公开(公告)号：US06596770B2

公开(公告)日：2003-07-22

申请号：US10044096

申请日：2002-01-11

申请人： Ching-San Lai ,  Vassil Vassilev

发明人： Ching-San Lai ,  Vassil Vassilev

IPC分类号： A61K3116

CPC分类号： A61K31/4025 ,  A61K31/4545 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/423 ,  Y10S514/851

摘要： The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

公开(公告)号：US06355666B1

公开(公告)日：2002-03-12

申请号：US09602688

申请日：2000-06-23

申请人： Ching-San Lai ,  Tingmin Wang

发明人： Ching-San Lai ,  Tingmin Wang

IPC分类号： A61K3148

CPC分类号： A61K47/555 ,  A61K47/54

摘要： In accordance with the present invention, there are provided normal modified forms of nonsteroidal anti-inflammatory drugs. Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

摘要翻译： 根据本发明，提供了非甾体抗炎药的正常修饰形式。 根据本发明的修饰的NSAID提供了一类新的抗炎剂，其提供NSAIDs的治疗益处，同时引起副作用的发生率低得多，然后通常用这些药剂观察到。

公开(公告)号：US06274627B1

公开(公告)日：2001-08-14

申请号：US09416619

申请日：1999-10-12

申请人： Ching-San Lai ,  Vassil P. Vassilev ,  Tingmin Wang

发明人： Ching-San Lai ,  Vassil P. Vassilev ,  Tingmin Wang

IPC分类号： A61K3116

CPC分类号： A61K47/55

摘要： In accordance with the present invention, there are provided conjugates of physiologically compatible free radical scavengers (e.g., dithiocarbamate disulfides (DD)) and pharmacologically active agents (e.g., NSAIDS). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of free radical overproduction induced thereby as a result of the co-production of free radical scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

摘要翻译： 根据本发明，提供了生理上相容的自由基清除剂（例如二硫代氨基甲酸酯二硫化物（DD））和药理活性剂（例如NSAIDS）的缀合物。 本发明共轭物提供了一类新的药理活性剂（例如抗炎剂），其由于通过改变如本文所述的药理学活性剂而赋予的保护作用，导致副作用的低得多的发生率。 此外，发明共轭物比未改性的药理学活性剂更有效，因为与药理活性剂接触的细胞和组织被保护免受由此引起的自由基过度产生的潜在的破坏性作用，这是由于自由基的共同产生 除了游离的药理学活性剂之外，当发明结合物被切割时，清除剂（例如，二硫代氨基甲酸盐）。

公开(公告)号：US4593248A

公开(公告)日：1986-06-03

申请号：US593900

申请日：1984-03-27

申请人： James S. Hyde ,  Wojciech Froncisz ,  Ching-San Lai

发明人： James S. Hyde ,  Wojciech Froncisz ,  Ching-San Lai

IPC分类号： G01R33/465 ,  G01R33/60 ,  G01R33/20

CPC分类号： G01R33/465 ,  G01R33/60

摘要： An ESR spectrometer is employed to measure the oxygen concentration in a sample material. Electron paramagnetic resonance is produced in a free radical mixed with a standard material of known oxygen concentration. The phase of the signal produced by this resonance is compared with the phase of the signal produced by the electron paramagnetic resonance of the free radical mixed with the sample material. The oxygen concentration in the sample material has a single valued functional relationship with respect to this phase difference and is calculated in a microprocessor-based control system. At low oxygen concentrations, the relationship is a linear one.

摘要翻译： 使用ESR光谱仪来测量样品材料中的氧浓度。 在与已知氧浓度的标准材料混合的自由基中产生电子顺磁共振。 将由该共振产生的信号的相位与由与样品材料混合的自由基的电子顺磁共振产生的信号的相位进行比较。 样品材料中的氧浓度相对于该相位差具有单值函数关系，并且在基于微处理器的控制系统中计算。 在低氧浓度下，这种关系是一个线性关系。

公开(公告)号：USRE41151E1

公开(公告)日：2010-02-23

申请号：US12194940

申请日：2008-08-20

申请人： Ching-San Lai ,  Tingmin Wang

发明人： Ching-San Lai ,  Tingmin Wang

IPC分类号： A61K31/48 ,  A61K31/405 ,  A61K31/255 ,  A61K31/40 ,  A61K31/34 ,  C07C69/66 ,  C07C69/67 ,  C07C69/612

CPC分类号： A61K47/555 ,  A61K47/54

摘要： In accordance with the present invention, there are provided normal modified forms of nonsteroidal anti-inflammatory drugs. Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

摘要翻译： 根据本发明，提供了非甾体抗炎药的正常修饰形式。 根据本发明的修饰的NSAID提供了一类新的抗炎剂，其提供NSAIDs的治疗益处，同时引起副作用的发生率低得多，然后通常用这些药剂观察到。

公开(公告)号：US06710086B1

公开(公告)日：2004-03-23

申请号：US09515043

申请日：2000-02-25

申请人： Ching-San Lai ,  Tingmin Wang ,  Vassil P. Vassilev

发明人： Ching-San Lai ,  Tingmin Wang ,  Vassil P. Vassilev

IPC分类号： A61K3116

CPC分类号： A61K47/555 ,  A61K47/54

摘要： In accordance with the present invention, there are provided conjugates of dithiocarbamates “DC”) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein.

摘要翻译： 根据本发明，提供二硫代氨基甲酸酯“DC”的缀合物和药理学活性剂（例如NSAID）。 本发明共轭物提供了一类新的药理活性剂（例如抗炎剂），其由于通过改变如本文所述的药理学活性剂而赋予的保护作用，导致副作用的低得多的发生率。

公开(公告)号：US06620813B1

公开(公告)日：2003-09-16

申请号：US10177683

申请日：2002-06-21

申请人： Tingmin Wang ,  Ching-San Lai

发明人： Tingmin Wang ,  Ching-San Lai

IPC分类号： A61K3153

CPC分类号： C07D253/08 ,  A61K31/425 ,  A61K31/53 ,  C07C259/06 ,  C07C259/10 ,  C07C271/08 ,  C07C311/48 ,  C07C317/44 ,  C07C323/60 ,  C07D209/28 ,  C07D277/36

摘要： In accordance with the present invention, there are provided novel chemical entities which have multiple utilities, e.g., as prodrugs of NSAIDs; as dual inhibitors of cyclooxygenase (COX) and 5-lipoxygenase (5-LO); as anticancer agents (through promoting apoptosis and/or inhibiting the matrix metalloproteinases (MMPs)), and the like. Invention compounds comprise a non-steroidal anti-inflammatory agent (NSAID), covalently linked to a hydroxamate. Invention compounds are useful for a variety of applications, such as, for example, treating inflammation and inflammation-related conditions; reducing the side effects associated with administration of anti-inflammatory agents; promoting apoptosis; inhibiting matrix metalloproteinases; and the like.

摘要翻译： 根据本发明，提供了具有多种用途的新型化学实体，例如作为NSAID的前药; 作为环氧合酶（COX）和5-脂氧合酶（5-LO）的双重抑制剂; 作为抗癌剂（通过促进细胞凋亡和/或抑制基质金属蛋白酶（MMPs））等。 本发明化合物包含与羟肟酸共价连接的非甾体抗炎剂（NSAID）。 本发明化合物可用于各种应用，例如治疗炎症和炎症相关病症; 减少与抗炎剂的施用相关的副作用; 促进凋亡; 抑制基质金属蛋白酶; 等等。

公开(公告)号：US06589991B1

公开(公告)日：2003-07-08

申请号：US09565665

申请日：2000-05-05

申请人： Ching-San Lai ,  Vassil Vassilev

发明人： Ching-San Lai ,  Vassil Vassilev

IPC分类号： A61K3116

CPC分类号： A61K31/145 ,  A61K31/4025 ,  A61K31/5377 ,  A61K45/06 ,  Y02A50/411 ,  Y10S514/825 ,  Y10S514/838 ,  Y10S514/851 ,  Y10S514/861 ,  Y10S514/863 ,  Y10S514/866 ,  Y10S514/885 ,  Y10S514/903 ,  Y10S514/909 ,  Y10S514/912 ,  Y10S514/925

摘要： The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

公开(公告)号：US5916910A

公开(公告)日：1999-06-29

申请号：US869158

申请日：1997-06-04

申请人： Ching-San Lai

发明人： Ching-San Lai

IPC分类号： A61K45/00 ,  A61K31/27 ,  A61K31/40 ,  A61K38/00 ,  A61P43/00 ,  C07C333/02 ,  C07C333/04 ,  C07C333/06 ,  C07C333/08 ,  C07D207/04 ,  C07D207/30

CPC分类号： C07C333/16

摘要： In accordance with the present invention, there are provided conjugates of nitric oxide scavengers (e.g., dithiocarbamates, or "DC") and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of nitric oxide overproduction induced thereby as a result of the co-production of nitric oxide scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

摘要翻译： 根据本发明，提供了一氧化氮清除剂（例如二硫代氨基甲酸盐或“DC”）和药理活性剂（例如NSAID）的缀合物。 本发明共轭物提供了一类新的药理活性剂（例如抗炎剂），其由于通过改变如本文所述的药理学活性剂而赋予的保护作用，导致副作用的低得多的发生率。 此外，发明共轭物比未改性的药理活性剂更有效，因为与药理活性剂接触的细胞和组织被保护免受由于一氧化氮的共同产生而导致的一氧化氮过量产生的潜在的破坏性作用 除了游离的药理学活性剂之外，当发明结合物被切割时，清除剂（例如，二硫代氨基甲酸盐）。

公开(公告)号：US5847004A

公开(公告)日：1998-12-08

申请号：US767125

申请日：1996-12-09

申请人： Ching-San Lai

发明人： Ching-San Lai

IPC分类号： A61K38/00 ,  A61K31/00 ,  A61K31/135 ,  A61K31/27 ,  A61K31/295 ,  A61K31/30 ,  A61K38/21 ,  A61K45/00 ,  A61P1/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/00 ,  A61P3/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/00 ,  A61P13/12 ,  A61P17/00 ,  A61P17/02 ,  A61P25/16 ,  A61P25/28 ,  A61P27/00 ,  A61P27/02 ,  A61P29/00 ,  A61P31/00 ,  A61P31/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P43/00 ,  C07C333/16 ,  C07F15/02 ,  A01N37/18

CPC分类号： A61K31/295 ,  C07C333/16

摘要： In accordance with the present invention, there are provided methods for the in vivo reduction of nitric oxide levels in a mammalian subject. In contrast to the inhibitory approach described in the prior art (i.e., wherein the function of the enzymes responsible for nitric oxide production is inhibited), the present invention employs a scavenging approach whereby overproduced nitric oxide is bound in vivo to a suitable nitric oxide scavenger. The resulting complex renders the nitric oxide harmless, and is eventually excreted in the urine of the host. An exemplary nitric oxide scavenger contemplated for use in the practice of the present invention is a dithiocarbamate-ferrous iron complex. This complex binds to .NO, forming a stable, water-soluble NO-containing complex having a characteristic three-line spectrum (indicative of a mononitrosyl-Fe complex) which can readily be detected at ambient temperatures by electron paramagnetic resonance (EPR) spectroscopy. The present invention relates to methods for reducing in vivo levels of .NO as a means of treating subjects afflicted with inflammatory and/or infectious disease. Nitric oxide scavengers are administered to a host in need of such treatment; these scavengers interact with in vivo produced .NO, forming a stable NO-containing complex. The NO-containing complex is then filtered through the kidneys, concentrated in the urine, and eventually excreted by the subject, thereby reducing in vivo .NO levels.

摘要翻译： 根据本发明，提供哺乳动物受试者体内还原一氧化氮水平的方法。 与现有技术中描述的抑制方法（即，其中负责一氧化氮生产的酶的功能被抑制）相反，本发明采用清除方法，其中过量产生的一氧化氮在体内结合到合适的一氧化氮清除剂 。 所得复合物使一氧化氮无害，最终在宿主的尿液中排泄。 考虑用于本发明实践的示例性一氧化氮清除剂是二硫代氨基甲酸盐 - 二价铁络合物。 该络合物结合到NO，形成稳定的水溶性含NO的络合物，其具有特征性的三线谱（表示单亚硝酰基-Fe络合物），其可以通过电子顺磁共振（EPR）光谱在环境温度下容易地检测 。 本发明涉及降低体内水平的方法，用于治疗患有炎性和/或感染性疾病的受试者的手段。 向需要这种治疗的宿主施用一氧化氮清除剂; 这些清除剂与体内生成的NONO相互作用，形成稳定的含NO复合物。 然后将含NO的复合物通过肾脏过滤，浓缩在尿液中，并最终被受试者排泄，从而在体内降低NO水平。