公开(公告)号：EP1521962B1

公开(公告)日：2009-12-23

申请号：EP03713278.4

申请日：2003-01-23

申请人： PION, INC.

发明人： AVDEEF, Alex ,  NIELSEN, Per, E. ,  DU, Chau, M.

IPC分类号： G01N33/50 ,  B01L3/00

CPC分类号： G01N13/04 ,  B01L3/50255 ,  G01N13/00 ,  G01N15/0826 ,  G01N35/028 ,  G01N2001/4016 ,  G01N2013/003 ,  Y10T436/115831

公开(公告)号：EP1250587A1

公开(公告)日：2002-10-23

申请号：EP01903291.1

申请日：2001-01-25

申请人： PION, INC.

发明人： AVDEEF, Alex ,  TSINMAN, Konstantin, L.

IPC分类号： G01N21/33

CPC分类号： G01N33/15 ,  G01N21/33 ,  G01N21/80 ,  Y10T436/25 ,  Y10T436/25375 ,  Y10T436/25625

摘要： This invention relates to a method and an analytical device for the determination of solubility of a compound. The basic method involves determinig 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 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 0.1 - 5% v/v), and (c) correcting concentrations determined from the UV absorbance values for impurities.

公开(公告)号：EP1521962A2

公开(公告)日：2005-04-13

申请号：EP03713278.4

申请日：2003-01-23

申请人： PION, INC.

发明人： AVDEEF, Alex ,  NIELSEN, Per, E. ,  DU, Chau, M.

IPC分类号： G01N33/50 ,  B01L3/00

CPC分类号： G01N13/04 ,  B01L3/50255 ,  G01N13/00 ,  G01N15/0826 ,  G01N35/028 ,  G01N2001/4016 ,  G01N2013/003 ,  Y10T436/115831

摘要： A new permeability equation is used, that takes into account (a) pH gradients between the two sides of the membrane barrier and (b) the retention of the molecules by the membrane, which the pH-gradient sink the condition is unable to eliminate entirely.

公开(公告)号：EP1768784A2

公开(公告)日：2007-04-04

申请号：EP05758774.3

申请日：2005-06-01

申请人： PION, INC.

发明人： AVDEEF, Alex ,  NIELSEN, Per, E.

IPC分类号： B01L3/00

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

摘要： 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.

公开(公告)号：EP1991864B1

公开(公告)日：2018-03-21

申请号：EP07701897.6

申请日：2007-02-27

申请人： F. Hoffmann-La Roche AG ,  PION Inc.

发明人： AVDEEF, Alex ,  KANSY, Manfred

IPC分类号： G01N33/15

CPC分类号： G01N33/15

摘要： 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.

公开(公告)号：EP1768784B1

公开(公告)日：2017-10-25

申请号：EP05758774.3

申请日：2005-06-01

申请人： PION, INC.

发明人： AVDEEF, Alex ,  NIELSEN, Per, E.

IPC分类号： B01L3/00 ,  B01D65/08 ,  C12M3/06

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

公开(公告)号：EP1991864A1

公开(公告)日：2008-11-19

申请号：EP07701897.6

申请日：2007-02-27

申请人： F.HOFFMANN-LA ROCHE AG ,  PION Inc.

发明人： AVDEEF, Alex ,  KANSY, Manfred

IPC分类号： G01N33/15

CPC分类号： G01N33/15

摘要： 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.

摘要翻译： 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，包括评价低溶解度化合物和 赋形剂在至少一个预定的pH值下。 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，化合物节约，成本效益高，而且相当准确，因此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。