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WO2005040228A2 - Disintegratable films for diagnostic devices - Google Patents

Disintegratable films for diagnostic devices Download PDF

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Publication number
WO2005040228A2
WO2005040228A2 PCT/US2004/035206 US2004035206W WO2005040228A2 WO 2005040228 A2 WO2005040228 A2 WO 2005040228A2 US 2004035206 W US2004035206 W US 2004035206W WO 2005040228 A2 WO2005040228 A2 WO 2005040228A2
Authority
WO
WIPO (PCT)
Prior art keywords
film
water soluble
reagent
molecular weight
testing device
Prior art date
Application number
PCT/US2004/035206
Other languages
French (fr)
Other versions
WO2005040228A3 (en
Inventor
William G. Meathrel
Nathan A. Meyer
Scott D. Barnhart
Andrew P. Full
Cathy M. Moritz
Original Assignee
Adhesives Research, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Adhesives Research, Inc. filed Critical Adhesives Research, Inc.
Priority to JP2006536864A priority Critical patent/JP4563393B2/en
Priority to AU2004284080A priority patent/AU2004284080B2/en
Priority to EP04796239.4A priority patent/EP1695094B1/en
Priority to CA2543350A priority patent/CA2543350C/en
Priority to DK04796239.4T priority patent/DK1695094T3/en
Priority to ES04796239T priority patent/ES2426990T3/en
Publication of WO2005040228A2 publication Critical patent/WO2005040228A2/en
Publication of WO2005040228A3 publication Critical patent/WO2005040228A3/en

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Classifications

    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/29—Titanium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/732—Starch; Amylose; Amylopectin; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/76—Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms

Definitions

  • the present invention is directed to disintegratable films, diagnostic devices containing such films, and methods for their use. More particularly, the present invention provides in one embodiment water soluble films containing soluble or dispersed reagents for use in diagnostic assay devices.
  • In-vitro diagnostic devices are widely used. Useful diagnostic assay devices depend on biospecific affinity reactions for detecting, isolating, and/or separating cells, proteins, bacteria, viruses, nucleic acid sequences, and various other materials or compounds of interest. Many medical diagnostic tests require the detection, isolation, and/or measurement of specific compounds present in biological fluids such as blood, saliva, and urine.
  • Diagnostic tests can be conducted using a variety of devices, for example, electronic devices, biosensors, lateral flow devices, test strips, and test cards, among others. Often the necessary materials to conduct a test are provided in the form of a test kit, which may include a particular testing device. Some testing devices include the reagent or reagents necessary to perform a particular test. For other testing devices, the reagent(s) is obtained separately and used in connection with the testing device.
  • Substances which can be detected, measured, and/or isolated using an in-vitro diagnostic device include, for example, glucose; cholesterol; proteins, for example, various enzymes, such as amylase and creatine kinase; substances- of -abuse, for example, drugs regulated by law with respect to possession and use, such as methamphetamines; cells; bacteria; viruses; and nucleic acid sequences; among others.
  • pregnancy testing can be conducted using test strips to detect human chorionic gonadotropin (hCG).
  • hCG human chorionic gonadotropin
  • 6,270,637 describes an electrochemical biosensor blood glucose test strip. Diagnostic testing, as described in US Patent No. 5,846,751, is used to detect helicobacter pylori bacterium in the human stomach to diagnose gastric disorders and duodenal ulcer disease. US Patent No. 6,645,731 describes the isolation of cancer cells from a biochemical matrix.
  • a lateral flow device includes a test strip, on which one or more reagents are present.
  • a fluid sample is deposited onto the strip and migrates by capillary action along the strip where chemical reactions take place depending upon the presence or absence of the analyte in situ.
  • at least one reagent is included which manifests a detectable signal, for example a color change, in the presence of a minimal amount of the analyte of interest.
  • aqueous solutions containing a reagent are localized on a supporting layer, which is a solid material, such as membrane support, an electrochemical sensor, cellulose or paper.
  • a reagent for example, enzymes or antibodies
  • the reagents are selected as necessary or helpful in detection of the analyte in question.
  • the reagent is placed on the membrane by spraying, coating, or striping and then dried.
  • Reagents can be expensive. Therefore, waste of reagents is undesirable.
  • Conventional preparation techniques for test strips such as spraying, coating or striping, can result in loss of reagent. Additionally, it is difficult to control the amount of reagent on the test strip using conventional techniques. Further, aqueous reagents can be cumbersome to handle. Some reagents are unstable in aqueous form and may require specialized storage, such as refrigeration.
  • Magnetic particles that have been functionalized with specific chemical reactive moieties also are known for use as reagents in immunoassays. In these assays, biochemical complexes are separated and isolated based on magnetic properties.
  • US Patent No. 6,120,856 refers to the use of ferro fluids in diagnostic techniques including imunoassays, cell separation, toxicity testing, food testing, and environmental analysis.
  • US Patent No. 6,672,458 describes the uses of functionalized paramagnetic particles for the separation and isolation of nucleic acid (DNA and RNA) from amplification techniques. Following amplification the cells are lysed and specific nucleic acid sequences are complexed to the functionalized paramagnetic particles.
  • the paramagnetic particles with the bound nucleic acid are separated from the remaining solution using the magnetic properties of the complex.
  • Plastic containers made from polystyrene and polypropylene are know to retain a static charge.
  • the static charge on test tubes and other components causes problems in dispensing quantitative amounts of particles due to particle attraction to plastic and glass surfaces.
  • the present invention provides disintegratable film reagent compositions prepared with a combination of components that yield films of sufficient film strength and desirable disintegration profiles for use in diagnostic testing.
  • a disintegratable film according to the present invention contains a mixture of high molecular weight and low molecular weight water soluble components.
  • the film also contains one or more reagents targeted to react with an analyte of interest or other reagents, such that the film can be used in a particular diagnostic test.
  • the films further contain a starch component, a glucose component, a plasticizer and/or a humectant.
  • the film can include a filler, which is a dispersed phase or particle within the film to modify the disintegration profile of the film.
  • an analyte is meant the molecule or other substance in the sample to be detected.
  • an analyte may be a ligand, which is mono- or polyepitopic, antigenic or haptenic; it may be a single compound, such as chorionic gonadotropin, glucose, prostate specific antigen, or a plurality of compounds which share at least one common epitopic site; it may be an epitopic site of a viral, bacterial, or other pathogen; it may also be a receptor or an antibody, or any other chemical or biological substance, compound, or material suspected of being present in a sample of interest, including, but not limited to, a toxic substance, such as a pollutant, or a biological or chemical warfare agent.
  • agents include, without limitation, specific antibodies or specific receptors, various iron oxide particles, magnetic, ferromagnetic or paramagnetic particles, and any substance that itself or in combination with other factors gives rise to a detectable signal or response when paired with an analyte of interest, for example, a pathogen (e.g., a bacteria, virus, or fungus); a protein (e.g., a growth factor, a lymphokine, a toxin, or a hormone); a cell surface (e.g., a cell adhesion molecule, a laminin, a fibronectin, an integrin, or a lectin); various drugs; metabolites; pesticides; or toxins.
  • a pathogen e.g., a bacteria, virus, or fungus
  • a protein e.g., a growth factor, a lymphokine, a toxin, or a hormone
  • a cell surface e.g., a cell adhesion molecule
  • a film according to an exemplary embodiment of the invention is preferably in the form of a monolayer.
  • the monolayer can be cut to any desired size or shape for use in diagnostic testing applications.
  • the invention further provides a diagnostic testing device, which includes a film according to an embodiment of the invention, and methods for their use to detect the presence of an analyte of interest.
  • FIG. 1 illustrates a diagnostic testing device according to an exemplary embodiment of the invention
  • FIG. 2 is a block diagram of a testing device according to another exemplary embodiment of the invention.
  • This invention incorporates test reagents and other chemical components into a dry disintegratable film.
  • the film can be die cut and placed in a testing device or test strip used in various diagnostic techniques, including, but not limited to, immunoassays, cell separations, toxicity testing, food testing, environmental analysis, and emergency response test kits.
  • a disintegratable film with a single reagent or multiple reagents can be used.
  • multiple disintegratable films with single or multiple reagents may also be used in a diagnostic test device.
  • the disintegratable films according to the invention are comprised of a mixture of high molecular weight and low molecular weight water soluble components.
  • the high molecular weight and low molecular weight water soluble components are water soluble polymers.
  • the film also includes one or more reagents, such that the film can be used in a particular diagnostic test.
  • the films may further include a starch component, a glucose component, a plasticizer and/or humectant; and/or other excipients in suitable amounts as described below, and which may be determined by one of ordinary skill in the art pursuant to the guidance provided by the examples and teachings herein.
  • the films will have a thickness in the range of about 0.4 mil to about 10 mil, and more preferably within the range of about 0.4 mil to about 2 mil, although various other thicknesses are suitable as desired for particular applications as described in more detail below.
  • Each film can be characterized by its film strength and its disintegration profile (the speed at which the film will disintegrate in an aqueous media such as saliva).
  • surfactants have been used to affect the disintegration speed and decrease the time required for complete film disintegration.
  • the present invention provides disintegratable film compositions that rapidly disintegrate upon application of a disintegration fluid, such as, but not limited to, blood, saliva, urine, and other aqueous biological and environmental fluids, and which, at the same time, have sufficient film strength without requiring the use of any surfactant.
  • a surfactant is optional in certain embodiments of the present invention, as described below, other embodiments are surfactant-free or substantially free of surfactants.
  • the term "essentially free of surfactants" refers to trace amounts or higher levels of surfactants that are sufficiently low so as not to substantially increase the disintegration rate of the film composition following contact with a disintegrating fluid.
  • a disintegratable film containing one or more reagents can improve the stability of the reagents. Additionally, the reagents can be used more effectively and efficiently, since the film can be localized to a particular area within a testing device and can be handled easily as compared to an aqueous solution. Further, providing reagents in film form promotes efficient use and minimizes reagent wastage since a film can be divided into individual segments having a desired amount of reagent and the need for spraying, coating, or striping a reagent can thus be eliminated, if desired.
  • the high molecular weight and low molecular weight water soluble components of the disintegratable films according to the present invention may include a water-soluble polymer, including but not limited to, water-soluble hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, sodium carboxy methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragacantha, guar gum, acacia gum, arabic gum, carrageenan, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, and various mixtures of the above and other known water-soluble polymers, cellulose derivatives, and/or gums, among others.
  • a water-soluble polymer including but not limited to, water-soluble hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvin
  • the water soluble components include a combination of low molecular weight polymers (e.g., those less than about 5,000 to about 60,000 daltons) and high molecular weight polymers (e.g., those of about 60,000 to about 150,000 daltons, and to about 500,000 daltons or higher).
  • low molecular weight polymers e.g., those less than about 5,000 to about 60,000 daltons
  • high molecular weight polymers e.g., those of about 60,000 to about 150,000 daltons, and to about 500,000 daltons or higher.
  • hydroxypropyl cellulose e.g., Klucel, grade JF, Hercules Inc., Aqualon Division
  • hydroxy lpropyl methylcellulose e.g., Methocel, grades E5, E50, E4M, and SG A16M by Dow Chemical
  • These water soluble cellulose derivative polymers have molecular weights of about 140,000; 30,000; 90,000; 400,000; greater than about 100,000 da
  • Additional water soluble polymers include polyvinyl pyrrolidone
  • PVP Plasdone K-29/32 by ISP Corp.
  • polyvinyl alcohol-polyethylene glycol copolymer such as Kollicoat IR by BASF Pharma, which has a molecular weight of about 49,000 daltons
  • acrylic polymer, sodium salt such as Acrysol by Rohm and Haas, which is available in various grades having different molecular weights.
  • a water soluble polymer may serve the function of an additional optional component.
  • polyethylene oxide such as, Polyox by Dow Chemical having a molecular weight of about 200,000 daltons, can serve as a high molecular weight water soluble polymer and a plasticizer, as discussed below.
  • the molecular weights of the water soluble polymers can be determined as described in Keary, "Characterization of METHOCEL Cellulose Ethers by Aqueous SEC with Multiple Detectors," Carbohydrate Polymers Vol. 45, pp. 293-303 (2001), which is incorporated herein by reference.
  • Various other polymers can be selected by one of ordinary skill in the art given the teachings herein, so long as the polymer is water soluble, and preferably includes a sufficient amount of a high molecular weight component to impart adequate film strength, and a sufficient amount of a low molecular weight component to facilitate the desired film property of rapid disintegration profile.
  • concentrations of each polymer may be utilized. Such concentrations will typically be in the range of about 2% to about 35% based on the total weight of the dry film. In one embodiment, the concentration for the high molecular weight polymer is about 5% to 10% and the concentration of the low molecular weight polymer is about 5% to 10% of the dry film.
  • the water soluble low molecular weight component need not be a water soluble polymer.
  • the low molecular weight component may be a low molecular weight monomer or a combination of various low molecular weight monomers.
  • the low molecular weight component can also serve the function of an additional optional component.
  • the low molecular weight component can also serve as the reagent, a glucose component, a plasticizer, starch, thickener, buffer, stabilizer, and/or additive, and may include any of the specific compounds listed below or other suitable compounds, which are water soluble and have a molecular weight less than about 60,000 daltons.
  • the low molecular weight component serves to promote rapid disintegration, but is present in an amount such that film strength is adequate for processing and dispensing.
  • concentrations of the low molecular weight component can be utilized. Such concentrations will typically be in the range of about 2% to about 80% or more based on the total weight of the dry film. In one embodiment, the concentration for the high molecular weight polymer is about 5% to 10% and the concentration of the low molecular weight component is about 30% to 80% of the dry film.
  • the amounts of high and low molecular weight components can be adjusted to achieve a desired disintegration profile for the film.
  • concentration of the high molecular weight component can be increased relative to the concentration of the low molecular weight component.
  • concentration of the low molecular weight component can be increased relative to the concentration of the high molecular weight component.
  • the thickness of the film can be adjusted to achieve a desired disintegration profile. To increase the disintegration time, the film thickness is increased. Adequate film strength should be maintained to allow for processing of the film.
  • the films according to the invention have adequate strength for processing, packaging, and administration without physical failure (e.g., breakage, fracture, or otherwise) during processing and normal handling prior to packaging and use in a desired diagnostic device or testing application.
  • the film strength specifically, film resilience, springiness and burst strength, can be determined using the TA.XT2i Texture Analyzer by Texture Technologies Corp. and the ASTM D3763 "High Speed Puncture Properties of Plastics Using Load and Displacement Sensors" test method. These properties of film strength and rapid disintegration are the result of the unique combination of the components described herein.
  • Rapid disintegration we mean that the reagent is released from the film matrix in less than about minute. Disintegration times can be determined using the test provided by (USP) 24, Disintegration ⁇ 701>. See United States Pharmacopoeia, 24th ed., Ch. 701, p. 1941 (2000), which is incorporated herein by reference.
  • the optional glucose component of thin films according to the invention can be added to promote disintegration of the film upon contact with a disintegrating fluid.
  • the glucose component comprises a water soluble polymer or mixture of polymers having D-glucose units.
  • the dextrose equivalent (DE) of the glucose component is preferably within the range of about 10 to about 25, or about 15 to about 20, although various other DE ranges can also be used.
  • the glucose component can be prepared, for example, by the partial hydrolysis of starch to yield D-glucose polymer mixtures. Suitable commercially available glucose components include, for example, maltodextrin, corn syrup solids, sucrose, and dextrose.
  • Suitable concentrations as a weight percentage of the dry film composition will typically be in the range of about 2% to 20%, or about 3% to about 15%, although other concentrations also may be used depending on the selection of other components and the desired film properties.
  • the optional starch component of films according to the present invention can be added to promote disintegration of the film upon contact with a disintegrating fluid.
  • the starch component can also serve to increase the solids content of the film and add bulk.
  • the starch component is a water soluble polysaccharide composition containing amylose and/or amylopectin.
  • Such compositions may be prepared by, for example, modifying natural starches, such as corn, wheat, rice, potato, or tapioca starch, to provide cold water soluble instant starches.
  • Various water soluble compositions of amylose and/or amylopectin polysaccharides can be used. Typically, these can be made by heating a natural starch with steam to modify the natural starch product so that it is cold water soluble.
  • the instant starch commercially available from GPC, Muscatine IA, as "Instant Pure Cote B792," (IPC B792) is an exemplary starch component for purposes of the present invention.
  • Other suitable commercially available instant starches include “Polartex Instant 12640,” available from Cargill, Inc., and various others may also be utilized.
  • the starch component will typically have an amylose to amylopectin ratio in the range, for example, of about 0 to about 2.5.
  • the starch can be incorporated in the wet film composition in any suitable amount, including, but not limited to, about 2% to 50%, or about 3% to about 35% by weight based on the dry film.
  • the disintegratable film compositions of the present invention may also optionally contain a plasticizer or humectant, for example, polyalcohols, sorbitan esters, and citric acid esters, to increase the flexibility of the films.
  • a plasticizer or humectant for example, polyalcohols, sorbitan esters, and citric acid esters, to increase the flexibility of the films.
  • the plasticizers can be added directly to the formulation during manufacture.
  • Suitable compounds include polyethylene glycol (PEG), such as Lutrol E 400, by BASF Pharma; polyethylene oxide, such as Polyox by Dow; polyoxamers, such as Lutrol F by BASF Pharma; polyvinyl alcohol; polyvinyl methyl ether, such as Lutanol by BASF; or mixtures of such polymers; triacetin; glycerin; mannitol; xylitol; and various other polyalcohols and other compounds having plasticizer and/or humectant properties can be satisfactorily employed.
  • PEG polyethylene glycol
  • Lutrol E 400 by BASF Pharma
  • polyethylene oxide such as Polyox by Dow
  • polyoxamers such as Lutrol F by BASF Pharma
  • polyvinyl alcohol polyvinyl methyl ether
  • Lutanol by BASF
  • triacetin triacetin
  • glycerin mannitol
  • xylitol mannitol
  • Sorbitol and PEG 400 are particularly suitable; although compounds having a higher molecular weight (e.g., Polyox N80) than PEG 400 can be desirable for certain applications, since they are typically less volatile than sorbitol and PEG 400.
  • the optional plasticizer and/or humectant may be present in any suitable range, including, for example about 3% to 30%, 10% to 20%, or 15% to 18% by weight of the dry film.
  • thickeners, buffers, stabilizers, additives and/or other components can be added to the film formulations according to the invention to provide a film having desired properties.
  • an additional component can be added to the film composition.
  • a thickener such as Carbopol 940 by Noveon, Inc. can be added.
  • the films according to the invention can contain a filler, which is a dispersed phase or particle.
  • the filler can add bulk to the film; increase the solids portion of the film, which can aid in coating; and/or can cause the films to disintegrate faster upon contact with the disintegrating fluid, i.e., biological sample or other aqueous material suspected of containing an analyte of interest.
  • the filler can be a reagent or an optional additional component.
  • the filler can be an optional non-active component. Examples of such components include titanium oxide and microcrystalline cellulose, which is available under the name Avicel, among others.
  • Air or other gasses can also be used as a filler according to the invention.
  • a surfactant e.g., sodium lauryl sulfate (SLS), available under the name Stepanol, Polysorbate 80, or Pluracare F87 Pril NF
  • SLS sodium lauryl sulfate
  • Stepanol Polysorbate 80
  • Pluracare F87 Pril NF Pluracare F87 Pril NF
  • the surfactant does not itself serve to significantly increase the rate of disintegration of the films. Instead, the surfactant aids in the processing and formation of the film. Specifically, the surfactant stabilizes the gaseous bubbles as a dispersed phase within a solution to allow the solution to be processed, as described in more detail below, to form the film
  • the particular components for a film can be chosen as desired and as are compatible with a particular testing scheme.
  • the optional glucose component would typically be omitted from a film to be employed in a blood glucose testing device.
  • the film compositions according to the invention may be prepared by several methods, including, but not limited to, adding the combination of high and low molecular weight water soluble components, the optional starch, and optional glucose ingredients to a. solvent that is capable of dissolving them, such as water or ethanol or a mixture of ethanol and water.
  • a solvent that is capable of dissolving them, such as water or ethanol or a mixture of ethanol and water.
  • the reagent and any of the other optional components such as plasticizers, colorants, and/or other components may be blended into the reagent-containing polymer solution.
  • all of the film components may be added and concurrently blended to form a solution or dispersion.
  • a dry blend can be compounded by a V-blender.
  • the dry blend can be subsequently used to form a solution or dispersion. Additionally, the dry blend can be subjected to a melt extrusion process to form a film upon cooling. It should be understood that no particular sequence of steps is required, except as needed to effectively prepare a desired film composition. For example, if a particular sequence yields an undesirable precipitate, an alternative sequence may be used.
  • the reagent may be soluble in the solution or it may be suspended or dispersed in the solution. Any reagent or combination of reagents suitable for a particular diagnostic test can be used. Suitable reagents for particular diagnostic tests are known in the art and continue to be discovered or created. Examples of reagents include, but are not limited to, proteins, enzymes, antibodies, substances that display magnetic properties, iron oxide, and other compounds or combinations of compounds which display a physical change, such as a color change upon exposure to a particular substance or magnetic field.
  • the reagent-containing solution or dispersion may be further processed into a film by any one of many casting, drawing, or extruding techniques.
  • the solution or dispersion may be sprayed onto a support such as a release-treated belt.
  • the solution or dispersion may be roll coated onto a release treated paper or film substrate.
  • the solvent may be removed by radiant energy (such as infra-red), heat, convection, vacuum, or any combination of these to yield a dry film containing one or more reagents.
  • radiant energy such as infra-red
  • heat such as heat
  • convection such as vacuum
  • vacuum such as vacuum
  • the resulting dry film can be wound up into a roll for storage prior to further processing into individual films for specific diagnostic devices. Whether stored for future processing or immediately following removal of the solvent, the resulting film can be removed from the support surface and subsequently processed for various end use applications.
  • the dry film can be further processed by any suitable technique, including, for example, by die-cutting or cutting across the width of a singular narrow roll to prepare segments of any desired geometric size or shape.
  • the segments may be subsequently packaged and/or further processed and incorporated into a testing device.
  • the efficiency of the manufacturing process can be improved.
  • the continuing processing of rolls of reagent containing film, die cutting, and reagent placement can be less wasteful than conventional spraying, coating, or striping processes.
  • Additional ingredients can be applied to the dried film by, for example, printing, spraying, dusting, or vapor adsorption processes, among others.
  • a testing device 1 including a disintegratable film 10 according to an exemplary embodiment of the invention is shown in FIG. 1.
  • the disintegratable film 10 is used to create a fluid channel upon application of a disintegrating fluid (not shown), such as blood, saliva, or urine.
  • the film 10 can be die cut from a roll to create a fluidic pathway pattern.
  • the film pattern can be sandwiched between adjacent layers such as adhesive coatings 12.
  • the adhesive coatings 12, can be, for example, Adhesives Research, Inc s ARcare 8890, ARcare 7840, or ARcare 7841, which are double faced adhesive constructions used in forming fluidic channels for testing devices.
  • a disintegratable film 20 can be used to protect and isolate a reactive layer 23 or reagent in a diagnostic testing device 2, as shown in FIG. 2.
  • the reactive layer 23 containing one or more reagents and the film 20 are within a fluid channel 27 and are supported by a support structure 25.
  • the fluid channel 27 may or may not be covered by a cover 28.
  • the cover 28 is preferably a transparent cover, and can be, for example an adhesive material heat bonded to the support structure 25.
  • the reactive layer 23 is a disintegratable film according to the invention.
  • the reactive layer 23 can be a conventional reactive layer.
  • the reactive layer 23 is isolated by the film 20 until the film is disintegrated by a disintegrating fluid (not shown).
  • the film 20 need not include a reagent.
  • the film 20 is configured to act as a barrier to the reactive layer 23.
  • a disintegrating fluid such as saliva, blood or urine
  • the barrier film 20 disintegrates allowing an analyte (not shown) contained in the fluid to encounter the reactive layer 23.
  • the interaction between reactive components in the testing device 2 can be controlled by choice of disintegration time and/or conditions (e.g., pH, temperature, ionic strength, among others).
  • FIGS. 1 and 2 are exemplary only, and the films according to the invention can be included in other testing devices, such as electronic devices, biosensors, various lateral flow devices, and test cards, among others.
  • the films may also be packaged and provided as part of a test kit.
  • Examples 1-3 illustrate films suitable for use in pregnancy testing in humans.
  • pregnancy testing is conducted by detecting human chorionic gonadotropin (hCG) in, for example, a urine or blood sample.
  • hCG human chorionic gonadotropin
  • the reagents listed in examples 1-3 specifically, the organic salt, organic base, inorganic base, organic acid, and protein, can be those known in the art which are suitable to permit the detection of hCG in a sample, such as those disclosed in US Patent 4,496,654 and 5,712,172.
  • each of the reagents may be a combination of individual ingredients.
  • the protein may be a combination of antibodies.
  • Example 1 is a composition for films suitable for use in an hCG test strip according to an exemplary embodiment of the invention.
  • the films of example 1 can be used together in a single test strip.
  • the first film contains two reagents, an organic acid and an inorganic base, and the second film contains two reagents, an organic salt and an organic amine.
  • the films each include a common base solution.
  • Examples 2 and 3 illustrate the composition for a single film suitable for use in an hCG test strip according to additional exemplary embodiments of the invention.
  • the films of examples 2 and 3 each include four reagents.
  • Examples 4 and 5 illustrate film compositions including iron oxide according to additional exemplary embodiments of the invention.
  • Methocel E5, Methocel E50, Maltrin M180 and Pure-Cote are added to boiling water with constant stirring.
  • the mixture is cooled to about room temperature under agitation to allow the components to solubilize.
  • the iron oxide is mixed with triacetin, polysorbate 80 and ethanol until the iron oxide is wetted out.
  • the aqueous solution is added to the iron oxide mixture and stirred to form a homogeneous mixture.
  • the mixture is deairated prior to coating onto a release liner.
  • the coating is dried at about 120 degrees C for about 5 minutes.
  • Examples 6-9 are prophetic examples, which illustrate exemplary film formulations according to the invention.
  • the reagent component(s) is not listed as being a specific reagent. Any suitable reagent can be used.
  • the films of examples 6-9 contain substantially no surfactants.

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Abstract

The invention provides disintegratable film compositions for diagnostic test devices. The films are prepared with a combination of components that yield films of sufficient film strength and desired disintegration profiles. A disintegratable film according to the present invention contains a water soluble high molecular weight component, a water soluble low molecular weight component, and one or more reagents for use in a diagnostic device. Optionally, the films further contain a starch component, a glucose component, a plasticizer and/or a humectant, and/or a filler. The invention further provides a diagnostic testing device, which includes a film according to an embodiment of the invention, and methods of using such devices.

Description

DISINTEGRATABLE FILMS FOR DIAGNOSTIC DEVICES
CROSS REFERENCE TO OTHER APPLICATION
[0001] This patent application claims the benefit of U.S. provisional patent application serial number 60/513,547, filed October 24, 2003, and titled RAPIDLY DISSOLVING FILMS FOR DELIVERY OF PHARMACEUTICAL OR COSMETIC AGENTS. U.S. provisional patent application serial number 60/513,547 is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention is directed to disintegratable films, diagnostic devices containing such films, and methods for their use. More particularly, the present invention provides in one embodiment water soluble films containing soluble or dispersed reagents for use in diagnostic assay devices.
BACKGROUND OF THE INVENTION
[0003] In-vitro diagnostic devices are widely used. Useful diagnostic assay devices depend on biospecific affinity reactions for detecting, isolating, and/or separating cells, proteins, bacteria, viruses, nucleic acid sequences, and various other materials or compounds of interest. Many medical diagnostic tests require the detection, isolation, and/or measurement of specific compounds present in biological fluids such as blood, saliva, and urine.
[0004] Diagnostic tests can be conducted using a variety of devices, for example, electronic devices, biosensors, lateral flow devices, test strips, and test cards, among others. Often the necessary materials to conduct a test are provided in the form of a test kit, which may include a particular testing device. Some testing devices include the reagent or reagents necessary to perform a particular test. For other testing devices, the reagent(s) is obtained separately and used in connection with the testing device.
[0005] Substances which can be detected, measured, and/or isolated using an in-vitro diagnostic device include, for example, glucose; cholesterol; proteins, for example, various enzymes, such as amylase and creatine kinase; substances- of -abuse, for example, drugs regulated by law with respect to possession and use, such as methamphetamines; cells; bacteria; viruses; and nucleic acid sequences; among others. For example, pregnancy testing can be conducted using test strips to detect human chorionic gonadotropin (hCG). Such a test is described in US Patent Nos. 6,403,298 and 4,496,654. Also, diabetics and health care professionals use test strips for measuring blood glucose levels. US Patent No. 6,270,637 describes an electrochemical biosensor blood glucose test strip. Diagnostic testing, as described in US Patent No. 5,846,751, is used to detect helicobacter pylori bacterium in the human stomach to diagnose gastric disorders and duodenal ulcer disease. US Patent No. 6,645,731 describes the isolation of cancer cells from a biochemical matrix.
[0006] Lateral flow testing devices are commonly used. Typically, a lateral flow device includes a test strip, on which one or more reagents are present. To use the lateral flow testing device, a fluid sample is deposited onto the strip and migrates by capillary action along the strip where chemical reactions take place depending upon the presence or absence of the analyte in situ. Often, at least one reagent is included which manifests a detectable signal, for example a color change, in the presence of a minimal amount of the analyte of interest.
[0007] To fabricate test strips, aqueous solutions containing a reagent, for example, enzymes or antibodies, are localized on a supporting layer, which is a solid material, such as membrane support, an electrochemical sensor, cellulose or paper. The reagents are selected as necessary or helpful in detection of the analyte in question. Typically, the reagent is placed on the membrane by spraying, coating, or striping and then dried.
[0008] Other diagnostic testing devices require the use of various aqueous reagents. The reagents are typically applied by pipette directly to the sample to be tested.
[0009] Reagents can be expensive. Therefore, waste of reagents is undesirable. Conventional preparation techniques for test strips, such as spraying, coating or striping, can result in loss of reagent. Additionally, it is difficult to control the amount of reagent on the test strip using conventional techniques. Further, aqueous reagents can be cumbersome to handle. Some reagents are unstable in aqueous form and may require specialized storage, such as refrigeration.
[0010] Magnetic particles that have been functionalized with specific chemical reactive moieties also are known for use as reagents in immunoassays. In these assays, biochemical complexes are separated and isolated based on magnetic properties. US Patent No. 6,120,856 refers to the use of ferro fluids in diagnostic techniques including imunoassays, cell separation, toxicity testing, food testing, and environmental analysis. US Patent No. 6,672,458 describes the uses of functionalized paramagnetic particles for the separation and isolation of nucleic acid (DNA and RNA) from amplification techniques. Following amplification the cells are lysed and specific nucleic acid sequences are complexed to the functionalized paramagnetic particles. The paramagnetic particles with the bound nucleic acid are separated from the remaining solution using the magnetic properties of the complex. [0011] However, it has been difficult to control the concentration of the magnetic particles due to static effects on the glass and plastic containers used in conventional diagnostic techniques. Plastic containers made from polystyrene and polypropylene are know to retain a static charge. The static charge on test tubes and other components causes problems in dispensing quantitative amounts of particles due to particle attraction to plastic and glass surfaces.
[0012] Accordingly, it would be desirable to provide reagent compositions and diagnostic devices that minimize or eliminate the above problems.
BRIEF SUMMARY OF THE INVENTION
[0013] The present invention provides disintegratable film reagent compositions prepared with a combination of components that yield films of sufficient film strength and desirable disintegration profiles for use in diagnostic testing. A disintegratable film according to the present invention contains a mixture of high molecular weight and low molecular weight water soluble components. The film also contains one or more reagents targeted to react with an analyte of interest or other reagents, such that the film can be used in a particular diagnostic test. Optionally, the films further contain a starch component, a glucose component, a plasticizer and/or a humectant. Also optionally, the film can include a filler, which is a dispersed phase or particle within the film to modify the disintegration profile of the film.
[0014] By "analyte" is meant the molecule or other substance in the sample to be detected. For example, an analyte, as used herein, may be a ligand, which is mono- or polyepitopic, antigenic or haptenic; it may be a single compound, such as chorionic gonadotropin, glucose, prostate specific antigen, or a plurality of compounds which share at least one common epitopic site; it may be an epitopic site of a viral, bacterial, or other pathogen; it may also be a receptor or an antibody, or any other chemical or biological substance, compound, or material suspected of being present in a sample of interest, including, but not limited to, a toxic substance, such as a pollutant, or a biological or chemical warfare agent.
[0015] Examples of "reagents" include, without limitation, specific antibodies or specific receptors, various iron oxide particles, magnetic, ferromagnetic or paramagnetic particles, and any substance that itself or in combination with other factors gives rise to a detectable signal or response when paired with an analyte of interest, for example, a pathogen (e.g., a bacteria, virus, or fungus); a protein (e.g., a growth factor, a lymphokine, a toxin, or a hormone); a cell surface (e.g., a cell adhesion molecule, a laminin, a fibronectin, an integrin, or a lectin); various drugs; metabolites; pesticides; or toxins.
[0016] A film according to an exemplary embodiment of the invention is preferably in the form of a monolayer. The monolayer can be cut to any desired size or shape for use in diagnostic testing applications.
[0017] The invention further provides a diagnostic testing device, which includes a film according to an embodiment of the invention, and methods for their use to detect the presence of an analyte of interest.
[0018] These and other advantages and features of the invention will be more readily understood from the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The foregoing and other advantages and features of the invention will become more apparent from the detailed description of exemplary embodiments provided below with reference to the accompanying drawings in which:
[0020] FIG. 1 illustrates a diagnostic testing device according to an exemplary embodiment of the invention; and
[0021] FIG. 2 is a block diagram of a testing device according to another exemplary embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0022] Reference will now be made in detail to the presently preferred embodiments of the invention, which, together with the following examples, serve to explain the principles of the invention. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized, and that various structural, biological, physical, and chemical changes may be made without departing from the spirit and scope of the present invention.
[0023] This invention incorporates test reagents and other chemical components into a dry disintegratable film. The film can be die cut and placed in a testing device or test strip used in various diagnostic techniques, including, but not limited to, immunoassays, cell separations, toxicity testing, food testing, environmental analysis, and emergency response test kits. A disintegratable film with a single reagent or multiple reagents can be used. Alternatively, multiple disintegratable films with single or multiple reagents may also be used in a diagnostic test device.
[0024] The disintegratable films according to the invention are comprised of a mixture of high molecular weight and low molecular weight water soluble components. In a preferred embodiment, the high molecular weight and low molecular weight water soluble components are water soluble polymers. The film also includes one or more reagents, such that the film can be used in a particular diagnostic test. Optionally, the films may further include a starch component, a glucose component, a plasticizer and/or humectant; and/or other excipients in suitable amounts as described below, and which may be determined by one of ordinary skill in the art pursuant to the guidance provided by the examples and teachings herein. Preferably the films will have a thickness in the range of about 0.4 mil to about 10 mil, and more preferably within the range of about 0.4 mil to about 2 mil, although various other thicknesses are suitable as desired for particular applications as described in more detail below.
[0025] Each film can be characterized by its film strength and its disintegration profile (the speed at which the film will disintegrate in an aqueous media such as saliva). In known dissolvable films, surfactants have been used to affect the disintegration speed and decrease the time required for complete film disintegration. The present invention provides disintegratable film compositions that rapidly disintegrate upon application of a disintegration fluid, such as, but not limited to, blood, saliva, urine, and other aqueous biological and environmental fluids, and which, at the same time, have sufficient film strength without requiring the use of any surfactant. While a surfactant is optional in certain embodiments of the present invention, as described below, other embodiments are surfactant-free or substantially free of surfactants. The term "essentially free of surfactants" refers to trace amounts or higher levels of surfactants that are sufficiently low so as not to substantially increase the disintegration rate of the film composition following contact with a disintegrating fluid.
[0026] A disintegratable film containing one or more reagents can improve the stability of the reagents. Additionally, the reagents can be used more effectively and efficiently, since the film can be localized to a particular area within a testing device and can be handled easily as compared to an aqueous solution. Further, providing reagents in film form promotes efficient use and minimizes reagent wastage since a film can be divided into individual segments having a desired amount of reagent and the need for spraying, coating, or striping a reagent can thus be eliminated, if desired.
[0027] The high molecular weight and low molecular weight water soluble components of the disintegratable films according to the present invention may include a water-soluble polymer, including but not limited to, water-soluble hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, sodium carboxy methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragacantha, guar gum, acacia gum, arabic gum, carrageenan, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, and various mixtures of the above and other known water-soluble polymers, cellulose derivatives, and/or gums, among others.
[0028] We have found that particularly beneficial properties of film strength and disintegration profile are obtained when the water soluble components include a combination of low molecular weight polymers (e.g., those less than about 5,000 to about 60,000 daltons) and high molecular weight polymers (e.g., those of about 60,000 to about 150,000 daltons, and to about 500,000 daltons or higher). For example, a combination of hydroxypropyl cellulose (e.g., Klucel, grade JF, Hercules Inc., Aqualon Division) and hydroxy lpropyl methylcellulose (e.g., Methocel, grades E5, E50, E4M, and SG A16M by Dow Chemical) is suitable. These water soluble cellulose derivative polymers have molecular weights of about 140,000; 30,000; 90,000; 400,000; greater than about 100,000 daltons, respectively.
[0029] Additional water soluble polymers include polyvinyl pyrrolidone
(PVP), such as Plasdone K-29/32 by ISP Corp., which has a molecular weight of about 58,000 daltons; polyvinyl alcohol-polyethylene glycol copolymer, such as Kollicoat IR by BASF Pharma, which has a molecular weight of about 49,000 daltons; and an acrylic polymer, sodium salt, such as Acrysol by Rohm and Haas, which is available in various grades having different molecular weights. Further, a water soluble polymer may serve the function of an additional optional component. For example, polyethylene oxide, such as, Polyox by Dow Chemical having a molecular weight of about 200,000 daltons, can serve as a high molecular weight water soluble polymer and a plasticizer, as discussed below.
[0030] The molecular weights of the water soluble polymers can be determined as described in Keary, "Characterization of METHOCEL Cellulose Ethers by Aqueous SEC with Multiple Detectors," Carbohydrate Polymers Vol. 45, pp. 293-303 (2001), which is incorporated herein by reference.
[0031] Various other polymers can be selected by one of ordinary skill in the art given the teachings herein, so long as the polymer is water soluble, and preferably includes a sufficient amount of a high molecular weight component to impart adequate film strength, and a sufficient amount of a low molecular weight component to facilitate the desired film property of rapid disintegration profile. Various concentrations of each polymer may be utilized. Such concentrations will typically be in the range of about 2% to about 35% based on the total weight of the dry film. In one embodiment, the concentration for the high molecular weight polymer is about 5% to 10% and the concentration of the low molecular weight polymer is about 5% to 10% of the dry film. [0032] According to another exemplary embodiment of the invention, the water soluble low molecular weight component need not be a water soluble polymer. Instead, the low molecular weight component may be a low molecular weight monomer or a combination of various low molecular weight monomers. The low molecular weight component can also serve the function of an additional optional component. For example, the low molecular weight component can also serve as the reagent, a glucose component, a plasticizer, starch, thickener, buffer, stabilizer, and/or additive, and may include any of the specific compounds listed below or other suitable compounds, which are water soluble and have a molecular weight less than about 60,000 daltons. The low molecular weight component serves to promote rapid disintegration, but is present in an amount such that film strength is adequate for processing and dispensing. Various concentrations of the low molecular weight component can be utilized. Such concentrations will typically be in the range of about 2% to about 80% or more based on the total weight of the dry film. In one embodiment, the concentration for the high molecular weight polymer is about 5% to 10% and the concentration of the low molecular weight component is about 30% to 80% of the dry film.
[0033] The amounts of high and low molecular weight components can be adjusted to achieve a desired disintegration profile for the film. When slower disintegration is desired, the concentration of the high molecular weight component can be increased relative to the concentration of the low molecular weight component. When faster disintegration is desired, the concentration of the low molecular weight component can be increased relative to the concentration of the high molecular weight component. Additionally, the thickness of the film can be adjusted to achieve a desired disintegration profile. To increase the disintegration time, the film thickness is increased. Adequate film strength should be maintained to allow for processing of the film. [0034] In addition to a desired disintegration time, the films according to the invention have adequate strength for processing, packaging, and administration without physical failure (e.g., breakage, fracture, or otherwise) during processing and normal handling prior to packaging and use in a desired diagnostic device or testing application. The film strength, specifically, film resilience, springiness and burst strength, can be determined using the TA.XT2i Texture Analyzer by Texture Technologies Corp. and the ASTM D3763 "High Speed Puncture Properties of Plastics Using Load and Displacement Sensors" test method. These properties of film strength and rapid disintegration are the result of the unique combination of the components described herein. By "rapid" disintegration, we mean that the reagent is released from the film matrix in less than about minute. Disintegration times can be determined using the test provided by (USP) 24, Disintegration <701>. See United States Pharmacopoeia, 24th ed., Ch. 701, p. 1941 (2000), which is incorporated herein by reference.
[0035] The optional glucose component of thin films according to the invention can be added to promote disintegration of the film upon contact with a disintegrating fluid. Preferably, the glucose component comprises a water soluble polymer or mixture of polymers having D-glucose units. The dextrose equivalent (DE) of the glucose component is preferably within the range of about 10 to about 25, or about 15 to about 20, although various other DE ranges can also be used. The glucose component can be prepared, for example, by the partial hydrolysis of starch to yield D-glucose polymer mixtures. Suitable commercially available glucose components include, for example, maltodextrin, corn syrup solids, sucrose, and dextrose. Maltodextrin having a DE of about 16.5 to 19.5, such as that commercially available from Grain Processing Corp. (GPC) under the trade name "Maltrin M180," is particularly suitable, although various other glucose containing polymers and mixtures can be utilized, including, for example, other grades of "Maltrin," "Lycatab DH" (Roquette Freres), and "Star-Dri" (A.E. Staley). Suitable concentrations as a weight percentage of the dry film composition will typically be in the range of about 2% to 20%, or about 3% to about 15%, although other concentrations also may be used depending on the selection of other components and the desired film properties.
[0036] The optional starch component of films according to the present invention can be added to promote disintegration of the film upon contact with a disintegrating fluid. The starch component can also serve to increase the solids content of the film and add bulk. Preferably, the starch component is a water soluble polysaccharide composition containing amylose and/or amylopectin. Such compositions may be prepared by, for example, modifying natural starches, such as corn, wheat, rice, potato, or tapioca starch, to provide cold water soluble instant starches. Various water soluble compositions of amylose and/or amylopectin polysaccharides can be used. Typically, these can be made by heating a natural starch with steam to modify the natural starch product so that it is cold water soluble.
[0037] The instant starch commercially available from GPC, Muscatine IA, as "Instant Pure Cote B792," (IPC B792) is an exemplary starch component for purposes of the present invention. Other suitable commercially available instant starches include "Polartex Instant 12640," available from Cargill, Inc., and various others may also be utilized. The starch component will typically have an amylose to amylopectin ratio in the range, for example, of about 0 to about 2.5. The starch can be incorporated in the wet film composition in any suitable amount, including, but not limited to, about 2% to 50%, or about 3% to about 35% by weight based on the dry film.
[0038] The disintegratable film compositions of the present invention may also optionally contain a plasticizer or humectant, for example, polyalcohols, sorbitan esters, and citric acid esters, to increase the flexibility of the films. The plasticizers can be added directly to the formulation during manufacture. Suitable compounds include polyethylene glycol (PEG), such as Lutrol E 400, by BASF Pharma; polyethylene oxide, such as Polyox by Dow; polyoxamers, such as Lutrol F by BASF Pharma; polyvinyl alcohol; polyvinyl methyl ether, such as Lutanol by BASF; or mixtures of such polymers; triacetin; glycerin; mannitol; xylitol; and various other polyalcohols and other compounds having plasticizer and/or humectant properties can be satisfactorily employed. Sorbitol and PEG 400 are particularly suitable; although compounds having a higher molecular weight (e.g., Polyox N80) than PEG 400 can be desirable for certain applications, since they are typically less volatile than sorbitol and PEG 400. The optional plasticizer and/or humectant may be present in any suitable range, including, for example about 3% to 30%, 10% to 20%, or 15% to 18% by weight of the dry film.
[0039] Further, thickeners, buffers, stabilizers, additives and/or other components can be added to the film formulations according to the invention to provide a film having desired properties. For example, in some cases it may be desirable to use films that exhibit different disintegration times or disintegrate under different conditions, such as at elevated pH. In such a case, an additional component can be added to the film composition. For example, to configure the film to disintegrate based in part on the pH level of the solublilizing fluid a thickener, such as Carbopol 940 by Noveon, Inc. can be added.
[0040] As noted above, according to one exemplary embodiment, the films according to the invention can contain a filler, which is a dispersed phase or particle. The filler can add bulk to the film; increase the solids portion of the film, which can aid in coating; and/or can cause the films to disintegrate faster upon contact with the disintegrating fluid, i.e., biological sample or other aqueous material suspected of containing an analyte of interest.
[0041] The filler can be a reagent or an optional additional component. The filler can be an optional non-active component. Examples of such components include titanium oxide and microcrystalline cellulose, which is available under the name Avicel, among others. Air or other gasses can also be used as a filler according to the invention. When air is employed as the filler, a surfactant (e.g., sodium lauryl sulfate (SLS), available under the name Stepanol, Polysorbate 80, or Pluracare F87 Pril NF) may be included in the film formulation. The surfactant does not itself serve to significantly increase the rate of disintegration of the films. Instead, the surfactant aids in the processing and formation of the film. Specifically, the surfactant stabilizes the gaseous bubbles as a dispersed phase within a solution to allow the solution to be processed, as described in more detail below, to form the film containing the gas or air as a dispersed phase filler.
[0042] The particular components for a film can be chosen as desired and as are compatible with a particular testing scheme. For example, the optional glucose component would typically be omitted from a film to be employed in a blood glucose testing device.
[0043] The film compositions according to the invention may be prepared by several methods, including, but not limited to, adding the combination of high and low molecular weight water soluble components, the optional starch, and optional glucose ingredients to a. solvent that is capable of dissolving them, such as water or ethanol or a mixture of ethanol and water. Upon forming a homogeneous solution, the reagent and any of the other optional components, such as plasticizers, colorants, and/or other components may be blended into the reagent-containing polymer solution. Alternatively, all of the film components may be added and concurrently blended to form a solution or dispersion. Also, a dry blend can be compounded by a V-blender. The dry blend can be subsequently used to form a solution or dispersion. Additionally, the dry blend can be subjected to a melt extrusion process to form a film upon cooling. It should be understood that no particular sequence of steps is required, except as needed to effectively prepare a desired film composition. For example, if a particular sequence yields an undesirable precipitate, an alternative sequence may be used.
[0044] The reagent may be soluble in the solution or it may be suspended or dispersed in the solution. Any reagent or combination of reagents suitable for a particular diagnostic test can be used. Suitable reagents for particular diagnostic tests are known in the art and continue to be discovered or created. Examples of reagents include, but are not limited to, proteins, enzymes, antibodies, substances that display magnetic properties, iron oxide, and other compounds or combinations of compounds which display a physical change, such as a color change upon exposure to a particular substance or magnetic field.
[0045] The reagent-containing solution or dispersion may be further processed into a film by any one of many casting, drawing, or extruding techniques. For example, the solution or dispersion may be sprayed onto a support such as a release-treated belt. Alternatively, for example, the solution or dispersion may be roll coated onto a release treated paper or film substrate.
[0046] After coating of the solution or dispersion onto a support surface, the solvent may be removed by radiant energy (such as infra-red), heat, convection, vacuum, or any combination of these to yield a dry film containing one or more reagents. The resulting dry film can be wound up into a roll for storage prior to further processing into individual films for specific diagnostic devices. Whether stored for future processing or immediately following removal of the solvent, the resulting film can be removed from the support surface and subsequently processed for various end use applications.
[0047] The dry film can be further processed by any suitable technique, including, for example, by die-cutting or cutting across the width of a singular narrow roll to prepare segments of any desired geometric size or shape. The segments may be subsequently packaged and/or further processed and incorporated into a testing device. When a film is incorporated into a device in place of a test strip manufactured by conventional processes, the efficiency of the manufacturing process can be improved. Specifically, the continuing processing of rolls of reagent containing film, die cutting, and reagent placement can be less wasteful than conventional spraying, coating, or striping processes. Additional ingredients can be applied to the dried film by, for example, printing, spraying, dusting, or vapor adsorption processes, among others.
[0048] A testing device 1 including a disintegratable film 10 according to an exemplary embodiment of the invention is shown in FIG. 1. The disintegratable film 10 is used to create a fluid channel upon application of a disintegrating fluid (not shown), such as blood, saliva, or urine. The film 10 can be die cut from a roll to create a fluidic pathway pattern. The film pattern can be sandwiched between adjacent layers such as adhesive coatings 12. The adhesive coatings 12, can be, for example, Adhesives Research, Inc s ARcare 8890, ARcare 7840, or ARcare 7841, which are double faced adhesive constructions used in forming fluidic channels for testing devices. Although the testing device 1 includes a single disintegratable film 10 according to the invention, the testing device 1 could instead include more than one film 10. Alternatively, a fluid channel can be created using, for example, a screen printed or jet printed high coat weight ink. [0049] According to another embodiment of the invention, a disintegratable film 20 can be used to protect and isolate a reactive layer 23 or reagent in a diagnostic testing device 2, as shown in FIG. 2. The reactive layer 23 containing one or more reagents and the film 20 are within a fluid channel 27 and are supported by a support structure 25. The fluid channel 27 may or may not be covered by a cover 28. The cover 28 is preferably a transparent cover, and can be, for example an adhesive material heat bonded to the support structure 25.
[0050] According to the embodiment shown in FIG. 2, the reactive layer 23 is a disintegratable film according to the invention. Instead, the reactive layer 23 can be a conventional reactive layer. The reactive layer 23 is isolated by the film 20 until the film is disintegrated by a disintegrating fluid (not shown). In such case, the film 20 need not include a reagent. The film 20 is configured to act as a barrier to the reactive layer 23. Upon application of a disintegrating fluid, such as saliva, blood or urine, to the fluid channel 27, the barrier film 20 disintegrates allowing an analyte (not shown) contained in the fluid to encounter the reactive layer 23. Thereby, the interaction between reactive components in the testing device 2 can be controlled by choice of disintegration time and/or conditions (e.g., pH, temperature, ionic strength, among others).
[0051] The devices of FIGS. 1 and 2 are exemplary only, and the films according to the invention can be included in other testing devices, such as electronic devices, biosensors, various lateral flow devices, and test cards, among others. The films may also be packaged and provided as part of a test kit.
[0052] The following illustrative examples provide a number of specific formulations within the scope of the present invention. These examples are by way of illustration only and are not intended to be limiting in any way. Various alternative components, concentrations, and optional excipients (plasticizers, humectants, fillers, preservatives, etc.) may be utilized given the teachings herein to yield thin films of suitable film strength and disintegration profile.
[0053] Specific embodiments of the invention are illustrated in the examples below. The examples are not meant to be limiting. Accordingly, additional formulations according to the invention can be made according to the teachings herein. The concentrations of the excipients are expressed as approximate parts per 100.
[0054] Examples 1-3 illustrate films suitable for use in pregnancy testing in humans. As is known in the art, pregnancy testing is conducted by detecting human chorionic gonadotropin (hCG) in, for example, a urine or blood sample. Such tests are described in US Patent Nos. 6,403,298; 5,712,172; and 4,496,654; which are incorporated herein by reference. The reagents listed in examples 1-3, specifically, the organic salt, organic base, inorganic base, organic acid, and protein, can be those known in the art which are suitable to permit the detection of hCG in a sample, such as those disclosed in US Patent 4,496,654 and 5,712,172. Further, each of the reagents may be a combination of individual ingredients. For example, the protein may be a combination of antibodies.
[0055] Example 1 is a composition for films suitable for use in an hCG test strip according to an exemplary embodiment of the invention. The films of example 1 can be used together in a single test strip. The first film contains two reagents, an organic acid and an inorganic base, and the second film contains two reagents, an organic salt and an organic amine. The films each include a common base solution.
Figure imgf000020_0001
Example 1
Film 1: Buffer com onent
Figure imgf000020_0002
[0056] Examples 2 and 3 illustrate the composition for a single film suitable for use in an hCG test strip according to additional exemplary embodiments of the invention. The films of examples 2 and 3 each include four reagents.
Example 2
Figure imgf000021_0001
Example 3
Figure imgf000021_0002
[0057] Examples 4 and 5 illustrate film compositions including iron oxide according to additional exemplary embodiments of the invention.
Example 4
Figure imgf000022_0001
[0058] Methocel E5, Methocel E50, Maltrin M180 and Pure-Cote are added to boiling water with constant stirring. The mixture is cooled to about room temperature under agitation to allow the components to solubilize. The iron oxide is mixed with triacetin, polysorbate 80 and ethanol until the iron oxide is wetted out. The aqueous solution is added to the iron oxide mixture and stirred to form a homogeneous mixture. The mixture is deairated prior to coating onto a release liner. The coating is dried at about 120 degrees C for about 5 minutes.
Example 5
Figure imgf000022_0002
[0059] Examples 6-9 are prophetic examples, which illustrate exemplary film formulations according to the invention. The reagent component(s) is not listed as being a specific reagent. Any suitable reagent can be used. The films of examples 6-9 contain substantially no surfactants.
Example 6
Figure imgf000023_0001
Example 7
Figure imgf000023_0002
Example 8
Figure imgf000024_0001
Example 9
Figure imgf000024_0002
[0060] The examples above illustrate disintegratable film formulations that disintegrate in biological fluids, such as saliva, urine or blood. The above examples are not meant to be limiting. Accordingly, many additional film compositions are possible within the scope of the invention, as defined by the appended claims and equivalents thereof.
[0061] The above description is only illustrative of preferred embodiments which achieve the objects, features and advantages of the present invention. It is not intended that the present invention be limited to the illustrated embodiments. Any modification of the present invention which comes with the spirit and scope of the following claims is considered part of the present invention.

Claims

CLAIMS What is claimed as new and desired to be protected by Letters Patent of the United States is:
1. A disintegratable film for a diagnostic device comprising: a first water soluble component having a molecular weight less than about 60,000 daltons; a second water soluble component having a molecular weight greater than about 60,000 daltons; and at least one reagent, wherein the film is in the form of a monolayer of a thickness sufficient to disintegrate upon contact with an aqueous fluid to release the reagent.
2. The film of claim 1 wherein the first and second water soluble components are water soluble polymers.
3. The film of claim 1 wherein at least one of the water soluble components comprises a cellulose derivative polymer.
4. The film of claim 1 wherein the concentration of the first and second water soluble components present in the film is about 2% to 80% of the weight of the film.
5. The film of claim 1 wherein the second water soluble component has a molecular weight of about 60,000 to about 500,000 daltons.
6. The film of claim 1 wherein at least one of the first and second water soluble components comprises hydroxypropyl cellulose.
7. The film of claim 1 wherein at least one of the first and second water soluble components comprises hydroxypropyl methylcellulose.
8. The film of claim 1 wherein at least one of the first and second water soluble components comprises a mixture of different polymers.
9. The film of claim 1 wherein the film disintegrates in less than about 60 seconds after contact with an aqueous fluid.
10. The film of clai 1 wherein the film has a thickness of about 0.4 to about 10 mil.
11. The film of claim 1 wherein the film is part of a multilayer device.
12. The film of claim 1 wherein the at least one reagent displays magnetic properties.
13. The film of claim 1 wherein the at least one reagent reacts with chorionic gonadotropin.
14. The film of claim 1 wherein the film is essentially free of surfactants.
15. The film of claim 1 wherein the first and second water soluble components comprise first and second polymers, respectively.
16. The film of claim 15 further comprising a third water soluble polymer.
17. The film of claim 15 wherein the second water soluble polymer comprises cellulose derivative polymers having a molecular weight in the range of about 60,000 to about 500,000 daltons, and wherein the first water soluble polymer comprises cellulose derivative polymers having a molecular weight of about 5,000 to about 60,000 daltons.
18. The film of claim 15 wherein the concentration of the first water soluble polymer is about 2% to 10% of the weight of the film and wherein the concentration of the second water soluble polymer is about 2% to 10% of the weight of the film.
19. The film of claim 1 further comprising a starch component.
20. The film of claim 19 wherein the concentration of the starch component is about 2% to 50% of the weight of the film.
21. The film of claim 19 wherein the starch component comprises instant starch.
22. The film of claim 1 further comprising a glucose component.
23. The film of claim 22 wherein the concentration of the glucose component is about 2% to 20% of the weight of the film.
24. The film of claim 22 wherein the glucose component comprises maltodextrin.
25. The film of claim 1 further comprising a plasticizer and/or humectant.
26. The film of claim 25 wherein the concentration of the plasticizer and/or humectant is about 3% to 30% of the weight of the film.
27. The film of claim 25 wherein the plasticizer comprises triacetin.
28. The film of claim 1 further comprising a filler.
29. The film of claim 28 wherein the filler is a dispersed particle.
30. The film of claim 28 wherein the filler is a dispersed phase.
31. A method of performing a diagnostic test using the composition of claim 1 wherein the composition is placed in contact with a sample for a sufficient period of time to disintegrate the film and release the at least one reagent.
32. A testing device comprising: a support structure; and at least one disintegratable film supported by the support structure, the disintegratable film comprising: a first water soluble polymer having a molecular weight from about 5,000 daltons to about 60,000 daltons; a second water soluble polymer having a molecular weight greater than about 60,000 daltons; and at least one reagent, wherein the film is capable of disintegrating upon contact with a disintegrating fluid.
33. The testing device of claim 32 wherein the at least one reagent displays magnetic properties.
34. The testing device of claim 32 further comprising a reagent for detecting the presence of human chorionic gonadotropin in the disintegrating fluid.
35. The testing device of claim 32 further comprising a plurality of films.
36. The testing device of claim 32 wherein the at least one reagent is within the film.
37. The testing device of claim 32 wherein the film is configured within the device to isolate the at least one reagent.
38. The testing device of claim 32 wherein the film is configured to disintegrate based in part on the pH of the disintegrating fluid.
39. The testing device of claim 32, wherein the device is a lateral flow device.
40. The testing device of claim 32, wherein the support structure is an adhesive coating.
41. A method of performing a diagnostic test using the testing device of claim 31 wherein a sample is placed in contact with the at least one disintegratable film for a sufficient period of time to disintegrate and release the one or more reagents.
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011012848A1 (en) 2009-07-27 2011-02-03 Suresensors Ltd Improvements relating to sensor devices
EP2316438A1 (en) 2009-10-30 2011-05-04 Johnson & Johnson GmbH Tape , in particular adhesive tape, for the treatment of skin disorders comprising at least one hyperkeratosis inhibitor and/or at least one keratinolytic agent
EP2316436A1 (en) 2009-10-30 2011-05-04 Johnson & Johnson GmbH Tape, in particular adhesive tape, for the treatment of skin disorders comprising a film , in particular dissolvable film, containing at least one enzyme
US8835157B2 (en) 2007-04-25 2014-09-16 3M Innovative Properties Company Supported reagents, methods, and devices
US9267167B2 (en) 2004-06-28 2016-02-23 Becton, Dickinson And Company Dissolvable films and methods including the same
US10932952B2 (en) 2015-11-11 2021-03-02 Biovotec As Dry biocompatible disintegratable films for delivering particulate egg shell membrane to a wound
WO2021082899A1 (en) * 2019-10-30 2021-05-06 烟台芥子生物技术有限公司 Dry immunoturbidimetric reagent, and preparation method and application thereof
US11045578B2 (en) 2015-06-24 2021-06-29 Biovotec As Tissue engineering scaffolds comprising particulate egg shell membrane
US20220323587A1 (en) * 2016-11-02 2022-10-13 Board Of Regents, The University Of Texas System Dissolvable films and methods of their use
US11992508B2 (en) 2014-10-28 2024-05-28 Biovotec As Micronized eggshell membrane particles and the use thereof to promote the healing of wounds

Families Citing this family (184)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11207805B2 (en) 2001-10-12 2021-12-28 Aquestive Therapeutics, Inc. Process for manufacturing a resulting pharmaceutical film
US20060039958A1 (en) * 2003-05-28 2006-02-23 Monosolrx, Llc. Multi-layer films having uniform content
US10285910B2 (en) 2001-10-12 2019-05-14 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
US8663687B2 (en) * 2001-10-12 2014-03-04 Monosol Rx, Llc Film compositions for delivery of actives
US20190328679A1 (en) 2001-10-12 2019-10-31 Aquestive Therapeutics, Inc. Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US20110033542A1 (en) 2009-08-07 2011-02-10 Monosol Rx, Llc Sublingual and buccal film compositions
US20070281003A1 (en) 2001-10-12 2007-12-06 Fuisz Richard C Polymer-Based Films and Drug Delivery Systems Made Therefrom
US7357891B2 (en) 2001-10-12 2008-04-15 Monosol Rx, Llc Process for making an ingestible film
US7666337B2 (en) * 2002-04-11 2010-02-23 Monosol Rx, Llc Polyethylene oxide-based films and drug delivery systems made therefrom
US8900498B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for manufacturing a resulting multi-layer pharmaceutical film
US8900497B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for making a film having a substantially uniform distribution of components
US8765167B2 (en) 2001-10-12 2014-07-01 Monosol Rx, Llc Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US7425292B2 (en) * 2001-10-12 2008-09-16 Monosol Rx, Llc Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
US8603514B2 (en) 2002-04-11 2013-12-10 Monosol Rx, Llc Uniform films for rapid dissolve dosage form incorporating taste-masking compositions
US8017150B2 (en) * 2002-04-11 2011-09-13 Monosol Rx, Llc Polyethylene oxide-based films and drug delivery systems made therefrom
CN102188409A (en) * 2002-07-22 2011-09-21 莫诺索尔克斯有限公司 Packaging and dispensing of rapid dissolve dosage form
US9248146B2 (en) * 2003-10-24 2016-02-02 Adhesives Research, Inc. Dissolvable adhesive films for delivery of pharmaceutical or cosmetic agents
EP1680079A4 (en) * 2003-10-24 2008-01-02 Adhesives Res Inc Rapidly disintegrating films for delivery of pharmaceutical or cosmetic agents
ITMI20032087A1 (en) 2003-10-27 2005-04-28 Pharmafilm S R L SELF-SUPPORTING FILMS FOR PHARMACEUTICAL AND FOOD USE.
CN101146595B (en) 2005-01-28 2012-07-04 杜克大学 Apparatuses and methods for manipulating droplets on a printed circuit board
KR101431775B1 (en) 2005-05-11 2014-08-20 듀크 유니버서티 Method and device for conducting biochemical or chemical reactions at multiple temperatures
DE102005033943A1 (en) * 2005-07-20 2007-02-22 Hexal Ag Non-spitting, oral, fast-disintegrating film for a neuroleptic
DE102005058569B4 (en) * 2005-12-08 2010-07-15 Lts Lohmann Therapie-Systeme Ag Foam wafer with polyvinyl alcohol-polyethylene glycol graft copolymer
CA2631431A1 (en) * 2005-12-27 2007-07-05 Monosol Rx, Llc Ph modulated films for delivery of actives
US20070192182A1 (en) * 2006-02-10 2007-08-16 Tovin Monaco Method of delivering coupons using customer data
US20070192438A1 (en) * 2006-02-10 2007-08-16 Esmond Goei System and method for on-demand delivery of media products
US20070192183A1 (en) * 2006-02-10 2007-08-16 Tovin Monaco System and architecture for providing retail buying options to consumer using customer data
US20070190013A1 (en) * 2006-02-13 2007-08-16 Yeli Zhang Film and film-forming compositions
US8986735B2 (en) * 2006-03-16 2015-03-24 Novartis Ag Solid dosage form containing a taste masked active agent
US20140193807A1 (en) 2006-04-18 2014-07-10 Advanced Liquid Logic, Inc. Bead manipulation techniques
US9476856B2 (en) 2006-04-13 2016-10-25 Advanced Liquid Logic, Inc. Droplet-based affinity assays
US8389297B2 (en) 2006-04-18 2013-03-05 Duke University Droplet-based affinity assay device and system
WO2007123908A2 (en) 2006-04-18 2007-11-01 Advanced Liquid Logic, Inc. Droplet-based multiwell operations
US8809068B2 (en) 2006-04-18 2014-08-19 Advanced Liquid Logic, Inc. Manipulation of beads in droplets and methods for manipulating droplets
US8927296B2 (en) * 2006-04-18 2015-01-06 Advanced Liquid Logic, Inc. Method of reducing liquid volume surrounding beads
US8716015B2 (en) 2006-04-18 2014-05-06 Advanced Liquid Logic, Inc. Manipulation of cells on a droplet actuator
US7901947B2 (en) 2006-04-18 2011-03-08 Advanced Liquid Logic, Inc. Droplet-based particle sorting
US10078078B2 (en) 2006-04-18 2018-09-18 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
US7439014B2 (en) 2006-04-18 2008-10-21 Advanced Liquid Logic, Inc. Droplet-based surface modification and washing
US8658111B2 (en) 2006-04-18 2014-02-25 Advanced Liquid Logic, Inc. Droplet actuators, modified fluids and methods
US8980198B2 (en) * 2006-04-18 2015-03-17 Advanced Liquid Logic, Inc. Filler fluids for droplet operations
US8637324B2 (en) 2006-04-18 2014-01-28 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
WO2009111769A2 (en) 2008-03-07 2009-09-11 Advanced Liquid Logic, Inc. Reagent and sample preparation and loading on a fluidic device
EP1867321A3 (en) * 2006-06-07 2008-11-19 Familplan Consulting Ltd. A pharmaceutical product adapted for oral transmucosal administration comprising a pharmaceutical agent
AU2013242845B2 (en) * 2006-06-20 2015-09-03 Izun Pharmaceuticals Corporation Anti-inflammatory dissolvable film
US8021696B2 (en) 2006-06-20 2011-09-20 Izun Pharmaceuticals Corporation Anti-inflammatory dissolvable film
AU2008206362A1 (en) * 2007-01-12 2008-07-24 Monosol Rx Llc High dose film compositions and methods of preparation
WO2008091848A2 (en) * 2007-01-22 2008-07-31 Advanced Liquid Logic, Inc. Surface assisted fluid loading and droplet dispensing
DK2111554T3 (en) 2007-02-09 2013-07-22 Advanced Liquid Logic Inc Drop actuator devices and methods for using magnetic grains
EP2109774B1 (en) 2007-02-15 2018-07-04 Advanced Liquid Logic, Inc. Capacitance detection in a droplet actuator
US8440392B2 (en) 2007-03-22 2013-05-14 Advanced Liquid Logic Inc. Method of conducting a droplet based enzymatic assay
CA2719549A1 (en) * 2007-04-10 2008-10-16 Advanced Liquid Logic, Inc. Droplet dispensing device and methods
US20080292683A1 (en) * 2007-05-24 2008-11-27 Monosolrx, Llc. Film shreds and delivery system incorporating same
US8951732B2 (en) 2007-06-22 2015-02-10 Advanced Liquid Logic, Inc. Droplet-based nucleic acid amplification in a temperature gradient
BRPI0811707A2 (en) * 2007-06-29 2014-09-30 Union Carbide Chem Plastic Dissolvable Film for Personal Care
JP2010532377A (en) * 2007-06-29 2010-10-07 ユニオン カーバイド ケミカルズ アンド プラスティックス テクノロジー エルエルシー Personal care dissolvable film
BRPI0815698A2 (en) * 2007-08-24 2017-06-13 Advanced Liquid Logic Inc bead manipulation in a droplet actuator.
WO2009028252A1 (en) * 2007-08-28 2009-03-05 Konica Minolta Opto, Inc. Cellulose ester film
WO2009032863A2 (en) 2007-09-04 2009-03-12 Advanced Liquid Logic, Inc. Droplet actuator with improved top substrate
FR2921835B1 (en) * 2007-10-05 2012-05-04 Soc Dexploitation De Produits Pour Les Industries Chimiques Seppic COATING COMPOSITION COMPRISING POLYDEXTROSE, PROCESS FOR PREPARING THE SAME, AND USE FOR COATING INFRINGABLE SOLID FORMS
US8460528B2 (en) * 2007-10-17 2013-06-11 Advanced Liquid Logic Inc. Reagent storage and reconstitution for a droplet actuator
WO2009052123A2 (en) * 2007-10-17 2009-04-23 Advanced Liquid Logic, Inc. Multiplexed detection schemes for a droplet actuator
WO2009052321A2 (en) * 2007-10-18 2009-04-23 Advanced Liquid Logic, Inc. Droplet actuators, systems and methods
US8298583B2 (en) 2007-10-19 2012-10-30 Monosol Rx, Llc Film delivery system for tetrahydrolipstatin
EP2232535A4 (en) * 2007-12-10 2016-04-13 Advanced Liquid Logic Inc Droplet actuator configurations and methods
AU2008345138B2 (en) * 2007-12-23 2014-05-29 Advanced Liquid Logic, Inc. Droplet actuator configurations and methods of conducting droplet operations
WO2009137415A2 (en) 2008-05-03 2009-11-12 Advanced Liquid Logic, Inc. Reagent and sample preparation, loading, and storage
EP2687846B1 (en) * 2008-06-13 2016-10-12 Alt Bioscience, Llc. Device for rapid determination of disease-associated thiol compounds
US20110189259A1 (en) * 2008-06-23 2011-08-04 Biodelivery Sciences International, Inc. Multidirectional mucosal delivery devices and methods of use
US20100040727A1 (en) * 2008-08-18 2010-02-18 Monosol Rx, Llc Method for Improving Uniformity of Content in Edible Film Manufacturing
US8282954B2 (en) * 2008-12-15 2012-10-09 Monosol Rx, Llc Method for manufacturing edible film
JP2010158173A (en) * 2009-01-06 2010-07-22 Lintec Corp Edible film, edible film composition, and method for producing edible film laminated body
US8877512B2 (en) 2009-01-23 2014-11-04 Advanced Liquid Logic, Inc. Bubble formation techniques using physical or chemical features to retain a gas bubble within a droplet actuator
WO2010086989A1 (en) 2009-01-29 2010-08-05 日東電工株式会社 Intraoral film-shaped base and preparation
JP5379499B2 (en) * 2009-01-29 2013-12-25 リンテック株式会社 Swallow package and edible film assembly
JP5674480B2 (en) * 2009-01-29 2015-02-25 日東電工株式会社 Intraoral film-form base and preparation
US20100285130A1 (en) * 2009-05-06 2010-11-11 Monosol Rx, Llc Coating of complexed actives in film formulations
US20100297232A1 (en) * 2009-05-19 2010-11-25 Monosol Rx, Llc Ondansetron film compositions
TWI396554B (en) * 2009-05-26 2013-05-21 Colgate Palmolive Co Oral care formulations that enhance amount of soluble zinc
JP5497358B2 (en) * 2009-07-28 2014-05-21 リンテック株式会社 Edible laminated film and method for producing the same
US8475832B2 (en) 2009-08-07 2013-07-02 Rb Pharmaceuticals Limited Sublingual and buccal film compositions
US8926065B2 (en) 2009-08-14 2015-01-06 Advanced Liquid Logic, Inc. Droplet actuator devices and methods
US8846414B2 (en) 2009-09-29 2014-09-30 Advanced Liquid Logic, Inc. Detection of cardiac markers on a droplet actuator
MY150626A (en) 2009-10-30 2014-02-07 Ix Biopharma Ltd Fast dissolving solid dosage form
WO2011057197A2 (en) 2009-11-06 2011-05-12 Advanced Liquid Logic, Inc. Integrated droplet actuator for gel electrophoresis and molecular analysis
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
WO2011072208A1 (en) * 2009-12-10 2011-06-16 Monosol Rx, Llc Ph sensitive compounds in taste masking within oral thin film strips
EP2516669B1 (en) 2009-12-21 2016-10-12 Advanced Liquid Logic, Inc. Enzyme assays on a droplet actuator
US20110160264A1 (en) * 2009-12-28 2011-06-30 Monosol Rx, Llc Orally administrable film dosage forms containing ondansetron
JP5588688B2 (en) * 2010-01-28 2014-09-10 日東電工株式会社 Film-form preparation
TWI435733B (en) 2010-01-29 2014-05-01 Colgate Palmolive Co Oral care formulations for malodor control
HUE027972T2 (en) 2010-02-25 2016-11-28 Advanced Liquid Logic Inc Method of making nucleic acid libraries
JP5751868B2 (en) * 2010-03-30 2015-07-22 日東電工株式会社 Film-form preparation and method for producing the same
EP2553473A4 (en) 2010-03-30 2016-08-10 Advanced Liquid Logic Inc Droplet operations platform
EP3524259B1 (en) * 2010-04-30 2021-10-13 Allovate, LLC Oral strip for allergic desensitization via the vestibular mucosal surface
EP2588322B1 (en) 2010-06-30 2015-06-17 Advanced Liquid Logic, Inc. Droplet actuator assemblies and methods of making same
GB201014041D0 (en) 2010-08-23 2010-10-06 Biofilm Ltd Soluble film
US9149959B2 (en) 2010-10-22 2015-10-06 Monosol Rx, Llc Manufacturing of small film strips
EA031156B1 (en) 2010-12-16 2018-11-30 Суновион Фармасьютикалз Инк. Sublingual films
US11357722B2 (en) 2011-02-04 2022-06-14 Seed Health, Inc. Method and system for preventing sore throat in humans
US11844720B2 (en) 2011-02-04 2023-12-19 Seed Health, Inc. Method and system to reduce the likelihood of dental caries and halitosis
US10085938B2 (en) 2011-02-04 2018-10-02 Joseph E. Kovarik Method and system for preventing sore throat in humans
US11951139B2 (en) 2015-11-30 2024-04-09 Seed Health, Inc. Method and system for reducing the likelihood of osteoporosis
US11951140B2 (en) 2011-02-04 2024-04-09 Seed Health, Inc. Modulation of an individual's gut microbiome to address osteoporosis and bone disease
US11998479B2 (en) 2011-02-04 2024-06-04 Seed Health, Inc. Method and system for addressing adverse effects on the oral microbiome and restoring gingival health caused by sodium lauryl sulphate exposure
US9423398B2 (en) * 2011-02-08 2016-08-23 The Board Of Regents For Oklahoma State University Apparatus and method for biologic sample rapid collection and recovery device, and convenient storage
CA2834212C (en) 2011-04-29 2019-05-14 Massachusetts Institute Of Technology Layer processing for pharmaceuticals
EP2711079B1 (en) 2011-05-09 2018-12-19 Advanced Liquid Logic, Inc. Microfluidic Feedback Using Impedance Detection
AU2012253595B2 (en) 2011-05-10 2016-10-20 Advanced Liquid Logic, Inc. Enzyme concentration and assays
US8901043B2 (en) 2011-07-06 2014-12-02 Advanced Liquid Logic, Inc. Systems for and methods of hybrid pyrosequencing
CN103733059B (en) 2011-07-06 2016-04-06 先进流体逻辑公司 Reagent on droplet actuator stores
US9513253B2 (en) 2011-07-11 2016-12-06 Advanced Liquid Logic, Inc. Droplet actuators and techniques for droplet-based enzymatic assays
WO2013016413A2 (en) 2011-07-25 2013-01-31 Advanced Liquid Logic Inc Droplet actuator apparatus and system
WO2013048779A1 (en) * 2011-09-29 2013-04-04 Rohm And Haas Chemicals Llc Personal care composition and methods incorporating low gelation temperature methylcellulose
US10731199B2 (en) 2011-11-21 2020-08-04 Advanced Liquid Logic, Inc. Glucose-6-phosphate dehydrogenase assays
JP5841433B2 (en) 2012-01-11 2016-01-13 日東電工株式会社 Intraoral film-form base and preparation
FR2990349B1 (en) 2012-05-11 2014-08-08 Pf Medicament FAST DISINTEGRATING MONOLAYER FILM AND ITS USE IN ORAL HYGIENE
US9223317B2 (en) 2012-06-14 2015-12-29 Advanced Liquid Logic, Inc. Droplet actuators that include molecular barrier coatings
WO2014004908A1 (en) 2012-06-27 2014-01-03 Advanced Liquid Logic Inc. Techniques and droplet actuator designs for reducing bubble formation
CA2878680C (en) 2012-07-23 2019-09-17 Crayola, Llc Dissolvable films and methods of using the same
US9863913B2 (en) 2012-10-15 2018-01-09 Advanced Liquid Logic, Inc. Digital microfluidics cartridge and system for operating a flow cell
CA2890757C (en) 2012-11-14 2021-10-26 Smith & Nephew, Inc. Stable thermolysin hydrogel
US9545376B2 (en) 2013-01-23 2017-01-17 Arx, Llc Production of unit dose constructs
FR3003168A1 (en) * 2013-03-14 2014-09-19 Urgo Lab FILMOGENE COMPOSITION AND USE THEREOF FOR THE TREATMENT OF SKIN CONDITIONS
CN105188891B (en) * 2013-03-14 2017-11-24 陶氏环球技术有限责任公司 Include the composite polyamide membranes of soluble polymer coating
US20140271787A1 (en) * 2013-03-15 2014-09-18 Monosol Rx, Llc Continuous single layer film structure including discrete domains
US11452698B2 (en) 2013-03-15 2022-09-27 Smith & Nephew, Inc. Dissolvable gel-forming film for delivery of active agents
TW201507726A (en) * 2013-05-10 2015-03-01 Glaxosmithkline Llc Nicotine lozenge formulation
JP6482552B2 (en) * 2013-07-31 2019-03-13 インテルジェンクス・コーポレイションＩｎｔｅｌＧｅｎｘ Ｃｏｒｐ． Oral film dosage form that is immediately wettable without surfactants and polyhydric alcohols
CN105408728B (en) 2013-08-13 2020-09-11 先进流体逻辑公司 Method for improving accuracy and precision of drop metering using an on-actuator reservoir as a fluid input
US20160199832A1 (en) 2013-08-30 2016-07-14 Advanced Liquid Logic France Sas Manipulation of droplets on hydrophilic or variegated-hydrophilic surfaces
US11969445B2 (en) 2013-12-20 2024-04-30 Seed Health, Inc. Probiotic composition and method for controlling excess weight, obesity, NAFLD and NASH
US11833177B2 (en) 2013-12-20 2023-12-05 Seed Health, Inc. Probiotic to enhance an individual's skin microbiome
US11998574B2 (en) 2013-12-20 2024-06-04 Seed Health, Inc. Method and system for modulating an individual's skin microbiome
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
US12005085B2 (en) 2013-12-20 2024-06-11 Seed Health, Inc. Probiotic method and composition for maintaining a healthy vaginal microbiome
US11980643B2 (en) 2013-12-20 2024-05-14 Seed Health, Inc. Method and system to modify an individual's gut-brain axis to provide neurocognitive protection
SG10201912516SA (en) 2014-04-29 2020-02-27 Illumina Inc Multiplexed single cell gene expression analysis using template switch and tagmentation
WO2015179461A1 (en) 2014-05-20 2015-11-26 Massachusetts Institute Of Technology Plasticity induced bonding
NZ727834A (en) * 2014-06-24 2020-08-28 Taho Pharmaceuticals Ltd Fast acting orally disintegrating film
JP6668336B2 (en) 2014-10-09 2020-03-18 イラミーナ インコーポレーテッド Method and apparatus for separating immiscible liquids and effectively isolating at least one liquid
DE102014119576A1 (en) 2014-12-23 2016-06-23 Ernst-Moritz-Arndt-Universität Greifswald Pharmaceutical form for administration to mucous membranes
KR101598752B1 (en) * 2015-01-28 2016-02-29 순천향대학교 산학협력단 Liposome formulations using surface area and porosity-modified sugar alcohol as a carrier and preparation methods thereof
RU2717491C2 (en) 2015-02-10 2020-03-23 Иллюмина, Инк. Method and composition for analyzing cellular components
WO2016154038A1 (en) 2015-03-20 2016-09-29 Illumina, Inc. Fluidics cartridge for use in the vertical or substantially vertical position
WO2016168224A1 (en) 2015-04-14 2016-10-20 The Procter & Gamble Company Solid conditioning composition
JP7211706B2 (en) * 2015-04-21 2023-01-24 サノヴィオン ファーマシュティカルズ インコーポレーテッド Method for treating Parkinson's disease by administering apomorphine to oral mucosa
GB2556713B (en) 2015-07-06 2021-06-23 Illumina Inc Balanced AC modulation for driving droplet operations electrodes
JP7220511B2 (en) * 2015-07-09 2023-02-10 モノソル リミテッド ライアビリティ カンパニー Food and its preparation method
US11480566B2 (en) * 2015-08-06 2022-10-25 Lia Diagnostics, Inc. Water dispersible assays
CN115369155A (en) 2015-08-14 2022-11-22 亿明达股份有限公司 System and method for determining genetic characteristics using magnetically responsive sensors
CN108350497B (en) 2015-08-28 2022-07-19 Illumina公司 Single cell nucleic acid sequence analysis
CN107921432A (en) 2015-09-02 2018-04-17 伊卢米纳剑桥有限公司 Improve the system and method for the droplet manipulation in flow control system
US10450598B2 (en) 2015-09-11 2019-10-22 Illumina, Inc. Systems and methods for obtaining a droplet having a designated concentration of a substance-of-interest
CN108290157B (en) 2015-10-22 2021-08-17 亿明达股份有限公司 Fill fluid for fluid devices
US10386376B2 (en) * 2015-11-09 2019-08-20 Jeimei, Llc Sample container with integrated test strip
WO2017095845A1 (en) 2015-12-01 2017-06-08 Illumina, Inc. Liquid storage and delivery mechanisms and methods
WO2017176896A1 (en) 2016-04-07 2017-10-12 Illumina, Inc. Methods and systems for construction of normalized nucleic acid libraries
BR112018072539A2 (en) 2016-05-05 2019-03-26 Aquestive Therapeutics, Inc. increased administration epinephrine compositions
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation
AU2017296066B2 (en) 2016-07-15 2022-09-15 Lia Diagnostics, Inc. Temporary hydrophobic matrix material treatments, materials, kits, and methods
US10329519B2 (en) 2016-10-19 2019-06-25 The Procter & Gamble Company Consumer product composition comprising a polyethyleneglycol carrier, silicone conditioner, and particulate spacer material
US20200181678A1 (en) * 2016-12-15 2020-06-11 Merck Sharp & Dohme Corp. Cell-Based Reporter Assay for Live Virus Vaccines
CA3045043A1 (en) 2016-12-31 2018-07-05 Bioxcel Therapeutics, Inc. Use of sublingual dexmedetomidine for the treatment of agitation
EP3565532A4 (en) * 2017-01-04 2020-10-28 Bonayo Lifesciences Private Limited Oral dispersible film composition
US10191044B2 (en) * 2017-01-04 2019-01-29 David R. Hall Flushable test strip
US10258261B2 (en) * 2017-01-06 2019-04-16 David R. Hall System for analyzing customized test strips
EP3565641B1 (en) * 2017-01-09 2021-06-23 The Procter & Gamble Company Barrier patch with soluble film and methods of improving skin appearance
CN209377448U (en) 2017-01-20 2019-09-13 泰普奈克斯医疗有限责任公司 Pumping equipment
WO2018166432A1 (en) * 2017-03-13 2018-09-20 Nano And Advanced Materials Institute Limited High loading and fast disintegration film for fast drug absorption
US10045760B2 (en) * 2017-04-13 2018-08-14 Xibo Wei Sampling device capable of continuously sampling content in a biological conduit and method thereof
FR3080042B1 (en) * 2018-04-17 2020-12-04 Roquette Freres FILM-GENERATING SYSTEM WITH BARRIER EFFECT, ESPECIALLY ANTI-ATMOSPHERIC POLLUTION, OF NATURAL ORIGIN AND USED IN COSMETICS
US10858619B2 (en) 2018-06-08 2020-12-08 The Procter & Gamble Company Water-soluble unit dose articles made from extruded films and containing household care compositions and methods for making the same
EP3813802B1 (en) * 2018-06-27 2024-10-23 Bioxcel Therapeutics, Inc. Film formulations containing dexmedetomidine and methods of producing them
JP7365409B2 (en) 2018-06-28 2023-10-19 エイアールエックス エルエルシー Dispensing method for producing soluble unit dose membrane constructs
US20200172768A1 (en) 2018-12-04 2020-06-04 Adhesives Research, Inc. Disintegrable thin film adhesive barrier
JP7396557B2 (en) * 2019-03-14 2023-12-12 エゾカップ アーゲー Pharmaceutical formulations for application to mucous membranes and methods for their production
KR20220049526A (en) 2019-07-19 2022-04-21 바이오엑셀 테라퓨틱스 인코포레이티드 Non-sedative dexmedetomidine treatment regimen
WO2022051703A1 (en) 2020-09-04 2022-03-10 Baebies, Inc. Microfluidic based assay for unbound bilirubin
CN114432272B (en) * 2020-11-02 2024-05-28 上海现代药物制剂工程研究中心有限公司 Orosity membrane, racecadotril orosity membrane agent and preparation method thereof
WO2022231611A1 (en) * 2021-04-30 2022-11-03 Hewlett-Packard Development Company, L.P. Microfluidic device
US11806334B1 (en) 2023-01-12 2023-11-07 Bioxcel Therapeutics, Inc. Non-sedating dexmedetomidine treatment regimens

Family Cites Families (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4136145A (en) * 1974-07-05 1979-01-23 Schering Aktiengesellschaft Medicament carriers in the form of film having active substance incorporated therein
US3983209A (en) 1975-01-28 1976-09-28 Alza Corporation Method for treating burns
US4029758A (en) * 1975-12-15 1977-06-14 Hoffmann-La Roche Inc. Preparation of pharmaceutical unit dosage forms
US4031200A (en) * 1975-12-15 1977-06-21 Hoffmann-La Roche Inc. Manufacture of pharmaceutical unit dosage forms
US4029757A (en) * 1975-12-15 1977-06-14 Hoffmann-La Roche Inc. Manufacture of pharmaceutical unit dosage forms
US4136415A (en) * 1977-04-29 1979-01-30 Blockburger James E Underwater release mechanism
US4496654A (en) * 1983-04-08 1985-01-29 Quidel Detection of HCG with solid phase support having avidin coating
JPS59193831A (en) * 1983-04-18 1984-11-02 Sankyo Co Ltd Preparation of enteric drug
ES2019275B3 (en) * 1985-10-09 1991-06-16 Desitin Arzneimittel Gmbh METHOD FOR THE PRODUCTION OF A METHOD OF ADMINISTRATION AND DOSAGE FOR REACTIVE DRUGS OR OTHER ACTIVE PRINCIPLES.
JPH0729915B2 (en) * 1986-02-01 1995-04-05 帝國製薬株式会社 Sheet-shaped oral patch
USRE33093E (en) * 1986-06-16 1989-10-17 Johnson & Johnson Consumer Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
US5110556A (en) * 1986-10-28 1992-05-05 Costar Corporation Multi-well test plate
WO1988009824A1 (en) 1987-06-05 1988-12-15 National Diagnostic Products (Australia) Pty. Limi Improvements in diagnostic test strips
DE3826057A1 (en) 1988-07-30 1990-02-01 Boehringer Mannheim Gmbh TEST TESTER FOR THE ANALYTICAL DETERMINATION OF AN INGREDIENT OF A LIQUID SAMPLE
DE3827561C1 (en) * 1988-08-13 1989-12-28 Lts Lohmann Therapie-Systeme Gmbh & Co Kg, 5450 Neuwied, De
EP0373417A1 (en) * 1988-11-30 1990-06-20 Schering Corporation Sustained release diltiazem formulation
US5049395A (en) 1989-03-09 1991-09-17 Micro Vesicular Systems, Inc. Controlled release vehicle
US5698271A (en) * 1989-08-22 1997-12-16 Immunivest Corporation Methods for the manufacture of magnetically responsive particles
JP3046346B2 (en) * 1990-03-12 2000-05-29 昭和電工株式会社 External preparation base or auxiliary agent and human or animal external preparation containing it
DE4018247A1 (en) * 1990-06-07 1991-12-12 Lohmann Therapie Syst Lts MANUFACTURING METHOD FOR QUICK-DISINFITTING FILM-SHAPED PHARMACEUTICAL FORMS
US6007999A (en) * 1991-07-31 1999-12-28 Idexx Laboratories, Inc. Reversible flow chromatographic binding assay
JP3093378B2 (en) * 1991-10-17 2000-10-03 日本合成化学工業株式会社 Method for producing composition containing angiotensin converting enzyme inhibitor
US5393528A (en) * 1992-05-07 1995-02-28 Staab; Robert J. Dissolvable device for contraception or delivery of medication
US5346701A (en) * 1993-02-22 1994-09-13 Theratech, Inc. Transmucosal delivery of macromolecular drugs
CN1134163A (en) * 1993-08-19 1996-10-23 辛勒斯治疗系统公司 Water-soluble pressure-sensitive mucoadhesive and devices provided therewith for emplacement in mucosa-lined body cavity
JPH07191035A (en) * 1993-11-17 1995-07-28 Toppan Printing Co Ltd Physiologically active material-immobilized sheet, its manufacture and preservation, and method for supplying physiologically active material using it
US5712172A (en) * 1995-05-18 1998-01-27 Wyntek Diagnostics, Inc. One step immunochromatographic device and method of use
US5614207A (en) * 1995-06-30 1997-03-25 Mcneil-Ppc, Inc. Dry mouth lozenge
DE19539361A1 (en) * 1995-10-23 1997-04-24 Basf Ag Process for the preparation of multilayer, solid pharmaceutical forms for oral or rectal administration
JPH09286314A (en) * 1996-02-21 1997-11-04 Aisin Seiki Co Ltd Brake power control device for vehicle
US5800832A (en) * 1996-10-18 1998-09-01 Virotex Corporation Bioerodable film for delivery of pharmaceutical compounds to mucosal surfaces
DE19646392A1 (en) 1996-11-11 1998-05-14 Lohmann Therapie Syst Lts Preparation for use in the oral cavity with a layer containing pressure-sensitive adhesive, pharmaceuticals or cosmetics for dosed delivery
JP3460538B2 (en) * 1997-10-08 2003-10-27 救急薬品工業株式会社 Fast dissolving film preparation
US5997817A (en) * 1997-12-05 1999-12-07 Roche Diagnostics Corporation Electrochemical biosensor test strip
US5948440A (en) * 1997-12-17 1999-09-07 Ranbaxy Laboratories Limited Modified release matrix formulation of cefaclor and cephalexin
US6500627B1 (en) 1998-02-03 2002-12-31 The Trustees Of Columbia University In The City Of New York Methods for predicting pregnancy outcome in a subject by HCG assay
US6365362B1 (en) * 1998-02-12 2002-04-02 Immunivest Corporation Methods and reagents for the rapid and efficient isolation of circulating cancer cells
US6403298B1 (en) * 1998-06-16 2002-06-11 All Technologies Corporation Method and apparatus for urine self-test intended for use in a toilet
US6596298B2 (en) * 1998-09-25 2003-07-22 Warner-Lambert Company Fast dissolving orally comsumable films
US6552024B1 (en) 1999-01-21 2003-04-22 Lavipharm Laboratories Inc. Compositions and methods for mucosal delivery
US6177906B1 (en) 1999-04-01 2001-01-23 Arraycomm, Inc. Multimode iterative adaptive smart antenna processing method and apparatus
US7067116B1 (en) * 2000-03-23 2006-06-27 Warner-Lambert Company Llc Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1
US6672458B2 (en) * 2000-05-19 2004-01-06 Becton, Dickinson And Company System and method for manipulating magnetically responsive particles fluid samples to collect DNA or RNA from a sample
JP4323797B2 (en) 2000-07-07 2009-09-02 エイ．ブイ．トップチーブ インスティテュート オブ ペトロケミカル シンセシス Preparation of hydrophilic pressure sensitive adhesives with optimized adhesive properties
US6946501B2 (en) 2001-01-31 2005-09-20 The Procter & Gamble Company Rapidly dissolvable polymer films and articles made therefrom
EP1389910A4 (en) * 2001-04-20 2005-11-02 Lavipharm Lab Inc Intraoral delivery of nicotine for smoking cessation
US6660292B2 (en) * 2001-06-19 2003-12-09 Hf Flavoring Technology Llp Rapidly disintegrating flavored film for precooked foods
US6656493B2 (en) * 2001-07-30 2003-12-02 Wm. Wrigley Jr. Company Edible film formulations containing maltodextrin
US6419903B1 (en) * 2001-08-20 2002-07-16 Colgate Palmolive Company Breath freshening film
WO2003030881A1 (en) * 2001-10-12 2003-04-17 Kosmos Pharma Glucan based film delivery systems
US20030118528A1 (en) * 2001-11-19 2003-06-26 Walters Kenneth A. Topical delivery of codrugs
US20040018156A1 (en) 2002-07-23 2004-01-29 Szeles Lori H Enzyme enhanced breath freshening film
AU2003297752A1 (en) * 2002-12-06 2004-06-30 Monosolrx Llc Thin film delivery systems for volatile decongestants
CA2520383C (en) 2003-03-26 2013-12-17 The Procter & Gamble Company Rapidly dissolving edible film compositions with improved film strength and stability
MXPA05010201A (en) 2003-03-26 2005-11-08 Procter & Gamble Rapidly dissolving edible film compositions with cellulose film forming polymers.
US7306812B2 (en) * 2003-05-09 2007-12-11 Cephalon, Inc. Dissolvable backing layer for use with a transmucosal delivery device
EP1680079A4 (en) 2003-10-24 2008-01-02 Adhesives Res Inc Rapidly disintegrating films for delivery of pharmaceutical or cosmetic agents
US9248146B2 (en) 2003-10-24 2016-02-02 Adhesives Research, Inc. Dissolvable adhesive films for delivery of pharmaceutical or cosmetic agents
CN101440098B (en) 2004-02-20 2011-07-13 盐野义制药株式会社 Crystal of oxacephem
US9267167B2 (en) * 2004-06-28 2016-02-23 Becton, Dickinson And Company Dissolvable films and methods including the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP1695094A4 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9267167B2 (en) 2004-06-28 2016-02-23 Becton, Dickinson And Company Dissolvable films and methods including the same
US9410185B2 (en) 2004-06-28 2016-08-09 Becton, Dickinson And Company Dissolvable films and methods including the same
US8835157B2 (en) 2007-04-25 2014-09-16 3M Innovative Properties Company Supported reagents, methods, and devices
WO2011012848A1 (en) 2009-07-27 2011-02-03 Suresensors Ltd Improvements relating to sensor devices
US9868974B2 (en) 2009-07-27 2018-01-16 SureSensors Ltd. Sensor devices
EP2316438A1 (en) 2009-10-30 2011-05-04 Johnson & Johnson GmbH Tape , in particular adhesive tape, for the treatment of skin disorders comprising at least one hyperkeratosis inhibitor and/or at least one keratinolytic agent
EP2316436A1 (en) 2009-10-30 2011-05-04 Johnson & Johnson GmbH Tape, in particular adhesive tape, for the treatment of skin disorders comprising a film , in particular dissolvable film, containing at least one enzyme
US11992508B2 (en) 2014-10-28 2024-05-28 Biovotec As Micronized eggshell membrane particles and the use thereof to promote the healing of wounds
US11045578B2 (en) 2015-06-24 2021-06-29 Biovotec As Tissue engineering scaffolds comprising particulate egg shell membrane
US10932952B2 (en) 2015-11-11 2021-03-02 Biovotec As Dry biocompatible disintegratable films for delivering particulate egg shell membrane to a wound
US20220323587A1 (en) * 2016-11-02 2022-10-13 Board Of Regents, The University Of Texas System Dissolvable films and methods of their use
WO2021082899A1 (en) * 2019-10-30 2021-05-06 烟台芥子生物技术有限公司 Dry immunoturbidimetric reagent, and preparation method and application thereof

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