CN108452418A - A kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings - Google Patents

A kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings Download PDF

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Publication number
CN108452418A
CN108452418A CN201810054269.6A CN201810054269A CN108452418A CN 108452418 A CN108452418 A CN 108452418A CN 201810054269 A CN201810054269 A CN 201810054269A CN 108452418 A CN108452418 A CN 108452418A
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China
Prior art keywords
antibacterial peptide
mdc
tracheal catheter
loaded
coatings
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CN201810054269.6A
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Chinese (zh)
Inventor
卢雪梅
桂水清
张伦
刘阿龙
唐亚男
陈朝霞
金小宝
朱家勇
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Guangdong Pharmaceutical University
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Guangdong Pharmaceutical University
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Priority to CN201810054269.6A priority Critical patent/CN108452418A/en
Priority to PCT/CN2018/083402 priority patent/WO2019140796A1/en
Publication of CN108452418A publication Critical patent/CN108452418A/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/04Tracheal tubes
    • A61M16/0402Special features for tracheal tubes not otherwise provided for
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08Materials for coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08Materials for coatings
    • A61L29/085Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/04Tracheal tubes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/02General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0205Materials having antiseptic or antimicrobial properties, e.g. silver compounds, rubber with sterilising agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/02General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0238General characteristics of the apparatus characterised by a particular materials the material being a coating or protective layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2207/00Methods of manufacture, assembly or production

Abstract

The invention belongs to biomedical materials fields, and in particular to a kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings.The tracheal catheter is fixed and sustained-release matrix with chitosan gel using antibacterial peptide MDC as antiseptic, carries out antibacterial surface coating to tracheal catheter, the tracheal catheter for being loaded with antibacterial peptide MDC coatings is made.Antibacterial peptide MDC sequences such as SEQ ID NO:Shown in 1.The tracheal catheter provided by the invention for being loaded with antibacterial peptide MDC coatings has significant anti-microbial property, can effectively prevent bacteria planting and growth.Therefore, the tracheal catheter provided by the invention for being loaded with antibacterial peptide MDC coatings is applied in artificial trachea cannula and lung ventilator, the generation of trachea cannula Ventilator Associated Pneumonia will be reduced or delays, the body and mind pain for reducing medical economy burden, mitigating patient has bright prospects.

Description

A kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings
Technical field
The invention belongs to biomedical materials fields, and in particular to a kind of tracheal catheter being loaded with antibacterial peptide MDC coatings and Preparation method and application.
Background technology
Trachea cannula is the simple and direct effective method that unobstructed air flue is established in critical patients rescue, and trachea cannula is established Artificial airway, become most important one " lifeline " with patient.Need progress trachea cannula machinery logical in clinic daily The patient of gas is countless, and the implantation material infections relating in complication becomes clinician's urgent problem to be solved.Machinery is logical Most common and most serious complication-Ventilator Associated Pneumonia during gas, incidence, case fatality rate are high, once occur again Less than effective control, patient, which will have to face, pulls out tracheal catheter, again intubation or tracheotomy, considerably increases patient and controls It treats risk and body and mind torments, medical economy burden will also be significantly greatly increased.The anti-infective therapy that takes at present, air flue humidification, effectively There is no the generations for reducing Ventilator Associated Pneumonia well for the measures such as nursing.Studies have shown that breathing caused by trachea cannula Road infect and the common pathogen of Ventilator Associated Pneumonia be escherichia coli, Acinetobacter bauamnnii, staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella Pneumoniae etc., and these bacteriums in intubation can in succession or overlapping occur, table Reveal multidrug resistant even general drug resistance, especially bacterial biofilm once being formed, the barrier action due to biomembrane and biology In film the features such as bacterium low metabolism, drug resistance can be improved hundreds and thousands of times so that curative effect causes anxiety, and patient is usually due to that can not have Effect control respiratory tract infection and it is dead.
Currently, the antibacterial surface that sight is focused on trachea cannula conduit by domestic and foreign scholars is modified, do not change original Conduit shape makes it obtain anti-microbial property, reduces bacterial growth, Ventilator Associated Pneumonia is prevented with this.Publication No. CN A kind of Chinese patent application " medical endotracheal tube with safe and efficient anti-microbial property " of 103948973A is with ethyl orthosilicate For silicon source, with gamma-methyl allyl acyloxypropyl trimethoxysilane, methyltriethoxysilane for organic phase precursor, with nothing Machine nano silver is that through sol-gel method organosilicon Ag-carried antibacterial colloidal sol is made, then using trachea cannula conduit as base in antiseptic Material carries out antibacterial surface coating, organosilicon Ag-carried antibacterial coating trachea cannula conduit is prepared, which not only has Efficient antibiotic property, and coating silver ion is hardly precipitated, the advantages such as surface is smooth not to adhere to sputum, and side reaction is extremely low, symbol Close the needs of clinical trachea cannula.The Chinese patent application of Publication No. CN 103933617A is " a kind of with anti-bacterial attachment The preparation method of tracheal catheter " is changed by preparing the colloidal sol of photocatalysis antibacterial containing iodine, carrying out surface hydroxylation to PVC tracheal catheters Property, on PVC tracheal catheters surface form photocatalysis antibacterial membrane modifying, the tracheal catheter that keeps surface modified has good Anti-bacterial attachment performance and visible light-inducing sterilization ability, durable antibacterial effect, chemical stability it is high.
However, the preparation method that above-mentioned published tracheal catheter antibacterial surface is modified is more complicated, and it is all made of inorganic Chemical classes antiseptic, there are some potential safety problemss, it is difficult to avoid the problem that residual toxicity.
The appearance of antibacterial peptide (Antimicrobial peptides, AMP) in recent years is tracheal catheter antibacterial surface coating Research bring new thinking.Antibacterial peptide is a kind of small molecule for resisting extraneous pathogenic infection that Immune System generates Polypeptide is widely present in insect, plant, animal and human body, and wherein insect antimicrobial peptide cecropin is that the mankind have found earliest A kind of antibacterial peptide.Antibacterial peptide has a series of noticeable biological activities, including antibacterial, anti-inflammatory, antiviral, anti-parasitism Worm inhibits tumour cell and immunoregulatory activity etc..Antibacterial peptide Musca domestica cecropin (MDC) are this seminars The areas the ORF overall length of a kind of insect antimicrobial peptide cloned from common house-fly grub fat-body cDNA library, the gene is 192bp, can be compiled The precursor protein of 63 amino acid of code, 1~23 amino acids are to guard the signal peptide of 4 peptides ending, and mature peptide contains 40 Amino acid, early-stage study find that antibacterial peptide MDC shows extremely strong in-vitro antibacterial to many reference cultures and clinical drug-resistant bacterial strain Activity can destroy bacterial cell membrane or act on intracellular target site across cell membrane, and mechanism of action is unique, thin to normal human Born of the same parents' toxicity, side effect is small.
Currently, not being used to prepare trachea cannula conduit about the antimicrobial component using antibacterial peptide MDC as biological coating Relevant report.
Invention content
In order to solve the problems existing in the prior art, the purpose of the present invention is to provide a kind of antibacterial peptide MDC coatings of being loaded with Tracheal catheter and preparation method thereof.
It is another object of the present invention to provide the tracheal catheters for being loaded with antibacterial peptide MDC coatings in artificial trachea Application in intubation and lung ventilator.
To achieve the goals above, the present invention is achieved by the following technical programs:
Antibacterial peptide MDC provided by the invention, amino acid sequence such as SEQ ID NO:Shown in 1, specifically, the amino Acid sequence is:GWLKKI GKKIE RVGQH TRDAT IQTIG VAQQA ANVAA TLKG.
Antibacterial peptide MDC provided by the invention is made using solid-state chemical reaction method method, specifically, is closed by Peptide synthesizer At polypeptide crude product;Then solid-phase synthesis synthesis polypeptide is used;The polypeptide of synthesis is carried out using reversed-phase high performance liquid chromatography again pure Change, and the polypeptide of synthesis is identified using electrospray mass spectrometry, to complete the preparation of polypeptide.
The present invention also provides a kind of preparation methods of the tracheal catheter being loaded with antibacterial peptide MDC coatings comprising with Lower step:
(1) medical chitose is dissolved in water for injection, the coagulant liquid that mass-volume concentration is 3~5% is made, is then added A certain amount of antibacterial peptide solution makes the final concentration of 0.2mg/mL of antibacterial peptide, mixed with 300 revs/min of speed stirring at 30 DEG C Even, prepares coating film liquid, at room temperature, with supersonic oscillations 20 minutes, the bubble removed in coating film liquid was several to get antibacterial peptide Tetrose composite membrane liquid;
(2) natural by antibacterial peptide chitosan composite membrane liquid dip-coating made from step (1) or curtain coating in tracheal catheter base material Drying or 50 DEG C of solidifications are dry to get tracheal catheter.
It is effective as antibacterial using chitosan gel as fixed and sustained-release matrix, antibacterial peptide MDC in above-mentioned preparation method Coating film liquid is made in ingredient, and the chitosan is the high-molecular compound chitin (chitin) purified by crab shell, through de- A kind of N-acetyl group manufactured poly glucosamine after deep processing again is that a kind of having good biocompatibility, biodegradable The medical high polymer polysaccharose substance of property and biological activity.Further medical chitose gel obtained it is nontoxic, it is nonirritant, Apyrogenetity, without challeng, haemolysis and there is no thermal stability, the adverse reactions such as no mutagenesis, lethal, also slight suppression Bacterium acts on, and fixes in the present invention as antibacterial peptide MDC and sustained-release matrix, makes its long-term antibacterial effect of performance.
The present invention chooses antibacterial peptide MDC as biological coating, so that the surface of trachea cannula conduit is obtained anti-microbial property, effectively Prevent bacteria planting and growth, will reduce or delay the generation of trachea cannula Ventilator Associated Pneumonia, when elongate catheter indwelling Between, strive for the quality time for patient's rescue, improves treatment success rate, the body and mind that can also reduce medical economy burden, mitigate patient Pain.In addition, the tracheal catheter for being loaded with antibacterial peptide MDC coatings of R & D design of the present invention, inanimate object adverse reaction meet clinic The needs of trachea cannula, are with a wide range of applications.
Compared with prior art, the invention has the advantages that:
(1) there is the tracheal catheter provided by the invention for being loaded with antibacterial peptide MDC coatings significant antibiotic property, sterilizing rate to reach 98% or more, the antibacterial peptide MDC mechanism of action is unique, is not likely to produce drug resistance, breaks through traditional antibacterials and is given birth to bacterium The limitation of object film effect provides the tracheal catheter with safe and efficient anti-microbial property for clinic.
(2) preparation process of the tracheal catheter provided by the invention for being loaded with antibacterial peptide MDC coatings is simple, safe, nothing Adverse reaction has a extensive future.
Description of the drawings
Fig. 1 is the high-efficient liquid phase chromatogram of antibacterial peptide MDC.
Fig. 2 is the mass spectrogram of antibacterial peptide MDC.
Fig. 3 is scanning electron microscopic observation blank control tracheal catheter surface Acinetobacter bauamnnii biomembrane morphosis.
Fig. 4 is scanning electron microscopic observation chitosan gel controls group tracheal catheter surface Acinetobacter bauamnnii biomembrane form knot Structure.
Fig. 5 is scanning electron microscopic observation antibacterial peptide MDC chitosan gel composite coating tracheal catheters surface Acinetobacter bauamnnii Biomembrane morphosis.
Specific implementation mode
The present invention is made with specific embodiment with reference to the accompanying drawings of the specification and further being elaborated, the embodiment It is served only for explaining the present invention, be not intended to limit the scope of the present invention.Test method used in following embodiments is such as without spy Different explanation, is conventional method;Used material, reagent etc., unless otherwise specified, for the reagent commercially obtained And material.
1 solid-state chemical reaction method method synthetic antibacterial peptide MDC of embodiment
The amino acid sequence of antibacterial peptide MDC is:Ac-GWLKKI GKKIE RVGQH TRDAT IQTIG VAQQA ANVAA TLKG-NH2, such as SEQ ID NO:Shown in 1, contain 40 amino acid, theoretical isoelectric point is 10.56, and theoretical molecular weight is 4299.04.The preparation of antibacterial peptide MDC carries out one by one from C-terminal to N-terminal, is completed by Peptide synthesizer, the specific steps are:
(1) Fmoc-X (X is first amino acid of antibacterial peptide MDC C-terminals) is linked into Wang resins first, then taken off X-Wang resins are obtained after removing Fmoc groups;By Fmoc-Y-Trt-OH, (9- fluorenes methoxy carboxyl-trimethyl-Y, Y is antibacterial peptide again Second amino acid of MDC C-terminals);It is synthesized to N-terminal from C-terminal successively according to this program, until synthesis finishes, obtains sloughing Fmoc The resin of the side chain protection of group;
(2) in peptide resin obtained above, cutting reagent is added, 20 DEG C are protected from light lower reaction 2h, filtering;Precipitation TFA (trifluoroacetic acid) washs, and washing lotion is mixed with above-mentioned filtrate, and Rotary Evaporators concentration adds the precooling nothing of 10 times or so volumes Water ether, -20 DEG C of precipitation 3h, is precipitated white powder object, centrifuges 10min with 2500g, collects precipitation, then washed with anhydrous ether Precipitation, vacuum drying, obtains polypeptide, wherein cutting reagent by TFA, water and TIS (tri isopropyl chlorosilane) according to mass ratio 95: 2.5:2.5 mixing;
(3) 0.2mol/L sodium sulphate (phosphoric acid is adjusted to pH7.5) is used to carry out column equilibration 30min, with 90% aqueous acetonitrile Liquid dissolves polypeptide, and filtering, C18 reverse phase normal pressure columns, using gradient elution, (eluant, eluent is methanol and aqueous sodium persulfate solution according to volume Than being 30:70~70:30 mixing), flow velocity 1mL/min, detection wave is 220nm, collects main peak, freeze-drying;
(4) reverse phase C18 columns are recycled to be further purified, eluent A is 0.1%TFA/ aqueous solutions;Eluent B is 0.1% TFA/ acetonitrile solutions, wash-out concentration is 25%B~40%B, elution time 12min, flow velocity 1mL/min, then is ibid collected Main peak is lyophilized to get refined antibacterial peptide MDC;
(5) refined antibacterial peptide MDC is obtained by reversed-phase high performance liquid chromatography and electron spray mass spectrometry analysis, reverse phase by above-mentioned High-efficient liquid phase chromatogram as shown in Figure 1, mass spectrogram as shown in Fig. 2, the results show that the purity of antibacterial peptide MDC be more than 95%, molecule Amount is 4299.36, almost the same with theoretical molecular weight.
It is prepared by the tracheal catheter that embodiment 2 is loaded with antibacterial peptide MDC coatings
(1) medical chitose is dissolved in water for injection, the coagulant liquid that mass-volume concentration is 4% is made, is then added one Quantitative antibacterial peptide solution is made the final concentration of 0.2mg/mL of antibacterial peptide, is stirred and evenly mixed with 300 revs/min of speed at 30 DEG C, Prepares coating film liquid with supersonic oscillations 20 minutes, removes the bubble in coating film liquid to get antibacterial peptide chitin at room temperature Sugared composite membrane liquid;
(2) by antibacterial peptide chitosan composite membrane liquid dip-coating made from step (1) or curtain coating in PVC tracheal catheter base materials, Natural drying or 50 DEG C of solidifications are dried to get the tracheal catheter of antibacterial peptide MDC coatings is loaded with.
Test example one, safety evaluatio
(1) cell toxicity test
According to cell toxicity test method as defined in GB/T16886.5-2003, to being loaded with the tracheae of antibacterial peptide MDC coatings Catheter samples carry out cell toxicity test.The tracheae for being loaded with antibacterial peptide MDC coatings is prepared with 10% calf serum MEM culture mediums Catheter samples leaching liquor culture NCTC colone929 cells (l cell), and with blank PVC trachea cannula conduits Sample leaching liquor makees negative control, and 5g/L phenol solutions make positive control.
Test result:The cellular morphology of negative control is normal, and adherent growth is good, there is discrete particle in endochylema, acellular Dissolving;The cell growth of positive control is bad, and 90% or more cell is rounded or cell dissolution;It is loaded with antibacterial peptide MDC coatings Cellular morphology is normal in tracheal catheter sample leaching liquor, and adherent growth is good, there is discrete particle, acellular dissolving in endochylema.It carries There are the tracheal catheter sample of antibacterial peptide MDC coatings and blank PVC trachea cannula conduit sample leaching liquors to be all chosen as nontoxic, judgement point Grade is 0 grade (it is qualified that cell-cytotoxic reaction, which is 0 grade or 1 grade).48 hours monitoring cell OD570 of culture and opposite increment degree, carry The tracheal catheter sample and blank PVC trachea cannula conduit samples leaching liquor for having antibacterial peptide MDC coatings all judge to be classified as 0 grade, The tracheal catheter sample cell toxicity test result for being loaded with antibacterial peptide MDC coatings is qualification.
(2) acute systemic toxicity
According to GB/T16886.11-2011 standards, observation is loaded with the tracheal catheter sample of antibacterial peptide MDC coatings to mouse urgency Property general toxic reaction.Blank PVC trachea cannula conduits sample and the tracheal catheter sample for being loaded with antibacterial peptide MDC coatings 0.9% sodium chloride injection leaching liquor is given in a single dose in a manner of tail vein injection, and accordingly to extract medium as blank control. 4,24,48 and 72h after injection observes mouse toxicity response situation.As a result, it has been found that:Blank control liquid group, blank PVC trachea cannulas Catheter samples and the tracheal catheter sample leaching liquor group for being loaded with antibacterial peptide MDC coatings are showed no abnormal response.The result shows that:It is loaded with The acute systemic toxicity result of the tracheal catheter sample leaching liquor of antibacterial peptide MDC coatings is to meet non-toxic requirement, and empty The acute systemic toxicity indifference of white PVC trachea cannula conduit samples.
Test example two, antibiotic property evaluation
Using Acinetobacter bauamnnii as representative, simulation clinic ICU Ventilator Acquired Acinetobacter bauamnnii biomembranes infection is built Vertical Acinetobacter bauamnnii biomembrane external model.Using blank tracheal catheter sample without any processing as blank control group, together When set chitosan gel controls group, liquid flowing state in simulated respiration machine conduit, each group tracheal catheter is impregnated in 1.0 × 105In Acinetobacter bauamnnii bacterium solution, culture for 24 hours, takes 10ul maceration extracts to be coated with inoculation on LB culture mediums, 35 DEG C are incubated overnight Afterwards, clump count is counted, the relative growth situation of bacterium is observed, to show its anti-microbial property.
The result of contrast experiment confirms:Blank tracheal catheter sample bacterium normal growth, chitosan gel controls group tracheae Catheter samples bacterial growth reduces unobvious, and sterilizing rate is 5% or so, and antibacterial peptide MDC chitosan gel composite coating tracheaes Catheter samples bacterial growth, which significantly reduces, even to disappear, and sterilizing rate is up to 98% or more.
Wherein, scanning electron microscopic observation tracheal catheter surface biological film morphosis is as shown in Figure 3-Figure 5, as a result shows:It is empty The white visible a large amount of bacterial adhesions of tracheal catheter (Fig. 3) that compare are agglomerating, form big blocky biomembrane;Chitosan gel controls group tracheae Conduit (Fig. 4) biofilm thickness and area are reduced;Antibacterial peptide MDC chitosan gel composite coating tracheal catheters (Fig. 5) It is rarely seen to be dispersed in bacterium and bacterium cell deforms, is broken, outer membrane is detached from, content leaks;
In addition, agar plate colony counting method result is also shown:Antibacterial peptide MDC chitosan gel composite coating tracheal catheters Surface viable count is substantially reduced compared with blank control group and chitosan gel controls group.
It the above is only the preferred embodiment of the present invention, it is noted that above-mentioned preferred embodiment is not construed as pair The limitation of the present invention, protection scope of the present invention should be subject to claim limited range.For the art For those of ordinary skill, without departing from the spirit and scope of the present invention, several improvements and modifications can also be made, these change Protection scope of the present invention is also should be regarded as into retouching.
Sequence table
<110>Guangdong pharmaceutical university
<120>A kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings
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Thr Ala Ala Ala Thr Ile Gly Thr Ile Gly Val Ala Gly Gly Ala Ala
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Ala Val Ala Ala Thr Leu Leu Gly
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Claims (6)

1. a kind of tracheal catheter, which is characterized in that the tracheal catheter surface is loaded with antibacterial peptide MDC as biological coating.
2. tracheal catheter according to claim 1, which is characterized in that the amino acid sequence such as SEQ of the antibacterial peptide MDC ID NO:Shown in 1.
3. the preparation method of tracheal catheter according to claim 1 or 2, which is characterized in that include the following steps:
(1) medical chitose is dissolved in water for injection, the coagulant liquid that mass-volume concentration is 3~5% is made, be then added certain The antibacterial peptide solution of amount is made the final concentration of 0.2mg/mL of antibacterial peptide, is stirred and evenly mixed with 300 revs/min of speed at 30 DEG C, system Standby coating film liquid with supersonic oscillations 20 minutes, removes the bubble in coating film liquid to get antibacterial peptide chitosan at room temperature Composite membrane liquid;
(2) by antibacterial peptide chitosan composite membrane liquid dip-coating made from step (1) or curtain coating in tracheal catheter base material, natural drying Or 50 DEG C of solidifications are dry to get tracheal catheter.
4. the preparation method of tracheal catheter according to claim 3, which is characterized in that the tracheal catheter base material is poly- Vinyl chloride.
5. according to application of any tracheal catheters of claim 1-4 in artificial trachea cannula and lung ventilator.
6. a kind of antibacterial peptide MDC, amino acid sequence such as SEQ ID NO:Shown in 1.
CN201810054269.6A 2018-01-19 2018-01-19 A kind of tracheal catheter and its preparation method and application being loaded with antibacterial peptide MDC coatings Pending CN108452418A (en)

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PCT/CN2018/083402 WO2019140796A1 (en) 2018-01-19 2018-04-17 Endotracheal tube loaded with antimicrobial peptide mdc coating and preparation method therefor and application thereof

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111973805A (en) * 2019-08-16 2020-11-24 苏州吉美瑞生医学科技有限公司 Application of antibacterial peptide hCAP18/LL-37 in anti-infection bioengineering lung
CN112057718A (en) * 2020-08-24 2020-12-11 浙江隆泰医疗科技股份有限公司 Barrier material for respiratory system
CN115666237A (en) * 2020-03-27 2023-01-31 山尼饮料责任有限公司 Antibacterial tubular catheter

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101628133A (en) * 2009-08-11 2010-01-20 中国人民解放军第三军医大学第一附属医院 Medical catheter carrying slow-release antibiotic coating and preparation method thereof
CN102675428A (en) * 2012-04-20 2012-09-19 广东药学院 Liver targeting cell-penetrating antiviral fusion polypeptide as well as coding gene and application thereof
CN103948973A (en) * 2014-04-21 2014-07-30 蒋旭宏 Medical tracheal catheter with safe and effective antibacterial performance

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101428157B (en) * 2008-12-23 2012-12-19 福州大学 Process for producing medical endotracheal tube with anti-bacterial adherence function and photoinduction disinfection function
CN103933617B (en) * 2014-05-04 2015-08-12 福州大学 A kind of preparation method with the endotracheal tube of anti-bacterial attachment
CN107459568B (en) * 2017-08-22 2020-12-25 广东药科大学 Musca domestica cecropin derived peptide M27-39 and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101628133A (en) * 2009-08-11 2010-01-20 中国人民解放军第三军医大学第一附属医院 Medical catheter carrying slow-release antibiotic coating and preparation method thereof
CN102675428A (en) * 2012-04-20 2012-09-19 广东药学院 Liver targeting cell-penetrating antiviral fusion polypeptide as well as coding gene and application thereof
CN103948973A (en) * 2014-04-21 2014-07-30 蒋旭宏 Medical tracheal catheter with safe and effective antibacterial performance

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
李思熳等: "蛇毒抗菌肽OH-CATH和壳聚糖作为人工植入物涂层的抗菌性研究", 《重庆医学》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111973805A (en) * 2019-08-16 2020-11-24 苏州吉美瑞生医学科技有限公司 Application of antibacterial peptide hCAP18/LL-37 in anti-infection bioengineering lung
CN115666237A (en) * 2020-03-27 2023-01-31 山尼饮料责任有限公司 Antibacterial tubular catheter
CN112057718A (en) * 2020-08-24 2020-12-11 浙江隆泰医疗科技股份有限公司 Barrier material for respiratory system

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