The invention relates to the chemistry of organic compounds, pharmacology and medicine and concerns therapy for obesity, psoriasis, Crohn's disease, colitis, irritable bowel syndrome, diarrhea, nausea and vomiting, as well as a number of other diseases associated with the activity of cathepsin S, cannabinoid receptors type 1, tachykinin receptors type 1 and 2, prokineticin receptors type 1 and 2, bradykinin receptors type 1, melanocortin receptors MC4R, serotonin receptors 5-HT2B and NB-kB signaling pathway, by using benzyl (2S)-2-[2-(4-hydroxyphenyl)acetamido]-3-phenylpropanoate compound. ##STR00001## The compound and pharmaceutically acceptable adducts, hydrates and solvates thereof are a cathepsin S inhibitor, cannabinoid receptor type 1 agonist, tachykinin receptor type 1 and 2 antagonist, prokineticin receptor type 1 and 2 antagonist, bradykinin receptor type 1 antagonist, melanocortin receptor MC4R antagonist, serotonin receptor 5-HT2B antagonist, and NB-kB signaling pathway inhibitor. The invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of the compound according to the invention.

The invention relates to the chemistry of organic compounds, pharmacology and medicine and concerns therapy for obesity, psoriasis, Crohn's disease, colitis, irritable bowel syndrome, diarrhea, nausea and vomiting, as well as a number of other diseases associated with the activity of cathepsin S, cannabinoid receptors type 1, tachykinin receptors type 1 and 2, prokineticin receptors type 1 and 2, bradykinin receptors type 1, melanocortin receptors MC4R, serotonin receptors 5-HT2B and NB-kB signaling pathway, by using benzyl (2S)-2-[2-(4-hydroxyphenyl)acetamido]-3-phenylpropanoate compound. ##STR00001## The compound and pharmaceutically acceptable adducts, hydrates and solvates thereof are a cathepsin S inhibitor, cannabinoid receptor type 1 agonist, tachykinin receptor type 1 and 2 antagonist, prokineticin receptor type 1 and 2 antagonist, bradykinin receptor type 1 antagonist, melanocortin receptor MC4R antagonist, serotonin receptor 5-HT2B antagonist, and NB-kB signaling pathway inhibitor. The invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of the compound according to the invention.

A method of inhibiting inflammation with milk oligosaccharides or glycoconjugates containing the oligosaccharides.

Provided herein are combination therapies comprising an alpha4beta7 inhibitor, e.g., an anti-alpha4beta7 antibody, e.g., vedolizumab, and an IL-23 inhibitor, e.g., an anti-IL-23 antibody.

Provided herein are combination therapies comprising an alpha4beta7 inhibitor, e.g., an anti-alpha4beta7 antibody, e.g., vedolizumab, and an IL-23 inhibitor, e.g., an anti-IL-23 antibody.

Disclosed herein are methods and compositions for disrupting an interaction between Galectin-3 and insulin receptor or integrins. Further disclosed herein are methods and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of diabetes mellitus, inflammatory bowel syndrome, non-alcoholic fatty liver disease, and nonalcoholic steatohepatitis.

Disclosed herein are methods and compositions for disrupting an interaction between Galectin-3 and insulin receptor or integrins. Further disclosed herein are methods and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of diabetes mellitus, inflammatory bowel syndrome, non-alcoholic fatty liver disease, and nonalcoholic steatohepatitis.

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The invention relates to a transdermal therapeutic system for the controlled release of water-soluble pharmaceutical active ingredients from an aqueous phase, comprising an occlusive back layer, a central device facing the skin for releasing the agent, an adhesive layer concentrically surrounding the dispensing device and a removable protective film. Said device is made from a stationary solid phase and a liquid phase containing the active ingredient in aqueous solution, the solid phase being formed from a solid with a fleecy or spongy structure.

There is disclosed herein a composition for treating gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux esophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron Disease or autism, the composition comprising: (i) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (ii) at least one anti-clostridial agent selected from the above combined with an opioid blocking agent. There is also disclosed herein a method of treating various gastrointestinal or neurological disorders, constipation, functional constipation, irritable bowel syndrome, diverticulitis, travelers diarrhoea, chronic idiopathic nausea, IBD-associated constipation and diarrhoea, pseudo-obstruction, diabetic gastroparesis, cyclic vomiting, reflux oesophagitis, autism enteropathy, flatulence, halitosis, chronic fatigue, bloating, proctalgia fugax, Parkinson's disease, MS, Alzheimer's Disease, Motor Neuron Disease or autism, the method comprising administering orally, via enema or by suppository: (i) a composition of the invention; (ii) at least two anti-clostridial agents selected from the group consisting of: vancomycin, vancomycin derivatives, a multi-valent polymer of vancomycin, aminoglycosides, nitroimidazoles, ansamysins, nifuroxazide, colchicine, prucalopride, prokinetic agent and 5-aminosalicylic acid; or (iii) at least one anti-clostridial agent selected from the above and an opioid blocking agent to a patient in need of such treatment.