CN113583454A - Antibacterial medical material and antibacterial medical instrument - Google Patents
Antibacterial medical material and antibacterial medical instrument Download PDFInfo
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- CN113583454A CN113583454A CN202110934599.6A CN202110934599A CN113583454A CN 113583454 A CN113583454 A CN 113583454A CN 202110934599 A CN202110934599 A CN 202110934599A CN 113583454 A CN113583454 A CN 113583454A
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- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
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- C08K5/10—Esters; Ether-esters
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- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
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Abstract
The invention discloses an antibacterial medical material and an antibacterial medical apparatus; the antibacterial medical material is prepared by performing a series of treatments on raw materials such as modified lactobacillus protein, tetrahydrofuran, polyimide, an antioxidant and a lubricant and then granulating in a blending mode. The antibacterial medical material and the antibacterial medical apparatus prepared by the specific method have the advantages of safety, no toxicity, good biocompatibility, strong antibacterial capability, high mechanical fatigue resistance and the like.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to an antibacterial medical material and an antibacterial medical instrument.
Background
Medical materials generally refer to a functional structural material that can be implanted into the interior of the human body. In recent decades, the industry has conducted extensive and intensive research on biomaterials, and has become more and more significant in the promotion and promotion of the medical industry. However, due to technical limitations, currently, implantable medical devices such as catheters, vascular grafts, cardiac pacemakers, etc. are often susceptible to microbial infection during or after the implantation process, which seriously threatens the health of the patient. Surface infections are more likely to lead to the formation of microbial biofilms than common solution infections, and up to a thousand-fold increase in antibiotics are not effective in delivering appropriate and effective treatments to patients. Today, the use of large amounts of antibiotics not only adds unnecessary cost to the treatment, but also results in an immeasurable increase in microbial resistance. Hospital infection, which is generally a harmful phenomenon commonly existing in hospitals, has been one of the difficulties deeply puzzling the medical field and seriously threatens the health and safety of human beings. Hospitals are places where a large number of complex and diverse patients are concentrated, various pathogenic microorganisms are often floated at high density in hospital environments, favorable external conditions are provided for the spread of various infectious phenomena or infectious diseases, and the occurrence probability of nosocomial infection is increased. Pathogenic bacteria causing nosocomial infections include, but are not limited to, Escherichia coli, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Streptococcus, Serratia rubens, Klebsiella pneumoniae, Acinetobacter baumannii, Acinetobacter lofoenii, and the like. Generally, complete sterility of medical materials is difficult to achieve, but there is still a need in the industry for a medical material that is effective in antimicrobial and non-toxic to humans in order to reduce or alleviate nosocomial infections.
Patent CN105218810A provides an antibacterial super-slippery medical material, a preparation method thereof and an antibacterial super-slippery catheter, which are prepared by reacting a medical material matrix with an amino-terminated lubricant in a solvent; the medical material substrate comprises a medical material loaded with an antibacterial substance and a poly-dopamine layer coated on the surface of the medical material loaded with the antibacterial substance, but the performance of the obtained antibacterial medical material cannot meet increasingly harsh market requirements, the antibacterial effect is poor, and the problems of embrittlement, cracking and the like of a product after long-term use are not solved.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides an antibacterial medical material and an antibacterial medical apparatus.
In order to solve the technical problems, the invention adopts the technical scheme that:
a preparation method of an antibacterial medical material comprises the following steps:
h1 mixing the modified lactobacillus protein with tetrahydrofuran, and stirring to obtain a protein solution;
h2, mixing the polyimide with tetrahydrofuran, and stirring to obtain a polyimide solution;
h3, mixing the protein solution and the polyimide solution, and then stirring to obtain a reaction solution A;
h4, mixing the reaction solution A with water, stirring, standing, and collecting a bottom precipitate A;
h5, mixing and stirring the bottom precipitate A and water, filtering, and drying filter residues to obtain protein polyimide;
h6, putting the protein polyimide, the antioxidant and the lubricant into a high-speed mixer, and then blending to obtain a mixture;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material.
The outer surfaces of a plurality of lactobacilli are coated with a layer of protein, namely surface protein, so that the lactobacillus has remarkable recognition and resistance effects on a plurality of harmful microorganisms, and the lactobacillus is inoculated into a polyimide matrix with good biocompatibility to obtain an antibacterial medical material with good toughness, high strength and good antibacterial effect.
The invention polymerizes the modified lactobacillus protein prepared by a specific method and polyimide to obtain protein polyimide which has high mechanical strength, good biological affinity and effective antibiosis; then, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate containing benzoyloxy and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite containing phosphorous acid groups are further added as the antioxidant, so that the stability and the environmental tolerance of the antibacterial medical material are enhanced, and the antibacterial effect of the medical material is further enhanced, and good biocompatibility and low cytotoxicity are maintained to play an unexpected role; in the adopted lubricant, the hydroxyphenyl in the N- (4-hydroxyphenyl) stearic acid amide and the phthalic acid structure in the N, N-hydrogenated tallow phthalic acid amide can further enhance the antibacterial effect of the medical material, and the amide structures of the N- (4-hydroxyphenyl) stearic acid amide and the N, N-hydrogenated tallow phthalic acid amide can show good compatibility with a protein polyimide matrix, thereby improving the mechanical strength and toughness of the medical material including the rubbing resistance and the tensile strength, and simultaneously still maintaining good biocompatibility and low cytotoxicity, thereby playing an unexpected role. The polyimide and the denatured lactobacillus protein prepared by the specific method have better free energy matching relationship, so that the medical material with stronger reliability and effectiveness is prepared by combining the polyimide and the denatured lactobacillus protein.
One preferred scheme is that the preparation method of the antibacterial medical material comprises the following steps:
h1 mixing the denatured lactobacillus protein with tetrahydrofuran at bath ratio (3-5) g:100mL, stirring at 34-39 deg.C and 1200rpm for 20-40min to obtain protein solution;
h2 mixing polyimide and tetrahydrofuran at a bath ratio of (7-10) g:100mL, stirring at the rotation speed of 1000-1200rpm at 34-39 ℃ for 20-40min to obtain a polyimide solution;
h3, mixing the protein solution and the polyimide solution according to the mass ratio of 1 (4-6), and stirring at the rotating speed of 250-350rpm at 63-68 ℃ for 4-5H to obtain a reaction solution A;
h4, mixing the reaction liquid A and water according to the mass ratio of 1 (3.5-6) at 48-52 ℃, stirring at the rotating speed of 120-350rpm for 20-30min, standing for 60-80min, and collecting bottom sediment A;
h5, mixing the bottom precipitate A with water according to a bath ratio of 1g (200- & lt280) & gt mL, stirring at a rotation speed of 150- & lt300 rpm & gt for 20-40min, filtering, and drying filter residue at 40-45 ℃ for 5-7H to obtain protein polyimide;
h6, putting 140-160 parts by weight of the protein polyimide, 1-4 parts by weight of antioxidant and 2-5 parts by weight of lubricant into a high-speed mixer, and then blending for 25-40min at 65-70 ℃ and at the rotating speed of 400-600rpm to obtain a mixed material;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material; the temperature of the extruder from the feeding port to the die head is sequentially 150-.
The antioxidant is 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and/or bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite. In a preferred embodiment, the antioxidant is a mixture of 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite in a mass ratio of (1-3) to (1-3).
The lubricant is N- (4-hydroxyphenyl) stearic acid amide and/or N, N-hydrogenated tallow phthalic acid amide. In a preferred embodiment, the lubricant is a mixture of N- (4-hydroxyphenyl) stearic acid amide and N, N-hydrogenated tallow phthalic acid amide in a mass ratio of (2-5) to (2-5).
The preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing the lactobacillus protein and the ethanol water solution, and then stirring to obtain a mycoprotein dispersion liquid;
g2 mixing the carbon olefine acid, 1, 4-butanediol vinyl ether, tromethamine and the mycoprotein dispersion liquid, and then stirring to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet rays to obtain a denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein.
The method comprises the steps of firstly carrying out secondary sterilization, secondary denaturation and surface modification on the lactobacillus protein by using high-concentration ethanol, and then modifying the space interlacing structure of the lactobacillus protein and the surface of polypeptide chains of the space interlacing structure by using olefine acid, 1, 4-butanediol vinyl ether and tromethamine as modification raw materials. Wherein, the combination of the long carbon chain and the carbon-carbon double bond structure in the carbon olefine acid and the side chain in the lactobacillus protein enhances the non-polarity of the lactobacillus protein molecule, thereby enhancing the compatibility of the lactobacillus protein in a polyimide matrix; and because the specific three-dimensional folding structure of the modified lactobacillus protein has high elastic deformation capacity and elastic restoring force, the mechanical strength and toughness of the obtained protein polyimide including the rubbing resistance and the tensile strength are enhanced. The specific distance between the carbon-carbon double bonds in the all-cis-6, 9, 12-octadecatrienoic acid and the branched double-long carbon chain structure of the 8-vinyl-10-octadecenedioic acid can further effectively enhance the compatibility of the modified lactobacillus protein in the polyimide matrix and the mechanical strength and toughness of the obtained protein polyimide, thereby enhancing the anti-kneading performance of the medical material.
The 1, 4-butanediol vinyl ether can effectively influence the overlapping degree of peptide chains of the lactobacillus protein due to the relative orientation relation of two oxygen atoms and carbon-carbon double bonds in the molecule, thereby enhancing the polymerization efficiency and degree of the lactobacillus protein and a polyimide matrix. The relative positions and molecular weights of three hydroxyl groups and amino groups in tromethamine are sufficient to be associated with amino groups in the lactobacillus protein under the action of charges, so that the denatured lactobacillus protein does not lose the unique three-dimensional space folding structure with high elastic deformation capability and elastic restoring force when polymerized with a polyimide matrix.
After the lactobacillus protein is denatured by a specific method, the mechanical toughness including the rubbing resistance and the tensile strength of the polyimide substrate is enhanced, and the space folding conformation and the modified branched chain structure for catalyzing the decomposition of the germ cell wall can inhibit the activity of harmful germs by interfering the normal distribution and flowing condition of cations such as sodium ions in the cell membranes of the harmful germs including escherichia coli and staphylococcus aureus, so that the bacteriostatic effect is achieved.
The addition of the carbonic acid alkene enables the catalytic activity center of the modified lactobacillus protein to be pushed to one side of the free space through the charge effect when the modified lactobacillus protein is polymerized with the polyimide, and the proportion of the catalytic activity center of the protein exposed outside is increased, so that the bacteriostatic performance of the medical material is improved. Tromethamine enhances the stability of the denatured lactobacillus protein by a negative potential equivalent center consisting of a plurality of oxygen atoms contained in the tromethamine, and ensures that the denatured lactobacillus protein does not have the problem of premature failure in the transportation and storage processes.
The ultrahigh pressure treatment can ensure that the two adopted protective agents are fully blended into the overlapped conformation of the lactobacillus protein, and the elasticity performance of the modified lactobacillus protein is enhanced, and simultaneously, the capability of the obtained modified lactobacillus protein for decomposing the cell wall of pathogenic bacteria and interfering the internal and external electric potentials of the cell membrane of the pathogenic bacteria is enhanced.
In a preferred embodiment, the method for preparing the denatured lactobacillus protein comprises the following steps:
g1 mixing the lactobacillus protein and 75-82% ethanol water solution according to the bath ratio of 1G (70-85) mL, and then stirring at the rotation speed of 600-700rpm at the temperature of 32-36 ℃ for 20-30min to obtain the bacterial protein dispersion;
g2 mixing the carbon olefine acid, 1, 4-butanediol vinyl ether, tromethamine and the mycoprotein dispersion liquid according to the mass ratio of (5-7) to (12-16) to (1-3) to (51-55), and then stirring for 30-40min at the rotating speed of 600-800rpm at the temperature of 45-52 ℃ to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid 105-179 nm by ultraviolet rays with the power of 220-250W and the wavelength of 176-179nm for 120min to obtain a denaturing liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the prefreezing temperature is (-35) - (-30) deg.C, the prefreezing time is 3-4h, the sublimation temperature is 20-22 deg.C, the resolution temperature is 40-43 deg.C, the vacuum degree is (-0.1) - (-0.09) MPa, and the vacuum freeze-drying time is 30-35 h.
According to the invention, ultraviolet rays with specific wavelengths are used for promoting the full influence degree of the carbonic acid, the 1, 4-butanediol vinyl ether and the tromethamine on the folding condition of the polypeptide chain of the lactobacillus protein, so that the denaturation degree is more full.
The carbon olefine acid is all cis-6, 9, 12-octadecatrienoic acid and/or 8-vinyl-10-octadecenedioic acid. In a preferred scheme, the carbon olefine acid is a mixture of all-cis-6, 9, 12-octadecatrienoic acid and 8-vinyl-10-octadecenedioic acid in a mass ratio of (1-4) to (1-4).
The specific distance between the carbon-carbon double bonds in the all-cis-6, 9, 12-octadecatrienoic acid and the branched double-long carbon chain structure of the 8-vinyl-10-octadecenedioic acid can further effectively enhance the compatibility of the modified lactobacillus protein in the polyimide matrix and the mechanical strength and toughness of the obtained protein polyimide, thereby enhancing the anti-kneading performance of the medical material.
The preparation method of the lactobacillus protein comprises the following steps:
d1 inoculating the zymophyte into the fermentation medium, filtering after culturing and taking the solid A;
d2 drying the solid A to obtain a solid B;
d3, mixing and stirring the solid B and a protective agent, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein.
In a preferred embodiment, the preparation method of the lactobacillus protein comprises the following steps:
d1 at 104-105Inoculating the fermentation bacteria into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 36-38 ℃ for 175-;
d2, drying the solid A for 3-4h at 45-50 ℃ under the air pressure of 40-50kPa to obtain a solid B;
d3, mixing the solid B and the protective agent according to the mass ratio (34-37):1, stirring at the rotating speed of 600-900rpm at the temperature of 33-35 ℃ for 12-18min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 608-615MPa, and the loading time is 72-80 s.
The zymocyte is lactobacillus plantarum and/or lactobacillus rhamnosus. One preferred scheme is that the zymocyte is a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of (1-5) to (1-5).
The protective agent is zinc acetylacetonate and/or zinc isooctanoate. In a preferred scheme, the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of (1-3) to (1-3).
The number of hydrogen bond acceptors in the zinc acetylacetonate and the number of rotatable chemical bonds in the zinc isooctanoate enable the lactobacillus protein to be compounded to be used as the protective agent, so that the change degree of the space folding of small molecular peptide chains in the ultrahigh pressure treatment process of the lactobacillus protein can be further increased, and the subsequent chemical agent denaturation treatment is facilitated.
The fermentation medium contains the following raw materials: beef extract, peptone, hydrolyzed yeast protein, sodium acetate, magnesium sulfate and water. In a preferred embodiment, the fermentation medium contains the following raw materials: beef extract, peptone, hydrolyzed yeast protein, zinc gluconate, sodium acetate, magnesium sulfate, zinc lactate and water.
The zinc lactate and the zinc gluconate have obvious enhancement effect on the proliferation and development processes of the lactobacillus plantarum and the lactobacillus rhamnosus selected by the invention, so that the yield of the lactobacillus can be increased by applying the zinc lactate and the zinc gluconate to the fermentation processes of the lactobacillus plantarum and the lactobacillus rhamnosus.
In a more preferable scheme, the fermentation medium contains the following raw materials in parts by weight: 15-18 parts of beef extract, 12-15 parts of peptone, 4-8 parts of hydrolyzed yeast protein, 0.2-2.5 parts of zinc gluconate, 0.1-2 parts of sodium acetate, 0.1-1.5 parts of magnesium sulfate, 0.1-2 parts of zinc lactate and 80-87 parts of water.
The invention also provides an antibacterial medical instrument which is processed by adopting the antibacterial medical material through a conventional process.
The antibacterial medical apparatus comprises a disposable drainage bag tube, a disposable flusher, a disposable brain drainage bag, a negative pressure drainage device, a disposable liquid suction device and a disposable sputum aspirator; wherein, the negative pressure drainage device comprises a continuous pressurization type negative pressure drainage device and an adjustable high negative pressure drainage device.
The disposable drainage bag tube covers various operation requirements of thoracic cavity, abdominal cavity and the like, consists of a catheter fixing device, a drainage tube and a drainage bag, and has the functions of drainage, fixation, flushing, administration, non-operation replacement and the like during blockage. The drainage tube has the advantages of clean and thorough drainage, convenient flushing, firmness in fixation and obvious effect on reducing inflammation and placing effusion.
The disposable flushing and sucking device comprises a flushing and sucking pipe, a handle, a liquid sucking pipe and a flushing pipe. The disposable flushing and sucking device is used for flushing and sucking in an operation. The disposable flushing and sucking device can be used for flushing and sucking freely, can keep the wound surface clean, is beneficial to vascular anastomosis and improves the operation quality; the irrigator has a self-cleaning function, can always keep smooth, is provided with a large-caliber suction head, can conveniently suck out blood clots, broken bone residues and muscle and adipose tissues dropped off in an operation, and cannot cause blockage.
The disposable brain drainage bag consists of an air filter, an intracranial adjusting bottle, a drainage hose, a blocker, a liquid accumulation bag, a flow adjusting switch, a ventricular catheter, a guide steel needle and a conical joint. Is suitable for extracranial drainage for intracranial hypertension diseases caused by human cerebrospinal fluid and cerebral hemorrhage.
The negative pressure drainage device comprises a drainage liquid storage device, a liquid outlet, a bottle plug, a drainage connecting pipe, a regulator, a joint and the like; for negative pressure drainage.
The disposable sputum aspirator consists of a liquid storage bottle, a bottle cap, a sputum suction pipe, a negative pressure pipe and a vacuum control connector.
The invention has the beneficial effects that:
1. an antibacterial medical material and an antibacterial medical apparatus are provided, wherein the antibacterial medical apparatus is processed by the antibacterial medical material through a conventional process; the antibacterial medical material takes protein polyimide and the like as materials, has good biocompatibility and antibacterial capacity, is resistant to kneading, and has good toughness, strength and mechanical fatigue resistance.
2. The modified lactobacillus protein and the like prepared by the specific method are used as raw materials to prepare the antibacterial medical material, so that the antibacterial medical material with better biocompatibility, stronger antibacterial performance and rubbing resistance and the antibacterial medical apparatus prepared from the antibacterial medical material are obtained.
3. The lactobacillus protein which can be used for the modified lactobacillus protein and the preparation method thereof is obtained by taking lactobacillus plantarum and lactobacillus rhamnosus as source strains of the lactobacillus protein through ultrahigh pressure treatment and compound chemical protection of zinc acetylacetonate and zinc isooctanoate, and is further used for the antibacterial medical material.
Detailed Description
The above summary of the present invention is described in further detail below with reference to specific embodiments, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples.
Introduction of some raw materials in this application:
lactobacillus plantarum: lactobacillus plantarum, provided by China general microbiological culture Collection center, CGMCC: 1.12934.
lactobacillus rhamnosus: lactobacillus rhamnosus, provided by China general microbiological culture Collection center, CGMCC: 1.576.
polyimide, CAS: 26023-21-2, offered by Hongkingjiu, Japan, processing method: extruded, brand: ULTEM 1040A, molecular weight: 2 ten thousand.
2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate, CAS: 4196-86-5, available from Anhuzel technologies, Inc., numbered: 369373.
bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite, CAS: 126505-35-9, Shibei Shinshun Biotech, Inc.
N- (4-hydroxyphenyl) stearic acid amide, CAS: 103-99-1, available from golden Carlo chemical Co.
N, N-hydrogenated tallow phthalic acid amide, CAS: 51365-71-0, available from Shenzhen RigJi Biotech, Inc.
1, 4-butanediol vinyl Ether, CAS: 3891-33-6, available from mazell chemical technologies, inc.
All cis-6, 9, 12-octadecatrienoic acid, CAS: 506-26-3, supplied by the Merrel chemical technologies, Inc. of Shanghai.
8-vinyl-10-octadecenedioic acid, CAS: 34990-46-0, available from Michelle chemical technology, Inc. of Shanghai.
Hydrolyzed yeast protein, CAS: 100684-36-4, manufactured by Shikubei Shishui Biotech, Inc.
Example 1
A preparation method of an antibacterial medical material comprises the following steps:
h1 mixing the modified lactobacillus protein with tetrahydrofuran at bath ratio of 4g:100mL, stirring at 35 deg.C at 1200rpm for 20min to obtain protein solution;
h2 mixing the polyimide with tetrahydrofuran at a bath ratio of 9g:100mL, and stirring at the rotating speed of 1200rpm at 35 ℃ for 20min to obtain a polyimide solution;
h3, mixing the protein solution and the polyimide solution according to the mass ratio of 1:5, and stirring at 65 ℃ for 4H at the rotating speed of 320rpm to obtain a reaction solution A;
h4, mixing the reaction solution A and water at a mass ratio of 1:4 at 50 ℃, stirring at a rotating speed of 200rpm for 25min, standing for 70min, and collecting bottom sediment A;
h5, mixing the bottom precipitate A with water according to a bath ratio of 1g:220mL, stirring at a rotating speed of 180rpm for 25min, filtering, and drying filter residue at 45 ℃ for 6H to obtain protein polyimide;
h6, putting 150 parts by weight of the protein polyimide, 3 parts by weight of antioxidant and 5 parts by weight of lubricant into a high-speed mixer, and then blending for 30min at 70 ℃ at a rotating speed of 500rpm to obtain a mixture;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material; the temperature of the extruder from the feeding port to the die head was 155 deg.C, 175 deg.C, 185 deg.C, 195 deg.C, 205 deg.C in this order, and the rotation frequency of the main machine was 40 Hz.
The antioxidant is a mixture of 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite in a mass ratio of 1: 2.
The lubricant is a mixture of N- (4-hydroxyphenyl) stearic acid amide and N, N-hydrogenated tallow phthalic acid amide in a mass ratio of 3: 4.
The preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing lactobacillus protein and 80% ethanol water solution at bath ratio of 1G:85mL, and stirring at 35 deg.C and 650rpm for 25min to obtain mycoprotein dispersion;
g2 mixing the carbon olefine acid, the 1, 4-butanediol vinyl ether, the tromethamine and the mycoprotein dispersion liquid according to the mass ratio of 6:15:2:53, and then stirring at 50 ℃ and the rotating speed of 700rpm for 35min to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet ray of 240W power and 177nm wavelength for 110min to obtain denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the pre-freezing temperature is-30 deg.C, the pre-freezing time is 3h, the sublimation temperature is 20 deg.C, the resolution temperature is 40 deg.C, the vacuum degree is-0.1 MPa, and the vacuum freeze-drying time is 33 h.
The carbon olefine acid is a mixture of all-cis-6, 9, 12-octadecatrienoic acid and 8-vinyl-10-octadecenedioic acid in a mass ratio of 3: 2.
The preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 2
Essentially the same as example 1, except that: the protective agent is zinc acetylacetonate.
Example 3
Essentially the same as example 1, except that: the protective agent is zinc isooctoate.
Example 4
Essentially the same as example 1, except that:
the preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, stirring the solid B at 35 ℃ for 15min at the rotating speed of 800rpm, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 5
Essentially the same as example 1, except that:
the preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, and stirring at 35 ℃ at the rotating speed of 800rpm for 15min to obtain the lactobacillus protein; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 6
Essentially the same as example 1, except that:
the preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing lactobacillus protein and 80% ethanol water solution at bath ratio of 1G:85mL, and stirring at 35 deg.C and 650rpm for 25min to obtain mycoprotein dispersion;
g2 mixing 1, 4-butanediol vinyl ether, tromethamine and the mycoprotein dispersion liquid according to the mass ratio of 15:2:53, and then stirring at 50 ℃ at the rotating speed of 700rpm for 35min to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet ray of 240W power and 177nm wavelength for 110min to obtain denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the pre-freezing temperature is-30 deg.C, the pre-freezing time is 3h, the sublimation temperature is 20 deg.C, the resolution temperature is 40 deg.C, the vacuum degree is-0.1 MPa, and the vacuum freeze-drying time is 33 h.
The preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 7
Essentially the same as example 1, except that:
the preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing lactobacillus protein and 80% ethanol water solution at bath ratio of 1G:85mL, and stirring at 35 deg.C and 650rpm for 25min to obtain mycoprotein dispersion;
g2 mixing the carbon olefine acid, the 1, 4-butanediol vinyl ether and the mycoprotein dispersion liquid according to the mass ratio of 6:15:53, and then stirring at 50 ℃ and the rotating speed of 700rpm for 35min to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet ray of 240W power and 177nm wavelength for 110min to obtain denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the pre-freezing temperature is-30 deg.C, the pre-freezing time is 3h, the sublimation temperature is 20 deg.C, the resolution temperature is 40 deg.C, the vacuum degree is-0.1 MPa, and the vacuum freeze-drying time is 33 h.
The carbon olefine acid is a mixture of all-cis-6, 9, 12-octadecatrienoic acid and 8-vinyl-10-octadecenedioic acid in a mass ratio of 3: 2.
The preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 8
Essentially the same as example 1, except that:
the preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing lactobacillus protein and 80% ethanol water solution at bath ratio of 1G:85mL, and stirring at 35 deg.C and 650rpm for 25min to obtain mycoprotein dispersion;
g2 mixing the carbon olefine acid, the 1, 4-butanediol vinyl ether, the tromethamine and the mycoprotein dispersion liquid according to the mass ratio of 6:15:2:53, and then stirring at 50 ℃ and the rotating speed of 700rpm for 35min to obtain a prefabricated liquid;
g3 filtering the prefabricated liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the modified lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the pre-freezing temperature is-30 deg.C, the pre-freezing time is 3h, the sublimation temperature is 20 deg.C, the resolution temperature is 40 deg.C, the vacuum degree is-0.1 MPa, and the vacuum freeze-drying time is 33 h.
The carbon olefine acid is a mixture of all-cis-6, 9, 12-octadecatrienoic acid and 8-vinyl-10-octadecenedioic acid in a mass ratio of 3: 2.
The preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 9
A preparation method of an antibacterial medical material comprises the following steps:
h1 mixing lactobacillus protein and tetrahydrofuran at bath ratio of 4g:100mL, stirring at 35 deg.C at 1200rpm for 20min to obtain protein solution;
h2 mixing the polyimide with tetrahydrofuran at a bath ratio of 9g:100mL, and stirring at the rotating speed of 1200rpm at 35 ℃ for 20min to obtain a polyimide solution;
h3, mixing the protein solution and the polyimide solution according to the mass ratio of 1:5, and stirring at 65 ℃ for 4H at the rotating speed of 320rpm to obtain a reaction solution A;
h4, mixing the reaction solution A and water at a mass ratio of 1:4 at 50 ℃, stirring at a rotating speed of 200rpm for 25min, standing for 70min, and collecting bottom sediment A;
h5, mixing the bottom precipitate A with water according to a bath ratio of 1g:220mL, stirring at a rotating speed of 180rpm for 25min, filtering, and drying filter residue at 45 ℃ for 6H to obtain protein polyimide;
h6, putting 150 parts by weight of the protein polyimide, 3 parts by weight of antioxidant and 5 parts by weight of lubricant into a high-speed mixer, and then blending for 30min at 70 ℃ at a rotating speed of 500rpm to obtain a mixture;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material; the temperature of the extruder from the feeding port to the die head was 155 deg.C, 175 deg.C, 185 deg.C, 195 deg.C, 205 deg.C in this order, and the rotation frequency of the main machine was 40 Hz.
The antioxidant is a mixture of 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite in a mass ratio of 1: 2.
The lubricant is a mixture of N- (4-hydroxyphenyl) stearic acid amide and N, N-hydrogenated tallow phthalic acid amide in a mass ratio of 3: 4.
The preparation method of the lactobacillus protein comprises the following steps:
d1 at 104Inoculating the zymophyte into a fermentation culture medium according to the inoculation amount of CFU/mL, culturing at 38 ℃ for 180 hours, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Example 10
A preparation method of an antibacterial medical material comprises the following steps:
h1 mixing the modified lactobacillus protein with tetrahydrofuran at bath ratio of 4g:100mL, stirring at 35 deg.C at 1200rpm for 20min to obtain protein solution;
h2 mixing polyurethane and tetrahydrofuran at a bath ratio of 9g:100mL, and stirring at 35 ℃ at a rotation speed of 1200rpm for 20min to obtain a polyurethane solution;
h3, mixing the protein solution and the polyimide solution according to the mass ratio of 1:5, and stirring at 65 ℃ for 4H at the rotating speed of 320rpm to obtain a reaction solution A;
h4, mixing the reaction solution A and water at a mass ratio of 1:4 at 50 ℃, stirring at a rotating speed of 200rpm for 25min, standing for 70min, and collecting bottom sediment A;
h5, mixing the bottom precipitate A with water according to a bath ratio of 1g:220mL, stirring at a rotating speed of 180rpm for 25min, filtering, and drying filter residue at 45 ℃ for 6H to obtain protein polyurethane;
h6, putting 150 parts by weight of protein polyurethane, 3 parts by weight of antioxidant and 5 parts by weight of lubricant into a high-speed mixer, and then blending for 30min at 70 ℃ at a rotating speed of 500rpm to obtain a mixture;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material; the temperature of the extruder from the feeding port to the die head was 155 deg.C, 175 deg.C, 185 deg.C, 195 deg.C, 205 deg.C in this order, and the rotation frequency of the main machine was 40 Hz.
The antioxidant is a mixture of 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite in a mass ratio of 1: 2.
The lubricant is a mixture of N- (4-hydroxyphenyl) stearic acid amide and N, N-hydrogenated tallow phthalic acid amide in a mass ratio of 3: 4.
The preparation method of the modified lactobacillus protein comprises the following steps:
g1 mixing lactobacillus protein and 80% ethanol water solution at bath ratio of 1G:85mL, and stirring at 35 deg.C and 650rpm for 25min to obtain mycoprotein dispersion;
g2 mixing the carbon olefine acid, the 1, 4-butanediol vinyl ether, the tromethamine and the mycoprotein dispersion liquid according to the mass ratio of 6:15:2:53, and then stirring at 50 ℃ and the rotating speed of 700rpm for 35min to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet ray of 240W power and 177nm wavelength for 110min to obtain denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein; the process conditions of vacuum freeze-drying are as follows: the pre-freezing temperature is-30 deg.C, the pre-freezing time is 3h, the sublimation temperature is 20 deg.C, the resolution temperature is 40 deg.C, the vacuum degree is-0.1 MPa, and the vacuum freeze-drying time is 33 h.
The carbon olefine acid is a mixture of all-cis-6, 9, 12-octadecatrienoic acid and 8-vinyl-10-octadecenedioic acid in a mass ratio of 3: 2.
The preparation method of the lactobacillus protein comprises the following steps:
d1 inoculating the zymophyte into the fermentation medium with the inoculation amount of 104CFU/mL, culturing at 38 ℃ for 180h, filtering and taking a solid A; the fermentation bacteria are a mixture of lactobacillus plantarum and lactobacillus rhamnosus in a mass ratio of 4: 3;
d2, drying the solid A for 3h at 50 ℃ under the pressure of 50kPa to obtain a solid B;
d3, mixing the solid B and a protective agent according to the mass ratio of 35:1, stirring at 35 ℃ at the rotating speed of 800rpm for 15min, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein; the pressure adopted in the ultrahigh pressure treatment is 610MPa, and the loading time is 75 s; the protective agent is a mixture of zinc acetylacetonate and zinc isooctanoate in a mass ratio of 2: 1.
The fermentation medium contains the following raw materials in parts by weight: 16 parts of beef extract, 14 parts of peptone, 7 parts of hydrolyzed yeast protein, 2 parts of zinc gluconate, 2 parts of sodium acetate, 1 part of magnesium sulfate, 1 part of zinc lactate and 85 parts of water.
Test example 1
And (3) testing the antibacterial performance: the antibacterial performance of the antibacterial medical material obtained by the examples of the invention is tested according to GB/T31402-2015 test method for the antibacterial performance of the plastic surface.
Selecting Escherichia coli (ATCC 8739) and Staphylococcus aureus (ATCC 6538P) as test strains; the antibacterial medical material obtained in each example of the invention is prepared into a specification of 50mm multiplied by 50mm and 1mm in thickness, and a common PU sheet is used as a negative control, and is sterilized for standby after being irradiated by ultraviolet for 30 min; the bacterial concentration in the liquid bacterial suspension is 6.0 multiplied by 105CFU/mL; the culture condition is 35 ℃, the relative humidity is 90%, and the culture time is 24 h; each set of experiments was repeated 3 times. The antibacterial performance of the obtained antibacterial medical material is expressed by the antibacterial rate (%), and the specific calculation formula is that the antibacterial rate (%) - (average viable colony number of the ordinary PU sheet-average viable colony number of the antibacterial medical material obtained in each example)/average viable colony number of the ordinary PU sheet is multiplied by 100%.
The test results are shown in table 1.
TABLE 1 antibacterial Properties of antibacterial medical Material
The antibacterial property test result shows that the antibacterial medical material has quite remarkable antibacterial effect on escherichia coli, staphylococcus aureus and pseudomonas aeruginosa. After the lactobacillus protein is denatured by a specific method, the mechanical toughness including the rubbing resistance and the tensile strength of the polyimide substrate is enhanced, and the space folding conformation and the modified branched chain structure for catalyzing the decomposition of the germ cell wall can inhibit the activity of harmful germs by interfering the normal distribution and flowing condition of cations such as sodium ions in the cell membranes of the harmful germs including escherichia coli and staphylococcus aureus, so that the bacteriostatic effect is achieved. The addition of the carbonic acid alkene enables the catalytic activity center of the modified lactobacillus protein to be pushed to one side of the free space through the charge effect when the modified lactobacillus protein is polymerized with the polyimide, and the proportion of the catalytic activity center of the protein exposed outside is increased, so that the bacteriostatic performance of the medical material is improved. Tromethamine enhances the stability of the denatured lactobacillus protein by a negative potential equivalent center consisting of a plurality of oxygen atoms contained in the tromethamine, and ensures that the denatured lactobacillus protein does not have the problem of premature failure in the transportation and storage processes. The ultrahigh pressure treatment can ensure that the two adopted protective agents are fully blended into the overlapped conformation of the lactobacillus protein, and the elasticity performance of the modified lactobacillus protein is enhanced, and simultaneously, the capability of the obtained modified lactobacillus protein for decomposing the cell wall of pathogenic bacteria and interfering the internal and external electric potentials of the cell membrane of the pathogenic bacteria is enhanced. The polyimide and the denatured lactobacillus protein prepared by the specific method have better free energy matching relationship, so that the medical material with stronger reliability and effectiveness is prepared by combining the polyimide and the denatured lactobacillus protein. In a reactant system of the carbon-carbon olefine acid, the tromethamine and the lactobacillus protein, ultraviolet rays with specific wavelengths guide the space folding orientation and degree of polypeptide chains accessed with nonpolar side chains by influencing carbon-carbon double bonds in the carbon-carbon olefine acid and amino groups in the tromethamine, so that a three-dimensional space folding structure of the obtained modified lactobacillus protein has high elastic deformation capacity and elastic restoring force, the mechanical strength and toughness of the obtained protein polyimide including the rubbing resistance and the tensile strength are enhanced, and meanwhile, the free energy of a catalytic active center of the modified lactobacillus protein is increased, and the capacities of catalytically decomposing germ cell walls and interfering with the internal and external membrane potential balance of germ cell membranes of the modified lactobacillus protein are enhanced.
Test example 2
Cytotoxicity test: according to GB/T16886.5-2017 part 5 of the biological evaluation of medical devices: in vitro cytotoxicity test (MTT method) was used to measure the cytotoxicity of the antibacterial medical material obtained in examples 1 to 3 of the present invention. In each case, 5 replicates were run and the results averaged.
The test results are shown in table 2.
TABLE 2 cytotoxicity of antibacterial medical Material
| Cytotoxicity rating | |
| Example 1 | 0 |
| Example 2 | 0 |
| Example 3 | 0 |
The cytotoxicity test results show that the cytotoxicity grades of the antibacterial medical materials obtained in the examples 1-3 are all 0 grade, which indicates that the antibacterial medical material obtained by the invention has good biocompatibility and meets the biosafety requirement.
Test example 3
Anti-rub test: according to YY/T0681.12-2014 sterile medical device packaging test method part 12: condition A of the Soft Barrier film anti-rub Property test the anti-rub property of the antibacterial medical material obtained in each example of the present invention. The temperature of the test environment is 23 ℃ and the relative humidity is 50 percent; before the test is started, the sample is adjusted for 24 hours in an environment with the temperature of 23 ℃ and the relative humidity of 50 percent; the thickness of the test specimen was 0.5 mm. In each case, 5 replicates were run and the results averaged.
The test results are shown in Table 3.
TABLE 3 rub resistance of antibacterial medical Material
Test example 4
And (3) testing tensile strength: determination of tensile Properties of plastics according to GB/T1040.3-2006 part 3: test conditions for films and sheets the tensile strength of the antibacterial medical materials obtained in examples 1 to 4 of the present invention was measured. The width of the sample is 15mm, the length is 180mm, and the thickness is 0.8 mm; the test speed was 300 mm/min. Five samples were tested in each case and the results averaged.
The test results are shown in Table 4.
TABLE 4 tensile Strength of antibacterial medical Material
The outer surfaces of a plurality of lactobacilli are coated with a layer of protein, namely surface protein, so that the lactobacillus has remarkable recognition and resistance effects on a plurality of harmful microorganisms, and the lactobacillus is inoculated into a polyimide matrix with good biocompatibility to obtain an antibacterial medical material with good toughness, high strength and good antibacterial effect. The invention polymerizes the modified lactobacillus protein prepared by a specific method and polyimide to obtain protein polyimide which has high mechanical strength, good biological affinity and effective antibiosis; then, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate containing benzoyloxy and bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite containing phosphorous acid groups are further added as the antioxidant, so that the stability and the environmental tolerance of the antibacterial medical material are enhanced, and the antibacterial effect of the medical material is further enhanced, and good biocompatibility and low cytotoxicity are maintained to play an unexpected role; in the adopted lubricant, the hydroxyphenyl in the N- (4-hydroxyphenyl) stearic acid amide and the phthalic acid structure in the N, N-hydrogenated tallow phthalic acid amide can further enhance the antibacterial effect of the medical material, and the amide structures of the N- (4-hydroxyphenyl) stearic acid amide and the N, N-hydrogenated tallow phthalic acid amide can show good compatibility with a protein polyimide matrix, thereby improving the mechanical strength and toughness of the medical material including the rubbing resistance, and simultaneously still maintaining good biocompatibility and low cytotoxicity, thereby playing an unexpected role.
The method comprises the steps of firstly carrying out secondary sterilization, secondary denaturation and surface modification on the lactobacillus protein by using high-concentration ethanol, and then modifying the space interlacing structure of the lactobacillus protein and the surface of polypeptide chains of the space interlacing structure by using olefine acid, 1, 4-butanediol vinyl ether and tromethamine as modification raw materials. Wherein, the combination of the long carbon chain and the carbon-carbon double bond structure in the carbon olefine acid and the side chain in the lactobacillus protein enhances the non-polarity of the lactobacillus protein molecule, thereby enhancing the compatibility of the lactobacillus protein in a polyimide matrix; and because the specific three-dimensional folding structure of the modified lactobacillus protein has high elastic deformation capacity and elastic restoring force, the mechanical strength and toughness of the obtained protein polyimide including the rubbing resistance and the tensile strength are enhanced. The specific distance between the carbon-carbon double bonds in the all-cis-6, 9, 12-octadecatrienoic acid and the branched double-long carbon chain structure of the 8-vinyl-10-octadecenedioic acid can further effectively enhance the compatibility of the modified lactobacillus protein in the polyimide matrix and the mechanical strength and toughness of the obtained protein polyimide, thereby enhancing the anti-kneading performance of the medical material. The 1, 4-butanediol vinyl ether can effectively influence the overlapping degree of peptide chains of the lactobacillus protein due to the relative orientation relation of two oxygen atoms and carbon-carbon double bonds in the molecule, thereby enhancing the polymerization efficiency and degree of the lactobacillus protein and a polyimide matrix. The relative positions and molecular weights of three hydroxyl groups and amino groups in tromethamine are sufficient to be associated with amino groups in the lactobacillus protein under the action of charges, so that the denatured lactobacillus protein does not lose the unique three-dimensional space folding structure with high elastic deformation capability and elastic restoring force when polymerized with a polyimide matrix. In a reactant system of the carbon-carbon olefine acid, the tromethamine and the lactobacillus protein, ultraviolet rays with specific wavelengths guide the space folding orientation and degree of polypeptide chains accessed with nonpolar side chains by influencing carbon-carbon double bonds in the carbon-carbon olefine acid and amino groups in the tromethamine, so that a three-dimensional space folding structure of the obtained modified lactobacillus protein has high elastic deformation capacity and elastic restoring force, the mechanical strength and toughness of the obtained protein polyimide including the rubbing resistance and the tensile strength are enhanced, and meanwhile, the free energy of a catalytic active center of the modified lactobacillus protein is increased, and the capacities of catalytically decomposing germ cell walls and interfering with the internal and external membrane potential balance of germ cell membranes of the modified lactobacillus protein are enhanced. The number of hydrogen bond receptors in the zinc acetylacetonate and the number of rotatable chemical bonds in the zinc isooctanoate enable the modified lactobacillus protein to be more fully changed in the spatial folding of small molecular peptide chains in the ultrahigh pressure treatment process when the modified lactobacillus protein is compounded to be used as the protective agent, and the obtained modified lactobacillus protein has stronger capacity of decomposing the cell walls of pathogenic bacteria and interfering the intracellular and extracellular potentials of the pathogenic bacteria; the obtained modified lactobacillus protein has three-dimensional space conformation with high elastic deformation capacity and elastic restoring force, and simultaneously, the long carbon chain of the carbon olefine acid connected to the side chain of the protein molecule extends to the external space, so that the modified lactobacillus protein is favorable for fusion between the modified lactobacillus protein and a polyimide matrix in the subsequent modification of a chemical reagent, and the good compatibility effect can enhance the service reliability and the mechanical toughness including the kneading resistance and the tensile strength of the medical material.
After the lactobacillus protein is denatured by a specific method, the mechanical toughness including the rubbing resistance and the tensile strength of the polyimide substrate is enhanced, and the space folding conformation and the modified branched chain structure for catalyzing the decomposition of the germ cell wall can inhibit the activity of harmful germs by interfering the normal distribution and flowing condition of cations such as sodium ions in the cell membranes of the harmful germs including escherichia coli and staphylococcus aureus, so that the bacteriostatic effect is achieved.
The addition of the carbonic acid alkene enables the catalytic activity center of the modified lactobacillus protein to be pushed to one side of the free space through the charge effect when the modified lactobacillus protein is polymerized with the polyimide, and the proportion of the catalytic activity center of the protein exposed outside is increased, so that the bacteriostatic performance of the medical material is improved. Tromethamine enhances the stability of the denatured lactobacillus protein by a negative potential equivalent center consisting of a plurality of oxygen atoms contained in the tromethamine, and ensures that the denatured lactobacillus protein does not have the problem of premature failure in the transportation and storage processes.
The ultrahigh pressure treatment can ensure that the two adopted protective agents are fully blended into the overlapped conformation of the lactobacillus protein, and the elasticity performance of the modified lactobacillus protein is enhanced, and simultaneously, the capability of the obtained modified lactobacillus protein for decomposing the cell wall of pathogenic bacteria and interfering the internal and external electric potentials of the cell membrane of the pathogenic bacteria is enhanced.
The polyimide and the denatured lactobacillus protein prepared by the specific method have better free energy matching relationship, so that the medical material with stronger reliability and effectiveness is prepared by combining the polyimide and the denatured lactobacillus protein.
Claims (10)
1. A preparation method of lactobacillus protein is characterized by comprising the following steps:
d1 inoculating the zymophyte into the fermentation medium, filtering after culturing and taking the solid A;
d2 drying the solid A to obtain a solid B;
d3, mixing and stirring the solid B and a protective agent, and then carrying out ultrahigh pressure treatment to obtain the lactobacillus protein.
2. The method for producing a lactobacillus protein according to claim 1, wherein: the zymocyte is lactobacillus plantarum and/or lactobacillus rhamnosus.
3. A lactobacillus protein characterized by: the method for producing a lactobacillus protein according to claim 1 or 2.
4. A method for preparing modified lactobacillus protein is characterized by comprising the following steps:
g1 mixing the lactobacillus protein of claim 3 with an aqueous solution of ethanol, and then stirring to obtain a mycoprotein dispersion;
g2 mixing the carbon olefine acid, 1, 4-butanediol vinyl ether, tromethamine and the mycoprotein dispersion liquid, and then stirring to obtain a prefabricated liquid;
g3 irradiating the prefabricated liquid with ultraviolet rays to obtain a denatured liquid;
g4 filtering the denatured liquid to obtain filter residue, and then carrying out vacuum freeze-drying treatment on the filter residue to obtain the denatured lactobacillus protein.
5. The method for producing a denatured lactobacillus protein as set forth in claim 4, characterized in that: the carbon olefine acid is all cis-6, 9, 12-octadecatrienoic acid and/or 8-vinyl-10-octadecenedioic acid.
6. A denatured Lactobacillus protein, characterized in that: the modified Lactobacillus protein of claim 4 or 5, which is obtained by the method.
7. The preparation method of the antibacterial medical material is characterized by comprising the following steps:
h1 mixing the modified lactobacillus protein of claim 6 with tetrahydrofuran, stirring to obtain a protein solution;
h2, mixing the polyimide with tetrahydrofuran, and stirring to obtain a polyimide solution;
h3, mixing the protein solution and the polyimide solution, and then stirring to obtain a reaction solution A;
h4, mixing the reaction solution A with water, stirring, standing, and collecting a bottom precipitate A;
h5, mixing and stirring the bottom precipitate A and water, filtering, and drying filter residues to obtain protein polyimide;
h6, putting the protein polyimide, the antioxidant and the lubricant into a high-speed mixer, and then blending to obtain a mixture;
h7, putting the mixture into a hopper of an extruder, and extruding and granulating to obtain the antibacterial medical material.
8. The method for preparing an antibacterial medical material as claimed in claim 7, wherein: the antioxidant is 2, 2-bis [ (benzoyloxy) methyl ] -1, 3-propanediol dibenzoate and/or bis (2,4, 6-tri-tert-butylphenyl) pentaerythritol diphosphite.
9. The antibacterial medical material is characterized in that: the antibacterial medical material according to claim 7 or 8.
10. An antibacterial medical device, characterized in that: the antibacterial medical material as claimed in claim 9 is processed by conventional process.
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Application publication date: 20211102 |