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1. 发明申请

WO2016198864A1 FOCUSED ULTRASOUND HYPERTHERMIA 审中-公开
标题翻译：聚焦超声波超声波
公开(公告)号：WO2016198864A1
公开(公告)日：2016-12-15
申请号：PCT/GB2016/051695
申请日：2016-06-08
申请人： KING'S COLLEGE LONDON
发明人： THANOU, Maria , WRIGHT, Michael James Lee , CENTELLES, Miguel , MILLER, Andrew David , GEDROYC, Wladyslaw
IPC分类号： A61N7/02
CPC分类号： A61N7/02 , A61B5/0035 , A61B5/0071 , A61B5/055 , A61B18/04 , A61B2018/00577 , A61K9/1272 , A61K31/4745 , A61K41/0052 , A61K47/543 , A61K47/6911 , A61M37/0092 , A61M2037/0007 , A61N5/025 , A61N2007/0052
摘要： The invention relates to a hyperthermia (focused ultrasound - FUS) method where an energy source is applied, repeatedly, to a desired part of the body to induce hyperthermia, e.g. using image guidance. Hyperthermia is applied after a drug or biopharmaceutical ( API) and/or their labelled equivalents (theranostics) and/or their drug delivery systems has been administered to the live subject to cause the enhanced tissue distribution and/ or controlled release of the drug, previously encapsulated in thermo-sensitive (lipid nano)particles, to a desired site of the body. Hyperthermia (Ultrasound) is then halted, and the site of interest. Hyperthermia is then applied again using image guidance to monitor drug's accumulation in the tissue. The drug and or the drug delivery system are also labelled (for imaging) to allow real time monitoring and modulation of the API in the human body which can be used to direct and guide the FUS at the site of interest.
摘要翻译：本发明涉及一种高热（聚焦超声 - FUS）方法，其中将能源重复地施加到身体的所需部位以诱导高热，例如，使用图像引导。在药物或生物药物（API）和/或其标记的等同物（主要药物）和/或其药物递送系统已经施用于活体受试者之后施用热疗以引起增强的组织分布和/或控制释放的药物封装在热敏（脂质纳米）颗粒中，到达人体所需的位置。然后，超热（超声）被停止，并且感兴趣的部位。然后使用图像引导再次应用热疗来监测药物在组织中的积累。药物和/或药物递送系统也被标记（用于成像），以允许人体内的API的实时监测和调节，其可以用于引导和引导感兴趣部位的FUS。

2. 发明申请

WO2016198862A1 NANOPARTICLES 审中-公开
标题翻译：纳米粒子
公开(公告)号：WO2016198862A1
公开(公告)日：2016-12-15
申请号：PCT/GB2016/051693
申请日：2016-06-08
申请人： KING'S COLLEGE LONDON
发明人： THANOU, Maria , WRIGHT, Michael James Lee , CENTELLES, Miguel , MILLER, Andrew David , GEDROYC, Wladyslaw
IPC分类号： A61K9/127 , A61K49/08 , A61K49/10 , A61K49/18 , A61K31/4745 , A61K31/704
CPC分类号： A61K9/1272 , A61K31/4745 , A61K31/704 , A61K41/0052 , A61K49/085 , A61K49/106 , A61K49/1812 , A61K49/1839
摘要： The invention provides a (drug-containing) lipid nanoparticle with: (i) at least one phospholipid; (ii) at least one lysolipid; and (iii) at least one phospholipid comprising a hydrophilic polymer;and (iv) at least one structural lipid of formula (I) which has the following general structure: (I) wherein R and R' are long hydrocarbyl hydrophobic chains, Y is a linker element, and PHG is a polar head group described as large according to its van der Waals radius, and which is different from the phospholipid (i). The lipid nanoparticle can release a drug (or API) from within the lipid nanoparticleas a result of focussed ultrasound (FUS) applied continuously, at least twice, to a desired part of the body to induce hyperthermia (an increase in temperature). FUS is applied after the lipid nanoparticle containing the drug has been administered to the live subject, and causes controlled release of the drug at the desired site of the body. Ultrasound is then halted, and the site of interest allowed to cool. Ultrasound is then applied again. Lipidnanoparticles can be labelled (for MRI, NIRF imaging),enablin greal time monitoring of the drug in the human body. Imaging information can be used to direct and guide the nature of the FUS applied to the site of interest.
摘要翻译：本发明提供了一种（含药物）脂质纳米颗粒，其具有：（i）至少一种磷脂; （ii）至少一种溶脂剂; 至少一种包含亲水性聚合物的磷脂;和（iv）至少一种具有以下一般结构的式（I）结构脂质：（I）其中R和R'是长烃基疏水链，Y是连接体元件，PHG是根据其范德华半径描述为大的极性头基，并且与磷脂（i）不同。脂质纳米颗粒可以从脂质纳米颗粒内释放药物（或API），这是聚焦超声（FUS）连续施用至少两次到身体所需部位以诱发高热（温度升高）的结果。在含有药物的脂质纳米颗粒已经施用于活体受试者之后施用FUS，并且导致药物在体内所需位点的受控释放。然后停止超声波，感兴趣的部位允许冷却。然后再次应用超声波。脂质体纳米颗粒可以被标记（用于MRI，NIRF成像），对人体中药物的安定时间进行时间监测。成像信息可用于指导和指导应用于感兴趣的站点的FUS的性质。

3. 发明申请

WO2016198859A1 PRECISION THERAPEUTICS 审中-公开
标题翻译：精密治疗
公开(公告)号：WO2016198859A1
公开(公告)日：2016-12-15
申请号：PCT/GB2016/051690
申请日：2016-06-08
申请人： GLOBALACORN LTD. , KING'S COLLEGE LONDON
发明人： THANOU, Maria , WRIGHT, Michael James Lee , CENTELLES, Miguel , MILLER, Andrew David , GEDROYC, Wladyslaw , SPENCE, Paul
IPC分类号： A61K41/00 , A61K49/18 , A61K47/48 , A61K9/127 , A61P35/00
CPC分类号： A61K49/1812 , A61K9/0007 , A61K9/127 , A61K41/0028 , A61K41/0052 , A61K47/6911
摘要： The invention provides a pharmaceutical composition comprising (a combination of): - imaging lipid nanoparticles (imaging LNPs); and - one or more therapeutic agent(s). The one or more therapeutic agent(s) may be separate from said imaging LNPs, and/or entrapped within said imaging LNPs to form theranostic nanoparticles (TNPs). Imaging LNPs (or TNPs) may have receptor-targeting ligands. Post administration, when sufficient imaging LNPs (or TNPs) reach target sites such as cancerous lesions, then targets may become identified using clinically relevant imaging modalities such as MRI. Image-guided hyperthermia (IgFHT) applied to target sites enables imaging LNPs (or TNPs) still in the blood pool, along with (additional) therapeutic agent(s), to partition substantially into target tissues for therapy by means of hyperpermeability and retention (HPR). Confirmation of therapeutic outcomes can be followed by clinically relevant imaging modalities such as MRI.
摘要翻译：本发明提供了一种药物组合物，其包含（组合）：成像脂质纳米颗粒（成像LNPs）; 和 - 一种或多种治疗剂。所述一种或多种治疗剂可以与所述成像LNP分离，和/或包埋在所述成像LNPs内以形成纳米颗粒（TNPs）。成像LNPs（或TNP）可能具有受体靶向配体。后行管理，当足够的成像LNP（或TNP）到达目标部位如癌性病变时，则可以使用临床相关的成像方式（例如MRI）鉴定目标。应用于靶位点的图像引导热疗（IgFHT）使得仍然在血液池中的LNP（或TNP）与（附加的）治疗剂一起成像以通过高渗透性和保留性将其基本分配到靶组织进行治疗 HPR）。治疗结果的确认可以跟随临床相关的成像方式，如MRI。

4. 发明公开

EP3302702A1 FOCUSED ULTRASOUND HYPERTHERMIA 审中-公开
标题翻译：聚焦超声高温
公开(公告)号：EP3302702A1
公开(公告)日：2018-04-11
申请号：EP16729332.3
申请日：2016-06-08
申请人： King's College London
发明人： THANOU, Maria , WRIGHT, Michael James Lee , CENTELLES, Miguel , MILLER, Andrew David , GEDROYC, Wladyslaw
IPC分类号： A61N7/02
CPC分类号： A61N7/02 , A61B5/0035 , A61B5/0071 , A61B5/055 , A61B18/04 , A61B2018/00577 , A61K9/1272 , A61K31/4745 , A61K41/0052 , A61K47/543 , A61K47/6911 , A61M37/0092 , A61M2037/0007 , A61N5/025 , A61N2007/0052
摘要： The invention relates to a hyperthermia (focused ultrasound—FUS) method where an energy source is applied, repeatedly, to a desired part of the body to induce hyperthermia, e.g. using image guidance. Hyperthermia is applied after a drug or biopharmaceutical (API) and/or their labelled equivalents (theranostics) and/or their drug delivery systems has been administered to the live subject to cause the enhanced tissue distribution and/or controlled release of the drug, previously encapsulated in thermo-sensitive (lipid nano)particles, to a desired site of the body. Hyperthermia (Ultrasound) is then halted, and the site of interest. Hyperthermia is then applied again using image guidance to monitor drug's accumulation in the tissue. The drug and or the drug delivery system are also labelled (for imaging) to allow real time monitoring and modulation of the API in the human body which can be used to direct and guide the FUS at the site of interest.

5. 发明公开

EP3302434A1 NANOPARTICLES 审中-实审转让
标题翻译：纳米粒子
公开(公告)号：EP3302434A1
公开(公告)日：2018-04-11
申请号：EP16729331.5
申请日：2016-06-08
申请人： King's College London
发明人： THANOU, Maria , WRIGHT, Michael James Lee , CENTELLES, Miguel , MILLER, Andrew David , GEDROYC, Wladyslaw
IPC分类号： A61K9/127 , A61K49/08 , A61K49/10 , A61K49/18 , A61K31/4745 , A61K31/704
CPC分类号： A61K9/1272 , A61K31/4745 , A61K31/704 , A61K41/0052 , A61K49/085 , A61K49/106 , A61K49/1812 , A61K49/1839
摘要： The lipid nanoparticle can release a drug (or API) from within the lipid nanoparticle as a result of focused ultrasound (FUS) applied continuously, at least twice, to a desired part of the body to induce hyperthermia (an increase in temperature). FUS is applied after the lipid nanoparticle containing the drug has been administered to the live subject, and causes controlled release of the drug at the desired site of the body. Ultrasound is then halted, and the site of interest allowed to cool. Ultrasound is then applied again. Lipid nanoparticles can be labelled (for MRI, NIRF imaging), enabling real time monitoring of the drug in the human body. Imaging information can be used to direct and guide the nature of the FUS applied to the site of interest.

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