公开(公告)号：US08461208B2

公开(公告)日：2013-06-11

申请号：US13273807

申请日：2011-10-14

申请人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： A61K31/16

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts and pharmaceutical compositions thereof. Also disclosed are methods of using bis(thio-hydrazide amide) disalts to treat cancer.

摘要翻译： 公开了双（硫代酰肼酰胺）二盐及其药物组合物。 还公开了使用双（硫代酰肼酰胺）狄尔斯治疗癌症的方法。

公开(公告)号：US20060135595A1

公开(公告)日：2006-06-22

申请号：US11157213

申请日：2005-06-20

申请人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： A61K31/4015 ,  A61K31/16

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

摘要翻译： 公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地是-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或R 1， SUB和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4结合在一起 与其键合的碳原子和氮原子形成任选地稠合到芳香环的非芳族杂环。 Z是-O或-S。 M + +是药学上可接受的一价阳离子，M 2 +是药学上可接受的二价阳离子。 还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。 进一步公开的是用癌症治疗受试者的方法。 所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

公开(公告)号：US07795313B2

公开(公告)日：2010-09-14

申请号：US12503661

申请日：2009-07-15

申请人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： A61K31/16

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

摘要翻译： 公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。 还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。 进一步公开的是用癌症治疗受试者的方法。 所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

公开(公告)号：US07579503B2

公开(公告)日：2009-08-25

申请号：US12148312

申请日：2008-04-18

申请人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： C07C327/38 ,  A61K31/16

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation.Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

摘要翻译： 公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。 还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。 进一步公开的是用癌症治疗受试者的方法。 所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。

公开(公告)号：US5286495A

公开(公告)日：1994-02-15

申请号：US880866

申请日：1992-05-11

申请人： Chris Batich ,  Farid Vaghefi

发明人： Chris Batich ,  Farid Vaghefi

IPC分类号： A61K9/16 ,  A61K9/50 ,  A61K9/52 ,  A61K35/12 ,  A61K35/74 ,  C12N11/04

CPC分类号： A61K9/1652 ,  A61K35/74 ,  A61K9/5026 ,  A61K9/5031 ,  A61K9/5073 ,  C12N11/04 ,  Y10S514/866 ,  Y10S514/891 ,  Y10S514/963 ,  Y10S514/965

摘要： Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the alginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 .mu.m) alginate microcapsules were made for injection as means of implantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.

摘要翻译： 将生物降解酶和细菌包封以进行肠溶和腹膜内给药。 我们已经表明，通过藻酸盐微胶囊化生物标记物，酶活性保留了数月。 开发了一种加强藻酸盐微胶囊及其对柠檬酸盐处理的耐受性的新工艺。 制造更小的（30-50（my）m）藻酸盐微胶囊用于注射作为植入手段。 对于口服给药，制备聚-2-乙烯基吡啶（pKa = 3.5）中的邻苯二甲酸纤维素的多包封微球体，以保护酶免于胃液。

公开(公告)号：US06429851B1

公开(公告)日：2002-08-06

申请号：US09373922

申请日：1999-08-12

申请人： Kimberly Vaghefi ,  Farid Vaghefi

发明人： Kimberly Vaghefi ,  Farid Vaghefi

IPC分类号： G09G508

CPC分类号： G06F3/0383 ,  G06F3/03543 ,  G06F3/03549

摘要： A graphic user interface, such as a standard functioning mouse or track ball, which has the shape and/or appearance of various different characters, such as animals and which may be sized for use by children. The graphic user interface also has various removable and interchangable parts so that its appearance can be changed without interfering with functioning of the device. The graphic user interface can have added features such as sound an/or light generating features so that normal operation of the buttons causes the production of a sound or sounds which depends on the shape applied to the graphic user interface. Depressing the buttons can also cause bulbs or LCDs positioned on the graphic user interface body, particularly in the eyes of the character, to light. Additionally, one or more graphic user interfaces incorporating features of the invention can be connected in tandem with a standard mouse so that users could alternatively use a normal graphic user interface without the necessity of disconnecting the added graphic user interface.

摘要翻译： 具有标准功能的鼠标或轨迹球的图形用户界面，其具有诸如动物的各种不同角色的形状和/或外观，并且其大小适合儿童使用。 图形用户界面还具有各种可拆卸和可互换的部件，使得其外观可以改变而不会干扰设备的功能。 图形用户界面可以具有诸如声音/或发光特征的功能，使得按钮的正常操作导致产生根据应用于图形用户界面的形状的声音或声音。 按下按钮也可能导致位于图形用户界面主体上的灯泡或LCD，特别是在人物眼睛中亮起。 此外，结合本发明的特征的一个或多个图形用户界面可以与标准鼠标串联连接，使得用户可以替代地使用普通图形用户界面，而不需要断开附加的图形用户界面。

公开(公告)号：US06242230B1

公开(公告)日：2001-06-05

申请号：US09442925

申请日：1999-11-18

申请人： Chris Batich ,  Farid Vaghefi

发明人： Chris Batich ,  Farid Vaghefi

IPC分类号： C12N1100

CPC分类号： A61K9/1652 ,  A61K9/5026 ,  A61K9/5031 ,  A61K9/5073 ,  A61K35/74 ,  C12N11/04 ,  Y10S514/866 ,  Y10S514/891 ,  Y10S514/963 ,  Y10S514/965

摘要： Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the alginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 &mgr;m) alginate microcapsules were made for injection as means of implantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.

摘要翻译： 将生物降解酶和细菌包封以进行肠溶和腹膜内给药。 我们已经表明，通过藻酸盐微胶囊化生物标记物，酶活性保留了数月。 开发了一种加强藻酸盐微胶囊及其对柠檬酸盐处理的耐受性的新工艺。 制备更小的（30-50um）藻酸盐微胶囊用于注射作为植入手段。 对于口服给药，制备聚-2-乙烯基吡啶（pKa = 3.5）中的邻苯二甲酸纤维素的多包封微球体，以保护酶免于胃液。

公开(公告)号：US6033888A

公开(公告)日：2000-03-07

申请号：US891189

申请日：1997-07-10

申请人： Chris Batich ,  Farid Vaghefi

发明人： Chris Batich ,  Farid Vaghefi

IPC分类号： A61K9/16 ,  A61K9/50 ,  A61K9/52 ,  A61K35/12 ,  A61K35/74 ,  C12N11/04 ,  C12N11/10 ,  B01J13/22

CPC分类号： A61K9/1652 ,  A61K35/74 ,  A61K9/5026 ,  A61K9/5031 ,  A61K9/5073 ,  C12N11/04 ,  Y10S514/866 ,  Y10S514/891 ,  Y10S514/963 ,  Y10S514/965

摘要： Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the aliginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 .mu.m) aliginate microcapsules were made for injection as means of impantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.

摘要翻译： 将生物降解酶和细菌包封以进行肠溶和腹膜内给药。 我们已经表明，通过藻酸盐微胶囊化生物标记物，酶活性保留了数月。 开发了一种新方法，加强了血浆微胶囊及其对柠檬酸盐治疗的耐受性。 制备更小的（30-50微米）的凝胶微胶囊作为注射的手段。 对于口服给药，制备聚-2-乙烯基吡啶（pKa = 3.5）中的邻苯二甲酸纤维素的多包封微球体，以保护酶免于胃液。

公开(公告)号：US20120035266A1

公开(公告)日：2012-02-09

申请号：US13273807

申请日：2011-10-14

申请人： Keizo KOYA ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo KOYA ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： A61K31/16 ,  A61P35/00

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts and pharmaceutical compositions thereof. Also disclosed are methods of using bis(thio-hydrazide amide) disalts to treat cancer.

摘要翻译： 公开了双（硫代酰肼酰胺）二盐及其药物组合物。 还公开了使用双（硫代酰肼酰胺）狄尔斯治疗癌症的方法。

公开(公告)号：US20100324143A1

公开(公告)日：2010-12-23

申请号：US12871587

申请日：2010-08-30

申请人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

发明人： Keizo Koya ,  Lijun Sun ,  Elena Kostik ,  Farid Vaghefi ,  Shoujun Chen ,  Noriaki Tatsuta ,  Guiqing Liang ,  Takayo Inoue ,  Zhi-Qiang Xia

IPC分类号： A61K31/166 ,  A61P35/00 ,  A61P35/02

CPC分类号： C07D305/14 ,  C07C327/56 ,  C07C2601/02

摘要： Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I): Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is —O or —S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

摘要翻译： 公开了由结构式（I）表示的双（硫代 - 酰肼酰胺）二醛：Y是共价键或取代或未取代的直链烃基。 R 1 -R 4独立地为-H，脂族基团，取代的脂族基团，芳基或取代的芳基，或者R 1和R 3与它们所键合的碳原子和氮原子一起，和/或R 2和R 4 与它们所键合的碳原子和氮原子一起形成任选地与芳环稠合的非芳族杂环。 Z是-O或-S。 M +是药学上可接受的一价阳离子，M2 +是药学上可接受的二价阳离子。 还公开了包含上述双（硫代 - 酰肼酰胺）二盐的药物组合物。 进一步公开的是用癌症治疗受试者的方法。 所述方法包括施用有效量的上述双（硫代 - 酰肼酰胺）二盐的步骤。