The present invention relates to a family of N-acylhydrazonic compounds structurally derived from 1-methyl-1H-imidazole-2-carboxaldehyde, or pharmaceutically acceptable salts thereof, and the use of said compounds to prevent and/or treat amyloid (such as Alzheimer's, Parkinson's and type 2 diabetes) and non-amyloid (such as cataracts) degenerative aggregopathies These compounds act as attenuators of the metal-protein interaction, preventing and/or decreasing protein oligomerization through competition with the target peptide or protein for the binding of physiological metal ions and, possibly, by modulating the protein-protein interaction itself. The invention also details four compounds specifically described as examples of N-acylhydrazones derived from 1-methyl-1H-imidazole-2-carboxaldehyde, namely: 1-methyl-1H-imidazole carboxaldehyde isonicotinoyl hydrazone, 1-methyl-1H-imidazole-2-carboxaldehyde benzoyl hydrazone, 1-methyl-1H-imidazole-2-carboxaldehyde 2-furoyl hydrazone and 1-methyl-1H-imidazole-2-carboxaldehyde 2-thiophenyl hydrazone. The current application also comprises pharmaceutical compositions.

The present invention relates to novel biologically active compounds, in particular dicarboxylic acid bisamide derivatives of general formula I:

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or pharmaceutically acceptable salts thereof, which are able to form complexes with or chelate metal ions. The invention also relates to the use of said compounds as an agent for the prevention and/or treatment of cardiovascular, viral, cancer, neurodegenerative and inflammatory diseases, diabetes, age-related diseases, diseases caused by microbial toxins, alcoholism and alcoholic cirrhosis, anaemia, porphyria cutanea tarda, and transition metal salt poisoning. The present invention also relates to novel methods for preparing dicarboxylic acid bisamide derivatives of general formula I.

The invention relates to soluble melatonin tripartate adduct comprising three structurally distinct regions and optionally trehalose, its stable sterile lyophilized powder and preservative-free aqueous solution or ointment, and to related pharmaceutical forms thereof, wherein the active melatonin moiety is adducted to a nucleoside in an optimal ratio range, with or without the presence of C.sub.2-C.sub.5 short chain amino acid. The invention further relates to the pharmaceutical field, more precisely it refers to the ophthalmic use of said melatonin tripartate adduct and to the method to prevent or treat serious ophthalmic pathologies in mammals and humans, more precisely rare and severe eye sight-threatening conditions and neuro-ophthalmic disorders in human and veterinary medicine, wherein said acute and chronic pathophysiological alterations and oculopathies are mainly caused by oxidative stress and related hypoxia-inducible factors (HIFs) and inflammation affecting the eyes. The pharmaceutical composition of said melatonin tripartate adduct may optionally contain either retinol or sodium hyaluronidate, or hyaluronic acid, L-carnosine, L-acetylcarnosine or a mixture thereof. Viscosity enhancers may be optionally included in the composition. Furthermore, the pharmaceutical composition of the invention is chemically and physically stable and safe.

Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc.

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The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a canine animal, preferably where the metabolic disorder is one or more selected from ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, and/or Syndrome X (metabolic syndrome), wherein preferably the development of hyperglycemia induced cataract formation is prevented or remission is achieved and/or wherein preferably the development of metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, is prevented or progression is slowed or remission is achieved.

One or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof are provided for use in the treatment and/or prevention of a metabolic disorder in a canine animal, preferably where the metabolic disorder is one or more selected from ketoacidosis, pre-diabetes, insulin dependent diabetes mellitus, insulin resistance diabetes, insulin resistance, obesity, hyperglycemia, hyperglycemia induced cataract formation, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, hepatic lipidosis, inflammation of the pancreas, metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, and/or Syndrome X (metabolic syndrome), wherein preferably the development of hyperglycemia induced cataract formation is prevented or remission is achieved and/or wherein preferably the development of metabolic disorder consequences, such as hypertension, renal dysfunction and/or musculoskeletal disorders, is prevented or progression is slowed or remission is achieved.

The present invention relates to a process for preparing a crosslinked gel of at least one polysaccharide or a salt thereof, comprising at least the steps consisting in: a) providing a solution formed from an aqueous medium comprising at least said polysaccharide(s) or a salt thereof in a non-crosslinked form, at least one difunctional or multifunctional epoxide crosslinking agent chosen from butanediol diglycidyl ether, diepoxyoctane, 1,2-bis(2,3-epoxypropyl)-2,3-ethylene, and mixtures thereof, and at least one phosphate salt; b) crosslinking the solution from step a) and, where appropriate; c) recovering said crosslinked gel formed.

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

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The present subject matter relates to a non-invasive optical imaging method for monitoring early pathological events specific to Alzheimer's disease (AD), such as the development, amount and location of amyloid plaques. The ability to monitor such events provides a basis for, among other things, AD diagnosis, prognosis and assessment of potential therapies. In addition, the present subject matter introduces novel methods for treating AD and retinal ailments associated with AD. Aβ-plaque detection in living brains is extremely limited, especially at high resolution; therefore the present invention is based on studies focusing on the eyes as an alternative to brain-derived tissue that can be imaged directly, repetitively and non-invasively.