84 results about "Prostanoid" patented technology

The invention relates to the gene encoding the mammalian prostaglandin H synthase-2 and its product. More specifically, the invention relates to the diagnosis of aberrant PGHS-2 gene or gene product; the identification, production, and use of compounds which modulate PGHS-2 gene expression or the activity of the PGHS-2 gene product including but not limited to nucleic acid encoding PGHS-12 and homologues, analogues, and deletions thereof, as well as antisense, ribozyme, triple helix, antibody, and polypeptide molecules as well as small inorganic molecules; and pharmaceutical formulations and routes of administration for such compounds.

The instant invention is drawn to methods and compositions useful for the assessment of cardiovascular risk in a mammal. The methods utilize biomarkers including prostanoid metabolites and isoprostanes as sensitive and stable markers of cardiovascular risk. The methods are particularly useful in a mammal that is contemplating undergoing coxib therapy, is undergoing coxib therapy, is undergoing antioxidant therapy, has ceased coxib therapy or has never undergone coxib therapy. The invention also includes kits useful for the assessment of cardiovascular risk in a mammal.

This invention provides a compound of the formula:or its pharmaceutically acceptable salt thereof, wherein A is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (I) are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring; R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

Compositions and methods that employ various combinations of such factors as retinoic acid signaling inhibitors, antioxidants, BMP4, VEGF, prostaglandin E2 pathway stimulants, TPO, SCF, FLT-3, EPO, TGFβ1, p38 MAPK inhibitors, beta adrenergic receptor agonists, cell cycle inhibitors, RXR agonists, Cripto, and chromatin remodelers to drive differentiation of pluripotent stem cells towards primitive blood cells. Uses of such primitive blood cells are provided.

This invention provides a compound of the following formula:or the pharmaceutically acceptable salts thereof wherein Z is OH, C1-6 alkoxy, -NR2R3 or heterocycle; Q is selected from the following: (a) an optionally substituted phenyl, (b) an optionally substituted 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), (c) an optionally substituted 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, (d) an optionally substituted C3-7 cycloalkyl and (e) an optionally substituted benzo-fuzed heterocycle; R1 is hydrogen, C1-4 alkyl or halo; R2 and R3 are independently hydrogen, OH, C1-4 alkoxy, C1-4 alkyl or C1-4 alkyl substituted with halo, OH, C1-4 alkoxy or CN; X is independently selected from H, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, OH, C1-4 alkoxy, halo-substituted C1-4 alkoxy, C1-4 alkylthio, NO2, NH2, di-(C1-4 alkyl)amino and CN; and n is 0, 1, 2, 3 and 4.This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

The present invention provides methods and compositions useful for the elimination of latent HIV reservoirs that persist despite HAART. The methods and compositions overcome this latent barrier by inducing the replication of HIV in latently infected T cells while preventing the spread of the newly produced virions to uninfected cells by providing HAART simultaneously. Compositions of the invention comprise an activator of latent HIV expression, such as prostratin, and an inhibitor of histone deacetylase, such as TSA. A surprising finding of this invention is that the inhibitor of the histone deacetylase synergizes the effect of prostratin thus, allowing administering to a patient a lower, non-toxic dose of prostratin.

A method for quantifying a neurodegenerative disorder in a patient that includes obtaining a fluid sample from the subject; measuring a protein biomarker complex in said fluid sample and correlating the measurement with mild cognitive impairment or Alzheimer's disease status. The biomarkers include those that comprise at least one of a transthyretin protein and / or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and / or serotransferrin protein.

A compound comprising or a pharmaceutically acceptable salt or a prodrug thereof, wherein the dashed line represents the presence or absence of a double bond; J is C═O or CHOH; A is —(CH2)6—, or cis —CH2CH═CH—(CH2)3—, wherein 1 or 2 carbons may be substituted with S or O; B is CO2H, or CO2R, CONR2, CONHCH2CH2OH, CON(CH2CH2OH)2, CH2OR, P(O)(OR)2, CONRSO2R, SONR2, or R is H, C1-6 alkyl; D is —(CH2)n—, —X(CH2)n, or —(CH2)nX—, wherein n is from 0 to 3 and X is S or O; and E is an aromatic or heteroaromatic moiety having from 0 to 4 substituents, said substituents each comprising from 1 to 6 non-hydrogen atoms is disclosed herein. Methods, compositions, and medicaments related thereto, as well as experimental results showing prostaglandin EP4 selective agonist activity for certain compounds disclosed herein, are also disclosed.

A method for quantifying a neurodegenerative disorder in a patient that includes obtaining a fluid sample from the subject; measuring a protein biomarker complex in said fluid sample and correlating the measurement with mild cognitive impairment or Alzheimer's disease status. The biomarkers include those that comprise at least one of a transthyretin protein and / or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and / or serotransferrin protein;

This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.

The quick releasing vagina tablet includes various active medicinal components, such as antibiotic, antifungal, antiviral, hormone, prostanoid, etc.; and medicinal supplementary material stuffing, adhesive and disintegrating agent. The stuffing includes water soluble stuffing and water insoluble stuffing. The quick releasing vagina tablet, after contacting with vagina secretion, can disintegrate to disperse or dissolve so that it is absorbed via vagina mucous membrane to produce local treatment effect and made to enter body circulation to produce bodily treatment effect. It is convenient and accommodative.

The present invention provides cell lines expressing endogenous PGD2-specific receptors, methods for increasing expression of the receptors and assays utilizing the hereindisclosed cell lines for identifying modulators of the PGD2-specific receptors. Increasing expression of PGD2-specific receptors is achieved by treating the disclosed cell lines with an agent that induces differentiation.

N-fatty acid-amino acid conjugates and J2 prostanoid-amino acid conjugates are disclosed along with methods for making such conjugates and methods of using these conjugates in the treatment of conditions that involved dysfunctional lipid metabolism, insulin sensitivity, glucose homeostasis, and / or inflammation.

A composition for intravenous injection, which gradually decomposed instead of fat particles, has sufficient sustained release effects, has an excellent encapsulation ratio of lipid-soluble agents, and has such sustained release effects at lesion sites; a production method thereof; and a preparation containing the composition. The composition for intravenous injection is produced by encapsulating a prostanoid or steroid in a poly(lactic-co-glycolic acid) or poly(lactic acid) microparticle, and allowing lecithin or similar surfactant to be adsorbed on the surface or the above poly(lactic-co-glycolic acid) or poly(lactic acid) microparticle. A method for producing the composition comprises: dissolving esterified prostanoic acid or esterified steroid and a poly(lactic-co-glycolic acid) or poly(lactic acid) in an organic solvent such as dichloromethane or dimethylsulfoxide; and emulsilfying the obtained mixture in water, using the lecithin or similar surfactant capable of adjusting the diameter of the copolymer or particle to between 50 and 500 nm, employing an ultrasonic generator, a Polytron Homogenizer, or the like.

There are provided inter alia methods and compounds useful for decreasing choroidal neovascularization in a subject in need thereof.

Human Ckβ-9 polypeptides and DNA (RNA) encoding such chemokine polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such Ckβ-9 polypeptides for the treatment of leukemia, tumors, chronic infections, autoimmune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such polypeptides and their use as a therapeutic to treat rheumatoid arthritis, autoimmune and chronic inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed. Diagnostic assays are also disclosed which detect the presence of mutations in the Ckβ-9 coding sequence and over-expression of the Ckβ-9 protein.

The present invention provides compositions, methods, and kits for treating inflammation and regulating inflammatory responses including cytokine, prostanoid, prostaglandin, and growth factor expression.

Human chemokine Beta-10 polypeptides and DNA (RNA) encoding such chemokine polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemokine polypeptides for the treatment of leukemia, tumors, chronic infections, autoimmune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such chemokine polypeptides and their use as a therapeutic to treat rheumatoid arthritis, autoimmune and chronic inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed.

The present invention provides, inter alia, methods for treating or ameliorating the effects of a disease, such as cancer, in a subject. The methods include: administering to a subject in need thereof (a) a therapeutically effective amount of a monoclonal antibody or antigen binding fragment of the present invention, and (b) a therapeutically effective amount of a combination therapy including bevacizumab and at least one additional therapeutic agent; or a therapeutically effective amount of at least one additional therapeutic agent selected from the group consisting of a COX-2 inhibitor (COXIB), a non-steroidal anti-inflammatory drug (NSAID), a prostaglandin E2 (PGE2) synthase inhibitor, and combinations thereof. Compositions, including pharmaceutical compositions, and kits for treating diseases, such as cancer, are also provided herein.

The present invention relates to an ophthalmic composition comprising at least two active pharmaceutical ingredients. In particular, the active pharmaceutical ingredients are selected from the group consisting of: an alpha 2 adrenergic receptor agonist; a beta-adrenergic receptor agonist; an immunosuppressant; a lymphocyte associated antigen antagonist; an anti-inflammatory; a beta-blocker; a prostaglandin analog; a histamine receptor antagonist; a carbonic anhydrase inhibitor; and an antibiotic. In some embodiments, the composition of the invention is a nanoemulsion formulation. In one particular embodiment, the first active pharmaceutical ingredient is an alpha 2 adrenergic receptor agonist. The present invention also provides a method for treating various clinical conditions associated with an eye disorder or eye disease using the composition of the invention.

The invention relates to a method for improving osteogenic differentiation efficiency of human amniotic mesenchymal stem cells. The method adds an induction composition in the human amniotic mesenchymal stem cells, wherein the composition comprises 0.1-2g / L of hyaluronic acid, 0-200mg / L of prostaglandin receptor-2 selective agonist, 1-100nmol / L of dexamethasone, 0-10nmol / L of beta-glycerophosphate and 1-100mg / L of ascorbic acid. Compared with a conventional inducing method, the osteogenic differentiation efficiency of the human amniotic mesenchymal stem cells can be significantly improved, expression and activity of alkaline phosphatase are promoted, and expression of osteogenesis-related genes of RunX2, Osx, BSP, Ocn, ALP, Col1a1 and the like and formation of mineralized calcium nodules are enhanced. The method for improving the osteogenic differentiation efficiency of the human amniotic mesenchymal stem cells can be applied in osteogenic differentiation of the human mesenchymal stem cells, and applied in bone diseases of bone defects, bone trauma and the like.

The present invention relates to azaindole acetic acid derivatives of formula (I),wherein R1 and R2 are as described in the description, and their use as prostaglandin receptor modulators, most particularly as prostaglandin D2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.

The invention encompasses compositions and methods for effectively treating and / or preventing the development and / or progression of osteoporosis and related disorders such as osteoarthritis and rheumatoid arthritis, and for promoting overall bone and joint health. This is accomplished by addressing multiple key mechanisms that lead to such disorders. The invention includes compositions comprising a combination of agents having biological activities that effectively suppress, regulate or interfere with the various key biochemical processes and mechanisms that increase the risk for development and / or progression of osteoporosis. The present compositions and methods simultaneously promote bone formation and reduce bone resorption by (a) stimulating osteoblast formation and osteogenesis; (b) suppressing adipocyte differentiation; (c) inhibiting osteoclast formation; and (d) increasing apoptosis of osteoclasts. The inventive compositions used for administration to human and other mammalian subjects having or at risk for development of osteoporosis comprise (1) at least one agent capable of modulating expression and / or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT / enhancer binding protein-α (C / EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent that activates expression and / or activity of one or more of the osteogenic transcription factors (Runx2 / Cbfα1, Dlx5, Osterix, Msx2); (3) at least one agent that activates expression and / or activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4), alkaline phosphatase (ALP), and osteocalcin; (4) at least one agent capable of activating Wnt / β-catenin signaling pathway; (5) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (6) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); and (7) at least one agent that induces the expression of and / or activates one or more of adenosine monophosphate-activated protein kinase (AMPK), sirtuin (SIRT1) and adiponectin (AP).

Molecular cloning and expression of a prostaglandin F2alpha receptor which is linked to the signal transduction pathways via guanine nucleotide binding regulatory (G) proteins and measured by, for example, cAMP, IP3 or intracellular calcium. By constructing cell lines that express a prostaglandin F2alpha receptor, the affinities and efficacies of agonist and antagonist drugs with the receptor can be assessed. A recombinant DNA construct includes a vector and a DNA fragment encoding a prostaglandin F2alpha receptor. A host cell is transformed with a recombinant DNA construct, so that the DNA fragment is expressed and a prostaglandin F2alpha receptor is produced. Suitable host systems include eukaryotic and prokaryotic cells, especially mamalian cells such as rat or human. Additionally, for diagnostic purposes, antibodies to a prostaglandin F2alpha receptor can be prepared by producing all or a portion of the receptor protein and injecting these into various types of mammals. Using the resulting antibodies, expression of an F2alpha receptor cDNA, i.e. receptor protein in tissue and cells can be measured.