A composition containing a compound represented by General Formula (I) below (see the definition in the specification for the symbols in the formula) or a salt thereof has an excellent CaSR agonistic effect and provides a pharmaceutical agent, a CaSR agonistic agent, a prophylactic or therapeutic agent for a disease that can be ameliorated through CaSR activation as well as seasonings and an agent for imparting kokumi. ##STR00001##

A compound of formula (I) ##STR00001##
wherein X is 0, C=0 or S; Y is N or CH; R.sub.2 and R.sub.4 are each independently H, —(CH.sub.2).sub.pCOOH, —(CH.sub.2).sub.pCON(R.sup.5).sub.2 or —(CH.sub.2).sub.pCOOC.sub.1-6alkyl; or R.sub.2 and R.sub.4 together form a 6-membered phenyl ring fused to the five membered ring; each R.sub.1 is independently selected from H, halo (e.g. fluoro or chloro), C.sub.6-10aryl, C.sub.7-12arylalkyl, C.sub.2-12 alkenyl; OC.sub.1-12 alkyl, OC.sub.2-12 alkenyl or a C.sub.1-12 alkyl group; each R.sup.5 is H or C.sub.1-6 alkyl; each p is 0 to 3; n is 1 to 4; or a salt, ester, solvate, N-oxide, or prodrug thereof, e.g. a salt thereof.

The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors. ##STR00001##
wherein A, Y, Z, X.sub.1, X.sub.2, X.sub.3, R.sub.1, R.sub.3, ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

Anti-human CD40L antibodies engineered to lack the ability to activate platelets and methods for treating patients having a CD40L-associated disease.

The present invention relates to a liquid composition for use in the treatment of gastroesophageal reflux. The composition of the present invention comprises a mixture which comprises or, alternatively, consists of a combination of Aloe vera gel, hyaluronic acid and honey and, optionally, food or pharmaceutical grade additives and/or technological excipients. The composition of the present invention also relates to a medical device comprising a mixture which comprises or, alternatively, consists of a combination of Aloe vera gel, hyaluronic acid and honey and, optionally, food or pharmaceutical grade additives and/or technological excipients. Said composition or composition for a medical device being for use in the preventive and/or curative treatment of the symptoms associated with gastroesophageal reflux and the disease caused thereby, as well as for use in the preventive and/or curative treatment of gastroesophageal reflux disorders.

The present invention relates to a liquid composition for use in the treatment of gastroesophageal reflux. The composition of the present invention comprises a mixture which comprises or, alternatively, consists of a combination of Aloe vera gel, hyaluronic acid and honey and, optionally, food or pharmaceutical grade additives and/or technological excipients. The composition of the present invention also relates to a medical device comprising a mixture which comprises or, alternatively, consists of a combination of Aloe vera gel, hyaluronic acid and honey and, optionally, food or pharmaceutical grade additives and/or technological excipients. Said composition or composition for a medical device being for use in the preventive and/or curative treatment of the symptoms associated with gastroesophageal reflux and the disease caused thereby, as well as for use in the preventive and/or curative treatment of gastroesophageal reflux disorders.

The present invention relates to a composition which comprises a mixture which comprises or, alternatively, consists of an extract (a) of a fruit of at least one plant of the genus Vaccinium and at least one ingredient (b) acceptable for pharmaceutical or food use and the use thereof in the prevention and/or treatment of diverticular disease or of a pathology deriving therefrom or correlated thereto.

A method of treating intestinal gastrointestinal, or bowel disorders in a subject in need thereof includes administering to the subject a therapeutically effective amount of 15-PGDH inhibitor alone or in combination with a corticosteroid and/or TNF alpha antagonist.