US20060083792A1 - Therapeutic treatments using the direct application of antimicrobial metal compositions - Google Patents
Therapeutic treatments using the direct application of antimicrobial metal compositions Download PDFInfo
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- US20060083792A1 US20060083792A1 US11/284,507 US28450705A US2006083792A1 US 20060083792 A1 US20060083792 A1 US 20060083792A1 US 28450705 A US28450705 A US 28450705A US 2006083792 A1 US2006083792 A1 US 2006083792A1
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- antimicrobial
- tissue
- atomic disorder
- antimicrobial metals
- metals
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Definitions
- This invention relates to therapeutic treatments in general, and more particularly to therapeutic treatments using the direct application of antimicrobial metal compositions.
- Localized infections affect millions of people each year. If not timely treated, localized infections may spread, can result in unnecessary pain, may require increasingly more aggressive treatment, can result in developmental delays and permanent disability and, in severe cases, can even result in death.
- a common form of treatment for localized infections is oral antibiotic therapy.
- this treatment is systemic, requires multiple dosages, frequently causes side effects, and can give rise to the evolution of antibiotic-resistant bacteria.
- debates are common among healthcare professionals and the general population regarding the over-use of antibiotics.
- Nucryst has determined that its antimicrobial metals with atomic disorder provide excellent therapeutic benefits. More particularly, antimicrobial metals with atomic disorder have been found to serve effectively as an antimicrobial agent, an anti-inflammatory agent, an immuno modulator agent, an enzyme modulator agent, and/or an anti-tumor agent, for human and/or animal use. Among other things, antimicrobial metals with atomic disorder have proven to be a broad spectrum (e.g., gram positive, gram negative, fungus and drug resistant) bacteriocidal agent with little likelihood of fostering resistant bacteria and having a sustained antimicrobial activity (for example, antimicrobial activity lasting over seven days has been consistently demonstrated with. antimicrobial metals with atomic disorder).
- a broad spectrum e.g., gram positive, gram negative, fungus and drug resistant
- Nucryst has recently discovered new ways of forming its antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form.
- the ability to form antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form has greatly expanded the possibilities for using these selected nanocrystalline compositions for therapeutic purposes.
- the ability to form antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form has lead to the further discovery that it is possible to utilize antimicrobial metals with atomic disorder in a radical new way, i.e., for direct application to a wide range of different tissues so as to therapeutically treat a wide range of different medical disorders.
- therapeutic treatments may be applied to internal anatomy as well as to surface anatomy.
- the present invention utilizes selected structures of antimicrobial metals.
- the antimicrobial metals are preferably selected noble metals such as silver, gold, platinum, palladium, etc.
- the structures are formed with atomic disorder, such that ions, clusters, atoms or molecules of the metals are released at a concentration sufficient to provide a localized therapeutic effect.
- the structures are preferably in nanocrystalline form.
- Antimicrobial metals with atomic disorder may be prepared in the manner taught in International Patent Publication No. WO 93/23092, published Nov. 25, 1993; International Patent Publication No. WO 95/13704, published May 26, 1995; and International Patent Publication No. WO 98/41095, published Sep. 24, 1998, which documents are incorporated herein by reference.
- Metal or “metals” includes one or more metals whether in the form of substantially pure metals, alloys or compounds such as oxides, nitrides, borides, sulphides, halides or hydrides.
- Antimicrobial metals are silver, gold, platinum, palladium, iridium, zinc, copper, tin, antimony, bismuth, or mixtures of these metals with same or other metals, silver, gold, platinum and palladium being preferred, and silver being most preferred.
- Noble metals are silver, gold, platinum and palladium, or mixtures of such metals with same or other metals, with silver metal being the most preferred.
- Antimicrobial effect means that atoms, ions, molecules or clusters of the antimicrobial or noble metal are released into the electrolyte which the coating contacts in concentration sufficient to inhibit microbial growth on and in the vicinity of the coating.
- the most common methods of measuring an antimicrobial effect are a zone of inhibition test (which indicates an inhibitory effect, whether microbiostatic or microbiocidal) or a logarithmic reduction test (which indicates a microbiocidal effect).
- ZOI zone of inhibition test
- the material to be tested is placed on a bacterial lawn (or a lawn of other microbial species) and incubated. A relatively small or no ZOI (ex.
- a logarithmic reduction test in viable bacteria is a quantitative measure of the efficacy of an antibacterial treatment; for example, a 5 log reduction means a reduction in the number of microorganisms by 100,000-fold (e.g., if a product contained 100,000 pertinent microorganisms, a 5 log reduction would reduce the number of pertinent microorganisms to 1). Generally, a 3 log reduction represents a bactericidal effect.
- the logarithmic reduction test involves combining the inoculum with the test treatment, recovering the bacteria or other microbial species, and enumerating the bacteria or other microbial species using serial dilutions.
- Anti-inflammatory effect means a reduction in one or more of the symptoms of erythema (redness), edema (swelling), pain and pruritus which are characteristic of inflammatory skin conditions.
- “Inflammatory skin conditions” refers to those conditions of the skin in which inflammatory cells (e.g., polymorphonuclear neutrophils and lymphocytes) infiltrate the skin with no overt or known infectious etiology, but excluding psoriasis and its related conditions. Symptoms of inflammatory skin conditions generally include erythema (redness), edema (swelling), pain, pruritus, increased surface temperature and loss of function.
- inflammatory cells e.g., polymorphonuclear neutrophils and lymphocytes
- Symptoms of inflammatory skin conditions generally include erythema (redness), edema (swelling), pain, pruritus, increased surface temperature and loss of function.
- inflammatory skin conditions include, but are not limited to, eczema and related conditions, insect bites, erythroderma, mycosis fungoides and related conditions, pyoderma gangrenosum, erythema multiforme, rosacea, onychomycosis, and acne and related conditions, but excluding psoriasis and its related conditions.
- Biocompatible means generating no significant undesirable host response for the intended utility. Most preferably, biocompatible materials are non-toxic for the intended utility. Thus, for human utility, biocompatible is most preferably non-toxic to humans or human tissues.
- sustained release or “sustainable basis” are used to define release of atoms, molecules, ions or clusters of a antimicrobial metal that continues over time measured in hours or days, and thus distinguishes release of such metal species from the bulk metal, which release such species at a rate and concentration which is too low to be therapeutically effective, and from highly soluble salts of antimicrobial metals such as silver nitrate, which releases silver ions virtually instantly, but not continuously, in contact with an alcohol or electrolyte.
- “Atomic disorder” includes high concentrations of one or more of: point defects in a crystal lattice, vacancies, line defects such as dislocations, interstitial atoms, amorphous regions, grain and sub grain boundaries and the like relative to its normal ordered crystalline state. Atomic disorder leads to irregularities in surface topography and inhomogeneities in the structure on a nanometer scale.
- Normal ordered crystalline state means the crystallinity normally found in bulk metal materials, alloys or compounds formed as cast, wrought or plated metal products. Such materials contain only low concentrations of such atomic defects as vacancies, grain boundaries and dislocations.
- “Diffusion”, when used to describe conditions which limit diffusion in processes to create and retain atomic disorder, i.e. which freeze-in atomic disorder, means diffusion of atoms (adatom diffusion) and/or molecules on the surface or in the matrix of the material being formed.
- Alcohol or water-based electrolyte is meant to include any alcohol or water-based electrolyte that the antimicrobial materials of the present invention might contact in order to activate (i.e. cause the release of species of the antimicrobial metal) into same.
- the term is meant to include alcohols (short chain (C 6 or less) and preferably C 4 or less), water, gels, fluids, solvents, and tissues containing, secreting, or exuding water or water-based electrolytes, including body fluids (for example blood, urine, or saliva), and body tissue (for example skin).
- Bioabsorbable as used herein in association includes substrates which are useful in medical devices, that is which are biocompatible, and which are capable of bioabsorption in period of time ranging from hours to years, depending on the particular application.
- Bioabsorption means the disappearance of materials from their initial application site in the body (human or mammalian) with or without degradation of the dispersed polymer molecules.
- Cold change is meant to include changes of intensity of light under monochromatic light as well as changes of hue from white light containing more than one wavelength.
- An “interference colour” is produced when light impinges on two or more partly reflective surfaces separated by a distance which bears the right relationship to the wavelength of the light to be removed by destructive interference.
- Partly reflective when used to describe the base or top layer materials, means that the material has a surface which reflects a portion of incident light, but which also transmits a portion of the incident light. Reflection occurs when a ray of incoming light encounters a boundary or interface characterized by a change in refractive index between two media.
- That interface is with air.
- the base layer the interface is with the top layer. The reflectance of the base and top layers is balanced so as to generate an interference colour.
- Partly light transmissive when used to describe a thin film of the top layer material means that the thin film is capable of transmitting at least a portion of incident visible light through the thin film.
- Detectable when used to describe a colour change means an observable shift in the dominant wavelength of the reflected light, whether the change is detected by instrument, such as a spectrophotometer, or by the human eye.
- the dominant wavelength is the wavelength responsible for the colour being observed.
- Cold working indicates that the material has been mechanically worked such as by milling, grinding, hammering, mortar and pestle or compressing, at temperatures lower than the recrystallization temperature of the material. This ensures that atomic disorder imparted through working is retained in the material.
- “Pharmaceutically- or therapeutically-acceptable” is used herein to denote a substance which does not significantly interfere with the effectiveness or the biological activity of the active ingredients (antimicrobial and anti-inflammatory activities) and which has an acceptable toxic profile for the host to which it is administered.
- “Therapeutically effective amount” is used herein to denote any amount of a formulation of the antimicrobial or noble metals which will exhibit either or both of an antimicrobial and optionally an anti-inflammatory effect, or some other therapeutic effect, when applied to the affected area of the tissue.
- a single application of the formulations of the present invention may be sufficient, or the formulations may be applied repeatedly over a period of time, such as several times a day for a period of days or weeks.
- the amount of the active ingredient, that is the antimicrobial or noble metal in the form of a coating, powder or dissolved in liquid solution will vary with the conditions being treated, the stage of advancement of the condition, the age and type of host, and the type and concentration of the formulation being applied. Appropriate amounts in any given instance will be readily apparent to those skilled in the art or capable of determination by routine experimentation.
- Carrier means a suitable vehicle including one or more solid, semisolid or liquid diluents, excipients or encapsulating substances which are suitable for administration to the skin.
- Nanocrystalline is used herein to denote single-phase or multi-phase polycrystals, the grain size of which is less than about 100, more preferably ⁇ 50, even more preferably ⁇ 40, even more preferably ⁇ 30, and most preferably ⁇ 25 nanometers in at least one dimension.
- the term, as applied to the crystallite or grain size in the crystal lattice of coatings, powders or flakes of the antimicrobial or noble metals, is not meant to restrict the particle size of the materials when used in a powder form.
- Powder is used herein to include particulates of the antimicrobial or noble metals ranging from nanocrystalline (less than 100 nm) to submicron sized powders up to flakes.
- powders of the antimicrobial or noble metals used in the present invention are sized at less than 100 ⁇ m, and more preferably less than 40 ⁇ m, and most preferably less than 10 ⁇ m.
- Gram size or “crystallite size” means the size of the largest dimension of the crystals in the antimicrobial metal coating or powder.
- “Hydrocolloid” means a synthetically prepared or naturally occurring polymer capable of forming a thickened gel in the presence of water and polyols (swelling agent).
- the swelling agent must be capable of swelling the hydrocolloid chosen in order to form the gel phase.
- Hydrocolloid means a hydrocolloid swollen with water or another hydrophilic liquid which is used for absorbing or retaining moisture or water.
- Gel means a composition that is of suitable viscosity for such purposes, e.g., a composition that is of a viscosity that enables it to be applied and remain on the skin.
- nanocrystalline antimicrobial metal and similar terminology, such as “nanocrystalline coatings or powders” is meant to refer to antimicrobial metals formed with atomic disorder and having a nanocrystalline grain size.
- Antimicrobial metals with atomic disorder may be provided in free-standing powder form in a variety of different ways.
- antimicrobial metals with atomic disorder may be provided in free-standing powder form by vapor deposition on a fixed element, with the deposited material thereafter being stripped off so as to yield the desired free-standing powder.
- antimicrobial metals with atomic disorder may be provided in free-standing powder form by vapor deposition on an NGRC (“next generation roll coater”) apparatus. More particularly, a continuous belt is coated with antimicrobial metals with atomic disorder using vapor deposition techniques, with the antimicrobial metals with atomic disorder being scraped off the belt further down the line so as to yield the free-standing powder form of the antimicrobial metals with atomic disorder.
- NGRC next generation roll coater
- This last-mentioned method for making the free-standing powder form of the antimicrobial metals with atomic disorder is particularly advantageous, inasmuch as it can quickly and easily yield a relatively large supply of free-standing powder at a relatively low cost.
- Crystalline powder forms of the antimicrobial or noble metals can be prepared as free standing powders, by coating powdered substrates, or from coatings on substrates which are then collected, for example by scraping and then sized.
- the powders may be prepared as pure metals, metal alloys or compounds such as metal oxides or metal salts, by vapour deposition, mechanical working, or compressing to impart the atomic disorder.
- the crystalline powders are formed with atomic disorder in accordance with the techniques set out above and as published in the prior patent applications of Burrell et al., see for example WO 93/23092, published Nov. 25, 1993, and WO 95/13704, published May 26, 1995.
- the atomic disorder will most typically be formed in the metal powders during physical vapour deposition as set out above for coatings or by mechanically imparting the disorder, such as by milling, grinding, hammering, mortar and pestle or compressing, under conditions of low temperature (i.e., temperatures less than the temperature of recrystallization of the material) to ensure that annealing or recyrstallization does not take place.
- the powders may be formed by inert-gas condensation techniques, which are modified to provide atomic disorder in the powder produced, as taught in WO 95/13704 to Burrell et al.
- Powders of the antimicrobial or noble metals are preferably formed by physical vapour deposition (PVD) onto a substrate such as a cold finger, a silicon wafer, solid plates, a rotating cylinder, a continuous belt in a roll coater, or on steel collectors in known PVD coaters.
- PVD physical vapour deposition
- Preparation of powders of the present invention by sputtering onto a continuous belt in a roll coater, or other some other moving or rotating substrate surface is particularly advantageous, inasmuch as it can quickly and easily yield a relatively large supply of free-standing powder at a relatively low cost.
- a stainless-steel belt can be used in the roll coating process without the need to provide additional cooling of the substrate.
- the powders or coatings are then scraped off to form a powder, and may be sized to avoid overly large particulates.
- the powders are scraped off the moving surface with scrapers which contact the moving surface at an angle sufficient to remove the coating in flake or powder form.
- the coating may be scraped off with scrapers angled for forward cutting of the coating from the moving surface, or with scrapers which remove the coating from the moving surface by reverse dragging action on the surface.
- the scrapers may be suspended above the belt, and either weighted or spring loaded to apply pressure sufficient to remove the coating from the moving surface. With a continuous belt, the scrapers can conveniently be located above the end rollers to remove the coating with a reverse dragging action as the belt rounds the end roller.
- the powders of the antimicrobial or noble metals may be formed on powdered substrates which are biocompatible, or otherwise compatible for the end use of the powder.
- powdered substrates are hydrocolloids, particularly those which are bioabsorbable and/or hygroscopic powders such as chitin.
- Exemplary bioabsorbable and/or hygroscopic powders are composed of:
- Synthetic Bioabsorbable Polymers for example polyesters/polyactones such as polymers of polyglycolic acid, glycolide, lactic acid, lactide, dioxanone, trimethylene carbonate etc., polyanhydrides, polyesteramides, polyortheoesters, polyphosphazenes, and copolymers of these and related polymers or monomers.
- Naturally Derived Polymers Proteins: albumin, fibrin, collagen, elastin; Polysaccharides: chitosan, alginates, hyaluronic acid; and Biosynthetic Polyesters: 3-hydroxybutyrate polymers.
- the powders may be incorporated into or onto medical dressings or pharmaceutical formulations, by any methods known in the art.
- the powders may be layered onto the substrates (dressings or powders), mechanically fixed within the fibres of the dressings, impregnated into dressings by physical blowing, or added to topical pharmaceutical ingredients.
- powders of the present invention are sized at less than 100 ⁇ m, and more preferably less than 40 ⁇ m, and most preferably about 3-5 ⁇ m in size.
- antimicrobial metals with atomic disorder Once antimicrobial metals with atomic disorder have been provided in free-standing powder form, they can then be used therapeutically in that form, or the free-standing powder can be used to form solutions or suspensions of the antimicrobial metals with atomic disorder prior to being used to therapeutically treat tissue.
- Antimicrobial metals with atomic disorder in free-standing powder form may be sprinkled lightly onto surface anatomy (e.g., the skin) in therapeutically effective amounts so as to provide an antimicrobial treatment to that surface anatomy, e.g., to an infected cut.
- antimicrobial metals with atomic disorder may be mixed with one or more other materials prior to being sprinkled onto the skin, where these other materials may be biologically active materials (e.g., growth promoters) or biologically neutral materials acting as a “filler” to facilitate easier deployment of relatively small quantities of antimicrobial metals with atomic disorder.
- antimicrobial metals with atomic disorder in free-standing powder form can be applied to the lungs using a so-called dry powder inhaler.
- Antimicrobial metals with atomic disorder in free-standing powder form may also be injected, by small-needle or needle-less injection, into the interior of the body in therapeutically effective amounts so as to provide their therapeutic benefit to interior anatomy.
- the antimicrobial metals with atomic disorder can be delivered to interior anatomy via a small-needle drug delivery system or via a needle-less drug delivery system.
- Such systems are available from Powderject Research Limited of Oxford, United Kingdom (see, for example, U.S. Pat. Nos. 5,899,880; 6,010,478 and 6,013,050, which patents are hereby incorporated herein by reference) and Bioject, Inc. of Portland, Oreg. (see, for example, U.S. Pat. Nos. 4,596,556; 4,790,824; 5,064,413; 5,312,335; 5,383,851; 5,399,163; 5,520,639; 6,096,002; and Des. 349,958, which patents are also hereby incorporated herein by reference). Delivery of antimicrobial metals with atomic disorder with such drug delivery systems provides local therapy to the interior anatomy.
- the particulate size be less than 2 microns, and preferably less than 1 micron, so as so minimize any adverse reaction to the presence of the particulate in the tissue.
- Many health afflictions can be addressed by delivering antimicrobial metals with atomic disorder, in free-standing powder form, to an interior anatomical site with small-needle and/or needle-less drug delivery systems.
- examples of some of these applications include: (1) dermal drug delivery for skin conditions such as, but not limited to, acne, psoriasis, eczema and skin infections; (2) localized infections such as, but not limited to, middle ear infections, endocardititis, pericarditis, prostatitis, sinusitis, osteomyelitis and onychomycosis; (3) mouth, gum and throat afflictions; (4) arthritis; and (5) direct-to-tumor chemotherapeutic delivery.
- antimicrobial metals with atomic disorder may be injected directly into psoriatic plaques.
- antimicrobial metals with atomic disorder may be injected by small-needle or needle-less injection through the eardrum (i.e., through the tympanic membrane) into the middle ear, whereby to provide a localized antimicrobial, anti-inflammatory treatment for middle ear infections.
- long-acting antimicrobial metals with atomic disorder may be injected into the prostate gland for difficult-to-treat prostate infections.
- antimicrobial metals with atomic disorder may be injected into the tissues of the oral cavity and throat to treat sore throats, thrush (candida infections) and periodontal diseases such as gingivitis.
- antimicrobial metals with atomic disorder may be injected into arthritic joints to reduce destructive inflammation.
- long-acting antimicrobial metals with atomic disorder of platinum can be injected into tumors that are responsive to chemotherapy with platinum compounds.
- antimicrobial metals with atomic disorder in solution form.
- the solution form of antimicrobial metals with atomic disorder can be advantageous in many anatomical applications, since there is substantially no particulate present which might irritate tissue.
- Antimicrobial metals with atomic disorder may be provided in solution form in a variety of different ways.
- a solution of antimicrobial metals with atomic disorder is created by dissolving a free-standing powder of antimicrobial metals with atomic disorder in water.
- the free-standing powder of antimicrobial metals with atomic disorder may be packaged in a “tea-bag” type pouch, such that undissolved antimicrobial metals with atomic disorder remain captured within the pouch.
- a solution of antimicrobial metals with atomic disorder may be provided by immersing, in water, a substrate carrying deposited antimicrobial metals with atomic disorder.
- a carrier strip may be coated with antimicrobial metals with atomic disorder by vapor deposition, and then the carrier strip may be immersed in water so as to create the solution of antimicrobial metals with atomic disorder.
- a bandage may be coated with antimicrobial metals with atomic disorder by vapor deposition, and then the bandage may be immersed in water so as to create the solution of antimicrobial metals with atomic disorder.
- the solution of antimicrobial metals with atomic disorder may be prepared in advance. (e.g., at a manufacturing plant) or on site at the time of use. Where a solution of antimicrobial metals with atomic disorder is prepared in advance (e.g., at a manufacturing plant), it is preferred that the solution be created by immersing a “tea-bag” type pouch of the free-standing powder form of antimicrobial metals with atomic disorder in water and leaving it there until the time of use, or by immersing a substrate carrying deposited antimicrobial metals with atomic disorder in water and leaving it there until the time of use.
- a solution of antimicrobial metals with atomic disorder may be applied to tissue as a liquid or as an aerosol.
- the. dosage is dependent, to at least some extent, on the concentration of antimicrobial metals with atomic disorder present in the solution.
- concentration of antimicrobial metals with atomic disorder it may be desirable to raise the concentration of antimicrobial metals with atomic disorder in the solution.
- the pH of the solution can be lowered by adding acid to the solution.
- CO 2 is added to the solution: the CO 2 creates carbonic acid, thus lowering the pH of the solution and increasing the concentration of antimicrobial metals with atomic disorder in the solution.
- a solution of antimicrobial metals with atomic disorder may be applied to tissue as a liquid or as an aerosol.
- a solution of antimicrobial metals with atomic disorder may be applied, in liquid form, and in various viscosities, to a wide range of different tissues in therapeutically effective amounts so as to therapeutically treat a wide range of different medical disorders.
- a solution of antimicrobial metals with atomic disorder can be applied as a rinse or bath or wash to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections.
- a solution of antimicrobial metals with atomic disorder can be applied as a rinse or bath or wash to treat a wound or a surgical site.
- a solution of antimicrobial metals with atomic disorder can be applied to mouth tissue (e.g., the gums) as an oral rinse.
- a solution of antimicrobial metals with atomic disorder can be applied to throat tissue as a gargle.
- a solution of antimicrobial metals with atomic disorder can be applied to nasal passages and the sinus, e.g., to treat sinusitis and allergic rhinitis.
- a solution of antimicrobial metals with atomic disorder can be applied to the eyes as eyedrops.
- a solution of antimicrobial metals with atomic disorder can be applied to the ears as ear drops.
- a solution of antimicrobial metals with atomic disorder may be introduced by catheter into the bladder to treat a bladder infection; or injected into the middle ear to treat middle ear infections; or injected or instilled or otherwise introduced into the abdomen to treat a post-surgical abdominal abscess or to treat an infection from peritoneal dialysis; or injected or instilled or otherwise introduced into other internal anatomical structures, including body cavities, so as to treat conditions such as, but not limited to, endocardititis, pericarditis, prostatitis, sinusitis, osteomyelitis and onychomycosis; or injected into skin tissue to treat acne, psoriasis, eczema and/or or other skin conditions; etc.
- a solution of antimicrobial metals with atomic disorder may also be applied, in aerosol form, to a wide range of different tissues in therapeutically effective amounts so as to therapeutically treat a wide range of different medical disorders.
- a solution of antimicrobial metals with atomic disorder may be applied in aerosol form to surface tissues as a spray.
- a solution of antimicrobial metals with atomic disorder can be applied as a spray to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections.
- a solution of antimicrobial metals with atomic disorder can be applied as a spray to treat or clean a wound or a surgical site.
- a solution of antimicrobial metals with atomic disorder in aerosol form, may be inhaled by a patient for deployment to the throat, the nasal and sinus passages and/or the lungs.
- the aerosol of antimicrobial metals with atomic disorder may be created by passing a liquid solution of antimicrobial metals with atomic disorder through a mechanical mister (e.g., a simple spray bottle or nebulizer) and may be applied directly (e.g., via a hand inhaler) or through some other delivery system (e.g., an oxygen tent, etc.).
- a mechanical mister e.g., a simple spray bottle or nebulizer
- some other delivery system e.g., an oxygen tent, etc.
- the droplet size of the aerosol can be important for at least two reasons.
- the droplet size of the aerosol can affect the dosage of antimicrobial metals with atomic disorder being applied to the tissue, i.e., a larger droplet size results in delivery of more antimicrobial metals with atomic disorder to the tissue.
- the droplet size of the aerosol can also affect delivery of the antimicrobial metals with atomic disorder to the target tissue, e.g., where the aerosol is inhaled through the mouth, big droplets tend to stay in the throat whereas small droplets (e.g., approximately 10 microns or so) tend to travel to the lungs.
- droplet size can be regulated, to at least some extent, by the device (e.g., the mechanical mister) which is used to produce the aerosol.
- the device e.g., the mechanical mister
- the aerosol's droplet size can be adjusted, to at least some extent, by modifying the surface tension of the solution. More particularly, the solution of antimicrobial metals with atomic disorder has water as its solvent, and water has a relatively high surface tension, so it is relatively straightforward to create an aerosol having a relatively small droplet size.
- surfactants can be added to the solution so as to reduce the surface tension of the solution, whereby to create an aerosol having a relatively large droplet size.
- surfactants may comprise phospholipids, e.g., lecithin, sphingomyelin, etc.
- antimicrobial metals with atomic disorder in suspension form.
- the suspension form of antimicrobial metals with atomic disorder can be advantageous in many applications, since it has a relatively long storage life and, perhaps even more importantly, has a relatively long-lasting therapeutic life.
- Antimicrobial metals with atomic disorder may be provided in suspension form in a variety of different embodiments. More particularly, a suspension of antimicrobial metals with atomic disorder can be created in free-standing form or as a dried gel applied to a medical device.
- a suspension of antimicrobial metals with atomic disorder can comprise a free-standing form, i.e., it can comprise a liquid such as a lotion; or a semi-solid such as a gel (i.e. a water-based hydrocolloid) or an emulsion (i.e., an oil-in-water or water-in-oil suspension) such as a cream or ointment.
- Formulations can include carboxymethyl cellulose (“CMC”), polyvinyl alcohol, methyl parabin, proply parabin, and 0.1% antimicrobial metals with atomic disorder in powder form.
- a suspension of antimicrobial metals with atomic disorder can comprise a dried gel applied to a medical device.
- a hydrated form of the gel is created, applied to a medical device, and then dehydrated. During use, the gel becomes rehydrated, whereby the antimicrobial metals with atomic disorder are released to provide their therapeutic effect to tissue.
- the suspension may also include biologically active agents such as cytoconductive agents, etc.
- biologically active agents such as cytoconductive agents, etc.
- betaglucan a complex carbohydrate which appears to have cytoconductive properties, may be added to the suspension.
- glycerol can be deleterious to the therapeutic effect of the antimicrobial metals with atomic disorder, and should be avoided.
- a suspension of antimicrobial metals with atomic disorder can comprise a free-standing form, i.e., it can comprise a liquid such as a lotion; or a semi-solid such as a gel (i.e. a water-based hydrocolloid) or an emulsion (i.e., an oil-in-water or water-in-oil suspension) such as a cream or ointment.
- a free-standing form of the suspension are intended to be applied topically to the tissue which is to be treated, in therapeutically effective amounts, and can be used to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections.
- the free-standing forms of the suspension can be applied topically to treat a wound or a surgical site, etc.
- a suspension of antimicrobial metals with atomic disorder in the form of a dried gel applied to medical devices.
- the hydrated form of the gel is created, applied to a medical device (e.g., during manufacture of the medical device), and then dehydrated. During use, the gel becomes rehydrated, whereby the antimicrobial metals with atomic disorder are released in therapeutically effective amounts so as to provide their therapeutic effect to tissue.
- Examples of medical devices which are prime candidates for a dried gel coating include catheters (e.g., urological catheters, in-dwelling catheters, drainage catheters, etc.), bone screws, total joints, vascular grafts, hernia meshes, surgical dressings, surgical packing materials, etc.
- catheters e.g., urological catheters, in-dwelling catheters, drainage catheters, etc.
- bone screws e.g., urological catheters, in-dwelling catheters, drainage catheters, etc.
- total joints e.g., vascular grafts, hernia meshes, surgical dressings, surgical packing materials, etc.
- the dried gel can be quite stable and easy to handle when dehydrated, but very slippery when rehydrated.
- dried gels can be particularly advantageous with certain types of medical devices which might otherwise require lubrication during use, since the rehydrated gel automatically provides such lubrication.
- Urological catheters are one example of a medical device which generally requires lubrication during use, and which would benefit from the natural lubrication provided by the rehydrated gel.
- 0.5 milligrams of antimicrobial metals with atomic disorder, in free-standing powder form, are injected, using a small-needle drug delivery system or a needle-less drug delivery system, into gum tissue so as to treat gingivitis.
- the treatment is repeated every 3 days until the therapeutic effects are no longer needed.
- a solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water.
- the solution of antimicrobial metals with atomic disorder is applied as a rinse or bath or wash to a wound site so as to provide an antimicrobial treatment to the wound site. The treatment is repeated every 24 hours until the therapeutic effects are no longer needed.
- a solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water.
- the solution of antimicrobial metals with atomic disorder is applied to the interior of the bladder via a catheter so as to provide antimicrobial treatment to the bladder. The treatment is repeated every 8 hours until the therapeutic effects are no longer needed.
- a solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water.
- the solution of antimicrobial metals with atomic disorder is injected (using a small-needle or needle-less injection system) under the toenails or into the nail bed and/or the surrounding tissue of a person suffering from onychomycosis so as to provide an antimicrobial treatment to the tissue.
- the treatment is repeated 2 times a day until the therapeutic effects are no longer needed.
- Solutions of nanocrystalline noble metals were prepared by immersing Acticoat® burn dressings (distributed by Smith & Nephew) in reverse osmosis water that had been pretreated with CO 2 in order to reduce the pH. Two different concentrations of antimicrobial metals with atomic disorder solutions were prepared by this method, the concentrations being 85 ⁇ g/mL and 318 ⁇ g/mL. Solutions of silver nitrate were also prepared to use as comparisons in the experiments. The concentrations of the silver nitrate were 103 ppm of silver and 295 ppm of silver as determined by Atomic Absorption Spectroscopy.
- the solutions were in turn placed in an ultrasonic nebulizer that created small droplets containing dissolved and suspended parts of the solution of nanocrystalline noble metals.
- the output from the nebulizer was directed into a chamber made from a stainless steel frame and base.
- Petri dishes containing Mueller Hinton agar streaked with 4 h old cultures of Pseudomonas aerugiona and Staphylococcus aureus were exposed to nanocrystalline noble metal aerosols and the silver nitrate aerosols.
- the delivery of antimicrobial materials may most expeditiously be accomplished by using aerosols (e.g., in the treatment of pneumonia).
- aerosols e.g., in the treatment of pneumonia.
- the drawback of aerosols is the requirement for a high concentration of the active ingredient to ensure that a sufficient amount is delivered to achieve the biological effect desired without causing problems with the carrier solvent (e.g., water).
- the essential requirement of the equipment for producing an aerosol that contains dissolved and suspended components of antimicrobial metals with atomic disorder is that it must form droplets of aerosol directly from the liquid form, and the aerosol droplets must be small enough to reach the lungs. This means that the droplets should be preferably less than approximately 10 ⁇ m.
- the aerosol cannot be created by first evaporating the liquid and then condensing it to form droplets, since this would remove the desired antimicrobial metals with atomic disorder from the aerosol.
- the method used to create an aerosol for these tests was the mechanical method in the form of an ultrasonic nebulizer.
- an ultrasonic humidifier was used for convenience.
- the liquid containing the dissolved and suspended antimicrobial metals with atomic disorder was placed in the water reservoir of the humidifier.
- aerosol droplets of dissolved and suspended antimicrobial metals with atomic disorder were generated and flowed from the output nozzle.
- a test chamber was constructed using a stainless steel frame with a transparent plastic covering.
- the frame was placed on a stainless steel plate.
- the output nozzle from the humidifier was modified so that the aerosol could be directed into the chamber at a height of approximately 30 cm from the base.
- the plates and other test samples were placed on the stainless steel plate and exposed to the aerosol for a prescribed length of time.
- a solution of antimicrobial metals with atomic disorder was prepared by immersing 518 sq. inches of Acticoat® burn dressing in 1 L of reverse osmosis water, which was treated with CO 2 to maintain a pH of 6.5. After 20 minutes the concentration of silver in the water was 85 ⁇ g/mL.
- a solution containing 370 ⁇ g/mL of silver from a Acticoat® dressing was prepared as follows: 1 L of reverse osmosis water was purged with commercial grade carbon dioxide until the pH was 4.3. Sufficient Acticoat® dressing was added to bring the pH up to 6.5. At that time, the silver concentration was 370 ⁇ g/mL.
- Ag as AgNo 3 was prepared by dissolving 0.157 g of AgNo 3 into 1 L of reverse osmosis water and mixed until dissolved. The solution was analyzed by Atomic Absorption Spectroscopy and found to be 102.9 ppm of silver.
- Ag as AgNO 3 was prepared by dissolving 0.427 of AgNO 3 into 1 L of reverse osmosis water and mixed until dissolved. The solution was analyzed by Atomic Absorption Spectroscopy and found to be 295 ppm of silver.
- Petri dishes containing Mueller Hinton agar, were streaked with 4 h old cultures of Pseudomonas aeruginosa or Staphylococcus aureus . The plates were then weighed and their exposed outer surfaces were coated with Parafilm to prevent condensation from occurring on these surfaces. These plates were placed in the aerosol chamber uncovered. The ultrasonic nebulizer was then started and run for 53 minutes. The plates were then removed from the chamber, the plastic was removed and the dishes re-weighed so that the amount of moisture loss/gain could be determined.
- the plates were then placed in a 35° C. incubator for 16 h. After incubation the pattern and amount of growth was assessed on the plates for both organisms.
- the Acticoat® dressing generated silver was effective at controlling the growth of both organisms while the silver nitrate only prevented the growth of Ps. aeruginosa .
- Viability tests showed that at the low concentration, neither form of silver was completely bactericidal although the poor growth on the plates treated with antimicrobial metals with atomic disorder compared to the silver nitrate treated plates suggests that a significant log reduction occurred in the plates treated with the aerosol of antimicrobial metals with atomic disorder.
- both antimicrobial metals with atomic disorder (37.0 ⁇ g/mL) and AgNo 3 (300 ⁇ g/mL) were effective at controlling P. aeruginosa . Since no re-growth occurred, it is assumed that the agent at this concentration was bactericidal. Antimicrobial silver with atomic disorder was more effective than AgNO 3 at controlling S. aureus . No re-growth occurred on any plates or in the broth indicating a total kill of the organism while, in the AgNO 3 treatment, a large number of organisms grew at 16h.
- a dose per unit area can be calculated. In each case for Solution 1, the dose was 8.5 ⁇ g/sq. inch, while for Solution 2, the dose was 38 ⁇ g/sq. inch. These doses, on a per lung basis, would be less than 10 mg of silver per hour of treatment. Each hour of treatment with antimicrobial silver with atomic disorder aerosols appears to provide at least 48 h of protection. Therefore, the dose per day, from the high concentration treatment, would be about 5 mg or a little less than the silver released by 2 sq. inches of SSD per day.
- the most significant advantage of using antimicrobial silver with atomic disorder may be the lack of a toxic action such as NO 3 or sulfadiazine.
- Aerosols of antimicrobial metals with atomic disorder transmit the antimicrobial activity of the dressings to remote sites.
- Aerosols of antimicrobial metals with atomic disorder are more effective than comparable concentrations of silver nitrate.
- Gel products of antimicrobial metals with atomic disorder encompass both “wet” and “dry” materials.
- a “wet” gel product of antimicrobial metals with atomic disorder is a product that provides moisture to a dry skin condition (psoriasis, eczema, acne, wound, etc.) and facilitates autolytic debridement of necrotic tissue. It also delivers the antimicrobial and anti-inflammatory properties of the suspended antimicrobial metals with atomic disorder powders.
- biologically active molecules it is also beneficial to supply biologically active molecules to elicit a specific response such as cell migration, etc. Since these biologically active molecules are susceptible to microbial degradation if not protected, it is beneficial to include them in gels of antimicrobial metals with atomic disorder that will provide the necessary protection.
- “Dry” gel products of antimicrobial metals with atomic disorder are physically stabilized (dry or cross-linked) materials that provide lubricious, antimicrobial, antithrombogenic, and anti-inflammatory properties to a variety of implantable, trancutaneous or topically applied devices.
- the coatings may also provide other benefits such as accelerating or otherwise facilitating tissue integration by creating a favorable environment for cell proliferation. This favorable environment may be created by including cytoconductive agents or anti-adhesion agents such as bone morphogenetic proteins, B-glucan hyaluronic acids in the gel.
- the gel may be stabilized by cross-linking the gel components (collagen, gelatin, etc.) or by drying the coated materials.
- CMC Carboxymethyl cellulose
- PVA Polyvinyl alcohol
- Collagen 0.1-10 Pectin 0.1-10 Gelatin 0.1-10 Chitin 0.1-10 Chitosan 0.1-10 Alginate 0.1-10 Poly ( ⁇ -amino acids) Polyester Poly-1-caprolactone PEG Cocoa butter Sepigel
- a commercial carboxymethyl cellulose/pectin gel (Duoderm Convatec) was combined with antimicrobial metals with atomic disorder powder to produce a gel with 0.1% silver.
- a logarithmic reduction test was performed as follows in the gel using Pseudomonas aeruginosa.
- the inoculum was prepared by placing 1 bacteriologic loopful of the organism in 5 mL of trypticase soy broth and incubating it for 3-4 h. The inoculum (0.1 mL) was then added to 0.1 mL of gel and vortexed (triplicate samples). The mixture was incubated for one-half hour. Then 1.8 mL of sodium thioglycollate-saline (STS) solution was added to the test tube and vortexed. Serial dilutions were prepared on 10 ⁇ 1 to 10 ⁇ 7 . A 0.1 mL aliquot of each dilution was plated in duplicate into Petri plates containing Mueller-Hinton agar. The plates were incubated for 48 h and then colonies were counted. Surviving members of organisms were determined and the logarithmic reduction compared to the initial inoculum was calculated.
- STS sodium thioglycollate-saline
- Carboxymethyl cellulose (CMC) fibers were coated directly to produce a defective nanocrystalline antimicrobial coating.
- the CMC was then gelled in water by adding 2.9 g to 100 mL volume. This material was tested using the method of No. 1. The material generated a 5.2 logarithmic reduction of Pseudomonas aeruginosa , demonstrating that the gel had a significant bactericidal effect.
- alginate fibrous substrate was directly coated with a defective nanocrystalline antimicrobial coating.
- the alginate (5.7 g) was added to 100 mL volume of water to create a gel.
- This material was tested using the method of No. 1. The material generated a 5.2 logarithmic reduction of Pseudomonas aeruginosa , demonstrating that the gel had a significant bactericidal effect.
- a commercial gel containing CMC and alginate (Purilin gel Coloplast) was mixed with a defective nanocrystalline silver powder to give a product with 0.1% silver. This was tested as above with both Pseudomonas aeruginosa and Staphylococcus aureus . Zone of inhibition data was also generated for this gel as follows.
- An inoculum Pseudomonas aeruginosa and Staphylococcus aureus ) was prepared as in No. 1 and 0.1 mL of this was spread onto the surface of Mueller-Hinton agar in a Petri dish. A six mm hole was then cut into the agar at the center of the Petri dish and removed.
- the well was filled with either 0.1 mL of the silver containing gel, a mupirocin containing cream or a mupirocin containing ointment.
- the Petri plates were then incubated for 24 h and the diameter of the zone of inhibition was measured and recorded.
- the silver containing gel produced 9 mm zones against both Pseudomonas aeruginosa and Staphylococcus aureus , while the mupirocin cream and ointment produced 42 and 48 mm zones against Staphylococcus aureus and 0 mm zones against Pseudomonas aeruginosa.
- the silver containing gel reduced the Pseudomonas aeruginosa and Staphylococcus aureus properties 4.4 and 0.6 logs, respectively, showing good bactericidal activity.
- the mupirocin cream and ointment generated 0.4 and 0.8, and 0.8 and 1.6, log reductions against Staphylococcus aureus and Pseudomonas aeruginosa , respectively.
- the silver gel had both a greater bactericidal effect and spectrum of activity than the mupirocin containing products.
- Aeruginosa 5 2% 0.1% 11 13 1.4 >6 6 2% 0.5% 0.1% 0.1 0.02 14 15 3.3 >6 7 2% 0.5% 0.1% 13 14 2.0 N/A 8 2% 0.5% 0.1% 0.1 14 14 2.0 N/A 9 2% 0.5% 0.1% 0.20 14 14 2.0 N/A 10 2% 0.5% 0.1% 0.5 0.1 0.20 14 14 2.0 >6
- a commercially available gel (glyceryl polymethacrylate) was blended with antimicrobial metals with atomic disorder powder to produce a gel with a silver content of 0.1%. This gel was tested as in Nos. 5-10 and was found to produce zones of 15 mm against both Staphylococcus aureus and Pseudomonas aeruginosa . Log reductions of 1.7 and >5 were produced against Staphylococcus aureus and Pseudomonas aeruginosa . This gel product had a greeted spectrum of activity than did mupirocin cream or ointment.
- a gel coat for a urinary catheter was prepared using the formula in No. 6. The coating was applied to the catheter using a dipping method. The coating was air dried overnight.
- the dried gel coat was smooth and easy to handle. It was not tacky to touch and had excellent abrasion and adhesion properties. Upon rewetting, the surface became extremely slippery indicating excellent lubricious properties.
- a zone of inhibition test was performed against Pseudomonas aeruginosa using an inoculum as prepared in No. 1.
- the inoculum (0.1 mL) was spread over the surface of Mueller-Hinton agar in a Petri plate.
- the catheter was cut into 1′′ segments which were laid on their side into the middle of the Petri plate. Petri plates were incubated for 24 h and then the zone of inhibitions was measured.
- zones of inhibition were generated that ranged from 7-10 mm. This indicates that getting drying and rehydrating had no negative effect on the antimicrobial activity of the gel coat.
Abstract
Therapeutic treatments using the direct application of selected structures of antimicrobial metals in free-standing powder form, solution form and/or suspension form in therapeutically effective amounts. The selected structures of antimicrobial metals serve as an antimicrobial agent, an anti-inflammatory agent, an immuno modulator agent, an enzyme modulator agent, and/or an anti-tumor agent, for human and/or animal use.
Description
- This patent application:
- (1) claims benefit of pending prior U.S. Provisional Patent Application Ser. No. 60/285,884, filed Apr. 23, 2001 by Robert E. Burrell et al. for THERAPEUTIC TREATMENTS USING THE DIRECT APPLICATION OF NOBLE METAL COMPOSITIONS (Attorney's Docket No. WEST-1 PROV), which patent application is hereby incorporated herein by reference; and
- (2) is a continuation-in-part of pending prior U.S. patent application Ser. No. 09/840,637, filed Apr. 23, 2001 by Robert E. Burrell et al. for TREATMENT OF ACNE (Attorney's Docket No. 53-01), which patent application is also hereby incorporated herein by reference.
- This invention relates to therapeutic treatments in general, and more particularly to therapeutic treatments using the direct application of antimicrobial metal compositions.
- Localized infections affect millions of people each year. If not timely treated, localized infections may spread, can result in unnecessary pain, may require increasingly more aggressive treatment, can result in developmental delays and permanent disability and, in severe cases, can even result in death.
- A common form of treatment for localized infections is oral antibiotic therapy. However, this treatment is systemic, requires multiple dosages, frequently causes side effects, and can give rise to the evolution of antibiotic-resistant bacteria. Furthermore, debates are common among healthcare professionals and the general population regarding the over-use of antibiotics.
- As a result, there is a significant need for an improved treatment for localized infections.
- Nucryst Pharmaceuticals Corp. and its predecessors, all of Fort Saskatchewan, Alberta, Canada and sometimes collectively referred to herein as “Nucryst”, have developed selected structures of antimicrobial metals such as silver, gold, platinum, palladium, etc. See, for example, International Patent Publication No. WO 93/23092, published Nov. 25, 1993; International Patent Publication No. WO 95/13704, published May 26, 1995; and International Patent Publication No. WO 98/41095, published Sep. 24, 1998, which documents are hereby incorporated herein by reference. These selected structures of antimicrobial metals will hereinafter sometimes be collectively referred to as “antimicrobial metals with atomic disorder”.
- Nucryst has determined that its antimicrobial metals with atomic disorder provide excellent therapeutic benefits. More particularly, antimicrobial metals with atomic disorder have been found to serve effectively as an antimicrobial agent, an anti-inflammatory agent, an immuno modulator agent, an enzyme modulator agent, and/or an anti-tumor agent, for human and/or animal use. Among other things, antimicrobial metals with atomic disorder have proven to be a broad spectrum (e.g., gram positive, gram negative, fungus and drug resistant) bacteriocidal agent with little likelihood of fostering resistant bacteria and having a sustained antimicrobial activity (for example, antimicrobial activity lasting over seven days has been consistently demonstrated with. antimicrobial metals with atomic disorder).
- Furthermore, Nucryst has recently discovered new ways of forming its antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form. The ability to form antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form has greatly expanded the possibilities for using these selected nanocrystalline compositions for therapeutic purposes. In particular, the ability to form antimicrobial metals with atomic disorder in free-standing powder form, solution form and suspension form has lead to the further discovery that it is possible to utilize antimicrobial metals with atomic disorder in a radical new way, i.e., for direct application to a wide range of different tissues so as to therapeutically treat a wide range of different medical disorders.
- Furthermore, by combining the therapeutic benefits of antimicrobial metals with atomic disorder with recent advances in minimally invasive surgery, including small-needle and needle-less drug delivery systems, therapeutic treatments may be applied to internal anatomy as well as to surface anatomy.
- The present invention utilizes selected structures of antimicrobial metals. The antimicrobial metals are preferably selected noble metals such as silver, gold, platinum, palladium, etc. The structures are formed with atomic disorder, such that ions, clusters, atoms or molecules of the metals are released at a concentration sufficient to provide a localized therapeutic effect. The structures are preferably in nanocrystalline form. Antimicrobial metals with atomic disorder may be prepared in the manner taught in International Patent Publication No. WO 93/23092, published Nov. 25, 1993; International Patent Publication No. WO 95/13704, published May 26, 1995; and International Patent Publication No. WO 98/41095, published Sep. 24, 1998, which documents are incorporated herein by reference.
- As used herein, the terms and phrases set out below are intended to have the meanings as follows:
- “Metal” or “metals” includes one or more metals whether in the form of substantially pure metals, alloys or compounds such as oxides, nitrides, borides, sulphides, halides or hydrides.
- “Antimicrobial metals” are silver, gold, platinum, palladium, iridium, zinc, copper, tin, antimony, bismuth, or mixtures of these metals with same or other metals, silver, gold, platinum and palladium being preferred, and silver being most preferred.
- “Noble metals” are silver, gold, platinum and palladium, or mixtures of such metals with same or other metals, with silver metal being the most preferred.
- “Antimicrobial effect” means that atoms, ions, molecules or clusters of the antimicrobial or noble metal are released into the electrolyte which the coating contacts in concentration sufficient to inhibit microbial growth on and in the vicinity of the coating. The most common methods of measuring an antimicrobial effect are a zone of inhibition test (which indicates an inhibitory effect, whether microbiostatic or microbiocidal) or a logarithmic reduction test (which indicates a microbiocidal effect). In a zone of inhibition test (ZOI) the material to be tested is placed on a bacterial lawn (or a lawn of other microbial species) and incubated. A relatively small or no ZOI (ex. less than 1 mm) indicates a non-useful antimicrobial effect, while a larger ZOI (ex. greater than 5 mm) indicates a highly useful antimicrobial effect. The ZOI is generally reported as a corrected zone of inhibition (CZOI), wherein the size of the test sample is subtracted from the zone. A logarithmic reduction test in viable bacteria is a quantitative measure of the efficacy of an antibacterial treatment; for example, a 5 log reduction means a reduction in the number of microorganisms by 100,000-fold (e.g., if a product contained 100,000 pertinent microorganisms, a 5 log reduction would reduce the number of pertinent microorganisms to 1). Generally, a 3 log reduction represents a bactericidal effect. The logarithmic reduction test involves combining the inoculum with the test treatment, recovering the bacteria or other microbial species, and enumerating the bacteria or other microbial species using serial dilutions.
- “Anti-inflammatory effect” means a reduction in one or more of the symptoms of erythema (redness), edema (swelling), pain and pruritus which are characteristic of inflammatory skin conditions.
- “Inflammatory skin conditions” refers to those conditions of the skin in which inflammatory cells (e.g., polymorphonuclear neutrophils and lymphocytes) infiltrate the skin with no overt or known infectious etiology, but excluding psoriasis and its related conditions. Symptoms of inflammatory skin conditions generally include erythema (redness), edema (swelling), pain, pruritus, increased surface temperature and loss of function. As used herein, inflammatory skin conditions include, but are not limited to, eczema and related conditions, insect bites, erythroderma, mycosis fungoides and related conditions, pyoderma gangrenosum, erythema multiforme, rosacea, onychomycosis, and acne and related conditions, but excluding psoriasis and its related conditions.
- “Biocompatible” means generating no significant undesirable host response for the intended utility. Most preferably, biocompatible materials are non-toxic for the intended utility. Thus, for human utility, biocompatible is most preferably non-toxic to humans or human tissues.
- “Sustained release” or “sustainable basis” are used to define release of atoms, molecules, ions or clusters of a antimicrobial metal that continues over time measured in hours or days, and thus distinguishes release of such metal species from the bulk metal, which release such species at a rate and concentration which is too low to be therapeutically effective, and from highly soluble salts of antimicrobial metals such as silver nitrate, which releases silver ions virtually instantly, but not continuously, in contact with an alcohol or electrolyte.
- “Atomic disorder” includes high concentrations of one or more of: point defects in a crystal lattice, vacancies, line defects such as dislocations, interstitial atoms, amorphous regions, grain and sub grain boundaries and the like relative to its normal ordered crystalline state. Atomic disorder leads to irregularities in surface topography and inhomogeneities in the structure on a nanometer scale.
- “Normal ordered crystalline state” means the crystallinity normally found in bulk metal materials, alloys or compounds formed as cast, wrought or plated metal products. Such materials contain only low concentrations of such atomic defects as vacancies, grain boundaries and dislocations.
- “Diffusion”, when used to describe conditions which limit diffusion in processes to create and retain atomic disorder, i.e. which freeze-in atomic disorder, means diffusion of atoms (adatom diffusion) and/or molecules on the surface or in the matrix of the material being formed.
- “Alcohol or water-based electrolyte” is meant to include any alcohol or water-based electrolyte that the antimicrobial materials of the present invention might contact in order to activate (i.e. cause the release of species of the antimicrobial metal) into same. The term is meant to include alcohols (short chain (C6or less) and preferably C4 or less), water, gels, fluids, solvents, and tissues containing, secreting, or exuding water or water-based electrolytes, including body fluids (for example blood, urine, or saliva), and body tissue (for example skin).
- “Bioabsorbable” as used herein in association includes substrates which are useful in medical devices, that is which are biocompatible, and which are capable of bioabsorption in period of time ranging from hours to years, depending on the particular application.
- “Bioabsorption” means the disappearance of materials from their initial application site in the body (human or mammalian) with or without degradation of the dispersed polymer molecules.
- “Colour change” is meant to include changes of intensity of light under monochromatic light as well as changes of hue from white light containing more than one wavelength.
- An “interference colour” is produced when light impinges on two or more partly reflective surfaces separated by a distance which bears the right relationship to the wavelength of the light to be removed by destructive interference.
- “Partly reflective” when used to describe the base or top layer materials, means that the material has a surface which reflects a portion of incident light, but which also transmits a portion of the incident light. Reflection occurs when a ray of incoming light encounters a boundary or interface characterized by a change in refractive index between two media. For the top layer of the antimicrobial materials of this invention, that interface is with air. For the base layer, the interface is with the top layer. The reflectance of the base and top layers is balanced so as to generate an interference colour.
- “Partly light transmissive” when used to describe a thin film of the top layer material means that the thin film is capable of transmitting at least a portion of incident visible light through the thin film.
- “Detectable” when used to describe a colour change means an observable shift in the dominant wavelength of the reflected light, whether the change is detected by instrument, such as a spectrophotometer, or by the human eye. The dominant wavelength is the wavelength responsible for the colour being observed.
- “Cold working” as used herein indicates that the material has been mechanically worked such as by milling, grinding, hammering, mortar and pestle or compressing, at temperatures lower than the recrystallization temperature of the material. This ensures that atomic disorder imparted through working is retained in the material.
- “Pharmaceutically- or therapeutically-acceptable” is used herein to denote a substance which does not significantly interfere with the effectiveness or the biological activity of the active ingredients (antimicrobial and anti-inflammatory activities) and which has an acceptable toxic profile for the host to which it is administered.
- “Therapeutically effective amount” is used herein to denote any amount of a formulation of the antimicrobial or noble metals which will exhibit either or both of an antimicrobial and optionally an anti-inflammatory effect, or some other therapeutic effect, when applied to the affected area of the tissue. A single application of the formulations of the present invention may be sufficient, or the formulations may be applied repeatedly over a period of time, such as several times a day for a period of days or weeks. The amount of the active ingredient, that is the antimicrobial or noble metal in the form of a coating, powder or dissolved in liquid solution, will vary with the conditions being treated, the stage of advancement of the condition, the age and type of host, and the type and concentration of the formulation being applied. Appropriate amounts in any given instance will be readily apparent to those skilled in the art or capable of determination by routine experimentation.
- “Carrier” means a suitable vehicle including one or more solid, semisolid or liquid diluents, excipients or encapsulating substances which are suitable for administration to the skin.
- “Nanocrystalline” is used herein to denote single-phase or multi-phase polycrystals, the grain size of which is less than about 100, more preferably <50, even more preferably <40, even more preferably <30, and most preferably <25 nanometers in at least one dimension. The term, as applied to the crystallite or grain size in the crystal lattice of coatings, powders or flakes of the antimicrobial or noble metals, is not meant to restrict the particle size of the materials when used in a powder form.
- “Powder” is used herein to include particulates of the antimicrobial or noble metals ranging from nanocrystalline (less than 100 nm) to submicron sized powders up to flakes. Preferably, powders of the antimicrobial or noble metals used in the present invention are sized at less than 100 μm, and more preferably less than 40 μm, and most preferably less than 10 μm.
- “Grain size”, or “crystallite size” means the size of the largest dimension of the crystals in the antimicrobial metal coating or powder.
- “Hydrocolloid” means a synthetically prepared or naturally occurring polymer capable of forming a thickened gel in the presence of water and polyols (swelling agent). The swelling agent must be capable of swelling the hydrocolloid chosen in order to form the gel phase.
- “Hydrogels” means a hydrocolloid swollen with water or another hydrophilic liquid which is used for absorbing or retaining moisture or water.
- “Gel” means a composition that is of suitable viscosity for such purposes, e.g., a composition that is of a viscosity that enables it to be applied and remain on the skin.
- When used herein and in the claims, the term “nanocrystalline antimicrobial metal” and similar terminology, such as “nanocrystalline coatings or powders” is meant to refer to antimicrobial metals formed with atomic disorder and having a nanocrystalline grain size.
- Antimicrobial metals with atomic disorder may be provided in free-standing powder form in a variety of different ways.
- By way of example but not limitation, in International Patent Publication No. WO 93/23092, published Nov. 25, 1993; and/or International Patent Publication No. WO 95/13704, published May 26, 1995; and/or International Patent Publication No. WO 98/41095, published Sep. 24, 1998, it was disclosed that antimicrobial metals with atomic disorder may be provided in free-standing powder form by “cold working”.
- Furthermore, in International Patent Publication No. WO 93/23092, published Nov. 25, 1993; and/or International Patent Publication No. WO 95/13704, published May 26, 1995; and/or International Patent Publication No. WO 98/41095, published Sep. 24, 1998, it was disclosed that antimicrobial metals with atomic disorder may be provided in free-standing powder form by vapor deposition on a fixed element, with the deposited material thereafter being stripped off so as to yield the desired free-standing powder.
- In accordance with a further aspect of the present invention, it has recently been discovered that antimicrobial metals with atomic disorder may be provided in free-standing powder form by vapor deposition on an NGRC (“next generation roll coater”) apparatus. More particularly, a continuous belt is coated with antimicrobial metals with atomic disorder using vapor deposition techniques, with the antimicrobial metals with atomic disorder being scraped off the belt further down the line so as to yield the free-standing powder form of the antimicrobial metals with atomic disorder.
- This last-mentioned method for making the free-standing powder form of the antimicrobial metals with atomic disorder (i.e., vapor deposition on an NGRC apparatus) is particularly advantageous, inasmuch as it can quickly and easily yield a relatively large supply of free-standing powder at a relatively low cost.
- Crystalline powder forms of the antimicrobial or noble metals (particularly preferred being Ag, Au, Pt, and Pd) can be prepared as free standing powders, by coating powdered substrates, or from coatings on substrates which are then collected, for example by scraping and then sized. The powders may be prepared as pure metals, metal alloys or compounds such as metal oxides or metal salts, by vapour deposition, mechanical working, or compressing to impart the atomic disorder. The crystalline powders are formed with atomic disorder in accordance with the techniques set out above and as published in the prior patent applications of Burrell et al., see for example WO 93/23092, published Nov. 25, 1993, and WO 95/13704, published May 26, 1995. The atomic disorder will most typically be formed in the metal powders during physical vapour deposition as set out above for coatings or by mechanically imparting the disorder, such as by milling, grinding, hammering, mortar and pestle or compressing, under conditions of low temperature (i.e., temperatures less than the temperature of recrystallization of the material) to ensure that annealing or recyrstallization does not take place.
- Alternatively, the powders may be formed by inert-gas condensation techniques, which are modified to provide atomic disorder in the powder produced, as taught in WO 95/13704 to Burrell et al.
- Powders of the antimicrobial or noble metals are preferably formed by physical vapour deposition (PVD) onto a substrate such as a cold finger, a silicon wafer, solid plates, a rotating cylinder, a continuous belt in a roll coater, or on steel collectors in known PVD coaters. Preparation of powders of the present invention by sputtering onto a continuous belt in a roll coater, or other some other moving or rotating substrate surface is particularly advantageous, inasmuch as it can quickly and easily yield a relatively large supply of free-standing powder at a relatively low cost. A stainless-steel belt can be used in the roll coating process without the need to provide additional cooling of the substrate. The powders or coatings are then scraped off to form a powder, and may be sized to avoid overly large particulates. The powders are scraped off the moving surface with scrapers which contact the moving surface at an angle sufficient to remove the coating in flake or powder form. The coating may be scraped off with scrapers angled for forward cutting of the coating from the moving surface, or with scrapers which remove the coating from the moving surface by reverse dragging action on the surface. The scrapers may be suspended above the belt, and either weighted or spring loaded to apply pressure sufficient to remove the coating from the moving surface. With a continuous belt, the scrapers can conveniently be located above the end rollers to remove the coating with a reverse dragging action as the belt rounds the end roller.
- Alternatively, the powders of the antimicrobial or noble metals may be formed on powdered substrates which are biocompatible, or otherwise compatible for the end use of the powder. Particularly preferred powdered substrates are hydrocolloids, particularly those which are bioabsorbable and/or hygroscopic powders such as chitin. Exemplary bioabsorbable and/or hygroscopic powders are composed of:
- Synthetic Bioabsorbable Polymers: for example polyesters/polyactones such as polymers of polyglycolic acid, glycolide, lactic acid, lactide, dioxanone, trimethylene carbonate etc., polyanhydrides, polyesteramides, polyortheoesters, polyphosphazenes, and copolymers of these and related polymers or monomers.
- Naturally Derived Polymers: Proteins: albumin, fibrin, collagen, elastin; Polysaccharides: chitosan, alginates, hyaluronic acid; and Biosynthetic Polyesters: 3-hydroxybutyrate polymers.
- The powders may be incorporated into or onto medical dressings or pharmaceutical formulations, by any methods known in the art. For example, the powders may be layered onto the substrates (dressings or powders), mechanically fixed within the fibres of the dressings, impregnated into dressings by physical blowing, or added to topical pharmaceutical ingredients.
- Preferably, powders of the present invention are sized at less than 100 μm, and more preferably less than 40 μm, and most preferably about 3-5 μm in size.
- Once antimicrobial metals with atomic disorder have been provided in free-standing powder form, they can then be used therapeutically in that form, or the free-standing powder can be used to form solutions or suspensions of the antimicrobial metals with atomic disorder prior to being used to therapeutically treat tissue.
- Antimicrobial metals with atomic disorder in free-standing powder form may be sprinkled lightly onto surface anatomy (e.g., the skin) in therapeutically effective amounts so as to provide an antimicrobial treatment to that surface anatomy, e.g., to an infected cut. If desired, antimicrobial metals with atomic disorder may be mixed with one or more other materials prior to being sprinkled onto the skin, where these other materials may be biologically active materials (e.g., growth promoters) or biologically neutral materials acting as a “filler” to facilitate easier deployment of relatively small quantities of antimicrobial metals with atomic disorder.
- Or antimicrobial metals with atomic disorder in free-standing powder form can be applied to the lungs using a so-called dry powder inhaler.
- Antimicrobial metals with atomic disorder in free-standing powder form may also be injected, by small-needle or needle-less injection, into the interior of the body in therapeutically effective amounts so as to provide their therapeutic benefit to interior anatomy.
- The antimicrobial metals with atomic disorder can be delivered to interior anatomy via a small-needle drug delivery system or via a needle-less drug delivery system. Such systems are available from Powderject Research Limited of Oxford, United Kingdom (see, for example, U.S. Pat. Nos. 5,899,880; 6,010,478 and 6,013,050, which patents are hereby incorporated herein by reference) and Bioject, Inc. of Portland, Oreg. (see, for example, U.S. Pat. Nos. 4,596,556; 4,790,824; 5,064,413; 5,312,335; 5,383,851; 5,399,163; 5,520,639; 6,096,002; and Des. 349,958, which patents are also hereby incorporated herein by reference). Delivery of antimicrobial metals with atomic disorder with such drug delivery systems provides local therapy to the interior anatomy.
- Where the antimicrobial metals with atomic disorder are to be applied to the tissue in free-standing powder form by inhalation and/or injection, it is preferred that the particulate size be less than 2 microns, and preferably less than 1 micron, so as so minimize any adverse reaction to the presence of the particulate in the tissue.
- Many health afflictions can be addressed by delivering antimicrobial metals with atomic disorder, in free-standing powder form, to an interior anatomical site with small-needle and/or needle-less drug delivery systems. Examples of some of these applications include: (1) dermal drug delivery for skin conditions such as, but not limited to, acne, psoriasis, eczema and skin infections; (2) localized infections such as, but not limited to, middle ear infections, endocardititis, pericarditis, prostatitis, sinusitis, osteomyelitis and onychomycosis; (3) mouth, gum and throat afflictions; (4) arthritis; and (5) direct-to-tumor chemotherapeutic delivery.
- For example, antimicrobial metals with atomic disorder may be injected directly into psoriatic plaques. Or antimicrobial metals with atomic disorder may be injected by small-needle or needle-less injection through the eardrum (i.e., through the tympanic membrane) into the middle ear, whereby to provide a localized antimicrobial, anti-inflammatory treatment for middle ear infections. Or long-acting antimicrobial metals with atomic disorder may be injected into the prostate gland for difficult-to-treat prostate infections. And antimicrobial metals with atomic disorder may be injected into the tissues of the oral cavity and throat to treat sore throats, thrush (candida infections) and periodontal diseases such as gingivitis. Also, antimicrobial metals with atomic disorder may be injected into arthritic joints to reduce destructive inflammation. And long-acting antimicrobial metals with atomic disorder of platinum can be injected into tumors that are responsive to chemotherapy with platinum compounds.
- Numerous advantages are achieved by delivering antimicrobial metals with atomic disorder to the interior anatomy using such drug delivery systems. For one thing, local treatment (versus systemic treatment) results in lower total doses being required and in fewer side effects. For another thing, the broad spectrum antimicrobial activity of the antimicrobial metals with atomic disorder results in faster infection fighting with low likelihood of bacterial resistance. Furthermore, due to the long-acting nature of the antimicrobial metals with atomic disorder, a single dose or relatively infrequent (e.g., weekly) doses results in an easier therapy regimen than many conventional treatment regimens.
- It is also possible to provide antimicrobial metals with atomic disorder in solution form. The solution form of antimicrobial metals with atomic disorder can be advantageous in many anatomical applications, since there is substantially no particulate present which might irritate tissue.
- Antimicrobial metals with atomic disorder may be provided in solution form in a variety of different ways.
- In one form of the invention, a solution of antimicrobial metals with atomic disorder is created by dissolving a free-standing powder of antimicrobial metals with atomic disorder in water. The free-standing powder of antimicrobial metals with atomic disorder may be packaged in a “tea-bag” type pouch, such that undissolved antimicrobial metals with atomic disorder remain captured within the pouch.
- In another form of the invention, a solution of antimicrobial metals with atomic disorder may be provided by immersing, in water, a substrate carrying deposited antimicrobial metals with atomic disorder. By way of example, a carrier strip may be coated with antimicrobial metals with atomic disorder by vapor deposition, and then the carrier strip may be immersed in water so as to create the solution of antimicrobial metals with atomic disorder. Alternatively, a bandage may be coated with antimicrobial metals with atomic disorder by vapor deposition, and then the bandage may be immersed in water so as to create the solution of antimicrobial metals with atomic disorder.
- The solution of antimicrobial metals with atomic disorder may be prepared in advance. (e.g., at a manufacturing plant) or on site at the time of use. Where a solution of antimicrobial metals with atomic disorder is prepared in advance (e.g., at a manufacturing plant), it is preferred that the solution be created by immersing a “tea-bag” type pouch of the free-standing powder form of antimicrobial metals with atomic disorder in water and leaving it there until the time of use, or by immersing a substrate carrying deposited antimicrobial metals with atomic disorder in water and leaving it there until the time of use.
- Once a solution of antimicrobial metals with atomic disorder has been created, it may be applied to tissue as a liquid or as an aerosol.
- Regardless of how the solution of antimicrobial metals with atomic disorder is applied to tissue, the. dosage is dependent, to at least some extent, on the concentration of antimicrobial metals with atomic disorder present in the solution. Thus, where it is necessary to apply a strong dose of antimicrobial metals with atomic disorder, it may be desirable to raise the concentration of antimicrobial metals with atomic disorder in the solution. In this respect it has been discovered that by lowering the pH of the solution, a higher concentration of antimicrobial metals with atomic disorder can be obtained and, significantly, the antimicrobial metals with atomic disorder go into solution faster. The pH of the solution can be lowered by adding acid to the solution. In one preferred form of the invention, CO2 is added to the solution: the CO2 creates carbonic acid, thus lowering the pH of the solution and increasing the concentration of antimicrobial metals with atomic disorder in the solution.
- As noted above, once a solution of antimicrobial metals with atomic disorder has been created, it may be applied to tissue as a liquid or as an aerosol.
- A solution of antimicrobial metals with atomic disorder may be applied, in liquid form, and in various viscosities, to a wide range of different tissues in therapeutically effective amounts so as to therapeutically treat a wide range of different medical disorders.
- By way of example, a solution of antimicrobial metals with atomic disorder can be applied as a rinse or bath or wash to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections. Alternatively, a solution of antimicrobial metals with atomic disorder can be applied as a rinse or bath or wash to treat a wound or a surgical site.
- Or a solution of antimicrobial metals with atomic disorder can be applied to mouth tissue (e.g., the gums) as an oral rinse.
- Or a solution of antimicrobial metals with atomic disorder can be applied to throat tissue as a gargle.
- Or a solution of antimicrobial metals with atomic disorder can be applied to nasal passages and the sinus, e.g., to treat sinusitis and allergic rhinitis.
- Or a solution of antimicrobial metals with atomic disorder can be applied to the eyes as eyedrops.
- Or a solution of antimicrobial metals with atomic disorder can be applied to the ears as ear drops.
- It is also possible to apply a solution of antimicrobial metals with atomic disorder, in liquid form, to internal anatomy using a small-needle and/or needle-less drug delivery systems, including catheter-based drug delivery systems. Thus, for example, a solution of antimicrobial metals with atomic disorder may be introduced by catheter into the bladder to treat a bladder infection; or injected into the middle ear to treat middle ear infections; or injected or instilled or otherwise introduced into the abdomen to treat a post-surgical abdominal abscess or to treat an infection from peritoneal dialysis; or injected or instilled or otherwise introduced into other internal anatomical structures, including body cavities, so as to treat conditions such as, but not limited to, endocardititis, pericarditis, prostatitis, sinusitis, osteomyelitis and onychomycosis; or injected into skin tissue to treat acne, psoriasis, eczema and/or or other skin conditions; etc.
- A solution of antimicrobial metals with atomic disorder may also be applied, in aerosol form, to a wide range of different tissues in therapeutically effective amounts so as to therapeutically treat a wide range of different medical disorders.
- By way of example, a solution of antimicrobial metals with atomic disorder may be applied in aerosol form to surface tissues as a spray. Thus, a solution of antimicrobial metals with atomic disorder can be applied as a spray to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections. Alternatively, a solution of antimicrobial metals with atomic disorder can be applied as a spray to treat or clean a wound or a surgical site.
- By way of further example, a solution of antimicrobial metals with atomic disorder, in aerosol form, may be inhaled by a patient for deployment to the throat, the nasal and sinus passages and/or the lungs.
- The aerosol of antimicrobial metals with atomic disorder may be created by passing a liquid solution of antimicrobial metals with atomic disorder through a mechanical mister (e.g., a simple spray bottle or nebulizer) and may be applied directly (e.g., via a hand inhaler) or through some other delivery system (e.g., an oxygen tent, etc.).
- With respect to an aerosol of antimicrobial metals with atomic disorder, it should be appreciated that the droplet size of the aerosol can be important for at least two reasons.
- First, the droplet size of the aerosol can affect the dosage of antimicrobial metals with atomic disorder being applied to the tissue, i.e., a larger droplet size results in delivery of more antimicrobial metals with atomic disorder to the tissue.
- Second, the droplet size of the aerosol can also affect delivery of the antimicrobial metals with atomic disorder to the target tissue, e.g., where the aerosol is inhaled through the mouth, big droplets tend to stay in the throat whereas small droplets (e.g., approximately 10 microns or so) tend to travel to the lungs.
- Thus, depending on the dosage required and the. target tissue, it may be important to regulate the droplet size of the aerosol.
- In this respect, it has been found that droplet size can be regulated, to at least some extent, by the device (e.g., the mechanical mister) which is used to produce the aerosol.
- In addition, it has also been discovered that the aerosol's droplet size can be adjusted, to at least some extent, by modifying the surface tension of the solution. More particularly, the solution of antimicrobial metals with atomic disorder has water as its solvent, and water has a relatively high surface tension, so it is relatively straightforward to create an aerosol having a relatively small droplet size. In accordance with the present invention, it has also been discovered that surfactants can be added to the solution so as to reduce the surface tension of the solution, whereby to create an aerosol having a relatively large droplet size. By way of example, such surfactants may comprise phospholipids, e.g., lecithin, sphingomyelin, etc.
- It is also possible to provide antimicrobial metals with atomic disorder in suspension form. The suspension form of antimicrobial metals with atomic disorder can be advantageous in many applications, since it has a relatively long storage life and, perhaps even more importantly, has a relatively long-lasting therapeutic life.
- Antimicrobial metals with atomic disorder may be provided in suspension form in a variety of different embodiments. More particularly, a suspension of antimicrobial metals with atomic disorder can be created in free-standing form or as a dried gel applied to a medical device.
- Thus, in one form of the invention, a suspension of antimicrobial metals with atomic disorder can comprise a free-standing form, i.e., it can comprise a liquid such as a lotion; or a semi-solid such as a gel (i.e. a water-based hydrocolloid) or an emulsion (i.e., an oil-in-water or water-in-oil suspension) such as a cream or ointment. Formulations can include carboxymethyl cellulose (“CMC”), polyvinyl alcohol, methyl parabin, proply parabin, and 0.1% antimicrobial metals with atomic disorder in powder form.
- In another form of the invention, a suspension of antimicrobial metals with atomic disorder can comprise a dried gel applied to a medical device. In this embodiment, a hydrated form of the gel is created, applied to a medical device, and then dehydrated. During use, the gel becomes rehydrated, whereby the antimicrobial metals with atomic disorder are released to provide their therapeutic effect to tissue.
- Regardless of whether the suspension is free-standing or a dried gel applied to a medical device, the suspension may also include biologically active agents such as cytoconductive agents, etc. By way of example, betaglucan, a complex carbohydrate which appears to have cytoconductive properties, may be added to the suspension.
- Of course, when formulating the suspension, care must be taken to avoid generating a blend which might deactivate the therapeutic effect of the antimicrobial metals with atomic disorder. Thus, for example, glycerol can be deleterious to the therapeutic effect of the antimicrobial metals with atomic disorder, and should be avoided.
- As noted above, a suspension of antimicrobial metals with atomic disorder can comprise a free-standing form, i.e., it can comprise a liquid such as a lotion; or a semi-solid such as a gel (i.e. a water-based hydrocolloid) or an emulsion (i.e., an oil-in-water or water-in-oil suspension) such as a cream or ointment. These free-standing forms of the suspension are intended to be applied topically to the tissue which is to be treated, in therapeutically effective amounts, and can be used to treat a dermal condition such as, but not limited to, acne, psoriasis, eczema and skin infections. Alternatively, the free-standing forms of the suspension can be applied topically to treat a wound or a surgical site, etc.
- It is also possible to provide a suspension of antimicrobial metals with atomic disorder in the form of a dried gel applied to medical devices. The hydrated form of the gel is created, applied to a medical device (e.g., during manufacture of the medical device), and then dehydrated. During use, the gel becomes rehydrated, whereby the antimicrobial metals with atomic disorder are released in therapeutically effective amounts so as to provide their therapeutic effect to tissue.
- Examples of medical devices which are prime candidates for a dried gel coating include catheters (e.g., urological catheters, in-dwelling catheters, drainage catheters, etc.), bone screws, total joints, vascular grafts, hernia meshes, surgical dressings, surgical packing materials, etc.
- In this respect it should be appreciated that the dried gel can be quite stable and easy to handle when dehydrated, but very slippery when rehydrated. Thus, dried gels can be particularly advantageous with certain types of medical devices which might otherwise require lubrication during use, since the rehydrated gel automatically provides such lubrication. Urological catheters are one example of a medical device which generally requires lubrication during use, and which would benefit from the natural lubrication provided by the rehydrated gel.
- It is also possible to provide a dried gel which is less slippery, or even non-slippery, when rehydrated.
- 6 milligrams of antimicrobial metals with atomic disorder, in free-standing powder form, are sprinkled lightly onto 6.5 cm2 of burned tissue, and thereafter wet with a light spray of water or wound exudate or TDWL (Trans Dermal Water Loss) or other bodily fluids, so as to provide an antimicrobial treatment to the burned tissue. The treatment is repeated every 24 hours until the therapeutic effects are no longer needed.
- 0.5 milligrams of antimicrobial metals with atomic disorder, in free-standing powder form, are injected, using a small-needle drug delivery system or a needle-less drug delivery system, into gum tissue so as to treat gingivitis. The treatment is repeated every 3 days until the therapeutic effects are no longer needed.
- A solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water. The solution of antimicrobial metals with atomic disorder is applied as a rinse or bath or wash to a wound site so as to provide an antimicrobial treatment to the wound site. The treatment is repeated every 24 hours until the therapeutic effects are no longer needed.
- A solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water. The solution of antimicrobial metals with atomic disorder is applied to the interior of the bladder via a catheter so as to provide antimicrobial treatment to the bladder. The treatment is repeated every 8 hours until the therapeutic effects are no longer needed.
- A solution of antimicrobial metals with atomic disorder is prepared by dissolving 6 milligrams of antimicrobial metals with atomic disorder in 1 gram of water. The solution of antimicrobial metals with atomic disorder is injected (using a small-needle or needle-less injection system) under the toenails or into the nail bed and/or the surrounding tissue of a person suffering from onychomycosis so as to provide an antimicrobial treatment to the tissue. The treatment is repeated 2 times a day until the therapeutic effects are no longer needed.
- Solutions of nanocrystalline noble metals were prepared by immersing Acticoat® burn dressings (distributed by Smith & Nephew) in reverse osmosis water that had been pretreated with CO2 in order to reduce the pH. Two different concentrations of antimicrobial metals with atomic disorder solutions were prepared by this method, the concentrations being 85 μg/mL and 318 μg/mL. Solutions of silver nitrate were also prepared to use as comparisons in the experiments. The concentrations of the silver nitrate were 103 ppm of silver and 295 ppm of silver as determined by Atomic Absorption Spectroscopy.
- The solutions were in turn placed in an ultrasonic nebulizer that created small droplets containing dissolved and suspended parts of the solution of nanocrystalline noble metals. The output from the nebulizer was directed into a chamber made from a stainless steel frame and base. Petri dishes containing Mueller Hinton agar streaked with 4 h old cultures of Pseudomonas aerugiona and Staphylococcus aureus were exposed to nanocrystalline noble metal aerosols and the silver nitrate aerosols.
- The results of the tests show that nanocrystalline noble metal aerosols transmit the antimicrobial activity of the dressings to remote sites, and nanocrystalline noble metal aerosols are more effective than comparable concentrations of silver nitrate.
- In many instances the delivery of antimicrobial materials may most expeditiously be accomplished by using aerosols (e.g., in the treatment of pneumonia). The drawback of aerosols is the requirement for a high concentration of the active ingredient to ensure that a sufficient amount is delivered to achieve the biological effect desired without causing problems with the carrier solvent (e.g., water). The essential requirement of the equipment for producing an aerosol that contains dissolved and suspended components of antimicrobial metals with atomic disorder is that it must form droplets of aerosol directly from the liquid form, and the aerosol droplets must be small enough to reach the lungs. This means that the droplets should be preferably less than approximately 10 μm. To meet these requirements, the aerosol cannot be created by first evaporating the liquid and then condensing it to form droplets, since this would remove the desired antimicrobial metals with atomic disorder from the aerosol. There are two methods that can be used to relatively easily form the droplets directly: (1) mechanical disruption of the liquid; and (2) air, under pressure, passing through some form of orifice that combines the air and the liquid in a way that creates droplets instead of evaporating the liquid.
- Several experiments were carried out with antimicrobial metals with atomic disorder and silver nitrate solutions to determine if the antimicrobial activity of the dressing could be transferred through a direct droplet aerosol to a Petri dish.
- The method used to create an aerosol for these tests was the mechanical method in the form of an ultrasonic nebulizer. For convenience, an ultrasonic humidifier was used. The liquid containing the dissolved and suspended antimicrobial metals with atomic disorder was placed in the water reservoir of the humidifier. When power was applied to the humidifier, aerosol droplets of dissolved and suspended antimicrobial metals with atomic disorder were generated and flowed from the output nozzle.
- A test chamber was constructed using a stainless steel frame with a transparent plastic covering. The frame was placed on a stainless steel plate. The output nozzle from the humidifier was modified so that the aerosol could be directed into the chamber at a height of approximately 30 cm from the base. The plates and other test samples were placed on the stainless steel plate and exposed to the aerosol for a prescribed length of time.
- A solution of antimicrobial metals with atomic disorder was prepared by immersing 518 sq. inches of Acticoat® burn dressing in 1 L of reverse osmosis water, which was treated with CO2 to maintain a pH of 6.5. After 20 minutes the concentration of silver in the water was 85 μg/mL.
- A solution containing 370 μg/mL of silver from a Acticoat® dressing was prepared as follows: 1 L of reverse osmosis water was purged with commercial grade carbon dioxide until the pH was 4.3. Sufficient Acticoat® dressing was added to bring the pH up to 6.5. At that time, the silver concentration was 370 μg/mL.
- Ag as AgNo3 was prepared by dissolving 0.157 g of AgNo3 into 1 L of reverse osmosis water and mixed until dissolved. The solution was analyzed by Atomic Absorption Spectroscopy and found to be 102.9 ppm of silver.
- Ag as AgNO3 was prepared by dissolving 0.427 of AgNO3 into 1 L of reverse osmosis water and mixed until dissolved. The solution was analyzed by Atomic Absorption Spectroscopy and found to be 295 ppm of silver.
- Petri dishes, containing Mueller Hinton agar, were streaked with 4 h old cultures of Pseudomonas aeruginosa or Staphylococcus aureus. The plates were then weighed and their exposed outer surfaces were coated with Parafilm to prevent condensation from occurring on these surfaces. These plates were placed in the aerosol chamber uncovered. The ultrasonic nebulizer was then started and run for 53 minutes. The plates were then removed from the chamber, the plastic was removed and the dishes re-weighed so that the amount of moisture loss/gain could be determined.
- The plates were then placed in a 35° C. incubator for 16 h. After incubation the pattern and amount of growth was assessed on the plates for both organisms.
- Three of the six plates made for each organism were tested to determine if the antimicrobial effect was cidal or static in nature. This was accomplished by rinsing or placing a piece of the clear section of agar in the Petri dish plates into Tryptic soy broth in a test tube and incubating for 4 h or 16 h. If the medium turned turbid in 4 h it would indicate that the antimicrobial affect was bacteriostatic in nature. If the organism took more than 16 h to grow, as indicated by turbidity, it was considered an indication that both static and cidal effects occurred. If no growth occurred, the effect was bactericidal.
- The results for Solutions 1 and 2 are summarized in Tables 1 and 2, respectively.
TABLE 1 Solutions 1 and 3 Results Antimicrobial Metals With Atomic Disorder AgNo3 Organism Ps. S. Ps. S. Aeruginosa aureus Aeruginosa aureus Ag concentration 85 85 99 99 (μg/mL) pH of test 6.5 6.5 Approx. Approx. solution 6.5 6.5 Exposure time 53 53 53 53 (minutes) Exposed area 9.8 9.8 9.8 9.8 (sq. in) Weight gain (g) 0.8 0.8 1.05 1.05 Growth at 16 h 0 0 0 ++++ (0-++++) at 48 h 0 ++ 0 ++++ Viable 4 h No Yes No Yes 16 h Yes Yes Yes Yes -
TABLE 2 Solutions 2 and 4 Results Antimicrobial Metals With Atomic Disorder AgNo3 Organism Ps. S. Ps. S. aeruginosa aureus aeruginosa aureus Ag concentration 370 370 300 300 (μg/mL) pH of test 6.5 6.5 Approx. Approx. solution 6.3 6.3 Exposure time 53 53 53 53 (minutes) Exposed area 9.8 9.8 9.8 9.8 (sq. in) Weight gain (g) 1.14 1.14 1.12 1.12 Growth at 16 h 0 0 0 0 (0-++++) at 48 h 0 0 0 +++ Viable 4 h No No No No 16 h No No No N/A - At the low concentration of silver in solution, the Acticoat® dressing generated silver was effective at controlling the growth of both organisms while the silver nitrate only prevented the growth of Ps. aeruginosa. Viability tests showed that at the low concentration, neither form of silver was completely bactericidal although the poor growth on the plates treated with antimicrobial metals with atomic disorder compared to the silver nitrate treated plates suggests that a significant log reduction occurred in the plates treated with the aerosol of antimicrobial metals with atomic disorder.
- At a higher concentration of silver, both antimicrobial metals with atomic disorder (37.0 μg/mL) and AgNo3 (300 μg/mL) were effective at controlling P. aeruginosa. Since no re-growth occurred, it is assumed that the agent at this concentration was bactericidal. Antimicrobial silver with atomic disorder was more effective than AgNO3 at controlling S. aureus. No re-growth occurred on any plates or in the broth indicating a total kill of the organism while, in the AgNO3 treatment, a large number of organisms grew at 16h.
- Based on weight gain during aerosol treatments, a dose per unit area can be calculated. In each case for Solution 1, the dose was 8.5 μg/sq. inch, while for Solution 2, the dose was 38 μg/sq. inch. These doses, on a per lung basis, would be less than 10 mg of silver per hour of treatment. Each hour of treatment with antimicrobial silver with atomic disorder aerosols appears to provide at least 48 h of protection. Therefore, the dose per day, from the high concentration treatment, would be about 5 mg or a little less than the silver released by 2 sq. inches of SSD per day.
- The most significant advantage of using antimicrobial silver with atomic disorder may be the lack of a toxic action such as NO3 or sulfadiazine.
- (1) Aerosols of antimicrobial metals with atomic disorder transmit the antimicrobial activity of the dressings to remote sites.
- (2) Aerosols of antimicrobial metals with atomic disorder are more effective than comparable concentrations of silver nitrate.
- (3) The dose delivered is acceptable and would not appear to be excessive.
- (4) No toxic cations (NO3 or sulfadiazine) are introduced to the patient.
- Gel products of antimicrobial metals with atomic disorder encompass both “wet” and “dry” materials.
- A “wet” gel product of antimicrobial metals with atomic disorder is a product that provides moisture to a dry skin condition (psoriasis, eczema, acne, wound, etc.) and facilitates autolytic debridement of necrotic tissue. It also delivers the antimicrobial and anti-inflammatory properties of the suspended antimicrobial metals with atomic disorder powders.
- In many instances it is also beneficial to supply biologically active molecules to elicit a specific response such as cell migration, etc. Since these biologically active molecules are susceptible to microbial degradation if not protected, it is beneficial to include them in gels of antimicrobial metals with atomic disorder that will provide the necessary protection.
- “Dry” gel products of antimicrobial metals with atomic disorder are physically stabilized (dry or cross-linked) materials that provide lubricious, antimicrobial, antithrombogenic, and anti-inflammatory properties to a variety of implantable, trancutaneous or topically applied devices. The coatings may also provide other benefits such as accelerating or otherwise facilitating tissue integration by creating a favorable environment for cell proliferation. This favorable environment may be created by including cytoconductive agents or anti-adhesion agents such as bone morphogenetic proteins, B-glucan hyaluronic acids in the gel. The gel may be stabilized by cross-linking the gel components (collagen, gelatin, etc.) or by drying the coated materials.
- Examples of the primary gelling agents are listed in Table 3. Biologically active ingredients that may be used, in any combination with the primary gelling agents, are given in Table 4. Materials that should not be used with gels of antimicrobial silver with atomic disorder are given in Table 5.
TABLE 3 Material Percentage Composition Carboxymethyl cellulose (CMC) 0.1-10 Polyvinyl alcohol (PVA) 0.1-10 Collagen 0.1-10 Pectin 0.1-10 Gelatin 0.1-10 Chitin 0.1-10 Chitosan 0.1-10 Alginate 0.1-10 Poly (α-amino acids) Polyester Poly-1-caprolactone PEG Cocoa butter Sepigel -
TABLE 4 Biologically Active Ingredients Percentage Composition Methyl paraben <3 Propyl paraben <3 B-glucan <5 Hyaluronic acid <5 Epidermal growth factor <1 Platelet derived growth factor <1 Transforming growth factor <1 Vascular endothelial growth factor <1 Interleukins <1 Heparin <5 Bone morphogenetic proteins <1 -
TABLE 5 Non-Compatible Materials Percentage Composition Chloride salts >0.01 Aldehydes >0.01 Ketones >0.01 Long chain alcohols >0.01 Glycerol >0.01 Triethanolamine >0.01 - A commercial carboxymethyl cellulose/pectin gel (Duoderm Convatec) was combined with antimicrobial metals with atomic disorder powder to produce a gel with 0.1% silver. A logarithmic reduction test was performed as follows in the gel using Pseudomonas aeruginosa.
- The inoculum was prepared by placing 1 bacteriologic loopful of the organism in 5 mL of trypticase soy broth and incubating it for 3-4 h. The inoculum (0.1 mL) was then added to 0.1 mL of gel and vortexed (triplicate samples). The mixture was incubated for one-half hour. Then 1.8 mL of sodium thioglycollate-saline (STS) solution was added to the test tube and vortexed. Serial dilutions were prepared on 10−1 to 10−7. A 0.1 mL aliquot of each dilution was plated in duplicate into Petri plates containing Mueller-Hinton agar. The plates were incubated for 48 h and then colonies were counted. Surviving members of organisms were determined and the logarithmic reduction compared to the initial inoculum was calculated.
- The logarithmic reduction for this mixture was 6.2, indicating a significant bactericidal effect.
- Carboxymethyl cellulose (CMC) fibers were coated directly to produce a defective nanocrystalline antimicrobial coating. The CMC was then gelled in water by adding 2.9 g to 100 mL volume. This material was tested using the method of No. 1. The material generated a 5.2 logarithmic reduction of Pseudomonas aeruginosa, demonstrating that the gel had a significant bactericidal effect.
- An alginate fibrous substrate was directly coated with a defective nanocrystalline antimicrobial coating. The alginate (5.7 g) was added to 100 mL volume of water to create a gel. This material was tested using the method of No. 1. The material generated a 5.2 logarithmic reduction of Pseudomonas aeruginosa, demonstrating that the gel had a significant bactericidal effect.
- A commercial gel containing CMC and alginate (Purilin gel Coloplast) was mixed with a defective nanocrystalline silver powder to give a product with 0.1% silver. This was tested as above with both Pseudomonas aeruginosa and Staphylococcus aureus. Zone of inhibition data was also generated for this gel as follows. An inoculum (Pseudomonas aeruginosa and Staphylococcus aureus) was prepared as in No. 1 and 0.1 mL of this was spread onto the surface of Mueller-Hinton agar in a Petri dish. A six mm hole was then cut into the agar at the center of the Petri dish and removed. The well was filled with either 0.1 mL of the silver containing gel, a mupirocin containing cream or a mupirocin containing ointment. The Petri plates were then incubated for 24 h and the diameter of the zone of inhibition was measured and recorded.
- The silver containing gel produced 9 mm zones against both Pseudomonas aeruginosa and Staphylococcus aureus, while the mupirocin cream and ointment produced 42 and 48 mm zones against Staphylococcus aureus and 0 mm zones against Pseudomonas aeruginosa.
- The silver containing gel reduced the Pseudomonas aeruginosa and Staphylococcus aureus properties 4.4 and 0.6 logs, respectively, showing good bactericidal activity. The mupirocin cream and ointment generated 0.4 and 0.8, and 0.8 and 1.6, log reductions against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The silver gel had both a greater bactericidal effect and spectrum of activity than the mupirocin containing products.
- The formula for Nos. 5-10 are summarized in Table 6. Zones of inhibitions were determined in No. 4 and log reductions were determined in No. 1.
- All formulae provided a broader spectrum of activity and a greater bactericidal effect than did mupirocin in a cream or ointment form. The mupirocin cream produced zones of inhibition of 42 and 0, and log reduction of 0.4 and 0.8, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively.
TABLE 6 Antimicrobial Metals With Atomic Methyl Proply CZOI CZOI Log Reduction Log Reduction No. CMC PVA DisorderM Powder 0-glucan ParaBen Paraben s. aureus Ps. Aeruginosa S. Aureus Ps. Aeruginosa 5 2% 0.1% 11 13 1.4 >6 6 2% 0.5% 0.1% 0.1 0.02 14 15 3.3 >6 7 2% 0.5% 0.1% 13 14 2.0 N/A 8 2% 0.5% 0.1% 0.1 14 14 2.0 N/A 9 2% 0.5% 0.1% 0.20 14 14 2.0 N/A 10 2% 0.5% 0.1% 0.5 0.1 0.20 14 14 2.0 >6 - A commercially available gel (glyceryl polymethacrylate) was blended with antimicrobial metals with atomic disorder powder to produce a gel with a silver content of 0.1%. This gel was tested as in Nos. 5-10 and was found to produce zones of 15 mm against both Staphylococcus aureus and Pseudomonas aeruginosa. Log reductions of 1.7 and >5 were produced against Staphylococcus aureus and Pseudomonas aeruginosa. This gel product had a greeted spectrum of activity than did mupirocin cream or ointment.
- A gel coat for a urinary catheter was prepared using the formula in No. 6. The coating was applied to the catheter using a dipping method. The coating was air dried overnight.
- The dried gel coat was smooth and easy to handle. It was not tacky to touch and had excellent abrasion and adhesion properties. Upon rewetting, the surface became extremely slippery indicating excellent lubricious properties.
- A zone of inhibition test was performed against Pseudomonas aeruginosa using an inoculum as prepared in No. 1. The inoculum (0.1 mL) was spread over the surface of Mueller-Hinton agar in a Petri plate. The catheter was cut into 1″ segments which were laid on their side into the middle of the Petri plate. Petri plates were incubated for 24 h and then the zone of inhibitions was measured.
- In all cases, zones of inhibition were generated that ranged from 7-10 mm. This indicates that getting drying and rehydrating had no negative effect on the antimicrobial activity of the gel coat.
Claims (16)
1. A method for treating tissue, comprising:
forming a free-standing powder comprising at least one antimicrobial nanocrystalline metal with atomic disorder; and
injecting the free-standing powder in therapeutically effective amounts to the tissue which is to be treated.
2-22. (canceled)
23. A method for treating tissue, comprising;
forming a free-standing powder comprising at least one nanocrystalline metal; and
applying the free-standing powder in therapeutically-effective amounts to the tissue which is to be treated,
wherein the tissue comprises at least on e tissue selected from the group consisting of endocardium tissue, pericardium tissue, bone tissue, and joint tissue.
24-30. (canceled)
31. A method for treating tissue, comprising:
forming a solution at a site remote from the tissue which is to be treated by dissolving in water at least one nanocrystalline metal; and
applying the solution in therapeutically effective amounts to the tissue which is to be treated,
wherein the tissue comprises at least one tissue selected from the group consisting of endocardium tissue, pericardium tissue, bone tissue, and joint tissue.
32-46. (canceled)
47. The method of claim 1 , wherein the at least nanocrystalline metal comprises nanocrystalline silver.
48. The method of claim 23 , wherein the at least nanocrystalline metal comprises nanocrystalline silver.
49. The method of claim 31 , wherein the at least nanocrystalline metal comprises nanocrystalline silver.
50. The method of claim 49 , wherein the nanocrystalline silver is atomically disordered.
51. The method of claim 31 , wherein the at least one nanocrystalline metal is atomically disordered.
52. The method of claim 31 , wherein the solution is applied by passing it through a catheter to the tissue which is to be treated.
53. The method of claim 31 , wherein the solution is applied by injection into the tissue which is to be treated.
54. The method of claim 53 , wherein injection is effected by the use of a needle.
55. The method of claim 53 , wherein injection is needle-less injection.
56. The method of claim 31 , wherein the solution is applied by injection into a body cavity so as to contact the tissue which is to be treated.
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Cited By (1)
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US9440001B2 (en) | 2013-03-06 | 2016-09-13 | Specialty Fibres and Materials Limited | Absorbent materials |
Families Citing this family (311)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9119705B2 (en) | 1998-06-08 | 2015-09-01 | Thermotek, Inc. | Method and system for thermal and compression therapy relative to the prevention of deep vein thrombosis |
US7135195B2 (en) * | 1999-06-01 | 2006-11-14 | American Silver, Llc | Treatment of humans with colloidal silver composition |
US8535728B2 (en) | 1999-06-01 | 2013-09-17 | American Silver, Llc | Colloidal silver composition having antimicrobial properties |
US7179849B2 (en) * | 1999-12-15 | 2007-02-20 | C. R. Bard, Inc. | Antimicrobial compositions containing colloids of oligodynamic metals |
US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
US20060115541A1 (en) * | 2000-07-27 | 2006-06-01 | Gillis Scott H | Treatment of bladder conditions |
US7008647B2 (en) * | 2001-04-23 | 2006-03-07 | Nucryst Pharmaceuticals Corp. | Treatment of acne |
US20030185901A1 (en) * | 2000-07-27 | 2003-10-02 | Burrell Robert E. | Methods of treating conditions with a metal-containing material |
US7427416B2 (en) * | 2000-07-27 | 2008-09-23 | Nucryst Pharmaceuticals Corp. | Methods of treating conditions using metal-containing materials |
DE10043151A1 (en) * | 2000-08-31 | 2002-03-28 | Peter Steinruecke | Bone cement with antimicrobial effectiveness |
US7763769B2 (en) | 2001-02-16 | 2010-07-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
US7700819B2 (en) | 2001-02-16 | 2010-04-20 | Kci Licensing, Inc. | Biocompatible wound dressing |
CA2445729C (en) * | 2001-04-23 | 2013-07-02 | Nucryst Pharmaceuticals Corp. | Use of metals to treat mucosal membranes |
US20040092890A1 (en) * | 2001-05-10 | 2004-05-13 | Ash Stephen R. | Catheter lock solution including a photo-oxidant |
WO2003002243A2 (en) | 2001-06-27 | 2003-01-09 | Remon Medical Technologies Ltd. | Method and device for electrochemical formation of therapeutic species in vivo |
WO2003015707A2 (en) * | 2001-08-20 | 2003-02-27 | Transave, Inc. | Method for treating lung cancers |
DE10146050B4 (en) * | 2001-09-18 | 2007-11-29 | Bio-Gate Ag | Process for the preparation of an antimicrobial adhesive and coating material |
JP3795364B2 (en) * | 2001-09-27 | 2006-07-12 | シャープ株式会社 | Integrated circuit and receiver |
AU2002357050A1 (en) | 2001-12-03 | 2003-06-17 | C.R. Bard, Inc. | Microbe-resistant medical device, microbe-resistant polymeric coating and methods for producing same |
TWI255224B (en) * | 2002-01-09 | 2006-05-21 | Novartis Ag | Polymeric articles having a lubricious coating and method for making the same |
US7270653B2 (en) * | 2002-02-20 | 2007-09-18 | Abbott Research Group | Methods of treating abnormal biological conditions using metal oxides |
US6589216B1 (en) | 2002-02-20 | 2003-07-08 | Abbott Research Group, Inc. | Vaginal douches, vaginal douche applicators and methods of vaginal douching |
US8118789B2 (en) * | 2002-02-20 | 2012-02-21 | Abbott Research Group, Inc. | Deodorizer devices and systems for controlling perspiration-related body odor |
US7201925B2 (en) * | 2002-04-23 | 2007-04-10 | Nueryst Pharmaceuticals Corp. | Treatment of ungual and subungual diseases |
EP1518447A1 (en) * | 2002-06-21 | 2005-03-30 | Continental Teves AG & Co. oHG | Printed board for electronic devices controlling a motor vehicle |
US6865810B2 (en) * | 2002-06-27 | 2005-03-15 | Scimed Life Systems, Inc. | Methods of making medical devices |
US9186322B2 (en) * | 2002-08-02 | 2015-11-17 | Insmed Incorporated | Platinum aggregates and process for producing the same |
MXPA05001312A (en) * | 2002-08-02 | 2005-08-03 | Transave Inc | Platinum aggregates and process for producing the same. |
US8404751B2 (en) * | 2002-09-27 | 2013-03-26 | Hallux, Inc. | Subunguicide, and method for treating onychomycosis |
US7485259B2 (en) * | 2002-10-08 | 2009-02-03 | Eldred Bradley J | Organic compound and metal ion synergistic disinfection and purification system and method of manufacture |
WO2004072888A2 (en) * | 2002-10-09 | 2004-08-26 | California Institute Of Technology | Sensor web |
WO2004037187A2 (en) * | 2002-10-22 | 2004-05-06 | Nucryst Pharmaceuticals Corp. | Metal-containing materials, compositions and methods |
EP1567101A4 (en) * | 2002-10-22 | 2009-06-03 | Nucryst Pharm Corp | Prophylactic treatment methods |
US8066854B2 (en) * | 2002-12-18 | 2011-11-29 | Metascape Llc | Antimicrobial coating methods |
US8309117B2 (en) | 2002-12-19 | 2012-11-13 | Novartis, Ag | Method for making medical devices having antimicrobial coatings thereon |
US7666410B2 (en) | 2002-12-20 | 2010-02-23 | Kimberly-Clark Worldwide, Inc. | Delivery system for functional compounds |
US8409618B2 (en) * | 2002-12-20 | 2013-04-02 | Kimberly-Clark Worldwide, Inc. | Odor-reducing quinone compounds |
DE60311958T2 (en) * | 2003-02-03 | 2007-11-08 | Polaschegg, Hans-Dietrich, Dr. | Composition for the prevention of infections by subcutaneous prostheses |
US20040151716A1 (en) * | 2003-02-03 | 2004-08-05 | Hamer Richard A. | Material and method for treating microbial mediated dermatological conditions |
US20040156874A1 (en) * | 2003-02-11 | 2004-08-12 | Bradley Pharmaceuticals, Inc. | Urea- a topical anti-inflammatory |
CN1744917B (en) * | 2003-02-26 | 2010-05-05 | 大塚制药株式会社 | Sustained-release pharmaceutical composition for lung administration |
US20040180093A1 (en) * | 2003-03-12 | 2004-09-16 | 3M Innovative Properties Company | Polymer compositions with bioactive agent, medical articles, and methods |
US7488757B2 (en) * | 2003-03-24 | 2009-02-10 | Becton, Dickinson And Company | Invisible antimicrobial glove and hand antiseptic |
US20040236290A1 (en) * | 2003-04-23 | 2004-11-25 | Zimmermann Stephan A. | Minimally invasive vascular apparatus modified to minimize scarring at introduction site |
US6874165B2 (en) * | 2003-05-19 | 2005-04-05 | Mao-Sheng Lee | Modified NBR gloves |
PT1644024T (en) * | 2003-06-06 | 2019-10-24 | Univ Texas | Antimicrobial flush solutions |
DE10328261B4 (en) | 2003-06-23 | 2007-10-25 | Beiersdorf Ag | Disinfecting coating with silver coating and its use |
AU2004248898B2 (en) * | 2003-06-23 | 2010-03-18 | Beiersdorf Ag | Antimicrobial wounddressing |
US8734421B2 (en) * | 2003-06-30 | 2014-05-27 | Johnson & Johnson Consumer Companies, Inc. | Methods of treating pores on the skin with electricity |
US7480530B2 (en) * | 2003-06-30 | 2009-01-20 | Johnson & Johnson Consumer Companies, Inc. | Device for treatment of barrier membranes |
US20050025817A1 (en) * | 2003-07-03 | 2005-02-03 | Bhatia Kuljit S. | Delivery system for topical medications |
US8128672B2 (en) | 2006-05-09 | 2012-03-06 | Thermotek, Inc. | Wound care method and system with one or both of vacuum-light therapy and thermally augmented oxygenation |
US8574278B2 (en) * | 2006-05-09 | 2013-11-05 | Thermotek, Inc. | Wound care method and system with one or both of vacuum-light therapy and thermally augmented oxygenation |
DK200301128A (en) * | 2003-08-05 | 2005-02-06 | Thomsen Joern Oddershede | Grant Preparation |
US20050028563A1 (en) * | 2003-08-08 | 2005-02-10 | Milliken & Company | Garment for use with sensitive skin, and method and fabric for us in making same |
DE10340277B4 (en) * | 2003-08-29 | 2006-11-23 | Bio-Gate Bioinnovative Materials Gmbh | Personal care products containing silver agglomerates |
US8519146B2 (en) * | 2004-09-07 | 2013-08-27 | The University Of Akron | Metal complexes of N-heterocyclic carbenes as antibiotics |
US20050054774A1 (en) * | 2003-09-09 | 2005-03-10 | Scimed Life Systems, Inc. | Lubricious coating |
US7879350B2 (en) | 2003-10-16 | 2011-02-01 | Kimberly-Clark Worldwide, Inc. | Method for reducing odor using colloidal nanoparticles |
US7794737B2 (en) | 2003-10-16 | 2010-09-14 | Kimberly-Clark Worldwide, Inc. | Odor absorbing extrudates |
US7678367B2 (en) | 2003-10-16 | 2010-03-16 | Kimberly-Clark Worldwide, Inc. | Method for reducing odor using metal-modified particles |
US20050123590A1 (en) * | 2003-12-05 | 2005-06-09 | 3M Innovative Properties Company | Wound dressings and methods |
US7745509B2 (en) * | 2003-12-05 | 2010-06-29 | 3M Innovative Properties Company | Polymer compositions with bioactive agent, medical articles, and methods |
US20050123621A1 (en) * | 2003-12-05 | 2005-06-09 | 3M Innovative Properties Company | Silver coatings and methods of manufacture |
WO2005058199A1 (en) * | 2003-12-16 | 2005-06-30 | Avery Dennison Corporation | Electrostatically self-assembled antimicrobial coating for medical applications |
DE10359338B4 (en) * | 2003-12-17 | 2007-07-19 | Heraeus Kulzer Gmbh | Antimicrobial nanosilver additive for polymerizable dental materials |
GB0401821D0 (en) * | 2004-01-28 | 2004-03-03 | Qinetiq Nanomaterials Ltd | Method of manufacture of polymer composites |
US20050256553A1 (en) * | 2004-02-09 | 2005-11-17 | John Strisower | Method and apparatus for the treatment of respiratory and other infections using ultraviolet germicidal irradiation |
US7457667B2 (en) * | 2004-02-19 | 2008-11-25 | Silverleaf Medical Products, Inc. | Current producing surface for a wound dressing |
US7662176B2 (en) * | 2004-02-19 | 2010-02-16 | Vomaris Innovations, Inc. | Footwear apparatus and methods of manufacture and use |
WO2006016263A2 (en) * | 2004-03-03 | 2006-02-16 | Nucryst Pharmaceuticals Corp. | No-containing complexes |
US20070065522A1 (en) * | 2004-03-18 | 2007-03-22 | Transave, Inc. | Administration of high potency platinum compound formulations by inhalation |
CA2559722A1 (en) * | 2004-03-18 | 2005-09-29 | Transave, Inc. | Administration of cisplatin by inhalation |
US20050271746A1 (en) * | 2004-05-18 | 2005-12-08 | Abbott Chun L | Topical treatments for abnormal biological conditions and method of topically treating such conditions |
US7758892B1 (en) * | 2004-05-20 | 2010-07-20 | Boston Scientific Scimed, Inc. | Medical devices having multiple layers |
JP2008500397A (en) * | 2004-05-21 | 2008-01-10 | トランセイブ, インク. | Treatment of pulmonary and pre-pulmonary disease states |
DE102004031955A1 (en) * | 2004-06-24 | 2006-01-12 | Paul Hartmann Ag | wound dressing |
US20060002967A1 (en) * | 2004-07-01 | 2006-01-05 | Smestad Thomas L | Resorbable implant with lubricious coating |
US10016583B2 (en) | 2013-03-11 | 2018-07-10 | Thermotek, Inc. | Wound care and infusion method and system utilizing a thermally-treated therapeutic agent |
US10765785B2 (en) | 2004-07-19 | 2020-09-08 | Thermotek, Inc. | Wound care and infusion method and system utilizing a therapeutic agent |
US20060035039A1 (en) * | 2004-08-12 | 2006-02-16 | 3M Innovative Properties Company | Silver-releasing articles and methods of manufacture |
US20060034899A1 (en) * | 2004-08-12 | 2006-02-16 | Ylitalo Caroline M | Biologically-active adhesive articles and methods of manufacture |
CN2734238Y (en) * | 2004-08-25 | 2005-10-19 | 任晓艳 | Nano silver coated suture line |
US20060068024A1 (en) * | 2004-09-27 | 2006-03-30 | Schroeder Kurt M | Antimicrobial silver halide composition |
EP1811963A4 (en) * | 2004-11-08 | 2010-01-06 | Transave Inc | Methods of treating cancer with lipid-based platinum compound formulations administered intraperitoneally |
BRPI0516897A (en) * | 2004-11-23 | 2008-09-23 | Internat Bio Therapeutic Res I | Method for the administration of metal ions, alloys and therapeutic salts |
MX2007006726A (en) * | 2004-12-06 | 2008-03-10 | Novacentrix Corp | Anti-viral uses of metal nanomaterial compositions. |
JPWO2006064788A1 (en) * | 2004-12-13 | 2008-06-12 | アプト株式会社 | Mouthwash |
US7749529B2 (en) * | 2005-02-08 | 2010-07-06 | Ash Access Technology, Inc. | Catheter lock solution comprising citrate and a paraben |
WO2006090239A1 (en) * | 2005-02-23 | 2006-08-31 | Kerryne Krause-Neufeldt | Cosmetic product |
DE102005008416B4 (en) * | 2005-02-24 | 2011-09-29 | Lohmann & Rauscher Gmbh & Co. Kg | Process for the purification of marine collagen |
US8864730B2 (en) | 2005-04-12 | 2014-10-21 | Rochester Medical Corporation | Silicone rubber male external catheter with absorbent and adhesive |
US8399027B2 (en) * | 2005-04-14 | 2013-03-19 | 3M Innovative Properties Company | Silver coatings and methods of manufacture |
PL1888127T3 (en) * | 2005-05-02 | 2010-07-30 | Coloplast As | A method for sterilising a medical device having a hydrophilic coating |
US20060275223A1 (en) * | 2005-06-02 | 2006-12-07 | Burr James B | Erythritol compositions for teeth and gums |
WO2007015761A2 (en) * | 2005-07-21 | 2007-02-08 | Fmc Biopolymer As | Medical devices coated with a fast dissolving biocompatible coating |
WO2007013100A1 (en) * | 2005-07-26 | 2007-02-01 | Virchow Biotech Private Limited | Gel formulation comprising platelet derived growth factor |
DE102005041005B4 (en) * | 2005-08-29 | 2022-10-20 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Biocidal composition containing nanoparticulate silver, the use of this composition and a method for the production of biocidal products using this composition |
US20070185432A1 (en) * | 2005-09-19 | 2007-08-09 | Transport Pharmaceuticals, Inc. | Electrokinetic system and method for delivering methotrexate |
CN102014790A (en) * | 2005-10-18 | 2011-04-13 | 器官发生有限公司 | Antimicrobial collagenous constructs |
US9107824B2 (en) | 2005-11-08 | 2015-08-18 | Insmed Incorporated | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
WO2007056264A2 (en) * | 2005-11-08 | 2007-05-18 | Transave, Inc. | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
US20070190180A1 (en) * | 2005-11-08 | 2007-08-16 | Pilkiewicz Frank G | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intravenously |
WO2007056236A2 (en) * | 2005-11-08 | 2007-05-18 | Transave, Inc. | Methods of treating cancer with lipid-based platinum compound formulations administered intravenously |
WO2007064658A2 (en) * | 2005-11-30 | 2007-06-07 | Transave, Inc. | Safe and effective methods of administering therapeutic agents |
WO2007065118A2 (en) * | 2005-12-01 | 2007-06-07 | Innograft, Llc | Method for ionically cross-linking polysaccharide material for thin film applications and products produced therefrom |
US8840660B2 (en) | 2006-01-05 | 2014-09-23 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
US20070166399A1 (en) * | 2006-01-13 | 2007-07-19 | 3M Innovative Properties Company | Silver-containing antimicrobial articles and methods of manufacture |
US20070166344A1 (en) * | 2006-01-18 | 2007-07-19 | Xin Qu | Non-leaching surface-active film compositions for microbial adhesion prevention |
ES2612188T3 (en) * | 2006-02-01 | 2017-05-12 | Hollister Incorporated | Methods of applying a hydrophilic coating to a substrate and substrates having a hydrophilic coating |
US8089029B2 (en) | 2006-02-01 | 2012-01-03 | Boston Scientific Scimed, Inc. | Bioabsorbable metal medical device and method of manufacture |
WO2007089267A1 (en) | 2006-02-03 | 2007-08-09 | Jr Chem, Llc | Anti-aging treatment using copper and zinc compositions |
US7897800B2 (en) * | 2006-02-03 | 2011-03-01 | Jr Chem, Llc | Chemical compositions and methods of making them |
US7687650B2 (en) * | 2006-02-03 | 2010-03-30 | Jr Chem, Llc | Chemical compositions and methods of making them |
GB0603487D0 (en) * | 2006-02-22 | 2006-04-05 | Agt Sciences Ltd | Delivery means |
US20070212425A1 (en) * | 2006-03-09 | 2007-09-13 | Barna Ivan J | Cidal formulations and methods of use |
US20070224244A1 (en) * | 2006-03-22 | 2007-09-27 | Jan Weber | Corrosion resistant coatings for biodegradable metallic implants |
US20070224288A1 (en) * | 2006-03-22 | 2007-09-27 | Kiss Nail Products, Inc. | Antibacterial gel coating and pedicure spa with antibacterial function |
JP5226661B2 (en) * | 2006-04-06 | 2013-07-03 | ターロ ファーマシューティカルズ ノース アメリカ インコーポレイテッド | Novel spill-resistant formulation containing hydrocolloid polymer |
JP5049268B2 (en) * | 2006-04-07 | 2012-10-17 | 久光製薬株式会社 | Microneedle device and transdermal drug administration device with microneedle |
US8048150B2 (en) | 2006-04-12 | 2011-11-01 | Boston Scientific Scimed, Inc. | Endoprosthesis having a fiber meshwork disposed thereon |
US8273381B1 (en) | 2006-04-14 | 2012-09-25 | Auburn University | Compositions for and methods of controlling olfactory responses to odorants |
CN101213040B (en) | 2006-04-24 | 2011-10-12 | 纳米材料微型设备技术有限公司 | Functional nanomaterials with antibacterial and antiviral activity |
ATE473768T1 (en) | 2006-06-14 | 2010-07-15 | Nm Tech Ltd Nanomaterials And | NANOMATERIAL COVERS FOR OSTEOINTEGRATED BIOMEDICAL PROSTHESES |
US20070292397A1 (en) * | 2006-06-19 | 2007-12-20 | Mcnulty Amy K | Method for the detection and neutralization of bacteria |
US20110135742A1 (en) * | 2006-06-20 | 2011-06-09 | The Regents Of The University Of California | Controlled release encapsulated anti-bacterial and anti-inflammatory nanoparticles |
EP2043611A2 (en) * | 2006-06-30 | 2009-04-08 | Nucryst Pharmaceuticals Corp. | Metal-containing formulations and methods of use |
US8512294B2 (en) * | 2006-07-28 | 2013-08-20 | Becton, Dickinson And Company | Vascular access device antimicrobial materials and solutions |
US20080027410A1 (en) * | 2006-07-28 | 2008-01-31 | Becton, Dickinson And Company | Vascular access device non-adhering membranes |
US8197452B2 (en) * | 2006-07-28 | 2012-06-12 | Becton, Dickinson And Company | Vascular access device non-adhering surfaces |
EP2054537A2 (en) | 2006-08-02 | 2009-05-06 | Boston Scientific Scimed, Inc. | Endoprosthesis with three-dimensional disintegration control |
CA2663220A1 (en) | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Medical devices and methods of making the same |
CA2663198A1 (en) * | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Medical devices |
JP2010503494A (en) | 2006-09-15 | 2010-02-04 | ボストン サイエンティフィック リミテッド | Biodegradable endoprosthesis and method for producing the same |
WO2008034047A2 (en) * | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Endoprosthesis with adjustable surface features |
EP2210625B8 (en) * | 2006-09-15 | 2012-02-29 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis with biostable inorganic layers |
WO2008034050A2 (en) * | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Endoprosthesis containing magnetic induction particles |
EP2081616B1 (en) | 2006-09-15 | 2017-11-01 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
CA2663717A1 (en) * | 2006-09-18 | 2008-03-27 | Boston Scientific Limited | Controlling biodegradation of a medical instrument |
US20080071358A1 (en) * | 2006-09-18 | 2008-03-20 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8002821B2 (en) | 2006-09-18 | 2011-08-23 | Boston Scientific Scimed, Inc. | Bioerodible metallic ENDOPROSTHESES |
US7867522B2 (en) | 2006-09-28 | 2011-01-11 | Jr Chem, Llc | Method of wound/burn healing using copper-zinc compositions |
PL2452560T3 (en) * | 2006-10-12 | 2014-08-29 | Nm Tech Nanomaterials Microdevice Tech Ltd | Use of a composition having anti-microbial properties |
US20100098949A1 (en) * | 2006-10-18 | 2010-04-22 | Burton Scott A | Antimicrobial articles and method of manufacture |
US20080097577A1 (en) * | 2006-10-20 | 2008-04-24 | Boston Scientific Scimed, Inc. | Medical device hydrogen surface treatment by electrochemical reduction |
US20080103459A1 (en) * | 2006-10-30 | 2008-05-01 | Anthony Di Salvo | Enzyme inhibition using nanoparticles |
US20080122582A1 (en) * | 2006-11-29 | 2008-05-29 | Texas Instruments Incorporated | Location Based Portable Device Feature Disabler |
US20080132991A1 (en) * | 2006-11-30 | 2008-06-05 | Leonard Pinchuk | Method for Ionically Cross-Linking Gellan Gum for Thin Film Applications and Medical Devices Produced Therefrom |
US20080147734A1 (en) * | 2006-12-18 | 2008-06-19 | Cuticeuticals, Inc | Method of topical steroidal organization |
ES2506144T3 (en) | 2006-12-28 | 2014-10-13 | Boston Scientific Limited | Bioerodible endoprosthesis and their manufacturing procedure |
RU2009133446A (en) * | 2007-02-09 | 2011-03-20 | Пониард Фармасьютикалз, Инк. (Us) | STABILIZED PICOPLATIN DOSAGE FORM FOR ORAL USE |
WO2008112596A2 (en) * | 2007-03-09 | 2008-09-18 | Anthem Orthopaedics Llc | Implantable device with bioabsorbable layer, kit and method for use therewith, and apparatus for preparing same |
US20080226701A1 (en) * | 2007-03-15 | 2008-09-18 | John Deignan | Medicated patches |
EP2155324A1 (en) * | 2007-04-20 | 2010-02-24 | Nitric Biotherapeutics, Inc. | A single use applicator cartridge for an electrokinetic delivery system and method for self administration of medicaments |
US8309222B2 (en) * | 2007-04-25 | 2012-11-13 | Covidien Lp | Coated filaments |
US20100069957A1 (en) * | 2007-04-25 | 2010-03-18 | Ferass Abuzaina | Coated Filaments |
KR20080070482A (en) * | 2007-05-31 | 2008-07-30 | (주)디딤바이오텍 | A lubricating composition comprising agents which induce the mucosal immunity and a preparation method thereof |
WO2008157485A1 (en) * | 2007-06-15 | 2008-12-24 | Transport Pharmaceuticals, Inc. | Current concentration system and method for electrokinetic delivery of medicaments |
US8133553B2 (en) | 2007-06-18 | 2012-03-13 | Zimmer, Inc. | Process for forming a ceramic layer |
US8309521B2 (en) | 2007-06-19 | 2012-11-13 | Zimmer, Inc. | Spacer with a coating thereon for use with an implant device |
US20080319371A1 (en) * | 2007-06-19 | 2008-12-25 | Transport Pharmaceuticals, Inc. | Method and system for treating of onychomycosis with an applicator having a gel medicament layer |
JP5159183B2 (en) * | 2007-06-22 | 2013-03-06 | アイノベックス株式会社 | Composition for improvement or treatment of infertility |
DE102007031650A1 (en) | 2007-07-06 | 2009-01-08 | Stada Arzneimittel Ag | Dermatology for the treatment and / or care of the skin in atopic dermatitis |
US8052745B2 (en) | 2007-09-13 | 2011-11-08 | Boston Scientific Scimed, Inc. | Endoprosthesis |
CA2701009C (en) * | 2007-09-28 | 2017-03-21 | Johnson & Johnson Consumer Companies, Inc. | Electricity-generating particulates and the use thereof |
JP5451622B2 (en) * | 2007-10-03 | 2014-03-26 | スリーエム イノベイティブ プロパティズ カンパニー | Method for limiting the growth of microorganisms |
ES2319064B1 (en) * | 2007-10-05 | 2010-02-15 | Universidad De Santiago De Compostela | USE OF ATOMIC QUANTIC CLUSTERS (AQCS) AS ANTIMICROBIALS AND BIOCIDES. |
US20110230973A1 (en) * | 2007-10-10 | 2011-09-22 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
US8608049B2 (en) * | 2007-10-10 | 2013-12-17 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
US20090143855A1 (en) * | 2007-11-29 | 2009-06-04 | Boston Scientific Scimed, Inc. | Medical Device Including Drug-Loaded Fibers |
US20100008970A1 (en) * | 2007-12-14 | 2010-01-14 | Boston Scientific Scimed, Inc. | Drug-Eluting Endoprosthesis |
US8865227B2 (en) | 2007-12-20 | 2014-10-21 | Smith & Nephew (Overseas) Limited | Metal carbonate particles and methods of making thereof |
US20090163887A1 (en) * | 2007-12-20 | 2009-06-25 | Arehart Kelly D | Odor control cellulose granules with quinone compounds |
US8273791B2 (en) | 2008-01-04 | 2012-09-25 | Jr Chem, Llc | Compositions, kits and regimens for the treatment of skin, especially décolletage |
US20090187256A1 (en) * | 2008-01-21 | 2009-07-23 | Zimmer, Inc. | Method for forming an integral porous region in a cast implant |
US20090198286A1 (en) * | 2008-02-05 | 2009-08-06 | Zimmer, Inc. | Bone fracture fixation system |
BRPI0822264A2 (en) * | 2008-02-27 | 2014-09-30 | Allergan Inc | DAPSONA TO TREAT ROSE |
WO2009126967A1 (en) * | 2008-04-11 | 2009-10-15 | Pediadermics, Llc | Systems and methods for treatment kits |
JP5738753B2 (en) | 2008-04-24 | 2015-06-24 | メドトロニック,インコーポレイテッド | Rehydratable polysaccharide particles and sponges |
WO2009132228A1 (en) | 2008-04-24 | 2009-10-29 | Medtronic, Inc. | Chitosan-containing protective composition |
AU2009240512B2 (en) * | 2008-04-24 | 2014-07-10 | Medtronic, Inc. | Protective gel based on chitosan and oxidized polysaccharide |
AU2009240509B2 (en) | 2008-04-24 | 2014-08-21 | Medtronic, Inc. | Rehydratable thiolated polysaccharide particles and sponge |
US8506944B2 (en) * | 2008-05-07 | 2013-08-13 | The Regents Of The University Of California | Replenishment and enrichment of ocular surface lubrication |
CA2722913C (en) * | 2008-05-07 | 2018-02-27 | Schepens Eye Research Institute | Prg4 compositions and methods for therapeutic treatment of dry eye |
US7998192B2 (en) | 2008-05-09 | 2011-08-16 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8389583B2 (en) * | 2008-05-23 | 2013-03-05 | Zurex Pharma, Inc. | Antimicrobial compositions and methods of use |
US8236046B2 (en) * | 2008-06-10 | 2012-08-07 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
US20100004733A1 (en) * | 2008-07-02 | 2010-01-07 | Boston Scientific Scimed, Inc. | Implants Including Fractal Structures |
IT1391669B1 (en) * | 2008-07-23 | 2012-01-17 | Universita' Degli Studi Di Trieste | NANOCOMPOSITE MATERIALS FORMED FROM A POLYSACCHARIDIC MATRIX AND METALLIC NANOPARTICLES, THEIR PREPARATION AND USE |
US7985252B2 (en) | 2008-07-30 | 2011-07-26 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
US20100030170A1 (en) * | 2008-08-01 | 2010-02-04 | Keith Alan Keller | Absorptive Pad |
US20100082088A1 (en) * | 2008-08-27 | 2010-04-01 | Ali Fassih | Treatment of sweating and hyperhydrosis |
US8150525B2 (en) * | 2008-08-27 | 2012-04-03 | Johnson & Johnson Consumer Companies, Inc. | Treatment of hyperhydrosis |
WO2010027189A2 (en) * | 2008-09-02 | 2010-03-11 | 가톨릭대학교 산학협력단 | A new use for homoisoflavanone or a salt thereof |
US8382824B2 (en) * | 2008-10-03 | 2013-02-26 | Boston Scientific Scimed, Inc. | Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides |
EP2218447B1 (en) * | 2008-11-04 | 2017-04-19 | PharmaSol GmbH | Compositions containing lipid micro- or nanoparticles for the enhancement of the dermal action of solid particles |
US20100124568A1 (en) * | 2008-11-20 | 2010-05-20 | Med-Eez, Inc | Pharmaceutical articles coated with lubricious coatings |
US8551517B2 (en) * | 2008-12-16 | 2013-10-08 | Kimberly-Clark Worldwide, Inc. | Substrates providing multiple releases of active agents |
WO2010085753A1 (en) | 2009-01-23 | 2010-07-29 | Jr Chem, Llc | Rosacea treatments and kits for performing them |
EP2403546A2 (en) | 2009-03-02 | 2012-01-11 | Boston Scientific Scimed, Inc. | Self-buffering medical implants |
US20100229282A1 (en) * | 2009-03-11 | 2010-09-16 | Ansell Limited | Powder-Free Anti-Blocking Coated Glove |
US9149567B2 (en) * | 2009-03-11 | 2015-10-06 | Ansell Limited | Powder-free antimicrobial coated glove |
US20100234925A1 (en) * | 2009-03-16 | 2010-09-16 | PinPoint U.S.A., Inc. | Treatment of microbiological pathogens in a toe nail with antimicrobial light |
US20120089232A1 (en) | 2009-03-27 | 2012-04-12 | Jennifer Hagyoung Kang Choi | Medical devices with galvanic particulates |
BRPI1011316B8 (en) | 2009-05-26 | 2021-06-22 | Massachusetts Gen Hospital | apparatus for administering a substance to skin tissue |
WO2010144044A1 (en) * | 2009-06-10 | 2010-12-16 | Exthera Ab | Use of a composition for the treatment of mucositis |
US9192626B2 (en) | 2009-06-10 | 2015-11-24 | American Silver, Llc | Dental uses of silver hydrosol |
US8821455B2 (en) * | 2009-07-09 | 2014-09-02 | Becton, Dickinson And Company | Antimicrobial coating for dermally invasive devices |
US20110008271A1 (en) * | 2009-07-13 | 2011-01-13 | Jr Chem, Llc | Rosacea treatments using polymetal complexes |
US20110022158A1 (en) * | 2009-07-22 | 2011-01-27 | Boston Scientific Scimed, Inc. | Bioerodible Medical Implants |
US8814922B2 (en) * | 2009-07-22 | 2014-08-26 | New Star Lasers, Inc. | Method for treatment of fingernail and toenail microbial infections using infrared laser heating and low pressure |
US20110065798A1 (en) * | 2009-09-17 | 2011-03-17 | Becton, Dickinson And Company | Anti-infective lubricant for medical devices and methods for preparing the same |
US20110091571A1 (en) * | 2009-10-16 | 2011-04-21 | Moore Michael F | Method of controlling the propagation of mrsa, staph and other infections that colonize in the nose |
CN106913902A (en) | 2009-11-09 | 2017-07-04 | 聚光灯技术合伙有限责任公司 | Polysaccharide based aquagel |
US8795727B2 (en) | 2009-11-09 | 2014-08-05 | Spotlight Technology Partners Llc | Fragmented hydrogels |
BR112012011411A2 (en) * | 2009-11-13 | 2017-12-12 | Johnson & Johnson Consumer Companies Inc | galvanic skin care device |
US8701671B2 (en) | 2011-02-04 | 2014-04-22 | Joseph E. Kovarik | Non-surgical method and system for reducing snoring |
US9549842B2 (en) | 2011-02-04 | 2017-01-24 | Joseph E. Kovarik | Buccal bioadhesive strip and method of treating snoring and sleep apnea |
JP2011135009A (en) * | 2009-12-25 | 2011-07-07 | Tokyo Electron Ltd | Method and apparatus for drying substrate |
KR20110091461A (en) * | 2010-02-05 | 2011-08-11 | 존슨 앤드 존슨 컨수머 캄파니즈, 인코포레이티드 | Lip compositions comprising galvanic particulates |
US20110212042A1 (en) * | 2010-03-01 | 2011-09-01 | Prithwiraj Maitra | Skin care composition having desirable bulk color |
US8668732B2 (en) * | 2010-03-23 | 2014-03-11 | Boston Scientific Scimed, Inc. | Surface treated bioerodible metal endoprostheses |
US20110236491A1 (en) * | 2010-03-25 | 2011-09-29 | Jeannette Chantalat | Topical anti-inflammatory composition |
US9999702B2 (en) | 2010-04-09 | 2018-06-19 | Kci Licensing Inc. | Apparatuses, methods, and compositions for the treatment and prophylaxis of chronic wounds |
US20110301553A1 (en) * | 2010-06-04 | 2011-12-08 | Smiths Medical Asd, Inc. | Antimicrobial lubricant |
RU2452498C2 (en) * | 2010-07-20 | 2012-06-10 | Общество с ограниченной ответственностью "Научно-производственное объединение "Ликом" | Method for preparing anti-tuberculosis drug |
US9061056B2 (en) | 2010-08-27 | 2015-06-23 | Sienna Labs, Inc. | Compositions and methods for targeted thermomodulation |
US9572880B2 (en) | 2010-08-27 | 2017-02-21 | Sienna Biopharmaceuticals, Inc. | Ultrasound delivery of nanoparticles |
JP5646277B2 (en) * | 2010-10-25 | 2014-12-24 | クラシエホームプロダクツ株式会社 | Disinfectant and acne treatment / prevention agent |
US9572329B2 (en) * | 2010-11-18 | 2017-02-21 | Samuel P Hopkins | Antimicrobial containing fish hook and method of using and manufacturing same |
US8952057B2 (en) | 2011-01-11 | 2015-02-10 | Jr Chem, Llc | Compositions for anorectal use and methods for treating anorectal disorders |
US10687975B2 (en) | 2011-02-04 | 2020-06-23 | Joseph E. Kovarik | Method and system to facilitate the growth of desired bacteria in a human's mouth |
US10512661B2 (en) | 2011-02-04 | 2019-12-24 | Joseph E. Kovarik | Method and system for reducing the likelihood of developing liver cancer in an individual diagnosed with non-alcoholic fatty liver disease |
US11357722B2 (en) | 2011-02-04 | 2022-06-14 | Seed Health, Inc. | Method and system for preventing sore throat in humans |
US11523934B2 (en) | 2011-02-04 | 2022-12-13 | Seed Health, Inc. | Method and system to facilitate the growth of desired bacteria in a human's mouth |
US10548761B2 (en) | 2011-02-04 | 2020-02-04 | Joseph E. Kovarik | Method and system for reducing the likelihood of colorectal cancer in a human being |
US11844720B2 (en) | 2011-02-04 | 2023-12-19 | Seed Health, Inc. | Method and system to reduce the likelihood of dental caries and halitosis |
US10086018B2 (en) | 2011-02-04 | 2018-10-02 | Joseph E. Kovarik | Method and system for reducing the likelihood of colorectal cancer in a human being |
US9987224B2 (en) | 2011-02-04 | 2018-06-05 | Joseph E. Kovarik | Method and system for preventing migraine headaches, cluster headaches and dizziness |
US10245288B2 (en) | 2011-02-04 | 2019-04-02 | Joseph E. Kovarik | Method and system for reducing the likelihood of developing NASH in an individual diagnosed with non-alcoholic fatty liver disease |
KR20230160959A (en) | 2011-02-16 | 2023-11-24 | 더 제너럴 하스피탈 코포레이션 | Optical coupler for an endoscope |
US9707375B2 (en) | 2011-03-14 | 2017-07-18 | Rochester Medical Corporation, a subsidiary of C. R. Bard, Inc. | Catheter grip and method |
US8597264B2 (en) | 2011-03-24 | 2013-12-03 | Kci Licensing, Inc. | Apparatuses, methods, and compositions for the treatment and prophylaxis of chronic wounds |
US9387225B2 (en) * | 2011-03-30 | 2016-07-12 | GR INTELLECTUAL RESERVE, LLC, a Nevada LLC | Gold-platinum based bi-metallic nanocrystal suspensions, electrochemical manufacturing processes therefor and uses for the same |
CN103501827B (en) * | 2011-03-30 | 2015-08-19 | 大和纺控股株式会社 | Wound cladding material |
GB2497115A (en) * | 2011-12-01 | 2013-06-05 | Lrc Products | Coated condom |
JP6017883B2 (en) * | 2012-08-08 | 2016-11-02 | バイオエポック株式会社 | Manufacturing method of toothpaste |
ES2848025T3 (en) | 2012-09-04 | 2021-08-05 | Eleison Pharmaceuticals LLC | Prevention of lung cancer recurrence with lipid-complexed cisplatin |
CN102872159A (en) * | 2012-09-29 | 2013-01-16 | 广东同德药业有限公司 | Nano-silver chitosan gel foam preparation for treating vaginal bacterial inflammation, and preparation method thereof |
MX2015004524A (en) | 2012-10-11 | 2015-09-25 | Nanocomposix Inc | Silver nanoplate compositions and methods. |
EP2911677A4 (en) * | 2012-10-26 | 2016-10-12 | Nanocomposix Inc | Metastable silver nanoparticle composites |
CN102872160A (en) * | 2012-10-26 | 2013-01-16 | 广东同德药业有限公司 | Nano-silver foaming agent used for sterilizing wounds of scalds and burns and ulcer wounds |
US9872969B2 (en) | 2012-11-20 | 2018-01-23 | Rochester Medical Corporation, a subsidiary of C.R. Bard, Inc. | Catheter in bag without additional packaging |
US10092728B2 (en) | 2012-11-20 | 2018-10-09 | Rochester Medical Corporation, a subsidiary of C.R. Bard, Inc. | Sheath for securing urinary catheter |
US20140377318A1 (en) * | 2012-12-06 | 2014-12-25 | S. Douglas Cornell | Antimicrobial sanitizer systems and methods of killing or inhibiting pathogens |
EP2764876A1 (en) * | 2013-02-11 | 2014-08-13 | Lacerta Technologies Inc. | Bone substitute material with biologically active coating |
US9695323B2 (en) | 2013-02-13 | 2017-07-04 | Becton, Dickinson And Company | UV curable solventless antimicrobial compositions |
US9750928B2 (en) | 2013-02-13 | 2017-09-05 | Becton, Dickinson And Company | Blood control IV catheter with stationary septum activator |
US9750927B2 (en) | 2013-03-11 | 2017-09-05 | Becton, Dickinson And Company | Blood control catheter with antimicrobial needle lube |
US9327095B2 (en) | 2013-03-11 | 2016-05-03 | Becton, Dickinson And Company | Blood control catheter with antimicrobial needle lube |
EP2968886A1 (en) | 2013-03-14 | 2016-01-20 | Hallux, Inc. | Method of treating infections, diseases or disorders of nail unit |
US10398733B2 (en) | 2013-03-15 | 2019-09-03 | Cda Research Group, Inc. | Topical copper ion treatments and methods of treatment using topical copper ion treatments in the dermatological areas of the body |
US11083750B2 (en) | 2013-03-15 | 2021-08-10 | Cda Research Group, Inc. | Methods of treatment using topical copper ion formulations |
US20140271919A1 (en) * | 2013-03-15 | 2014-09-18 | Chun Lim Abbott | Topical Copper Ion Treatments and Methods of Treatment Using Topical Copper Ion Treatments in the Genital-Rectal Areas of the Body |
US11318089B2 (en) | 2013-03-15 | 2022-05-03 | Cda Research Group, Inc. | Topical copper ion treatments and methods of making topical copper ion treatments for use in various anatomical areas of the body |
US11000545B2 (en) | 2013-03-15 | 2021-05-11 | Cda Research Group, Inc. | Copper ion compositions and methods of treatment for conditions caused by coronavirus and influenza |
US11007143B2 (en) | 2013-03-15 | 2021-05-18 | Cda Research Group, Inc. | Topical copper ion treatments and methods of treatment using topical copper ion treatments in the oral-respiratory-otic areas of the body |
WO2014151107A1 (en) * | 2013-03-15 | 2014-09-25 | Kcl Licensing, Inc. | Wound healing compositions |
US9095566B1 (en) * | 2013-06-28 | 2015-08-04 | Edward Quicksilver Yavitz | Eyelash and eyelid margin infections |
US11833177B2 (en) | 2013-12-20 | 2023-12-05 | Seed Health, Inc. | Probiotic to enhance an individual's skin microbiome |
US10842834B2 (en) | 2016-01-06 | 2020-11-24 | Joseph E. Kovarik | Method and system for reducing the likelihood of developing liver cancer in an individual diagnosed with non-alcoholic fatty liver disease |
US11419903B2 (en) | 2015-11-30 | 2022-08-23 | Seed Health, Inc. | Method and system for reducing the likelihood of osteoporosis |
US11273187B2 (en) | 2015-11-30 | 2022-03-15 | Joseph E. Kovarik | Method and system for reducing the likelihood of developing depression in an individual |
US11826388B2 (en) | 2013-12-20 | 2023-11-28 | Seed Health, Inc. | Topical application of Lactobacillus crispatus to ameliorate barrier damage and inflammation |
US11839632B2 (en) | 2013-12-20 | 2023-12-12 | Seed Health, Inc. | Topical application of CRISPR-modified bacteria to treat acne vulgaris |
US20150182673A1 (en) | 2013-12-30 | 2015-07-02 | Boston Scientific Scimed, Inc. | Functionalized lubricious medical device coatings |
CN104814831A (en) * | 2014-01-30 | 2015-08-05 | 柯惠有限合伙公司 | Preparation of occlusive dressings |
US10376686B2 (en) | 2014-04-23 | 2019-08-13 | Becton, Dickinson And Company | Antimicrobial caps for medical connectors |
US9789279B2 (en) | 2014-04-23 | 2017-10-17 | Becton, Dickinson And Company | Antimicrobial obturator for use with vascular access devices |
US9675793B2 (en) | 2014-04-23 | 2017-06-13 | Becton, Dickinson And Company | Catheter tubing with extraluminal antimicrobial coating |
US10232088B2 (en) | 2014-07-08 | 2019-03-19 | Becton, Dickinson And Company | Antimicrobial coating forming kink resistant feature on a vascular access device |
MX2017002457A (en) | 2014-08-26 | 2017-05-19 | Bard Inc C R | Urinary catheter. |
US9459442B2 (en) | 2014-09-23 | 2016-10-04 | Scott Miller | Optical coupler for optical imaging visualization device |
CN104577135B (en) * | 2015-01-04 | 2017-01-18 | 哈尔滨工业大学 | Preparation method of three-dimensional silver mesh |
US10548467B2 (en) | 2015-06-02 | 2020-02-04 | GI Scientific, LLC | Conductive optical element |
CN108289595B (en) | 2015-07-21 | 2021-03-16 | 图像科学有限责任公司 | Endoscopic accessory with angularly adjustable exit port |
RU2611999C2 (en) * | 2015-08-05 | 2017-03-01 | Федеральное государственное бюджетное учреждение науки Иркутский институт химии им. А.Е. Фаворского Сибирского отделения Российской академии наук | Silver nanocomposite based on arabinogalactan conjugate and flavonoids with antimicrobial and antitumor action and preparation method thereof |
US10040957B2 (en) * | 2015-09-17 | 2018-08-07 | Eastman Kodak Company | Ink jettable, UV-curable compositions |
DE102015115878B4 (en) * | 2015-09-21 | 2018-03-29 | Aap Implantate Ag | A method of treating a metallic surface and bodies having a treated metallic surface |
US10493244B2 (en) | 2015-10-28 | 2019-12-03 | Becton, Dickinson And Company | Extension tubing strain relief |
US10792477B2 (en) | 2016-02-08 | 2020-10-06 | Orbusneich Medical Pte. Ltd. | Drug eluting balloon |
US20210196932A1 (en) * | 2016-02-08 | 2021-07-01 | Orbusneich Medical, Inc. | Drug Eluting Balloon |
BR102016016340A2 (en) * | 2016-07-14 | 2018-02-06 | Francisco Pianowski Luiz | ANTIMICROBIAN MUCOSAL FORMULATION AND USE OF ANTIMICROBIAN MUCOSAL FORMULATION |
US11330931B2 (en) | 2016-09-29 | 2022-05-17 | Levo Oil Infusion | Apparatus and method for infusing and dispensing oils, and drying and heating infusing materials |
US10537661B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
US10537658B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
CA3070865A1 (en) | 2017-09-19 | 2019-03-28 | C.R. Bard, Inc. | Urinary catheter bridging device, systems and methods thereof |
RU2659580C1 (en) * | 2017-10-16 | 2018-07-05 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Кировский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО Кировский ГМУ Минздрава России) | Method for obtaining agent for topical treatment of skin lesions based on nanoscale silver particles, ointment base and solid additives |
US10912739B2 (en) | 2017-10-16 | 2021-02-09 | Peace Out Inc. | Hydrocolloid-based skin treatment |
WO2020006073A1 (en) | 2018-06-28 | 2020-01-02 | Arx, Llc | Dispensing method for producing dissolvable unit dose film constructs |
CN108853557A (en) * | 2018-07-23 | 2018-11-23 | 衢州玛济克医疗科技有限公司 | A kind of wet erythema medical dressing of infant and its production method |
CN109646456A (en) * | 2018-12-31 | 2019-04-19 | 四川金凯医疗器械有限公司 | It is a kind of for treating the new type gel of periodontitis |
CN109731103B (en) * | 2019-01-20 | 2022-03-22 | 桂林理工大学 | Preparation method of P-type molecular sieve-chitosan-sodium alginate-potassium diformate sustained-release antibacterial agent |
US11193184B2 (en) | 2019-02-22 | 2021-12-07 | Cda Research Group, Inc. | System for use in producing a metal ion suspension and process of using same |
RU2730480C1 (en) * | 2019-07-30 | 2020-08-24 | Общество с ограниченной ответственностью "БиоМед" | Method of administering a pharmaceutical substance into a polymer substrate of a dressing |
WO2021202332A1 (en) * | 2020-03-28 | 2021-10-07 | Iview Therapeutics, Inc. | Aqueous formulations containing povidone iodine for effective treatment and prevention of virus infections |
DE102021205475A1 (en) * | 2021-05-28 | 2022-12-01 | FNT-GmbH | Antimicrobial composition, method of making an antimicrobial composition and use of an antimicrobial composition |
CN113479975A (en) * | 2021-07-01 | 2021-10-08 | 辽宁锦海医药科技有限公司 | Preparation method and application of oxidation potential acidic water |
KR20230081979A (en) * | 2021-11-30 | 2023-06-08 | 경희대학교 산학협력단 | Composition for anti-inflammation comprising gold nanoparticle-peanut sprout extract as an active ingredient |
US11684586B1 (en) | 2022-02-28 | 2023-06-27 | Peace Out, Llc | Anhydrous hydrocolloid matrix comprising homogeneously distributed encapsulated therapeutic agents |
Citations (72)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3757786A (en) * | 1970-11-06 | 1973-09-11 | D Smith | Synthetic surgical sutures |
US3800792A (en) * | 1972-04-17 | 1974-04-02 | Johnson & Johnson | Laminated collagen film dressing |
US3918446A (en) * | 1974-05-03 | 1975-11-11 | E Med Corp | Securement device for intravenous catheter and its tubing |
US4059105A (en) * | 1976-03-24 | 1977-11-22 | Omnimed, Inc. | Cannula securing device |
US4324237A (en) * | 1980-02-26 | 1982-04-13 | E-Med Corporation | Intravenous catheter and tubing securement and dressing device with a window over the puncture or wound site |
US4355636A (en) * | 1979-07-21 | 1982-10-26 | Dragerwerk Ag | Humdifier and heater for air to be inhaled for connection to an inhalation conduit of a respirator |
US4476590A (en) * | 1980-03-27 | 1984-10-16 | National Research Development Corporation | Antimicrobial surgical implants |
US4581028A (en) * | 1984-04-30 | 1986-04-08 | The Trustees Of Columbia University In The City Of New York | Infection-resistant materials and method of making same through use of sulfonamides |
US4596556A (en) * | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US4633863A (en) * | 1985-09-27 | 1987-01-06 | Filips Chester P | Arterial anchor bandage |
US4749572A (en) * | 1984-08-28 | 1988-06-07 | Pharmaceutical Holdings Limited | Pharmaceutical preparations |
US4790824A (en) * | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US4803066A (en) * | 1986-03-22 | 1989-02-07 | Smith & Nephew Associated Companies P.L.C. | Antibacterial and/or antifungal compositions for topical application |
US4828832A (en) * | 1983-09-07 | 1989-05-09 | Laboratorios Biochemie De Mexico | Method of manufacturing a composition for treating skin lesions |
US4847049A (en) * | 1985-12-18 | 1989-07-11 | Vitaphore Corporation | Method of forming chelated collagen having bactericidal properties |
US4952411A (en) * | 1987-02-25 | 1990-08-28 | Trustees Of Columbia University In The City Of New York | Method of inhibiting the transmission of AIDS virus |
US4960413A (en) * | 1985-11-09 | 1990-10-02 | The Shirley Institute | Wound dressing |
US5019096A (en) * | 1988-02-11 | 1991-05-28 | Trustees Of Columbia University In The City Of New York | Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same |
US5064413A (en) * | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US5122418A (en) * | 1985-12-09 | 1992-06-16 | Shiseido Company Ltd. | Composite powder and production process |
US5143717A (en) * | 1987-12-30 | 1992-09-01 | Code Blue Medical Corporation | Burn foam and delivery system |
US5236421A (en) * | 1986-05-28 | 1993-08-17 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Fixing system for fastening catheters, cannulas or the like to the skin surface and process for the sterile fastening thereof |
US5270358A (en) * | 1989-12-28 | 1993-12-14 | Minnesota Mining And Manufacturing Company | Composite of a disperesed gel in an adhesive matrix |
US5312335A (en) * | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
US5372589A (en) * | 1993-11-24 | 1994-12-13 | Davis; W. Gordon | Fenestrated transparent catheter securing device and method |
US5383851A (en) * | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
US5454889A (en) * | 1993-08-19 | 1995-10-03 | Ici Canada Inc. | Prill coating |
US5454886A (en) * | 1993-11-18 | 1995-10-03 | Westaim Technologies Inc. | Process of activating anti-microbial materials |
US5457015A (en) * | 1991-09-03 | 1995-10-10 | Minnesota Mining And Manufacturing Company | Silver halide coated organic polymeric films utilizing chitosan acid salt antistatic protection layers |
US5534288A (en) * | 1993-03-23 | 1996-07-09 | United States Surgical Corporation | Infection-resistant surgical devices and methods of making them |
US5563132A (en) * | 1994-06-21 | 1996-10-08 | Bodaness; Richard S. | Two-step cancer treatment method |
US5569207A (en) * | 1994-10-13 | 1996-10-29 | Quinton Instrument Company | Hydrocolloid dressing |
US5578073A (en) * | 1994-09-16 | 1996-11-26 | Ramot Of Tel Aviv University | Thromboresistant surface treatment for biomaterials |
US5631066A (en) * | 1993-01-25 | 1997-05-20 | Chronopol, Inc. | Process for making metalized films and films produced therefrom |
US5681575A (en) * | 1992-05-19 | 1997-10-28 | Westaim Technologies Inc. | Anti-microbial coating for medical devices |
US5770258A (en) * | 1992-12-25 | 1998-06-23 | Mitsubishi Denki Kabushiki Kaisha | Cathode-ray tube and method of producing the same |
US5774151A (en) * | 1993-01-01 | 1998-06-30 | Canon Kabushiki Kaisha | Liquid ejecting head, liquid ejecting apparatus and method of producing said liquid ejecting head |
US5792793A (en) * | 1993-11-05 | 1998-08-11 | Meiji Milk Products Co., Ltd. | Antibacterial, antifungal and antiviral agent |
US5837275A (en) * | 1992-05-19 | 1998-11-17 | Westaim Technologies, Inc. | Anti-microbial materials |
US5848995A (en) * | 1993-04-09 | 1998-12-15 | Walder; Anthony J. | Anti-infective medical article and method for its preparation |
US5895419A (en) * | 1996-09-30 | 1999-04-20 | St. Jude Medical, Inc. | Coated prosthetic cardiac device |
US5899880A (en) * | 1994-04-08 | 1999-05-04 | Powderject Research Limited | Needleless syringe using supersonic gas flow for particle delivery |
US5945032A (en) * | 1996-09-30 | 1999-08-31 | Basf Aktiengesellschaft | Polymer/hydrogen peroxide complexes |
US5965610A (en) * | 1994-03-28 | 1999-10-12 | The Trustees Of Columbia University In The City Of New York | Composition for inactivating irritants in fluids |
US5981822A (en) * | 1997-05-02 | 1999-11-09 | Johnson & Johnson Medical, Inc. | Absorbent wound dressings |
US6010478A (en) * | 1995-02-14 | 2000-01-04 | Powderject Research Limited | Trans-mucosal particle delivery |
US6013050A (en) * | 1995-10-20 | 2000-01-11 | Powderject Research Limited | Particle delivery |
US6022547A (en) * | 1994-12-06 | 2000-02-08 | Helene Curtis, Inc. | Rinse-off water-in-oil-in-water compositions |
US6071541A (en) * | 1998-07-31 | 2000-06-06 | Murad; Howard | Pharmaceutical compositions and methods for managing skin conditions |
US6071543A (en) * | 1997-06-02 | 2000-06-06 | Cellegy Pharmaceuticals, Inc. | Pyridine-thiols reverse mucocutaneous aging |
US6096002A (en) * | 1998-11-18 | 2000-08-01 | Bioject, Inc. | NGAS powered self-resetting needle-less hypodermic jet injection apparatus and method |
US6123925A (en) * | 1998-07-27 | 2000-09-26 | Healthshield Technologies L.L.C. | Antibiotic toothpaste |
US6126931A (en) * | 1993-12-20 | 2000-10-03 | Surfacine Development Company, Llc | Contact-killing antimicrobial devices |
US6165440A (en) * | 1997-07-09 | 2000-12-26 | Board Of Regents, The University Of Texas System | Radiation and nanoparticles for enhancement of drug delivery in solid tumors |
US6187290B1 (en) * | 1994-12-06 | 2001-02-13 | Giltech Limited | Physiologically acceptable foamable formulation and foam |
US6197351B1 (en) * | 1995-06-07 | 2001-03-06 | Robert S. Neuwirth | Intrauterine chemical necrosing method and composition |
US6201164B1 (en) * | 1996-07-11 | 2001-03-13 | Coloplast A/S | Hydrocolloid wound gel |
US6224898B1 (en) * | 2000-03-23 | 2001-05-01 | The United States Of America As Represented By The Secretary Of The Army | Antimicrobial dendrimer nanocomposites and a method of treating wounds |
US6258385B1 (en) * | 1999-04-22 | 2001-07-10 | Marantech Holding, Llc | Tetrasilver tetroxide treatment for skin conditions |
US20010010016A1 (en) * | 1999-03-31 | 2001-07-26 | Shanta Modak | Triclosan and silver compound containing medical devices |
US6277169B1 (en) * | 1997-02-24 | 2001-08-21 | Superior Micropowders Llc | Method for making silver-containing particles |
US6294186B1 (en) * | 1997-06-04 | 2001-09-25 | Peter William Beerse | Antimicrobial compositions comprising a benzoic acid analog and a metal salt |
US6333093B1 (en) * | 1997-03-17 | 2001-12-25 | Westaim Biomedical Corp. | Anti-microbial coatings having indicator properties and wound dressings |
US20020001628A1 (en) * | 1999-11-24 | 2002-01-03 | Mikio Ito | Pharmaceutical composition for preventing and/or curing digestive disorders |
US20020016585A1 (en) * | 2000-07-29 | 2002-02-07 | Sachse Hans E. | Catheter with a bio-resorbable coating for preventing ascending infections |
US20020025344A1 (en) * | 1998-11-09 | 2002-02-28 | Ira Jay Newman | Ionic silver complex |
US6365130B1 (en) * | 1998-11-23 | 2002-04-02 | Agion Technologies L.L.C. | Antimicrobial chewing gum |
US20020045049A1 (en) * | 1997-06-20 | 2002-04-18 | Madsen Niels Joergen | Hydrophilic coating and a method for the preparation thereof |
US20020051824A1 (en) * | 2000-07-27 | 2002-05-02 | Burrell Robert Edward | Treatment of hyperproliferative skin disorders and diseases |
US20020192298A1 (en) * | 2001-04-23 | 2002-12-19 | Burrell Robert Edward | Treatment of acne |
US20030170314A1 (en) * | 2000-07-27 | 2003-09-11 | Burrell Robert E. | Compositions of metal-containing compounds |
US6702006B2 (en) * | 2000-05-19 | 2004-03-09 | Alfa Laval Corporate Ab | Plate pack, flow distribution device and plate heat exchanger |
Family Cites Families (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB420052A (en) | 1932-10-17 | 1934-11-23 | Consortium Elektrochem Ind | Manufacture of shaped articles from polyvinyl alcohols |
FR732895A (en) | 1932-10-18 | 1932-09-25 | Consortium Elektrochem Ind | Articles spun in polyvinyl alcohol |
FR882M (en) | 1961-01-18 | 1961-10-06 | ||
GB1270410A (en) | 1969-09-25 | 1972-04-12 | Allor Corp | Colloidal composition and method of preparing the same |
US3988434A (en) * | 1972-08-07 | 1976-10-26 | Schole Murray L | Dental preparation |
DE2748882A1 (en) | 1977-11-02 | 1979-05-03 | Arnis Dr Med Rava | Plaster protecting wound against infection - esp. during application of intravenous catheter, permitting continuous use for ten days |
GB2073024B (en) | 1980-03-27 | 1984-06-27 | Nat Res Dev | Antimicrobial surgical implants |
DE3176658D1 (en) | 1981-12-10 | 1988-03-31 | Revlon | Process for making metallic leafing pigments |
JPS58126910A (en) | 1982-01-21 | 1983-07-28 | Nippon Steel Corp | Dephosphorizing method of molten metal |
GB2140684B (en) | 1983-04-25 | 1986-07-30 | Stavros Christodoulou | Mineral oil composition for use in the treatment of eczema |
JPS6021912A (en) | 1983-07-14 | 1985-02-04 | Mitsubishi Rayon Co Ltd | Manufacture of metallized synthetic fiber staple |
EP0136768A3 (en) | 1983-09-07 | 1986-07-30 | Laboratorios Biochemie De Mexico S.A. DE C.V. | Composition and method for treatingskin lesions |
JPS62185807A (en) | 1986-02-08 | 1987-08-14 | Mitsubishi Shindo Kk | Production of metallic flat powder |
GB8612598D0 (en) | 1986-05-23 | 1986-07-02 | Tarnpure Ltd | Liquid/gas interface apparatus |
EP0254413A3 (en) | 1986-06-13 | 1989-11-08 | Yoshiaki Matsuo | Silver-ionic water and its uses |
DE3807944A1 (en) | 1988-03-10 | 1989-09-21 | Braun Melsungen Ag | Device for fastening a catheter or a cannula on the skin surface |
NZ228367A (en) * | 1988-03-23 | 1992-02-25 | Smithkline Beecham Corp | Topical composition containing a gold compound for treating inflammatory conditions |
EP0355009A1 (en) | 1988-08-18 | 1990-02-21 | Konrad Minninger | Silver sulfadiazine containing pharmaceutical product for the local external therapy |
US4956350A (en) | 1988-08-18 | 1990-09-11 | Minnesota Mining And Manufacturing Company | Wound filling compositions |
US4908355A (en) | 1989-01-09 | 1990-03-13 | Dow Corning Corporation | Skin treatment method |
JP3169621B2 (en) | 1991-01-29 | 2001-05-28 | 株式会社タカミツ | Antimicrobial external preparation |
EP0570452A1 (en) | 1991-02-06 | 1993-11-24 | Minnesota Mining And Manufacturing Company | Improved surgical hardware with bacteriostatic silver coating, and method of using same |
US5484886A (en) * | 1991-04-25 | 1996-01-16 | Merck & Co., Inc. | Human neurokinin-1 receptor |
USD349958S (en) | 1992-07-24 | 1994-08-23 | Bioject Inc. | Needleless injector |
CN1034090C (en) | 1992-08-06 | 1997-02-19 | 蒋建华 | Long-acting broad-spectrum antiseptic fabric and its producing method |
IT1256111B (en) | 1992-11-23 | 1995-11-28 | Lifegroup Spa | SALTS OF TRAUMATIC ACID WITH CICATRIZING AND ANTIBACTERIAL ACTIVITY |
CA2136455C (en) * | 1993-11-18 | 1999-06-29 | Robert Edward Burrell | Process for producing anti-microbial effect with complex silver ions |
EP0681841A1 (en) | 1993-11-26 | 1995-11-15 | Kimurakogyo Co., Ltd. | $i(IN VIVO) FREE-RADICAL GENERATOR |
JPH07220702A (en) * | 1994-02-02 | 1995-08-18 | Nec Corp | Battery pack |
AU3708495A (en) * | 1994-08-01 | 1996-03-04 | Franz Hehmann | Selected processing for non-equilibrium light alloys and products |
US5744151A (en) | 1995-06-30 | 1998-04-28 | Capelli; Christopher C. | Silver-based pharmaceutical compositions |
DE19541735A1 (en) | 1995-11-09 | 1997-05-15 | Iris Roller | Use of hydrothermal rock deposits e.g. calcite precursors |
US5686096A (en) | 1995-12-22 | 1997-11-11 | Becton Dickinson And Company | Medical device for the protection of a catheter penetration site |
EP0834319A1 (en) * | 1996-10-07 | 1998-04-08 | Kartar Dr. Lalvani | Mineral and vitamin combinations in arthritic pain |
GB9623962D0 (en) * | 1996-11-15 | 1997-01-08 | Tillotts Pharma Ag | Pharmaceutical composition |
AU7484198A (en) | 1997-05-12 | 1998-12-08 | Sage Pharmaceuticals, Inc. | Topical spray for burn treatment and anti-infection |
DE19728489A1 (en) | 1997-07-03 | 1999-01-07 | Huels Chemische Werke Ag | Medical device for improving the skin fixation of indwelling catheters and other transcutaneous implants with a reduced risk of infection |
US6153210A (en) * | 1997-08-14 | 2000-11-28 | Periodontix, Inc. | Use of locally delivered metal ions for treatment of periodontal disease |
JP3411195B2 (en) * | 1997-08-18 | 2003-05-26 | 栄一 築地 | Active oxygen remover |
JPH11116488A (en) | 1997-10-08 | 1999-04-27 | Toagosei Co Ltd | Carcinostatic agent |
JP4039719B2 (en) * | 1997-10-17 | 2008-01-30 | 富士フイルム株式会社 | Antitumor agent |
US6312643B1 (en) * | 1997-10-24 | 2001-11-06 | The United States Of America As Represented By The Secretary Of The Air Force | Synthesis of nanoscale aluminum alloy powders and devices therefrom |
HU221676B1 (en) * | 1998-02-20 | 2002-12-28 | István Budai | Pharmaceutical composition, containing ethanol or water-ethanol solution having iodine and silver nitrate and process for producing it |
FR2775696B1 (en) * | 1998-03-05 | 2000-04-14 | Saint Gobain Vitrage | SUBSTRATE WITH PHOTOCATALYTIC COATING |
US20020014406A1 (en) * | 1998-05-21 | 2002-02-07 | Hiroshi Takashima | Aluminum target material for sputtering and method for producing same |
EP1131473B1 (en) * | 1998-10-23 | 2004-01-02 | Avery Dennison Corporation | Process for making metal flakes |
US6238986B1 (en) * | 1998-11-06 | 2001-05-29 | Advanced Micro Devices, Inc. | Formation of junctions by diffusion from a doped film at silicidation |
US6436422B1 (en) | 1998-11-23 | 2002-08-20 | Agion Technologies L.L.C. | Antibiotic hydrophilic polymer coating |
JP4454062B2 (en) | 1999-05-17 | 2010-04-21 | 敬 三宅 | Ultrafine particle silver milky body and method for producing the same |
EP1066825A1 (en) * | 1999-06-17 | 2001-01-10 | The Procter & Gamble Company | An anti-microbial body care product |
CN1161511C (en) | 1999-07-27 | 2004-08-11 | 蒋建华 | Long-acting wide-spectrum antiseptic nanometer silver fabric and its making method |
CN1108786C (en) | 1999-12-28 | 2003-05-21 | 天津市化妆品科学技术研究所 | Silver foil cosmetics |
WO2001049301A1 (en) * | 2000-01-06 | 2001-07-12 | Marantech Holding, Llc | Methods of using electron active compounds for managing cancer |
US7137968B1 (en) | 2000-03-13 | 2006-11-21 | Nucryst Pharmaceuticals Corp. | Transcutaneous medical device dressings and method of use |
US6719987B2 (en) * | 2000-04-17 | 2004-04-13 | Nucryst Pharmaceuticals Corp. | Antimicrobial bioabsorbable materials |
US6592888B1 (en) | 2000-05-31 | 2003-07-15 | Jentec, Inc. | Composition for wound dressings safely using metallic compounds to produce anti-microbial properties |
PT1395289E (en) * | 2000-06-08 | 2011-03-16 | Sang Dr Christine | Treatment of neuropathic pain with a n-methyl-d-aspartate (nmda) receptor antagonists |
CN1279222A (en) | 2000-07-31 | 2001-01-10 | 金华尖峰陶瓷有限责任公司 | Antibacterial inorganic ceramics and its production technology |
CN1291667A (en) | 2000-08-14 | 2001-04-18 | 骏安科技投资有限公司 | Nanometer silver anti-bacteria cloth and its industrial production technology |
CN1147640C (en) | 2000-09-19 | 2004-04-28 | 南京希科集团有限公司 | Antibacterial fabric containing nm-class silver powder and its making method |
CN1159488C (en) | 2001-01-20 | 2004-07-28 | 南京希科集团有限公司 | Antibacterial flexible material containing nm silver and its preparing process and application |
CN1179646C (en) | 2001-04-20 | 2004-12-15 | 朱红军 | Aggregation-preventing nanometer wide-spectrum antibacterial silve powder and its inductrial production process |
CA2445729C (en) * | 2001-04-23 | 2013-07-02 | Nucryst Pharmaceuticals Corp. | Use of metals to treat mucosal membranes |
CN1183285C (en) | 2001-04-25 | 2005-01-05 | 朱红军 | Aggregation-preventing wide-spectrum nanometer antibiotic silver yarn and its industrial production process |
-
2002
- 2002-04-23 CA CA 2445729 patent/CA2445729C/en not_active Expired - Fee Related
- 2002-04-23 AT AT02721904T patent/ATE322274T1/en active
- 2002-04-23 ES ES02721904T patent/ES2261659T3/en not_active Expired - Lifetime
- 2002-04-23 WO PCT/CA2002/000547 patent/WO2002085385A2/en active IP Right Grant
- 2002-04-23 JP JP2002582960A patent/JP2004529930A/en active Pending
- 2002-04-23 JP JP2002582958A patent/JP2004525980A/en active Pending
- 2002-04-23 US US10/128,208 patent/US6989156B2/en not_active Expired - Fee Related
- 2002-04-23 WO PCT/CA2002/000548 patent/WO2002085386A2/en not_active Application Discontinuation
- 2002-04-23 EP EP20020721904 patent/EP1383522B1/en not_active Expired - Lifetime
- 2002-04-23 US US10/131,568 patent/US20030021854A1/en not_active Abandoned
- 2002-04-23 JP JP2002582959A patent/JP2004529929A/en active Pending
- 2002-04-23 US US10/131,509 patent/US7087249B2/en not_active Expired - Lifetime
- 2002-04-23 EP EP02731461A patent/EP1390013A4/en not_active Withdrawn
- 2002-04-23 AU AU2002252881A patent/AU2002252881B2/en not_active Ceased
- 2002-04-23 WO PCT/US2002/012690 patent/WO2002085299A2/en active Search and Examination
- 2002-04-23 CA CA 2445740 patent/CA2445740A1/en not_active Abandoned
- 2002-04-23 EP EP20020721903 patent/EP1383521A2/en not_active Withdrawn
- 2002-04-23 CA CA002443587A patent/CA2443587A1/en not_active Abandoned
- 2002-04-23 WO PCT/CA2002/000549 patent/WO2002085387A2/en active IP Right Grant
- 2002-04-23 CA CA002445734A patent/CA2445734A1/en not_active Abandoned
- 2002-04-23 AU AU2002249046A patent/AU2002249046A1/en not_active Abandoned
- 2002-04-23 AU AU2002252879A patent/AU2002252879B2/en not_active Ceased
- 2002-04-23 JP JP2002582875A patent/JP2005507368A/en active Pending
- 2002-04-23 EP EP02721902.1A patent/EP1383520B1/en not_active Expired - Lifetime
- 2002-04-23 WO PCT/CA2002/000546 patent/WO2002085384A2/en not_active Application Discontinuation
- 2002-04-23 AU AU2002303438A patent/AU2002303438B2/en not_active Ceased
- 2002-04-23 US US10/131,513 patent/US6723350B2/en not_active Expired - Lifetime
- 2002-04-23 US US10/131,511 patent/US6939568B2/en not_active Expired - Lifetime
- 2002-04-23 DE DE2002610441 patent/DE60210441T2/en not_active Expired - Lifetime
-
2004
- 2004-02-05 US US10/772,672 patent/US20040157073A1/en not_active Abandoned
-
2005
- 2005-07-01 US US11/174,104 patent/US20050271743A1/en not_active Abandoned
- 2005-11-22 US US11/284,507 patent/US20060083792A1/en not_active Abandoned
-
2006
- 2006-05-16 US US11/434,958 patent/US20060204591A1/en not_active Abandoned
Patent Citations (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3757786A (en) * | 1970-11-06 | 1973-09-11 | D Smith | Synthetic surgical sutures |
US3800792A (en) * | 1972-04-17 | 1974-04-02 | Johnson & Johnson | Laminated collagen film dressing |
US3918446A (en) * | 1974-05-03 | 1975-11-11 | E Med Corp | Securement device for intravenous catheter and its tubing |
US4059105A (en) * | 1976-03-24 | 1977-11-22 | Omnimed, Inc. | Cannula securing device |
US4355636A (en) * | 1979-07-21 | 1982-10-26 | Dragerwerk Ag | Humdifier and heater for air to be inhaled for connection to an inhalation conduit of a respirator |
US4324237A (en) * | 1980-02-26 | 1982-04-13 | E-Med Corporation | Intravenous catheter and tubing securement and dressing device with a window over the puncture or wound site |
US4476590A (en) * | 1980-03-27 | 1984-10-16 | National Research Development Corporation | Antimicrobial surgical implants |
US4828832A (en) * | 1983-09-07 | 1989-05-09 | Laboratorios Biochemie De Mexico | Method of manufacturing a composition for treating skin lesions |
US4581028A (en) * | 1984-04-30 | 1986-04-08 | The Trustees Of Columbia University In The City Of New York | Infection-resistant materials and method of making same through use of sulfonamides |
US4749572A (en) * | 1984-08-28 | 1988-06-07 | Pharmaceutical Holdings Limited | Pharmaceutical preparations |
US4596556A (en) * | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US4633863A (en) * | 1985-09-27 | 1987-01-06 | Filips Chester P | Arterial anchor bandage |
US4960413A (en) * | 1985-11-09 | 1990-10-02 | The Shirley Institute | Wound dressing |
US5122418A (en) * | 1985-12-09 | 1992-06-16 | Shiseido Company Ltd. | Composite powder and production process |
US4847049A (en) * | 1985-12-18 | 1989-07-11 | Vitaphore Corporation | Method of forming chelated collagen having bactericidal properties |
US4803066A (en) * | 1986-03-22 | 1989-02-07 | Smith & Nephew Associated Companies P.L.C. | Antibacterial and/or antifungal compositions for topical application |
US5236421A (en) * | 1986-05-28 | 1993-08-17 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Fixing system for fastening catheters, cannulas or the like to the skin surface and process for the sterile fastening thereof |
US4952411A (en) * | 1987-02-25 | 1990-08-28 | Trustees Of Columbia University In The City Of New York | Method of inhibiting the transmission of AIDS virus |
US4790824A (en) * | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US5143717A (en) * | 1987-12-30 | 1992-09-01 | Code Blue Medical Corporation | Burn foam and delivery system |
US5019096A (en) * | 1988-02-11 | 1991-05-28 | Trustees Of Columbia University In The City Of New York | Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same |
US5064413A (en) * | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US5312335A (en) * | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
US5270358A (en) * | 1989-12-28 | 1993-12-14 | Minnesota Mining And Manufacturing Company | Composite of a disperesed gel in an adhesive matrix |
US5369155A (en) * | 1989-12-28 | 1994-11-29 | Minnesota Mining And Manufacturing Company | Composite of a dispersed gel in an adhesive matrix and method for preparing same |
US5457015A (en) * | 1991-09-03 | 1995-10-10 | Minnesota Mining And Manufacturing Company | Silver halide coated organic polymeric films utilizing chitosan acid salt antistatic protection layers |
US6017553A (en) * | 1992-05-19 | 2000-01-25 | Westaim Technologies, Inc. | Anti-microbial materials |
US5985308A (en) * | 1992-05-19 | 1999-11-16 | Westaim Technologies, Inc. | Process for producing anti-microbial effect with complex silver ions |
US6238686B1 (en) * | 1992-05-19 | 2001-05-29 | Westaim Technologies | Anti-microbial coating for medical devices |
US5958440A (en) * | 1992-05-19 | 1999-09-28 | Westaim Technologies, Inc. | Anti-microbial materials |
US5837275A (en) * | 1992-05-19 | 1998-11-17 | Westaim Technologies, Inc. | Anti-microbial materials |
US5681575A (en) * | 1992-05-19 | 1997-10-28 | Westaim Technologies Inc. | Anti-microbial coating for medical devices |
US5770255A (en) * | 1992-05-19 | 1998-06-23 | Westaim Technologies, Inc. | Anti-microbial coating for medical devices |
US5753251A (en) * | 1992-05-19 | 1998-05-19 | Westaim Technologies, Inc. | Anti-microbial coating for medical device |
US5399163A (en) * | 1992-07-24 | 1995-03-21 | Bioject Inc. | Needleless hypodermic injection methods and device |
US5383851A (en) * | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
US5520639A (en) * | 1992-07-24 | 1996-05-28 | Bioject, Inc. | Needleless hypodermic injection methods and device |
US5770258A (en) * | 1992-12-25 | 1998-06-23 | Mitsubishi Denki Kabushiki Kaisha | Cathode-ray tube and method of producing the same |
US5774151A (en) * | 1993-01-01 | 1998-06-30 | Canon Kabushiki Kaisha | Liquid ejecting head, liquid ejecting apparatus and method of producing said liquid ejecting head |
US5631066A (en) * | 1993-01-25 | 1997-05-20 | Chronopol, Inc. | Process for making metalized films and films produced therefrom |
US5534288A (en) * | 1993-03-23 | 1996-07-09 | United States Surgical Corporation | Infection-resistant surgical devices and methods of making them |
US5848995A (en) * | 1993-04-09 | 1998-12-15 | Walder; Anthony J. | Anti-infective medical article and method for its preparation |
US5454889A (en) * | 1993-08-19 | 1995-10-03 | Ici Canada Inc. | Prill coating |
US5792793A (en) * | 1993-11-05 | 1998-08-11 | Meiji Milk Products Co., Ltd. | Antibacterial, antifungal and antiviral agent |
US5454886A (en) * | 1993-11-18 | 1995-10-03 | Westaim Technologies Inc. | Process of activating anti-microbial materials |
US5372589A (en) * | 1993-11-24 | 1994-12-13 | Davis; W. Gordon | Fenestrated transparent catheter securing device and method |
US6126931A (en) * | 1993-12-20 | 2000-10-03 | Surfacine Development Company, Llc | Contact-killing antimicrobial devices |
US5965610A (en) * | 1994-03-28 | 1999-10-12 | The Trustees Of Columbia University In The City Of New York | Composition for inactivating irritants in fluids |
US5899880A (en) * | 1994-04-08 | 1999-05-04 | Powderject Research Limited | Needleless syringe using supersonic gas flow for particle delivery |
US5563132A (en) * | 1994-06-21 | 1996-10-08 | Bodaness; Richard S. | Two-step cancer treatment method |
US5578073A (en) * | 1994-09-16 | 1996-11-26 | Ramot Of Tel Aviv University | Thromboresistant surface treatment for biomaterials |
US5569207A (en) * | 1994-10-13 | 1996-10-29 | Quinton Instrument Company | Hydrocolloid dressing |
US6022547A (en) * | 1994-12-06 | 2000-02-08 | Helene Curtis, Inc. | Rinse-off water-in-oil-in-water compositions |
US6187290B1 (en) * | 1994-12-06 | 2001-02-13 | Giltech Limited | Physiologically acceptable foamable formulation and foam |
US6010478A (en) * | 1995-02-14 | 2000-01-04 | Powderject Research Limited | Trans-mucosal particle delivery |
US6197351B1 (en) * | 1995-06-07 | 2001-03-06 | Robert S. Neuwirth | Intrauterine chemical necrosing method and composition |
US6013050A (en) * | 1995-10-20 | 2000-01-11 | Powderject Research Limited | Particle delivery |
US6201164B1 (en) * | 1996-07-11 | 2001-03-13 | Coloplast A/S | Hydrocolloid wound gel |
US5895419A (en) * | 1996-09-30 | 1999-04-20 | St. Jude Medical, Inc. | Coated prosthetic cardiac device |
US5945032A (en) * | 1996-09-30 | 1999-08-31 | Basf Aktiengesellschaft | Polymer/hydrogen peroxide complexes |
US6277169B1 (en) * | 1997-02-24 | 2001-08-21 | Superior Micropowders Llc | Method for making silver-containing particles |
US6333093B1 (en) * | 1997-03-17 | 2001-12-25 | Westaim Biomedical Corp. | Anti-microbial coatings having indicator properties and wound dressings |
US5981822A (en) * | 1997-05-02 | 1999-11-09 | Johnson & Johnson Medical, Inc. | Absorbent wound dressings |
US6071543A (en) * | 1997-06-02 | 2000-06-06 | Cellegy Pharmaceuticals, Inc. | Pyridine-thiols reverse mucocutaneous aging |
US6294186B1 (en) * | 1997-06-04 | 2001-09-25 | Peter William Beerse | Antimicrobial compositions comprising a benzoic acid analog and a metal salt |
US20020045049A1 (en) * | 1997-06-20 | 2002-04-18 | Madsen Niels Joergen | Hydrophilic coating and a method for the preparation thereof |
US6165440A (en) * | 1997-07-09 | 2000-12-26 | Board Of Regents, The University Of Texas System | Radiation and nanoparticles for enhancement of drug delivery in solid tumors |
US6123925A (en) * | 1998-07-27 | 2000-09-26 | Healthshield Technologies L.L.C. | Antibiotic toothpaste |
US6071541A (en) * | 1998-07-31 | 2000-06-06 | Murad; Howard | Pharmaceutical compositions and methods for managing skin conditions |
US20020025344A1 (en) * | 1998-11-09 | 2002-02-28 | Ira Jay Newman | Ionic silver complex |
US6096002A (en) * | 1998-11-18 | 2000-08-01 | Bioject, Inc. | NGAS powered self-resetting needle-less hypodermic jet injection apparatus and method |
US6365130B1 (en) * | 1998-11-23 | 2002-04-02 | Agion Technologies L.L.C. | Antimicrobial chewing gum |
US20010010016A1 (en) * | 1999-03-31 | 2001-07-26 | Shanta Modak | Triclosan and silver compound containing medical devices |
US6258385B1 (en) * | 1999-04-22 | 2001-07-10 | Marantech Holding, Llc | Tetrasilver tetroxide treatment for skin conditions |
US20020001628A1 (en) * | 1999-11-24 | 2002-01-03 | Mikio Ito | Pharmaceutical composition for preventing and/or curing digestive disorders |
US6224898B1 (en) * | 2000-03-23 | 2001-05-01 | The United States Of America As Represented By The Secretary Of The Army | Antimicrobial dendrimer nanocomposites and a method of treating wounds |
US6702006B2 (en) * | 2000-05-19 | 2004-03-09 | Alfa Laval Corporate Ab | Plate pack, flow distribution device and plate heat exchanger |
US20020051824A1 (en) * | 2000-07-27 | 2002-05-02 | Burrell Robert Edward | Treatment of hyperproliferative skin disorders and diseases |
US20030170314A1 (en) * | 2000-07-27 | 2003-09-11 | Burrell Robert E. | Compositions of metal-containing compounds |
US20020016585A1 (en) * | 2000-07-29 | 2002-02-07 | Sachse Hans E. | Catheter with a bio-resorbable coating for preventing ascending infections |
US20020192298A1 (en) * | 2001-04-23 | 2002-12-19 | Burrell Robert Edward | Treatment of acne |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9440001B2 (en) | 2013-03-06 | 2016-09-13 | Specialty Fibres and Materials Limited | Absorbent materials |
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