Patents Assigned to Pion, Inc.
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Patent number: 10228358Abstract: An apparatus for the combined assessment of dissolution and permeability relies on a receiver chamber that is contained within a donor chamber. A membrane is provided between the two chambers. Measurements can be taken to determine solute amounts of a drug introduced in the donor chamber and amounts of permeated solute in the receiver chamber. Also described are techniques for the assessment of a dissolution rate and total amount of dissolved compound, together with their effect on absorption potential of a compound or a compound product as well as approaches for evaluating in vivo relevant differences between formulations of a compound through their effect on the absorption potential of the compound.Type: GrantFiled: April 14, 2016Date of Patent: March 12, 2019Assignee: PION INC.Inventors: Ajit S. Narang, Dan Tang, Scott P. Jennings, Neil Mathias, Konstantin L. Tsinman, Deren J. Dohoda, David A. Kwajewski, Michael G. Kelly
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Patent number: 10018584Abstract: The present invention relates to universal ion-selective electrode optimized for determinations of organic molecules. As opposed to the state of the art only one electrode composition is applicable to a variety of organic ions and ionizable molecules. It is accordingly an object of the present invention to provide an ISE composition that is optimized for the universal detection and determination of a very wide range of organic ions an ionizable organic molecules. As opposed to the state of the art this composition allows fast and sensitive detection of a very wide range of molecules independent of their chemical structure, class or number of charges. This optimized sensor can be used in different methodologies, e.g.: direct potentiometrie, standard addition, inline measurements and titration.Type: GrantFiled: June 14, 2013Date of Patent: July 10, 2018Assignee: PION INC.Inventor: Hugo Bohets
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Patent number: 9645107Abstract: Ion-selective electrodes (ISE's) optimized for analyte determinations and provides methods and apparatus for conditioning ion selective electrodes. The conditioning methods and apparatus are particularly useful for ISE's selective for, difficult to condition, less stable and temperature sensitive products, an are based on a concentration gradient and/or a short exposure to an increased temperature.Type: GrantFiled: March 7, 2011Date of Patent: May 9, 2017Assignee: Pion Inc.Inventor: Hugo Bohets
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Patent number: 8840849Abstract: The invention provides a permeation device (2) comprising a receiving vessel (6) having an aperture adapted for receiving an insert well (4). Both the vessel (6) and well (4) are used as either donor or acceptor compartments for permeability assays. The vessel (6) or well (4) comprises a porous suppor (8)t, which may comprise biological or biomimetic materials, adapted for a molecular entity to permeate therethrough. In one embodiment, a stirring member (24) disposed in the vessel (6) can provide solution agitation to reduce aqueous boundary layer thickness adjacent to the support (8). Boundary layer thicknesses can be reduced by a device (2) of the invention to less than about 15 um such that a molecular entity permeating the support closely approximates in vivo absorption and transport conditions.Type: GrantFiled: June 1, 2005Date of Patent: September 23, 2014Assignee: Pion, Inc.Inventors: Alex Avdeef, Per E. Nielsen
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Patent number: 8175815Abstract: The invention deals with a method for the assessment of the effect of excipients, pH and combinations thereof on the predicted absorption properties of low solubility compounds, comprising the step of assessing a change in a flux function for a combination of a low solubility compound and an excipient at at least one predefined pH value. The method allows a fast, accurate, and economic evaluation of an excipient being capable of optimizing the absorption of drug molecules, i.e. low solubility compounds. Furthermore, animal experiments can be excluded and use of compounds can be reduced in such evaluation. Thus, screening for future formulation efficacy (pH and excipient effects on solubility and permeability) of drug candidates can be justified, since the method is fast, compound-sparing, cost-effective, and reasonably accurate.Type: GrantFiled: February 27, 2007Date of Patent: May 8, 2012Assignees: F. Hoffmann-La Roche AG, pION Inc.Inventors: Alex Avdeef, Manfred Kansy
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Patent number: 8119998Abstract: An apparatus for evaluating physicochemical properties of sample materials contained in an array of vessels includes: a light detector; a light source for transmitting a light beam through the sample material in a vessel to the light detector; an analyzer for processing data from the light detector to determine concentration-related properties of the sample material as a function of time; and a mixing system. The mixing system includes: a plurality of magnetic stirrer elements, each for being placed in a sample material in a different one of the array of vessels; an array of magnetic drive elements, each associated with a different one of the array of vessels and being magnetically coupled with a magnetic stirrer element in an associated vessel; and a drive mechanism coupled to the array of magnetic drive elements for simultaneously moving each of the magnetic drive elements relative to an associated vessel.Type: GrantFiled: December 23, 2008Date of Patent: February 21, 2012Assignee: Pion, Inc.Inventors: Alex Avdeef, Dmytro Voloboy, Deren J. Dohoda, Per E. Nielsen, Michael J. DeMaria
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Publication number: 20100288944Abstract: An apparatus for evaluating physicochemical properties of sample materials contained in an array of vessels includes: a light detector; a light source for transmitting a light beam through the sample material in a vessel to the light detector; an analyzer for processing data from the light detector to determine concentration-related properties of the sample material as a function of time; and a mixing system. The mixing system includes: a plurality of magnetic stirrer elements, each for being placed in a sample material in a different one of the array of vessels; an array of magnetic drive elements, each associated with a different one of the array of vessels and being magnetically coupled with a magnetic stirrer element in an associated vessel; and a drive mechanism coupled to the array of magnetic drive elements for simultaneously moving each of the magnetic drive elements relative to an associated vessel.Type: ApplicationFiled: December 23, 2008Publication date: November 18, 2010Applicant: Pion, Inc.Inventors: Alex Avdeef, Dmytro Voloboy, Deren J. Dohoda, Per E. Nielsen, Michael J. DeMaria
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Publication number: 20090187365Abstract: The invention deals with a method for the assessment of the effect of excipients, pH and combinations thereof on the predicted absorption properties of low solubility compounds, comprising the step of assessing a change in a flux function for a combination of a low solubility compound and an excipient at at least one predefined pH value. The method allows a fast, accurate, and economic evaluation of an excipient being capable of optimizing the absorption of drug molecules, i.e. low solubility compounds. Furthermore, animal experiments can be excluded and use of compounds can be reduced in such evaluation. Thus, screening for future formulation efficacy (pH and excipient effects on solubility and permeability) of drug candidates can be justified, since the method is fast, compound-sparing, cost-effective, and reasonably accurate.Type: ApplicationFiled: February 27, 2007Publication date: July 23, 2009Applicants: F. HOFFMANN-LA ROCHE AG, PION INC.Inventors: Alex Avdeef, Manfred Kansy
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Publication number: 20070251336Abstract: In many miniaturized high-throughput assays, effective stirring is difficult to achieve, and its consequences difficult to predict. Most microtitre plate-based in vitro assays of membrane permeability, such as Caco-2 and PAMPA, of sparingly soluble lipophilic test compounds in pharmaceutical research and development report permeability of water, and not of the intended membrane barrier. This is so because the aqueous boundary layer on both sides of the membrane barrier is rate limiting for these highly permeable molecules. The thickness of this water layer can be 1500-4000 ?m in unstirred assays. Under in vivo conditions, however, the aqueous boundary layer is believed to be 30-100 ?m thick in the intestine, and <1 ?m at the blood-brain barrier. Using plate shakers to stir microtitre plates cannot lower the thickness of the water layer to match that found in vivo.Type: ApplicationFiled: June 1, 2005Publication date: November 1, 2007Applicant: PION, INC.Inventors: Per Nielsen, Alex Avdeef
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Patent number: 7022528Abstract: This invention improves the PAMPA (parallel artificial membrane permeability assay) method used in pharmaceutical, biotechnological, and agrochemical R&D. This new high-throughput method and apparatus for measurement of permeability and membrane retention of compounds overcomes shortcomings of prior art and includes sensitivity and speed enhancing reagents. The phospholipid membranes used here consist of 10–74% wt/vol soybean lecithin extract dissolved in dodecane. Concentrations are measured by direct UV spectroscopy. To reduce membrane retention, surfactants, cyclodextrins, or water-soluble lipophilic polymers with low UV absorption are used in the acceptor comparment of the permeation cells and create an artificial sink state. A pH gradient established between donor and acceptor solutions creates a secondary sink state. This “double-sink” makes successful modeling of passive-diffusion transport of molecules possible.Type: GrantFiled: January 23, 2003Date of Patent: April 4, 2006Assignee: Pion, Inc.Inventors: Alex Avdeef, Per E. Nielsen, Chau M. Du
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Publication number: 20030219716Abstract: The invention described here improves the PAMPA (parallel artificial membrane permeability assay) high-throughput method used in lead compound selection and optimization in pharmaceutical and biotechnological research and development, and for identifying active compounds with the right plant distribution properties in agrochemical research and development. The invention described here is a robust method and apparatus for measurement of two physical properties, permeability and membrane retention of compounds, which overcomes several of the shortcomings in the prior art. This invention includes reagents specifically designed for enhancing the sensitivity of the assay, to allow a UV detection system to be used for concentration measurements, to accurately estimate and compensate for the effects of membrane retention and unstirred water layer, and to increase the speed of the assay.Type: ApplicationFiled: January 23, 2003Publication date: November 27, 2003Applicant: pION, INC.Inventors: Alex Avdeef, Per E. Nielsen, Chau M. Du
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Patent number: 6569686Abstract: This invention relates to a method for the determination of solubility of a compound and an analytical device for carrying out said method. The basic method involves determining solubility of a compound by measuring the UV spectrum of a reference solution of the compound, under conditions avoiding or suppressing precipitation, and comparing it to the UV spectrum of a saturated sample solution of the compound. Variations of the basic method include: (a) making reference solutions either by dilution of the sample solution to the point where precipitation is avoided, or making reference solutions by adding a water-miscible cosolvent to the sample solution so that precipitation is suppressed, and comparing the UV absorbances of the compound under reference conditions to the compound in a saturated solution, (b) determining the true aqueous solubility from the effect on the pKa that results from dissolving the compound in an aqueous solution containing some DMSO (typically 0.Type: GrantFiled: January 25, 2001Date of Patent: May 27, 2003Assignee: Pion, Inc.Inventors: Alex Avdeef, Konstantin L. Tsinman
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Publication number: 20020004244Abstract: This invention relates to a method for the determination of solubility of a compound and an analytical device for carrying out said method. The basic method involves determining solubility of a compound by measuring the UV spectrum of a reference solution of the compound, under conditions avoiding or suppressing precipitation, and comparing it to the UV spectrum of a saturated sample solution of the compound. Variations of the basic method include: (a) making reference solutions either by dilution of the sample solution to the point where precipitation is avoided, or making reference solutions by adding a water-miscible cosolvent to the sample solution so that precipitation is suppressed, and comparing the UV absorbances of the compound under reference conditions to the compound in a saturated solution, (b) determining the true aqueous solubility from the effect on the pKa that results from dissolving the compound in an aqueous solution containing some DMSO (typically 0.Type: ApplicationFiled: January 25, 2001Publication date: January 10, 2002Applicant: pION, Inc.Inventors: Alex Avdeef, Konstantin L. Tsinman