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 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 recrystallization (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.

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 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 recrystallization (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.

The present invention relates to piperazine phenothiazine derivatives useful as therapeutic agents for treating spasticity, particularly following an ischemia or traumatic injury, or compression syndrome. The invention further relates to a pharmaceutical composition comprising a compound of the invention for treating spasticity.

The present invention relates to diaminophenothiazinium derivatives of formula (I); in which R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and X.sup. are as defined in Claim 1, and also the methods for labelling oligonucleotides using such a derivative, labeling substrates and the oligonucleotides which can be obtained by means of such methods or from such labelling substrates.

The present invention relates to diaminophenothiazinium derivatives of formula (I); in which R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and X.sup. are as defined in Claim 1, and also the methods for labelling oligonucleotides using such a derivative, labeling substrates and the oligonucleotides which can be obtained by means of such methods or from such labelling substrates.

A redox polymer for forming an electrochemical sensor suitable for use in measurement over a long period (continuous monitoring) and excellent in stability, or a redox mediator constituting the same. The redox mediator is a phenothiazine-based compound having a hydrophilic moiety introduced therein, the compound being represented by the general formula (2A) or (2B). The redox polymer is a phenothiazine-based compound bound to a polymer, the compound being represented by the general formula (3A) or (3B). In the formulas, R.sup.9 and R.sup.10 are both substituents, or one of these moieties is a substituent, and the other moiety is a hydrogen atom, R(L).sup.1, R(L).sup.2, and R(L).sup.4 to R(L).sup.8 are each independently a predetermined group or atom, (QP).sup.1, (QP).sup.2, and (QP).sup.4 to (QP).sup.8 are each independently a polymeric structure derived from a high molecular weight polymer which is present when their corresponding R(L).sup.1, R(L).sup.2, and R(L).sup.4 to R(L).sup.8 are a specific group.

A redox polymer for forming an electrochemical sensor suitable for use in measurement over a long period (continuous monitoring) and excellent in stability, or a redox mediator constituting the same. The redox mediator is a phenothiazine-based compound having a hydrophilic moiety introduced therein, the compound being represented by the general formula (2A) or (2B). The redox polymer is a phenothiazine-based compound bound to a polymer, the compound being represented by the general formula (3A) or (3B). In the formulas, R.sup.9 and R.sup.10 are both substituents, or one of these moieties is a substituent, and the other moiety is a hydrogen atom, R(L).sup.1, R(L).sup.2, and R(L).sup.4 to R(L).sup.8 are each independently a predetermined group or atom, (QP).sup.1, (QP).sup.2, and (QP).sup.4 to (QP).sup.8 are each independently a polymeric structure derived from a high molecular weight polymer which is present when their corresponding R(L).sup.1, R(L).sup.2, and R(L).sup.4 to R(L).sup.8 are a specific group.

The present invention describes synthesis of Toluidine blue O for a formulation to be used for screening and biopsy site identification in oral cancer. The invention discloses two formulations and a method of delivery of the said formulations via a kit. The method described is a reproducible method of synthesis of pharmaceutical grade Toluidine blue O of acceptable purity and good colorimetric value. The present invention also discloses a kit that includes one formulation of a cleaning solution containing an organic acid and another formulation that is a vital stain formulation. The kit is packaged as a dual chamber sprayer having two pump dispensers, that facilitates ready to use, convenient dental chair side delivery, and allows mass screening.

The present invention describes synthesis of Toluidine blue O for a formulation to be used for screening and biopsy site identification in oral cancer. The invention discloses two formulations and a method of delivery of the said formulations via a kit. The method described is a reproducible method of synthesis of pharmaceutical grade Toluidine blue O of acceptable purity and good colorimetric value. The present invention also discloses a kit that includes one formulation of a cleaning solution containing an organic acid and another formulation that is a vital stain formulation. The kit is packaged as a dual chamber sprayer having two pump dispensers, that facilitates ready to use, convenient dental chair side delivery, and allows mass screening.

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.