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1. 发明申请

WO2011002285A1 DRUG DELIVERY SYSTEM COMPRISING POLYOXAZOLINE AND A BIOACTIVE AGENT 审中-公开
标题翻译：包含聚氧杂环丁烷和生物活性剂的药物递送系统
公开(公告)号：WO2011002285A1
公开(公告)日：2011-01-06
申请号：PCT/NL2010/050403
申请日：2010-06-28
申请人： BENDER ANALYTICAL HOLDING B.V. , BENDER, Johannes Caspar Mathias Elizabeth , HOOGENBOOM, Richard , VAN VLIET, Patrick Andreas Anton
发明人： BENDER, Johannes Caspar Mathias Elizabeth , HOOGENBOOM, Richard , VAN VLIET, Patrick Andreas Anton
IPC分类号： A61K9/70 , A61K9/16 , A61K9/20 , A61K9/40
CPC分类号： A61K9/0056 , A61K9/006 , A61K9/1641 , A61K9/1694 , A61K9/2031 , A61K9/4816 , A61K9/7007
摘要： The invention relates to drug delivery systems comprising a water-soluble polymer matrix and a bioactive agent entrained therein, said water soluble polymer matrix containing at least 50 wt. % of polyoxazoline having a molar mass of at least 5 40,000 g/mol. The drug delivery systems of the present invention offer the advantage that the bioactive agent is readily released when the drug delivery system is contacted with water. The drug delivery system can be in the form of a solid dispersion, a mucoadhesive sheet, a tablet, a powder, a capsule.
摘要翻译：本发明涉及包含水溶性聚合物基质和夹带在其中的生物活性剂的药物递送系统，所述水溶性聚合物基质含有至少50wt。摩尔质量为至少5 40,000g / mol的聚恶唑啉的％。本发明的药物递送系统提供了当药物递送系统与水接触时生物活性剂容易释放的优点。药物递送系统可以是固体分散体，粘膜粘附片，片剂，粉末，胶囊的形式。

2. 发明申请

WO2012057628A2 CROSS-LINKED POLYMERS AND IMPLANTS DERIVED FROM ELECTROPHILICALLY ACTIVATED POLYOXAZOLINE 审中-公开
标题翻译：交联聚合物和来自电泳激活的聚恶唑啉的植入物
公开(公告)号：WO2012057628A2
公开(公告)日：2012-05-03
申请号：PCT/NL2012/050001
申请日：2012-01-02
申请人： BENDER ANALYTICAL HOLDING B.V. , HOOGENBOOM, Richard , BENDER, Johannes Caspar Mathias Elizabeth , VAN HEST, Jan Cornelis Maria
发明人： HOOGENBOOM, Richard , BENDER, Johannes Caspar Mathias Elizabeth , VAN HEST, Jan Cornelis Maria
IPC分类号： A61K47/48 , A61L27/18 , A61L31/06 , A61L31/14 , C08G73/02 , C08J3/24
CPC分类号： A61L24/046 , A61K47/50 , A61L24/06 , A61L27/18 , A61L31/06 , C08G73/0233 , C08J3/246 , C08J2300/10 , C08J2379/02 , C08L79/02
摘要： One aspect of the invention relates to a biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent, said electrophilically activated POX comprising m electrophilic groups; and said nucleophilic cross-linking agent comprising n nucleophilic groups, wherein the m electrophilic groups are capable of reaction with the n nucleophilic groups to form covalent bonds; wherein m≥2, n≥2 and m+n ≥5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m≥3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. The invention further relates to biocompatible medical products comprising such a cross-linked POX-polymer. Also provided is a kit for producing a biocompatible, cross-linked POX-polymer. The invention further provides a tissue adhesive medical product comprising at least 1% by weight of dry matter of EL-POX, said EL-POX comprising at least 2 electrophilic groups, including at least one pendant electrophilic group. The polymers according to the invention have excellent implant and/or sealing characteristics.
摘要翻译：本发明的一个方面涉及通过使亲电活化的聚恶唑啉（EL-POX）与亲核性交联剂反应获得的生物相容性共价交联聚合物，所述亲电活化的POX 包含m个亲电子基团; 并且所述亲核交联剂包含n个亲核基团，其中所述m个亲电子基团能够与所述n个亲核基团反应以形成共价键; 其中m≥2，n≥2且m +n≥5; 其中所述m个亲电子基团中的至少一个是侧基亲电子基团和/或其中m≥3; 并且其中相对于亲核交联剂中所含的亲核基团的量，EL-POX包含过量的亲电子基团。本发明进一步涉及包含这种交联的POX-聚合物的生物相容性医疗产品。还提供了用于生产生物相容性交联POX聚合物的试剂盒。本发明还提供了包含至少1重量％干物质EL-POX的组织粘附医药产品，所述EL-POX包含至少2个亲电子基团，包括至少一个侧挂亲电子基团。根据本发明的聚合物具有优异的植入和/或密封特性。

3. 发明申请

WO2011112082A1 STERILE ALGINATE-BASED AQUEOUS COMPOSITION FOR MEDICAL USE AND PROCESS FOR THE PREPARATION THEREOF 审中-公开
标题翻译：用于医疗用途的基于ALT的碱性水性组合物及其制备方法
公开(公告)号：WO2011112082A1
公开(公告)日：2011-09-15
申请号：PCT/NL2011/050160
申请日：2011-03-08
申请人： BENDER ANALYTICAL HOLDING B.V. , BENDER, Johannes Caspar Mathias Elizabeth , PELLIKAAN, Hubert Clemens
发明人： BENDER, Johannes Caspar Mathias Elizabeth , PELLIKAAN, Hubert Clemens
IPC分类号： A61K31/734
CPC分类号： A61K31/734 , A61K9/0024 , A61K47/02 , A61K47/36
摘要： The present invention relates to ready-to-use sterile, alginate-based, aqueous compositions for medical use. More particularly, the invention relates to an aqueous composition for medical use that has been sterilized by heat sterilization and having a viscosity at 25 ºC of at least 300 cP (Helipath® T F spindle, 100 rpmat 25 °C), said composition having a pH in the range of 6.5-7.5; containing 0.5-10 wt.% of an alginate salt; and further containing 10-500 mM of one or more dissolved C 2 -C 7 mono-or dicarboxylates that are optionally substituted with up to 2 hydroxyl groups. The alginate-based composition of the present invention has excellent storage stability and is easy to manufacture. The alginate-based aqueous compositions of the present invention can advantageously be used, for instance, to prevent adhesions between a healing trauma site and adjacent surrounding tissue. These compositions can further be used in implants or in pharmaceutical preparations for oral administration.
摘要翻译：本发明涉及用于医疗用途的即用型无菌藻酸盐基水性组合物。更具体地说，本发明涉及用于医疗用途的水性组合物，其已经通过热灭菌灭菌，并且在25℃下的粘度为至少300cP（Helipath？TF锭子，25 rpm，100 rpm），所述组合物具有pH 在6.5-7.5的范围内; 含有0.5-10重量％的藻酸盐; 并进一步含有10-500mM的一个或多个可任选被至多2个羟基取代的溶解的C 2 -C 7单或二羧酸酯。本发明的基于藻酸盐的组合物具有优异的储存稳定性，易于制造。本发明的藻酸盐基水性组合物可以有利地用于例如防止愈合创伤部位和相邻的周围组织之间的粘连。这些组合物还可以用于植入物或用于口服给药的药物制剂中。

4. 发明申请

WO2009154440A1 METHOD FOR REMOVING IMPURITIES FROM BIOPOLYMER MATERIAL 审中-公开
标题翻译：从生物玻璃材料中去除污染物的方法
公开(公告)号：WO2009154440A1
公开(公告)日：2009-12-23
申请号：PCT/NL2008/050396
申请日：2008-06-19
申请人： Bender Analytical Holding B.V. , BENDER, Johannes Caspar Mathias Elizabeth , VERMEULEN, Pieter, Sebastiaan
发明人： BENDER, Johannes Caspar Mathias Elizabeth , VERMEULEN, Pieter, Sebastiaan
IPC分类号： C08B37/00 , A61L24/08
CPC分类号： C08B37/0084 , A61L24/001 , A61L24/08 , C08B1/00 , C08B37/006 , C08B37/0072 , C08H1/00 , C08L5/04
摘要： The present invention relates to a method for removing impurities from biopolymer material, e.g. polysaccharides, polypeptides or polynucleotides. More particularly, the present invention provides a method of reducing lipopolysaccharide levels in a lipopolysaccharide containing biopolymer material, comprising the successive steps of: a) providing an aqueous solution containing 0.05 - 50 wt.% of dissolved lipopolysaccharide-containing biopolymer material; 0.001-10 wt.% of a surfactant; 0.05 -15 wt.% of solid adsorbent; and at least 50 wt.% of water; b) allowing the adsorbent to adsorb lipopolysaccharides; c) separating the solid adsorbent containing adsorbed lipopolysaccharides from the remaining aqueous solution; and d) recovering the biopolymer material containing a reduced level of lipopolysaccharide from the separated aqueous solution.
摘要翻译：本发明涉及从生物聚合物材料中除去杂质的方法，例如，多糖，多肽或多核苷酸。更具体地说，本发明提供一种减少含脂多糖生物聚合物材料中的脂多糖水平的方法，其包括以下连续步骤：a）提供含有0.05-50重量％的含有脂多糖的生物聚合物材料的水溶液; 0.001-10重量％的表面活性剂; 0.05-15重量％的固体吸附剂; 和至少50重量％的水; b）允许吸附剂吸附脂多糖; c）从剩余的水溶液中分离含有吸附的脂多糖的固体吸附剂; 和d）从分离的水溶液中回收含有降低水平的脂多糖的生物聚合物材料。

5. 发明申请

WO2010117266A1 IN SITU GELLING ALGINATE SYSTEMS 审中-公开
标题翻译：在SITU GALLING ALGINATE SYSTEMS
公开(公告)号：WO2010117266A1
公开(公告)日：2010-10-14
申请号：PCT/NL2010/050174
申请日：2010-04-06
申请人： Broockeville Corporation N.V. , BENDER, Johannes Caspar Mathias Elizabeth , MANN, Maryssa Gudrun Ailsa , KAMPS, Michael
发明人： BENDER, Johannes Caspar Mathias Elizabeth , MANN, Maryssa Gudrun Ailsa , KAMPS, Michael
IPC分类号： A61F2/46 , B01F11/00 , B01F13/00 , B05C17/005 , A61K9/00
CPC分类号： A61K9/0024 , A61K47/36 , A61L24/0031 , A61L24/08 , B01F5/061 , B01F13/002 , B01F13/0023 , B01F15/0087 , C08L5/08
摘要： The present invention relates to a dispensing system that can be used to introduce a gel-forming fluid into or onto the body that will produce a homogeneous gel in situ. The system according to the present invention comprises: a first reservoir comprising a first flowable composition in the form of an aqueous solution of ionically cross-linkable alginate; a second reservoir comprising a second flowable composition, said second flowable composition containing one or more polyols; a first outlet from the first reservoir; a second outlet from the second reservoir, said first outlet and said second outlet being arranged in such a way that the first flowable composition is mixed with the second flowable composition when both compositions are simultaneously expelled from the respective reservoirs thereby forming the gel- forming fluid; wherein the first and/or second flowabel composition contains a cross- linking agent and upon admixture of the first flowable composition with the second flowable composition said cross-linking agent initiates the formation of a solid or semi-solid ionically cross- linked alginate gel. The presence of a substantial amount of polyol in the second flowable composition favourably affects the cross-linking reaction between the cross-linking agent and the alginate.
摘要翻译：本发明涉及一种分配系统，其可用于将凝胶形成流体引入到体内或体内，其将在原位产生均匀的凝胶。根据本发明的系统包括：第一储存器，包括可离子交联的藻酸盐水溶液形式的第一可流动组合物; 第二储存器，包括第二可流动组合物，所述第二可流动组合物含有一种或多种多元醇; 第一个水库的第一个出口; 所述第一出口和所述第二出口被布置成使得当两种组合物同时从相应的储存器排出时，使第一可流动组合物与第二可流动组合物混合，从而形成凝胶形成流体 ; 其中第一和/或第二流动标签组合物含有交联剂，并且当第一可流动组合物与第二可流动组合物混合时，所述交联剂引发固体或半固体离子交联藻酸盐凝胶的形成。在第二可流动组合物中存在大量的多元醇有利地影响交联剂和藻酸盐之间的交联反应。

6. 发明申请

WO2008033023A2 GRANULATE CONTAINING A PHARMACEUTICALLY ACTIVE SUBSTANCE AND METHOD FOR ITS MANUFACTURE 审中-公开
标题翻译：含有药物活性物质的颗粒及其制造方法
公开(公告)号：WO2008033023A2
公开(公告)日：2008-03-20
申请号：PCT/NL2007/050448
申请日：2007-09-14
申请人： FEYECON DEVELOPMENT & IMPLEMENTATION B.V. , PELLIKAAN, Hubert Clemens , VERMEULEN, Pieter Sebastiaan , BENDER, Johannes Caspar Mathias Elizabeth , FERNANDEZ CID, Maria, Vanesa
发明人： PELLIKAAN, Hubert Clemens , VERMEULEN, Pieter Sebastiaan , BENDER, Johannes Caspar Mathias Elizabeth , FERNANDEZ CID, Maria, Vanesa
CPC分类号： A61K9/2059 , A61K9/1617 , A61K9/1623 , A61K9/1694 , A61K9/2013 , A61K9/2018
摘要： One aspect of the present invention relates to a granulate having a volume weighted mean diameter of 1-200 m and containing: at least 0.1 wt.% of a pharmaceutically active substance; at least 10 wt.% of emulsifier selected from the group consisting of sugar fatty acid esters, mono-glycerides, di-glycerides, diacetyl tartaric acid ester of monoglyceride, diacetyl tartaric acid esters of diglyceride, polyglycerol esters, calcium stearoyl lactylate, sodium stearoyl lactylate and combinations thereof; and 0-89.9 wt.% of a water-dispersible saccharide; the combination of the pharmaceutically active substance, the emulsifier and the water-dispersible saccharide together represening at least 60 wt.% of the granulate; wherein the granulate is monophasic or wherein the granulate comprises a dispersed phase containing the pharmaceutically active substance, said dispersed phase having a volume weighted mean diameter of less than 300 nm. The granulates of the present invention enable the manufacture of transmucosal dosage units that exhibit improved solubility and/or bioavailability of the pharmaceutically active substance. Another aspect of the invention relates to a process for the preparation of a granulate containing a pharmaceutically active substance, which process employs: a pumpable emulsion comprising (i) a continuous phase containing a polar solvent and (ii) a dispersed phase containing an emulsifier and a pharmaceutically active substance; an extractant comprising a supercritical, subcritical or liquefied gas; said solvent being substantially more soluble in the extractant than said emulsifier; the process comprising the successive steps of : a. combining the pumpable emulsion with the extractant under mixing conditions; b. allowing the formation of granules containing the emulsifier and the pharmaceutically active substance; c. collect ing the granules and separating them from the extractant.
摘要翻译：本发明的一个方面涉及体积加权平均直径为1-200μm并含有至少0.1wt％的药物活性物质的颗粒; 至少10重量％的选自糖脂肪酸酯，单甘油酯，二甘油酯，甘油单酯的二乙酰酒石酸酯，甘油二酯的二乙酰酒石酸酯，聚甘油酯，硬脂酰乳酸钙，硬脂酰基硬脂酸钠乳酸盐及其组合; 和0-89.9重量％的水分散性糖; 药物活性物质，乳化剂和水分散性糖的组合共同表示至少60重量％的颗粒; 其中所述颗粒是单相的或其中所述颗粒包含含有所述药物活性物质的分散相，所述分散相的体积加权平均直径小于300nm。本发明的颗粒能够制造显示改善的药物活性物质的溶解度和/或生物利用度的经粘膜剂量单位。本发明的另一方面涉及一种制备含有药物活性物质的颗粒的方法，该方法采用：可泵送乳液，其包含（i）含有极性溶剂的连续相和（ii）含有乳化剂的分散相和药物活性物质; 包括超临界，亚临界或液化气体的萃取剂; 所述溶剂比所述乳化剂在萃取剂中更可溶; 该过程包括以下连续步骤：a。将可泵送乳液与萃取剂在混合条件下结合; 湾允许形成含有乳化剂和药物活性物质的颗粒; C。收集颗粒并将其与萃取剂分离。

7. 发明授权

EP2416741B1 IN SITU GELLING ALGINATE SYSTEMS 有权转让
标题翻译： ALGINATSYSTEMEFÜRIN-SITU-GELBILDUNG
公开(公告)号：EP2416741B1
公开(公告)日：2015-03-11
申请号：EP10711941.4
申请日：2010-04-06
申请人： Bender Analytical Holding B.V.
发明人： BENDER, Johannes Caspar Mathias Elizabeth , MANN, Maryssa Gudrun Ailsa , KAMPS, Michael , PELLIKAAN, Hubert, Clemens
IPC分类号： A61F2/46 , B01F11/00 , B01F13/00 , B05C17/005 , A61K9/00
CPC分类号： A61K9/0024 , A61K47/36 , A61L24/0031 , A61L24/08 , B01F5/061 , B01F13/002 , B01F13/0023 , B01F15/0087 , C08L5/08

8. 发明授权

EP2294092B1 METHOD FOR REMOVING IMPURITIES FROM BIOPOLYMER MATERIAL 有权转让
标题翻译：程序对去除污染物的生物聚合物从
公开(公告)号：EP2294092B1
公开(公告)日：2017-02-22
申请号：EP08766819.0
申请日：2008-06-19
申请人： Bender Analytical Holding B.V.
发明人： BENDER, Johannes Caspar Mathias Elizabeth , VERMEULEN, Pieter, Sebastiaan
IPC分类号： C08B37/00 , A61L24/08
CPC分类号： C08B37/0084 , A61L24/001 , A61L24/08 , C08B1/00 , C08B37/006 , C08B37/0072 , C08H1/00 , C08L5/04

9. 发明授权

EP2544695B1 STERILE ALGINATE-BASED AQUEOUS COMPOSITION FOR MEDICAL USE AND PROCESS FOR THE PREPARATION THEREOF 有权转让
标题翻译：基于用于医疗用途以及其用于制备方法的含水组合物的无菌藻
公开(公告)号：EP2544695B1
公开(公告)日：2015-01-07
申请号：EP11708587.8
申请日：2011-03-08
申请人： Bender Analytical Holding B.V.
发明人： BENDER, Johannes Caspar Mathias Elizabeth , PELLIKAAN, Hubert Clemens
IPC分类号： A61K31/734 , A61K9/00 , A61K47/02 , A61K47/36
CPC分类号： A61K31/734 , A61K9/0024 , A61K47/02 , A61K47/36

10. 发明公开

EP2661283A2 CROSS-LINKED POLYMERS AND IMPLANTS DERIVED FROM ELECTROPHILICALLY ACTIVATED POLYOXAZOLINE 有权转让
标题翻译： VERNETZTE POLYMERE UND VON ELEKTROPHIL AKTIVIERTEM POLYOXAZOLIN STAMMENDE IMPLANTATE
公开(公告)号：EP2661283A2
公开(公告)日：2013-11-13
申请号：EP12703598.8
申请日：2012-01-02
申请人： Bender Analytical Holding B.V.
发明人： HOOGENBOOM, Richard , BENDER, Johannes Caspar Mathias Elizabeth , VAN HEST, Jan Cornelis Maria
IPC分类号： A61K47/48 , A61L27/18 , A61L31/06 , A61L31/14 , C08G73/02 , C08J3/24
CPC分类号： A61L24/046 , A61K47/50 , A61L24/06 , A61L27/18 , A61L31/06 , C08G73/0233 , C08J3/246 , C08J2300/10 , C08J2379/02 , C08L79/02
摘要： One aspect of the invention relates to a biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent, said electrophilically activated POX comprising m electrophilic groups; and said nucleophilic cross-linking agent comprising n nucleophilic groups, wherein the m electrophilic groups are capable of reaction with the n nucleophilic groups to form covalent bonds; wherein m≧2, n≧2 and m+n≧5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m≧3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. The invention further relates to biocompatible medical products comprising such a cross-linked POX-polymer. Also provided is a kit for producing a biocompatible, cross-linked POX-polymer. The invention further provides a tissue adhesive medical product comprising at least 1% by weight of dry matter of EL-POX, said EL-POX comprising at least 2 electrophilic groups, including at least one pendant electrophilic group. The polymers according to the invention have excellent implant and/or sealing characteristics.
摘要翻译：本发明的一个方面涉及通过使亲电子活化的聚恶唑啉（EL-POX）与亲核交联剂反应而获得的生物相容的，共价交联的聚合物，所述亲电活化的POX包含m个亲电子基团; 并且所述亲核交联剂包含n个亲核基团，其中m个亲电基团能够与n个亲核基团反应以形成共价键; 其中m≥2，n> = 2和m + n> = 5; 其中所述m亲电子基团中的至少一个是侧链亲电子基团和/或其中m≥3; 并且其中所述EL-POX相对于所述亲核交联剂中所含的亲核基团的量包含过量的亲电子基团。本发明还涉及包含这种交联的POX-聚合物的生物相容性医疗产品。还提供了用于生产生物相容的交联POX-聚合物的试剂盒。本发明还提供了包含至少1重量％的EL-POX干物质的组织粘合剂医疗产品，所述EL-POX包含至少2个亲电子基团，包括至少一个亲电子基团。根据本发明的聚合物具有优异的植入物和/或密封特性。

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