The disclosure discloses a new anti-metabolic disorder FGF analog and an application thereof, and belongs to the technical field of medicines. According to the disclosure, modification is performed based on an FGF19 mutant NGM282 to obtain a new FGF19 analog, which has the effects of being more long-acting and stable compared with NGM282, can better ameliorate liver impairment and correct diseases such as metabolic disorders, obesity, overweight, metabolic syndrome, diabetes and dyslipidemia and has no side effects of elevated cholesterol and dietary decline caused by the original FGF19 mutant NGM282 in a therapeutic process.

The disclosure discloses a new anti-metabolic disorder FGF analog and an application thereof, and belongs to the technical field of medicines. According to the disclosure, modification is performed based on an FGF19 mutant NGM282 to obtain a new FGF19 analog, which has the effects of being more long-acting and stable compared with NGM282, can better ameliorate liver impairment and correct diseases such as metabolic disorders, obesity, overweight, metabolic syndrome, diabetes and dyslipidemia and has no side effects of elevated cholesterol and dietary decline caused by the original FGF19 mutant NGM282 in a therapeutic process.

A pre-fermented symbiotic matrix based on a cereal suspension containing encapsulated probiotics and prebiotics, the manufacturing process and the corresponding use are disclosed. The invention complements the actual functional food market solving problems inherent to reduced shelf-life of foods due to loss of probiotic viability to values below the minimum limits needed to promote biological activity. The invention also improves the enzymatic process in the preparation of the cereal base and the fermentative process conditions at different levels, namely the ability to control the concentration of sugars in the cereal suspension without adding sugars, increase protein and fiber content, reduce fermentation time to reduce energy consumption during the process and reduce the risk of contamination as well as promote long term microbial stability maintenance. The invention is designed for cases where intolerance and/or allergy to dairy products occur, as wells for the pharmaceutical, cosmetic and food industries, including pet food.

The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic cardiac failure), cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral artery disease, intermittent claudication, chronic obstructive pulmonary disease s, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer, pulmonary hypertension, Alzheimer disease, vascular dementia, glaucoma, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ischemic optic neuropathy or chronic kidney disease. The present invention relates to a compound of the formula [I-a], or a pharmaceutically acceptable salt thereof:

##STR00001##

wherein each symbol is as defined in the DESCRIPTION.

A method for effecting weight loss by administering a combination of topiramate and phentermine is provided. The phentermine is generally administered in immediate release form, in a daily dose in the range of 2 mg to 8 mg, in combination with a daily dose of topiramate selected to prevent the loss of effectiveness of phentermine alone. Methods for treating obesity, conditions associated with obesity, and other indications are also provided, as are compositions and dosage forms containing low doses of phentermine and topiramate, e.g., 3.75 mg phentermine and 23 mg topiramate.

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.

Provided herein are formulations of PCSK9-binding polypeptides, such as those comprising evolocumab, that comprise N-acetyl arginine and have reduced viscosities when compared to formulations lacking N-acetyl arginine. Provided herein are also methods of formulating such compositions that are advantageous in that they conserve certain components. Such formulations comprising PCSK9-binding polypeptides can be administered to patients to treat and/or prevent PCSK9-related diseases, conditions, and disorders.

The invention provides compounds of formula (I), their pharmaceutically acceptable salts and prodrugs thereof for use in preventing, inhibiting or treating a disease caused by a mutation in the gene coding for hydroxymethylbilane synthase, in particular for preventing, inhibiting or treating acute intermittent porphyria: (I) wherein: A is selected from N and CR.sup.10 (wherein R.sup.10 is H, —NO.sub.2, C.sub.1-6 haloalkyl or —C(O)R.sup.17 in which R.sup.17 is H or C.sub.1-6 alkyl); Z is selected from N and CR.sup.9 (wherein R.sup.9 is H, halogen (e.g. F, Cl, Br or I) or —OR.sup.16 in which R.sup.16 is H, C.sub.1-6 haloalkyl, or optionally substituted C.sub.1-6 alkyl); L is selected from —CH.sub.2—, —C(O)—, —CH(OH)—, —C(O)—NR′—, and —NR′—C(O)— (wherein R′ is H or C.sub.1-3 alkyl, e.g. —CH.sub.3); R.sup.1 is H; R.sup.2 is selected from H, halogen (e.g. F, Cl, Br or I), —NR.sup.11R.sup.12 (wherein R.sup.11 and R.sup.12 are independently selected from H and C.sub.1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered saturated ring), and —OR13 (wherein R.sup.13 is H or C.sub.1-6 alkyl); R.sup.3 is selected from H, —CH.sup.2OH and —C(O)R.sup.14 (wherein R.sup.14 is H or C.sub.1-6 alkyl); R.sup.4 is selected from H, halogen (e.g. F, Cl, Br or I) and —OR.sup.15 (where R.sup.15 is H or C.sub.1-6 alkyl); R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is selected from H, —NO.sub.2 and halogen (e.g. F, Cl, Br or I); R.sup.7 is H; and R.sup.8 is selected from H, C.sub.1-6 alkyl, and halogen (e.g. F, Cl, Br or I); or wherein: R.sup.7 and R.sup.8 together with the intervening ring carbon atoms form an unsaturated ring, preferably an aryl ring.

##STR00001##

The present invention relates to an active pharmaceutical ingredient selected from N-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride, its stereoisomers and the acid addition salts thereof; specifically arimoclomol, for use in methods of treating Gaucher disease (GD).

The present invention relates to a pyrazine derivative, an application thereof in inhibiting SHP2, and a compound of formula (I) or pharmaceutically acceptable salts, esters, isomers, solvates, prodrugs or isotope labels thereof. The structure of the compound of formula (I) is as follows. The novel pyrazine derivative provided by the present invention has excellent inhibition of SHP2 activity and can be used to prevent and/or treat non-receptor protein tyrosine phosphatase-mediated or dependent diseases or disorders.