Abstract: The present invention relates generally to methods and materials for use in the treatment or prophylaxis of diseases, for example cognitive disorders, using diaminophenothiazines. In particular it relates to treatments having optimised pharmacokinetic properties, and dosage forms are intended to improve the relative cognitive or CNS benefits of the diaminophenothiazines, for instance compared to haematological effects.

Abstract: Enantomerically purified phenothiazines are provided as active ingredients of medicaments to limit activity of bone resorbing cells so as to reduce bone loss. Novel phenothiazine derivatives are provided. A method of synthesizing enantiomerically pure phenothiazine derivatives is provided that avoids post-synthetic enantiomeric resolution.

Abstract: The present invention relates to substituted phenothiazines with a double bond and physiologically acceptable salts thereof, and their use as a medicament.

Abstract: Compositions and methods for treating intoxication by poisonous agents are described. In one aspect the pharmaceutical compositions include a phenothiazine compound, a dioic acid compound and a pharmaceutically acceptable carrier. In another aspect the pharmaceutical composition can include a phenothiazine compound, a nitroester compound, ethanol and a pharmaceutically acceptable carrier.

Abstract: The present invention includes a composition for enhancing the antimicrobial efficacy of photodynamic disinfection against Gram-negative organism that is receptive to paraben potentiation using a composition comprising a photosensitizer and at least one paraben. The present invention also includes a method for photodynamic disinfection comprising applying the composition to a desired treatment area and applying light to the desired treatment area at a wavelength absorbed by the photosensitizer so as to inhibit Gram-negative organism located within the treatment area wherein the Gram-negative organism is receptive to paraben potentiation.

Abstract: Provided herein are pharmaceutical compositions comprising phenothiazines or derivatives thereof that are formulated for nasal administration. Also provided herein are methods of utilizing the same.

Abstract: Novel 2,8-diaminophenothiazine compounds, a method for preparing the same, and uses of the novel 2,8-diaminophenothiazine compounds in the field of treating liquid or gaseous fluids, especially influents and industrial or domestic effluents.

Abstract: Methods and compositions are provided for treating neuropsychiatric disorders such as schizophrenia, depression, attention deficit disorder, mild cognitive impairment, dementia, and bipolar disorder. The methods entail administering to a patient diagnosed as having a neuropsychiatric disorder (e.g., schizophrenia, depression, attention deficit disorder, mild cognitive impairment, dementia bipolar disorder, etc.) or as at risk for a neuropsychiatric disorder a benzoic acid, benzoic acid salt, and/or benzoic acid derivative, and/or a sorbic acid, sorbic acid salt, and/or sorbic acid derivative, in combination with a neuropharmacological agent (e.g., an antipsychotic, an antidepressant, medications for attention deficit and hyperactivity disorder, cognitive impairment, or dementia, etc.) where the benzoic acid, benzoic acid salt, or benzoic acid derivative, and/or a sorbic acid, sorbic acid salt, and/or sorbic acid derivative, is in an amount sufficient to increase the efficacy of the neuropharmacological agent.

Abstract: The present invention relates generally to methods and materials based on diaminophenothiazines for use in the treatment of Mild Cognitive Impairment (MCI).

Abstract: The present invention discloses dye-sulfenate derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and free radicals at the lesion of interest.

Abstract: This invention relates to compositions, methods, devices and kits relating to the infusion of a catheter lock solution into an indwelling catheter. Inventive compositions, methods, devices and kits aid in diminishing the effects of microbial infection in catheters and occlusion of the catheters. A lock solution provided by the invention includes citrate and a paraben. The solution preferably has a density suitable for retention of the solution in a catheter during the lock period. Another lock solution provided by the invention includes citrate, a paraben and a photo-oxidant, such as, for example, methylene blue.

Abstract: The present invention relates to new benzisoxazole modulators of D2 receptors and/or 5-HT2A receptors, pharmaceutical compositions thereof, and methods of use thereof.

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-diaminophenothiazin-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). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g.

Abstract: The present invention relates to a pharmaceutical composition which contains a compound of formula in which R1, R2, R3 and R4 are each n-butyl, where XP? is a counteranion and P is 1, 2 or 3, together with a pharmaceutically acceptable carrier, excipient or adjuvant.

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.

Abstract: A methylene blue—curcumin hybrid useful in treating Alzheimer's Disease.

Abstract: A method for determining the Braak stage of neurofibrillary degeneration associated with a tauopathy in a subject having neurofibrillary degeneration is disclosed. The method comprises the steps of (i) administering to the subject a conjugated, chelated or detectable chemical group-associated ligand that labels aggregated paired helical filament (PHF) tau protein and is capable of crossing the blood brain barrier; (ii) determining the presence and\or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, and (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. Preferred ligands include sulphonated-benzothiazole-like compounds and diamonophenothiazines.

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.

Abstract: The invention concerns the use of a phenothiazine derivative of formula (I), wherein: R represents the hydrogen atom, an alkyl radical, arylalkyl, or —C(O)R?, for preparing a medicine for preventing and/or treating hearing loss.

Abstract: The present invention provides methods for treating neurological diseases and disorders. Compounds that replace or enhance the function of SMN or alleviate or reduce a phenotype of cells with low SMN protein levels are provided. Screening methods and kits for identifying such compounds also are provided.

Abstract: The present invention is directed to a method of enhancing TGF-? signaling in a subject comprising administering to said subject a clathrin-dependent endocytosis inhibitor in an amount sufficient to enhance TGF-? signaling. In another aspect, the invention is directed to a method of treating a condition associated with decreased TGF-? signaling in a patient in need thereof comprising administering to said patient a clathrin-dependent endocytosis inhibitor in a therapeutically effective amount.

Abstract: A formulation or preparation for treating and preventing arterial and venous thrombi is provided. This preparation includes a non-metal containing photodynamic dye and a fat soluble vitamin. A method of administration for treatment and prophylaxis of arterial and venous thrombi is also provided. This method includes steps of: combining a non-metal containing photodynamic dye and a fat soluble vitamin; combining the non-metal containing photodynamic dye and fat soluble vitamin with a sodium solution; and administering the combination of non-metal containing photodynamic dye, fat soluble vitamin, and sodium solution as an intravenous drip.

Abstract: The present invention provides a photosensitising composition comprising a mixture of: at least one surfactant; at least one alcohol; and/or water, with the proviso that when the at least one surfactant is an alcohol, it is different from the at least one alcohol. In particular, the composition may comprise a mixture of glycerol, ethanol and water. Alternatively, the composition may comprise a mixture of polyethylene glycol, ethanol and water. The photosensitising composition may further comprise at least one photosensitising compound. The present invention also provides a method of treating and/or preventing conditions caused by microorganisms in a subject.

Abstract: The present invention includes a composition for treating fungal infections, particularly onychomycosis. The composition includes a photosensitizer, an effective amount of antifungal agent, and a pharmaceutically acceptable delivery system.

Abstract: The invention relates generally to the use of diaminophenothiazine compounds to inhibit or reverse the aggregation of synuclein, and for their use in the manufacture of medicaments for this purpose (e.g. for the treatment of Parkinson's Disease). Also provided are related methods of detecting or labelling of aggregated synuclein.

Abstract: The present invention relates to substituted imidazo-pyridinones and imidazo-pyridazinones of general formula wherein Y and R1 to R4 are defined as in claim 1, the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Abstract: The present invention relates to methods for the detection of substances capable of modulating or inhibiting pathological tau-tau protein association. The methods of the present invention are particularly useful in screening substances for the prophylaxis and treatment of Alzheimer's disease.

Abstract: The compounds of the present invention are of formula I: wherein A, R3, R4 is as defined herein, are useful as ligands for nicotinic receptors.

Abstract: A process of performing photodynamic therapy is provided along with a photosensitizer composition suitable for the process. The photosensitizer composition comprises at least one photoactive ingredient in a chemically reduced state. According to the process, the photosensitizer composition having at least one photoactive ingredient in a chemically reduced state is provided. The photosensitizer composition is applied to tissue or other substrate such that the at least one photoactive ingredient is at or travels to a location adjacent a target medium and the at least one photoactive ingredient is then altered to a photoactive state. The at least one photoactive ingredient is then exposed to light energy for assisting in inhibiting at least one pathogen at the target medium.

Abstract: The present invention is directed to methods for the treatment or prophylaxis of a tauopathy comprising administering to a patient in need thereof a medicament comprising a phenothiazine.

Abstract: Methods of treating headache with antipsychotics are provided. A kit for treating headache is also provided, comprising an antipsychotic and a device for rapid delivery of the antipsychotic.

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: An antimicrobial composition suitable for cleaning inanimate surfaces and human skin comprises two or more cationic biocides and two or more biocides which are slower acting than the cationic biocides, wherein each cationic biocide is independently either: (i) a quaternary ammonium compound at a concentration of at least 0.1% w/v; or (ii) a biguanide compound.

Abstract: In general, this application is directed to medical devices that exhibit antimicrobial activity and to methods for preparing and using the medical devices. The medical devices of the present application include a polymeric portion that has been impregnated with a paraben and an organic dye in a manner whereby the paraben and organic dye exhibiting antibacterial properties. In one form, the paraben is impregnated into the polymeric portion before impregnation thereof with the organic dye. In another form, it is contemplated that the polymeric material may include methyl paraben, propyl paraben, and methylene blue. It is further contemplated that the polymeric material is effective in releasing at least one of the paraben and organic dye to prohibit bacterial growth in surrounding tissue and/or fluid.

Abstract: A phenothiazinium compound of Formula (I) wherein: A and B each independently is in which R? and R? each independently is a linear, branched or cyclic hydrocarbon group, or R? and R? together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; and where XP? is a counteranion and P is 1, 2 or 3; except for the compounds in which A and B are both either —N(CH3)2 or —N(CH2CH3)2 for use in a treatment that requires removal, deactivation or killing of unwanted tissues or cells.

Abstract: The invention relates to a formulation for the treatment of acute manic episodes associated with Bipolar I Disorder comprising an antipsychotic agent selected from the group consisting of: a dibenzothiazepine derivative; lithium; and divalproex. The formulation comprises a first component which comprises a first population the antipsychotic agent and at least one subsequent component which comprises a subsequent population of the antipsychotic agent and which allows for the modified release of the agent. The combination of the first and the subsequent components in operation deliver the antipsychotic agent in a pulsed or controlled manner over a period of up to twenty-four hours.

Abstract: The present invention relates to a phenothiazinium compound of Formula (I): wherein: A and B each independently is in which R? and R? each independently is a linear, branched or cyclic hydrocarbon group, or R? and R? together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; and where XP? is a counteranion and P is 1, 2 or 3; except for the compounds in which A and B are both either —N(CH3)2 or —N(CH2CH3)2 for use in a treatment that requires removal, deactivation or killing of unwanted tissues or cells. The invention also relates to compositions comprising the compounds of Formula I, to selected compounds of Formula I, use of the compounds of Formula I as medicaments and as a PDT agent or a photodiagnostic agent, a conjugate or composite formed between a compound of Formula I and a polymer; and to a method for sterilising fluids in which the fluid is passed over the conjugate or composite whilst it is illuminated.

Abstract: A topical pharmaceutical preparation suitable for use as an antihistamine or anti-nausea drug comprises an emu oil gel base and a therapeutic amount of promethazine.HCl. The preparation may further comprise an antioxidant. The preparation is preferably packaged as a single unit dose. A method for preparing the topical pharmaceutical preparation comprises the steps of combining a clear gel with an emu oil mixture and adding a therapeutic amount of promethazine.HCl solution.

Abstract: Histamine H3 inverse agonists or histamine H3 antagonists are useful, alone or in combination with a neuroleptic agent, for treating or preventing movement disorders, including tremor, such as essential tremor, and tremor associated with Parkinson's disease, cranofacial trauma, multiple sclerosis, stroke, dystonia, and neuropathic, toxic or drug induced tremor.

Abstract: The present invention relates to photo-activated disinfection. In particular, the present invention relates to photo-activated disinfection in the oral cavity. We describe a dental apparatus comprising a light source producing light at a predetermined wavelength and power, and optical transmission means to train the light from the light source onto at least one external side of a tooth. Preferably, the optical transmission means comprises at least one optical guide. In a preferred embodiment, the optical transmission means comprises a pair of substantially parallel elongate light guides each light guide having a distal end provided with a reflective surface inclined at 45° to the direction of light transmission along the light guides, the reflective surfaces of the light guides being opposed such that light emitted from each light guide is parallel but opposite in direction.

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.

Abstract: The present invention relates to the use of phenothiaziniums and microbial MDR inhibitors to inactivate microorganisms. Methods of the present invention are useful in the treatment of living subjects and in the decontamination of inanimate objects and substances.

Abstract: The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

Abstract: The subject invention provides a composition comprising a mixture of polypeptides in the form of a tannate salt wherein each polypeptide is a copolymer of the amino acids L-glutamic acid, L-alanine, L-tyrosine and L-Lysine, methods of preparation and uses thereof.

Abstract: A phenothiazinium compound of Formula (I): wherein: A and B each independently is in which R? and R? each independently is a linear, branched or cyclic hydrocarbon group, or R? and R? together with the N atom to which they are attached form an optionally substituted 5-, 6- or 7-membered ring; and where XP? is a counteranion and P is 1, 2 or 3; except for the compounds in which A and B are both either —N(CH3)2 or —N(CH2CH3)2 for use in a treatment that requires removal, deactivation or killing of unwanted tissues or cells.

Abstract: The present method involves the photodynamic treatment of hyperactive gland disorders. The method involves the topical administration of a photosensitizer composition comprising hydrophobic and/or lipophilic green porphyrins such as lemuteporfin, polyethylene glycol and skin penetration enhancers such as oleyl alcohol and TRANSCUTOL™ to affected skin and subsequent exposure of that skin to energy of a wavelength capable of activating the photosensitizer.

Abstract: Disclosed are methods for determining the stage of neurofibrillary degeneration associated with a tauopathy in a subject believed to suffer from the disease, by (i) introducing into the subject a ligand capable of labeling aggregated paired helical filament (PHF) tau protein, (ii) determining the presence and/or amount of ligand bound to extracellular aggregated PHF tau in the medial temporal lobe of the brain of the subject, (iii) correlating the result of the determination made in (ii) with the extent of neurofibrillary degeneration in the subject. The methods can be used for pre-mortem diagnosis and staging of tauopathies such as Alzheimer's Disease. Preferred ligands include sulphonated-benzothiazole-like compounds and diaminophenothiazines.

Abstract: This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. There orotate derivatives are equally efficacious in inhibiting the SCCAKI-1 kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HCl suggests a reduction in toxicity induced by free radical generation by the anthrracyclines.

Abstract: The present invention relates to the use of the dye methylene blue (MB) or a related compound to prevent or reverse an exaggerated hemodynamic reaction in animals in need thereof, including humans. More specifically, the present invention concerns the use of MB or a related compound to prevent or reverse hypotension, unstable angina, myocardial infarction or shock caused by the concomitant ingestion of a phosphodiesterase inhibitor, such as sildenafil citrate, and a NO-donor, such as L-arginine, or an organic nitrate, such as nitroglycerin.

Abstract: The invention features a method for treating a patient having a cancer or other neoplasm by administering to the patient two compounds simultaneously or within 14 days of each other in amounts sufficient to treat the patient.