公开(公告)号：WO2007098625A1

公开(公告)日：2007-09-07

申请号：PCT/CH2007/000097

申请日：2007-02-27

Applicant: F. HOFFMANN-LA ROCHE AG ,  PION ,  AVDEEF, Alex ,  KANSY, Manfred

Inventor： AVDEEF, Alex ,  KANSY, Manfred

IPC: G01N33/15

CPC classification number: G01N33/15

Abstract: 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.

Abstract translation: 本发明涉及评估赋形剂，pH及其组合对低溶解度化合物预测吸收性能的影响的方法，包括评估低溶解度化合物和 赋形剂在至少一个预定的pH值。 该方法允许对能够优化药物分子（即低溶解度化合物）的吸收的赋形剂的快速，准确和经济的评价。 此外，可以排除动物实验，并且可以减少化合物的使用。 因此，由于该方法快速，复合，节省成本，并且相当准确，筛选候选药物的未来制剂功效（pH和赋形剂对溶解性和渗透性的影响）是合理的。

公开(公告)号：WO2005118141A2

公开(公告)日：2005-12-15

申请号：PCT/US2005019196

申请日：2005-06-01

Applicant: PION INC ,  AVDEEF ALEX ,  NIELSEN PER E

Inventor： AVDEEF ALEX ,  NIELSEN PER E

IPC: B01F13/08 ,  B01L3/00 ,  C12M3/06

CPC classification number: B01F13/1013 ,  B01D65/08 ,  B01D2321/2041 ,  B01F13/0818 ,  B01F13/1022 ,  B01L3/50255 ,  B01L2200/025 ,  B01L2200/143 ,  B01L2300/0609 ,  B01L2300/0681 ,  B01L2300/0829 ,  C12M25/04

Abstract: The invention provides a permeation device comprising a receiving vessel having an aperture adapted for receiving an insert well. Both the vessel and well are used as either donor or acceptor compartments for permeability assays. The vessel or well comprise a porous support, which comprises, for example, biological or biomimetic materials, adapted for a molecular entity to permeate therethrough. A permeation device of the invention can be used for a Caco-2 type cell assay or PAMPA. In one embodiment, a stirring member disposed in the vessel can provide solution agitation to reduce aqueous boundary layer(s) thickness adjacent to the support. Boundary layer thicknesses can be reduced by a device of the invention to less than about 15 pm such that a molecular entity permeating the support closely approximates in vivo absorption and transport conditions. The invention also provides a method for changing boundary layer thicknesses using such a device.

Abstract translation: 本发明提供了一种渗透装置，其包括具有适于接收插入孔的孔的接收容器。 容器和孔均用作供体或受体室用于渗透性测定。 容器或井包括多孔载体，其包含例如生物或仿生材料，适于使分子实体渗透通过其中。 本发明的渗透装置可用于Caco-2型细胞试验或PAMPA。 在一个实施例中，设置在容器中的搅拌构件可以提供溶液搅拌以减少邻近载体的水边界层的厚度。 可以通过本发明的装置将边界层厚度减小到小于约15μm，使得渗透载体的分子实体在体内吸收和运输条件下接近。 本发明还提供了一种使用这种装置来改变边界层厚度的方法。

公开(公告)号：WO2009088781A1

公开(公告)日：2009-07-16

申请号：PCT/US2008/088211

申请日：2008-12-23

Applicant: PION INC. ,  AVDEEF, Alex ,  VOLOBOY, Dmytro ,  DOHODA, Deren, J. ,  NIELSEN, Per, E. ,  DEMARIA, Michael, J.

Inventor： AVDEEF, Alex ,  VOLOBOY, Dmytro ,  DOHODA, Deren, J. ,  NIELSEN, Per, E. ,  DEMARIA, Michael, J.

IPC: G01N33/15

CPC classification number: G01N21/253 ,  G01N21/0332 ,  G01N21/272 ,  G01N21/82 ,  G01N2201/122

Abstract: 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.

Abstract translation: 用于评估包含在容器阵列中的样品材料的物理化学性质的装置包括：光检测器; 用于将光束通过容器中的样品材料传输到光检测器的光源; 用于处理来自光检测器的数据的分析器，以确定作为时间的函数的样品材料的浓度相关性质; 和混合系统。 混合系统包括：多个磁力搅拌器元件，每个磁力搅拌器元件被放置在不同容器阵列中的样品材料中; 一组磁性驱动元件，每个磁性驱动元件与不同的容器阵列相关联并且与相关联的容器中的磁力搅拌器元件磁耦合; 以及耦合到磁驱动元件阵列的驱动机构，用于相对于相关联的容器同时移动每个磁驱动元件。

公开(公告)号：WO2005118141A3

公开(公告)日：2005-12-15

申请号：PCT/US2005/019196

申请日：2005-06-01

Applicant: PION INC ,  AVDEEF, Alex ,  NIELSEN, Per, E.

Inventor： AVDEEF, Alex ,  NIELSEN, Per, E.

IPC: B01L3/00

Abstract: 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.