of 0.5-10 mg / ml; wherein the pH of the solution is 7-10, the reaction time is 12-48 hours, and the reaction temperature is 2-10°C; D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

9. The method for preparing an antibacterial coating based on modified parylene according to claim 5, characterized in that: The grafting of guanidine salt in step (4) comprises the following steps: A. Activate the carboxyl-containing substrate in a MES solution containing EDC and Sulfo-NHS; wherein the EDC concentration is 5-10 mg / ml, the Sulfo-NHS concentration is 0.5-5 mg / ml, the pH of the solution is 3-6, the reaction time is 1-12 hours, and the reaction temperature is 2-10°C; B. washing the obtained substrate with MES solution three times and drying with nitrogen flow to obtain a substrate after activation of carboxyl groups; C. treating the activated substrate with a PBS solution having a guanidine salt concentration of 2-20 mg / ml; wherein the pH of the solution is 7.5-10, the reaction time is 6-48 hours, and the reaction temperature is 2-25°C; D. The substrate after the reaction was washed with water, dried with a nitrogen stream, and stored at 4°C.

10. The method for preparing an antibacterial coating based on modified parylene according to claim 5, characterized in that: The room temperature is 23-26°C.

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