WO2000024438A1 - Composition indicatrice d"activite microbienne et couche de revetement - Google Patents

Composition indicatrice d"activite microbienne et couche de revetement Download PDF

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Publication number
WO2000024438A1
WO2000024438A1 PCT/US1999/025089 US9925089W WO0024438A1 WO 2000024438 A1 WO2000024438 A1 WO 2000024438A1 US 9925089 W US9925089 W US 9925089W WO 0024438 A1 WO0024438 A1 WO 0024438A1
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WO
WIPO (PCT)
Prior art keywords
medical device
microbial
composition
microbial indicator
indicator
Prior art date
Application number
PCT/US1999/025089
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English (en)
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WO2000024438A9 (fr
Inventor
Rabih O. Darouiche
Steven J. Ferry
Original Assignee
Baylor College Of Medicine
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Filing date
Publication date
Application filed by Baylor College Of Medicine filed Critical Baylor College Of Medicine
Priority to AU23436/00A priority Critical patent/AU2343600A/en
Publication of WO2000024438A1 publication Critical patent/WO2000024438A1/fr
Publication of WO2000024438A9 publication Critical patent/WO2000024438A9/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions

Definitions

  • the present invention relates to a composition for coating medical devices that indicate when, and if. the medical device is contaminated with microorganisms, and in particularly to a microbial activity indicator composition for coating medical devices which indicate the presence of microbial activity on the surface of the medical devices.
  • Infection is the most common serious complication of implantable and insertable medical devices.
  • the most common microorganisms causing these complications are Staphylococcus epidermidis and Staphylococcus aureus which account for about two-thirds of cases of contamination or infection.
  • Other gram-positive bacteria, gram-negative bacteria, viruses, and fungal microorganisms such as Candida, account for the remaining one-third of cases.
  • infected medical devices Management of infected medical devices is very expensive and in most instances requires the removal of the infected device to establish cure. Replacement medical devices must then be inserted or implanted in place ofthe contaminated medical device which may require taking an x-ray to ensure proper insertion or implantation ofthe medical device. Accordingly, removal and replacement of medical devices is costly to hospitals and patients. In patients with indwelling medical devices who develop fever, the possibility of device- related infection is always considered. In order to accurately determine if the medical device is the source of infection, the medical device must be removed and cultured to observe whether microbial activity is present on the medical device. Accordingly, even if the medical device turns out not to be the source of infection, it has already been removed, and a new medical device has been put in place of the suspect medical device.
  • microbial indicator composition coating for medical devices, method of coating medical devices, or coated medical device, which: enables inspection ofthe medical device to determine whether microbial activity is present on the surface ofthe medical device without requiring removal of the medical device, thereby realizing cost savings to hospitals, and thus, patients; and allows monitoring of the medical device to determine the level of microbial activity present on the surface of the medical device at a given time thereby assisting the decision making process in determining whether the medical device should be replaced.
  • the art has sought a microbial indicator composition coating for medical devices, method of coating medical devices, or coated medical device, which: enables inspection ofthe medical device to determine whether microbial activity is present on the surface ofthe medical device without requiring removal of the medical device, thereby realizing cost savings to hospitals, and thus, patients; and allows monitoring of the medical device to determine the level of microbial activity present on the surface of the medical device at a given time thereby assisting the decision making process in determining whether the medical device should be replaced. It is believed that the present invention will achieve these objectives and overcome the disadvantages of other medical devices and techniques in the field ofthe invention, but its results or effects are still dependent upon the skill and training of the operator.
  • a further feature of the composition is that the coating may further comprise a base material.
  • Another feature of the composition is that the at least one microbial indicator agent
  • the composition may include at least one tetrazolium salt.
  • the at least one microbial indicator agent may include at least one fluorescent indicator.
  • the at least one microbial indicator agent may include at least one thermochromic indicator.
  • the base material may include at least one tetrazolium salt.
  • the foregoing advantages have also been achieved through the present method for coating a medical device, having at least one surface, for indicating the presence of bacterial activity on the at least one surface of the medical device
  • a medical device having at least one surface; providing a microbial indicator composition, and applying the microbial indicator composition to the medical device in an amount sufficient to signify the presence of bacterial activity on the at least one surface of the medical device.
  • a further feature of the method for coating a medical device is that the microbial indicating composition may be formed by mixing 2J,5-Triphenyltetrazolium chloride (TTC) powder in silicone.
  • TTC Triphenyltetrazolium chloride
  • An additional feature of the method for coating a medical device is that the microbial indicator composition may be applied to the medical device by contacting the microbial indicator composition with the medical device for a period of time sufficient to form a layer ofthe microbial indicator composition on the at least one surface of the medical device.
  • the microbial indicator composition may be applied to the medical device by integrating the microbial indicator composition with the material forming the medical device during formation of the medical device.
  • a medical device (a) a medical device; and (b) a microbial indicator composition coating for signifying the presence of bacterial activity on the medical device, the microbial indicator composition coating being disposed upon the at least one surface.
  • the microbial indicator composition coating may include at least one microbial indicator agent.
  • the microbial indicator composition coating may further include a base material.
  • the at least one microbial indicator agent may include at least one tetrazolium salt.
  • the at least one microbial indicator agent may include at least one fluorescent indicator.
  • the at least one microbial indicator agent may include at least one thermochromic indicator. Another feature ofthe coated medical
  • the base material may be selected from the group consisting of rubbers,
  • thermoplastics and elastomers.
  • the foregoing advantages have also been achieved through the present composition for indicating fungal activity on the surface of a medical device comprising at least one microbial indicator agent.
  • a further feature of the composition is that the coating may further comprise a base material.
  • the at least one microbial indicator agent may include at least one tetrazolium salt other than triphenyltetrazolium chloride.
  • the at least one microbial indicator agent may include at least one fluorescent indicator.
  • the at least one microbial indicator agent may include at least one thermochromic indicator.
  • the base material may be selected from the group consisting of rubbers, thermoplastics, and elastomers.
  • the foregoing advantages have also been achieved through the present method for coating a medical device, having at least one surface, for indicating the presence of fungal activity on the at least one surface of the medical device comprising: providing a medical device having at least one surface; providing a microbial indicator composition, and applying the microbial indicator composition to the medical device in an amount sufficient to signify the presence of fungal activity on the at least one surface ofthe medical device.
  • a further feature ofthe method for coating a medical device is that the microbial indicator composition may be applied to the medical device by contacting the microbial indicator
  • compositions with the medical device for a period of time sufficient to form a layer of the microbial indicator composition on the at least one surface ofthe medical device.
  • An additional feature of the method for coating a medical device is that the microbial indicator composition may be applied to the medical device by integrating the microbial indicator composition with the material forming the medical device during formation ofthe medical device.
  • a medical device (a) a medical device; and (b) a microbial indicator composition coating for signifying the presence of fungal activity on the medical device, the microbial indicator composition coating being disposed upon the at least one surface.
  • the microbial indicator composition coating may include at least one microbial indicator agent.
  • the microbial indicator composition coating may further include a base material.
  • the at least one microbial indicator agent may include at least one tetrazolium salt other than triphenyltetrazolium salt.
  • the at least one microbial indicator agent may include at least one fluorescent indicator.
  • the at least one microbial indicator agent may include at least one thermochromic indicator.
  • the base material may be selected from the group consisting of rubbers, thermoplastics, and elastomers.
  • a further feature of the composition is that the coating may further comprise a base material.
  • the at least one microbial indicator agent may include at least one tetrazolium salt.
  • the at least one microbial indicator agent may include at least one fluorescent indicator.
  • the at least one microbial indicator agent may include at least one thermochromic indicator.
  • the resin may be selected from the group consisting of rubbers, thermoplastics, and elastomers.
  • indicating the presence of viral activity on the at least one surface of the medical device comprising: providing a medical device having at least one surface; providing a microbial
  • the microbial indicator composition and applying the microbial indicator composition to the medical device in an amount sufficient to signify the presence of viral activity on the at least one surface ofthe
  • a further feature of the method for coating a medical device is that the microbial indicator composition may be applied to the medical device by contacting the microbial indicator composition with the medical device for a period of time sufficient to form a layer of the microbial indicator composition on the at least one surface ofthe medical device.
  • An additional feature of the method for coating a medical device is that the microbial indicator composition may be applied to the medical device by integrating the microbial indicator composition with material forming the medical device during formation ofthe medical device.
  • a medical device (a) a medical device; and (b) a microbial indicator composition coating for signifying the presence of viral activity on the medical device, the microbial indicator composition coating being disposed upon the at least one surface.
  • the microbial indicator composition coating may include at least one microbial indicator agent.
  • the microbial indicator composition coating may include a base material.
  • the microbial indicator agent may include at least one tetrazolium salt.
  • the microbial indicator agent may include at least one fluorescent indicator.
  • the microbial indicator agent may include at least one thermochromic indicator.
  • the base material may be selected from the group consisting of rubbers, thermoplastics, and elastomers.
  • the microbial indicator composition coating for medical devices, method of coating medical devices, and coated medical device when compared with previously proposed prior coatings for medical devices, methods of coating medical devices, or coated medical devices have the advantages of: enabling inspection ofthe medical device to determine whether microbial activity is present on the surface ofthe medical device without requiring removal ofthe medical device, thereby realizing cost savings to hospitals, and thus, patients; and allowing the medical device to be monitored to determine the level of microbial activity present on the surface ofthe medical device at a given time thereby assisting the decision making process in determining whether the medical device should be replaced. It is believed that the present invention will achieve these objectives and overcome the disadvantages of other medical devices and techniques in the field ofthe invention, but its results or effects are still dependent upon the skill and training ofthe operator.
  • FIG. 1 is a specific embodiment of a catheter insertion seal having a microbial indicator composition incorporated into an adhesive layer located on the catheter insertion seal.
  • the present invention is directed to a microbial indicator composition, or microbial indicator composition coating, or coating, which is applied to medical devices and which indicates the presence of microbial activity.
  • the microbial indicator composition may indicate the presence of microbial activity by any manner know to persons skilled in the art, e.g., changes in pH, metabolic by-product, biochemical reaction, heat, and/or color.
  • the microbial indicator composition indicates the presence of microbial activity visually, by change in color.
  • the microbial indicator composition coating includes a microbial indicator agent which, in its activated state, indicates the presence of microbial activity on the surface of the medical device.
  • the microbial indicator composition coating for medical devices may be formulated to indicate the presence of gram-positive bacteria, such as Staphylococcus epidermidis, gram-negative bacteria, such as Pseudomonas aeruginosa, fungi, such as Candida albicans. and/or viruses. While the microbial indicator composition coating may include a microbial indicator agent alone, preferably, the microbial indicator composition coating includes a base material and a microbial indicator agent. The microbial indicator composition may also include more than one microbial indicator agent as desired or necessary to indicate the presence of other microbes.
  • Medical devices are herein defined as disposable or permanent catheters, (e.g., central venous catheters, dialysis catheters, long-term tunneled central venous catheters, short-term central venous catheters, peripherally inserted central catheters, peripheral venous catheters, pulmonary artery Swan-Ganz catheters, urinary catheters, and peritoneal catheters), long-term urinary devices, tissue bonding urinary devices, vascular grafts, vascular catheter ports, wound drain tubes, ventricular catheters, hydrocephalus shunts, heart valves, heart assist devices (e.g., left ventricular assist devices), pacemaker capsules, incontinence devices, small or temporary joint replacements, urinary dilator, cannulas, elastomers, hydrogels, dental instruments, tubings, such as intravenous tubes, breathing tubes, dental water lines, dental drain tubes, and feeding tubes, fabrics, paper, indicator strips (e.g., paper indicator strips or plastic indicator strips), adhesives (e.
  • Medical devices also include any other surface which may be desired or necessary to indicate the presence of microbial activity, such as the surfaces of equipment in operating rooms, emergency rooms, hospital rooms, and bathrooms.
  • the microbial indicator composition is integrated into an adhesive, such as tape, thereby providing an adhesive which may indicate microbial activity on the surface ofthe adhesive.
  • Implantable medical devices include orthopedic implants which may be inspected for microbial activity indicating contamination or infection using endoscopy.
  • Insertable medical devices include catheters and shunts which can be inspected without invasive techniques such as endoscopy.
  • the medical devices may be formed of any suitable metallic materials or non- metallic materials known to persons skilled in the art. Examples of metallic materials include, but are not limited to, tivanium. titanium, and stainless steel. Examples of non-metallic materials include, but are not limited to, thermoplastic or polymeric materials such as rubber, plastic, polyesters, polyethylene, polyurethane, silicone, Gortex (polytetrafluoroethylene), Dacron
  • the medical devices include at least one surface for applying the microbial indicator composition.
  • the microbial indicator composition is applied to the entire medical device.
  • the microbial indicator composition may include any number of microbial indicator agents and base materials provided the microbial indicator composition is biocompatible with human beings or other animals in which the coated medical device is inserted or implanted.
  • Biocompatible is herein defined as compatible with living tissues, such that the medical device is not rejected or does not cause harm to the living tissue.
  • the microbial indicator agent may be any microbial indicator agent known to persons skilled in the art which indicates the presence of microbial activity and which is biocompatible with human beings and other animals.
  • “Microbial activity” is herein defined as any biological function of gram-positive bacteria, gram-negative bacteria, fungi or viruses which indicates the gram-positive bacteria, gram-negative bacteria, fungi or virus is living or proliferating on the surface ofthe medical device, thereby contaminating or infecting at least one surface ofthe medical device.
  • Microbial activity includes bacterial activity, fungal activity, and viral activity.
  • Bacterial activity is herein defined as any biological function of gram-positive bacteria or gram-negative bacteria living or proliferating on the surface ofthe medical device.
  • the gram- positive and gram-negative bacteria include, but are not limited to. all spherical, rod-shaped, and spiral bacteria. Some examples include Staphylococcus epidermidis, Staphylococcus aureus, Enter vcoccus faecalis, Pseudomonas aeruginosa, and Esche ⁇ chia coli.
  • Fungal activity is herein defined as any biological function of fungi living or proliferating on the surface ofthe medical device.
  • fungus is Candida albicans.
  • Virtual activity is herein defined as any biological function of viruses living or proliferating on the surface ofthe medical device.
  • Suitable microbial indicators agents include chemical indicators, florescent indicators, and thermochromic indicators.
  • Suitable chemical indicators include tetrazolium salts such as tetrazolium blue, tetrazolium violet, neotetrazolium chloride, tetrazolium red (i.e., 2,3,5- Triphenyltetrazolium chloride (TTC)), nitroblue tetrazolium, tetranitroblue tetrazolium, and thiocarbamio nitroblue tetrazolium.
  • concentration ofthe chemical indicator in the microbial indicator composition may be in the range from about 0.1% to 25% based upon the total weight ofthe microbial indicator composition.
  • chemical indicator is present in the microbial indicator composition at a concentration of about 1% to about 15%.
  • the tetrazolium salts function as color indicators of microbial activity.
  • the tetrazolium salts change color in the presence of microbial activity.
  • TTC has an off-white color which turns red in the presence of microbial oxidative metabolism.
  • the utilization of chemical indicators provide a system of identifying potentially pathogenic microbes by the chemical reaction between the chemical indicators and a protein, enzyme, or metabolic by-product ofthe infecting microbe or by indicating oxidation or reduction chemical reactions resulting from the presence of microbes contacting the chemical indicators.
  • One benefit of utilizing the tetrazolium salts is that the color change ofthe tetrazolium salts can be detected visually, thereby providing easy detection of infection without the need for removing the medical device and culturing the medical device, and without the use of any other diagnostic device or test. Therefore, the utilization ofthe tetrazolium salts provides in situ examination of the medical device to determine whether microbial infection has occurred. Accordingly, preferred chemical indicators provide colormetric indication of microbial activity in the same manner as the tetrazolium salts.
  • powder TTC is combined with silicone to form the microbial indicator composition.
  • concentration of TTC in the microbial indicator composition may be in the range of 0.1% to 25% TTC.
  • the TTC is present in the microbial indicator composition at a concentration of about 1% to 15%.
  • other chemical indicators such as tetrazolium salts, as well as fluorescent and thermochromic indicators, may indicate the presence of fungal activity
  • the microbial indicator compositions including TTC do not detect the presence of fungal activity of at least one fungus, Candida albicans. Accordingly, the absence of activation of the TTC, and thus the absence of a change in color in the microbial indicator composition, maybe helpful in differentiating between bacterial activity and the fungal activity of Candida albicans.
  • the microbial indicator agents are fluorescent indicators.
  • suitable fluorescent indicators include fluorescein, fluoresceine. fluoresamine, fluoresceine sodium salt, and lumazine.
  • the concentration of fluorescent indicator in the microbial indicator composition may be in the range from about 0.1% to 25% based upon the total weight ofthe microbial indicator composition.
  • fluorescent indicator is present in the microbial indicator composition at a concentration of about 1% to about 15%.
  • the utilization of fluorescent indicators provides a system of identifying potentially pathogenic microbes by a chemical reaction utilizing color changes in the ultraviolet light range.
  • the microbial indicator agents Upon contacting the fluorescent microbial indicator agent to proteins, enzymes, or metabolic byproduct, or chemical reactions such as oxidation or reduction reactions of the microbes, the microbial indicator agents are activated, i.e., become fluorescent at a specific wave length in the ultraviolet light range.
  • the activation ofthe microbial indicator agent may be detected by means of a portable ultraviolet light source so that microbial activity on the surface of the medical device can be detected visually. Therefore, the utilization of the fluorescent indicators provides in situ examination ofthe medical device to determine whether microbial infection has occurred, thereby providing easy detection of infection without the need for removing the medical device and culturing the medical device. It is contemplated that fluorescent indicators may be used to detect bacterial activity, fungal activity, and/or viral activity.
  • the microbial indicator agents are thermochromic indicators.
  • suitable thermochromic indicators utilized to indicate the presence of microbial activity on the surface of the medical devices include thermochromic liquid crystals and leucodyes.
  • the concentration of thermochromic indicator in the microbial indicator composition may be in the range from about 0.1% to 25% based upon the total weight of the microbial indicator composition.
  • thermochromic indicator is present in the microbial indicator composition at a concentration of about 1% to about 15%.
  • Thermochromic indicators are activated, and thus indicate the presence of microbial activity by a temperature change caused by the microbial colonization. Microbial colonization, or contamination, results in a localized or systemic temperature rise at the site of the medical device insertion or implantation.
  • the microbial activity increases the temperature ofthe tissue surrounding the medical device and, it is contemplated, the surface temperature ofthe medical device itself. Therefore, by detecting this rise in temperature, the thermochromic indicators indicate the presence of microbial activity.
  • thermochromic indicators may be used to detect bacterial activity, fungal activity, and/or viral activity.
  • thermochromic liquid crystals are similar to liquid crystal displays used in lap top computers, except that the thermochromic liquid crystals change color depending on the temperature range whereas computer displays change color depending on changes in voltage.
  • Thermochromic liquid crystals can be formulated to change temperatures from -25 °F to 250 °F
  • thermochromic liquid crystals are usually black below their formulated temperature range and progress to brown, red, yellow, green, blue, and violet at the peak temperature range. Once exceeded, the thermochromic liquid crystal will revert to black once again. Given the small tolerable range of temperature fluctuations in the body's basal temperature, approximately 5.4 degrees from normal, thermochromic liquid crystals would not run through the entire chromic scale. In other words, the thermochromic liquid crystals can be formulated such that, as the basal body temperature rises, the thermochromic liquid crystal's change in color would not revert back to its original, threshold color, i.e., the color at the body's normal basal temperature, 98.6°F.
  • thermochromic liquid crystals may be formulated to have a threshold color of black at 98.6 °F, a brown color at 99.6 °F, a red color at 100.6°F, a yellow color at 101.6 °F. a green color at 102.6 °F, a blue color at 103.6 °F, and a violet color at 104.6°F.
  • the microbial indicator composition utilizing thermochromic liquid crystals as the microbial indicator agent could be developed as a "positive/negative" indicator when the localized area or basal body temperature rises above a threshold temperature.
  • the inactivated, threshold, color would indicate "negative” contamination
  • any increase in the basal body temperature above 98.6°F would activate, i.e., change the color of, the thermochromic liquid crystal indicator to indicate "positive" contamination.
  • Leucodyes are a class of thermochromic materials which change from a color at a cold, inactive temperature, to clear upon heating to a specified temperature threshold. It is contemplated that leucodyes may be applied to medical devices in a manner similar to the thermochromic liquid crystal materials and detect changes in temperature. These materials may also be designed to be reversible, i.e., as the temperature returns to its threshold temperature, the leucodyes change from clear to their threshold color. Therefore, as the microbial contamination is treated and abolished from the surface of the medical device, the leucodye indicator would change from its activated state, i.e., clear, to its inactivated, or threshold, state, i.e., colored.
  • the same medical device could be left in place to indicate subsequent contamination.
  • the leucodye indicator may be designed to be irreversible. Therefore, once the leucodye indicator changes from color to clear, the device would be required to be replaced with a new medical device to indicate any subsequent microbial activity.
  • base material is defined herein as any of a group of materials which effectively disperses the microbial indicator agent at an effective concentration to indicate microbial activity.
  • the base material also facilitates the adhesion of the microbial indicator composition to at least one surface ofthe medical device and prevents the microbial indicator composition from being easily removed from the surface ofthe medical device, thereby facilitating the utilization of the microbial indicator composition to coat at least one surface of a medical device.
  • suitable base materials include polyvinyl, polyethylene, polyurethane, polypropylene, silicone (e.g., silicone elastomers and silicone adhesives), polycarboxylic acids, (e.g., polyacrylic acid, polymethacrylic acid, polymaleic acid, poly-(maleic acid monoester), polyaspartic acid, polyglutamic acid, aginic acid or pectimic acid), polycarboxylic acid anhydrides (e.g., polymaleic anhydride, polymethacrylic anhydride or polyacrylic acid anhydride), polyamines, polyamine ions (e.g., polyethylene imine, polyvinylamine.
  • silicone e.g., silicone elastomers and silicone adhesives
  • polycarboxylic acids e.g., polyacrylic acid, polymethacrylic acid, polymaleic acid, poly-(maleic acid monoester), polyaspartic acid, polyglutamic acid, aginic acid or pectimic acid
  • polylysine poly-(dialkylamineoethyl methacrylate), poly-(dialkylaminomethyl styrene) or poly-(vinylpyridine)), polyammonium ions (e.g., poly-(2-methacryloxyethyl trialkyl ammonium ion), poly-(vinylbenzyI trialkyl ammonium ions), poly-(N.N.-alkylypyridinium ion) or poly-(dialkyloctamethylene ammonium ion) and polysulfonates (e.g. poly-(vinyl sulfonate) or poly-(styrene sulfonate)), collodion, nylon, rubber, plastic, polyesters, Gortex
  • polytetrafluoroethylene Dacron (polyethylene tetraphthalate), Teflon (polytetrafluoroethylene), latex, and derivatives thereof, elastomers and Dacron sealed with gelatin, collagen or albumin, cyanoacrylates, methacrylates, papers with porous barrier films, adhesives, e.g., hot melt adhesives, solvent based adhesives, and adhesive hydrogels, fabrics, and crosslinked and non- crosslinked hydrogels, and any other polymeric materials which facilitate dispersion of the
  • Linear copolymers, cross-linked copolymers, graft polymers, and block polymers, containing monomers as constituents ofthe above exemplified polymers may also be used.
  • polyvinyl is defined herein as any of a group of polymerized vinyl compounds such as PV-coA-coA (Polyvinyl butyryl-co-vinyl alcohol-co-vinylacetate), PV-coA-coA plus hydroxylapatite, PVP (Polyvinyl pyrrolidone), PVP-co-VA (Polyvinyl pyrrolidone co-vinyl acetate dissolved in 2-propanol) and combinations thereof.
  • nylon is defined herein as any of a group of synthetic long-chain polymeric amides with recurring amide groups having great strength and elasticity, such as polycaprolactam, polylauryl-lactam and polyhexamethylene sebacamide.
  • collodion is defined herein as any of a group of colorless or pale-yellow, viscous solutions of pyroxylin or nitrocellulose in a mixture of alcohol and ether, which dries quickly and forms a tough, elastic film.
  • the term "effective concentration" means that a sufficient amount of the microbial indicator agent is added to indicate the presence of microbial activity on the at least one surface. The amount will vary for each ofthe microbial indicator agents and upon known factors such as pharmaceutical characteristics; the type of medical device; age, sex, health and weight of the recipient; and the use and length of use. It is within the ability of a person of ordinary skill in the art to relatively easily determine an effective concentration for each microbial indicator agent.
  • the invention is directed to a method for coating a medical device.
  • the method for coating a medical device includes the steps of providing a medical device, providing, or forming, a microbial indicator composition as described in greater detail above, and applying the microbial indicator composition to at least one surface ofthe medical device in an amount sufficient to indicate microbial activity on the at least one surface of the medical device.
  • the method of coating a medical device includes the steps of forming a microbial indicator composition of an effective concentration for activating the microbial indicator agent, and thus indicating microbial activity on the surface of the medical device, wherein the microbial indicator composition is formed by combining a microbial indicator agent and a base material. At least one surface ofthe medical device is then contacted with the microbial indicator composition under conditions wherein the microbial indicator composition covers at least one surface ofthe medical device.
  • Contacting includes, but is not limited to, impregnating, compounding, mixing, integrating, coating, spraying and dipping.
  • the step of forming a microbial indicator composition may also include any one or all of the steps of adding an organic solvent, a penetrating agent, or adding an alkalinizing agent to the microbial indicator composition, to enhance the reactivity of the surface of the medical device with the microbial indicator composition to facilitate adhesion ofthe microbial indicator composition to at least one surface of the medical device.
  • organic solvent is herein defined as solvents that can be used to dissolve microbial indicator agents, including alcohols, e.g., methanol and ethanol, ketones, e.g., acetone and methylethylketone, ethers, e.g., tetrahydrofuran, aldehydes, e.g.,. formaldehyde, acetonitrile, acetic acid, methylene chloride, chloroform, carbonates, water, and alkyl hydrocarbons, e.g., hexane and heptane, and xylene.
  • alcohols e.g., methanol and ethanol
  • ketones e.g., acetone and methylethylketone
  • ethers e.g., tetrahydrofuran
  • aldehydes e.g.,. formaldehyde, acetonitrile
  • acetic acid e.g., he
  • penetrating agent is herein defined as an organic compound that can be used to promote penetration of the microbial indicator agent into the surface ofthe medical device.
  • Suitable penetrating agents include esters, e.g., ethyl acetate, propyl acetate, butyl acetate, amyl acetate, and combination thereof, ketones, e.g., acetone and methylethylketone, methylene chloride, chloroform, and xylene.
  • alkalinizing agent is herein defined as organic and inorganic bases including sodium hydroxide potassium hydroxide, alkyl hydroxides, ammonia in water (27% ammonium hydroxide), diethylamine and triethylamine.
  • high ionic strength salts is herein defined as salts exhibiting high ionic strength, such as sodium chloride, potassium chloride, ammonium acetate. These salts may act both as an alkalinizing agent and as a penetrating agent to enhance the reactivity ofthe surface ofthe medical device. Therefore, in one specific embodiment, high ionic strength salts may also be used in the step of forming the microbial indicator composition.
  • the microbial indicator composition is preferably formed by combining a microbial indicator agent and a base material and heating the microbial indicator composition at a temperature ranging from about 30°C to 70°C prior to applying the microbial indicator composition to a surface ofthe medical device.
  • the medical device may be contacted with the heated microbial indicator composition for a period of time sufficient for the microbial indicator composition to adhere to at least one surface ofthe medical device. After the microbial indicator composition is applied to a surface ofthe medical device, it is allowed to dry.
  • the medical device is preferably placed in contact with the heated microbial indicator composition by dipping the medical device in the microbial indicator composition for a period of time ranging from about 5 seconds to about 120 minutes.
  • the medical device is placed in contact with the heated microbial indicator composition by dipping the medical device in the microbial indicator composition for about 60 minutes.
  • the medical device is then removed from the heated microbial indicator composition and the microbial indicator composition is allowed to dry.
  • the medical device may be placed in an oven, or other heated environment for a period of time sufficient for the microbial indicator composition to dry.
  • the medical device is placed in an heated environment having a temperature of about 80 °F to about 180 °F for about 3 minutes to about 30 minutes.
  • the medical device is placed in an oven at a temperature ranging from about 120°F to about 160°F for about 10 minutes to about 20 minutes.
  • the medical device is contacted with the microbial indicator composition three times, allowing the microbial indicator composition to dry on at least one surface of the medical device prior to contacting the medical device with the microbial indicator composition for each subsequent layer.
  • the medical device preferably includes three coats, or layers, ofthe microbial indicator composition on at least one surface of the medical device.
  • the method of coating medical devices with a microbial indicator composition includes the steps of forming a microbial indicator composition of an effective concentration to indicate the presence of microbial activity on at least one surface of the medical device by dissolving a microbial indicator in an organic solvent, combining a penetrating agent to the microbial indicator and organic solvent, and combining an alkalinizing agent to the microbial indicator, organic solvent, and penetrating agent to improve the reactivity ofthe material ofthe medical device.
  • the microbial indicator composition is then heated to a temperature ranging from about 30 °C to about 70 °C to enhance the adherence ofthe microbial indicator composition to at least one surface of the medical device.
  • the microbial indicator composition is applied to at least one surface ofthe medical device, preferably by contacting the microbial indicator composition to the at least one surface ofthe medical device for a sufficient period of time for the microbial indicator composition to adhere to at least one surface of the medical device.
  • the medical device is removed from the microbial indicator composition and allowed to dry. The medical device may then be rinsed with a liquid, such as water.
  • a catheter was coated with a microbial indicator composition wherein the microbial indicator agent was TTC.
  • the microbial indicator composition was formed by combining 10.35 g of polydimethylsiloxane adhesive with 140 ml xylene and stirred for 40 minutes. Two and one-half (2.5) grams of TTC powder was pre-solubilized in 10 ml of acetone to form a TTC solution.
  • TTC microbial indicator composition having a 0.86 gram silicone to gram of TTC (i.e., 7% TTC).
  • concentration of TTC present in the microbial indicator composition may be adjusted as desired or necessary without undue experimentation by persons skilled in the art.
  • a 1.5% TTC microbial indicator composition may be formed by combining 0.53 g TTC powder in the 10 ml acetone and then following the remaining steps as described above.
  • the beaker containing the TTC microbial indicator composition was then covered and the TTC microbial indicator solution was mixed for 1 hour using a stir bar. After one hour, the covered beaker was allowed to stand for 24 hours.
  • the TTC microbial indicator composition was then applied to the catheter by contacting the catheter to the TTC microbial indicator composition for approximately ten seconds. This was done by dipping the catheter into the TTC microbial indicator composition. The catheter was then removed from the TTC microbial indicator composition and the coating of TTC microbial indicator composition was allowed to air dry onto the catheter for five minutes. The catheter was then placed in an oven at 140°F for fifteen minutes. The catheter was then removed from the
  • the microbial indicator composition was formed by dissolving 450 mg of sodium hydroxide in 45 ml of methanol while stirring until clear, yielding a concentration of 10 mg sodium hydroxide per ml of methanol.
  • the dissolution was more rapidly achieved while stirring on a hot plate at a temperature of about 45°C.
  • the final pH was about 12J, taking into consideration that the pH in organic solvents may not be very reproducible.
  • Catheters (whole silicone catheters, polyurethane shafts and polyethylene shafts) were dipped in the microbial indicator composition for 1 hour at 45 °C. The catheters were removed from the microbial indicator composition and allowed to dry for at least 8 hours, and preferably, overnight. The catheters were rinsed and gently milked under a water faucet to ensure uniform color, then allowed to dry for at least 2 hours.
  • the method of coating the medical devices with a microbial indicator composition includes the steps of forming the microbial indicator composition and incorporating the microbial indicator composition into the material forming the medical device during the formation ofthe medical device.
  • the microbial indicator composition may be combined with the material forming the medical device, e.g., silicone, polyurethane, polyethylene, Gortex (polytetrafluoroethylene), Dacron (polyethylene tetraphthalate), Teflon (polytetrafluoroethylene), and/or polypropylene, and extruded with the material forming the medical device, thereby incorporating the microbial indicator composition into material forming the medical device.
  • the microbial indicator composition may be incorporated in a septum or adhesive which is placed at the medical device insertion or implantation site.
  • a coated medical device having a microbial indicator composition incorporated into the material forming the medical device in accordance with this embodiment is the catheter insertion seal having an adhesive layer described below in greater detail.
  • the invention is directed to coated medical devices.
  • the coated medical devices include a microbial indicator composition applied to at least one surface of the medical device. Suitable medical devices and microbial indicator compositions are described above in greater detail.
  • the microbial indicator composition may be applied to at least one surface ofthe medical devices in any suitable manner.
  • the microbial indicator composition may be applied to the medical devices following any of the methods described above in greater detail.
  • a septum, or adhesive layer is made of a breathable material which has small enough porosity to allow moisture to pass, but functions as a barrier to microbes thereby facilitating a lower incidence of microbial colonization and resulting contamination or infection.
  • the adhesive layer may also include a layer of gauze to facilitate a lower incidence of microbial colonization and resulting contamination or infection.
  • the coated medical devices in this specific embodiment permit only limited contact ofthe microbial indicator composition with the body and/or blood, thereby decreasing the potential for allergic reactions.
  • the invention is directed to a catheter insertion seal 10 which includes the microbial indicator composition 15.
  • the catheter insertion seal 10 includes a first end 1 1, a second end 12, and an aperture 13 connecting first end 11 in second end 12. Aperture 13 runs through the catheter insertion seal 10, thereby connecting first end 11 and second end 12.
  • Second end 12 includes an adhesive layer 14 which facilitates securing the catheter insertion seal 10 to the external surface of a human being or animal, i.e., the skin.
  • adhesive layer 14 may be an integral part ofthe catheter insertion seal 10.
  • a catheter (not shown) may then be placed through the catheter insertion seal 10 by passing the catheter through the aperture 13.
  • Aperture 13 may be connected to first end 1 1 and second end 12 at an angle (not shown) less than 90 degrees, to facilitate insertion ofthe catheter through the aperture 13 and into the human being or animal.
  • the catheter may then be secured to the catheter insertion seal 10 by any method known to persons skilled in the art.
  • the catheter insertion seal 10 may include tabs (not shown) or flanges (not shown) which are reciprocal to tabs or flanges on the catheter, which, when engaged with one another, secure the catheter to the catheter insertion seal 10.
  • a mechanical interference fit between the aperture 13 and the outer diameter of the catheter may also secure the catheter to the catheter insertion seal 10.
  • the adhesive layer 14 may be formed out of any material known to persons skilled in the art provided the adhesive layer 14 includes at least one side having a "sticky" adhesive for securing the catheter insertion seal 10 to the external surface ofthe human being or other animal.
  • adhesive layer 14 may be formed out of any of the materials identified above regarding medical devices and base material.
  • the microbial indicator composition 15 may be incorporated into the adhesive layer 14 by any method known to persons skilled in the art.
  • the microbial indicator composition may be incorporated into the adhesive layer 14 as discussed above in greater detail.
  • the adhesive layer 14 facilitates securing the catheter insertion seal 10, and thus the catheter, to the external surface of the human being or other animal, indicates the presence of microbial activity on the surface ofthe human being or other animal and along the surface ofthe catheter, and provides a defense from contamination or infection at the insertion or implantation site by keeping microbes away from the insertion or implantation site.
  • microbial indicator compositions may be formed having lower concentrations of a microbial indicator agent which are capable of indicating microbial activity.
  • microbial indicator compositions may be formed at concentrations sufficient for indicating lower levels of microbial activity depending on the cause ofthe microbial contamination.
  • Candida albicans as well as on agar plates that had been freshly inoculated with bacterial suspensions (10 9 cfu/ml) of Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans.
  • the TTC coated tubings were compared with six uncoated silicone tubings (the "uncoated tubings").
  • the eventual color ofthe tubings originally a yellowish cream color for the TTC coated tubings and white for the uncoated tubings was observed after 24 hours of incubation.
  • the TTC coated tubings placed in bacterial suspension and agar plate of
  • Staphylococcus epidermidis were red after 24 hours.
  • the TTC coated tubings placed in bacterial suspension and agar plate of Pseudomonas aeruginosa were moderately red after 24 hours.
  • the TTC coated tubings placed in bacterial suspension and agar plate of Candida albicans were not red after 24 hours. None of the uncoated tubings were red after 24 hours in the bacterial suspensions of the agar plates of Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans. Accordingly, a 1.5% TTC microbial indicator composition applied to silicone tubing indicated the presence of bacterial activity caused by Staphylococcus epidermidis and
  • the coated tubings were placed in 37 °C in varying bacterial suspensions of Staphylococcus epidermidis. Uncoated tubings were compared with the coated tubings. The coated and uncoated tubings were monitored every hour to determine the amount of time required for the coated and uncoated tubings to turn red. The results are in Table II. One of each ofthe coated and uncoated tubings were then placed in a sonication device and another of each ofthe coated and uncoated tubings were placed on a roll plate to determine the concentration of Staphylococcus epidermidis on the coated and uncoated tubings.
  • the concentration of Staphylococcus epidermidis was determined by sonication and roll-plate analysis in the same manner as the coated tubings.
  • the number of colonies forming units retrieved from both types of coated tubings and from the uncoated tubings were comparable for each of the two studied concentrations of Staphylococcus epidermidis (10 3 cfu/ml and 10 7 cfu/ml).
  • Staphylococcus epidermidis Staphylococcus epidermidis
  • the microbial indicator composition may be combined with antimicrobial agents or antimicrobial compositions to provide medical devices having microbial indicating capabilities and antimicrobial capabilities. Accordingly, the invention is therefore to be limited only by the scope of the appended claims and equivalents thereof.

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  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
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  • Apparatus For Disinfection Or Sterilisation (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne une composition indicatrice d"activité microbienne destinée à revêtir des dispositifs médicaux et capable d"indiquer la présence d"une activité microbienne sur ces dispositifs médicaux. Cette composition indicatrice d"activité microbienne qui inclut un agent indicateur microbien, peut également comporter un matériau de base. L"invention concerne également, non seulement des dispositifs médicaux revêtus d"une telle composition indicatrice d"activité microbienne, mais également un procédé se rapportant à l"application d"une couche de cette composition indicatrice d"activité microbienne sur des dispositifs médicaux.
PCT/US1999/025089 1998-10-27 1999-10-26 Composition indicatrice d"activite microbienne et couche de revetement WO2000024438A1 (fr)

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AU23436/00A AU2343600A (en) 1998-10-27 1999-10-26 Microbial activity indicator composition and coating

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US17950998A 1998-10-27 1998-10-27
US09/179,509 1998-10-27

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EP2052712A1 (fr) * 2007-10-26 2009-04-29 3M Innovative Properties Company Composition dentaire
WO2009055530A3 (fr) * 2007-10-26 2009-10-29 3M Innovative Properties Company Composition dentaire destinée à la détection de bactéries, kit de parties, et utilisations de ceux-ci
US7909773B2 (en) 2005-06-03 2011-03-22 Tyco Healthcare Group Lp Post-operative bacteria test strip spool and method
WO2012120517A1 (fr) * 2011-03-07 2012-09-13 Mekorot Water Company, Ltd. Procédés et dispositifs permettant de traiter le bioencrassement
US8883177B2 (en) 2011-06-28 2014-11-11 Nian Wu Pharmaceutical compositions for parenteral administration
WO2014193402A1 (fr) * 2013-05-31 2014-12-04 Empire Technology Development Llc Détection de colonisation de lumière de sonde vésicale
US9228996B2 (en) 2013-05-31 2016-01-05 Empire Technology Development Llc Method and device for detecting device colonization
EP3100748A1 (fr) 2016-04-14 2016-12-07 Sefar AG Pansement
US9535043B2 (en) 2013-05-31 2017-01-03 Empire Technology Development Llc Color change indicator of biofilm formation
EP3187594A1 (fr) * 2015-12-30 2017-07-05 Palo Alto Research Center, Incorporated Systèmes, procédés et dispositifs de détection thermochromique
EP3187593A1 (fr) * 2015-12-30 2017-07-05 Palo Alto Research Center, Incorporated Dispositifs, systèmes et procédés de détection thermochromique
EP3292845A1 (fr) 2016-09-08 2018-03-14 Sefar AG Support d'indicateur et procede d'affichage d'une contamination, en particulier d'une plaie
CN110463832A (zh) * 2019-08-13 2019-11-19 广州悦蜂生物防治科技有限公司 一种天敌昆虫人工液态营养饲料品质的专用指示剂
US10598554B2 (en) 2015-12-30 2020-03-24 Palo Alto Research Center Incorporated Thermochromic sensing for nanocalorimetry
EP2021767B1 (fr) * 2006-05-08 2020-10-07 Becton, Dickinson and Company Indication de l'état de nettoyage d'un dispositif d'accès vasculaire

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CN108998500A (zh) * 2018-07-12 2018-12-14 浙江省产品质量安全检测研究院 一种材料抗菌性能快速检测方法

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Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7909773B2 (en) 2005-06-03 2011-03-22 Tyco Healthcare Group Lp Post-operative bacteria test strip spool and method
US8372014B2 (en) 2005-06-03 2013-02-12 Covidien Lp Post-operative bacteria test strip spool and method
EP2021767B1 (fr) * 2006-05-08 2020-10-07 Becton, Dickinson and Company Indication de l'état de nettoyage d'un dispositif d'accès vasculaire
US8834851B2 (en) 2007-10-26 2014-09-16 3M Innovative Properties Company Dental composition for detecting bacteria, kit of parts and use thereof
WO2009055530A3 (fr) * 2007-10-26 2009-10-29 3M Innovative Properties Company Composition dentaire destinée à la détection de bactéries, kit de parties, et utilisations de ceux-ci
EP2052712A1 (fr) * 2007-10-26 2009-04-29 3M Innovative Properties Company Composition dentaire
US9637770B2 (en) 2011-03-07 2017-05-02 Mekorot Water Company, Ltd. Methods and devices for handling biofouling
WO2012120517A1 (fr) * 2011-03-07 2012-09-13 Mekorot Water Company, Ltd. Procédés et dispositifs permettant de traiter le bioencrassement
JP2014510275A (ja) * 2011-03-07 2014-04-24 メコロット ウォーター カンパニー、リミテッド 生物付着に対処するための方法及びデバイス
US8883177B2 (en) 2011-06-28 2014-11-11 Nian Wu Pharmaceutical compositions for parenteral administration
WO2014193402A1 (fr) * 2013-05-31 2014-12-04 Empire Technology Development Llc Détection de colonisation de lumière de sonde vésicale
US9228996B2 (en) 2013-05-31 2016-01-05 Empire Technology Development Llc Method and device for detecting device colonization
US9535043B2 (en) 2013-05-31 2017-01-03 Empire Technology Development Llc Color change indicator of biofilm formation
US10724067B2 (en) 2015-12-30 2020-07-28 Palo Alto Research Center Incorporated Thermochromic sensing devices, systems, and methods
US11543303B2 (en) 2015-12-30 2023-01-03 Palo Alto Research Center Incorporated Thermochromic sensing for nanocalorimetry
JP2017118870A (ja) * 2015-12-30 2017-07-06 パロ アルト リサーチ センター インコーポレイテッド サーモクロミックセンシングデバイス、システム、および方法
EP3187593A1 (fr) * 2015-12-30 2017-07-05 Palo Alto Research Center, Incorporated Dispositifs, systèmes et procédés de détection thermochromique
US11718867B2 (en) 2015-12-30 2023-08-08 Palo Alto Research Center Incorporated Thermochromic sensing devices, systems, and methods
US9963732B2 (en) 2015-12-30 2018-05-08 Palo Alto Research Center Incorporated Thermochromic sensing devices, systems, and methods
US11655443B2 (en) 2015-12-30 2023-05-23 Palo Alto Research Center Incorporated Thermochromic sensing devices, systems, and methods
US10598554B2 (en) 2015-12-30 2020-03-24 Palo Alto Research Center Incorporated Thermochromic sensing for nanocalorimetry
EP3187594A1 (fr) * 2015-12-30 2017-07-05 Palo Alto Research Center, Incorporated Systèmes, procédés et dispositifs de détection thermochromique
WO2017121507A1 (fr) 2016-04-14 2017-07-20 Sefar Ag Pansement
EP3100748A1 (fr) 2016-04-14 2016-12-07 Sefar AG Pansement
EP3292845A1 (fr) 2016-09-08 2018-03-14 Sefar AG Support d'indicateur et procede d'affichage d'une contamination, en particulier d'une plaie
WO2018046270A1 (fr) 2016-09-08 2018-03-15 Sefar Ag Élément indicateur à appliquer et procédé pour indiquer le niveau de prolifération des germes, notamment dans une plaie
CN110463832A (zh) * 2019-08-13 2019-11-19 广州悦蜂生物防治科技有限公司 一种天敌昆虫人工液态营养饲料品质的专用指示剂

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AU2343600A (en) 2000-05-15

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