公开(公告)号：US07790881B2

公开(公告)日：2010-09-07

申请号：US11575845

申请日：2005-09-21

Applicant: John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan

Inventor： John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan

IPC: C07D279/20 ,  A61K31/5415

CPC classification number: C09B19/02 ,  C07D279/18

Abstract: This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases. Wherein: each of R1 and R9 is independently selected from: —H; C1-4 alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C4-1 alkyl; each of R7NA and R7NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C1-4 alkyl; and X is one or more anionic counter ions to achieve electrical neutrality.

Abstract translation: 本发明一般涉及化学合成和纯化领域，更具体地涉及合成和纯化包括甲基硫堇（MTC）在内的某些3,7-二氨基吩噻嗪-5-肟化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法， （也称为亚甲蓝）。 在一个实施方案中，该方法包括以下步骤：按顺序：亚硝基化（NOS）; 亚硝酰还原（NR）; 硫代磺酸形成（TSAF）; 氧化偶合（OC）; Cr（VI）还原（CR）; 两性离子中间体（IAPOZI）的分离和纯化; 闭环（RC）; 氯化物盐形成（CSF）; 一种：硫化物处理（ST）; 二甲基二硫代氨基甲酸酯处理（DT）; 碳酸盐处理（CT）; 乙二胺四乙酸处理（EDTAT）; 有机萃取（OE）; 和重结晶（RX）。 本发明还涉及所得的（高纯度）化合物，包含它们的组合物（例如片剂，胶囊）及其在灭活病原体的方法中的用途，以及治疗和诊断方法等，例如对于tau蛋白病 ，阿尔茨海默病（AD），皮肤癌，黑素瘤，病毒性疾病，细菌性疾病或原生动物疾病。 其中R 1和R 9各自独立地选自：-H; C 1-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; 并且X是一种或多种阴离子抗衡离子以实现电中性。

公开(公告)号：US20090054419A1

公开(公告)日：2009-02-26

申请号：US12294599

申请日：2007-03-28

Applicant: Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

Inventor： Claude Michel Wischik ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC: A61K31/5415 ,  C07D279/30 ,  C07D279/20 ,  C07K1/113

CPC classification number: A61K31/5415 ,  C07D279/20 ,  C07D279/22 ,  C09B21/00 ,  Y02A50/393 ,  Y02A50/411

Abstract: This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7 diamino-10H-phenothiazine (DAPTZ) compounds of the following formula wherein: each of R1 and R9 is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: —H; C1-4alkyl; C2-4alkenyl; and halogenated C1-4alkyl; each of HX1 and HX2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methythioninium chloride, MTC).

Abstract translation: 本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，具体地，下列通式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物其中：R 1和R 9各自独立地选自 从：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些化合物可用作药物，例如用于治疗tau蛋白病如阿尔茨海默氏病，以及作为相应的氧化硫堇药物（例如氯化甲硫氨酸，MTC）的前药。

公开(公告)号：US20080207603A1

公开(公告)日：2008-08-28

申请号：US11575845

申请日：2005-09-21

Applicant: John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

Inventor： John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

IPC: A61K31/5415 ,  C07D279/20 ,  C12N13/00 ,  A61P25/28 ,  A61P35/04 ,  A61P31/00

CPC classification number: C09B19/02 ,  C07D279/18

Abstract: This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases. Wherein: each of R1 and R9 is independently selected from: —H; C1-4 alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C4-1 alkyl; each of R7NA and R7NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C1-4 alkyl; and X is one or more anionic counter ions to achieve electrical neutrality.

公开(公告)号：US09242946B2

公开(公告)日：2016-01-26

申请号：US12875465

申请日：2010-09-03

Applicant: John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

Inventor： John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

IPC: C07D279/18 ,  C09B19/02

CPC classification number: A61K31/5415 ,  A61K9/0019 ,  A61K49/006 ,  C07D279/18 ,  C09B19/02 ,  G01N33/52 ,  Y02A50/393

Abstract: This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methylhioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

Abstract translation: 本发明一般涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基 - 吩噻嗪-5-鎓化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法，包括甲基氯化铑（MTC）（ 也称为亚甲基蓝）。 在一个实施方案中，该方法包括以下步骤：按顺序：亚硝基化（NOS）; 亚硝酰还原（NR）; 硫代磺酸形成（TSAF）; 氧化偶合（OC）; Cr（VI）还原（CR）; 两性离子中间体（IAPOZI）的分离和纯化; 闭环（RC）; 氯化物盐形成（CSF）; 一种：硫化物处理（ST）; 二甲基二硫代氨基甲酸酯处理（DT）; 碳酸盐处理（CT）; 乙二胺四乙酸处理（EDTAT）; 有机萃取（OE）; 和重结晶（RX）。 本发明还涉及所得的（高纯度）化合物，包含它们的组合物（例如片剂，胶囊）及其在灭活病原体的方法中的用途，以及治疗和诊断方法等，例如对于tau蛋白病 ，阿尔茨海默病（AD），皮肤癌，黑素瘤，病毒性疾病，细菌性疾病或原生动物疾病。

公开(公告)号：US20110021510A1

公开(公告)日：2011-01-27

申请号：US12875465

申请日：2010-09-03

Applicant: John Mervyn David STOREY ,  James Peter SINCLAIR ,  Colin MARSHALL ,  Han Wan TAN ,  Claude Michel WISCHIK

Inventor： John Mervyn David STOREY ,  James Peter SINCLAIR ,  Colin MARSHALL ,  Han Wan TAN ,  Claude Michel WISCHIK

IPC: A61K31/5415 ,  C07D279/20 ,  A01N43/84 ,  A61P31/12 ,  A61P33/02 ,  A61P35/00 ,  A61P31/14 ,  A61P31/18 ,  A61P25/28 ,  A61P31/04

CPC classification number: A61K31/5415 ,  A61K9/0019 ,  A61K49/006 ,  C07D279/18 ,  C09B19/02 ,  G01N33/52 ,  Y02A50/393

Abstract: This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methylhioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

Abstract translation: 本发明一般涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基 - 吩噻嗪-5-鎓化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法，包括甲基氯化铑（MTC）（ 也称为亚甲基蓝）。 在一个实施方案中，该方法包括以下步骤：按顺序：亚硝基化（NOS）; 亚硝酰还原（NR）; 硫代磺酸形成（TSAF）; 氧化偶合（OC）; Cr（VI）还原（CR）; 两性离子中间体（IAPOZI）的分离和纯化; 闭环（RC）; 氯化物盐形成（CSF）; 一种：硫化物处理（ST）; 二甲基二硫代氨基甲酸酯处理（DT）; 碳酸盐处理（CT）; 乙二胺四乙酸处理（EDTAT）; 有机萃取（OE）; 和重结晶（RX）。 本发明还涉及所得的（高纯度）化合物，包含它们的组合物（例如片剂，胶囊）及其在灭活病原体的方法中的用途，以及治疗和诊断方法等，例如对于tau蛋白病 ，阿尔茨海默病（AD），皮肤癌，黑素瘤，病毒性疾病，细菌性疾病或原生动物疾病。

公开(公告)号：US20070116943A1

公开(公告)日：2007-05-24

申请号：US10482129

申请日：2002-06-25

Applicant: Peter Sinclair ,  Mark Watson

Inventor： Peter Sinclair ,  Mark Watson

IPC: B32B27/30 ,  B32B27/20 ,  B32B3/26 ,  B05D3/12 ,  B05D1/12 ,  B05D3/02

CPC classification number: D21H19/66 ,  B29C59/026 ,  B29C59/046 ,  B29K2105/165 ,  D21H21/54 ,  G03H1/0252 ,  G03H1/028 ,  G03H2250/14 ,  G03H2250/43 ,  Y10T428/249972 ,  Y10T428/31504 ,  Y10T428/31855 ,  Y10T428/31935

Abstract: A durable holographically imaged paper, plastic film or other product is produced by embossing the image into a thermoplastic coating thereon which comprises plastic pigment particles. The plastic pigment particles are preferably hollow but may be solid. The coating preferably also comprises a thermoplastic polymer or copolymer, for example a copolymer of vinyl acetate and versatic acid, an acrylic polymer, a styrene-acrylic or other acrylic copolymer, a vinyl chloride-vinyl acetate-ethylene terpolymer, a polyvinyl acetate or a polyvinyl alcohol. Preferably, the polymer or copolymer has a glass transition temperature (Tg value) in the range 20° C. to 110° C. The thermoplastic coating may also contain inorganic pigments, for example precipitated calcium carbonate (PCC), ground natural calcium carbonate, or kaolin or other clays, and/or a starch binder. Embossing is preferably carried out directly on the thermoplastic coating by means of a holographically engraved shim.

Abstract translation: 通过将图像压印在其上的包含塑料颜料颗粒的热塑性涂层中来制造耐久的全息成像的纸，塑料膜或其它产品。 塑料颜料颗粒优选是中空的，但可以是固体。 涂层优选还包含热塑性聚合物或共聚物，例如乙酸乙烯酯和叔碳酸的共聚物，丙烯酸聚合物，苯乙烯 - 丙烯酸或其它丙烯酸共聚物，氯乙烯 - 乙酸乙烯酯 - 乙烯三元共聚物，聚乙酸乙烯酯或 聚乙烯醇。 优选地，聚合物或共聚物的玻璃化转变温度（Tg值）在20℃至110℃的范围内。热塑性涂层还可以含有无机颜料，例如沉淀碳酸钙（PCC），研磨天然碳酸钙， 或高岭土或其它粘土，和/或淀粉粘合剂。 压花优选通过全息雕刻的垫片直接在热塑性涂层上进行。

公开(公告)号：US20050245588A1

公开(公告)日：2005-11-03

申请号：US10527615

申请日：2003-09-17

Applicant: Amjad Ali ,  Susan Aster ,  James Balkovec ,  Donald Graham ,  Julianne Hunt ,  Florida Kallashi ,  Peter Sinclair ,  James Tata ,  Gayle Taylor ,  Joung Goulet

Inventor： Amjad Ali ,  Susan Aster ,  James Balkovec ,  Donald Graham ,  Julianne Hunt ,  Florida Kallashi ,  Peter Sinclair ,  James Tata ,  Gayle Taylor ,  Joung Goulet

IPC: A61K20060101 ,  A61K31/4162 ,  C07D231/44 ,  C07D231/54 ,  C07D417/00

CPC classification number: C07J71/0047 ,  C07D231/54 ,  C07D401/12 ,  C07D403/04 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D491/113

Abstract: The present invention encompasses compounds of Formula I: or pharmaceutically acceptable salts or hydrates thereof, which are useful as selective glucocorticoid receptor ligands for treating a variety of autoimmune and inflammatory diseases or conditions. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明包括式I化合物或其药学上可接受的盐或水合物，其可用作治疗各种自身免疫性和炎性疾病或病症的选择性糖皮质激素受体配体。 还包括药物组合物和使用方法。

公开(公告)号：USD440131S1

公开(公告)日：2001-04-10

申请号：US29109753

申请日：1999-08-23

Applicant: Hans Peter Aglassinger ,  Peter Sinclair

Designer： Hans Peter Aglassinger ,  Peter Sinclair

公开(公告)号：US4833002A

公开(公告)日：1989-05-23

申请号：US201393

申请日：1988-05-25

Applicant: Peter Sinclair

Inventor： Peter Sinclair

IPC: C09J7/04

CPC classification number: C09J7/042 ,  Y10T428/24802 ,  Y10T428/24934 ,  Y10T428/252 ,  Y10T428/273 ,  Y10T428/28 ,  Y10T428/283 ,  Y10T428/2865 ,  Y10T428/2878 ,  Y10T428/2891

Abstract: Paper coated uniformly with discrete dots of remoistenable adhesive, especially based on starch or polyvinyl alcohol, has curl stability comparable with particle gum coated papers. Preferably, the dots are less than 0.3 mm in diameter and typically spaced 0.5 to 1 mm (centers) apart. The product is made by screen coating dots of aqueous adhesive mix onto base paper.

Abstract translation: 特别是基于淀粉或聚乙烯醇的可再粘合粘合剂的离散点均匀涂布的纸具有与颗粒胶涂布纸相当的卷曲稳定性。 优选地，点的直径小于0.3mm，并且通常间隔开0.5至1mm（中心）。 该产品通过将水性粘合剂混合物的点的丝网涂布在原纸上制成。

公开(公告)号：US4396670A

公开(公告)日：1983-08-02

申请号：US247150

申请日：1981-03-24

Applicant: Peter Sinclair

Inventor： Peter Sinclair

IPC: B01J13/02 ,  B01J13/18 ,  B41M5/165 ,  B32B3/26

CPC classification number: B41M5/165 ,  B01J13/18 ,  Y10T428/249997

Abstract: In a process for the production of microcapsules containing a liquid fill material, a dispersion-stabilizing species is produced in an aqueous acidic medium by interaction of a melamine formaldehyde precondensate and a water soluble polymer, neither of which alone is dispersion stabilizing with respect to the liquid fill material, and the precondensate is condensed by acid catalysis to produce a condensate which separates from solution and enwraps the liquid fill material to produce microcapsules.

Abstract translation: 在制备含有液体填充材料的微胶囊的方法中，通过三聚氰胺甲醛预缩合物和水溶性聚合物的相互作用在酸性介质中产生分散体稳定化物质，这两者都不是相对于 液体填充材料，并且预缩合物通过酸催化而缩合以产生从溶液中分离并包裹液体填充材料以产生微胶囊的冷凝物。