Liquid vancomycin containing compositions having extended shelf life are disclosed. The compositions contain vancomycin or a pharmaceutically acceptable salt thereof, a polyol such as glycerol, and lactic acid or a lactate. The compositions are ready to use and easily transferred into larger parenteral solutions prior to administration to patients in need thereof.

Liquid vancomycin containing compositions having extended shelf life are disclosed. The compositions contain vancomycin or a pharmaceutically acceptable salt thereof, a polyol such as glycerol, and lactic acid or a lactate. The compositions are ready to use and easily transferred into larger parenteral solutions prior to administration to patients in need thereof.

Disclosed are compounds of Formula A, or a pharmaceutically acceptable salt thereof: ##STR00001##
where A, X, R.sup.1, and R.sup.2 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

Pharmaceutical compositions comprising amphiphilic peptides are provided. The pharmaceutical compositions are useful in treating or preventing various orthopedic and dental-related infectious and/or inflammatory conditions.

Pharmaceutical compositions comprising amphiphilic peptides are provided. The pharmaceutical compositions are useful in treating or preventing various orthopedic and dental-related infectious and/or inflammatory conditions.

Peptides are provided herein, wherein the peptide bearing one or more amino acid sequence differences relative to SEQ ID NO: 1, with the amino acid sequence differences comprising at least one cysteine replacement.

Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called ‘cryptic’ or ‘silent’ pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.

Provided is a conjugate formed between one or more linear polysaccharide chains and a peptide selected from one or more of the peptide components (a), (b), (c) or (d) as defined below: (a) a peptide component of formula (I), A-Q-B I wherein Q represents a structural fragment of formula (II), wherein: the squiggly lines and m have meanings given in the description and A and B have meanings given in the description, but may represent a peptide component of the amino acid sequence: [W-Lys-X1-Ser-U-X2-Y] n-W-Lys-X1-Ser-U-X2-Y--- (SEQ ID No: 3), wherein the dashed line, n, W, X1, U, X2 and Y have meanings given in the description; (b) a peptide component of the amino acid sequence: [Ala-Lys-X1-Ser-U-X2-Y] p-Ala-Lys-X1-Ser-U-X1-Y-G (SEQ ID No: 4) wherein p, G, X1, U, X2 and Y have meanings given in the description; (c) a peptide component of the amino acid sequence: W-Lys-X1-Ser-U-X2-Y-G (SEQ ID No: 5), wherein W, X1, U, X2, Y and G have meanings given in the description; or (d) a peptide component of the amino acid sequence: K-W1-Lys-X1-Ser-U1-X2-Y1-I-J (SEQ ID No: 6), wherein K, W1, U1, Y1, I, J, X1 and X2 have meanings as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugates, which conjugates are particularly useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynaecological diseases and dental diseases. Preferred linear polysaccharides include hyaluronic acid.

##STR00001##

Provided is a conjugate formed between one or more linear polysaccharide chains and a peptide selected from one or more of the peptide components (a), (b), (c) or (d) as defined below: (a) a peptide component of formula (I), A-Q-B I wherein Q represents a structural fragment of formula (II), wherein: the squiggly lines and m have meanings given in the description and A and B have meanings given in the description, but may represent a peptide component of the amino acid sequence: [W-Lys-X1-Ser-U-X2-Y] n-W-Lys-X1-Ser-U-X2-Y--- (SEQ ID No: 3), wherein the dashed line, n, W, X1, U, X2 and Y have meanings given in the description; (b) a peptide component of the amino acid sequence: [Ala-Lys-X1-Ser-U-X2-Y] p-Ala-Lys-X1-Ser-U-X1-Y-G (SEQ ID No: 4) wherein p, G, X1, U, X2 and Y have meanings given in the description; (c) a peptide component of the amino acid sequence: W-Lys-X1-Ser-U-X2-Y-G (SEQ ID No: 5), wherein W, X1, U, X2, Y and G have meanings given in the description; or (d) a peptide component of the amino acid sequence: K-W1-Lys-X1-Ser-U1-X2-Y1-I-J (SEQ ID No: 6), wherein K, W1, U1, Y1, I, J, X1 and X2 have meanings as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugates, which conjugates are particularly useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynaecological diseases and dental diseases. Preferred linear polysaccharides include hyaluronic acid.

##STR00001##

Provided herein are compounds of Formula (I), as well as compositions comprising a compound of Formula (I) and uses thereof.

##STR00001##