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1. 发明授权

US07803350B2 Radioactive arsenic-containing compounds and their uses in the treatment of tumors 失效
标题翻译：放射性含砷化合物及其在肿瘤治疗中的应用
公开(公告)号：US07803350B2
公开(公告)日：2010-09-28
申请号：US11881901
申请日：2007-07-30
申请人： Te-Wei Lee , Chun-Ying Huang , Ming-Shiuan Wu , Te-Jung Chen , Kwo-Ping Chang , Shiang-Rong Chang , Shyh-Yi Chyi , Chih-Hsien Chang , Yin-Mao Hsu , Kuo-Hsien Fan , Wei-Chuan Hsu , Ying-Kai Fu , Charng-Feng Kao
发明人： Te-Wei Lee , Chun-Ying Huang , Ming-Shiuan Wu , Te-Jung Chen , Kwo-Ping Chang , Shiang-Rong Chang , Shyh-Yi Chyi , Chih-Hsien Chang , Yin-Mao Hsu , Kuo-Hsien Fan , Wei-Chuan Hsu , Ying-Kai Fu , Charng-Feng Kao
IPC分类号： A61K51/00 , A61K36/14
CPC分类号： A61K51/02 , A61K41/009 , A61K51/121
摘要： This invention provides a process for producing a radioactive arsenic-containing compound, comprising the steps of: (i) subjecting an arsenic-containing compound to a neutron irradiation treatment, said arsenic-containing compound being selected from a group consisting of As2O3, As2S3, As2S2, and a combination thereof, such that the arsenic element contained in the arsenic-containing compound is converted to a radioactive arsenic isotope; and (ii) recovering the resultant product from step (i).This invention also provides a pharmaceutical composition comprising a therapeutically effective amount of the radioactive arsenic-containing compound and a pharmaceutically acceptable carrier. The pharmaceutical composition can be used in the treatment of tumors/cancers such as hematological malignancies and solid tumors.
摘要翻译：本发明提供一种放射性含砷化合物的制造方法，其特征在于，包括以下工序：（i）对含砷化合物进行中子照射处理，所述含砷化合物选自As2O3，As2S3， As2S2及其组合，使含砷化合物中所含的砷元素转化为放射性砷同位素; 和（ii）从步骤（i）中回收所得产物。本发明还提供包含治疗有效量的放射性含砷化合物和药学上可接受的载体的药物组合物。药物组合物可用于治疗肿瘤/癌症如血液恶性肿瘤和实体瘤。

2. 发明申请

US20080003177A1 Radioactive arsenic-containing compounds and their uses in the treatment of tumors 失效
标题翻译：放射性含砷化合物及其在肿瘤治疗中的应用
公开(公告)号：US20080003177A1
公开(公告)日：2008-01-03
申请号：US11881901
申请日：2007-07-30
申请人： Chun-Ying Huang , Ming-Shiuan Wu , Te-Wei Lee , Te-Jung Chen , Kwo-Ping Chang , Shyh-Yi Chyi , Yin-Mao Hsu , Kuo-Hsien Fan , Wei-Chuan Hsu , Ying-Kai Fu , Charng-Feng Kao , Shiang-Rong Chang , Chih-Hsien Chang
发明人： Chun-Ying Huang , Ming-Shiuan Wu , Te-Wei Lee , Te-Jung Chen , Kwo-Ping Chang , Shyh-Yi Chyi , Yin-Mao Hsu , Kuo-Hsien Fan , Wei-Chuan Hsu , Ying-Kai Fu , Charng-Feng Kao , Shiang-Rong Chang , Chih-Hsien Chang
IPC分类号： A61K51/02 , A61P35/00
CPC分类号： A61K51/02 , A61K41/009 , A61K51/121
摘要： This invention provides a process for producing a radioactive arsenic-containing compound, comprising the steps of: (i) subjecting an arsenic-containing compound to a neutron irradiation treatment, said arsenic-containing compound being selected from a group consisting of As2O3, As2S3, As2S2, and a combination thereof, such that the arsenic element contained in the arsenic-containing compound is converted to a radioactive arsenic isotope; and (ii) recovering the resultant product from step (i). This invention also provides a pharmaceutical composition comprising a therapeutically effective amount of the radioactive arsenic-containing compound and a pharmaceutically acceptable carrier. The pharmaceutical composition can be used in the treatment of tumors/cancers such as hematological malignancies and solid tumors.
摘要翻译：本发明提供了一种制备放射性含砷化合物的方法，包括以下步骤：（i）对含砷化合物进行中子照射处理，所述含砷化合物选自： 2 3 3 3 3 SUB>及其组合，使含砷化合物中所含的砷元素转化为放射性砷同位素; 和（ii）从步骤（i）中回收所得产物。本发明还提供包含治疗有效量的放射性含砷化合物和药学上可接受的载体的药物组合物。药物组合物可用于治疗肿瘤/癌症如血液恶性肿瘤和实体瘤。

3. 发明授权

US5889146A Method for synthesis of bifunctional chelating agents-peptides 失效
标题翻译：双功能螯合剂 - 肽的合成方法
公开(公告)号：US5889146A
公开(公告)日：1999-03-30
申请号：US978615
申请日：1997-11-26
申请人： Te-Wei Lee , Shui-Tein Chen , Shiang-Rong Chang , Shyh-Yi Chyi , Chang-Mau Shing , Tian-Fu Huang , Lie-Hang Shen , Zei-Tsan Tsai , Kung-Tsung Wang , Gann Ting
发明人： Te-Wei Lee , Shui-Tein Chen , Shiang-Rong Chang , Shyh-Yi Chyi , Chang-Mau Shing , Tian-Fu Huang , Lie-Hang Shen , Zei-Tsan Tsai , Kung-Tsung Wang , Gann Ting
IPC分类号： A61K51/08 , C07K7/06 , A61K38/12 , C07K5/00 , C07K7/00 , C07K17/00
CPC分类号： C07K7/06 , A61K51/083 , A61K51/088 , A61K2123/00
摘要： This invention is a novel synthesis of BCA-peptides (BCA: bifunctional chelating agents). In this method, the starting material--Fmoc-Thr(ol)-Terephthal-Acetal-Amide Resin is coupled with the various amino acids. The straight peptide-resin of D-Phe-Cys(Trt)-Phe-D-Trp(Boc)-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr(ol)-Terephthal-Acetal-Amide Resin was obtained. This compound reacted with iodine to give disulfide-containing peptide resin of ##STR1## Cleavage of the peptide from the resin was achieved by TFA. The cleavaged peptide was protected by the reaction of octreotide with di-t-butyldicarbonate. BCA was coupled to the selectively protected octreotide. This product was obtained by reaction of protected BCA-peptides with TFA. The final product was labeled by radioisotope .sup.111 InCl.sub.3 for tumor imaging radiopharmaceuticals.
摘要翻译：本发明是BCA肽（BCA：双功能螯合剂）的新型合成。在该方法中，起始物质-Fmoc-Thr（ol） - 对 - 对 - 乙酰胺树脂与各种氨基酸偶联。 D-Phe-Cys（Trt）-Phe-D-Trp（Boc）-Lys（Boc）-Thr（tBu）-Cys（Trt）-Thr（ol） - 对 - 缩醛酰胺树脂的直链肽 - 树脂获得。该化合物与碘反应，得到含二硫化物的肽树脂，通过TFA实现了树脂中肽的切割。通过奥曲肽与二碳酸二叔丁酯的反应来保护切割的肽。 BCA与选择性保护的奥曲肽偶联。该产物通过保护的BCA-肽与TFA的反应获得。最终产品用放射性同位素111InCl3标记用于肿瘤成像放射性药物。

4. 发明授权

US06476186B1 Process for preparing octreotide and derivatives thereof 有权
标题翻译：制备奥曲肽及其衍生物的方法
公开(公告)号：US06476186B1
公开(公告)日：2002-11-05
申请号：US09576769
申请日：2000-05-24
申请人： Yao-Tsung Hsieh , Shiang-Rong Chang , Shyh-Yi Chyi , Hui-Lan Wu , Shu-Ling Chen , Henton Huang , Te-Wei Lee , Tian-Fu Huang
发明人： Yao-Tsung Hsieh , Shiang-Rong Chang , Shyh-Yi Chyi , Hui-Lan Wu , Shu-Ling Chen , Henton Huang , Te-Wei Lee , Tian-Fu Huang
IPC分类号： C07K104
CPC分类号： C07K14/6555 , Y02P20/55
摘要： This invention relates a process for preparing octreotide and derivatives thereof. The starting material, Thr(ol)(tBu)-2-chlorotrityl resin is coupled with the various amino acids. The straight peptide-resin of D-Phe-Cys(Trt)-Phe-D-Trp(Boc)-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr(ol)(tBu)-2-chlorotrityl resin or D-Phe-Cys(Trt)-Tyr(tBu)-D-Trp(Boc)-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr(ol)(tBu)-2-chlorotrityl resin was obtained. Cleavage of the peptide from the resin was achieved by strong acid solution. The cleaved peptide reacted with charcoal to give disulfide-containing peptide of
摘要翻译：本发明涉及制备奥曲肽及其衍生物的方法。起始物质Thr（ol）（tBu）-2-氯三苯甲基树脂与各种氨基酸偶联。 D-Phe-Cys（Trt）-Phe-D-Trp（Boc）-Lys（Boc）-Thr（tBu）-Cys（Trt）-Thr（ol）（tBu）-2-氯三苯甲基树脂或D-Phe-Cys（Trt）-Tyr（tBu）-D-Trp（Boc）-Lys（Boc）-Thr（tBu）-Cys（Trt）-Thr（ol）（tBu）-2-氯三苯甲基树脂获得。通过强酸溶液从树脂中切下肽。裂解的肽与木炭反应，得到含二硫化物的肽

5. 发明授权

US5639439A Gallium dimercaptosuccinate as a novel tumor imaging agent 失效
标题翻译：二巯基琥珀酸镓作为新型肿瘤成像剂
公开(公告)号：US5639439A
公开(公告)日：1997-06-17
申请号：US356895
申请日：1994-12-15
申请人： Te-Wei Lee , Wei-Lian Chen , Ming-Der Yu , Lie-Hang Shen , Zei-Tsan Tsai , Shyh-Yi Chyi
发明人： Te-Wei Lee , Wei-Lian Chen , Ming-Der Yu , Lie-Hang Shen , Zei-Tsan Tsai , Shyh-Yi Chyi
IPC分类号： A61K51/04 , A61K51/00 , A61M36/14
CPC分类号： A61K51/0402 , A61K2123/00
摘要： Novel tumor imaging agents in which the dimercaptosuccinic acid was dissolved in phosphate buffer and labelled with radioisotope gallium. The product of gallium dimercaptosuccinate has been characterized by a variety of experiments including serum stability, biodistribution and imaging experiment. As the results, the compound of gallium dimercaptosuccinate has been confirmed as a novel radiopharmaceutical for tumor imaging agent.
摘要翻译：新的肿瘤显像剂，其中二巯基琥珀酸溶解在磷酸盐缓冲液中并用放射性同位素镓标记。二巯基琥珀酸镓的产物已经通过多种实验表征，包括血清稳定性，生物分布和成像实验。结果表明，二巯基琥珀酸镓的化合物已被证实为新型的肿瘤显像剂用放射性药物。

6. 发明申请

US20120107232A1 KIT FOR PREPARING A RADIOLABELED LIPOSOME AND A METHOD USING THE SAME 审中-公开
标题翻译：用于制备放射性脂质体的试剂盒和使用其的方法
公开(公告)号：US20120107232A1
公开(公告)日：2012-05-03
申请号：US13169268
申请日：2011-06-27
申请人： WEI-CHUAN HSU , Te-Wei Lee , Shu-Pei Chiu , Yi-Ting Tsai , Gann Ting
发明人： WEI-CHUAN HSU , Te-Wei Lee , Shu-Pei Chiu , Yi-Ting Tsai , Gann Ting
IPC分类号： A61K51/12 , A61P35/00
CPC分类号： A61K51/1234
摘要： A kit for preparing a radiolabeled liposome is provided, the kit including a liposome suspension and a radionuclide, wherein the liposome suspension includes a conjugate with a structure of [chelator-hydrophilic polymer-lipid]. A method for preparing a radiolabeled liposome using the kit is also disclosed herein, thereby the radiolabeled liposome being produced with the conjugate connected to the surface therein. The advantages of the present disclose such as simple, convenient and without purifying for the produced radiolabeled liposome are thus achieved. Further, the produced radiolabeled liposome has a high specific activity and a high sensitivity and suits for the clinical use.
摘要翻译：提供了用于制备放射性标记的脂质体的试剂盒，该试剂盒包括脂质体悬浮液和放射性核素，其中脂质体悬浮液包括具有[螯合剂 - 亲水性聚合物 - 脂质]结构的缀合物。本文还公开了使用试剂盒制备放射性标记的脂质体的方法，由此产生放射性标记的脂质体，其中缀合物连接到其表面。因此实现了本发明公开的优点，例如简单，方便和不需要纯化用于所制备的放射性标记的脂质体。此外，所制备的放射性标记的脂质体具有高比活度和高灵敏度，适用于临床应用。

7. 发明申请

US20110158903A1 ONE POT PROCESSES OF PREPARING MULTIFUNCTIONAL LIPOSOME DRUG FOR IMAGING, DELIVERY AND TARGETING IN CANCER DIAGNOSIS AND THERAPY 审中-公开
标题翻译：制备多功能药物药物的一个方法用于癌症诊断和治疗中的成像，传递和定向
公开(公告)号：US20110158903A1
公开(公告)日：2011-06-30
申请号：US12650793
申请日：2009-12-31
申请人： SHU-PEI CHIU , Te-Wei Lee , Chia-Yu Yu , Su-Jung Chen , Chung-Li Ho , Wei-Chuan Hsu , Ya-Jen Chang
发明人： SHU-PEI CHIU , Te-Wei Lee , Chia-Yu Yu , Su-Jung Chen , Chung-Li Ho , Wei-Chuan Hsu , Ya-Jen Chang
IPC分类号： A61K51/12 , A61P35/00
CPC分类号： A61K51/1234 , A61K47/543 , A61K47/60
摘要： One pot process of preparing multifunctional liposome drug is provided. In this one pot process, liposome reacted with radionuclide labeled solution, chemotherapy drug, and targeted ligand at appropriate temperature. The product in this invention for preparation multifunctional liposome drugs in for imaging, delivery and targeting in cancer diagnosis and therapy has proved to be more simple, convenient, effective and easier than the prior art is.
摘要翻译：提供了制备多功能脂质体药物的一锅法。在这一锅法中，脂质体与放射性核素标记溶液，化疗药物和靶向配体在合适的温度下反应。本发明中用于制备用于癌症诊断和治疗中的成像，递送和靶向的多功能脂质体药物的产品被证明比现有技术更简单，方便，有效和更容易。

8. 发明授权

US08467588B2 Volume-of-interest segmentation system for use with molecular imaging quantization 有权
标题翻译：用于分子成像量化的兴趣分割系统
公开(公告)号：US08467588B2
公开(公告)日：2013-06-18
申请号：US13283762
申请日：2011-10-28
申请人： An-Jim Long , Chih-Hsien Chang , Te-Wei Lee
发明人： An-Jim Long , Chih-Hsien Chang , Te-Wei Lee
IPC分类号： G06K9/00
CPC分类号： A61B6/508 , G06T7/11 , G06T7/149 , G06T2207/10081 , G06T2207/10088 , G06T2207/10104 , G06T2207/10108 , G06T2207/20092 , G06T2207/30004
摘要： The present invention relates to a volume-of-interest segmentation system for use with molecular imaging quantization, which includes: a set of template for segmentation of organ/anatomical region-of-interest, an animal size/weight/location calculator, an animal spine position calculator, and a texture analyzer. It can be used for saving time and reducing cost for segmentation of interested regions and increasing the precision of molecular image quantization.
摘要翻译：本发明涉及一种用于分子成像量化的兴趣体积分割系统，其包括：用于分解器官/解剖学兴趣区域的模板，动物体重/体重/位置计算器，动物脊柱位置计算器和纹理分析器。可用于节省时间，降低感兴趣区域分割成本，提高分子图像量化精度。

9. 发明申请

US20080139703A1 Method for Preparing Lipid-Spacer-Reactive Functional Group-Peptide 审中-公开
标题翻译：脂质间隔反应性功能团肽的制备方法
公开(公告)号：US20080139703A1
公开(公告)日：2008-06-12
申请号：US12029324
申请日：2008-02-11
申请人： Te-Wei Lee , Shu-Pei Chiu , Chiu-Yu Yu , Tsui-Jung Chang , Chih-Hsien Chang
发明人： Te-Wei Lee , Shu-Pei Chiu , Chiu-Yu Yu , Tsui-Jung Chang , Chih-Hsien Chang
IPC分类号： C08L89/00
CPC分类号： A61K9/1271 , A61K9/1278 , A61K47/62 , A61K47/6911 , C07K14/6555 , Y02P20/55
摘要： The present invention discloses a method for preparing lipid-spacer-reactive functional group-peptide, wherein the peptide consists of 3 to 16 amino acid residues in which at least one amino acid residue is lysine (Lys), the reactive functional group is a formula of —X—CO—Y—CO—, wherein X represents an oxygen atom or a nitrogen atom, and Y represents C1-6 alkylene which may be interrupted by one or two oxygen or nitrogen atom(s), the spacer is a hydrophilic polymer, and the lipid is phosphatidylethanoaminecarbonyl represented by the formula (I): R1 and R2 are the same or different and individually represent linear or branch C7-30 alkyl or linear or branch C7-30 alkenyl; which is characterized in that the reaction is carried out in a liquid phase and comprises the following steps of (a) firstly protecting Lys amino acid residue in the peptide through a protection group; (b) subsequently reacting the peptide with the lipid-spacer-reactive functional group; and (c) finally removing the protection group from Lys amino acid residue in the peptide.
摘要翻译：本发明公开了一种制备脂质 - 间隔物反应性官能团肽的方法，其中肽由3至16个氨基酸残基组成，其中至少一个氨基酸残基为赖氨酸（Lys），反应性官能团为式的-X-CO-Y-CO-，其中X表示氧原子或氮原子，Y表示可被一个或两个氧或氮原子间隔的C 1-6亚烷基（ s），间隔基是亲水性聚合物，并且脂质是由式（I）表示的磷脂酰硫代氨基羰基：R 1和R 2都相同或不同，并且各自代表直链或支链C 7-30烷基或直链或支链C 7-30链烯基; 其特征在于反应在液相中进行，并包括以下步骤：（a）首先通过保护基保护肽中的Lys氨基酸残基; （b）随后使肽与脂质 - 间隔物反应性官能团反应; 和（c）最后从肽中的Lys氨基酸残基中除去保护基团。

10. 发明申请

US20140377169A1 Automated synthesis device to produce Re-188-Liposome and method thereof 审中-公开
标题翻译：自动合成装置生产Re-188-脂质体及其方法
公开(公告)号：US20140377169A1
公开(公告)日：2014-12-25
申请号：US13921217
申请日：2013-06-19
申请人： Ming-Hsin Li , Shu-Pei Chiu , Chih-Hsien Chang , Te-Wei Lee
发明人： Ming-Hsin Li , Shu-Pei Chiu , Chih-Hsien Chang , Te-Wei Lee
IPC分类号： B01J19/00 , A61K51/12
CPC分类号： B01J19/004 , A61K51/1234 , C07B59/001
摘要： An automated synthesis device to produce Re-188-BMEDA solution including: a plurality of reagent vials, three-way solenoid valves, gel filtration columns and micro pumps, and a reaction vial, a product vial, a temporary storage vial, a filter membrane, and a waste vial, wherein the plurality of reagent vials include first reagent vial and second reagent vials being connected to the reaction vial through first micro pump, the third reagent vial and fourth reagent vial being connected to the reaction vial through second micro pump, fifth reagent vial being connected to the reaction vial through third micro pump, and sixth reagent vial being connected to the temporary storage vial through fourth micro pump, wherein the reaction vial is connected to the plurality of gel filtration columns through the micro-pump, respectively. The automated synthesis device is operable with program to upgrade yield and avoid contamination.
摘要翻译：一种用于生产Re-188-BMEDA溶液的自动化合成装置，包括：多个试剂瓶，三通电磁阀，凝胶过滤柱和微型泵，以及反应瓶，产品小瓶，临时储存小瓶，过滤膜以及废物小瓶，其中所述多个试剂小瓶包括通过第一微泵连接到所述反应小瓶的第一试剂小瓶和第二试剂小瓶，所述第三试剂小瓶和第四试剂小瓶通过第二微泵连接到所述反应小瓶，第五试剂小瓶通过第三微泵连接到反应小瓶，第六试剂小瓶通过第四微泵连接到临时存储小瓶，其中反应小瓶分别通过微型泵连接到多个凝胶过滤柱。自动合成装置可与程序一起操作，以提高产量并避免污染。

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