WO2001070380A1 - Lipid membrane, method for measuring membrane permeability, and method for screening - Google Patents
Lipid membrane, method for measuring membrane permeability, and method for screening Download PDFInfo
- Publication number
- WO2001070380A1 WO2001070380A1 PCT/JP2001/002346 JP0102346W WO0170380A1 WO 2001070380 A1 WO2001070380 A1 WO 2001070380A1 JP 0102346 W JP0102346 W JP 0102346W WO 0170380 A1 WO0170380 A1 WO 0170380A1
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- Prior art keywords
- membrane
- lipid
- substance
- permeability
- lipid membrane
- Prior art date
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 229960004940 sulpiride Drugs 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N15/082—Investigating permeability by forcing a fluid through a sample
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N15/082—Investigating permeability by forcing a fluid through a sample
- G01N15/0826—Investigating permeability by forcing a fluid through a sample and measuring fluid flow rate, i.e. permeation rate or pressure change
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N2015/086—Investigating permeability, pore-volume, or surface area of porous materials of films, membranes or pellicules
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/104165—Lipid, cholesterol, or triglyceride standard or control
Definitions
- the present invention relates to a lipid membrane, and more particularly, the present invention relates to a lipid membrane that can be used for measuring the permeability of a substance.
- lipid membranes have been used as sensors or detection membranes of measurement devices, and are used for detecting or measuring various substances such as metal ions, cyanide ions, alcohols, and enzymes.
- a lipid membrane is also used to evaluate the permeability of the biological membrane.
- lipid membrane permeability of a drug is closely related to gastrointestinal absorption in an oral preparation and tissue transportability in a living body, and is an important property in drug development.
- evaluation of membrane permeability is important not only for drugs but also for substances that are harmful to living organisms (eg, toxic substances, carcinogenic substances, etc.).
- in vitro measurement of a substance's membrane permeability includes a method using an isolated organ and a method using cells derived from gastrointestinal epithelium.
- these methods have a problem in measuring many substances quickly due to their slow processing speed.
- a method of measuring membrane permeability by creating an artificial lipid membrane in a 96-well plate (KA NS Y, Man fred, SENNER, Franck, GUBERNATO R, Kl au s; Jou rna lof Med ici na l Chemis ry 1998, 41, 1007-1010), etc., and such a lipid membrane is composed of a lipid and an organic solvent.
- This measurement method has features such as the ability to measure many substances at the same time, and the running cost is low because only a small amount of substances are used.
- the membrane used in the disclosed technique has not only a poor correlation with the permeability of the substance of the biological membrane in vivo, but also the low permeability of the substance, which makes it difficult to evaluate a low-permeability substance.
- drawbacks such as a long measurement time.
- a membrane for measuring the membrane permeability of a substance As a membrane for measuring the membrane permeability of a substance, a method in which a membrane component collected from a living body (rat) is dissolved in n-decane (I NUI, Ken-ichi, TABARA, Katsue) , HIRI, Ryohei, KANEDA, Akemi, MURAN ISHI, Shozo, SEZAKI, Hitoshi; Jou rna lof Pharrmacy and Pharmacology, 1977, 29, 22-26), etc. It has been known.
- This membrane has a characteristic that it has a good correlation with the permeability of substances in biological membranes, but has the drawbacks that it is difficult to evaluate low-permeability substances due to the low permeability of substances and that the measurement time is long. .
- An object of the present invention is to provide a lipid membrane which overcomes these drawbacks, has a high substance permeability, has a high correlation with the substance permeability of a biological membrane, and is suitable for a rapid measurement method.
- the present inventors have conducted intensive studies and found that by using an unsaturated hydrocarbon having 7 to 9 carbon atoms, it is possible to obtain a lipid membrane having a high substance permeability and suitable for a rapid measurement method. This led to the completion of the present invention.
- the use of unsaturated hydrocarbons having 7 to 9 carbon atoms, substances having a negative charge near neutrality, and lipids having a negative charge near Z or neutrality makes the drug highly transparent and in vivo.
- the present inventors have found that a lipid membrane suitable for a rapid measurement method can be obtained, which has a high correlation with the drug permeability of a biological membrane in the present invention, and has completed the present invention.
- the present invention provides a lipid membrane comprising an unsaturated hydrocarbon having 7 to 9 carbon atoms and a lipid.
- the lipid membrane further contains a substance having a negative charge near neutrality.
- the lipid has a negative charge near neutrality.
- the unsaturated hydrocarbon having 7 to 9 carbon atoms is hebutadiene, octadiene or nonadiene. More preferably, it is 1,6-butadiene, 1,7-butadiene or 1,8-nonadiene.
- lipid membrane of the present invention may be added.
- a carrier for transporting a specific substance (specific transporter) may be added.
- the present invention provides a measuring method, comprising a step of measuring the membrane permeability of a substance using the above-mentioned lipid membrane.
- the present invention provides a membrane permeability measurement kit comprising an unsaturated hydrocarbon having 7 to 9 carbon atoms and a lipid.
- a measurement kit may further include a support (for example, a filter paper) that can support a lipid membrane composed of an unsaturated hydrocarbon having 7 to 9 carbon atoms and a lipid.
- the present invention provides a method of screening a substance, comprising: a step of measuring the membrane permeability of a substance using the above-mentioned lipid membrane; and a step of selecting a substance having a predetermined membrane permeability. I do.
- the present invention provides a screening kit comprising an unsaturated hydrocarbon having 7 to 9 carbon atoms, a lipid, and an instruction for use.
- the measurement method of the present invention may be combined with a method of measuring active transport of a membrane, and a screening method including such a method and a kit used therefor are also provided. It is included in the scope of the present invention.
- the lipid membrane of the present invention can be applied not only to the evaluation of the permeability of a substance through a biological membrane but also to a sensor or a measuring device for a chemical substance or the like.
- the unsaturated hydrocarbon having 7 to 9 carbon atoms used in the present invention may be linear or branched, and includes, for example, hebutadiene, octadiene and nonadiene.
- hebutadiene examples include (Z) —1,3-heptadiene, (Z) —1,4-heptadiene, (Z) —1,5-heptadiene, 1,6-heptadiene, and (E) — 1,3-butadiene, (E) — 1,4-butadiene, (E) — 1,5—butadiene, (2 Z, 4 Z) -2,4 butadiene, (2Z, 5 Z) 1,2-butadiene, (2Z, 4E) -2,4-butadiene, (2Z, 5E) -2,5 butadiene, (2E, 4Z) 1,2,4-butadiene, (2E, 5Z)-2,5-butadiene, (2E, 4E) -2,4 butadiene, (2E, 5E) -2,5_butadiene, (3Z, 5Z) 1,3-butadiene, (3Z, 5E)-3,5_butadiene, (3E, 5Z) 1,
- the lipid membrane of the present invention comprises, as an organic solvent, only an unsaturated hydrocarbon having 7 to 9 carbon atoms. It may contain a mixture of another organic solvent and an unsaturated hydrocarbon having 7 to 9 carbon atoms.
- Examples of the lipid used in the present invention include saturated fatty acids, unsaturated fatty acids, phospholipids, and cholesterol.
- saturated fatty acids examples include lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, and behenic acid.
- unsaturated fatty acids include palmitoleic acid, linolenic acid, linoleic acid, oleic acid, and arachidonic acid.
- Examples of the phospholipid include phosphatidylcholine, phosphatidylglycerol, phosphatidylinosyl, phosphatidylserine, phosphatidylethanolamine, sphingomyelin and the like.
- One of these lipids or a mixture of two or more thereof may be used.
- Examples of the substance having a negative charge near neutrality used in the present invention include stearic acid, phosphatidylserine, phosphatidylinositol and the like. These may be used alone or in combination of two or more.
- the ratio of lipid to unsaturated hydrocarbon having 7 to 9 carbon atoms (lipid weight / weight of unsaturated hydrocarbon having 7 to 9 carbon atoms) in the lipid membrane of the present invention is preferably 0.1 to 20%. It is more preferably 1 to 10%, particularly preferably 1 to 2%.
- the lipid membrane of the present invention contains a substance having a negative charge near neutrality, it should be contained at a ratio of about 0.2 mmo1 / L to about 50 mmo1 / L with respect to the entire lipid membrane. And more preferably in a ratio of about 2 mmo 1 ZL to about 25 mmo 1 / L.
- near neutral generally means a range of pH 5.0 to 9.0, preferably pH 5.5 to 8.0, and more preferably pH 6.0 to 7.0. It is 5.
- having a negative charge near neutral means having a negative charge in a predetermined solvent near neutral.
- the lipid membrane of the present invention may contain components other than those described above, and these components can be appropriately selected in consideration of a substance to be evaluated, characteristics of a living body or a tissue, and the like.
- it may contain a carrier (specific transporter) for transporting a specific substance.
- the thickness of the lipid membrane of the present invention is appropriately selected depending on the substance to be evaluated, the characteristics of a living body or a tissue, and the like.
- the lipid membrane of the present invention may be formed on any support.
- a porous sheet-like material or a film-like material such as a filter paper is preferable.
- a hydrophobic substance is preferable, and for example, PTFE (polytetrafluoroethylene) and hydrophobic PVDF (polyvinylidene difluoride) can be used.
- PTFE polytetrafluoroethylene
- PVDF polyvinylidene difluoride
- hydrophobic PVDF is used.
- Those having a pore size of 0.01 to 20 m, preferably 0.05 to: L0xm, more preferably 0.1 to 5 m, and particularly preferably about 0.1 to 1 m are used.
- the lipid membrane of the present invention may be formed so as to cover an opening of a pore having a diameter of about 0.5 to 2 mm, preferably about 1 mm.
- the lipid membrane of the present invention is obtained by mixing the above-mentioned unsaturated hydrocarbon having 7 to 9 carbon atoms and lipid by a usual method, for example, KANSY, Manfred, SENNER, Franck, GUBERNATOR, Klaus It can be produced according to the method described in JournalofMedicinal Chemistry 1998, 41, 1007-1010.
- the measurement method of the present invention includes a step of measuring the membrane permeability of a substance using the lipid membrane of the present invention.
- the lipid membrane used for the measurement is formed and stored prior to the measurement. Alternatively, it may be formed immediately before the measurement.
- the lipid membrane is preferably formed on a support, more preferably on a hydrophobic support.
- the solvent on the B side is preferably the same as the solvent of the test substance solution on the A side.
- the amount of the test substance that has passed through the lipid membrane from side A to side B is measured.
- the amount of test substance that has permeated through the lipid membrane is calculated by measuring the amount of test substance remaining on the B side without permeating through the lipid membrane May be.
- the lipid membrane may be installed in any direction with respect to gravity.
- the lipid membrane may be installed parallel or perpendicular to gravity.
- the direction in which the substance permeates is not particularly limited. For example, even if the direction is the same as the gravity, Or vertical.
- one container may be divided into two compartments using a lipid membrane.
- a container for the test substance solution and a container for the solvent without the test substance may be separately prepared.
- a cylindrical upper container having a filter at the bottom and a lower container having an open top can be used in combination.
- the lower end of the upper container and the upper end of the lower container have the same size.
- the filter can be fixed between the upper and lower containers so that the liquid does not leak from the upper and lower containers with the filter sandwiched between the upper and lower containers. Rubber packing or the like may be used. Also, the filter need not necessarily be fixed to the bottom of the upper container.
- a well plate having a plurality of wells In order to quickly measure the membrane permeability of a plurality of test substances, it is also preferable to use a well plate having a plurality of wells.
- a well plate with multiple wells as the lower container, fill each well with a solvent that does not contain the test substance, cover it with a porous membrane such as Filler paper, and then match each well.
- An upper plate (used as an upper container) with through holes at the position may be placed, a lipid membrane may be formed on the porous membrane in each through hole, and the test substance solution may be charged.
- a filter may be provided at the bottom of each through hole of the upper plate.
- a chemoplate such as chemotaxis 3 ⁇ 4
- the upper container may contain the solvent without the test substance and the lower container may contain the test substance solution.
- Methods for quantifying substances permeating the lipid membrane include, for example, absorbance measurement, HPLC method, TLC (thin layer chromatography) method, GC-MS (gas chromatography mass spectrum) method, LC-MS (liquid chromatography-mass spectrum) Method, fluorescence method, NMR method, IR method, CE (capillary electrophoresis) method and the like can be used, but P method, HPLC method, and LC-MS method are preferably used.
- KAN SY Manf
- the membrane permeability of a substance was measured according to the method described in J. rn lof Medicinl Chemistry 1998, 41, 1007-1010.
- the membrane permeability of the test substance is measured as described above, and a test substance having a predetermined membrane permeability is selected. At this time, some reference substance may be used to select a substance having higher or lower membrane permeability than that substance. Alternatively, a test substance having the same membrane permeability as the substance may be selected.
- the screening kit of the present invention is useful for performing such a screening method quickly and easily, and includes an unsaturated hydrocarbon having 7 to 9 carbon atoms, a lipid, and an instruction manual.
- Membrane support eg, filter paper, preferably hydrophobic filter paper, etc.
- gel plate used for measuring membrane permeability
- solvent e.g., water
- reference material e.g., solvent
- carrier for transporting specific substances e.g., a lipid formed on a support.
- a membrane may be included.
- the present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
- the thickness of the prepared lipid membrane, the lipid concentration, the pH of the buffer solution, and the like can be appropriately changed according to the substance to be evaluated, the characteristics of the living body or tissue, and the like.
- the membrane of Example 5 was formed on a part of the filter by adding 4 to 5 ⁇ L of a solution of phosphatidylcholine: 1,8-nonagen: 2: 98 to each filter.
- sample solutions 100 to 200 zL (amount of added sample solution: Vdn) of 0.5 mmol ZL buffer solution of each compound shown in Tables 2 and 3 was prepared. This sample solution was added to each of the wells on which a film was formed as described above, and the plate was covered and left for 2 to 15 hours (transmission time: t). After removing the filter plate, 200 solutions were collected from each well of the lower well plate and used as a test solution.
- the absorbance (ODac) of the obtained test solution (200 L) was measured at each wavelength of 250 to 450 nm (interval of 10 to 20 nm).
- As the standard solution each of the sample solutions used in Example 1 or 3 (an undiluted standard solution) or a solution obtained by diluting the sample solution 4.8-fold (V / V) with a buffer solution (dilution) Standard solution). That is, the absorbance was measured in the same manner as in the test solution using 200 L of either the undiluted standard solution or the diluted standard solution (ODref), and the transmission coefficient was calculated according to the following equation.
- V ac Volume of each well of the lower plate (360 L)
- V dn added sample solution volume 100-200 L
- VdnXVac for undiluted standard solution
- Tables 2 and 3 show the obtained transmission coefficients (P).
- Table 2 shows the obtained correlation coefficient (R) and the gastrointestinal absorption (Fa) of each compound in humans.
- lipid membrane having high permeability of a substance, having a high correlation with the permeability of a biological membrane, and suitable for rapid measurement can be provided, and is extremely useful.
Landscapes
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Dispersion Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Fluid Mechanics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT01914209T ATE270581T1 (de) | 2000-03-23 | 2001-03-23 | Lipidmembran, verfahren zur messung der membranpermeabilität und screeningmethode |
JP2001568565A JP3954847B2 (ja) | 2000-03-23 | 2001-03-23 | 脂質膜、膜透過性の測定方法およびスクリーニング方法 |
EP01914209A EP1266684B1 (en) | 2000-03-23 | 2001-03-23 | Lipid membrane, method for measuring membrane permeability, and method for screening |
US10/239,522 US6861260B2 (en) | 2000-03-23 | 2001-03-23 | Lipid membrane, method for measuring membrane permeability, and method for screening |
DE60104190T DE60104190T2 (de) | 2000-03-23 | 2001-03-23 | Lipidmembran, verfahren zur messung der membranpermeabilität und screeningmethode |
AU2001239564A AU2001239564A1 (en) | 2000-03-23 | 2001-03-23 | Lipid membrane, method for measuring membrane permeability, and method for screening |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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JP2000082177 | 2000-03-23 | ||
JP2000-82177 | 2000-03-23 | ||
JP2000184973 | 2000-06-20 | ||
JP2000-184973 | 2000-06-20 |
Publications (1)
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WO2001070380A1 true WO2001070380A1 (en) | 2001-09-27 |
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ID=26588168
Family Applications (1)
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PCT/JP2001/002346 WO2001070380A1 (en) | 2000-03-23 | 2001-03-23 | Lipid membrane, method for measuring membrane permeability, and method for screening |
Country Status (7)
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---|---|
US (1) | US6861260B2 (ja) |
EP (1) | EP1266684B1 (ja) |
JP (1) | JP3954847B2 (ja) |
AT (1) | ATE270581T1 (ja) |
AU (1) | AU2001239564A1 (ja) |
DE (1) | DE60104190T2 (ja) |
WO (1) | WO2001070380A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007118003A (ja) * | 2005-10-27 | 2007-05-17 | Becton Dickinson & Co | 透過性測定用の固定化多層人工膜(pampa) |
JP2009250727A (ja) * | 2008-04-03 | 2009-10-29 | Nissan Chem Ind Ltd | 人工膜を用いた膜透過性の評価方法及びスクリーニング方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7611630B2 (en) | 2004-03-30 | 2009-11-03 | Bend Research, Inc. | Method and device for evaluation of pharmaceutical compositions |
DE102005044071A1 (de) * | 2005-09-07 | 2007-03-08 | Nimbus Biotechnologie Gmbh | Verfahren zur Messung der Permeation einer Substanz durch eine Barriere |
WO2010151609A1 (en) * | 2009-06-24 | 2010-12-29 | Photoswitch Biosciences Inc. | Photoswitch-enabled ion channel assay system |
EP2773327A4 (en) | 2011-11-02 | 2015-06-03 | Univ California | NEW PROGRAMMING OF CELL ADHESION |
GB2541832B (en) * | 2014-05-23 | 2020-08-19 | Indian Institute Of Tech Madras | System and method for measuring permeability of drugs/toxic/chemical compounds |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0344807A2 (en) * | 1988-06-03 | 1989-12-06 | Hamamatsu Photonics K.K. | Method for evaluating the permeability of a thin membrane |
JPH08173780A (ja) * | 1994-12-26 | 1996-07-09 | Asahi Chem Ind Co Ltd | 高級脂肪酸エステル化多孔性膜 |
JPH1190214A (ja) * | 1997-09-18 | 1999-04-06 | Tokuyama Corp | 生体物質超薄膜の製造方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3107527A1 (de) * | 1981-02-27 | 1982-09-16 | Klaus Prof. Dr. 8400 Regensburg Heckmann | Hyperfiltrationsmembranen mit trennschichten aus monomolekularen filmen von tensiden |
US4490216A (en) * | 1983-02-03 | 1984-12-25 | Molecular Devices Corporation | Lipid membrane electroanalytical elements and method of analysis therewith |
US4637861A (en) * | 1985-12-16 | 1987-01-20 | Allied Corporation | Stabilized, lipid membrane-based device and method of analysis |
US4962022A (en) * | 1986-09-22 | 1990-10-09 | Becton Dickinson And Company | Storage and use of liposomes |
US5141751A (en) * | 1988-06-29 | 1992-08-25 | Daiichi Pharmaceutical Co., Ltd. | Lipid membrane structures |
JPH0731871A (ja) * | 1993-05-18 | 1995-02-03 | Canon Inc | 膜構造物 |
ATE332306T1 (de) * | 1998-08-31 | 2006-07-15 | Gryphon Therapeutics Inc | Chemische anknüpfung unter einbeziehung von einer lipid-matrix und herstellung von membranpolypeptiden |
TW427001B (en) * | 1998-12-30 | 2001-03-21 | United Microelectronics Corp | Manufacturing method of DRAM capacitor |
-
2001
- 2001-03-23 AU AU2001239564A patent/AU2001239564A1/en not_active Abandoned
- 2001-03-23 DE DE60104190T patent/DE60104190T2/de not_active Expired - Lifetime
- 2001-03-23 WO PCT/JP2001/002346 patent/WO2001070380A1/ja active IP Right Grant
- 2001-03-23 US US10/239,522 patent/US6861260B2/en not_active Expired - Fee Related
- 2001-03-23 AT AT01914209T patent/ATE270581T1/de not_active IP Right Cessation
- 2001-03-23 EP EP01914209A patent/EP1266684B1/en not_active Expired - Lifetime
- 2001-03-23 JP JP2001568565A patent/JP3954847B2/ja not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0344807A2 (en) * | 1988-06-03 | 1989-12-06 | Hamamatsu Photonics K.K. | Method for evaluating the permeability of a thin membrane |
JPH08173780A (ja) * | 1994-12-26 | 1996-07-09 | Asahi Chem Ind Co Ltd | 高級脂肪酸エステル化多孔性膜 |
JPH1190214A (ja) * | 1997-09-18 | 1999-04-06 | Tokuyama Corp | 生体物質超薄膜の製造方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007118003A (ja) * | 2005-10-27 | 2007-05-17 | Becton Dickinson & Co | 透過性測定用の固定化多層人工膜(pampa) |
JP2009250727A (ja) * | 2008-04-03 | 2009-10-29 | Nissan Chem Ind Ltd | 人工膜を用いた膜透過性の評価方法及びスクリーニング方法 |
Also Published As
Publication number | Publication date |
---|---|
ATE270581T1 (de) | 2004-07-15 |
JP3954847B2 (ja) | 2007-08-08 |
EP1266684B1 (en) | 2004-07-07 |
DE60104190D1 (de) | 2004-08-12 |
DE60104190T2 (de) | 2005-07-21 |
AU2001239564A1 (en) | 2001-10-03 |
US20030111406A1 (en) | 2003-06-19 |
US6861260B2 (en) | 2005-03-01 |
EP1266684A4 (en) | 2003-06-18 |
EP1266684A1 (en) | 2002-12-18 |
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