公开(公告)号：US6024878A

公开(公告)日：2000-02-15

申请号：US183047

申请日：1998-10-30

申请人： Douglas T. Gjerde ,  Paul D. Taylor ,  Robert M. Hae Fele

发明人： Douglas T. Gjerde ,  Paul D. Taylor ,  Robert M. Hae Fele

IPC分类号： C12N15/09 ,  B01D15/08 ,  B01D15/36 ,  B01J20/26 ,  B01J20/32 ,  C12N15/10 ,  C12Q1/68 ,  G01N30/34 ,  G01N30/88

CPC分类号： B01D15/366

摘要： Mixtures of dsDNA fragments are separated by Matched Ion Polynucleotide Chromatography (MIPC) using an isocratic mobile phase to elute polynucleic acid from an MIPC column. The use of isocratic elution conditions provides a marked improvement in the separation of dsDNA fragments compared to gradient elution conditions. Isocratic elution can also be used to effect an improved separation of heteroduplex and homoduplex mixtures when the chromatography is performed under partially denaturing conditions. In addition, dsDNA fragments are bound to the stationary phase under isocratic conditions until a solvent concentration is reached which releases fragments of a particular base pair length range. This separation process is different from the equilibrium partitioning process observed under gradient elution conditions.

摘要翻译： 通过使用等度流动相的匹配离子多核苷酸色谱（MIPC）分离dsDNA片段的混合物以从MIPC柱洗脱多核酸。 与梯度洗脱条件相比，使用等度洗脱条件提供了dsDNA片段分离的显着改善。 当在部分变性条件下进行层析时，等度洗脱也可用于改进异源双链和同源双链混合物的分离。 此外，双链DNA片段在等度条件下与固定相结合，直至达到溶剂浓度，释放特定碱基对长度范围的片段。 该分离过程不同于在梯度洗脱条件下观察到的平衡分配过程。

公开(公告)号：US5986085A

公开(公告)日：1999-11-16

申请号：US65913

申请日：1998-04-24

申请人： Douglas T. Gjerde ,  Robert M. Haefele ,  Paul D. Taylor

发明人： Douglas T. Gjerde ,  Robert M. Haefele ,  Paul D. Taylor

IPC分类号： C12N15/10 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/101

摘要： A batch process for obtaining polynucleotide fragments, such as dsDNA, having a selected size from a mixture of polynucleotide fragments including the steps of a) applying a solution of the mixture of polynucleotide fragments and a counterion agent to a binding medium having a hydrophobic surface; b) contacting the binding medium with a first stripping solvent and counterion agent, the first stripping solvent having a concentration of organic component sufficient to release from the binding medium all polynucleotide fragments having a size smaller than the selected size, and removing the first stripping solvent from the binding medium; and c) contacting the binding medium with a second stripping solvent having a concentration of organic component sufficient to release from the binding medium the polynucleotide fragments having the selected size, and removing the second stripping solvent from the binding medium. The binding medium can be organic polymer or inorganic particle beads. The mixture of polynucleotides can be the product of a PCR amplification. The binding medium can be contained within a column, a web or a container.

摘要翻译： 用于从多核苷酸片段的混合物中获得具有选定大小的多核苷酸片段（例如dsDNA）的分批方法，包括以下步骤：a）将多核苷酸片段和抗衡离子混合物的溶液施用于具有疏水性表面的结合介质; b）使所述结合介质与第一剥离溶剂和抗衡离子剂接触，所述第一剥离溶剂具有足以从所述结合介质释放的有机组分的浓度，所述多个片段的尺寸小于所选择的尺寸，并且除去所述第一剥离溶剂 从结合介质; 和c）使所述结合介质与第二剥离溶剂接触，所述第二剥离溶剂具有足以从所述结合介质释放具有所选择尺寸的多核苷酸片段的有机组分浓度，以及从所述结合介质中除去所述第二剥离溶剂。 结合介质可以是有机聚合物或无机颗粒珠。 多核苷酸的混合物可以是PCR扩增的产物。 结合介质可以包含在柱，网或容器中。

公开(公告)号：US5393888A

公开(公告)日：1995-02-28

申请号：US204577

申请日：1994-03-02

申请人： Francis B. Minnock ,  Paul D. Taylor

发明人： Francis B. Minnock ,  Paul D. Taylor

IPC分类号： C07D207/26 ,  C07D207/267 ,  C07D201/08

CPC分类号： C07D207/267

摘要： This invention relates to a liquid phase process for producing 2-pyrrolidone in high yield and selectivity in the absence of catalyst and extraneous solvents which involves contacting ammonia with butyrolactone in a molar ratio of from 0.5:1 to 0.85:1 at high temperature and pressure sufficient to maintain the liquid phase.

摘要翻译： 本发明涉及在不存在催化剂和外来溶剂的情况下以高产率和选择性生产2-吡咯烷酮的液相方法，该方法包括使氨与丁酸内酯在摩尔比为0.5:1至0.85:1的高温和高压下接触 足以维持液相。

公开(公告)号：US5347021A

公开(公告)日：1994-09-13

申请号：US656388

申请日：1991-02-19

申请人： Paul D. Taylor ,  Waldo De Thomas ,  Donald W. Buchanan, Jr.

发明人： Paul D. Taylor ,  Waldo De Thomas ,  Donald W. Buchanan, Jr.

IPC分类号： B01J23/80 ,  B01J35/10 ,  B01J37/18 ,  C07B61/00 ,  C07D307/33 ,  C07D315/00

CPC分类号： C07D315/00 ,  B01J23/80 ,  B01J37/18

摘要： Vapor phase catalytic hydrogenation of maleic anhydride to gamma-butyrolactone is achieved in a conversion of 95% or more and a selectivity of 80% or more during a prolonged period of production. The process uses an activated catalyst prepared by reducing a catalyst composition comprising 30-65% by weight of CuO, 18-50% by weight of ZnO and 8-22% by weight of Al.sub.2 O.sub.3, and activating the reduced catalyst composition in hydrogen at an activation temperature of at least 400.degree. C., preferably 400.degree. to 525.degree. C., and optimally about 425.degree. C. The process suitably is carried out under predetermined and advantageous process conditions, including a defined molar ratio of hydrogen to maleic anhydride in the vapor reactant stream, a selected pressure during hydrogenation, a defined feed rate space velocity, a predetermined contact time, and a suitable reaction temperature.

摘要翻译： 在长时间的生产过程中，将马来酸酐与γ-丁内酯的气相催化氢化达到95％以上的转化率和80％以上的选择性。 该方法使用通过还原包含30-65重量％的CuO，18-50重量％的ZnO和8-22重量％的Al 2 O 3的催化剂组合物制备的活化催化剂，并且在氢气中活化还原的催化剂组合物 活化温度至少为400℃，优选为400至525℃，最佳为约425℃。该方法适合在预定和有利的工艺条件下进行，包括规定的氢与马来酸酐的摩尔比 蒸汽反应物流，氢化期间的选定压力，限定的进料速率空速，预定的接触时间和合适的反应温度。

公开(公告)号：US5227509A

公开(公告)日：1993-07-13

申请号：US520042

申请日：1990-05-07

申请人： Kolazi S. Narayanan ,  Paul D. Taylor

发明人： Kolazi S. Narayanan ,  Paul D. Taylor

IPC分类号： C07B61/00 ,  C07C331/20

CPC分类号： C07B61/00 ,  C07C331/20

摘要： A method for preparing (R)X.sub.m-p A.sub.p by reacting (R)X.sub.m and MA in N-methylpyrrolidone and recovering the by-product MX as a precipitate wherein:X is halide;R contains from 1 to 8 carbon atoms, can be substituted or unsubstituted, and is straight or branched chain alkyl, cycloaliphatic, aralkyl, alkylene, alkenyl, alkenylene, alkynyl or alkynylene with the proviso that X is not attached to a carbon atom having a double bond;A.sup.- is a monovalent anion soft base selected from the group consisting of halide different from X, SCN.sup.-, SH.sup.-, SO.sub.3 H.sup.-, R.sub.2 PO.sub.4.sup.-, PF.sub.6.sup.-, and [SP(Z) (OR.sup.1).sub.2 ].sup.- wherein R.sup.1 is lower alkyl and z i sulfur or oxygen;M is an alkali metal or NH.sub.4.sup.+ ;m is an integer from 1 to 3 with the proviso that m is 1 or 2 when R has one carton; andP is an integer from 1 to m.

摘要翻译： 一种通过（R）Xm和MA在N-甲基吡咯烷酮中反应制备（R）Xm-pAp的方法，并回收作为沉淀物的副产物MX，其中X是卤化物; R包含1至8个碳原子，可以是取代或未取代的，并且是直链或支链烷基，脂环族，芳烷基，亚烷基，烯基，亚烯基，炔基或亚炔基，条件是X不连接到具有 双键; A-是选自不同于X，SCN-，SH-，SO 3 - ，R 2 PO 4 - ，PF 6 - 和[SP（Z）（OR 1）2] - 的卤素的一价阴离子软碱，其中R1较低 烷基和i硫或氧; M是碱金属或NH4 +; m是1至3的整数，条件是当R具有一个纸箱时，m为1或2; P为1〜m的整数。

公开(公告)号：US5206386A

公开(公告)日：1993-04-27

申请号：US675367

申请日：1991-03-20

申请人： Kolazi S. Narayanan ,  Paul D. Taylor

发明人： Kolazi S. Narayanan ,  Paul D. Taylor

IPC分类号： C07D207/26 ,  C07D207/27

CPC分类号： C07D207/27

摘要： N-substituted cyclic lactam esters are made from biologically active organic acids and N-haloalkyl substituted cyclic lactam, preferably N-chloromethyl pyrrolidone. Such esters provide slow release of the organic acids in situ through slow hydrolysis of the ester to release the organic acid and the N-alkyl substituted cyclic lactam. The esters are useable for delivering a large variety of biologically active organic acids in slow release fashion to target organisms and promote effective long term therapeutic treatment. In particular, an ester made from acetyl salicyclic acid and chloromethyl pyrrolidone provides a vehicle for dermal penetration and slow release of aspirin for long term treatment.

摘要翻译： N-取代的环状内酰胺酯由生物活性有机酸和N-卤代烷基取代的环状内酰胺，优选N-氯甲基吡咯烷酮制成。 这种酯通过缓慢水解酯释放有机酸和N-烷基取代的环状内酰胺，从而提供了原位缓慢释放有机酸。 酯可用于以缓释方式将大量各种各样的生物活性有机酸递送至靶生物并促进有效的长期治疗治疗。 特别地，由乙酰水杨酸和氯甲基吡咯烷酮制成的酯提供用于长期治疗的阿司匹林的皮肤渗透和缓慢释放的载体。

公开(公告)号：US06576133B2

公开(公告)日：2003-06-10

申请号：US09753856

申请日：2001-01-02

申请人： Douglas T. Gjerde ,  David P. Hornby ,  Christopher P. Hanna ,  Alexander I. Kuklin ,  Robert M. Haefele ,  Paul D. Taylor

发明人： Douglas T. Gjerde ,  David P. Hornby ,  Christopher P. Hanna ,  Alexander I. Kuklin ,  Robert M. Haefele ,  Paul D. Taylor

IPC分类号： B01D1508

CPC分类号： B01D15/366 ,  C12N15/101

摘要： A Matched Ion Polynucleotide Chromatography method and system for size-based segregation of a mixture of RNA molecules. The method includes applying the mixture to a polymeric separation medium having non-polar surfaces and eluting the RNA molecules with a mobile phase which includes counterion reagent and an organic component. The preferred surfaces are characterized by being substantially free from multivalent cations which are free to interfere with RNA segregation. The elution is preferably performed at a temperature sufficient to denature the RNA. The method can be used in segregating RNA molecules having lengths in the range of about 100 to 20,000 nucleotides. Improved segregation is obtained using a chromatography column having an ID greater than about 5 mm. Examples of separation media include beads and monolithic columns.

摘要翻译： 匹配的离子多核苷酸色谱法和基于尺寸的RNA分子混合物分离的系统。 该方法包括将混合物施加到具有非极性表面的聚合物分离介质中，并用包含抗衡离子试剂和有机组分的流动相洗脱RNA分子。 优选的表面的特征在于基本上不含可以干扰RNA分离的多价阳离子。 洗脱优选在足以使RNA变性的温度下进行。 该方法可用于分离长度在约100至20,000个核苷酸范围内的RNA分子。 使用ID大于约5mm的色谱柱获得改进的分离。 分离介质的实例包括珠粒和整体柱。

公开(公告)号：US06521123B2

公开(公告)日：2003-02-18

申请号：US09848385

申请日：2001-05-02

申请人： Douglas T. Gjerde ,  Paul D. Taylor ,  Robert M. Haefele

发明人： Douglas T. Gjerde ,  Paul D. Taylor ,  Robert M. Haefele

IPC分类号： B01D1508

CPC分类号： B01D15/366 ,  C12N15/101

摘要： Non-polar polymeric separation media, such as beads or monoliths, are suitable for chromatographic separation of mixtures of polynucleotides when the surfaces of the media are unsubstituted or substituted with a hydrocarbon group having from one to 1,000,000 carbons and when the surfaces are substantially free from mutivalent cation contamination. The polymeric media provide efficient separation of polynucleotides using Matched Ion Polynucleolide Chromatography. Methods for maintaining and storing the polymeric media include treatment with multivalent cation binding agents.

摘要翻译： 非极性聚合物分离介质，例如珠粒或整料适用于当介质的表面未被取代或被具有1至1,000,000个碳原子的烃基取代时的多核苷酸混合物的色谱分离，并且当表面基本上不含 多价阳离子污染 聚合物介质使用匹配离子多核苷酸色谱法提供多核苷酸的有效分离。 维持和储存聚合物介质的方法包括用多价阳离子结合剂进行处理。

公开(公告)号：US06355417B2

公开(公告)日：2002-03-12

申请号：US09039061

申请日：1998-03-13

申请人： Douglas T. Gjerde ,  Paul D. Taylor

发明人： Douglas T. Gjerde ,  Paul D. Taylor

IPC分类号： C12Q168

CPC分类号： G01N27/44721 ,  G01N30/8651

摘要： A method and apparatus for representing double stranded nucleic acid fragments which have been separated by a chromatographic process as an array of bands which can be accurately quantified, optimized and stored. Using, for example, a Matched Ion Polynucleotide Chromatography (MIPC) process, an analog output from a UV detector is digitized and input to a computer. The digitized signal is converted to a linear array of bands which may be displayed on a video display terminal. The intensity and/or color of a band may correlate to the amount of double stranded nucleic acid in the respective fraction or the respective double stranded nucleic acid fragment above a user selected threshold level at a corresponding point in the digitized signal. The calculated base pair length, concentration, and retention time of each band in the array of bands may be displayed in alphanumeric form.

摘要翻译： 用于表示已经通过色谱法分离的双链核酸片段的方法和装置可以被精确量化，优化和储存的条带阵列。 使用例如匹配离子多核苷酸色谱（MIPC）方法，将来自UV检测器的模拟输出数字化并输入到计算机。 数字化信号被转换成可以显示在视频显示终端上的线性阵列阵列。 条带的强度和/或颜色可以与在数字化信号的对应点处的用户选择的阈值水平之上的相应级分或相应双链核酸片段中的双链核酸的量相关。 频带阵列中每个频带的计算的碱基对长度，浓度和保留时间可以以字母数字形式显示。

公开(公告)号：US06355165B1

公开(公告)日：2002-03-12

申请号：US09580302

申请日：2000-05-26

申请人： John E. Sutton ,  Douglas T. Gjerde ,  Paul D. Taylor

发明人： John E. Sutton ,  Douglas T. Gjerde ,  Paul D. Taylor

IPC分类号： B01D1508

CPC分类号： B01J20/287 ,  B01D15/161 ,  B01D15/20 ,  B01D15/366 ,  G01N30/30 ,  G01N30/54 ,  G01N30/96

摘要： A liquid chromatography apparatus with stationary and mobile phase temperature controls suitable for polynucleotide separations by MIPC and DMIPC processes. The apparatus includes heater means with a temperature control system; a matched ion polynucleotide chromatography separation column having an inlet end; a coil of capillary tubing having an inlet end and an outlet end. The outlet end of the capillary tubing is connected with the inlet end of the separation column. The inlet end of the capillary tubing comprising means for receiving process liquid, the tubing having a length of from 6 to 400 cm having a linear tubing length of heating means. The separation column and the coil of capillary tubing are enclosed in the heater means. The capillary tubing preferably is PEEK or titanium. The heater means can be an air batch oven. Preferably, it is a heat-conducting block having a first heat transfer surface, a separation column receptacle, and a capillary coil receptacle. A separation column is positioned within the separation column receptacle in heat conducting relationship with an inner wall thereof. A coil of capillary tubing is positioned in the capillary coil receptacle, the outer extremities of the coil being in heat conducting relationship with an inner wall of the capillary coil receptacle. Optimally, the heating means is a Peltier heating and cooling unit in heat conducting relationship with a heat transfer surface of the heating block.

摘要翻译： 具有适用于MIPC和DMIPC工艺的多核苷酸分离的固定和流动相温度控制的液相色谱仪。 该装置包括具有温度控制系统的加热器装置; 具有入口端的匹配离子多核苷酸色谱分离柱; 具有入口端和出口端的毛细管线圈。 毛细管的出口端与分离柱的入口端连接。 毛细管的入口端包括用于接收处理液体的装置，该管道具有6至400cm的长度，其具有加热装置的线性管长度。 分离柱和毛细管线圈封闭在加热器装置中。 毛细管优选为PEEK或钛。 加热器装置可以是空气分批炉。 优选地，它是具有第一传热表面，分离柱容器和毛细管线圈容器的导热块。 分离柱位于分离塔容器内，与其内壁呈导热关系。 毛细管线圈定位在毛细管线圈容器中，线圈的外端与毛细管线圈容器的内壁处于热传导关系。 最佳地，加热装置是与加热块的传热表面导热关系的珀尔帖加热和冷却单元。