Wista Laboratories Ltd.

Other

The University Court of the University of Aberdeen

Genting Taurx Diagnostic Centre Sdn Bhd

Gtinvent Limited

Charles Robert Harrington

Janet Elizabeth Rickard

David Horsley

Claude Michel Wischik

Taurx Therapeutics Management Ltd.

John Mervyn David Storey

James Peter Sinclair

Colin Marshall

Thomas Craven Baddeley

John Mervyn Storey

Scott Clunas

Björn Olaf Schelter

Damon Jude Wischik

Han Wan Tan

Karrar Ahmad Khan

Craig Williamson

Michael Simpson

Ahtsham Ishaq

Barry Alan Wood

Yin Sze Loh

Christopher Paul Larch

Martin Roth

Patricia Carol Edwards

Aaron Klug

Helen Christine Shiells

Tobias Heinrich

Michael Philip Mazanetz

Steven John Kemp

Franz Theuring

Linda Sommerlade

Claudia Zabke

John M D Storey

Aaron King

Karsten Stamer

Suzannah Marie Morson

Dominic Venay Harbaran

Gernot Riedel

Serena Deiana

Elizabeth Anne Goatman

Alison Dorothy Murray

Roger Todd Staff

Lynda Jane Storey

Louise Charlotte Serpell

Saskia Julie Pollack

Karen Elizabeth Marshall

Mohammad Arastoo

Tobias Kerst Heinrich

A method, a computer implemented method, and a device, all for adaptively testing a subjects neurological state. The method comprising the steps of: administering one or more seed questions; obtaining one or more answer(s) to the one or more seed questions; calculating a score value of a latent subject trait from the answers to the one or more seed questions; the method comprising an adaptive test loop, comprising: (a) selecting, based on the score value, one or more further questions from a bank of questions; (b) administering the one or more further questions to the subject; (c) updating the score value based on the answers to the one or more further questions; (d) determining whether a test completion criteria has been met; wherein the method repeats steps (a)-(d) in sequence until the test completion criteria has been met, and provides an output of the test based on the score value which is indicative of the subjects neurological state.

Adaptive neurological testing method

Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: Rand Rare independently selected from: —H; Calkyl; Calkenyl; and halogenated Calkyl; each of Rand Ris independently selected from: —H; Calkyl; Calkenyl; and halogenated Calkyl; each of Rand Ris independently selected from: —H; Calkyl; Calkenyl; and halogenated Calkyl; each of HXand HXis independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

3, 7-diamino-10H-phenothiazine salts and their use

The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of a acetylcholinesterase levels.

Administration and dosage of diaminophenothiazines

The invention provides novel dosing regimens for Leuco-Methylthioninium (LMT) compounds which maximise the proportion of subjects in which the MT concentration will exceed concentrations in which therapeutic efficacy in relation to treatment of neurodegenerative disorders such as Alzheimer's disease and rontotemporal dementias can be achieved, while maintaining a desirable clinical profile. Also provided are LMT-containing dosage units and other compositions.

Optimised dosage of diaminophenothiazines in populations

The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of acetylcholinesterase levels.

Disclosed are compounds of general formula (I): and pharmaceutically acceptable salts thereof, formulations, methods and uses in, for example, the treatment of disease.

Phenothiazine diaminium salts and their use

Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds ('diaminophenothiazinium compounds') including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

Methods of synthesis and/or purification of diaminophenothiazinium compounds

Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: Rand Rare independently selected from: &#x2014;H; Calkyl; Calkenyl; and halogenated Calkyl; each of Rand Ris independently selected from: &#x2014;H; Calkyl; Calkenyl; and halogenated Calkyl; each of Rand Ris independently selected from: &#x2014;H; Calkyl; Calkenyl; and halogenated Calkyl; each of HXand HXis independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

This disclosure 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 Methythioninium 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). Also disclosed 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.

Medical methods utilising high purity diaminophenothiazinium compounds

Growing community of inventors

Aberdeen, United Kingdom

Claude Michel Wischik