CN103751854B - Antibiotic medical catheter - Google Patents
Antibiotic medical catheter Download PDFInfo
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- CN103751854B CN103751854B CN201410024761.0A CN201410024761A CN103751854B CN 103751854 B CN103751854 B CN 103751854B CN 201410024761 A CN201410024761 A CN 201410024761A CN 103751854 B CN103751854 B CN 103751854B
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Abstract
The invention discloses a kind of antibiotic medical catheter and preparation method thereof, antibiotic medical catheter component contains silver series inorganic antibiosis material and medical macromolecular materials, it is characterized in that: described silver series inorganic antibiosis material mainly comprises zirconium phosphate and carries silver; Zirconium phosphate carries silver: zirconium phosphate carries silver-colored 0.01%-10%; Medical macromolecular materials 90%-99.99%; The weight percent content that zirconium phosphate carries silver element in silver is 1-20%; Zirconium phosphate carries silver and has desirable volume average particle size, grain-size characteristic parameter and specific surface area; Make the antibiotic medical catheter of the present invention meet high security, widely antibacterial bacterium spectrum, high antibacterial, antibacterial components slow release, antibacterial effect persistent period long, Clinical practice safety, the feature such as convenient is applicable to all kinds of medical catheter demand.
Description
Technical field
The invention belongs to technical field of medical instruments, relate to a kind of antibiotic medical catheter, particularly relate to a kind of antibiotic medical catheter containing the anti-material of silver-based inorganic.
Background technology
The extensive use in daily life of antibacterial concept, technology and product; For medical applications, antimicrobial medical devices and product are very important indispensable especially.Wherein, medical catheter is the necessary of medical act already, usually implant into body is needed to carry out traumatic diagnosis and treatment, such as at Ink vessel transfusing inlying catheter, central vein catheter, use catheter, tracheal intubation in urinary tract treatment, be all in the necessary and medical act frequently carried out of general curative operation.Except above-mentioned conventional medical conduit, along with medical skill rapid progress, the conduit of multitube chamber and composite pipeline pattern also produces successively, and put and stay the time in body relatively to increase, also become the important tool of carrying out the medical acts such as blood flow monitoring, transfusion, hemodialysis, administration and intravenous nutrition support now, the utilization and the demand that show medical catheter acutely increase.
But, the use of medical catheter is used to invariably accompany the risk infected, such as, Catheter Related Bloodstream Infection (catheter-related bloodstream infections), it is modal infection kind in multiple position nosocomial infection, medical catheter has become the key factor of concurrent conduit dependency nosocomial infection, and especially immunodeficiency or diabetics, infant, old people etc. more easily catheter-related Infections: Clinical Study occur.
For example, urinary tract infection accounts for 40% of nosocomial infection, is one of modal nosocomial infection and wherein relevant to conduit infection accounts for about 50%.In the use procedure of catheter, once the incidence rate of bacteriuria disease is about 1%-5% after simple urethral catheterization usually, and during repeated multiple times urethral catheterization, the incidence rate of bacteriuria disease about reaches 50%, and if the urethral catheterization time more than 14 days, urinary tract infection incidence rate is up to 90%-100%.And for example, about have 30%-50% to need to accept through vein fluid infusion or other associated treatment in inpatient, causing blood system to infect after Vein pipe insertion is main and common complication.Also have report to point out in addition, catheter in blood vessel infections relating is that sb.'s illness took a turn for the worse and one of main causes of death for critical patient.In the U.S., will consume nearly 5,000,000 central venous catheters (CVC) every year in the treatment, the infection relevant to conduit is more than 800,000 examples, and the medical expenses such as consequent extra infection are up to tens billion of dollar.Also as, tracheal intubation is important measures and the means of rescuing acute and chronic respiratory failure, after tracheal intubation, because trachea-bronchial epithelial cell contacts with the direct of external environment, lose the defense reaction of nasal meatus and oropharynx, and often form bacterial biofilm (biofilm) on tracheal intubation surface, also easily there is nosocomial infection.
As can be seen here, there is antibacterial or antiviral medical catheter can help to reduce above-mentioned infection risk, therefore, promote the antibiotic property of medical catheter, pathogen is avoided directly or indirectly to cause infection via conduit, and providing the various medical catheter that can maintain anti-microbial property for a long time, is the urgent problem needing to solve.
In view of the foregoing, current antibiotic medical catheter mainly contains following several, but its defect using restriction and not yet overcome of each tool, be described as follows:
1, coating type antibiotic medical catheter: medical catheter surface is coated with antibacterial or relies on adhesive that antibacterial is coated in uses catheter surface.Main preparation methods is distributed in silicone oil or other materials by anti-biotic material, then plated film or be coated to medical catheter surface.The defect of this conduit is that coating easily comes off, and antibiotic substance slow-releasing is poor, and antibacterial effect can not be lasting, and coming off of coating is potential risk factor, and safety is lower.
2, flood osmosis type antibiotic medical catheter: medical catheter be impregnated in quaternary ammonium salt, antibiotic or other antibacterial, make antibiotic substance infiltrate medical catheter.The defect of this conduit is that antibiotic substance release is uneven, and early stage, burst size was large, and the antibacterial effect persistent period is short, only about 7 days, and there is potential safety hazard equally.
3, mix antibacterial to medical catheter: adopt the porous material such as montorillonite clay to adsorb organic antibacterial agent as support materials, then this support materials is joined in silicone rubber make medical catheter.The antibacterial bacterium spectrum of this kind of anti-microbial catheter is narrower, and antibiotic substance release is too fast, and antibacterial effect persistence is poor, and the pot-life is shorter.In addition, its antibacterial temperature tolerance is poor, and can only be applied to silicone rubber anti-microbial catheter, limitation is large.
Obvious, the safety of above-mentioned antibiotic medical catheter lower, the antibacterial persistent period shorter (ageing short), antibacterial bacterium spectrum is narrower, the pot-life is shorter, the restriction of material aspect is comparatively large, antibacterial existence itself is peeled off or discharges uneven or discharge too fast risk and drawback.
The focus that the art very pays close attention to is still about antibacterial subject under discussion.Except above-mentioned antibiotic medical catheter, the metal ions such as known silver, copper, zinc have anti-microbial property, and are widely used in antibacterial application.Wherein, silver antibacterial effect mainly rely in silver ion and antibacterial-SH group combine kill antibacterial, can not drug resistance be produced to antibacterial; And silver ion as disinfectant and antibacterial time, usually exist with the form of silver nitrate, but use with silver nitrate solution form, both inconvenient, its purposes is also limited; In addition, be unstable, easily can be reduced into argent, cause the problem of variable color and long-time stability aspect when silver ion is exposed in light and heat, therefore, people turn to the solid antimicrobial of exploitation metal ion.
The solid antimicrobial technology developed now mainly utilizes inorganic carrier to carry out loaded metal ion, and this kind of inorganic carrier material comprises zeolitic material, the Montmorillonitum of ion-exchange type carrier; And the silicon oxide, zinc oxide etc. of nonionic crossover carrier.Prepared in conjunction with silver-series antibacterial agent and inorganic carrier and the performance of silver series inorganic antibiosis material that is that obtain still has it to limit, such as, the acid resistance of the framing structure of the clay mineral such as zeolitic material, Montmorillonitum itself is poor, easily make silver ion stripping in an acidic solution, therefore cause antibacterial effect there is no persistence; And for example zeolite based material is lower for the load capacity of silver, therefore effective antibacterial effect is provided as enough silver will be reached, the then addition of necessary desilver series inorganic antibiosis material, the mechanical performance of medical catheter goods certainly will be affected, be difficult to meet and carry flexibility required by antibacterial venous cannulation and lubricity.
In addition, the research and development object that ion-exchange type carrier zirconium phosphate material also becomes inorganic carrier is in recent years belonged to.As a rule, the reason why zirconium phosphate is applicable to carrier is its layer structure feature, be conducive to receiving load antibacterial metal ions, and it has the excellent characteristics such as thermostability, chemical-resistant, low heat expansion.When zirconium phosphate is as ion-exchange type carrier, mainly contain two kinds of microscopic appearances, a kind of the hexahedron of the length of side such as is, another kind is approximate circle lamellar, and adopt zirconium phosphate load silver to be namely the gap structure utilizing zirconium phosphate as antibacterial, by adjustment Ag ion exchange technique, zirconium phosphate can be obtained and carry ag material, there is high silver carrying.Generally speaking, the load silver element percentage by weight that the zirconium phosphate of high silver carrying carries the antibacterial powder obtained by ag material is greater than 12%, under this state, the zirconium phosphate antibacterial powder of carrying obtained by ag material has broad spectrum antibacterial and excellent bactericidal property, its antibacterial effect, far beyond other inorganic antiseptics, has the feature that the organic antibacterial agents such as slow-releasing is good, safety is good, flexibility (adaptability) of operation is good, discoloration-resistant performance is good are incomparable simultaneously.
But, when applying silver series inorganic antibiosis material to medical catheter, then must consider following problem:
1, few additive requires: the inconsistency that the mechanical performance of the antibacterial effect produced as above-mentioned high silver carrying and medical catheter goods has.Therefore, in response to the lubricity of antibacterial venous cannulation and the requirement of flexibility, the addition of silver series inorganic antibiosis material must reduce, and just can avoid the lubricity on antibacterial venous cannulation, flexibility produces excessive impact, to meet the mechanical property requirements of antibacterial venous cannulation.
2, the requirement of high anti-microbial property: as previously mentioned, due to silver series inorganic antibiosis material, in antibiotic medical catheter, can only add with extremely low amount, and high anti-microbial property is very important fundamental importance for medical catheter, therefore, the silver series inorganic antibiosis material of employing must have high anti-microbial property to overcome the problem of few additive.
3, high security performance: antibiotic medical catheter is used for human body and implants, and in silver series inorganic antibiosis material or antibacterial powder, requires that its material purity is also very high, and can not as catheter product, a large amount of plastic dispersing agent that adopts is processed.
4, desirable powder granularity distribution: because silver series inorganic antibiosis material uses its superfine powder mostly, in order to reduce the impact on antibiotic medical catheter pliability, needing silver series inorganic antibiosis powder to have ultra-fine granularity and granularity narrow ditribution and could reduce impact to antibiotic medical catheter key property.
In sum, how a high antibiotic property, safety take into account the antibiotic medical catheter of Practical Performance are provided, become the primary problem solved at present.
Summary of the invention
, good anti-bacterial effect, antibacterial components slow release wide for above-described bacterium safe to use, antibacterial spectrum, antibacterial effect persistent period long, Clinical practice safety, the demand for medical catheter such as convenient, and prior art level urgently needs the technical problem that overcomes, the object of this invention is to provide one and meets the demand medical catheter.
According to object of the present invention, medical catheter proposed by the invention is reached high resistance bacterium property under carrying ag material addition at limited zirconium phosphate and is had both above-mentioned ideal performance, thus replacing medical catheter number of times can be reduced, Clinical practice safely, conveniently, the conduit dependency nosocomial infection that effective reduction produces because using medical catheter, show the related medical expenses such as reduction infection, save medical resources.
In addition, technical scheme of the present invention combines silver system antibacterial components and zirconium phosphate inorganic carrier, preparation draws the zirconium phosphate Ag-carried antibacterial material of particle size distribution characteristic excellence, this zirconium phosphate Ag-carried antibacterial material is mixed in medical catheter material, medical catheter can be made to have the features such as high antibiotic property, slow release, safety.
Object of the present invention can be implemented by the following technical programs: provide a kind of antibiotic medical catheter, and its component contains silver series inorganic antibiosis material and medical macromolecular materials, it is characterized in that: described silver series inorganic antibiosis material mainly comprises zirconium phosphate and carries silver; Described zirconium phosphate carries silver: zirconium phosphate carries silver-colored 0.01%-10%; Medical macromolecular materials 90%-99.99%; The weight percent content that described zirconium phosphate carries silver element in silver is 1-20%; The volume average particle size that described zirconium phosphate carries silver is 0.3-10 μm; The grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-2 μm; D (0.5)=0.3-5 μm; D (0.9)=0.3-10 μm; The specific surface area that described zirconium phosphate carries silver is 1-20m
2/ g.
According to aforesaid antibiotic medical catheter of the present invention, the weight percent of percentage by weight and described medical macromolecular materials that described zirconium phosphate carries silver is: zirconium phosphate carries silver-colored 0.1%-8%; Medical macromolecular materials 92%-99.9%.According to aforementioned antibiotic medical catheter, the weight percent of percentage by weight and described medical macromolecular materials that described zirconium phosphate carries silver is: zirconium phosphate carries silver-colored 0.5%-5%; Medical macromolecular materials 95%-99.5%.
According to aforesaid antibiotic medical catheter of the present invention, the weight percent content that described zirconium phosphate carries silver element in silver is 2-15%.According to aforementioned antibiotic medical catheter, the weight percent content that described zirconium phosphate carries silver element in silver is 4-10%.
According to aforesaid antibiotic medical catheter of the present invention, the volume average particle size that described zirconium phosphate carries silver is 0.4-5 μm.According to aforementioned antibiotic medical catheter, the volume average particle size that described zirconium phosphate carries silver is 0.5-3 μm.
According to aforesaid antibiotic medical catheter of the present invention, the grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-1.5 μm; D (0.5)=0.4-3 μm; D (0.9)=0.5-8 μm.According to aforementioned antibiotic medical catheter, the grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.4-1 μm; D (0.5)=0.5-2 μm; D (0.9)=0.6-5 μm.
According to aforesaid antibiotic medical catheter of the present invention, the specific surface area that described zirconium phosphate carries silver is 1.5-15m
2/ g.According to aforementioned antibiotic medical catheter, the specific surface area that described zirconium phosphate carries silver is 2-10m
2/ g.
According to described antibiotic medical catheter, described medical macromolecular materials can be selected from medical plastic or medical grade silicon rubber.Wherein, described medical plastic is optional from polyurethane (PU), polrvinyl chloride (PVC), polypropylene (PP) or polyethylene (PE); Described medical grade silicon rubber can be selected from dimethyl silicone rubber, Methylethyl silicone rubber, methyl phenyl vinyl silicone rubber or fluorosioloxane rubber.
According to described antibiotic medical catheter, described antibiotic medical catheter can further containing being selected from barium sulfate, calcium carbonate, titanium dioxide and toner or or the filler of their combination.
According to object and the technical scheme of aforementioned the present invention, the present invention proposes a kind of method preparing antibiotic medical catheter simultaneously,
Described method prepares after zirconium phosphate carries silver in advance, more described zirconium phosphate is carried silver and make described antibiotic medical catheter with medical macromolecular materials, it is characterized in that comprising following steps:
(1) zirconium phosphate that a crystalline phase is single is provided;
(2) with alkylamide compound, pre-intercalation is carried out to described zirconium phosphate, described alkylamide compound is inserted the single zirconium phosphate of described crystalline phase, obtain the intercalation zirconium phosphate product that interlamellar spacing increases;
(3) described intercalation zirconium phosphate product and silver ion are exchanged, thus obtain zirconium phosphate and carry silver; And
(4) described zirconium phosphate is carried silver and prepare described antibiotic medical catheter with described medical macromolecular materials;
Wherein, it is 1-20% that the described zirconium phosphate be prepared into according to described method carries the weight percent content that silver has a silver element; The volume average particle size that described zirconium phosphate carries silver is 0.3-10 μm; The grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-2 μm; D (0.5)=0.3-5 μm; D (0.9)=0.3-10 μm; The specific surface area that described zirconium phosphate carries silver is 1-20m
2/ g; It is 0.01%-10% at the weight percent of described antibiotic medical catheter that described method makes described zirconium phosphate carry silver; And the weight percent of described medical macromolecular materials is 90%-99.99%.
According to the described method preparing antibiotic medical catheter, it is characterized in that, described alkylamide compound component is selected from n-butylamine, n-propylamine and their combination.
Accompanying drawing explanation
The existing zirconium phosphate of Fig. 1 carries the powder granularity distribution characteristics datagram of silver products.
Fig. 2 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 1 gained.
Fig. 3 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 2 gained.
Fig. 4 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 3 gained.
Fig. 5 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 4 gained.
Fig. 6 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 5 gained.
Fig. 7 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 6 gained.
Fig. 8 carries the powder granularity distribution characteristics datagram of silver according to the zirconium phosphate of the embodiment of the present invention 7 gained.
Detailed description of the invention
First illustrate, the reagent that the present invention adopts, the source of solvent are without any restriction, and reagent, the solvent of any commercialization all can be used as raw material, and rank is also without specific restriction.Test or reagent, material used in embodiment, except indicating especially, all come from common market channel.In addition, as herein without dated especially, the percentage % about adopting time " content " and " ratio " is below used all to refer to that percentage by weight forms.
Term of the present invention " antibacterial " is a kind of health concept of strick precaution microorganism of broad sense, it is made a general reference in fact and is present in external pathogenic microorganisms as caused the health concept of live infection risk in the biological intrusive bodies such as antibacterial, mycete, virus for preventing or lowering, therefore, the Antibacterial Mechanism mentioned by the present invention, correlation technique and product are all covered by the category of this broad sense.The present invention's it " antibacterial " is focussed in particular on the PI problem caused by medical catheter equipment in medical procedure, and related notion and technology have been known by the art personnel, therefore no longer repeat specification.
In the past in organic antibacterial agent field, the antibacterial being often suitable for plastics and rubber processing mainly contained phenolic compound, organo-metallic compound, substituted arene compound, heterocyclic compound, aminated compounds etc.Representative kind comprises: BCM(2-benzimidazole carbamate), TBZ(2-(4-thiazolyl) phenylpropyl alcohol thiazole), DCOIT(4, the chloro-Kathon of 5-bis-), triclosan (trichloro hydroxyl diphenyl ether), copper 8-quinolinolate, OBPA(10,10 '-oxo two fen master oh give a tongue-lashing), the iodo-2-propargyl butyl carbamate of IPBC(3-), OPP(2-xenol) etc.But these organic antibacterial agents are applied to directly to enter in medical catheter that human body uses and make eventually have safety risks, such as: above-mentioned, BCM, DCOIT8-copper quinolinate has skin irritation; OBPA, containing arsenic, can not be used as medical catheter antibacterial.
On the other hand, owing to adopting plastic processing when medical catheter manufactures, be indispensable operation, wherein, more need through high-temperature technology process, and organic antibacterial agent be usually thermo-labile.Therefore, the antibacterial inorganic material that the present invention adopts thermal stability good as the heat resistant type anti-biotic material meeting plastic processing and require, and proposes a kind ofly to meet the biological safety of height, the desirable medical catheter of stable performance.
Such as, but the active component of antibacterial inorganic material is metal ion mostly: arsenic ion (As
2+), antimony ion (Sb
2+), cadmium ion (Cd
2+), plasma selenium (Se
2+), mercury ion (Hg
2+), zinc ion (Zn
2+), copper ion (Cu
2+), silver ion (Ag
+) etc., but the inorganic material that the huge toxicity that wherein arsenic, antimony, cadmium, selenium, hydrargyrum plasma cause directly gets rid of these classifications is used in the medical instruments field of human body cannula material.For other zinc ion, copper ion, silver ion, investigate through excess syndrome, it in the toxicity intensity sequence for people is: zinc ion > copper ion > silver ion; And the antibacterial for the source of infection, it kills competency degree sequence is then silver ion > copper ion > zinc ion.Therefore and safety low to people's toxicity is selected, to high " silver ion " of cytotoxin as main antibacterial active constituents.
About the antibacterial taking silver ion as active component, mainly comprise: " silver compound ", " nanometer silver " and " carrier silver ", differ from one another and defect to be overcome.Be described as follows.
Silver compound mainly comprises silver chloride, organic silver etc., and silver compound is in the plastic cement course of processing, and silver ion is easily reduced into silver-colored simple substance, causes antibacterial activity to decline and plastic material variable color, is extremely unfavorable for preparing medical catheter material.
The antibacterial that nanometer silver is is active component with silver-colored individual particle, its particle diameter is at about 1-50nm, can exist with monodisperse status in water, but, in plastic processing, because device of plastic processing by the particle dispersion of below 100nm, so the industrial scattering problem that cannot solve nanometer silver, cannot hinder the progress of correlation technique.
Carrier silver is then be active component with silver, rely on carrier structure load silver element as antibacterial, and carrier comprises titanium dioxide, zeolite, glass, zirconium phosphate etc.Wherein, TiO 2 carrying ag material and zeolite carry ag material development the earliest.TiO 2 carrying silver technology is using titanium dioxide granule as matrix, relies on nanotechnology ag material to be deposited to the technology of titanium dioxide surface, the carrier silver that this technology is produced, and its discoloration is poor, and anti-microbial property is also poor.Zeolite carries the gap structure load silver ion that ag material relies on zeolite, and its space is comparatively large, and the dissolution rate of silver ion is very fast, and silver ion is easy to dissociate to carrier surface in a large number, causes ionic silver to be reduced into elemental silver, causes anti-microbial property to reduce and variable color.Glass carries the material that silver is the lattice defect load silver element relying on glass, and its silver carrying amount of this material is low, generally all below 3%, causes its anti-microbial property, discoloration-resistant performance poor.
On the other hand, about inorganic antibacterial agent material, its Antibacterial Mechanism mainly can be divided into two large classes: rely on photocatalysis or rely on the activity of metal ion own to reach anti-microbial property, but photocatalysis mode needs light source just can be effective, it has been used to limit, again in the actual use of medical catheter, obviously cannot meet this lighting requirements, therefore photocatalysis antibacterial material is not suitable for medical catheter material.
For above-mentioned defect, present invention employs zirconium phosphate and carry silver, its space shows and is less than Zeolite support, on silver ion rate of release controlling good, discharge even, antibacterial bacterium spectrum and activity is better, discoloration-resistant performance is good, do not need to rely on light source, the ability of negative silver carrying amount is good, be more satisfactory inorganic antibacterial material.
Therefore, the present invention is directed to the technical scheme that above-mentioned technical problem and demand propose is adopt silver ion as antibacterial active constituents, and in conjunction with inorganic material zirconium phosphate, draw the silver series inorganic antibiosis material (zirconium phosphate carries silver) of anti-microbial property excellence, and described silver series inorganic antibiosis material and multiple medical macromolecular materials are arranged in pairs or groups use, making anti-microbial property comparatively conventional medical conduit more preferably medical catheter, is the technological deficiency of antibiotic medical catheter technical field and demand and the concrete solution of proposition.
Below describe technical scheme proposed by the invention in detail, and correspondence enumerates experimental example and embodiment, to absolutely prove the excellent effect that the antibiotic medical catheter of the present invention can be reached.
First illustrate, medical catheter proposed by the invention, its component contains silver series inorganic antibiosis material and medical macromolecular materials, as the medical catheter of human body intubate.Wherein, silver series inorganic antibiosis material mainly comprises zirconium phosphate and carries silver.So-called " zirconium phosphate carries silver " refers to material based on zirconium phosphate herein, in any form the such as mode such as ion exchange or absorption, the material obtained by composition of load " silver ".Wherein, the kind of zirconium phosphate and pattern are not limited substantially; According to the preferred embodiment of the present invention, zirconium phosphate more preferably kind is the zirconium phosphate with three-layer laminated structure or pore structure, has good Adsorption For Ag ionic nature.
And the kind of the composition of above-mentioned " silver " comprises the salt of silver element, silver ion or argentiferous, if can actually have antibiotic property containing silver components, be all applicable to the present invention; And according to the preferred embodiment of the present invention, ideal with silver ion, ion-exchange process simple and easyly can be utilized to be loaded on zirconium phosphate, there is the feature of handled easily.
The medical macromolecular materials general reference that antibiotic medical catheter of the present invention adopts is all is customarily used in the natural material source or made plastics, fiber, resin, rubber, silica gel and other elastomers of preparing conduit.For example, current is fiber and plastic resin at the macromolecular material that medical industry is the most frequently used, wherein PVC and PP plastic material is comparatively general, other materials comprises: Merlon (PC), acrylonitrile-butadiene-styrene copolymer, (ABS), Merlon and acrylonitrile-butadiene-styrene copolymer (PC/ABS) plastic material etc.
Specifically because the performance purposes of antibiotic medical catheter with use object, described medical macromolecular materials are more preferably be selected from medical plastic or medical grade silicon rubber is ideal.Wherein, medical plastic is selected from polyurethane (PU), polrvinyl chloride (PVC), polypropylene (PP) or polyethylene (PE); Described medical grade silicon rubber can be selected from dimethyl silicone rubber, Methylethyl silicone rubber, methyl phenyl vinyl silicone rubber or fluorosioloxane rubber.In addition, antibiotic medical catheter of the present invention can use barium sulfate, calcium carbonate, titanium dioxide and toner further or be selected from aforesaid barium sulfate, calcium carbonate, titanium dioxide and toner mutually combine the filler that forms, adjust its product properties with the demand of the goods (such as centre pipe, catheter, tracheal intubation) further according to variety classes antibiotic medical catheter.
Silver and described medical macromolecular materials are carried about aforementioned phosphate zirconium, both weight percents in overall antibiotic medical catheter are the 0.01%-10% that zirconium phosphate carries that silver accounts for medical catheter integral duct weight, and the medical macromolecular materials of correspondence account for the 90%-99.99% of medical catheter integral duct weight; Preferred ratio is, accounts for the 0.1%-8% of medical catheter integral duct weight, and the medical macromolecular materials of correspondence account for the 92%-99.9% of medical catheter integral duct weight; Preferred ratio is that zirconium phosphate carries silver and accounts for the 0.5%-5% of medical catheter integral duct weight and the medical macromolecular materials of correspondence account for the 95%-99.5% of medical catheter integral duct weight.
Zirconium phosphate based on the invention described above carries silver, for the content of silver, because already described and the present invention is not limited the kind of the composition of " silver " above, the therefore salt of silver element, silver ion or argentiferous, as long as what actually can have antibiotic property contains silver components, be all applicable to the present invention.In fact, according to the technical contradiction between the requirement of high anti-microbial property and conduit mechanical performance, silver-based inorganic antibacterial agent, in antibiotic medical catheter, can only add with extremely low amount, and this just requires that the silver-based inorganic antibacterial agent adopted has high anti-microbial property.Therefore, in response to above-mentioned requirements, solution provided by the invention is to provide a kind of zirconium phosphate and carries silver, and have the weight percent content (under be called " silver carrying amount ") of desirable silver element, the silver carrying amount that zirconium phosphate of the present invention carries silver is 1-20%; Preferred 2-15%; More preferably 4-10%.
For the zirconium phosphate further illustrating this carries the silver-colored effect brought for anti-microbial property, first the anti-microbial property overview of existing commercially available conventional antibacterial is described.
First, anti-microbial property about medical catheter is assessed, owing to causing the main bacteria seed of bacteriological infection to be escherichia coli, staphylococcus aureus, Candida albicans and bacillus pyocyaneus (Pseudomonas aeruginosa) etc. by medical catheter clinically, therefore following according to these four basic strains of escherichia coli, staphylococcus aureus, Candida albicans and bacillus pyocyaneus, anti-microbial property zirconium phosphate being carried to silver is verified.
In addition, in order to contrast is existing conventional organic antibacterial agent, and wherein, TBZ is better to the effect of fungi and yeasts, poor to the effect of antibacterial; The minimum inhibitory concentration (MIC) of triclosan (Triclosan) to escherichia coli, staphylococcus aureus, pneumobacillus and Candida albicans is very little, to escherichia coli and staphylococcus aureus at 1ppm (μ g/ml) below, but to bacillus pyocyaneus, its minimum inhibitory concentration is greater than 1000ppm, almost do not have antibacterial effect, antibacterial bacterium spectrum is narrow; IPBC and OPP is fine to antifungal effect, but very poor to antibacterial, and if colibacillary MIC value is 1000ppm, staphylococcus aureus is 200ppm.Aforementioned now conventional organic antibacterial agent antibacterial bacterium spectrum is narrower as can be seen here, can not meet clinical screened antibacterial scope, be difficult to the requirement meeting anti-microbial catheter broad-spectrum antiseptic.
For the zirconium phosphate further illustrating this carries the effect brought for its anti-microbial property under different silver carrying amount condition of silver, illustrate with following experimental example 1.
Experimental example 1: zirconium phosphate of the present invention carries the anti-microbial property of silver
For inspection zirconium phosphate carries the anti-microbial property of silver in different silver carrying amount situation, the zirconium phosphate being 3.0%, 6.0%, 9.0% for silver carrying amount respectively carries silver and has carried out minimum inhibitory concentration test (MIC).Method of testing is GB15979-2002 " disinfection technology standard " 2.1.8.3 minimum inhibitory concentration testing experiment (agar dilution), and test strain is escherichia coli, staphylococcus aureus, Candida albicans and bacillus pyocyaneus.The minimum inhibitory concentration test result of the silver-loaded zirconium phosphate antibacterial powder of three kinds of different silver carrying amounts is as shown in table 1, and the less expression of its numerical value is better to the antibacterial ability of this strain.
For the anti-microbial property of inorganic antiseptic, current national standard: the MIC test request of inorganic antiseptic to escherichia coli, staphylococcus aureus, Candida albicans is 800ppm(i.e. 800 μ g/ml).Therefore from the test result presented of table 1, the anti-microbial property of three kinds of silver carrying amounts (3.0%, 6.0%, 9.0%), all far above national standard, can obtain very good anti-microbial property.
Wherein, silver carrying amount be 6.0% zirconium phosphate carry silver antibacterial performance outstanding especially, silver carrying amount be 6.0% the zirconium phosphate MIC that carries silver be obviously better than silver carrying amount be 3.0% zirconium phosphate carry silver, and the zirconium phosphate that MIC and silver carrying amount that the zirconium phosphate that silver carrying amount is 6.0% carries silver are 9% carries silver-colored MIC is more or less the same.
It should be noted that, silver carrying amount be 6.0% zirconium phosphate carry silver except all having good anti-microbial property to escherichia coli, staphylococcus aureus, Candida albicans, bacillus pyocyaneus, silver carrying amount be 6.0% zirconium phosphate carry silver close to the MIC value of each test strain, show it and there is good broad spectrum antibacterial performance and outstanding bactericidal property.Therefore, silver carrying amount of the present invention is that 6.0% zirconium phosphate carries silver and belongs to comparatively ideal implementation condition.
The zirconium phosphate Ag-carried antibacterial the performance test results of table 1, different silver carrying amount of the present invention
According to above-mentioned data, continuing for silver carrying amount is the anti-microbial property assessment that 6.0% zirconium phosphate carries that silver carries out clinical strains.Assessing the method for testing adopted is with reference to GB15979-2002 " disinfection technology standard " 2.1.8.3 minimum inhibitory concentration testing experiment (agar dilution), test Pseudomonas cepacia, the standard strains such as bacillus pyocyaneus, escherichia coli, Pseudomonas Maltophilia, the three kinds of strains simultaneously clinical separation obtained: staphylococcus epidermidis #1, staphylococcus epidermidis #2, staphylococcus epidermidis #3 carry out minimum inhibitory concentration (MIC) test.Result of the test is as shown in table 2.1 Yu table 2.2.
Table 2.1, silver carrying amount of the present invention are that 6.0% zirconium phosphate carries silver for standard strain anti-microbial property test result
Table 2.2, silver carrying amount of the present invention are that 6.0% zirconium phosphate carries silver for clinical strain anti-microbial property test result
From the data of table 2.1 and table 2.2, silver carrying amount is that 6.0% zirconium phosphate carries silver and has excellent antibacterial bacterium spectrum (broad-spectrum antimicrobial effect) and anti-microbial property, shows zirconium phosphate of the present invention and carries the component material that silver is desirable antibiotic medical catheter.Especially contrasting current national standard for the requirement of inorganic antiseptic is: inorganic antiseptic requires to be 800 μ g/ml to the MIC of escherichia coli, staphylococcus aureus, Candida albicans, the antibacterial powder anti-microbial property that the present invention proposes to carry for the preparation of the zirconium phosphate of antibiotic medical catheter silver is higher than national standard 10 times, can guarantee to reach high anti-microbial property with extremely low addition.
Therefore, according to aforesaid data, the invention provides a kind of antibiotic medical catheter overcoming existing technical problem, when zirconium phosphate being used for medical catheter technology according to the present invention, bedded zirconium phosphate is adopted to carry silver-colored technology, the zirconium phosphate obtaining high silver carrying carries the antibacterial powder of silver, when being actually used in manufacture medical catheter, can reduce the addition that zirconium phosphate carries the antibacterial powder of silver.Wherein, zirconium phosphate carry silver silver carrying amount thinks silver carrying amount 4-10% most preferably, wherein with silver carrying amount 6% zirconium phosphate carry silver antibacterial performance the most outstanding.
In addition, in order to reduce the impact to antibiotic medical catheter key property, the active component of medical catheter that the present invention proposes is that the zirconium phosphate of superfine powder carries silver, its obtained antibacterial powder is adopted to be prepared the operation of antibiotic medical catheter, there is desirable powder granularity distribution characteristics and specific surface area character, comprise: fine granularity and granularity narrow ditribution; Specifically, the volume average particle size that the zirconium phosphate that the present invention proposes carries silver is 0.3-10 μm, preferred 0.4-5 μm, more preferably 0.5-3 μm.D (0.1) numerical value that the zirconium phosphate that the present invention proposes carries silver-colored grain-size characteristic parameter is 0.3-2 μm, preferred 0.3-1.5 μm, more preferably 0.4-1 μm; D (0.5) numerical value is 0.3-5 μm, preferred 0.4-3 μm, more preferably 0.5-2 μm; D (0.9) numerical value is 0.3-10 μm, preferred 0.5-8 μm, more preferably 0.6-5 μm.The specific surface area that the zirconium phosphate that the present invention proposes carries silver is 1-20m
2/ g, preferred 1.5-15m
2/ g, more preferably 2-10m
2/ g.
Moreover, the zirconium phosphate that the invention described above proposes carries the grain diameter characteristic of silver, and to show its granularity not only fine and concentrated, more fully avoid the particle diameter that zirconium phosphate carries silver to fall into the nanoscale scope may producing harm to organism, achieve the balance between material improvement with compromise between security.Its reason is, the material of known nanoscale can penetrate blood brain barrier, blood-eye barrier and blood-testis barrier, thus may jeopardize the safety of organism.And research shows that nano material can have an impact to biology in cellular level, subcellsular level, gene, protein level and whole animal level.Compare with the micron-sized granule of material of the same race, the biological activity of general nano-particle is stronger, also may be larger to the potential hazard of body.Therefore zirconium phosphate according to the present invention carries aluminium powder particle size distribution and is all greater than 0.3 μm, is beneficial to the material getting rid of known nanoscale produces safely harm hidden danger to organism, guarantees to be applied to medical catheter to human safety.
The zirconium phosphate that above the present invention proposes carries silver, achieves and reduces the impact of antibacterial powder on antibiotic medical catheter pliability and the security performance for human body that zirconium phosphate carries silver.Above scheme, medical catheter of the present invention contains zirconium phosphate, and to carry silver-colored purity high and without the need to adopting plastic dispersing agent to process in a large number, achieve the requirement of medical catheter high safety performance.
According to technical scheme proposed by the invention, aforementioned every feature that zirconium phosphate of the present invention carries silver comprises silver carrying amount, volume average particle size, particle size distribution characteristics, grain-size characteristic parameter, specific surface area etc., is all the key factors of giving antibiotic medical catheter ideal performance of the present invention.
First, zirconium phosphate of the present invention carries the solution that silver-colored excellent granularity characteristic brings existing antibiotic medical catheter technical problem, the zirconium phosphate that have impact on that the particle property that zirconium phosphate carries silver shows carries silver-colored antibacterial product performance, the demand of the silver carrying amount of zirconium phosphate is reduced, maintains the product attribute after it makes medical catheter simultaneously and reach good anti-microbial property.Specifically, the volume average particle size that the zirconium phosphate that the present invention proposes carries silver is 0.3-10 μm; Be preferably 0.4-5 μm; Be more preferably 0.5-3 μm.The granule that the zirconium phosphate that aforementioned volume average particle size shows the present invention carries silver is tiny, is extremely conducive to load silver ion, and and is beneficial to operations such as being applied to follow-up plastic processing or high-temperature process.
Zirconium phosphate for the present invention carries the particle property of silver, characterizes with grain-size characteristic parameter d (0.1), d (0.5), d (0.9).About the definition of grain-size characteristic parameter d (0.1), d (0.5), d (0.9); that granule well-known to those skilled in the art or dusty material are by grading; to estimate the definition characteristic manner of powder percentage grain at different levels, no longer describe in detail in this.In brief, via grain size analysis the definition of numerical value indication of grain-size characteristic parameter be respectively: the numerical value of d (0.1): detect in sample total amount, the diameter of 10% content particles is less than the numerical value of d (0.1); The numerical value of d (0.5): detect in sample total amount, the diameter of 50% content particles is less than the numerical value of d (0.5); The numerical value of d (0.9): detect in sample total amount, the diameter of 90% content particles is less than the numerical value of d (0.9).
According to aforementioned definitions, carry silver according to the zirconium phosphate of the present invention, its grain-size characteristic parameter be d (0.1)=0.3-2 μm, d (0.5)=0.3-5 μm, d (0.9)=0.3-10 μm; Be preferably d (0.1)=0.3-1.5 μm, d (0.5)=0.4-3 μm, d (0.9)=0.5-8 μm; Be more preferably d (0.1)=0.4-1 μm, d (0.5)=0.5-2 μm, d (0.9)=0.6-5 μm.It is not only tiny that the zirconium phosphate that this grain-size characteristic parameter shows the present invention carries Argent grain, and its distribution situation also evenly and concentrate, presents the feature of granularity narrow ditribution, is conducive to improving the dispersive property that zirconium phosphate carries silver.Therefore, using this kind of zirconium phosphate to carry silver in time preparing the antibiotic medical catheter of the present invention, more can reduce the impact of silver series inorganic antibiosis material interpolation on antibiotic medical catheter pliability.
Zirconium phosphate for different grain size characteristic carries the impact that silver produces the performance of conduit, as further illustrated when the practical operation with prior art, it is specifically: when the particle mean size that zirconium phosphate carries silver is 10-20 μm and particle size distribution amplitude is wider, zirconium phosphate carries aluminium powder and adds that catheter surface made by tube material is coarse, hardness becomes large, product properties is not good, even causes using.
But, zirconium phosphate according to aforementioned the present invention carries silver, its particle mean size is at 0.3-10 μm, and there is desirable grain-size characteristic parameter, this zirconium phosphate carries antibacterial powder body that silvery obtains and adds that catheter surface made by tube material is smooth, hardness is almost unchanged, still maintain the softness needed for medical catheter, can normally use without anxiety.
The present invention proposes a kind of method preparing antibiotic medical catheter simultaneously, uses and reaches excellent antibiotic medical catheter usefulness.In specific words, the method preparing antibiotic medical catheter that the present invention proposes prepares after zirconium phosphate carries silver in advance, more described crystallizing layer is carried silver apart from desirable zirconium phosphate make described antibiotic medical catheter with medical macromolecular materials, and its method step is as follows:
(1) zirconium phosphate that a crystalline phase is single is provided;
(2) with alkylamide compound, pre-intercalation is carried out to described zirconium phosphate, described alkylamide compound is inserted the single zirconium phosphate of described crystalline phase, obtain the intercalation zirconium phosphate product that interlamellar spacing increases;
(3) described intercalation zirconium phosphate product and silver ion are exchanged, thus obtain zirconium phosphate and carry silver; And
(4) described zirconium phosphate is carried silver and prepare described antibiotic medical catheter with described medical macromolecular materials;
Preferably concrete scheme is, in time preparing zirconium phosphate and carry silver, carry out pre-intercalation, be in advance using alkylamide compound component as initiator, and the zirconium phosphate that described alkylamide compound is inserted crystalline phase single carries out upgrading, to obtain the pre-intercalation zirconium phosphate product that interlamellar spacing increases, recycle described pre-intercalation zirconium phosphate product and silver ion exchanges, thus obtain zirconium phosphate and carry silver.Wherein, aforementioned alkylamide compound component is the combination being selected from n-butylamine, n-propylamine and n-butylamine, n-propylamine.
Therefore, it is 1-20% that the described zirconium phosphate be prepared into according to preceding method carries the weight percent content that silver has a silver element; And zirconium phosphate carry silver there is following sign: volume average particle size is 0.3-10 μm; The grain-size characteristic parameter that zirconium phosphate carries silver is d (0.1)=0.3-2 μm; D (0.5)=0.3-5 μm; D (0.9)=0.3-10 μm; The specific surface area that zirconium phosphate carries silver is 1-20m
2/ g; And it is 0.01%-10% at the weight percent of described antibiotic medical catheter that described method makes described zirconium phosphate carry silver; And the weight percent of described medical macromolecular materials is 90%-99.99%.
Moreover, outside the effect that the grain size characteristic tripped out according to preceding method is relevant, due to the zirconium phosphate of the single crystalline phase that the present invention adopts, the well-regulated layer structure of tool in micro structure, interlamellar spacing is 7.6nm, and charge density is large, as adopted the zirconium phosphate of this form, silver ion enters interlayer difficulty greatly, causes load capacity on the low side, have impact on performance and releasing effect that zirconium phosphate loads with silver.Therefore, according to the proposed method, be the defect that the technical scheme that have employed pre-intercalation processing solves the zirconium phosphate of above-mentioned single crystalline phase and has.Specifically: the present invention utilizes components such as inserting alkylamide compound (n-butylamine, n-propylamine) in advance as initiator and increases zirconium phosphate layer spacing, readjust the pre-intercalation zirconium phosphate product that the rear output of laminate arrangement is desirable, exchange with silver ion again, thus the zirconium phosphate obtaining high capacity amount carries silver, therefore, according to the silver ion mode of loading that the method is reached, load for silver ion is response type, but not simple physical absorption, and the silver-colored effect of releasing that the zirconium phosphate obtained by such upgrading carries silver have also been obtained improvement.The zirconium phosphate of above manufacture method gained carries silver, and to have reached silver carrying amount, high security high and can the effect of slow release stripping silver ion.
Except particle size distribution feature, the specific surface area that the zirconium phosphate of the present invention carries silver is desirable, can silver ion that fully suction is enough, is conducive to equally preparing antibiotic medical catheter, and after making antibiotic medical catheter, steadily discharges silver ion.Be noted that the present invention is for characterizing specific surface area (specific surface area; Unit m
2/ g) parameter refer to and be well known to those skilled in the art the surface area that concrete dynamic modulus solid matter or powder body have in unit mass, do not describe in detail at this.Specifically, the zirconium phosphate of the present invention carries silver-colored specific surface area is 1-20m
2/ g, preferred 1.5-15m
2/ g, more preferably 2-10m
2/ g.For the antibiotic medical catheter further illustrating the present invention has the feature of slow release silver ion, refer to the explanation of following experimental example 2.
Experimental example 2: the silver-colored active component slow release effect of antibiotic medical catheter of the present invention
By silver carrying amount be 6% zirconium phosphate carry silver and be dispersed in polyurethane material, the ratio in 1% is added in the medical macromolecular materials that medical catheter uses, and makes antibacterial venous cannulation by Shooting Technique.Then, inject deionized water in the catheter, conduit two ends are sealed, preserve at normal temperatures after 30 days, water in conduit is taken out, adopt the silver content in ICP-AES method test water, test result finds, silver content free in water is lower than instrument test lower limit 30ppb, and the burst size of its silver ion is very low, display slow release effect and safety.
For the antibiotic medical catheter further illustrating the present invention has desirable anti-microbial property really, save and be described by following experimental example 3.
Experimental example 3: the antibacterial activity checking of antibiotic medical catheter of the present invention
By silver carrying amount be 6% zirconium phosphate carry silver, the ratio in 1% is added in the medical macromolecular materials that medical catheter uses, and makes the conduit that internal diameter is 3mm; Then, antibacterial test is carried out in the standard of " evaluation methodology of ISO22196:2007 surface of plastic products anti-microbial property " of being adopted international standards by the medical catheter made and the evaluation methodology of antibacterial activity, confirms its effect (the antibacterial activity value 5.2 to colibacillary antibacterial activity value 4.8, staphylococcus aureus) preventing escherichia coli and staphylococcus aureus and grow.
For further illustrating the biological safety of the antibiotic medical catheter of the present invention, saving and being described by following experimental example 4.
Experimental example 4: zirconium phosphate of the present invention carries the assessment of the security performance of silver
Known silver-zirconium phosphate antimicrobial does not have teratogenesis degeneration.By silver carrying amount be 6% zirconium phosphate Ag-carried antibacterial powder transfer to Shanghai preventive medicine academy carry out chmice acute Oral toxicity experiment and rabbit intact skin irritant experiment.According to results of animal display, it is 5000mg/kg to the LDs of Mouse oral toxicity that zirconium phosphate carries silver, belongs to actual nontoxic level; To the skin irritation of white rabbit for there is no an intact skin zest.The bio-safety performance that zirconium phosphate Ag-carried antibacterial powder of the present invention has height is shown from test result.
For the zirconium phosphate further illustrating the present invention carries the storage stability of silvery for antibiotic medical catheter, save and be described by following experimental example 5.
Experimental example 5: zirconium phosphate of the present invention carries the storage stability assessment of silver
Take zirconium phosphate Ag-carried antibacterial powder proposed by the invention, be scattered in neutral in water, and water insoluble and organic solvent, acidproof, salt and weak base, present high stability.
Adopt zirconium phosphate Ag-carried antibacterial powder proposed by the invention to carry out ultra violet lamp test, result display zirconium phosphate Ag-carried antibacterial powder is in ultra violet lamp invariant color in 24 hours.
Zirconium phosphate Ag-carried antibacterial powder proposed by the invention deposits invariant color in 2 years in printing opacity sample bottle.
Zirconium phosphate Ag-carried antibacterial proposed by the invention, heatproof test result shows its temperature tolerance and surpasses 400 DEG C, can meet the processing request of plastic, and the course of processing can not produce the situation of variable color.
In sum, save by technical scheme proposed by the invention, the slowly released type antibiotic medical catheter be most widely used clinically can be obtained, as antibiotic catheters, antibacterial central vein catheter and antibacterial tracheal intubation etc.
Below more list multinomial embodiment, use and technical scheme proposed by the invention more specifically and is fully described.First illustrate, the following example is all according to this case preferred implementation: adopt the feature of aforementioned the present invention the silver carrying amount that defines be that the zirconium phosphate of 4-10% carries silver.About medical macromolecular materials, be all adopt commercially available medical grade medical-grade plastics tube material, use the various antibiotic medical catheter of preparation.
About its be adopt zirconium phosphate carry out obtained by Ag ion exchange Method And Principle, its preparation method summary is as follows: first prepare zirconium phosphate: be raw material with solubility zirconates (zirconium oxysulfate, zirconium oxycarbonate), phosphoric acid and Fluohydric acid., in atmospheric conditions, reaction temperature is 60-90 DEG C, response time 2-4 hour, obtains zirconium phosphate inorganic carrier.Then carry out silver-colored complex ion exchange: added in silver nitrate solution by zirconium phosphate and stir 2-4 hour, the pH value then controlling solution is more than or equal to 10, carries out Ag ion exchange further.Finally, carry in silver and add dispersant molecular weight polyolefin obtaining zirconium phosphate, then sinter, control sintering temperature is 980-1200 DEG C, and obtaining product is white powder.Above-mentioned condition has been made a summary the key condition of preparation this case invention, and other details of operation is conventional fine chemical-process, be technique well known to those skilled in the art, therefore does not describe in detail at this.
It is emphasized that, the present invention can carry silver (such as by the zirconium phosphate of the different silver carrying amount of demand, in effective scope, suitably reduce silver carrying amount, to reduce costs or to change the mechanical performance of medical catheter goods) and different medical catheter material adapteds make the slow release of different size and model, effective, lasting antibiotic medical catheter.
Concrete grammar about preparation antibiotic medical catheter of the present invention is carried by zirconium phosphate after silver mixes medical macromolecular materials to make, preferred method comprises: first medical macromolecular materials and zirconium phosphate are carried silver blended make agglomerate material after, then by this agglomerate material further routinely processes make antibiotic medical catheter; Or adding zirconium phosphate in the polymerization process of medical macromolecular materials carries silver, after obtaining a composite antibacterial medical catheter material, this composite antibacterial medical catheter material is made antibiotic medical catheter by technique routinely further.
Carrying the feature of silver-colored particle size distribution for further illustrating zirconium phosphate of the present invention, first enumerating existing zirconium phosphate and carrying the powder granularity distribution characteristics datagram of silver products as shown in Figure 1; Fig. 1 shows existing zirconium phosphate, and to carry silver products particle size distribution wide and uneven.Below multiple embodiment is enumerated further, so that the technical scheme of the present invention to be described.
Embodiment 1. prepares medical catheter
First, obtained zirconium phosphate carry silver element percentage by weight be 6% zirconium phosphate carry silver powder (namely silver carrying amount be 6% zirconium phosphate carry silver).By analysis this silver carrying amount be 6% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.712 μm; D (0.1)=0.893 μm; D (0.5)=1.601 μm; D (0.9)=2.708 μm; Specific surface area 4.15m
2/ g, as shown in Figure 2, particle size distribution is concentrated and even.This zirconium phosphate is carried silver powder as silver-based inorganic antibacterial agent, and the ratio in 1% is added in medical macromolecular materials, makes the medical catheter that internal diameter is 3mm.
Embodiment 2. prepares polyurethane (PU) central vein antibiotic medical catheter
1. prepare silver carrying amount be 4% zirconium phosphate carry silver
Obtained silver carrying amount be 4% zirconium phosphate carry silver powder (namely silver carrying amount be 4% zirconium phosphate carry silver).By analysis this silver carrying amount be 4% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.887 μm; D (0.1)=0.995 μm; D (0.5)=1.725 μm; D (0.9)=3.007 μm; Specific surface area 3.79m
2/ g, as shown in Figure 3, particle size distribution is concentrated and even.
2. prepare PU mother particles of antibacterial plastics
Be zirconium phosphate Ag-carried antibacterial powder and 3 kilograms of barium sulfate admixture of powder of 4% by 1 kilogram of silver carrying amount, then join in 6 kilograms of PU resins, blending extrusion is processed, and obtains the PU mother particles of antibacterial plastics that phosphoric acid zirconium Ag-carried antibacterial powder is 10%.
3. preparing centre venous duct
By 5 kilograms of PU sterilizing plastic cement master batches and 45 kilograms of PU raw materials blended, routinely by relevant tube-making process, obtained central vein antibiotic medical catheter.
Embodiment 3. prepares polrvinyl chloride (PVC) antibiotic catheters
1. prepare silver carrying amount be 6% zirconium phosphate carry silver
Obtained silver carrying amount be 6% zirconium phosphate carry silver powder (namely silver carrying amount be 6% zirconium phosphate carry silver).By analysis this silver carrying amount be 6% zirconium phosphate carry the parameter of silver powder: volume average particle size is 0.575 μm; D (0.1)=0.301 μm; D (0.5)=0.531 μm; D (0.9)=0.918 μm; Specific surface area 13m
2/ g, as shown in Figure 4, particle size distribution is concentrated and even.
2. by 1 kilogram of silver carrying amount be 6% zirconium phosphate Ag-carried antibacterial powder and 99 kilograms of PVC powder blended, abundant mix homogeneously, obtains antibiotic catheters by catheter production technology routinely.
Embodiment 4. prepares polrvinyl chloride (PVC) antibiotic catheters
1. prepare silver carrying amount be 10% zirconium phosphate carry silver
Obtained silver carrying amount be 10% zirconium phosphate carry silver powder (namely silver carrying amount be 10% zirconium phosphate carry silver).By analysis this silver carrying amount be 10% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.730 μm; D (0.1)=0.853 μm; D (0.5)=1.581 μm; D (0.9)=2.834 μm; Specific surface area 4.24m
2/ g, as shown in Figure 5, particle size distribution is concentrated and even.
2. prepare PVC antibacterial matrices
By 1 kilogram of silver carrying amount be 10% zirconium phosphate Ag-carried antibacterial powder and 4 kilograms of PVC particles blended, by twin screw extrusion process, obtain the antibacterial PVC master batch that phosphoric acid zirconium Ag-carried antibacterial powder is 20%.
3. prepare antibiotic catheters
5 kilograms of antibacterial PVC master batches and 95 kilograms of PVC are cut into slices blended, obtains antibiotic catheters by catheter production technology routinely.
Embodiment 5. prepares silicone rubber antibiotic medical catheter
1. prepare silver carrying amount be 8% zirconium phosphate carry silver
Obtained silver carrying amount be 8% zirconium phosphate carry silver powder (namely silver carrying amount be 8% zirconium phosphate carry silver).By analysis this silver carrying amount be 8% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.021 μm; D (0.1)=0.501 μm; D (0.5)=0.922 μm; D (0.9)=1.696 μm; Specific surface area 7.24m
2/ g, as shown in Figure 6, particle size distribution is concentrated and even.
2. be zirconium phosphate Ag-carried antibacterial powder and 99 kilograms of raw-silastic continuously mixing of 8% by 1 kilogram of silver carrying amount, obtain silver series inorganic antibiosis powder and rubber mixture by banburying process routinely, then obtain antibacterial medical pipe by sulfuration tube-making process routinely.
Embodiment 6. prepares polrvinyl chloride (PVC) antibacterial tracheal intubation
1. prepare silver carrying amount be 10% zirconium phosphate carry silver
Obtained silver carrying amount be 10% zirconium phosphate carry silver powder (namely silver carrying amount be 10% zirconium phosphate carry silver).By analysis this silver carrying amount be 10% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.895 μm; D (0.1)=0.964 μm; D (0.5)=1.733 μm; D (0.9)=3.056 μm; Specific surface area 3.83m
2/ g, as shown in Figure 7, particle size distribution is concentrated and even.
2. prepare PVC antibacterial matrices
By 1 kilogram of silver carrying amount be 10% zirconium phosphate Ag-carried antibacterial powder and 4 kilograms of PVC particles blended, by twin screw extrusion process, obtain the antibacterial PVC master batch that silver series inorganic antibiosis powder content is 20%.
3. prepare antibacterial tracheal intubation
5 kilograms of antibacterial PVC master batches and 95 kilograms of PVC are cut into slices blended, obtains antibacterial tracheal intubation by tracheal intubation preparation technology routinely.
Embodiment 7. prepares antibacterial tracheal intubation
1. prepare silver carrying amount be 6% zirconium phosphate carry silver
Obtained silver carrying amount be 6% zirconium phosphate carry silver powder (namely silver carrying amount be 6% zirconium phosphate carry silver).By analysis this silver carrying amount be 6% zirconium phosphate carry the parameter of silver powder: volume average particle size is 1.810 μm; D (0.1)=0.866 μm; D (0.5)=1.599 μm; D (0.9)=2.978 μm; Specific surface area 4.17m
2/ g, as shown in Figure 8, particle size distribution is concentrated and even.
2. by 1 kilogram of silver carrying amount be 6% zirconium phosphate Ag-carried antibacterial powder and 99 kilograms of PVC powder blended, abundant mix homogeneously, obtains antibacterial tracheal intubation by tracheal intubation preparation technology routinely.
Antibiotic medical catheter time above-mentioned described in embodiment is carried out effect duration experiment, and result shows that effect duration was more than 2 years, showed the stability of its long term storage.In addition, zoopery shows, use antibiotic medical catheter of the present invention, its antibacterial effect can continue more than three months, realizes excellent long-term anti-microbial property.
Antibiotic medical catheter of the present invention is admixed in medical-grade plastics tube material due to silver-based inorganic antibacterial agent, and with medical-grade plastics tube material locked engagement, therefore can not come off, safety is good; The Antibacterial Mechanism of antibiotic medical catheter of the present invention belongs to contact sterilization, rely on-the SH of silver ion and antibacterial to combine and kill antibacterial, drug resistance can not be produced to antibacterial, and there is slow-releasing, broad spectrum activity, the feature such as flexibility (adaptability) of operation is good, discoloration-resistant performance is good, be existing commercially available antibiotic medical catheter incomparable.
In sum, antibiotic medical catheter of the present invention obviously meets the requirement such as " few additive requirement ", " requirement of high anti-microbial property ", " high security performance " and " desirable powder granularity distributes ".Therefore, medical catheter safety of the present invention is high, has a broad antifungal spectrum, antibacterial effect persistent period are long, Clinical practice need not often be changed, safely, convenient, effectively can reduce the conduit dependency nosocomial infection because using medical catheter to produce, show the related medical expenses such as reduction infection, save medical resources.
Claims (16)
1. an antibiotic medical catheter, its component contains silver series inorganic antibiosis material and medical macromolecular materials, it is characterized in that: described silver series inorganic antibiosis material mainly comprises zirconium phosphate and carries silver; Described zirconium phosphate carries silver: zirconium phosphate carries silver-colored 0.01%-10%; Medical macromolecular materials 90%-99.99%; The weight percent content that described zirconium phosphate carries silver element in silver is 1-20%; The volume average particle size that described zirconium phosphate carries silver is 0.3-10 μm; The grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-2 μm; D (0.5)=0.3-5 μm; D (0.9)=0.3-10 μm; The specific surface area that described zirconium phosphate carries silver is 1-20m
2/ g.
2. antibiotic medical catheter according to claim 1, is characterized in that, the weight percent of percentage by weight and described medical macromolecular materials that described zirconium phosphate carries silver is: zirconium phosphate carries silver-colored 0.1%-8%; Medical macromolecular materials 92%-99.9%.
3. antibiotic medical catheter according to claim 2, is characterized in that, the weight percent of percentage by weight and described medical macromolecular materials that described zirconium phosphate carries silver is: zirconium phosphate carries silver-colored 0.5%-5%; Medical macromolecular materials 95%-99.5%.
4. antibiotic medical catheter according to claim 1, is characterized in that, the weight percent content that described zirconium phosphate carries silver element in silver is 2-15%.
5. antibiotic medical catheter according to claim 4, is characterized in that, the weight percent content that described zirconium phosphate carries silver element in silver is 4-10%.
6. antibiotic medical catheter according to claim 1, is characterized in that, the volume average particle size that described zirconium phosphate carries silver is 0.4-5 μm.
7. antibiotic medical catheter according to claim 6, is characterized in that, the volume average particle size that described zirconium phosphate carries silver is 0.5-3 μm.
8. antibiotic medical catheter according to claim 1, is characterized in that, the grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-1.5 μm; D (0.5)=0.4-3 μm; D (0.9)=0.5-8 μm.
9. antibiotic medical catheter according to claim 8, is characterized in that, the grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.4-1 μm; D (0.5)=0.5-2 μm; D (0.9)=0.6-5 μm.
10. antibiotic medical catheter according to claim 1, is characterized in that, the specific surface area that described zirconium phosphate carries silver is 1.5-15m
2/ g.
11. antibiotic medical catheters according to claim 10, is characterized in that, the specific surface area that described zirconium phosphate carries silver is 2-10m
2/ g.
12. antibiotic medical catheters according to claim 1, is characterized in that, described medical macromolecular materials can be selected from medical plastic or medical grade silicon rubber.
13. antibiotic medical catheters according to claim 12, is characterized in that, described medical plastic is optional from polyurethane (PU), polrvinyl chloride (PVC), polypropylene (PP) or polyethylene (PE); Described medical grade silicon rubber can be selected from dimethyl silicone rubber, Methylethyl silicone rubber, methyl phenyl vinyl silicone rubber or fluorosioloxane rubber.
14. antibiotic medical catheters according to claim 1, is characterized in that, described antibiotic medical catheter can further containing the filler being selected from barium sulfate, calcium carbonate, titanium dioxide and toner or their combination.
15. 1 kinds of methods preparing antibiotic medical catheter, described method prepares after zirconium phosphate carries silver in advance, more described zirconium phosphate is carried silver and make described antibiotic medical catheter with medical macromolecular materials, it is characterized in that comprising following steps:
(1) zirconium phosphate that a crystalline phase is single is provided;
(2) with alkylamide compound, pre-intercalation is carried out to described zirconium phosphate, described alkylamide compound is inserted the single zirconium phosphate of described crystalline phase, obtain the intercalation zirconium phosphate product that interlamellar spacing increases;
(3) described intercalation zirconium phosphate product and silver ion are exchanged, thus obtain zirconium phosphate and carry silver; And
(4) described zirconium phosphate is carried silver and prepare described antibiotic medical catheter with described medical macromolecular materials;
Wherein, it is 1-20% that the described zirconium phosphate be prepared into according to described method carries the weight percent content that silver has a silver element; The volume average particle size that described zirconium phosphate carries silver is 0.3-10 μm; The grain-size characteristic parameter that described zirconium phosphate carries silver is d (0.1)=0.3-2 μm; D (0.5)=0.3-5 μm; D (0.9)=0.3-10 μm; The specific surface area that described zirconium phosphate carries silver is 1-20m
2/ g; It is 0.01%-10% at the weight percent of described antibiotic medical catheter that described method makes described zirconium phosphate carry silver; And the weight percent of described medical macromolecular materials is 90%-99.99%.
16. methods preparing antibiotic medical catheter according to claim 15, is characterized in that, described alkylamide compound component
Be selected from n-butylamine, n-propylamine and their combination.
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| CN107185052A (en) * | 2017-05-31 | 2017-09-22 | 苏州蔻美新材料有限公司 | A kind of inhibiting bacteria and diminishing inflammation lubricates the preparation method of catheter |
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| CN104403229A (en) * | 2014-11-24 | 2015-03-11 | 苏州市贝克生物科技有限公司 | Medical antibacterial PVC(polyvinyl chloride) film and preparation method thereof |
| PE20181295A1 (en) | 2015-09-01 | 2018-08-07 | First Wave Bio Inc | METHODS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH AN ABNORMAL INFLAMMATORY RESPONSE |
| CN109266011A (en) * | 2018-09-03 | 2019-01-25 | 苏州歌诗夫新材料有限公司 | Medical bottle stopper silica gel material without fluorescer and preparation method thereof |
| US20210114973A1 (en) * | 2019-10-18 | 2021-04-22 | First Wave Bio, Inc. | Pharmaceutical formulations |
| US10980756B1 (en) | 2020-03-16 | 2021-04-20 | First Wave Bio, Inc. | Methods of treatment |
| CN114870186B (en) * | 2022-07-07 | 2022-09-16 | 中国人民解放军总医院第一医学中心 | Endotracheal intubation with antibacterial coating |
| CN117447832A (en) * | 2023-11-17 | 2024-01-26 | 安徽美立刻医疗器械有限公司 | Antibacterial coating and preparation method of TPU dental film containing antibacterial coating |
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| CN102897737A (en) * | 2012-09-24 | 2013-01-30 | 常州大学 | Method for preparation of pillared zirconium phosphate material by self-assembly technology |
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| CN107185052A (en) * | 2017-05-31 | 2017-09-22 | 苏州蔻美新材料有限公司 | A kind of inhibiting bacteria and diminishing inflammation lubricates the preparation method of catheter |
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