WO2011071904A2 - Inhibiting bacterial infection and biofilm formation - Google Patents
Inhibiting bacterial infection and biofilm formation Download PDFInfo
- Publication number
- WO2011071904A2 WO2011071904A2 PCT/US2010/059261 US2010059261W WO2011071904A2 WO 2011071904 A2 WO2011071904 A2 WO 2011071904A2 US 2010059261 W US2010059261 W US 2010059261W WO 2011071904 A2 WO2011071904 A2 WO 2011071904A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- biofilm
- antimicrobial
- antimicrobial composition
- wound
- forming microorganisms
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/131—Amines acyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/38—Silver; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the present invention relates generally to the field of treating bacterial infections. More particularly, it relates to antimicrobial agents and methods of eliminating biofilm and planktonic cells using these antimicrobial agents.
- Biofilm formation and planktonic proliferation by undesired microorganisms are well known phenomena in domestic as well as industrial settings. For example, it is believed that all wounds are colonized by microbes. If the microbes reach a level of clinical infection, their presence is believed to impair healing and may be a contributing factor to wound chronicity. Recently researchers have proposed that it may not be planktonic but rather biofilm communities which contribute to wound chronicity.
- Biofilms are polymicrobial groupings of bacteria which are held together in an extracellular polymeric substance consisting of protein, DNA, and polysaccarhides and are not totally susceptible to antibiotic treatment.
- recent research James et ah, 2008
- 60% of the chronic wounds tested contained biofilm Therefore, one of the most important aspects of wound treatment is the concept of controlling bioburden, or the microbial levels during processing and handling.
- the present invention relates generally to the field of treating bacterial infections. More particularly, it relates to antimicrobial agents and methods of eliminating biofilm and planktonic cells using these antimicrobial agents.
- the present invention provides an antimicrobial agent formulation comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose; an antimicrobial metal; and a zwitterionic detergent.
- a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose
- an antimicrobial metal comprising lactoperoxidase, glucose oxidase, and glucose
- a zwitterionic detergent a zwitterionic detergent.
- one or more of the agents in the formulation are encapsulated.
- the encapsulating agent is a multi-layered microsphere of surfactants. In other embodiments, the agents in the formulation are not encapsulated.
- the enzyme and substrate components may be present in any suitable ratio, as would be recognized by a person having skill in the art.
- the enzyme and substrate components may be present in a 1 :1, 1 :5, 1 :10, 1 :15, 1 :20, 1 :25, 1 :30, and/or 1 :40 ratio, or any ratio derivable in between.
- the enzyme and substrate components are present in a 1 :20 ratio.
- Alternate embodiments may utilize other sugars as the enzyme substrate, such as sucrose or fructose, in which case the ratio of substrate to enzyme will change to match the reaction requirements for the pairing.
- the enzyme and substrate components combine to form 1% to 5% (v/v) of the final formulation.
- the enzyme and substrate components combine to form 1.25% to 2% (v/v) of the final formulation.
- the antimicrobial metal may be any metal having antimicrobial properties. Such metals are known to those having skill in the art.
- the antimicrobial metal is gallium, copper, zinc, or silver.
- the antimicrobial agent contains two or more antimicrobial metals. In still other embodiments these metals are present in an oxide form or in organically available forms, such as silver oxide or silver taurate.
- the detergent can be any suitable detergent known to a person having skill in the art.
- the detergent is a zwitterionic detergent.
- the zwitterionic detergent is lauramine oxide, cocamidopropylamine oxide, or decylamine oxide.
- the detergent is a non-ionic detergent.
- the non-ionic detergent is polysorbate 80, polysorbate 20, polysorbate 40 or polysorbate 60.
- the antimicrobial agent formulation may be in any formulation known to those having skill in the art.
- the formulation is an emulsion, spray, cream, lotion, ointment, hydrogel, or electroporation device cartridge.
- the antimicrobial agent is an a hydrophilic solution.
- the antimicrobial agent formulation may further comprise additional ingredients known to those having skill in the art.
- the additional ingredient may be an antioxidant, a buffering system, a mild surfactant, or a pharmaceutical ingredient.
- the present invention provides a method of eliminating microorganisms in a biofilm comprising contacting the biofilm with an antimicrobial agent comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose; an antimicrobial metal; and a zwitterionic detergent.
- an antimicrobial agent comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose
- an antimicrobial metal comprising lactoperoxidase, glucose oxidase, and glucose
- a zwitterionic detergent comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose.
- the biofilm may be located on a patient or a surface, such as a surgical instrument, infected hardware, or an implanted device.
- the patient is a human patient.
- the patient may have an injury.
- the injury may be a burn, abrasion, cut, scrape, denuding tissue injury or combinations thereof.
- the patient may be afflicted with a chronic wound.
- the chronic wound is a venous ulcer, diabetic ulcer, arterial ulcer, pressure ulcer, radiation ulcer, traumatic wound, non-healing wound or combinations thereof.
- the biofilm may be contacted by the antimicrobial agent in any suitable manner.
- contacting the biofilm comprises applying the antimicrobial agent to a wound.
- contacting the biofilm comprises administering the composition topically.
- administering the composition topically is selected from administering by hand, administering by an extruder, spray delivery, applying a dressing including the composition, and combinations thereof.
- contacting the biofilm comprises applying the composition to a dressing prior to applying the dressing to the patient.
- the antimicrobial agent is contacted topically, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostaticaly, intrapleurally, intratracheally, intraocularly, intranasally, intravitreally, intravaginally, intrarectally, intramuscularly, intraperitoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, via a catheter, or via a lavage.
- the biofilm is contacted with the antimicrobial agent two or more times.
- the biofilm may be formed by any bacteria capable of forming biofilms. Such bacteria are known to those of skill in the art.
- the biofilm is formed by Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus sanguis, Legionella, Neisseria gonorrhoeae, Staphylococcus aureus or Enterococcus sp. bacteria.
- the biofilm is formed by a Pseudomonas or Staphylococcus bacteria.
- the present invention provides a method of eliminating biofilm- forming microorganisms comprising contacting the biofilm-forming microoganisms with an antimicrobial agent comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose; an antimicrobial metal; and a zwitterionic detergent.
- an antimicrobial agent comprising a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose
- an antimicrobial metal comprising lactoperoxidase, glucose oxidase, and glucose
- a zwitterionic detergent a zwitterionic detergent.
- the biofilm-forming microorganisms are in a planktonic state.
- terapéuticaally effective refers to an amount of cells and/or therapeutic composition (such as a therapeutic polynucleotide and/or therapeutic polypeptide) that is employed in methods of the present invention to achieve a therapeutic effect, such as wherein at least one symptom of a condition being treated is at least ameliorated, and/or to the analysis of the processes or materials used in conjunction with these cells.
- therapeutic composition such as a therapeutic polynucleotide and/or therapeutic polypeptide
- FIG. 1 A flow chart representing the function of the enzyme substrate system.
- FIG. 2 A graph showing the results of a biofilm disruption study on a porcine biofilm model of skin wounds.
- Control no treatment
- NPWT treatment with V.A.C.® Therapy (only) at -125 mmHg
- Solution 1 treatment with lactoperoxidase, glucose oxidase, glucose, lauramine oxide, gallium chloride, Tris HC1; pH 5.3 - 5.9
- Solution 2 treatment with lactoperoxidase, glucose oxidase, and glucose encapsulated in SpherulitesTM, Lauramine oxide, gallium chloride, Tris HC1, water; pH 5.2 - 5.9.
- the current disclosure presents a formulation of an antimicrobial agent system that is effective in eliminating both cells in a biofilm and planktonic cells. Coupling such an antimicrobial agent system with a method to mechanically disrupt the biofilm may further expedite biofilm eradication and wound healing.
- a biofilm is an aggregate of microorganisms in which cells are stuck to each other and/or to a surface.
- planktonic cells are single-cells that may float or swim in a liquid medium.
- the adherent cells found in biofilm are frequently embedded within a self- produced matrix of extracellular polymeric substance, may form on living or non-living surfaces, and represent a prevalent mode of microbial life in natural, industrial and hospital settings.
- Biofilms form in response to many factors, which may include cellular recognition of specific or non-specific attachment sites on a surface, nutritional cues, or in some cases, by exposure of planktonic cells to sub-inhibitory concentrations of antibiotics. Bacteria cells in a planktonic state may form into a biofilm if left untreated.
- Biofilms and planktonic cells are known to be involved in a wide variety of microbial infections in the body. Infectious processes in which biofilms have been implicated include common problems such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque, gingivitis, coating contact lenses, endocarditis, and infections in cystic fibrosis. Biofilms can also be formed on the inert surfaces of implanted devices such as catheters, prosthetic cardiac valves and intrauterine devices. Bacterial biofilms may also impair cutaneous wound healing and reduce topical antibacterial efficiency in healing or treating infected skin wounds.
- biofilms A person having skill in the art would recognize that many bacterias form biofilms. Wolcott et al., 2008 and James et al, 2008. For example, Pseudomonas aeruginosa is known to form biofilms and is an important opportunistic pathogen and causative agent of emerging nosocomial infections.
- Dental plaque is a biofilm on the surfaces of the teeth and consists of bacterial cells (mainly Streptococcus mutans and Streptococcus sanguis), salivary polymers and bacterial extracellular products. Legionella bacteria are known to grow under certain conditions in biofilms, in which they are protected against disinfectants.
- Neisseria gonorrhoeae is an exclusive human pathogen that has been demonstrated as forming biofilms on glass surfaces and over human cells.
- Other types of bacteria that form biofilms include Staphylococcus aureus and Enterococcus sp.
- biofilms are typically less susceptible to antibiotics, antimicrobials, and biocides.
- bacteria in a biofilm can be up to 4,000 times more resistant (i.e., less susceptible) than the same organism in a planktonic state.
- Minimum inhibitory concentration (MIC) describes the amount of an active agent delivered to planktonic microorganisms necessary to inhibit biofilm formation.
- minimum biofilm eradication concentration (MBEC) describes the minimum concentration of an active agent delivered to a biofilm necessary to inhibit or eradicate biofilm growth. The differential that can be seen in these amounts illustrates that biofilm-forming microorganisms are much less susceptible to antimicrobial agents at standard therapeutic concentrations.
- the current formulation has efficacy against both biofilm and planktonic organisms.
- the disclosed multi-part antimicrobial agent formulation is also effective against both the persistence and depth within tissues that are characteristic traits of biofilms.
- the antimicrobial activity of the present formulation is based on a natural enzyme and substrate system comprising lactoperoxidase, glucose oxidase, and glucose.
- Lactoperoxidase is a peroxidase enzyme found in milk, and is known to have antimicrobial and antioxidant properties.
- Glucose (Glc) is a monosaccharide and is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate. Glucose is one of the main products of photosynthesis and starts cellular respiration in both prokaryotes, including bacteria, and eukaryotes.
- the glucose oxidase enzyme binds to beta-D-glucopyranose and aids in breaking the sugar down into its metabolites.
- Glucose oxidase acts as a natural preservative by reducing atmospheric 0 2 to hydrogen peroxide (H 2 0 2 ), which acts as an antimicrobial barrier.
- the enzymatic composition is sold by Arch Personal Care Products, L.P. under the tradename "Biovert Enzyme & Substrate.” Without wishing to be bound by any particular theory, it is believed that in the presence of glucose, the glucose oxidase generates hydrogen peroxide.
- hypoiodite and hypothiocyanate (FIG. 1). Both hypoiodite and hypothiocyanate have good antimicrobial activity that results in the rapid death of the microbial cell.
- the enzyme and substrate components are used at a range of stoichiometric ratios including 1 :1, 1 :5, 1 :10, 1 :15, 1 :20, 1 :25, 1 :30, and/or 1 :40 ratio, or any ratio derivable in between.
- the enzyme and substrate components are used at a 1 :20 ratio.
- Alternate embodiments may utilize other sugars as the enzyme substrate, such as sucrose or fructose, in which case the ratio of substrate to enzyme will change to match the reaction requirements for the pairing.
- the enzyme and substrate components combine to form 1% to 5% (v/v) of the final formulation. In particular embodiments, the enzyme and substrate components combine to form 1.25% to 2% (v/v) of the final formulation.
- the antimicrobial agent formulation further comprises a detergent.
- the detergent can be any suitable detergent known to a person having skill in the art. Ananthapadmanabhan et al., 2004. The addition of the detergent helps to emulsify components of the biofilm, making them more susceptible to inhibition or damage by the enzyme system. The detergent also aids penetration of the agent into the affected tissues.
- the antimicrobial agent formulation comprises a low level of a detergent. A low level of the detergent may be anywhere from 0.25% to 5% (v/v). In particular embodiments, the level of the detergent is 0.25% to 1.5% (v/v). In some embodiments, the detergent is a gentle zwitterionic detergent.
- the detergent may be one of several Generally Regarded As Safe (GRAS) designated detergents, examples include but are not limited to lauramine oxide, cocamidopropylamine oxide or decylamine oxide.
- suitable detergents include non-ionic detergents, such as polysorbate 80, polysorbate 20, polysorbate 40 or polysorbate 60 or other gentle zwitterionic detergents.
- GRAS Generally Regarded As Safe
- the antimicrobial agent formulation also contains an antimicrobial metal, which synergistically boosts the efficacy of the enzyme system.
- Metals having known antimicrobial properties are known to those of skill in the art. Michels 2009 and Kaneko 2007.
- gallium, copper, zinc, and silver possess known antimicrobial properties.
- the antimicrobial metal is gallium.
- Gallium is known to have anti-biofilm properties and is active against bacteria, planktonic cells, and biofilms because it competes with iron. It is believed that substitution of gallium for iron inactivates iron- containing enzymes necessary for bacterial growth.
- other metals such as copper, zinc, or silver with known antimicrobial properties may be added to the formulation.
- the antimicrobial agent contains two or more antimicrobial metals. In still other embodiments these metals are present in an oxide form or in organically available forms, such as silver oxide or silver taurate.
- additional ingredients known to those having skill in the art may be added to the formulation. These include, but are not limited to, those discussed below.
- Non-limiting examples of antioxidants that can be used with the antimicrobial agent of the present invention include acetyl cysteine, ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butyl hydroquinone, cysteine, cysteine HCI, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters of ascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters, hydroquinone, isooct
- the antimicrobial agent formulation further comprises a buffering system to maintain the formulation at an optimal pH.
- a buffering system would be recognized by those having skill in the art, and include but are not limited to acetic acid/acetate, citric acid/citrate, glutamic acid/glutamate, and phosphoric acid/phosphate.
- concentration of pH buffering system depends on the desired pH of the formulation. Any buffering system that is known to a person of skill in the art could be used with the antimicrobial agents.
- the buffering system is Trizma HC1.
- the buffer is a MES or HEPES buffer.
- the antimicrobial agent formulation further comprises a surfactant.
- the surfactant can be any suitable surfactant, which are well known to a person having skill in the art. Surfactants are wetting agents that lower the surface tension of a liquid to allow easier spreading and lower the interfacial tension between two liquids.
- the surfactant is added to help to open up the biofilm to the antimicrobial properties of the formulation by emulsifying the mucopolysaccharides of the biofilm. The surfactant also aids the penetration of the formulation to address sub-surface biofilms.
- the surfactant is a mild surfactant. In other embodiments, the surfactant is a non-ionic surfactant.
- Non-limiting examples of pharmaceutical ingredients include anti-inflammatory agents including non-steroidal antiinflammatory drugs, antibiotics, antifungals, antivirals, antimicrobials, anti-cancer actives, scabicides, pediculicides, antineoplastics, antiperspirants, antipruritics, antipsoriatic agents, antiseborrheic agents, biologically active proteins and peptides, burn treatment agents, cauterizing agents, depigmenting agents, depilatories, diaper rash treatment agents, enzymes, hemostatics, kerotolytics, canker sore treatment agents, cold sore treatment agents, dental and periodontal treatment agents, photosensitizing actives, skin protectant/barrier agents, steroids including hormones and corticosteroids, sunburn treatment agents, sunscreens, transdermal actives, and nasal actives.
- anti-inflammatory agents including non-steroidal antiinflammatory drugs, antibiotics, antifungals, antivirals, antimicrobials, anti-cancer actives, scabicides, pedicul
- compositions may further include deodorizers, antibiotics (such as erythromycin), antivirals, antiseptics (such as benzylthonium or benzylkonium chloride), and iron chelators that are antimicrobial, such as lactoferrin.
- deodorizers such as erythromycin
- antibiotics such as erythromycin
- antivirals such as erythromycin
- antiseptics such as benzylthonium or benzylkonium chloride
- iron chelators that are antimicrobial, such as lactoferrin.
- compositions of the present invention can be formulated into all types of vehicles.
- suitable vehicles include emulsions (e.g., oil-in- water, water-in-oil, silicone-in-water, water-in-silicone, water-in-oil-in-water, oil-in-water, oil-in-water-in-oil, oil- in-water-in-silicone, etc.), creams, lotions, solutions (both aqueous and hydro-alcoholic), anhydrous bases (such as lipsticks and powders), gels, ointments, pastes, milks, liquids, aerosols, solid forms, sprays, hydrogels, or electroporation device cartridges.
- emulsions e.g., oil-in- water, water-in-oil, silicone-in-water, water-in-silicone, water-in-oil-in-water, oil-in-water, oil-in-water-in-oil, oil- in-water-in-silicone,
- the formulation may be a hydrophilic solution, a thixotropic spray, or other hydrophillic topical. Variations and other appropriate vehicles will be apparent to the skilled artisan and are appropriate for use in the present invention.
- the concentrations and combinations of the ingredients can be selected in such a way that the combinations are chemically compatible and do not form complexes which precipitate from the finished product.
- the formulation may be immobilized on a surface, such as a dressing, and activated by a glucose wash.
- the invention provides for the use of an antimicrobial formulation such as those described above to treat or eliminate cells of a biofilm or planktonic biofilm-forming microorganisms.
- the antimicrobial formulation may be applied to a surface or wound where biofilm exists or where planktonic biofilm-forming microorganism may be present and there is a high likelihood of a biofilm forming.
- the antimicrobial agent is contacted to the biofilm or potential biofilm to reduce or eliminate the cells of an existing biofilm or inhibit the growth of or eliminate cells of a biofilm-forming microorganisms.
- compositions may be applied to a wound on a patient or applied to a surface, such as surgical instruments or infected hardware.
- the antimicrobial agent as currently described may be used to solve problematic infections.
- infections include, but are not limited to, common problems such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque, gingivitis, coating contact lenses, endocarditis, infections in cystic fibrosis, infections associated with osteomyelitis, tinea corporis or tinea cruris, diaper rash, and nail fungus.
- the antimicrobial agent may be used as a coating for inert surfaces of implanted devices such as catheters, prosthetic cardiac valves, intrauterine devices, and tubes having entry sites to tissue.
- the formulations may be used to facilitate cutaneous wound healing and increase topical antibacterial efficiency in healing or treating infected skin wounds. In other embodiments, it may be used in skin preps to protect periwound skin.
- the lethal dosage for treatment of biofilm- forming microorganisms may be significantly higher than the standard therapeutically effective amount determined for planktonic microorganisms (i.e., a lethal amount or a lethal dosage) typically used by one of ordinary skill in the art.
- the standard therapeutically effective amount would be the amount of antimicrobial agent necessary to treat biofilm-forming microorganisms.
- a “standard therapeutic amount” or “standard therapeutic dose” may also refer to an amount of an agent sufficient to reduce or eliminate planktonic microorganisms.
- treatment of biofilms and biofilm-forming microorganisms may require two or more doses of the antimicrobial agent. H. Combination treatments
- the treatment methods of the present invention may be used on their own or in combination with additional methods of treatment.
- additional methods of treatment In order to increase the effectiveness of a treatment with the compositions of the present invention or to augment the protection of another (second) therapy, it may be desirable to combine these compositions and methods with other agents and methods effective in the treatment, reduction of risk, or prevention of infections, for example, anti-bacterial, anti-viral, and/or anti-fungal treatments.
- iontophoresis can be used to drive agents into tissues for the purpose of labeling or eradicating biolfilms.
- V.A.C.® Therapy KCI International, San Antonio, TX).
- V.A.C.® Therapy delivers negative pressure at the wound site through a patented dressing to help draw wound edges together, remove infectious materials, and actively promote granulation at the cellular level.
- Instillation Therapy is adapted to using separate reservoirs of enzyme and substrate solutions allows for the separation of substrate from the enzyme.
- the enzyme and substrate are only mixed at the tissue surface by introducing the two components in the delivery apparatus and mixing them with known static- mixer devices prior to introduction of the combined fluids into the wound space. This makes the formulation inherently more stable by storing the individual components of the formulation separately and preparing the whole formulation only at the site of use. 1. Examples
- Pseudomonas aeruginosa and Staphylococcus aureus were grown to form biofilms glass slides. Triplicate samples of each organism were exposed to one of three antimicrobial preparations (cocodimethylamine oxide, dicyldimethylamine oxide, and lauramine oxide) for 10 minutes. After exposure, the remaining organism on each slide was assayed to determine the effects of each antimicrobial solution on each organism.
- the pH of the final solution should be between 5.2 - 5.9. In certain instances the pH may need to be adjusted using IN NaOH.
- TSA Tryptic Soy Agar
- TSA Tryptic Soy Agar
- the biofilm formation protocol was taken from Harrison-Belestra et al. (2003) and is summarized as follows. Glass cover slips, cleaned with isopropyl alcohol, were suspended in a culture of each organism for 36-48 hours at 37°C and lightly agit
- Triplicate prepared slides of each organism were exposed to each antimicrobial solution by spraying the slide with a predetermined volume of solution. Samples were exposed in sets of 3 slides 10 minutes. An additional set of prepared slides not exposed to an antimicrobial was prepared to determine the initial load of each organism.
- Total surviving microorganisms were enumerated as total colony-forming units per slide (CFU/slide). Individual slides were rinsed with sterile buffered peptone water (BPW, BD) and plated onto Pseudomonas Isolation Agar (PIA, BD) or Baird-Parker Agar (BP,BD) using an Eddy Jet spiral plater (IUL Instruments, Barcelona, Spain). Plates were incubated for 48 ⁇ 2 hours at 35 ⁇ 2°C and enumerated on an automated plate count reader (Flash and Go, IUL Instruments).
- BPW sterile buffered peptone water
- PIA Pseudomonas Isolation Agar
- BP,BD Baird-Parker Agar
- Eddy Jet spiral plater IUL Instruments, Barcelona, Spain
- Results of the sample enumerations are shown in Tables 1 and 2 below, including the treatment applied to the slide, the observed amount of organism for each replicate, the average result of all three replicates, the logio of the average, and (for the antimicrobial treatments) the log reduction from the untreated control. Table 1. Pseudomonas spp. enumerations
- Dicyldimethylamine oxide (DO) and lauramine oxide (LO) were effective at reducing more than 5 logs of Pseudomonas aeruginosa and Staphylococcus aureus. After 10 minutes of exposure with the antimicrobials, no organism was recoverable from the surface, a reduction of more than 5 logs from the untreated control samples. Cocodimethylamine oxide (CDO) was also able to reduce the test organisms, but at a lower efficacy (2.70 logs of reduction again Psuedomonas and 2.20 logs of reduction against S. aureus).
- Porcine skin explants are a recognized model for the study of biofilms ⁇ see, e.g., Phillips et al, "Effects of Antimicrobial Agents on an In Vitro Biofilm Model of Skin Wounds," Advances in Wound Care, 1 :299-304 (2010)).
- a Pseudomonas biofilm was grown on pig skin explants that were 5 inches wide by 7 inches long. Small wounds were made in the pig skin and the biofilm was developed in these wounds. All wounds in a particular pigskin were treated with the same agents.
- NPWT - treatment with V.A.C.® Therapy (only) at -125 mmHg and no solutions;
- Solution 1 treatment Lactoperoxidase, glucose oxidase, glucose, lauramine oxide, gallium chloride, Tris HC1; pH 5.3 - 5.9;
- SpherulitesTM Lactoperoxidase, glucose oxidase, and glucose encapsulated in SpherulitesTM, Lauramine oxide, gallium chloride, Tris HC1, water; pH 5.2 - 5.9.
- SpherulitesTM are multi-layered microspheres of surfactants that are used for the encapsulation of active ingredients. SpherulitesTM can provide increased skin penetration and adhesion to biological surfaces, as well as time-release of active ingredients.
- Solution 1 treatment led to an approximate 2 log reduction in bacteria (FIG. 2).
- FOG. 2 After 6, 10 minute applications of the solution over the course of 24 hours, 93.2% of the Pseudomonas in the biofilm were killed. With Solution 2 77.1% of the Pseudomonas were killed. A >1 log reduction of bacteria is generally considered significant.
- the reduction achieved with Solution 1 treatment was significant, whereas the reduction achieved by Solution 2 was not necessarily significant.
- the application of negative pressure alone was not sufficient to cause a significant decrease in biofilm bacteria.
- compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of some embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2010328283A AU2010328283A1 (en) | 2009-12-09 | 2010-12-07 | Inhibiting bacterial infection and biofilm formation |
EP10836535.4A EP2509622B1 (de) | 2009-12-09 | 2010-12-07 | Hemmung der bakterieninfektion und biofilmbildung |
CN2010800553550A CN102647997A (zh) | 2009-12-09 | 2010-12-07 | 抑制细菌感染和生物膜形成 |
JP2012543203A JP2013513608A (ja) | 2009-12-09 | 2010-12-07 | 細菌感染およびバイオフィルム形成の抑制 |
CA2782789A CA2782789A1 (en) | 2009-12-09 | 2010-12-07 | Inhibiting bacterial infection and biofilm formation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28500909P | 2009-12-09 | 2009-12-09 | |
US61/285,009 | 2009-12-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2011071904A2 true WO2011071904A2 (en) | 2011-06-16 |
WO2011071904A3 WO2011071904A3 (en) | 2011-11-17 |
Family
ID=44082250
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/059261 WO2011071904A2 (en) | 2009-12-09 | 2010-12-07 | Inhibiting bacterial infection and biofilm formation |
Country Status (8)
Country | Link |
---|---|
US (1) | US20110135621A1 (de) |
EP (1) | EP2509622B1 (de) |
JP (1) | JP2013513608A (de) |
CN (1) | CN102647997A (de) |
AU (1) | AU2010328283A1 (de) |
CA (1) | CA2782789A1 (de) |
TW (1) | TW201143794A (de) |
WO (1) | WO2011071904A2 (de) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013142372A1 (en) * | 2012-03-20 | 2013-09-26 | Kci Licensing, Inc. | Targeted enzymatic degradation of quorum-sensing peptides |
JP2014181247A (ja) * | 2013-03-18 | 2014-09-29 | Fujitsu Ltd | バイオフィルム除去剤、バイオフィルム除去方法、及び情報処理装置 |
WO2020129374A1 (ja) * | 2018-12-20 | 2020-06-25 | 住友化学株式会社 | リチウム複合金属酸化物、リチウム二次電池用正極活物質、リチウム二次電池用正極及びリチウム二次電池 |
US11185080B2 (en) | 2014-04-30 | 2021-11-30 | Matoke Holdings Limited | Antimicrobial compositions |
US11464232B2 (en) | 2014-02-19 | 2022-10-11 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US11470847B2 (en) | 2014-02-19 | 2022-10-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101801521B (zh) | 2007-05-14 | 2015-06-17 | 纽约州立大学研究基金会 | 生物膜中细菌细胞内的生理学分散响应诱导 |
TWI415572B (zh) | 2011-06-17 | 2013-11-21 | Univ Chang Gung | 利用1,2,3,4,6-五-o-沒食子醯基-d-葡哌喃糖來抑制生物膜形成 |
US11039621B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
EP3223833B1 (de) * | 2014-11-24 | 2019-05-15 | Matoke Holdings Limited | Vorbeugung und behandlung von mikrobiellen infektionen |
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 |
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 |
GB201716986D0 (en) | 2017-10-16 | 2017-11-29 | Matoke Holdings Ltd | Antimicrobial compositions |
US11541105B2 (en) | 2018-06-01 | 2023-01-03 | The Research Foundation For The State University Of New York | Compositions and methods for disrupting biofilm formation and maintenance |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0277383A1 (de) | 1987-01-08 | 1988-08-10 | Douwe Egberts Koninklijke Tabaksfabriek- Koffiebranderijen-Theehandel N.V. | Mittel zur oralen Hygiene |
Family Cites Families (109)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1355846A (en) * | 1920-02-06 | 1920-10-19 | David A Rannells | Medical appliance |
US2547758A (en) * | 1949-01-05 | 1951-04-03 | Wilmer B Keeling | Instrument for treating the male urethra |
US2632443A (en) * | 1949-04-18 | 1953-03-24 | Eleanor P Lesher | Surgical dressing |
US2682873A (en) * | 1952-07-30 | 1954-07-06 | Johnson & Johnson | General purpose protective dressing |
NL189176B (nl) * | 1956-07-13 | 1900-01-01 | Hisamitsu Pharmaceutical Co | Pleister op basis van een synthetische rubber. |
US2969057A (en) * | 1957-11-04 | 1961-01-24 | Brady Co W H | Nematodic swab |
US3367332A (en) * | 1965-08-27 | 1968-02-06 | Gen Electric | Product and process for establishing a sterile area of skin |
US3520300A (en) * | 1967-03-15 | 1970-07-14 | Amp Inc | Surgical sponge and suction device |
US3568675A (en) * | 1968-08-30 | 1971-03-09 | Clyde B Harvey | Fistula and penetrating wound dressing |
US3682180A (en) * | 1970-06-08 | 1972-08-08 | Coilform Co Inc | Drain clip for surgical drain |
BE789293Q (fr) * | 1970-12-07 | 1973-01-15 | Parke Davis & Co | Pansement medico-chirugical pour brulures et lesions analogues |
US3826254A (en) * | 1973-02-26 | 1974-07-30 | Verco Ind | Needle or catheter retaining appliance |
DE2527706A1 (de) * | 1975-06-21 | 1976-12-30 | Hanfried Dr Med Weigand | Einrichtung zum einleiten von kontrastmittel in einen kuenstlichen darmausgang |
NL7710909A (nl) * | 1976-10-08 | 1978-04-11 | Smith & Nephew | Samengestelde hechtstrook. |
GB1562244A (en) * | 1976-11-11 | 1980-03-05 | Lock P M | Wound dressing materials |
US4080970A (en) * | 1976-11-17 | 1978-03-28 | Miller Thomas J | Post-operative combination dressing and internal drain tube with external shield and tube connector |
US4139004A (en) * | 1977-02-17 | 1979-02-13 | Gonzalez Jr Harry | Bandage apparatus for treating burns |
US4184510A (en) * | 1977-03-15 | 1980-01-22 | Fibra-Sonics, Inc. | Valued device for controlling vacuum in surgery |
US4165748A (en) * | 1977-11-07 | 1979-08-28 | Johnson Melissa C | Catheter tube holder |
US4256109A (en) * | 1978-07-10 | 1981-03-17 | Nichols Robert L | Shut off valve for medical suction apparatus |
SE414994B (sv) * | 1978-11-28 | 1980-09-01 | Landstingens Inkopscentral | Venkateterforband |
US4382441A (en) * | 1978-12-06 | 1983-05-10 | Svedman Paul | Device for treating tissues, for example skin |
US4284079A (en) * | 1979-06-28 | 1981-08-18 | Adair Edwin Lloyd | Method for applying a male incontinence device |
US4261363A (en) * | 1979-11-09 | 1981-04-14 | C. R. Bard, Inc. | Retention clips for body fluid drains |
US4569348A (en) * | 1980-02-22 | 1986-02-11 | Velcro Usa Inc. | Catheter tube holder strap |
US4297995A (en) * | 1980-06-03 | 1981-11-03 | Key Pharmaceuticals, Inc. | Bandage containing attachment post |
US4333468A (en) * | 1980-08-18 | 1982-06-08 | Geist Robert W | Mesentery tube holder apparatus |
US4465485A (en) * | 1981-03-06 | 1984-08-14 | Becton, Dickinson And Company | Suction canister with unitary shut-off valve and filter features |
US4392853A (en) * | 1981-03-16 | 1983-07-12 | Rudolph Muto | Sterile assembly for protecting and fastening an indwelling device |
US4373519A (en) * | 1981-06-26 | 1983-02-15 | Minnesota Mining And Manufacturing Company | Composite wound dressing |
US4392858A (en) * | 1981-07-16 | 1983-07-12 | Sherwood Medical Company | Wound drainage device |
SE429197B (sv) * | 1981-10-14 | 1983-08-22 | Frese Nielsen | Anordning for behandling av sar |
DE3146266A1 (de) * | 1981-11-21 | 1983-06-01 | B. Braun Melsungen Ag, 3508 Melsungen | Kombinierte vorrichtung fuer eine medizinische saugdrainage |
US4475909A (en) * | 1982-05-06 | 1984-10-09 | Eisenberg Melvin I | Male urinary device and method for applying the device |
US4548202A (en) * | 1983-06-20 | 1985-10-22 | Ethicon, Inc. | Mesh tissue fasteners |
US4540412A (en) * | 1983-07-14 | 1985-09-10 | The Kendall Company | Device for moist heat therapy |
US4543100A (en) * | 1983-11-01 | 1985-09-24 | Brodsky Stuart A | Catheter and drain tube retainer |
US4525374A (en) * | 1984-02-27 | 1985-06-25 | Manresa, Inc. | Treating hydrophobic filters to render them hydrophilic |
US4897081A (en) * | 1984-05-25 | 1990-01-30 | Thermedics Inc. | Percutaneous access device |
US5215522A (en) * | 1984-07-23 | 1993-06-01 | Ballard Medical Products | Single use medical aspirating device and method |
GB8419745D0 (en) * | 1984-08-02 | 1984-09-05 | Smith & Nephew Ass | Wound dressing |
US4872450A (en) * | 1984-08-17 | 1989-10-10 | Austad Eric D | Wound dressing and method of forming same |
US4826494A (en) * | 1984-11-09 | 1989-05-02 | Stryker Corporation | Vacuum wound drainage system |
US4655754A (en) * | 1984-11-09 | 1987-04-07 | Stryker Corporation | Vacuum wound drainage system and lipids baffle therefor |
US4605399A (en) * | 1984-12-04 | 1986-08-12 | Complex, Inc. | Transdermal infusion device |
US5037397A (en) * | 1985-05-03 | 1991-08-06 | Medical Distributors, Inc. | Universal clamp |
US4640688A (en) * | 1985-08-23 | 1987-02-03 | Mentor Corporation | Urine collection catheter |
US4758220A (en) * | 1985-09-26 | 1988-07-19 | Alcon Laboratories, Inc. | Surgical cassette proximity sensing and latching apparatus |
US4733659A (en) * | 1986-01-17 | 1988-03-29 | Seton Company | Foam bandage |
US4838883A (en) * | 1986-03-07 | 1989-06-13 | Nissho Corporation | Urine-collecting device |
JPS62281965A (ja) * | 1986-05-29 | 1987-12-07 | テルモ株式会社 | カテ−テルおよびカテ−テル用固定部材 |
GB8621884D0 (en) * | 1986-09-11 | 1986-10-15 | Bard Ltd | Catheter applicator |
US4743232A (en) * | 1986-10-06 | 1988-05-10 | The Clinipad Corporation | Package assembly for plastic film bandage |
JPS63135179A (ja) * | 1986-11-26 | 1988-06-07 | 立花 俊郎 | 薬物の経皮投与具 |
GB8706116D0 (en) * | 1987-03-14 | 1987-04-15 | Smith & Nephew Ass | Adhesive dressings |
US4863449A (en) * | 1987-07-06 | 1989-09-05 | Hollister Incorporated | Adhesive-lined elastic condom cathether |
US5176663A (en) * | 1987-12-02 | 1993-01-05 | Pal Svedman | Dressing having pad with compressibility limiting elements |
US4906240A (en) * | 1988-02-01 | 1990-03-06 | Matrix Medica, Inc. | Adhesive-faced porous absorbent sheet and method of making same |
US4985019A (en) * | 1988-03-11 | 1991-01-15 | Michelson Gary K | X-ray marker |
US4919654A (en) * | 1988-08-03 | 1990-04-24 | Kalt Medical Corporation | IV clamp with membrane |
US5059596A (en) * | 1989-01-16 | 1991-10-22 | Roussel Uclaf | Azabicyclo compounds |
US5100396A (en) * | 1989-04-03 | 1992-03-31 | Zamierowski David S | Fluidic connection system and method |
US5527293A (en) * | 1989-04-03 | 1996-06-18 | Kinetic Concepts, Inc. | Fastening system and method |
JP2719671B2 (ja) * | 1989-07-11 | 1998-02-25 | 日本ゼオン株式会社 | 創傷被覆材 |
US5358494A (en) * | 1989-07-11 | 1994-10-25 | Svedman Paul | Irrigation dressing |
US5232453A (en) * | 1989-07-14 | 1993-08-03 | E. R. Squibb & Sons, Inc. | Catheter holder |
GB9002422D0 (en) * | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
US5134994A (en) * | 1990-02-12 | 1992-08-04 | Say Sam L | Field aspirator in a soft pack with externally mounted container |
US5092858A (en) * | 1990-03-20 | 1992-03-03 | Becton, Dickinson And Company | Liquid gelling agent distributor device |
US5149331A (en) * | 1991-05-03 | 1992-09-22 | Ariel Ferdman | Method and device for wound closure |
US5278100A (en) * | 1991-11-08 | 1994-01-11 | Micron Technology, Inc. | Chemical vapor deposition technique for depositing titanium silicide on semiconductor wafers |
US5645081A (en) * | 1991-11-14 | 1997-07-08 | Wake Forest University | Method of treating tissue damage and apparatus for same |
US5636643A (en) * | 1991-11-14 | 1997-06-10 | Wake Forest University | Wound treatment employing reduced pressure |
US5279550A (en) * | 1991-12-19 | 1994-01-18 | Gish Biomedical, Inc. | Orthopedic autotransfusion system |
US6004438A (en) * | 1991-12-31 | 1999-12-21 | 3M Innovative Properties Company | Biofilm reduction sterilizer |
FR2690617B1 (fr) * | 1992-04-29 | 1994-06-24 | Cbh Textile | Pansement adhesif transparent. |
US5322520A (en) * | 1992-11-12 | 1994-06-21 | Implemed, Inc. | Iontophoretic structure for medical devices |
US5342376A (en) * | 1993-05-03 | 1994-08-30 | Dermagraphics, Inc. | Inserting device for a barbed tissue connector |
US6241747B1 (en) * | 1993-05-03 | 2001-06-05 | Quill Medical, Inc. | Barbed Bodily tissue connector |
AU6721494A (en) * | 1993-05-13 | 1994-12-12 | Unilever Plc | Oral compositions containing triclosan for the treatment of aphthous ulcers |
US5344415A (en) * | 1993-06-15 | 1994-09-06 | Deroyal Industries, Inc. | Sterile system for dressing vascular access site |
US5437651A (en) * | 1993-09-01 | 1995-08-01 | Research Medical, Inc. | Medical suction apparatus |
US5549584A (en) * | 1994-02-14 | 1996-08-27 | The Kendall Company | Apparatus for removing fluid from a wound |
US5556375A (en) * | 1994-06-16 | 1996-09-17 | Hercules Incorporated | Wound dressing having a fenestrated base layer |
US5607388A (en) * | 1994-06-16 | 1997-03-04 | Hercules Incorporated | Multi-purpose wound dressing |
WO1997032480A1 (en) * | 1996-03-06 | 1997-09-12 | Novo Nordisk A/S | A method of killing or inhibiting microbial cells |
US6100080A (en) * | 1996-12-18 | 2000-08-08 | Novo Nordisk A/S | Method for enzymatic treatment of biofilm |
AUPO690997A0 (en) * | 1997-05-20 | 1997-06-12 | Novapharm Research (Australia) Pty Ltd | Alkylpolyglucosides containing disinfectant compositions active against pseudomonas microorganism |
US6135116A (en) * | 1997-07-28 | 2000-10-24 | Kci Licensing, Inc. | Therapeutic method for treating ulcers |
GB9719520D0 (en) * | 1997-09-12 | 1997-11-19 | Kci Medical Ltd | Surgical drape and suction heads for wound treatment |
US6071267A (en) * | 1998-02-06 | 2000-06-06 | Kinetic Concepts, Inc. | Medical patient fluid management interface system and method |
US6287316B1 (en) * | 1999-03-26 | 2001-09-11 | Ethicon, Inc. | Knitted surgical mesh |
US7799004B2 (en) * | 2001-03-05 | 2010-09-21 | Kci Licensing, Inc. | Negative pressure wound treatment apparatus and infection identification system and method |
US6856821B2 (en) * | 2000-05-26 | 2005-02-15 | Kci Licensing, Inc. | System for combined transcutaneous blood gas monitoring and vacuum assisted wound closure |
AU5471000A (en) * | 1999-06-23 | 2001-01-09 | Dial Corporation, The | Antibacterial compositions |
US6991643B2 (en) * | 2000-12-20 | 2006-01-31 | Usgi Medical Inc. | Multi-barbed device for retaining tissue in apposition and methods of use |
US6540705B2 (en) * | 2001-02-22 | 2003-04-01 | Core Products International, Inc. | Ankle brace providing upper and lower ankle adjustment |
GB0301034D0 (en) * | 2003-01-16 | 2003-02-19 | Dupont Teijin Films Us Ltd | Polymeric film and coating |
US20050123560A1 (en) * | 2003-12-04 | 2005-06-09 | Sinnott Robert A. | High purity and water dispersible extract and formulations of larrea tridentata leaf resin, and methods of making and using the same |
WO2005055723A1 (en) * | 2003-12-04 | 2005-06-23 | The University Of Iowa Research Foundation | Gallium inhibits biofilm formation |
EP3025704B1 (de) * | 2005-03-10 | 2019-01-16 | 3M Innovative Properties Company | Verfahren zur verringerung von mikrobieller kontamination |
US20060289354A1 (en) * | 2005-06-15 | 2006-12-28 | Buckman Laboratories International, Inc. | Method and composition to control the growth of microorganisms in aqueous systems and on substrates |
JP4999842B2 (ja) * | 2005-07-01 | 2012-08-15 | ケーン バイオテク インコーポレイテッド | 医療用デバイス上における微生物バイオフィルムの生育および増殖を抑制するための抗菌性組成物 |
US20070042094A1 (en) * | 2005-08-22 | 2007-02-22 | Alcide Corporation | Oxidation method and compositions therefor |
EP1956929A2 (de) * | 2005-10-21 | 2008-08-20 | Danisco A/S | Essbare zusammensetzung |
EP1978976A2 (de) * | 2006-01-30 | 2008-10-15 | Titan Pharmaceuticals, Inc. | Verwendung von gallium zur behandlung von biofilm-assoziierten infektionen |
CN101374532A (zh) * | 2006-01-30 | 2009-02-25 | 泰坦医药品公司 | 镓用于治疗与生物膜有关的感染的用途 |
US20080286235A1 (en) * | 2006-02-28 | 2008-11-20 | Beierle John W Jack | Antimicrobials and related methods |
JP2008156389A (ja) * | 2006-12-20 | 2008-07-10 | Lion Corp | バイオフィルム用処理剤 |
-
2010
- 2010-12-07 CN CN2010800553550A patent/CN102647997A/zh active Pending
- 2010-12-07 EP EP10836535.4A patent/EP2509622B1/de active Active
- 2010-12-07 WO PCT/US2010/059261 patent/WO2011071904A2/en active Application Filing
- 2010-12-07 CA CA2782789A patent/CA2782789A1/en not_active Abandoned
- 2010-12-07 JP JP2012543203A patent/JP2013513608A/ja active Pending
- 2010-12-07 US US12/961,896 patent/US20110135621A1/en not_active Abandoned
- 2010-12-07 AU AU2010328283A patent/AU2010328283A1/en not_active Abandoned
- 2010-12-09 TW TW099143074A patent/TW201143794A/zh unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0277383A1 (de) | 1987-01-08 | 1988-08-10 | Douwe Egberts Koninklijke Tabaksfabriek- Koffiebranderijen-Theehandel N.V. | Mittel zur oralen Hygiene |
Non-Patent Citations (10)
Title |
---|
ANANTHAPADMANABHAN ET AL., DERMATOLOGIC THERAPY, vol. 17, 2004, pages 16,25 |
FRANK ET AL., ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, pages 888 - 895 |
HARRISON-BELESTRA ET AL., DERMATOL SURG., vol. 29, no. 6, 2003, pages 631 - 635 |
JAMES ET AL., WOUND REPAIR REGEN., vol. 16, no. 1, 2008, pages 37 - 44 |
KANEKO ET AL., J. CLINICAL INVEST., vol. 117, no. 4, 2007, pages 877 - 888 |
MICHELS ET AL., SOC. APPLIED MICROBIOL. LETT. APPLIED MICROBIOL., vol. 49, 2009, pages 191 - 195 |
PHILLIPS ET AL., ADVANCES IN WOUND CARE, vol. 1, 2010, pages 299 - 304 |
PHILLIPS ET AL.: "Effects of Antimicrobial Agents on an In Vitro Biofilm Model of Skin Wounds", ADVANCES IN WOUND CARE, vol. 1, 2010, pages 299 - 304 |
See also references of EP2509622A4 |
WOLCOTT ET AL., J. WOUND CARE, vol. 17, no. 8, 2008, pages 333 - 341 |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013142372A1 (en) * | 2012-03-20 | 2013-09-26 | Kci Licensing, Inc. | Targeted enzymatic degradation of quorum-sensing peptides |
US9169319B2 (en) | 2012-03-20 | 2015-10-27 | Kci Licensing, Inc. | Targeted enzymatic degradation of quorum-sensing peptides |
JP2014181247A (ja) * | 2013-03-18 | 2014-09-29 | Fujitsu Ltd | バイオフィルム除去剤、バイオフィルム除去方法、及び情報処理装置 |
US11464232B2 (en) | 2014-02-19 | 2022-10-11 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US11470847B2 (en) | 2014-02-19 | 2022-10-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US11751570B2 (en) | 2014-02-19 | 2023-09-12 | Corning Incorporated | Aluminosilicate glass with phosphorus and potassium |
US11185080B2 (en) | 2014-04-30 | 2021-11-30 | Matoke Holdings Limited | Antimicrobial compositions |
US11311017B2 (en) | 2014-04-30 | 2022-04-26 | Matoke Holdings Limited | Antimicrobial compositions |
WO2020129374A1 (ja) * | 2018-12-20 | 2020-06-25 | 住友化学株式会社 | リチウム複合金属酸化物、リチウム二次電池用正極活物質、リチウム二次電池用正極及びリチウム二次電池 |
US11557762B2 (en) | 2018-12-20 | 2023-01-17 | Sumitomo Chemical Company, Limited | Lithium composite metal oxide, positive electrode active material for lithium secondary batteries, positive electrode for lithium secondary batteries, and lithium secondary battery |
Also Published As
Publication number | Publication date |
---|---|
CN102647997A (zh) | 2012-08-22 |
CA2782789A1 (en) | 2011-06-16 |
EP2509622A4 (de) | 2013-05-22 |
TW201143794A (en) | 2011-12-16 |
EP2509622B1 (de) | 2014-08-20 |
EP2509622A2 (de) | 2012-10-17 |
AU2010328283A1 (en) | 2012-06-14 |
US20110135621A1 (en) | 2011-06-09 |
WO2011071904A3 (en) | 2011-11-17 |
JP2013513608A (ja) | 2013-04-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2509622B1 (de) | Hemmung der bakterieninfektion und biofilmbildung | |
AU2019202045B2 (en) | Treatment of Microbial Infections | |
US8846009B2 (en) | Antimicrobial agents and methods of use | |
US8968793B2 (en) | Antiseptic compositions and uses thereof | |
RU2529799C2 (ru) | Композиции для усиления антибактериальной активности миелопероксидазы и способы их применения | |
US11096992B2 (en) | Use of seaprose to remove bacterial biofilm | |
US20080020025A1 (en) | Composition for wound care and method of using same | |
WO2014134701A1 (en) | Antimicrobial-antibiofilm compositions and methods of use thereof | |
US11628207B2 (en) | Use of thermolysin to reduce or eliminate bacterial biofilms from surfaces | |
US20180228837A1 (en) | Stable iodine solutions with medical applications | |
US11413300B2 (en) | Synergistic combination of thermolysin and an antibacterial agent to reduce or eliminate bacterial biofilms from surfaces | |
US20230022880A1 (en) | Antimicrobial Composition | |
JP2023505875A (ja) | 抗菌剤組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201080055355.0 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10836535 Country of ref document: EP Kind code of ref document: A1 |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10836535 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2010328283 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2782789 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2012543203 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2010328283 Country of ref document: AU Date of ref document: 20101207 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2010836535 Country of ref document: EP |