公开(公告)号：US4224313A

公开(公告)日：1980-09-23

申请号：US859240

申请日：1977-12-09

申请人： Ulrich Zimmermann ,  Gunter Pilwat ,  Karin Bock ,  Hermann-Josef Buers

发明人： Ulrich Zimmermann ,  Gunter Pilwat ,  Karin Bock ,  Hermann-Josef Buers

IPC分类号： A61K9/50 ,  A61K35/12 ,  A61K35/18 ,  A61K37/48 ,  A61K35/14 ,  A61K43/00 ,  C12B3/12

CPC分类号： A61K9/5068 ,  A61K35/12 ,  A61K35/18

摘要： A material capable of forming hydrogen bonds or covalent bonds with loading materials incorporated in loaded cells is introduced into the cells with the loading materials to inhibit the destruction of the cell membranes by the loading material after the permeability of the membranes is brought back down to its normal value. In order to provide for the hydrogen bond formation with common loading materials, such as methotrexate, proteins such as albumin and sugars such as sucrose are effective. The time period during which these materials inhibit a destructive effect on the membranes of loaded cells is well defined. Accordingly, when cells are loaded with a medicament for interaction with substances external to the cells in a physiological solution in which they are placed, which materials have no destructive effect on the cell membranes, it is advantageous to load the cells also with a material having such a destructive effect, such as pronase P, and at the same with a sugar or a protein for delaying its effect, so that the medicament will be released by destruction of the cell membranes after a predetermined time. In this manner, by injection into an animal bloodstream of a suspension of loaded cells prepared according to the invention suspended in a physiological solution, the timing of the release of a medicament into the bloodstream can be controlled.

摘要翻译： 能够与加载的细胞中的负载材料形成氢键或共价键的材料被引入到具有负载材料的细胞中，以在将膜的渗透性降低到其之后抑制由装载材料破坏细胞膜 正常值 为了提供与普通负载材料如甲氨蝶呤形成氢键，蛋白质如白蛋白和糖如蔗糖是有效的。 这些材料抑制对负载细胞膜的破坏作用的时间周期是明确的。 因此，当细胞装载有用于与放置它们的生理溶液中的细胞外部的物质相互作用的药物时，哪些材料对细胞膜没有破坏作用，有利的是用具有 这样的破坏性作用，例如链霉蛋白酶P，并且与用于延迟其作用的糖或蛋白质相同，使得药物将在预定时间后破坏细胞膜而释放。 以这种方式，通过注射到悬浮在生理溶液中的根据本发明制备的负载细胞的悬浮液的动物血液中，可以控制药物释放到血流中的时间。

公开(公告)号：US4289756A

公开(公告)日：1981-09-15

申请号：US860570

申请日：1977-12-14

申请人： Ulrich Zimmermann ,  Gunter Pilwat ,  Karin Bock ,  Hermann J. Buers

发明人： Ulrich Zimmermann ,  Gunter Pilwat ,  Karin Bock ,  Hermann J. Buers

IPC分类号： A61K9/50 ,  A61K35/12 ,  A61K35/18 ,  A61K37/48 ,  A61K35/14 ,  A61K43/00

CPC分类号： A61K9/5068 ,  A61K35/12 ,  A61K35/18 ,  Y10T436/101666 ,  Y10T436/107497 ,  Y10T436/108331

摘要： Loaded cells suspended in a physiological solution are prepared in a process in which their volume is expanded by osmotic pressure. Cells so prepared suspended in a physiological solution, when injected into the bloodstream of a living body are preferentially accumulated in the spleen and liver of the body, which treats them as foreign bodies, even though the original cells may have been cells of an animal of the same species. Similarly by storing the loaded cells in a solution containing substances such as glutadialdehyde, formaldehyde that react with the protein phase of membranes or which, like difluoro dinitrobenzene, react with the lipid layer thereof, the loaded cells can also be caused to be broken down by the spleen and/or liver. Premature release of the contents of the loaded cells is prevented and timely release of such contents is assured by incorporating other materials into the loaded cells during the preparation process in accordance with the related application of the same inventors, Ser. No. 859,240 filed Dec. 9, 1977, now U.S. Pat. No. 4,224,313, issued Sept. 23, 1980.

摘要翻译： 在其通过渗透压膨胀其体积的过程中制备悬浮在生理溶液中的负载细胞。 悬浮在生理溶液中的细胞在注射到生物体的血液中时优先蓄积在身体的脾脏和肝脏中，即将其视为异物，尽管原始细胞可能是动物的细胞 相同的物种 类似地，通过将​​负载的细胞储存在含有诸如谷丙二醛，甲醛与膜的蛋白质相反应的物质的溶液中，或者像二氟二硝基苯一样与其脂质层反应的负载细胞也可以被分解， 脾脏和/或肝脏。 防止负载的电池的内容物的过早释放，根据相同发明人的相关申请，在制备过程中，通过将其它材料并入加载的电池中来确保这些内容物的及时释放。 1977年12月9日提交的第859,240号，现为美国专利 1980年9月23日发布的第4,224,313号。

公开(公告)号：US4081340A

公开(公告)日：1978-03-28

申请号：US762320

申请日：1977-01-25

申请人： Ulrich Zimmermann ,  Friedrich Riemann ,  Gunter Pilwat

发明人： Ulrich Zimmermann ,  Friedrich Riemann ,  Gunter Pilwat

IPC分类号： G01N27/07 ,  A61K9/50 ,  C02F1/28 ,  C12M1/26 ,  C12M1/42 ,  C12M3/00 ,  C12N1/00 ,  C12N1/08 ,  C12N5/06 ,  C12N13/00 ,  C12Q1/00 ,  G01N27/00 ,  G01N27/40

CPC分类号： C12N13/00 ,  A61K9/5068 ,  C02F1/286 ,  C12M35/02

摘要： A method of and device for increasing the permeability of the skin of cellsf living beings, according to which the respective cells are introduced in the form of a suspension into an electrically conductive liquid. Thereby there is formed a physiological electrolyte solution which is passed into one of two chambers through a passage of a partition. This partition separates a container into these two chambers, each chamber having an electrode. This passage surrounds the focus of an electric field. The cells in the electrolyte solution are exposed to the electric field while passing from one chamber to the other chamber until macromolecules having a radius of at least 5 A are exchanged through the cell skin between the solution in the interior of the cells and the physiological electrolyte solution.

摘要翻译： 用于增加生物细胞的皮肤的渗透性的方法和装置，根据该方法，将各细胞以悬浮液的形式引入导电液体中。 从而形成生理电解质溶液，该生理电解质溶液通过隔板的通道进入两个室之一。 该隔板将容器分成这两个室，每个室具有电极。 这个通道围绕电场的焦点。 电解质溶液中的细胞在从一个室到另一个室通过时暴露于电场，直到具有至少5A的半径的大分子通过细胞内部的溶液与生理电解质之间的细胞皮肤交换 解。

公开(公告)号：US4292408A

公开(公告)日：1981-09-29

申请号：US19436

申请日：1979-03-12

申请人： Ulrich Zimmermann ,  Gunter Pilwat

发明人： Ulrich Zimmermann ,  Gunter Pilwat

IPC分类号： B01J20/24 ,  B01D15/00 ,  C02F1/28 ,  C12M1/34 ,  C12N1/12 ,  C12N13/00 ,  C12P3/00 ,  C12R1/89 ,  C22B3/18 ,  G21F9/18 ,  C02F3/00 ,  C12N1/20

CPC分类号： B01D15/00 ,  C02F1/286 ,  C12N13/00 ,  C22B3/18 ,  G21F9/18 ,  Y02P10/234 ,  Y10S423/17

摘要： A mass, and method of preparing such mass, and using the same for adsorbing metal ions from a physiological solution by means of living cells suspended in the solution. The cells suspended in the solution at a density of up to 20% by weight are exposed to an electric field of such intensity and over such a period of time that the membrane of the cells will be so changed that substances present in the interior of the cells and having a diameter within the range of from 2 to 50 A, such as potassium and proteins, pass from the interior of the cells into the physiological solution. The electric force or intensity is limited in such a way that the changes in the membrane of the cells can be healed by regeneration of the cells. The mass is introduced into the aqueous solution, such as sea water, lake water or waste water, and left therein until the mass as adsorbed therefrom the metal at a desired concentration, whereupon the mass is separated from the aqueous solution.

摘要翻译： 一种质量和制备这种物质的方法，并且使用它们通过悬浮在溶液中的活细胞从生理溶液中吸附金属离子。 以高达20重量％的密度悬浮在溶液中的细胞暴露于这样强度的电场，并且在这样的时间段内，细胞的膜将被改变，使得存在于内部的物质 细胞并且具有2至50A范围内的直径，例如钾和蛋白质，从细胞内部通过生理溶液。 电力或强度受限于细胞膜的变化可以通过细胞的再生来治愈。 将质量引入水溶液，例如海水，湖水或废水中，并留在其中，直到质量以所需浓度吸附到金属上，然后将该物质与水溶液分离。

公开(公告)号：US4220916A

公开(公告)日：1980-09-02

申请号：US29842

申请日：1979-04-13

申请人： Ulrich Zimmermann ,  Gunter Pilwat ,  Michael Groves

发明人： Ulrich Zimmermann ,  Gunter Pilwat ,  Michael Groves

IPC分类号： G01N15/02 ,  C12M3/00 ,  G01N15/12 ,  G01N33/487 ,  G01R31/12 ,  G01N27/07

CPC分类号： G01R31/1263 ,  G01N15/1245 ,  G01N33/48728

摘要： A method of and an apparatus for determining the dielectric breakdown chateristics and size of membrane-sheathed particles such as living-organism cells and the apparent size of such particles after breakdown of the membrane, makes use of two measuring orifices traversed by an electrolyte across which an increasing electric field is applied during the measuring process in which the particles successively traverse one of the orifices. The current through the measuring orifice deviates from the linear with increasing field generated preferably by a sawtooth voltage, the current change being used to measure the particle variables stated.

摘要翻译： 用于确定诸如活体细胞的膜护套颗粒的绝缘击穿特性和尺寸的方法和装置，以及膜破裂后这种颗粒的表观尺寸，利用由电解质横穿的两个测量孔 在颗粒连续地穿过其中一个孔的测量过程中施加增加的电场。 通过测量孔的电流优选地通过锯齿电压产生的增加磁场偏离线性，电流变化用于测量所述的粒子变量。

公开(公告)号：US4350767A

公开(公告)日：1982-09-21

申请号：US264022

申请日：1981-05-15

申请人： Ulrich Zimmermann ,  Mohammed Saleemuddin ,  Gunter Pilwat

发明人： Ulrich Zimmermann ,  Mohammed Saleemuddin ,  Gunter Pilwat

IPC分类号： B01D15/00 ,  B01J20/24 ,  C12N9/00 ,  C12N9/02 ,  C12N9/88 ,  C12N9/04

CPC分类号： C12N9/0008 ,  C12N9/00 ,  C12N9/88 ,  C12Y102/01009 ,  Y10S435/815

摘要： A method and adsorption medium for isolating and purifying enzymes from a crude enzyme solution of animal organs or tissues. An adsorption medium for bringing about the binding of a predetermined enzyme is introduced into the crude enzyme solution and is left therein until the binding takes place, whereupon the adsorption medium is removed from the crude enzyme solution and the enzyme is separated from the adsorption medium by extraction or elution with a suitable solution. The adsorption medium is in the form of membranes of human or animal erythrocytes which have been hemolyzed by osmosis. Those enzymes which have the same or nearly the same affinity as regards binding on the membranes as does the predetermined enzyme which is to be bound are separated from the membranes prior to introducing the membranes into the crude enzyme solution. The amount of the enzymes first removed that is bound being less than the amount of erythrocytes used to form the membranes.

摘要翻译： 一种用于从动物器官或组织的粗酶溶液中分离和纯化酶的方法和吸附介质。 将用于实现预定酶的结合的吸附介质引入粗酶溶液中并留在其中直到发生结合，然后从粗酶溶液中除去吸附介质，并通过 用合适的溶液萃取或洗脱。 吸附介质是通过渗透溶血的人或动物红细胞的膜的形式。 在将膜引入粗酶溶液之前，将与膜结合相同或几乎相同的亲和力的酶与膜结合的预定酶分离。 首先除去的酶结合量少于用于形成膜的红细胞的量。

公开(公告)号：US4269826A

公开(公告)日：1981-05-26

申请号：US859563

申请日：1977-12-12

申请人： Ulrich Zimmermann ,  Gunter Pilwat

发明人： Ulrich Zimmermann ,  Gunter Pilwat

IPC分类号： A61K9/50 ,  A61K35/12 ,  A61K35/18 ,  A61K45/08 ,  C12N13/00 ,  A61K35/14 ,  A61K37/48 ,  A61K43/00

CPC分类号： A61K35/18 ,  A61K35/12 ,  A61K9/5068 ,  A61K9/5094

摘要： Magnetic substances in particles of a diameter in the range between 1 and 20 nm are suspended in the physiological solution by which cells are loaded with materials when their cell membranes have increased permeability, the magnetic materials being provided in such dosing, that when the cells are loaded, separated from the loading solution and prepared for use in a fresh physiological solution, thereafter injected to a living body, they can be collected and held fast at a predetermined location, for example, at the location of a tumor, by the effect of an external magnetic field. Ferritin, magnetite, cobalt ferrite, nickel ferrite and other ferrimagnetic, ferromagnetic or even paramagnetic compounds can be incorporated into loaded cells for this purpose.

摘要翻译： 直径在1至20nm范围内的颗粒中的磁性物质悬浮在生理溶液中，细胞在其细胞膜具有增加的渗透性时被装载材料，磁性材料以这种剂量提供，当细胞为 加载，与装载溶液分离并准备用于新鲜的生理溶液中，然后注射到生物体中，可以在预定的位置（例如在肿瘤的位置）快速收集和保持，通过 外部磁场。 铁素体，磁铁矿，钴铁氧体，镍铁氧体和其他铁磁性，铁磁性或甚至顺磁性化合物可以结合到装载的电池中用于此目的。

公开(公告)号：US4154668A

公开(公告)日：1979-05-15

申请号：US750677

申请日：1976-12-15

申请人： Ulrich Zimmermann ,  Friedrich Riemann ,  Gunter Pilwat

发明人： Ulrich Zimmermann ,  Friedrich Riemann ,  Gunter Pilwat

IPC分类号： G01N27/07 ,  A61K9/50 ,  C02F1/28 ,  C12M1/26 ,  C12M1/42 ,  C12M3/00 ,  C12N1/00 ,  C12N1/08 ,  C12N5/06 ,  C12N13/00 ,  C12Q1/00 ,  G01N27/00 ,  G01N27/40

CPC分类号： C12N13/00 ,  A61K9/5068 ,  C02F1/286 ,  C12M35/02

摘要： A device for increasing the permeability of the skin of cells of living bgs, according to which the respective cells are introduced in the form of a suspension into an electrically conductive liquid thereby there is formed a physiological electrolyte solution which is passed into one of two chambers through a passage of a partition. This partition separates a container into these two chambers, each chamber having an electrode. This passage surrounds the focus of an electric field. The cells in the electrolyte solution are exposed to the electric field while passing from one chamber to the other chamber until macromolecules having a radius of at least 5.degree. are exchanged through the cell skin between the solution in the interior of the cells and the physiological electrolyte solution.

摘要翻译： 一种用于增加生物细胞的皮肤的渗透性的装置，根据该装置，将各细胞以悬浮液的形式引入导电液体中，从而形成生理电解质溶液，该生理电解质溶液通过两个室 通过分隔的通道。 该隔板将容器分成这两个室，每个室具有电极。 这个通道围绕电场的焦点。 电解质溶液中的细胞在从一个室传递到另一个室时暴露于电场，直到具有至少5°的半径的大分子通过细胞内部的溶液和生理电解质之间的细胞皮肤交换 解。

公开(公告)号：US4055799A

公开(公告)日：1977-10-25

申请号：US651337

申请日：1976-01-22

申请人： Hans Coster ,  Gunter Pilwat ,  Ulrich Zimmermann

发明人： Hans Coster ,  Gunter Pilwat ,  Ulrich Zimmermann

IPC分类号： G01N27/22 ,  A61B5/05 ,  A61B5/145 ,  C12M1/34 ,  G01N15/00 ,  G01N15/10 ,  G01N15/12 ,  G01N27/00 ,  G01N33/483 ,  G01N33/487 ,  G01R27/26

CPC分类号： G01N33/48728 ,  A61B5/05 ,  C12M35/02 ,  G01N15/1245 ,  G01R27/2658 ,  G01N2015/0073 ,  G01N2015/1006

摘要： A method of and device for ascertaining elastic and di-electric propertiesf the diaphragm of individual living cells of living beings or of the diaphragms of such living cells in a physiological liquid in suspension or of such living cells in an association in the form of a layer. One or more of such cells or one or more layers of such cells is or are introduced into a physiological liquid which has a temperature of between 0.degree. and 40.degree. C and which is electrically conductive and forms an electrolyte solution. The cell, cells or layer of cells are located between two electrodes in such a way that the flow lines of an electric field provided between the two electrodes penetrate the diaphragm of the cell, cells or layer of cells introduced into the electrolyte solution. Thereupon a succession of voltage pulses with a constant pulse duration of from 1 .mu.s and 10 ms is applied to the electrodes and the amplitude of the voltage pulses between 100 mV and 5V is increased until at the obtainment of the break-down voltage the resulting current pulses greatly increase. The break-down voltage will then be measured by means of two measuring electrodes.

摘要翻译： 一种用于确定生物体的活细胞或这些活细胞在悬浮液或这种活细胞中的生理液体中的隔膜的弹性和二电性质的方法和装置，其形式为 层。 一种或多种这样的细胞或一层或多层这样的细胞被引入生理液体中，该生理液体的温度在0〜40℃之间，并且是导电的并形成电解质溶液。 细胞，细胞或细胞层位于两个电极之间，使得提供在两个电极之间的电场的流​​动线穿过细胞的隔膜，引入电解质溶液的细胞或细胞层。 因此，对电极施加了持续脉冲持续时间为1μs和10ms的一系列电压脉冲，并且在100mV和5V之间的电压脉冲的幅度增加，直到获得了分解电压，从而得到 电流脉冲大大增加。 然后通过两个测量电极测量击穿电压。

公开(公告)号：US4887434A

公开(公告)日：1989-12-19

申请号：US235367

申请日：1988-08-23

申请人： Gunter Pilwat ,  Jochen Rudolph

发明人： Gunter Pilwat ,  Jochen Rudolph

IPC分类号： B01D8/00 ,  G01N30/00

CPC分类号： B01D8/00 ,  G01N30/00

摘要： Samples of trace substances are cryogenically concentrated by passing a gas sample through a U-bend immersed in liquid nitrogen. The U-bend is surrounded by a chamber wall and the chamber is vented so that liquid nitrogen can rise into the chamber when the vent is open but is driven out when the vent is closed and the enrichment pipe is heated to desorb the accumulated trace substances from the adsorbent in the enrichment pipe.

摘要翻译： 通过将气体样品通过浸没在液氮中的U形弯曲而将痕量物质的样品低温浓缩。 U形弯曲部被室壁包围，并且腔室被排出，使得当通风口打开时液氮可以上升到室中，但是当通风口关闭时被驱出并且富集管被加热以解吸积累的痕量物质 从富集管中的吸附剂。