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  Antimicrobial conjugatesUSPTO Application #: 20080050448Title: Antimicrobial conjugates Abstract: The present invention presents a metallic nanoparticle-ligand-photosensitiser conjugate, a method of making such conjugate, and a method of using such mixture for killing or preventing the growth of microbes. (end of abstract) Agent: Dobrusin & Thennisch PC - Pontiac, MI, US Inventors: Mike Wilson, Ivan P. Parkin, Sean Nair, Jesus J. Gil-Tomas USPTO Applicaton #: 20080050448 - Class: 424490000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Particulate Form (e.g., Powders, Granules, Beads, Microcapsules, And Pellets), Coated (e.g., Microcapsules) The Patent Description & Claims data below is from USPTO Patent Application 20080050448. Brief Patent Description - Full Patent Description - Patent Application Claims
CLAIM OF BENEFIT OF FILING DATE [0001] This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/821,423 titled: "Antimicrobial Mixtures" filed on Aug. 4, 2006, U.S. Provisional Patent Application Ser. No. 60/868,130 titled: "Antimicrobial Conjugates" filed on Dec. 1, 2006, and United Kingdom Patent Application No. 0712287.2 titled: "Antimicrobial Conjugates" filed on Jun. 22, 2007. FIELD OF INVENTION [0002] The present invention relates to mixtures comprising charge-stabilized metallic nanoparticles and a photosensitiser, and their use as light activated antimicrobials. The present invention also relates to metallic nanoparticle-ligand-photosensitiser conjugates and their use as light activated antimicrobials. BACKGROUND OF THE INVENTION [0003] Photosensitisers, such as toluidine blue O, act as light-activated antimicrobial agents. Although they may have no antimicrobial activity at low concentrations in the dark, when irradiated with light of a certain wavelength (such as 633 nm for toluidine blue O) they are able to kill a wide range of microbes. Killing is thought to be due to the singlet oxygen produced on irradiation of the compound. There is considerable interest in enhancing the activity of existing photosensitisers. The present invention focuses on one method of achieving this. [0004] US 2005/0058713 describes that singlet oxygen production by a photosensitiser (zinc phthalocyanine) is enhanced by covalently linking it to gold nanoparticles (see also Duncan C. Hone, Peter I. Walker, Richard Evans-Gowing, Simon FitzGerald, Andrew Beeby, Isabelle Chambrier, Michael J. Cook, and David A. Russell. Langmuir 2002, 18, 2985-7). However, this increase in singlet oxygen generation has been reported to be due, at least in part, to the presence of tetraoctylammonium bromide--a reagent used in the preparation of the phthalocyanine-nanogold. The authors concluded, therefore, that the singlet oxygen generating system was, in fact, a three-component system consisting of nanogold, the phthalocyanine and the tetraoctylammonium bromide. Although the phthalocyanine/nanogold/tetraoctylammonium bromide was found to increase singlet oxygen generation, it was not demonstrated that these particles were able to kill either mammalian cells or microbes. [0005] Nanoparticle suspensions are inherently unstable, and the nanoparticles tend to associate, or clump together. Two methods are used to counter this. One is ligand-stabilization, which is employed, for example, in US 2005/0058713. The other is charge-stabilization. [0006] The present inventors have found that, surprisingly, simple mixing of charge-stabilized metallic nanoparticles with a photosensitiser results in enhancement of antimicrobial activity. [0007] The present inventors have also found that, surprisingly, metallic nanoparticle-ligand-photosensitiser conjugates, in which a photosensitiser is directly bound, via the ligand, to ligand-stabilised nanoparticles, have enhanced antimicrobial properties. SUMMARY OF THE INVENTION [0008] In one aspect of the invention there is provided a mixture comprising charge-stabilized metallic nanoparticles and a photosensitiser. The invention also provides a process for preparing such a mixture. [0009] In another aspect, the present invention provides use of the mixtures as antimicrobials. [0010] In yet another aspect, the present invention provides use of the mixtures in the manufacture of a medicament for killing or preventing the growth of microbes. [0011] The present invention also provides a process of killing or preventing the growth of microbes, comprising using the mixtures of the present invention. [0012] In another aspect, the present invention provides use of a metallic nanoparticle-ligand-photosensitiser conjugate, wherein: the ligand is a water-solubilising ligand; and the metallic nanoparticle and photosensitiser are chosen such that the conjugate generates singlet oxygen and/or free radicals as a light-activated antimicrobial. [0013] In one aspect, the use as an antimicrobial is for inanimate objects and surfaces. [0014] In another aspect, the present invention provides the above-mentioned conjugates for use in killing or preventing the growth of microbes or for ameliorating or reducing the incidence of proliferative cell disorders such as cancer in the human or animal body. [0015] The present invention also provides new metallic nanoparticle-ligand-photosensitiser conjugates, comprising gold, tiopronin and toluidine blue, and a process for making these and other conjugates useful in the present invention. Photodisinfection can meet the need to treat infections and decolonize microbes residing in body cavities without the use of antibiotics. BRIEF DESCRIPTION OF THE DRAWINGS [0016] FIG. 1 shows the effect of TBO and the TBO-tiopronin-gold nanoparticle conjugate on viability of S. aureus 6571 following exposure to white light for 30 minutes, or incubation in the dark with TBO or the TBO-tiopronin-gold nanoparticle conjugate. The white bar (.quadrature.) in FIG. 1 denotes the viable count of the original bacterial suspension, and the dotted bar () represents the viable count of the bacterial suspension after exposure to white light alone. The diagonal stripe bar () represents the viable count of the bacterial suspension after incubation in the dark with TBO. The horizontal strip bar () represents the viable count of the bacterial suspension after incubation in the dark with the TBO-tiopronin-gold nanoparticle conjugate. The grey bar () represents the viable count of the bacterial suspension after TBO and exposure to white light. The black bar (.box-solid.) represents the viable count of the bacterial suspension after TBO-tiopronin-gold nanoparticle conjugate and exposure to white light. [0017] FIG. 2 shows the effect of TBO and the TBO-tiopronin-gold nanoparticle conjugate on viability of S. aureus 6571 following exposure to HeNe laser light for 1 minute, or incubation in the dark with TBO or the TBO-tiopronin-gold nanoparticle conjugate. The white bar (.quadrature.) in FIG. 2 denotes the viable count of the original bacterial suspension, and the dotted bar () represents the viable count of the bacterial suspension after exposure to HeNe laser light alone. The diagonal stripe bar () represents the viable count of the bacterial suspension after incubation in the dark with TBO. The horizontal strip bar () represents the viable count of the bacterial suspension after incubation in the dark with the TBO-tiopronin-gold nanoparticle conjugate. The grey bar () represents the viable count of the bacterial suspension after TBO and exposure to HeNe laser light. The black bar (.box-solid.) represents the viable count of the bacterial suspension after TBO-tiopronin-gold nanoparticle conjugate and exposure to HeNe laser light. DESCRIPTION OF THE PREFERRED EMBODIMENT I. NANOPARTICLE-PHOTOSENSITISER MIXTURES Continue reading... Full patent description for Antimicrobial conjugates Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Antimicrobial conjugates patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Antimicrobial conjugates or other areas of interest. ### Previous Patent Application: Niosome-hydrogel drug delivery Next Patent Application: Fast release composition including melt granules of a moisture sensitive drug and process for manufacturing thereof Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Antimicrobial conjugates patent info. 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