Abstract: Novel compounds are disclosed that have a Formula represented by the following: wherein X, R1, R2a, R2b, R2c, R3aR3b, R4a, R4b, R4c, and m1 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cachexia, osteoporosis, sarcopenia, a decline in libido and/or sexual dysfunction.

Abstract: A method for treating the symptoms of multiple sclerosis and related neurodegenerative conditions, using a histamine compound that is methylated in vitro prior to being introduced into the body of the patient. The histamine compound is suitably histamine diphosphate, and may be methylated in vitro by mixing in combination with at least one thiol compound in the presence of at least one methyl group donor compound. The thiol compound is suitably L-reduced glutathione and the methyl group donor is suitably betaine hydrochloride. The compounds are mixed vigorous in an acid environment, to create a shearing force that facilitates exchange of the methyl group from the donor compound to the histamine diphosphate. The resulting methylated histamine compound is suitably administered to the patient by transdermal application. The method also provides a medicament for treatment the symptoms of multiple sclerosis and related neurodegenerative conditions, and a method for preparation of such a medicament.

Abstract: The present invention provides novel pyrazolines that are useful as cannabinoid receptor blockers and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, inflammatory disorders, cardiometabolic disorders, hepatic disorders, and/or cancers.

Abstract: Membrane permeable prodrugs of creatine phosphate analogs, pharmaceutical compositions comprising membrane permeable prodrugs of creatine phosphate analogs, and methods of treating diseases such as ischemia, heart failure, and neurodegenerative disorders comprising administering prodrugs of creatine phosphate analogs, or pharmaceutical compositions thereof are disclosed.

Abstract: The invention relates to tetra-substituted heteroarylic compounds of the formula (I) wherein X1, X3 and X4 are independently C or N, Y is C—H, N—H or N, wherein the total number of nitrogen atoms represented by X1, X3, X4 and Y is 1 or 2; rings A and B are independently selected from phenyl or pyridyl; R1, R4, R?, R?, n and m are as defined herein. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

Abstract: The present invention is related to the composition and methods of manufacture of orally-dissolvable, edible films as a vehicle for the non-invasive administration of active drugs through the mucosal tissues of the oral cavity. The films include a water soluble film-forming polymer such as pullulan. Methods for producing the films are also disclosed.

Abstract: The present invention relates to the use of creatine compounds such as, for example, creatine, creatine phosphate or analogs of creatine, such as creatine-pyruvate, creatine-ascorbate, cyclocreatine, 3 guanidinopropionic acid, guanidinoacetate, homocyclocreatine, guanidino benzoates as energy generating systems and antioxidants for preservation of skin against adverse aging effects and damage secondary to insults such as harmful sun radiations, stress and fatigue. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) molecules that mimic the biological activity of creatine (3) molecules that modulate the creatine kinase system.

Abstract: Nanoparticulate bisphosphonate compositions, having an effective average particle size of less than 2000 nm, are described. The compositions are useful in treating bone resorption in a mammal.

Abstract: The present invention relates to novel derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.

Abstract: The present invention relates to a series of substituted 3-aminopropane phosphinic acid derivatives of formula I: wherein R, R1, P1, P2 and P3 are as defined herein. The compounds of this invention are useful in treating a variety of diseases including but not limited to depression, anxiety, certain psychiatric symptoms, cognitive impairment and schizophrenia.

Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, U, X, R1, R2, R3, and R4 are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including cardiovascular diseases, cognitive and neurodegenerative diseases.

Abstract: A multilayer protein film has a mass of greater than 0.5 ?g/cm2 and consists essentially of protein. A drug delivery device comprises the multilayer protein film onto which a pharmaceutically active agent can be loaded. A biomedical implant comprises an implant substrate and the multilayer protein film on at least a portion of the implant substrate surface. A method of making a multilayer protein film having a mass of greater than 0.5 ?g/cm2 comprises contacting a substrate with a protein solution at a temperature of from about 30° C. to about 95° C., wherein a multilayer protein film having a mass of greater than 0.5 ?g/cm2 is formed on the substrate.

Abstract: The present invention provides a method for detecting autoantibodies to osteoprotegerin (OPG). The method comprises the step of providing a biological sample from a subject with, or at risk of osteoporosis and detecting whether or not any antibodies against osteoprotegerin (OPG) are present in said sample. In addition the invention provides methods useful in aiding the diagnosis/prognosis and/or therapeutic regimen for autoimmune and/or vascular disease in general.

Abstract: THE INVENTION RELATES TO compounds, proteins and methods of treatment therewith. Aspects of embodiments of the invention further relates to compounds and methods of treatment for bone, bone marrow, and bone tissue.

Abstract: The present invention is directed to a method for treating aneurysms in vascular tissue. The method includes administering a bisphosphonate compound to a subject in an amount which is effective against the formation or progression of aneurysm, or which is effective to induce regression of an established aneurysm. In alternative methods, an anti-RANKL neutralizing antibody is administered to the subject to achieve analogous anti-aneurysm effect. The methods of particular advantage in the treatment of subjects having an abdominal aortic aneurysm, a relatively common, and life-threatening, condition.

Abstract: The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.

Abstract: A pharmaceutical product comprises a container containing a bisphosphonate solution, in which at least the internal surface of the container comprises a plastic material and in which the container is heat sterilisable, and which is in the form of an infusion solution preconcentrate for administration of the bisphosphonate to a patient in need of bisphosphonate treatment.

Abstract: Prodrugs of C-17-heterocyclic-steroidal drugs providing improved oral bioavailability and pharmacokinetics are described. The drugs are inhibitors of human CYP 17 enzyme, as well as potent antagonists of both wild type and mutant androgen receptors (AR), and are useful for the treatment of urogenital and/or androgen-related cancers, diseases and/or conditions, such as human prostate cancer, breast cancer, and prostate hyperplasia. The disclosure describes methods of synthesizing and using the prodrugs in cancer therapy.

Abstract: This invention relates to biomaterials, said biomaterials for use in methods to control and/or induce bone growth. Particularly, the invention relates to macroporous calcium phosphate biomaterials pre-loaded with certain amounts of osteoclastic activity inhibitors for use in methods to control and/or induce bone growth in primates.

Abstract: The present invention provides for novel compounds of Formulas I and II and pharmaceutically acceptable salts and co-crystals thereof which have glucokinsae activator activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucokinase activator is indicated, including Type 1 and 2 diabetes, impaired glucose tolerance, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formulas I and II, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

Abstract: The invention is related to phosphorus substituted compounds with antiviral activity, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: Zoledronic Acid is used for treatment of hypercalcemia of malignancy, for the treatment of bone metastasis associated with malignancies such as prostate and breast cancer, for the prevention of and treatment of osteoporosis and for the treatment of Paget's disease. Administration of Zoledronic Acid is complicated by what is described as “post-dosing syndrome” (PDS) and osteonecrosis of the jaw (ONJ). Inflammation may be the cause of these side effects, which could be decreased by the co-administration of steroids. This application is a method of use patent for the co-administration of steroids (oral, IV, IM, rectal, or by inhalation) with Zoledronic Acid and a composition of matter patent for mixing Methyl Prednisolone with Zoledronic Acid for infusion.

Abstract: (Unsubstituted or substituted phenyl)-alkyl-substituted [(imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic, as well as methods or processes for their manufacture, their use in the manufacture of pharmaceutical formulations, their use in the treatment of diseases, methods of using them in the treatment of diseases, pharmaceutical formulations encompassing them and/or the compounds for use in the treatment of diseases, are disclosed. The compounds are able to inhibit excessive or inappropriate bone resorption. The compounds are of the formula I, wherein one of R1 and R2 are as defined in the specification, and can be in free form, in the form of an ester, and/or of a salt.

Abstract: Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more anti-neoplastic agents.

Abstract: This invention discloses methods and compositions that can treat a variety of tissue injuries and infections. Tissue-derived leukocyte chemotactic factors are rapidly released after injury to mammalian tissue and can act as the initial signal leading to the initiation and amplification of acute and chronic inflammation associated with injury and infection. The present invention generally provides methods and compositions to prevent and treat injury of cells, tissue, or organs by blocking or inhibiting the release of leukocyte chemotactic factors, by administering certain effective compositions to the tissue.

Abstract: C2-C5-Alkyl-substituted [imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acids, as well as methods or processes for their manufacture, their use in the manufacture of pharmaceutical formulations, their use in the treatment of diseases, methods of using them in the treatment of diseases, pharmaceutical formulations encompassing them and/or the compounds for use in the treatment of diseases, are described. The compounds are able to inhibit excessive or inappropriate bone resorption and for the treatment of other diseases which are caused by excessive prenylation of target proteins, such as Hutchinson-Gilford progeria syndrome. The compounds are of the formula I, wherein one of R1 and R2 is hydrogen and the other is C2-C5-alkyl that is branched or unbranched, and can be in free form, in the form of an ester, and/or of a salt.

Abstract: Compounds of the formula I in which the substituents are as defined in claim 1 are suitable for use as microbiocides.

Abstract: Phosphoramidate alkylator prodrugs can be used to treat cancer when administered alone or in combination with one or more anti-neoplastic agents.

Abstract: This invention relates to a composition that comprises inositol phosphates and/or bisphosphonates, and to the use thereof to prevent the loss of substances of biological interest in the body of patients subjected to dialysis and to maintain sufficient physiological levels of said substances to regulate physiological and/or pathological processes, these substances being inhibitors of pathological crystallisation.

Abstract: C2-C5-Alkyl-substituted [(imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acids, as well as methods or processes for their manufacture, their use in the manufacture of pharmaceutical formulations, their use in the treatment of diseases, methods of using them in the treatment of diseases, pharmaceutical formulations encompassing them and/or the compounds for use in the treatment of diseases, are described. The compounds are able to inhibit excessive or inappropriate bone resorption and for the treatment of other diseases which are caused by excessive prenylation of target proteins, such as Hutchinson-Gilford progeria syndrome. The compounds are of the formula I, wherein one of R1 and R2 is hydrogen and the other is C2-C5-alkyl that is branched or unbranched, and can be in free form, in the form of an ester, and/or of a salt.

Abstract: The subject matter of the invention is a cosmetic and/or dermatological composition for use in the treatment of skin and/or hair disorders. More particularly, the invention relates to a cosmetic and/or dermatological composition comprising an inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, an inhibitor of farnesyl pyrophosphate synthase, or an inhibitor of one of the physiologically acceptable salts thereof and a cosmetic and/or dermatological product. The present invention finds, for example, a very advantageous use in the treatment of the effects of early ageing, in particular in terms of the skin and the hair system.

Abstract: The present disclosure relates to salts and compositions of isophosphoramide mustard and isophosphoramide mustard analogs. In one embodiment the salts can be represented by the formula wherein A+ represents an ammonium species selected from the protonated (conjugate acid) or quaternary forms of aliphatic amines and aromatic amines, including basic amino acids, heterocyclic amines, substituted and unsubstituted pyridines, guanidines and amidines; and X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.

Abstract: Provided are a nanoparticle/dispersant complex having excellent dispersibility and long-term stability in a dispersion medium, a production method therefor, and a nanoparticle dispersion liquid and a nanoparticle/matrix-material complex which are colorless and transparent even at high concentrations. In the nanoparticle/dispersant complex, a nanoparticle is covered with a dispersant containing a heterocyclic cationic group and one of an oxo acid group containing a sulfur atom or a phosphorus atom and an anion moiety of the oxo acid group; in the nanoparticle dispersion liquid, the nanoparticle/dispersant complex is dispersed into a dispersion medium; in the nanoparticle/matrix-material complex, the nanoparticle/dispersant complex is dispersed into a matrix material; and the production method for a nanoparticle/dispersant complex comprises forming, under a presence of the dispersant, a nanoparticle covered with the dispersant from a nanoparticle precursor.

Abstract: Disclosed are compounds according to formula (I) as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including inhibiting LPA activity on an LPA receptor, modulating LPA receptor activity, treating cancer, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermatological condition.

Abstract: Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n—Z—(CH2)mPO(OR7)(OR8), —(CH2)nZ—(CH2)m—PO(OR7)R9, —(CH2)n—Z—(CH2)m—OPO(OR7)R9, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from H, alkyl and halogen; Y is R7(CH2)s or is absent; and X, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

Abstract: Disclosed herein are compositions and methods for decreasing vascular permeability in a blood vessel and treating or preventing conditions associated with defects or injuries of vascular endothelium. For example, the disclosed compositions and methods can be used to treat a vascular dysplasia such as cerebral cavernous malformation (CCM). These methods relate generally to the use of compositions that inhibit RhoA GTPase levels or activity, such as inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.

Abstract: The present invention relates to the use of a bisphosphonate derivative according to general Formula I and/or a pharmaceutically acceptable salt thereof, wherein R1 and/or R2 are independently selected out of a group comprising hydrogen, hydroxyl, halogen, pseudohalogen, formyl, carboxy- and/or carbonyl derivatives, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, halogenalkyl, aryl, arylene, halogenaryl, heteroaryl, heteroarylene, heterocycloalkylene, heterocycloalkyl, halogenheteroaryl, alkenyl, halogenalkenyl, alkinyl, halogenalkinyl, keto, ketoaryl, halogenketoaryl, ketoheteroaryl, ketoalkyl, halogenketoalkyl, ketoalkenyl, halogenketoalkenyl, phosphoalkyl, phosphonate, phosphate, phosphine, phosphine oxide, phosphoryl, phosphoaryl, suiphonyl, sulphoalkyl, sulphoarenyl, sulphonate, sulphate, sulphone, amine, polyether, silylalkyl, silylalkyloxy, and wherein at appropriate residues one or more non-adjacent CH2-groups may be replaced independently from each other with —O—, —S—, —NH—, —NRo

Abstract: The invention is directed to a method of treating chronic spinal mechanical pain by intravenous administration to a subject in need of chronic spinal mechanical pain relief of an effective amount of bisphosphonate.

Abstract: The present invention relates to depot formulations comprising a poorly water soluble salt of a bisphosphonate forming together with one or more biocompatible polymers, to poorly water-soluble salts of such bisphosphonates, to crystalline forms of the free compounds and the salts and to other related aspects, where the compounds are of the Formula (I), where R1 and R2 are as described in the specification. Compounds of the Formula (I) and their forms mentioned in the disclosure are useful for the treatment of bone-related disorders and cancer.

Abstract: Preparation, in-vitro and in vivo characterization of novel forms of (1-hydroxy-2-imidazol-1-yl-1-phosphono-ethyl)phosphonic acid, suitable for pharmaceutical compositions in drug delivery systems for humans.

Abstract: A bone implant comprises an active agent on at least a portion thereof. The active agent is locally deliverable to bone proximate the implant in at least a two-phased release scheme. A first phase rapidly releases a first quantity of the active agent, and at least a second phase gradually releases a second quantity of the active agent, whereby bone formation stimulated by the active agent is modulated. In one embodiment, a porous implant comprises a porous portion coated with a calcium phosphate compound and which is contacted with a bisphosphonate compound to form a bisphosphonate layer chemically bound to the calcium phosphate at the surface of the porous portion and to form bisphosphonate molecules being non-chemically attached inside the pores of the porous portion. The non-chemically attached bisphosphonate molecules are released in the subject at a rate greater than that of the chemically bound bisphosphonate layer.

Abstract: The invention provides a combination comprising a cytotoxic compound, a signalling inhibitor, an ancillary agent, or two or more further anti-cancer agents, and a compound having the formula (Ib): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4—; A is a bond, C?O, NRg(C?O) or O(C?O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from fluorine, hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g.

Abstract: Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Abstract: The invention provides methods for treating epilepsy, mental disorders and/or deficits in sensory organ by administering to patients therapeutically effective amounts of AMPA receptor antagonists in combination with one or more other active ingredients useful for treating epilepsy, mental disorders and/or deficits in sensory organ. The invention also provides pharmaceutical combinations, kits, and pharmaceutical compositions comprising therapeutically effective amounts of AMPA receptor antagonists, and optionally, one or more other active ingredients that are useful for treating epilepsy, mental disorders and/or deficits in sensory organ.

Abstract: The present invention relates to compounds of general formula (I) as tublin polymerisation inhibitors and methods for preparing such compounds.

Abstract: The invention is directed to a method of administering hydrogen sulfide (H2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to amide compounds, processes for their preparation, pharmaceutical compositions containing these compounds and to their use in the treatment of disorders, conditions or disorders such as allergic disorders, inflammatory disorders and disorders of the immune system.

Abstract: There is provided a composition comprising the reaction product of: (a) one or more phosphate derivatives of one or more hydroxylated actives; and (b) one or more complexing agents selected from the group consisting of amphoteric surfactants, cationic surfactants, amino acids having nitrogen functional groups and proteins rich in these amino acids.

Abstract: The invention relates to devices, methods and formulation for subcutaneous administration of a bisphosphonate. In such a device, a drug core, comprising a bisphosphonate, is disposed in a tube. The devices may be administered to a patient in need of subcutaneously wherein the release of the bisphosphonate is desired to provide sustained release of a therapeutically effective dose of the bisphosphonate.

Abstract: The invention relates to a pharmaceutical composition and oral dosage forms comprising a bisphosphonate in combination with an enhancer to enhance intestinal delivery of the bisphosphonate to the underlying circulation. Preferably, the enhancer is a medium chain fatty acid or a medium chain fatty acid derivative having a carbon chain length of from 6 to 20 carbon atoms, and the solid oral dosage form is a controlled release dosage form such as a delayed release dosage form.