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1. 发明授权

US5110918A Process for preparing EDTA-free heparins, heparin fractions and fragments 失效
$Process for preparing EDTA-free heparins, heparin fractions and fragments$
标题翻译：制备不含EDTA的肝素，肝素级分和片段的方法
公开(公告)号：US5110918A
公开(公告)日：1992-05-05
申请号：US587605
申请日：1990-09-24
申请人： Benito Casu , Annamaria Naggi , Pasqua Oreste , Giangiacomo Torri , Giorgio Zoppetti , Giancarlo Sportoletti , Francesco De Santis
发明人： Benito Casu , Annamaria Naggi , Pasqua Oreste , Giangiacomo Torri , Giorgio Zoppetti , Giancarlo Sportoletti , Francesco De Santis
IPC分类号： C08B37/10 , A61K31/715 , A61P7/02 , C08B37/00
CPC分类号： C08B37/0075
摘要： Heparins, heparin fractions or fragments, optionally salified with pharmaceutically acceptable cations, having molecular weight ranging from 1.000 to 30.000 D, characterized by an EDTA content lower than 0.1%, by the absence, in the .sup.1 H--NMR spectra, of the signals due to EDTA between 2.50 and 4.00 p.p.m. and substantially free from bleeding effect and optionally free from signals, in the .sup.13 C--NMR spectrum, from 80 to 86 ppm.
摘要翻译：盐酸，肝素级分或片段，任选地与药学上可接受的阳离子盐化，其分子量范围为1.000至30.000D，其特征在于EDTA含量低于0.1％，在1H-NMR谱中不存在由于 EDTA在2.50和4.00 ppm之间并且在13 C-NMR光谱中基本上没有出血作用并且任选地没有信号，从80至86ppm。

2. 发明申请

US20050256079A1 Process for the manufacture of n-acyl-(epi)k5-amine-o-sulfate-derivatives and products thus obtained 审中-公开
标题翻译：制备由此获得的正酰基 - （环氧）k5-胺-O-硫酸酯衍生物和产物的方法
公开(公告)号：US20050256079A1
公开(公告)日：2005-11-17
申请号：US10518303
申请日：2003-06-17
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： A61K8/60 , A61K8/72 , A61K8/73 , A61K31/726 , A61K31/727 , A61K31/737 , A61P3/06 , A61P3/10 , A61P7/02 , A61P9/00 , A61P17/06 , A61P17/16 , A61P19/02 , A61P27/02 , A61P27/06 , A61P31/12 , A61P35/00 , A61P35/04 , A61P39/06 , A61P43/00 , C07H1/00 , C08B37/00 , C08B37/10
CPC分类号： A61K31/726 , A61K31/727 , A61K31/737 , C07H1/00 , C08B37/006 , C08B37/0075 , C08B37/0078
摘要： A new method is described for the oversulfation of (epi)KS-N sulfates to obtain (epi)K5-amine-O-oversulfates at extremely high degree of sulfation and for the transformation of these intermediates into new Nacyl-(epi)K5-amine-O-oversulfates basically free of activity on the coagulation parameters and useful in the cosmetic or pharmaceutical field. Also described are pharmaceutical compositions containing, as one of their active ingredients, an (epi)K5-amine-O-oversulfate.
摘要翻译：描述了用于（epi）KS-N硫酸盐过硫酸盐以获得（epi）极高硫酸化程度的（epi）K 5 - 胺-O-过硫酸盐的新方法，以及将这些中间体转化为新的Nacyl-（epi）K5- 胺-O-硫酸盐基本上没有凝结参数的活性，并且在化妆品或制药领域中是有用的。还描述了含有作为其活性成分之一的（epi）K5-胺-O-过硫酸盐的药物组合物。

3. 发明申请

US20050245736A1 Low molecular weight oversulfated polysaccharide 审中-公开
标题翻译：低分子量过硫酸多糖
公开(公告)号：US20050245736A1
公开(公告)日：2005-11-03
申请号：US10518229
申请日：2003-06-17
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： A61K8/60 , A61K8/72 , A61K8/73 , A61K31/726 , A61K31/727 , A61K31/737 , A61P3/06 , A61P3/10 , A61P7/02 , A61P9/00 , A61P17/06 , A61P17/16 , A61P19/02 , A61P27/02 , A61P27/06 , A61P31/12 , A61P35/00 , A61P35/04 , A61P39/06 , A61P43/00 , C07H1/00 , C08B37/00 , C08B37/10
CPC分类号： A61K31/726 , A61K31/727 , A61K31/737 , C07H1/00 , C08B37/006 , C08B37/0075 , C08B37/0078
摘要： LMW-K5-N,O-oversulfates are described, having a sulfation degree of from 3.2 to 4 and a mean molecular weight of from about 3,000 to about 6,000, obtainable by depolymerization of corresponding K5-N,O-oversulfates or starting from LMW-K5-N-sulfates by O-oversulfation of a tertiary amine or quaternary ammonium salt thereof and subsequent N-resulfation of the K5-amine-O-oversulfate thus obtained. Furthermore, pharmaceutical compositions containing these LMW-K5-N,Ooversulfates having antiangiogenetic and antiviral, in particular anti-HIV-1 activity. Intermediate LMW-K5-N-sulfates are also described.
摘要翻译：描述了LMW-K5-N，过硫酸盐，其硫酸化度为3.2至4，平均分子量为约3,000至约6,000，可通过相应的K5-N，O-硫酸盐解聚或从LMW开始获得 -K5-N-硫酸盐，其通过叔胺或其季铵盐的过氧化和随后的N-重硫化由此获得的K5-胺-O-硫酸盐。此外，含有具有抗血管发生和抗病毒药物的这些LMW-K5-N，过硫酸盐的药物组合物，特别是抗HIV-1活性。还描述了中间体LMW-K5-N-硫酸盐。

4. 发明授权

US06992183B2 Highly sulfated derivatives of K5 polysaccharide and their preparation 失效
标题翻译： K5多糖的高度硫酸化衍生物及其制备
公开(公告)号：US06992183B2
公开(公告)日：2006-01-31
申请号：US10469037
申请日：2002-02-26
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： C07H1/00 , A61K31/737
CPC分类号： C07H3/00 , A61K31/737 , C08B37/0063 , C08B37/0075 , Y02A50/473
摘要： The purification of the E.coli K5 polysaccharide by treatment with isopropyl alcohol and elimination of lipophilic substances is described. The purified product can be used to prepare, after N-deacetylation, new N,O-sulfated polysaccharides with high degree of sulfation.
摘要翻译：描述了通过用异丙醇处理和消除亲脂性物质来纯化大肠杆菌K5多糖。纯化的产物可用于在N-脱乙酰化后制备具有高程度硫酸化的新的N，O-硫酸化多糖。

5. 发明申请

US20060014718A1 Epimerized derivatives of k5 polysaccharide with a very high degree of sulfation 有权
标题翻译：具有非常高程度硫酸化的k5多糖的差向异构衍生物
公开(公告)号：US20060014718A1
公开(公告)日：2006-01-19
申请号：US10518302
申请日：2003-06-17
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： A61K31/737 , C07H11/00
CPC分类号： A61K31/726 , A61K31/727 , A61K31/737 , C07H1/00 , C08B37/006 , C08B37/0075 , C08B37/0078
摘要： A new method is described for the oversulfation of epiK-N sulfate to obtain an epiK5-amine-O-oversulfate with very high sulfation degree which, by subsequent N-sulfation, provides new epiK5-N,O-oversulfate-derivatives with a sulfation degree of at least 4, basically free of activity on the coagulation parameters and useful in the cosmetic or pharmaceutical field. Also described are new low molecular weight epiK5-N-sulfates useful as intermediates in the preparation of the corresponding LMW-epiK5-N,O-oversulfate-derivatives.
摘要翻译：描述了一种用于硫酸化epiK-N的硫酸化以获得具有非常高的硫酸化程度的epiK5-胺-O-硫酸盐的新方法，其通过随后的N-硫酸化提供新的具有硫酸化的epiK5-N，O-过硫酸盐衍生物至少4度，对凝结参数基本没有活性，在化妆品或制药领域有用。还描述了可用作制备相应的LMW-epiK5-N，过硫酸盐衍生物的中间体的新的低分子量epiK5-N-硫酸盐。

6. 发明授权

US06777398B2 Process for the preparation of chondroitin sulfates from K4 polysaccharide and obtained products 失效
标题翻译：从K4多糖制备硫酸软骨素的方法和获得的产品
公开(公告)号：US06777398B2
公开(公告)日：2004-08-17
申请号：US10274706
申请日：2002-10-21
申请人： Giorgio Zoppetti , Pasqua Oreste
发明人： Giorgio Zoppetti , Pasqua Oreste
IPC分类号： A61K31737
CPC分类号： C08B37/0069
摘要： New process for the preparation of chondroitin sulfates from the bacterial origin polysaccharide named K4, by defructosilation followed by selective sulfation.
摘要翻译：用于从细菌来源的多糖（称为K4）制备硫酸软骨素的新工艺，通过破碎扩散，然后进行选择性硫酸化。

7. 发明授权

US5958899A Polysaccharides having a high iduronic acid content 失效
标题翻译：具有高艾杜糖醛酸含量的多糖
公开(公告)号：US5958899A
公开(公告)日：1999-09-28
申请号：US628690
申请日：1996-04-12
申请人： Giorgio Zoppetti , Pasqua Oreste , Giovanni Cipolletti
发明人： Giorgio Zoppetti , Pasqua Oreste , Giovanni Cipolletti
IPC分类号： A61K31/715 , A61P7/02 , C08B37/00 , C12P19/26 , C08B37/10
CPC分类号： C12P19/26 , C08B37/0075
摘要： Process for the preparation of polysaccharides having a high iduronic acid content comprising:a) N-deacetylation of the polysaccharide K5 from E. coli or of the heparan sulfate or O-desulfation of heparin or heparan sulfate;b) N-sulfation of the product obtained from the stage a);c) epimerization in presence of the C5 epimerase enzyme;d) sulfation of at least some free hydroxy groups, wherein the stage c) is carried out in a reaction medium constituted by a classical buffer solution formed by HEPES, potassium chloride, EDTA and TRITON X-100 to which a suitable additive is added.
摘要翻译： PCT No.PCT / EP95 / 04241 Sec。 371日期：1996年4月12日 102（e）日期1996年4月12日PCT提交1995年10月30日PCT公布。出版物WO96 / 14425 日期1995年5月17日制备具有高艾杜糖醛酸含量的多糖的方法，其包括：a）多糖K5从大肠杆菌或硫酸乙酰肝素或硫酸脱乙酰或硫酸乙酰肝素的N-脱乙酰化; b）从a）阶段获得的产物的N-硫酸化; c）在C5差向异构酶存在下的差向异构化; d）至少一些游离羟基的硫酸化，其中阶段c）在由由其加入合适的添加剂的HEPES，氯化钾，EDTA和TRITON X-100形成的经典缓冲溶液构成的反应介质中进行。

8. 发明申请

US20080146793A1 Highly sulfated derivatives of K5 polysaccharide and their preparation 审中-公开
标题翻译： K5多糖的高度硫酸化衍生物及其制备
公开(公告)号：US20080146793A1
公开(公告)日：2008-06-19
申请号：US11984482
申请日：2007-11-19
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： C07H3/00 , C12P19/04
CPC分类号： C07H3/00 , A61K31/737 , C08B37/0063 , C08B37/0075 , Y02A50/473
摘要： The purification of the E. coli K5 polysaccharide by treatment with isopropyl alcohol and elimination of lipophilic substances is described. The purified product can be used to prepare, after N-deacetylation, new N,O-sulfated polysaccharides with high degree of sulfation.
摘要翻译：描述了通过用异丙醇处理和消除亲脂性物质来纯化大肠杆菌K5多糖。纯化的产物可用于在N-脱乙酰化后制备具有高程度硫酸化的新的N，O-硫酸化多糖。

9. 发明申请

US20070155694A1 Low molecular weight polysaccharides having antithrombotic activity 有权
标题翻译：具有抗血栓活性的低分子量多糖
公开(公告)号：US20070155694A1
公开(公告)日：2007-07-05
申请号：US10582687
申请日：2004-12-15
申请人： Pasqua Oreste , Giorgio Zoppetti
发明人： Pasqua Oreste , Giorgio Zoppetti
IPC分类号： A61K31/727 , C08B37/10
CPC分类号： C08B37/0063
摘要： Novel depolymerized-LMWepiK5-N,O-sulfates obtainable starting from a LMW-epiK5-N-sulfate prepared by nitrous depolymerization of an epiK5-N-sulfate or by C5-epimerization of a LMW-K5-N-sulfate obtained by nitrous depolymerization of a K5-N-sulfate. A process consists of submitting the starting depolymerized-LMW-epiK5-N-sulfate to four steps: a O-oversulfation, a partila O-desulfation, a 6-O-sulfation and a N-sulfation. The new depolymerized-LMWepiK5-N,O-sulfates present a di- or trisulfated 2,5-anhydromannitol unit at the reducing end of the majority of its chains, have a content of iduronic acid of 40-60%, a sulfation degree of from 2.3 to 2.9 and a mean molecular weight of from about 1,500 to about 12,000. They exhibit a good antithrombotic activity with a low pro-hemorrhagic risk.
摘要翻译：通过由epiK5-N-硫酸盐的亚硝解聚制备的LMW-epiK5-N-硫酸盐或通过亚硝解聚获得的LMW-K5-N-硫酸盐的C5差向异构体获得的新型解聚的LMWepiK5-N，O-硫酸盐的K5-N硫酸盐。一个过程包括将起始解聚的LMW-epiK5-N-硫酸盐递送到四个步骤：O-过硫酸盐，脱硫酸，6-氧硫酸化和N-硫酸化。新解聚的LMWepiK5-N，O-硫酸盐在其大多数链的还原末端呈现二硫酸化或三硫酸化的2,5-脱水甘露糖醇单元，其具有40-60％的艾杜糖醛酸含量，硫酸化度从2.3至2.9，平均分子量为约1,500至约12,000。它们具有良好的抗血栓形成活性，具有低的出血性风险。

10. 发明授权

US06288044B1 O-sulfated bacterial polysaccharides 失效
标题翻译： O-硫酸化细菌多糖
公开(公告)号：US06288044B1
公开(公告)日：2001-09-11
申请号：US09355211
申请日：1999-07-23
申请人： Giorgio Zoppetti , Pasqua Oreste , Giovanni Cipolletti
发明人： Giorgio Zoppetti , Pasqua Oreste , Giovanni Cipolletti
IPC分类号： A61K31715
CPC分类号： A61Q7/00 , A61K8/73 , A61K8/99
摘要： Process for the preparation of O-sulfated K4, K5 and K40 polysaccharides useful for the treatment of tumoral, HIV-1 and coagulation pathologies and in cosmetic preparations, wherein the K4, K5 or K40 polysaccharide in the form of sodium salt is suspended in an aprotic solvent and directly submitted to the reaction of O-sulfation with a pyridine-sulphur trioxide or trimetylamine-sulphur trioxide adduct or with chlorosulfonic acid.
摘要翻译：用于制备可用于治疗肿瘤，HIV-1和凝血病理学以及化妆品制剂的O-硫酸化K4，K5和K40多糖的方法，其中将钠盐形式的K4，K5或K40多糖悬浮于非质子溶剂，直接与O-硫酸化反应与吡啶 - 三氧化硫或三甲基胺 - 三氧化硫加合物或氯磺酸反应。

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