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1. 发明公开

EP0950660A1 A process for recovery of 6-aminopenicillanic acid from a mother liquor 失效
标题翻译： Ein Verfahren zurRückgewinnungvon 6-Aminopenizillansäureaus einer Mutterlauge
公开(公告)号：EP0950660A1
公开(公告)日：1999-10-20
申请号：EP98200897.1
申请日：1998-03-20
申请人： GIST-BROCADES B.V.
发明人： van der Does, Thomas , Kuipers, Rienk Hendrik , Kerkhof, Johannes H.P.M. , Kwant, Gerard Jan
IPC分类号： C07D499/42
CPC分类号： C07D499/00
摘要： The invention relates to a process for recovering 6-aminopenicillanic acid from a mother liquor, wherein 6-aminopenicillanic acid is extracted from the mother liquor with a recovery solution, which recovery solution is collected and re-used after 6-aminopenicillanic acid is isolated therefrom.
摘要翻译：本发明涉及从母液中回收6-氨基青霉烷酸的方法，其中用回收溶液从母液中提取6-氨基青霉烷酸，从其中分离出6-氨基青霉烷酸后，收集回收溶液并重新使用。。

2. 发明公开

EP0937084A1 PROCESS FOR THE PREPARATION OF SALTS AND ESTERS OF CLAVULANIC ACID 失效
标题翻译：用于生产盐和酯克拉维酸
公开(公告)号：EP0937084A1
公开(公告)日：1999-08-25
申请号：EP97951881.0
申请日：1997-11-10
申请人： GIST-BROCADES B.V.
发明人： BOOIJ, Johannes , VAN DEN HEUVEL, Antonius
IPC分类号： A61K31 , A61P31 , C07D503
CPC分类号： C07D503/00
摘要： An improved process for the preparation of pharmaceutically acceptable alkali metal salts or esters of clavulanic acid has been provided for. Furthermore, also potassium clavulanate with an extremely low amine content and pharmaceutical compositions comprising the same have been provided for.

3. 发明公开

EP0918878A1 IMPROVED PROCESS FOR THE FERMENTATIVE PRODUCTION OF CEPHALOSPORIN 失效
标题翻译：改进方法，发酵生产的头孢菌素
公开(公告)号：EP0918878A1
公开(公告)日：1999-06-02
申请号：EP98925484.0
申请日：1998-04-22
申请人： GIST-BROCADES B.V.
发明人： KRIJGSMAN, John , SMEETS, Jan, Willem, Hubert , DE BRAAL, Henriette, Elisabeth, Anna , DE VROOM, Erik , FASEL, Herman, Pieter
IPC分类号： C12P35
CPC分类号： C12P35/02
摘要： The present invention relates to a novel process for the preparation of cephalosporins having been deacylated at the 7-amino group, by fermentation of a cephalosporin producing microorganism in the presence of a side chain precursor, extraction of the N-substituted cephalosporin compound as present in the fermentation broth or fluid to an organic solvent, back extraction of the N-substituted cephalosporin compound to water, treatment of the aqueous phase with a dicarboxylate acylase and isolation of the crystalline cephalosporin compound according to formula (1) from the conversion solution, characterized in that the fermentation broth or fluid is incubated at acidic conditions and an elevated temperature prior to extraction of the N-substituted cephalosporin compound to an organic solvent. Further improvements of the process are obtained by washing the first organic solvent extract with acidified water and/or by extraction of the side chain to an organic solvent and/or by treating an aqueous cephalosporin solution produced at one or more stages in the process of the invention with carbon dioxide.

4. 发明公开

EP0912169A2 $g(b)-LACTAM GRANULES FREE OF ORGANIC SOLVENTS 失效
标题翻译：无有机溶剂的β-内酰胺含GRANULES
公开(公告)号：EP0912169A2
公开(公告)日：1999-05-06
申请号：EP97937508.0
申请日：1997-07-15
申请人： GIST-BROCADES B.V.
发明人： KWANT, Gerard, Jan , SCHEFFERS, Nicolaas, Henricus
IPC分类号： A61K9 , A61K31
CPC分类号： A61K9/1688 , A61K31/43
摘要： β-Lactam granules free of organic solvents have been provided for. Also a process to prepare the same by applying during the granulation only water as binding solvent has been disclosed.

5. 发明公开

EP0910620A1 METHOD FOR MAKING WORT HAVING IMPROVED FILTERABILITY AND/OR INCREASED YIELD 失效
标题翻译：用于生产WORT具有改进的过滤性和/或增加的产量
公开(公告)号：EP0910620A1
公开(公告)日：1999-04-28
申请号：EP97923033.0
申请日：1997-05-02
申请人： GIST-BROCADES B.V.
发明人： LAROYE, Marie-Paule , SOUPPE, Jerome
IPC分类号： C12C5 , C12C7 , C12P7
CPC分类号： C12C5/006 , C12C5/004 , C12C7/04 , C12C7/047 , C12P7/06 , Y02E50/17
摘要： The present invention provides worts with increased yield and improved filterability as well as a process for preparing said wort comprising the steps of: (a) preparing mash from malted or unmalted cereals, or a mixture of malted and unmalted cereals, in the presence of a mixture of enzyme activities, (b) filtering the mash so obtained to obtain the wort, wherein said mixture of enzyme activities is selected from a mixture comprising at least β-glucanase activity and α-L-arabinofuranose releasing activity or a mixture comprising at least β-glucanase activity endo-xylanase activity and α-arabinofuranose releasing activity.

6. 发明公开

EP0906414A2 PROCESS FOR THE PREPARATION OF A GRANULAR MICROBIAL BIOMASS AND ISOLATION OF VALUABLE COMPOUNDS THEREFROM 失效
标题翻译：用于生产粒状土壤微生物量有价值的成分微生物生物量的提取
公开(公告)号：EP0906414A2
公开(公告)日：1999-04-07
申请号：EP97916373.0
申请日：1997-03-21
申请人： GIST-BROCADES B.V.
发明人： BIJL, Hendrik, Louis , SCHAAP, Albert , VISSER, Johannes, Martinus, Jacobus
IPC分类号： A23D9 , A23K1 , A23L1 , A61K8 , A61Q19 , C07C51 , C11B1 , C12N1 , C12P7 , C12P17 , C12P19 , C12P23
CPC分类号： A61Q19/00 , A23D9/00 , A23K20/158 , A23L31/00 , A23L33/11 , A23L33/12 , A23L33/15 , A23V2002/00 , A61K8/375 , A61K8/67 , A61K8/92 , A61K8/9706 , A61K8/99 , A61K2800/85 , C07C51/47 , C11B1/02 , C11B1/10 , C12N1/005 , C12N1/14 , C12P7/6427 , C12P7/6472 , C12P17/06 , C12P19/42 , C12P23/00 , C07C57/12 , C07C57/03 , A23V2250/706 , A23V2250/1868
摘要： A process for the isolation of desired compound(s) from a microbial biomass is disclosed, wherein the microbial biomass (which, if necessary, is pretreated to give a dry matter content of from 25 to 80%) is granulated (e.g. by extrusion) and then dried to a dry matter content of at least 80%. The granulation of the biomass to granules significantly eases subsequent drying of the biomass (which can be stored as dried granules) and gives higher yields on extraction of the compound(s).

7. 发明授权

EP0731785B1 CERAMIDE 3 DERIVATIVES BASED ON MONOUNSATURATED FATTY ACIDS 失效
标题翻译：单不饱和脂肪CERAMIDE-3衍生物
公开(公告)号：EP0731785B1
公开(公告)日：1998-12-30
申请号：EP95934658.6
申请日：1995-10-02
申请人： GIST-BROCADES B.V.
发明人： LAMBERS, Johannes, Wilhelmus, Jacobus , VERWEIJ, Jan
IPC分类号： C07C233/20 , A61K7/48
CPC分类号： C07C233/20 , A61K8/68 , A61K2800/75 , A61Q19/00 , Y10S514/847
摘要： The present invention discloses ceramide 3 derivatives based on monounsaturated fatty acids. A preferred compound is N-oleoylphytosphingosine (Ceramide IIIB). A method for preparing these compounds is also disclosed. The solubility of these compounds is higher than the solubility of the corresponding saturated ceramide 3 derivatives, whereas their stability is comparable to saturated ceramide 3 stabilities. In addition, a method is described for maintaining the water permeability characteristics of the skin by topical application of a formulation containing a monounsaturated ceramide 3 derivative.

8. 发明公开

EP0859229A1 Detection of analytes using electrochemistry 失效
标题翻译： Nachweis von分析软件Verwendung von Elektrochemie
公开(公告)号：EP0859229A1
公开(公告)日：1998-08-19
申请号：EP98200370.9
申请日：1998-02-09
申请人： GIST-BROCADES B.V.
发明人： Van Es, Remco Maria
IPC分类号： G01N27/327 , G01N33/543 , G01N33/58
CPC分类号： G01N33/5438 , G01N33/54326 , G01N33/9446
摘要： The present invention relates to methods and means for carrying out diagnostic assays. In particular it relates to such assays whereby the detection means is based on electrochemical reactions. This means that the label to be detected provides an electric signal. Preferred labels are enzymes giving such a signal. Provided is a flow cell whereby a solid phase is provided in a flow stream of the sample, in close proximity to a working electrode to detect any electrical signal. In a typical embodiment, a sample is mixed with molecule having specific binding affinity for an analyte of which the presence in the sample is to be detected, whereby said specific binding molecule is provided with a label. The conjugate of labelled specific binding molecule and analyte is then immobilized on the solid phase in the vicinity of the working electrode, the flow cell is rinsed with a solution and afterwards a substrate solution for the label (an enzyme) is provided upon which an electrical signal is generated and can be detected by the working electrode. Normally the flow cell will also be provided with a reference electrode and optionally a counter electrode. The methods and devices of the present invention are particular useful for liquids which comprise many substances that may disturb measurement in conventional assays. The design of the flow cell allows for removal of said interfering substances before measurement. In a preferred embodiment at least part of the solid phase is provided in the form of magnetic beads. The magnetic beads can be immobilized near the working electrode by means of a magnetic field provided by a magnet of any kind. In this embodiment the solid phase can be mixed with the sample thereby creating a longer reaction time, a better sensitivity and a higher speed of the assay. Also the magnetic beads can be easily rinsed from the flow cell by removing the magnetic field. They can then be easily recycled.
摘要翻译：本发明涉及用于进行诊断测定的方法和手段。特别地，它涉及这样的测定，其中检测手段是基于电化学反应。这意味着要检测的标签提供电信号。优选的标记是产生这种信号的酶。提供了一种流动池，其中在样品的流动流中提供固相，靠近工作电极以检测任何电信号。在典型的实施方案中，将样品与待检测样品中存在的分析物具有特异性结合亲和力的分子混合，从而向所述特异性结合分子提供标记。然后将标记的特异性结合分子和分析物的缀合物固定在工作电极附近的固相上，用溶液冲洗流动池，然后提供用于标记（酶）的底物溶液，产生信号，并可由工作电极检测。通常流动池还将具有参考电极和任选的对电极。本发明的方法和装置特别适用于包含许多在常规测定中可能干扰测量的物质的液体。流动池的设计允许在测量之前去除所述干扰物质。在优选的实施方案中，固相的至少一部分以磁珠的形式提供。磁珠可以通过由任何类型的磁体提供的磁场固定在工作电极附近。在该实施方案中，可以将固相与样品混合，从而产生更长的反应时间，更好的灵敏度和更高的测定速度。此外，通过去除磁场，磁珠可以容易地从流动池中冲洗掉。然后可以方便地回收。

9. 发明公开

EP0843013A2 Novel bioprocess for preparing 7-ADCA 失效
标题翻译： Neues Bio-Verfahren zur Herstellung von 7-ADCA
公开(公告)号：EP0843013A2
公开(公告)日：1998-05-20
申请号：EP97203374.0
申请日：1992-09-11
申请人： GIST-BROCADES B.V.
发明人： Crawford, Lorilee , Conder, Michael J. , McAda, Phyllis C. , Rambosek, John A.
IPC分类号： C12N15/52 , C12P35/00 , C12N9/00 , C12N1/21
CPC分类号： C12N9/0071 , C12P35/00 , C12P37/04 , Y10S435/935
摘要： An important intermediate for preparing cephalopsporin antibotics, 7-aminodesacetoxy cephalosporanic acid (7-ADCA), is prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); and the in situ expression of an expandase gene, e.g., from Streptomyces clavuligerus , with which the P.chrysogenum has been transformed, converts the adipoyl-6-APA by ring expansion to the novel compound adipoyl-7-ADCA. The final product, 7-ADCA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The entire synthesis, accordingly, is carried out using bioprocesses, and is efficient and economical.
摘要翻译：通过新型生物工艺制备头孢菌素类抗生素7-氨基乙酰氧基头孢菌素酸（7-ADCA）的重要中间体，其中转化的产黄青霉菌株在己二酸原料存在下培养以产生己二酰基-6-APA（6 氨基青霉烷酸）; 并且例如来自产黄青霉的链霉菌（Streptomyces clavuligerus）的扩环酶基因的原位表达通过环扩增将己二酰基-6-APA转化为新化合物己二酰-7-ADCA。然后通过使用己二酰酰化酶裂解己二酰侧链制备最终产物7-ADCA。因此，整个合成使用生物工艺进行，并且是高效和经济的。

10. 发明公开

EP0817613A1 USE OF COMPOSITIONS COMPRISING STABILIZED BIOLOGICALLY EFFECTIVE COMPOUNDS 失效
标题翻译：组合物的使用稳定化的酶
公开(公告)号：EP0817613A1
公开(公告)日：1998-01-14
申请号：EP97904378.0
申请日：1997-01-31
申请人： GIST-BROCADES B.V.
发明人： EDENS, Luppo , TAN, Hong, Sheng , LAMBERS, Johannes, Wilhelmus, Jacobus
IPC分类号： A61K8 , A61K9 , A61K31 , A61K38 , A61K47 , A61Q5 , B05B11
CPC分类号： A61K9/10 , A61K9/08 , B05B11/3084
摘要： The present invention describes a dispensing system which allows for application of an aqueous composition containing a biologically effective compound which is adequately stabilized. A dual chamber dispensing system is used wherein a stabilized composition comprising a biologically effective compound and an aqueous basic composition are separately contained. Both compositions are simultaneously delivered from the dispensing system, whereupon the compositions are mixed to result in a final composition suitable for direct application.

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