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1. 发明公开

EP0314444A2 Novel oxathiolanes and derivatives thereof, pharmaceutical compositions containing them and the use thereof as medicaments 失效
标题翻译： Oxothiolane和衍生物，含有它们和它们作为药物的用途的药物组合物。
公开(公告)号：EP0314444A2
公开(公告)日：1989-05-03
申请号：EP88310040.6
申请日：1988-10-26
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Fisher, Abraham , Karton, Ishai
IPC分类号： C07D497/20 , C07B59/00 , A61K31/435 , A61K51/04
CPC分类号： C07D497/20
摘要： Novel spiro-oxathiolane/quinuclidine compounds correspond with the schematic structural formula (I)
and geometrical isomers, enantiomers, diastereoisomers, racemates and acid addition salts thereof, wherein one of Y and Z is O and the other is S (=O) n ; n is 0, 1 or 2; R′ and R˝ are each selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aminoalkyl, C₃₋₇ cycloalkyl, aryl, diarylmethylol and alkyl substituted by at least one aryl group, provided that at least R′ or R˝ is other than hydrogen; and each X is hydrogen, or when Y is O and Z is S(=O) n simultaneously, then each X may also be selected from the group consisting of deuterium and tritium, and provided further that when each X is hydrogen, Y is O and Z is S simultaneously, then at least one of R′ and R˝ is selected from the group consisting of alkenyl, alkynyl, cyclopropyl, cyclobutyl, cycloheptyl, hydroxyalkyl and aminoalkyl. These compounds are useful for manufacturing therapeutic and diagnostic agents applicable to disorders of or relating to the central nervous and cholinergic systems.
摘要翻译：新型螺环氧硫杂环戊烷/奎宁环化合物对应与示意性结构式（I）和几何异构体，对映异构体，非对映体，种族配合以及它们的酸加成盐，worin的Y之一，Z是O，另一个是S（= O ）n表示 n为0，1或2; R最小值和R秒各自选自被至少一个芳基选自氢，烷基，烯基，炔基，羟基烷基，氨基烷基，C 3-7环烷基，芳基和烷基diarylmethylol substituiertem的选择，至少提供没有R最小值或 ř秒不是氢; 且每个X是氢时，或当Y是O和Z是S（= O）N同时，则每个X可因此被选自氘和氚由......组成选择，并且提供Furtherwirt做当每个X是氢，Y是 O和Z为S同时，则至少R最小值和R秒一个是选自链烯基，炔基，环丙基，环丁基，环庚基，羟烷基和氨基烷基中选择的。这些化合物可用于制造治疗和诊断剂适用于病症或与之相关的中枢神经和胆碱能系统是有用的。

2. 发明授权

EP1381348B1 SKIN-PROTECTIVE COMPOSITIONS EFFECTIVE AGAINST VESICANTS AND PERCUTANEOUS CHEMICAL AGENTS 有权
标题翻译：皮肤保护剂效力反对VESIKANZIEN和经皮的化学药剂
公开(公告)号：EP1381348B1
公开(公告)日：2011-08-17
申请号：EP01274158.3
申请日：2001-12-31
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： BARNESS, Itzhak , KADAR, Tamar , FISHBINE, Eliezer
IPC分类号： A61K8/34 , A61K8/23 , A61Q17/00
CPC分类号： A61Q17/00 , A61K8/19 , A61K8/20 , A61K8/22 , A61K8/345 , A61K8/36 , A61K8/362 , A61K8/365 , A61K8/368 , A61K8/38 , A61K8/44 , A61K8/46 , A61K8/55 , A61K8/60 , A61K8/676 , A61K8/73 , A61K8/732 , A61K8/86 , A61K2800/75 , Y10T442/2516
摘要： A protective agent suitable to protect the human skin against lesions caused by vesicants or other percutaneous chemical agents, particularly against sulfur mustard gas injury and VX intoxication, which comprises a protective-effective amount of a hydrophilic water-based cream, alone or together with one or more additives selected from among the group consisting essentially of polyols, mono-, oligo- or polysaccharides, and salts of organic or inorganic acids. The additive polyol may be glycol, propylene glycol, polyglygcerol, glycerin, sorbitol, dulcitol, tritol, sorbitol or mannitol. The additive monosaccharide may be ribose, xylose, glucose, fructose, galactose or mannose. The additive oligosaccharide may be sucrose, maltose, lactose, raffinose or cellobiose.

3. 发明公开

EP0314444A3 Novel oxathiolanes and derivatives thereof, pharmaceutical compositions containing them and the use thereof as medicaments 失效
标题翻译：新型氧化剂及其衍生物，含有它们的药物组合物及其作为药物的用途
公开(公告)号：EP0314444A3
公开(公告)日：1990-11-07
申请号：EP88310040.6
申请日：1988-10-26
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Fisher, Abraham , Karton, Ishai
IPC分类号： C07D497/20 , C07B59/00 , A61K31/435 , A61K51/04
CPC分类号： C07D497/20
摘要： Novel spiro-oxathiolane/quinuclidine compounds correspond with the schematic structural formula (I)
and geometrical isomers, enantiomers, diastereoisomers, racemates and acid addition salts thereof, wherein one of Y and Z is O and the other is S (=O) n ; n is 0, 1 or 2; R′ and R˝ are each selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, aminoalkyl, C₃₋₇ cycloalkyl, aryl, diarylmethylol and alkyl substituted by at least one aryl group, provided that at least R′ or R˝ is other than hydrogen; and each X is hydrogen, or when Y is O and Z is S(=O) n simultaneously, then each X may also be selected from the group consisting of deuterium and tritium, and provided further that when each X is hydrogen, Y is O and Z is S simultaneously, then at least one of R′ and R˝ is selected from the group consisting of alkenyl, alkynyl, cyclopropyl, cyclobutyl, cycloheptyl, hydroxyalkyl and aminoalkyl. These compounds are useful for manufacturing therapeutic and diagnostic agents applicable to disorders of or relating to the central nervous and cholinergic systems.

4. 发明公开

EP0212880A1 Production of carcinoembryonic antigen 失效
标题翻译： Herstellung von Karzinoembryonalem抗原。
公开(公告)号：EP0212880A1
公开(公告)日：1987-03-04
申请号：EP86305869.9
申请日：1986-07-30
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Epstein, Nava , Ariel, Naomi , Reuveny, Shaul , Altboum, Ze'ev , Lazar, Arye
IPC分类号： C12P21/00 , C12N5/00 , A61K39/00
CPC分类号： C07K16/3007 , A61K38/00 , C07K14/705
摘要： A process for the production of carcionembryonic antigen (CEA), comprises the steps of cultivating a CEA-producing cell line in a monolayer culture; further cultivating the said cell line on particulate microcarriers with continuous agitation of the culture medium, in at least one further cultivation step; harvesting the medium containing the desired CEA secreted by the cells; and purifying the CEA until iodination grade product is obtained.
摘要翻译：一种生产癌胚抗原（CEA）的方法，包括在单层培养中培养产生CEA的细胞系的步骤; 在至少一个另外的培养步骤中，在培养基的连续搅拌下，进一步培养颗粒状微载体上的所述细胞系; 收获含有细胞分泌的所需CEA的培养基; 并纯化CEA直至获得碘化级产物。

5. 发明授权

EP0303391B1 Optical isomers of a spiroquinuclidine derivative 失效
标题翻译：一个Spirochinuclidinderivat的光学异构体。
公开(公告)号：EP0303391B1
公开(公告)日：1995-06-07
申请号：EP88307162.3
申请日：1988-08-03
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Fisher, Abraham , Karton, Ishai
IPC分类号： C07D497/20 , A61K31/435
CPC分类号： C07D497/20

6. 发明公开

EP0651055A2 Uses of modified cholinesterase and compositions containing them 失效
标题翻译： on。。。。。。。。。。。。。。。。。。。。。。。。
公开(公告)号：EP0651055A2
公开(公告)日：1995-05-03
申请号：EP94307882.4
申请日：1994-10-26
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Shafferman, Avigdor , Barak, Dov , Ordentlich, Arie , Kronman, Chanoch , Velan, Baruch
IPC分类号： C12N15/55 , C12N9/18 , A61K38/46 , C12S13/00 , B09C1/10 , A62D3/00
CPC分类号： C12N9/18 , A61K38/00 , A62D3/02 , A62D2101/02 , A62D2101/04 , A62D2101/26 , B09C1/10
摘要： Detoxification of humans who have been exposed to phosphylating agents, and decontamination of a locus containing phosphylating agents (e.g. organophosphorus insecticides or organophosphorus nerve gases), are effected by administration to the humans or applying to the locus, respectively, at least one recombinant cholinesterase mutant so as to form phosphylated cholinesterase mutant, in presence of intrinsic or extrinsic reactivator activity effective to reactivate the mutant by breaking the phosphyl/cholinesterase mutant covalent bond, the phosphylated mutant being more readily reconverted to nonphosphylated mutant, than the corresponding phosphylated non-mutated cholinesterase is reconverted to non-phosphylated non-mutated cholinesterase. Mutation sites in the amino acid sequence of HuAChE, or in equivalent positions in other cholinesterases, are preferably selected from at least one of (a) Ser2 3, Glu334, His447; (b) Gly122, Tyr133, Glu2 2, Ser229, Gly448, Glu45 ; (c) Leu76, Tyr77, Trp86, Tyr117, Tyr119, Gly12 , Gly121, Trp236, Phe295, Phe297, Tyr337, Phe338, Trp439, Tyr449; and/or (d) Tyr72, Asp74, Tyr124, Glu285, Trp286, Tyr341. The invention includes use of the (non-phosphylated) mutants for the manufacture of medicaments for detoxification, pharmaceutical formulations for detoxification, compositions for decontamination, and phosphylated and non-phosphylated recombinant cholinesterase mutants, per se .
摘要翻译：已经暴露于磷酸化剂的人的解毒以及含有磷酸化剂（例如有机磷杀虫剂或有机磷神经气体）的场所的去污是通过给予人类或分别施用至该基因座的至少一种重组胆碱酯酶突变体以便形成磷酸化胆碱酯酶突变体，在通过断裂磷酸/胆碱酯酶突变共价键有效重新激活突变体的本征或外源性激活剂活性存在下，磷酸化突变体比相应的磷酸化非突变胆碱酯酶更容易再转化为非磷酸化突变体被转化为非磷酸化的非突变型胆碱酯酶。 HuAChE的氨基酸序列中的突变位点或其他胆碱酯酶中的等位基因的优选选自以下中的至少一种：（a）Ser2 @ 3，Glu334，His447; （b）Gly122，Tyr133，Glu2 @ @ 2，Ser229，Gly448，Glu45; （c）Leu76，Tyr77，Trp86，Tyr117，Tyr119，Gly121，Gly121，Trp236，Phe295，Phe297，Tyr337，Phe338，Trp439，Tyr449; 和/或（d）Tyr72，Asp74，Tyr124，Glu285，Trp286，Tyr341。本发明包括使用（非磷酸化）突变体用于制造用于解毒的药物，用于解毒的药物制剂，用于去污的组合物，以及磷酸化和非磷酸化的重组胆碱酯酶突变体本身。

7. 发明公开

EP0586125A3 Method and kit for detecting explosives 失效
标题翻译：用于检测爆炸物的方法和检验试剂盒。
公开(公告)号：EP0586125A3
公开(公告)日：1995-01-18
申请号：EP93306401.6
申请日：1993-08-13
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Margalit, Yair
IPC分类号： G01N31/22
CPC分类号： G01N31/22 , F41H11/134 , F42B35/00 , G01N33/227 , Y10T436/17 , Y10T436/173076 , Y10T436/173845 , Y10T436/19
摘要： In a method for detecting particular classes of explosives, a suspect sample is subjected serially to reagents (1), (2), (3) and (4) in the liquid phase, the reagents after the first being applied only if no color reaction has been obtained in the preceding test, while reagents (2) and (3) only are applied in presence of the preceding reagent(s). (1) is an alkaline solution of a diazotizable aminoaromatic azo-dye precursor (for nitroaromatic explosives). (2) is a strongly acidic reagent containing a nitrate to nitrite ion reducing agent and a diazo-coupler (for organic nitrates and nitramines). (3) is zinc powder suspended in a liquid comprising at least one water-miscible solvent (for inorganic nitrates). (4) is an aniline salt in a homogeneous strongly acidic solution including a water-miscible organic solvent (for chlorates and bromates). The invention includes also a test kit, as well as reagents (3) and (4), for use in the method.

8. 发明公开

EP0303391A2 Optical isomers of a spiroquinuclidine derivative 失效
标题翻译： Optische Isomere von einem Spirochinuclidinderivat。
公开(公告)号：EP0303391A2
公开(公告)日：1989-02-15
申请号：EP88307162.3
申请日：1988-08-03
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Fisher, Abraham , Karton, Ishai
IPC分类号： C07D497/20 , A61K31/435
CPC分类号： C07D497/20
摘要： The (+)- cis -, (-)- cis -, (+)- trans - and (-)- trans - forms of 2-methylspiro(1,3-oxathiolan-5,3′)quinuclidine are prepared by optical resolution of each of the (±)- cis - and (±)- trans -isomers. These compounds find application in treating diseases of the central nervous system in mammals, especially diseases due to a deficiency in the central cholinergic system. Biological tests indicate that the (-)- cis -form, as well as the (±)- cis -isomer, shows particular promise for treating senile dementia of Alzheimer's type.
摘要翻译： 2-甲基螺（1,3-氧硫杂环戊烷-5,3分钟）奎宁环的（+） - 顺 - ，（ - ） - 顺 - ，（+） - 反 - 和（ - ） - 通过每种（+/-） - 顺式和（+/-） - 反式异构体的光学拆分制备。这些化合物可用于治疗哺乳动物中枢神经系统疾病，特别是由于中枢胆碱能系统缺乏引起的疾病。生物试验表明（ - ） - 顺式和（+/-） - 顺式异构体显示出治疗老年痴呆症老年痴呆症的特殊希望。

9. 发明公开

EP0586125A2 Method and kit for detecting explosives 失效
标题翻译： Verfahren und Testsatz zum Nachweis von Sprengstoffen。
公开(公告)号：EP0586125A2
公开(公告)日：1994-03-09
申请号：EP93306401.6
申请日：1993-08-13
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Margalit, Yair
IPC分类号： G01N31/22
CPC分类号： G01N31/22 , F41H11/134 , F42B35/00 , G01N33/227 , Y10T436/17 , Y10T436/173076 , Y10T436/173845 , Y10T436/19
摘要： In a method for detecting particular classes of explosives, a suspect sample is subjected serially to reagents (1), (2), (3) and (4) in the liquid phase, the reagents after the first being applied only if no color reaction has been obtained in the preceding test, while reagents (2) and (3) only are applied in presence of the preceding reagent(s). (1) is an alkaline solution of a diazotizable aminoaromatic azo-dye precursor (for nitroaromatic explosives). (2) is a strongly acidic reagent containing a nitrate to nitrite ion reducing agent and a diazo-coupler (for organic nitrates and nitramines). (3) is zinc powder suspended in a liquid comprising at least one water-miscible solvent (for inorganic nitrates). (4) is an aniline salt in a homogeneous strongly acidic solution including a water-miscible organic solvent (for chlorates and bromates). The invention includes also a test kit, as well as reagents (3) and (4), for use in the method.
摘要翻译：在用于检测特定类别的炸药的方法中，可疑样品在液相中连续进行试剂（1），（2），（3）和（4），只有在没有颜色反应在上述试验中已经获得，而试剂（2）和（3）仅在前一试剂存在下使用。（1）是可重氮氨基偶氮染料前体（用于硝基芳族炸药）的碱性溶液。（2）是含有硝酸盐至亚硝酸根离子还原剂和重氮 - 偶合剂（对于有机硝酸盐和硝胺）的强酸性试剂。（3）是悬浮在包含至少一种水混溶性溶剂（对于无机硝酸盐）的液体中的锌粉。（4）是均匀强酸性溶液中的苯胺盐，其包括与水可混溶的有机溶剂（对于氯酸盐和溴酸盐）。本发明还包括用于该方法的测试试剂盒以及试剂（3）和（4）。

10. 发明公开

EP0303391A3 Optical isomers of a spiroquinuclidine derivative 失效
标题翻译：螺旋体衍生物的光学异构体
公开(公告)号：EP0303391A3
公开(公告)日：1989-04-12
申请号：EP88307162.3
申请日：1988-08-03
申请人： State of Israel Represented by the Prime Minister's Office The Israel Institute for Biological Research
发明人： Fisher, Abraham , Karton, Ishai
IPC分类号： C07D497/20 , A61K31/435
CPC分类号： C07D497/20
摘要： The (+)- cis -, (-)- cis -, (+)- trans - and (-)- trans - forms of 2-methylspiro(1,3-oxathiolan-5,3′)quinuclidine are prepared by optical resolution of each of the (±)- cis - and (±)- trans -isomers. These compounds find application in treating diseases of the central nervous system in mammals, especially diseases due to a deficiency in the central cholinergic system. Biological tests indicate that the (-)- cis -form, as well as the (±)- cis -isomer, shows particular promise for treating senile dementia of Alzheimer's type.

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