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1. 发明授权

US06274121B1 Superparamagnetic particles, process for their manufacture and use 失效
标题翻译：超顺磁颗粒，其制造和使用过程
公开(公告)号：US06274121B1
公开(公告)日：2001-08-14
申请号：US09300532
申请日：1999-04-27
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61K4900
CPC分类号： B82Y30/00 , A61K9/5094 , A61K41/00 , A61K47/51 , A61K49/18 , B03C1/01 , G01N33/54326 , H01F1/0054 , H01F1/36 , H01F1/445 , Y10S436/806
摘要： Superparamagnetic particles consist of superparamagnetic one-domain particles and aggregates of superparamagnetic one-domain particles to whose surfaces are bound inorganic and optionally organic substances optionally having further binding sites for coupling to tissue-specific binding substances, diagnostic or pharmacologically active substances. The superparamagnetic particles consist of a mixture of small superparamagnetic one-domain particles with a particle size from 3 to 50 nm and stable, degradable aggregates of small superparamagnetic one-domain particles with a particle size from 10 to 1000 nm. They are made of iron hydroxyide, iron oxide hydrate, iron oxides, iron mixed oxides or iron to the surface of which are bound silicate group containing substances among the orthosilicic acids and their condensation products and phosphate-group containing substances among the ortho- or metaphosphoric acids and their condensation products. These substances may have further binding sites.
摘要翻译：超顺磁性颗粒由超顺磁单域颗粒和超顺磁性单畴颗粒的聚集体组成，其表面与无机和任选的有机物质结合，任选具有用于偶联至组织特异性结合物质，诊断或药理学活性物质的进一步结合位点。超顺磁性粒子由粒径为3〜50nm的小超顺磁性单畴粒子和粒径为10〜1000nm的小超顺磁性单畴粒子的稳定的可降解聚集体组成。它们由羟基磷酸铁，氧化铁水合物，氧化铁，铁混合氧化物或铁制成，其表面在原硅酸及其缩合产物中含有含硅酸盐的物质和邻磷或偏磷酸中含磷酸根的物质酸及其缩合产物。这些物质可能具有进一步的结合位点。

2. 发明申请

US20090317327A1 Aqueous Dispersion of Superparamagnetic Single-Domain Particles, Production and Use Thereof in Diagnosis and Therapy 审中-公开
标题翻译：超顺磁单畴颗粒的水分散体，其诊断和治疗的生产和应用
公开(公告)号：US20090317327A1
公开(公告)日：2009-12-24
申请号：US12096692
申请日：2006-12-07
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61K51/00 , A61K47/02
CPC分类号： G01N33/54326 , A61K41/0052 , A61K47/6923 , A61K47/6929 , A61K49/0002 , A61K49/1833 , A61K49/1836 , A61K49/1857 , A61K49/1863 , A61K49/1866 , A61K49/1872 , A61K51/1244 , B82Y5/00
摘要： The invention relates to an aqueous dispersion of superparamagnetic iron-containing particles bearing α-hydroxycarboxylic acids as stabilizer substances on their surface, said dispersion comprising N-methyl-D-glucamine (meglumine) and/or 2-amino-2-(hydroxymethyl)-1,3-propanediol (trometamol) and the content of free iron ions being lower than 1 mg of iron per liter. In a preferred embodiment the dispersion according to the invention may additionally include an iron-complexing agent. In another preferred embodiment the dispersion includes positively charged metal ions and/or compounds containing polyamino groups, which can be bound to substances having a therapeutic or diagnostic effect. The invention is also directed to a method of producing said dispersion, the use thereof as an MRT contrast medium as well as the use thereof as therapeutic agent, including the option of therapy follow-up using an imaging method.
摘要翻译：本发明涉及含有α-羟基羧酸作为其表面上的稳定剂物质的超顺磁性含铁颗粒的水性分散体，所述分散体包含N-甲基-D-葡萄糖胺（葡甲胺）和/或2-氨基-2-（羟甲基） -1,3-丙二醇（氨甲磺酸），游离铁离子的含量低于每升铁1毫克。在优选的实施方案中，根据本发明的分散体还可以包含铁络合剂。在另一个优选实施方案中，分散体包含带正电荷的金属离子和/或含有聚氨基的化合物，其可与具有治疗或诊断作用的物质结合。本发明还涉及一种制备所述分散体的方法，其作为MRT造影剂的用途以及其作为治疗剂的用途，包括使用成像方法的治疗随访的选择。

3. 发明授权

US5916539A Superparamagnetic particles, process for producing the same and their use 失效
标题翻译：超顺磁颗粒，其制造方法及其用途
公开(公告)号：US5916539A
公开(公告)日：1999-06-29
申请号：US530132
申请日：1995-09-12
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61N1/40 , A61K9/50 , A61K31/395 , A61K31/66 , A61K31/77 , A61K35/12 , A61K35/74 , A61K35/76 , A61K38/43 , A61K39/395 , A61K41/00 , A61K47/02 , A61K49/00 , A61K49/18 , A61N2/00 , A61P35/00 , A61P37/00 , B03C1/01 , C07F9/09 , C07H21/00 , C12N11/14 , C12Q1/68 , G01N33/543 , G01R33/28 , H01F1/00 , H01F1/36 , H01F1/44 , A61B5/055
CPC分类号： C07F9/091 , A61K41/0052 , A61K49/186 , A61K49/1887 , A61K9/5094 , B03C1/01 , B82Y25/00 , B82Y30/00 , B82Y5/00 , C07H21/00 , C12N11/14 , C12Q1/6834 , G01N33/5434 , H01F1/0054 , H01F1/36 , H01F1/44 , H01F1/445 , G01N2446/20 , G01N2446/84 , G01N2446/86 , G01R33/281
摘要： New superparamagnetic particles useful in medicine for destroying tumors, increasing immunity and diagnosing conditions are disclosed. For that purpose, very small superparamagnetic single-domain particles are aggregated and protected against further aggregation by chemical bonding of reactive stabilizer substances on the surface of the superparamagnetic particles. These new particles thus consist of stable, decomposable aggregates with a particle size in a range between 10 and 1000 nanometers and a defined behavior in a magnetic field. The aggregates consist of several small superparamagnetic single-domain particles of iron oxide, iron mixed oxide or iron, with a particle size in a range between 3 and 20 nanometers, bearing on their surface chemically bound organic substances from the group comprising the phosphate, diphosphate, polyphosphate, thiophosphate, phosphonate or group containing polyalkylene glycols, phosphate group containing nucleotides, their oligomers or polymers, as well as phosphate group containing carbohydrates, which may present further binding sites. Both the new disclosed superparamagnetic aggregates and reactive stabilizer substances may be active substances.
摘要翻译： PCT No.PCT / DE94 / 00314 Sec。 371 1995年9月12日第 102（e）日期1995年9月12日PCT 1994年3月17日PCT公布。出版物WO94 / 21240 1994年9月29日公开了用于破坏肿瘤，增加免疫力和诊断条件的药物中的新的超顺磁性颗粒。为此，非常小的超顺磁单畴颗粒被聚集和保护，以防止通过反应性稳定剂物质在超顺磁性颗粒的表面上化学键合进一步聚集。因此，这些新的颗粒由稳定的，可分解的聚集体组成，其粒度在10至1000纳米之间，并且在磁场中具有限定的行为。聚集体由几种小的超顺磁性单结构的氧化铁，铁混合氧化物或铁的粒子组成，粒径在3和20纳米之间，其表面具有化学结合的有机物质，它们包含磷酸盐，二磷酸盐，磷酸酯，硫代磷酸酯，膦酸酯或含聚亚烷基二醇的基团，含磷酸酯基团的核苷酸，它们的低聚物或聚合物，以及含磷酸酯基的碳水化合物，其可以存在进一步的结合位点。新公开的超顺磁性聚集体和反应性稳定剂物质都可以是活性物质。

4. 发明授权

US5928958A Superparamagnetic particles, process for their manufacture and usage 失效
标题翻译：超顺磁颗粒，其制造和使用过程
公开(公告)号：US5928958A
公开(公告)日：1999-07-27
申请号：US776131
申请日：1997-01-08
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61K9/16 , A61K9/50 , A61K41/00 , A61K47/48 , A61K49/18 , B03C1/00 , B03C1/01 , C07K14/00 , C12N11/00 , C12Q1/68 , G01N33/543 , G01N33/553 , H01F1/36 , H01F1/44 , C07K17/14
CPC分类号： B82Y30/00 , A61K41/00 , A61K47/48007 , A61K49/18 , A61K9/5094 , B03C1/01 , G01N33/54326 , H01F1/0054 , H01F1/36 , H01F1/445 , Y10S436/806
摘要： Superparamagnetic particles consist of superparamagnetic one-domain particles and aggregates of superparamagnetic one-domain particles to whose surfaces are bound organic substances optionally having further binding sites for coupling to tissue-specific binding substances, diagnostic or pharmacologically active substances. The superparamagnetic particles consist of a mixture of small superparamagnetic one-domain particles with a particle size from 3 to 50 nanometers and stable, degradable aggregates of small superparamagnetic one-domain particles with a particle size from 10 to 1000 nanometers. They are made of iron hydroxide, iron oxide hydrate, iron oxides, iron mixed oxides or iron to the surface of which are bound mono- and/or polyhydroxylic group-containing aromatic substances, polyglycerines, amino-acid-containing substances, silicate group-containing substances among the orthosilicic acids and their condensation products and phosphate group-containing substances among the ortho- or metaphosphoriic acids and their condensation products. These substances may have further binding sites. These new particles may be used to destroy tumors, increase immunity, in magnetic drug targeting, for cell fusion, gene transfers, as contrasting agents, for in vitro diagnosis, as magnetic ion exchangers and magnetic adsorbents, if required by exposure to magnetic fields.
摘要翻译： PCT No.PCT / DE95 / 01028 Sec。 371日期1997年1月8日 102（e）日期1997年1月8日PCT提交1995年7月27日PCT公布。公开号WO96 / 03653 日期1996年2月8日超顺磁性粒子由超顺磁单域粒子和超顺磁性单畴粒子的聚集体组成，其表面结合有机物质，任选具有用于偶联至组织特异性结合物质，诊断或药理学活性物质的进一步结合位点。超顺磁性颗粒由粒径为3至50纳米的小超顺磁单畴颗粒和粒径为10至1000纳米的小超顺磁单畴颗粒的稳定的可降解聚集体组成。它们由氢氧化铁，氧化铁水合物，氧化铁，铁混合氧化物或铁组成，其表面与单和/或含多羟基的芳族物质结合，聚甘油，含氨基酸的物质，硅酸盐基 - 邻位或偏磷酸及其缩合产物中的原硅酸及其缩合产物和磷酸酯基物质含有物质。这些物质可能具有进一步的结合位点。如果需要通过暴露于磁场，这些新的颗粒可用于破坏肿瘤，增加免疫力，磁性药物靶向，细胞融合，基因转移，作为对比剂，用于体外诊断，如磁性离子交换剂和磁性吸附剂。

5. 发明授权

US5160725A Magnetic liquid compositions 失效
标题翻译：磁性液体组合物
公开(公告)号：US5160725A
公开(公告)日：1992-11-03
申请号：US638134
申请日：1991-01-04
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： G01R33/28 , A61K9/10 , A61K9/107 , A61K9/50 , A61K33/26 , A61K39/00 , A61K39/395 , A61K47/00 , A61K47/48 , A61K49/00 , A61K49/04 , A61K49/18 , A61P7/02 , A61P7/06 , A61P31/04 , A61P31/12 , A61P35/00 , G01N33/50
CPC分类号： A61K33/26 , A61K49/1806 , A61K9/5094 , G01N2446/20 , G01N2446/80 , G01N2446/90 , Y10T436/24
摘要： Magnetic liquid compositions are prepared from physiologically tolerated dispersions of stabilized superparamegnetic particles in water or aqueous salt solution and reactive stabilizer substances chemically bonded over phosphate, phosphonate or carboxylate groups to the surface of the superparamagnetic particles. The reactive stabilizer substances stabilize and chemically bond diagnostic and pharmacologically active substances.
摘要翻译：磁性液体组合物由在水或盐水溶液中稳定的超临界颗粒的生理学耐受分散体和在磷酸盐，膦酸盐或羧酸盐基团上化学键合到超顺磁性颗粒表面的反应性稳定剂物质制备。活性稳定剂物质稳定化学键合诊断和药理活性物质。

6. 发明申请

US20060024235A1 Stabilised superparamagnetic particles 审中-公开
标题翻译：稳定的超顺磁性颗粒
公开(公告)号：US20060024235A1
公开(公告)日：2006-02-02
申请号：US10529457
申请日：2002-10-09
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61B5/055
CPC分类号： B82Y25/00 , A61K51/1251 , H01F1/0054 , H01F1/36
摘要： The invention relates to stabilized superparamagnetic particles which consist of superparamagnetic single domain particles and aggregations of superparamagnetic particles which are stabilized with aliphatic dicarboxylic or polycarboxylic acids and which contain charged ions of chemical elements on the surface of the small superparamagnetic single-domain particles and, optionally, an additional tissue binding substance or pharmacologically effective substance. The superparamagnetic particles consist of a mixture of small superparamagnetic single domain particles have a particle size ranging from 3 to 5 namometers and stable, degradable aggregations of small superparamagnetic particles having a particle size of 10-1000 nanometers, and are made of iron hydroxide, iron oxide hydrate, iron oxide, iron mixed oxide or iron. The novel particles can be used as bacteriostatics and radio pharmaceuticals harming tumors, in order to prevent restenosis, in order to combat inflammatory diseases, for the functional control of organs, for magnetic drug targeting, as MR contrasting agents, as magnetic ion exchangers and magnetic adsorbients for separation methods, in the production of extremely small metal particles, as magnetic particles for in vitro diagnosis, optionally in conjunction with magnetic fields.
摘要翻译：本发明涉及由超顺磁单结构域颗粒和超顺磁性颗粒聚集的稳定超顺磁性颗粒，其由脂族二羧酸或多元羧酸稳定并且含有小超超顺磁单结构域颗粒表面上的化学元素的带电离子，，另外的组织结合物质或药理学上有效的物质。超顺磁性颗粒由小超超顺磁单结构域颗粒的混合物组成，其粒度范围为3至5纳米，并且具有粒径为10-1000纳米的小超顺磁性颗粒的稳定且可降解的聚集体，并且由氢氧化铁，铁氧化物水合物，氧化铁，铁混合氧化物或铁。新型颗粒可用作抑制肿瘤的抑菌剂和放射性药物，以防止再狭窄，以抵抗炎性疾病，用于器官的功能性控制，用于磁性药物靶向的MR对比剂作为磁性离子交换剂和磁性用于分离方法的吸附剂，在极小金属颗粒的生产中，作为用于体外诊断的磁性颗粒，任选地与磁场结合。

7. 发明授权

US06638494B1 Super-paramagnetic particles with increased R1 relaxivity, process for producing said particles and use thereof 失效
标题翻译：具有增加的R1松弛度的超顺磁性颗粒，用于制备所述颗粒的方法及其用途
公开(公告)号：US06638494B1
公开(公告)日：2003-10-28
申请号：US09716709
申请日：2000-11-20
申请人： Herbert Pilgrimm
发明人： Herbert Pilgrimm
IPC分类号： A61B5055
CPC分类号： B82Y25/00 , A61K9/5094 , A61K49/1836 , A61K49/186 , G01N33/5434 , G01N2446/20 , G01N2446/84 , H01F1/0054 , H01F1/36 , H01F1/445
摘要： The invention relates to super-paramagnetic single domain particles with increased R1 relaxivity and with surface-stabilizer substances. The particles are characterized in that they consist of iron hydroxide, ferric hydrate, iron oxide, iron mixed oxide or iron; are between 1 and 10 nm in size, the mean particle diameter d50 being 2-4 nm; and have increased R1 relaxivity of between 2 and 50, the ratio of the relaxivities R2/R1 being less than 5. Stabilizer substances of special carboxylic acids are bound to the particle surfaces; these prevent aggregation and sedimentation under gravity or in a magnetic field. If necessary, the particles can also contain further known stabilizer substances and other pharmacological substances. The novel particles can be used for attacking tumors, boosting immunity, for cell fusion, gene transfer, or as contrasting agents in magnetic resonance diagnostics using magnetic fields where necessary.
摘要翻译：本发明涉及具有增加的R1松弛度和表面稳定剂物质的超顺磁性单结构域颗粒。其特征在于它们由氢氧化铁，水合铁，氧化铁，铁混合氧化物或铁组成; 尺寸为1〜10nm，平均粒径d50为2-4nm; 并且R1松弛度增加在2到50之间，松弛度R2 / R1的比例小于5.特殊羧酸的稳定剂物质结合到颗粒表面; 这些防止在重力或磁场中聚集和沉淀。如果需要，颗粒还可以含有另外已知的稳定剂物质和其它药物物质。该新型颗粒可用于攻击肿瘤，增强免疫力，用于细胞融合，基因转移，或作为对比剂在磁共振诊断中使用必要的磁场。

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