Abstract: Hydrophobically enhanced aminoglycosides have been prepared and shown to be effective antibacterial agents. These agents may be used in the treatment or prevention of various bacterial infections. Methods of preparing these agents also permit facile synthetic access. Formula (I).

Abstract: The present invention relates to water-soluble taxanes covalently bounded to hyaluronic acid or hyaluronic acid derivatives, and in particular to paclitaxel and docetaxel, useful for the preparation of pharmaceutical compositions to be used in the field of oncology, in the treatment of autoimmune disorders and of restenosis. The invention also relates to the process for preparing taxanes covalently bounded to hyaluronic acid or hyaluronic acid derivates by direct synthesis between molecules of hyaluronic acid and of taxane or by indirect synthesis by the introduction of a spacer between the hyaluronic acid derivative and the taxane.

Abstract: The present invention provides methods for preparing LPS antagonist lipodisaccharide B1287 and stereoisomers thereof, which compounds are useful as in the prophylactic and affirmative treatment of endotoxemia including sepsis, septicemia and various forms of septic shock. Also provided are synthetic intermediates useful for implementing the inventive methods.

Abstract: The present invention provides novel moenomycin analogs as well as pharmaceutical compositions thereof, methods of synthesis, and methods of use in treating an infection by administering an inventive compound to a subject in need thereof. The moenomycin analogs may be prepared synthetically, biosynthetically, or semi-synthetically. The analogs are particularly useful in treating or preventing infections caused by Gram-positive organisms. Certain inventive compounds may have a broader spectrum of coverage, which includes Gram-negative organisms.

Abstract: The present invention relates to a UV irradiation assisted method of surface modification, which comprises: introducing a functional group L onto the surface of a polymer material P through the photochemical reaction of a photosensitive group X under UV irradiation, wherein the photosensitive group X comprises at least one xanthone unit.

Abstract: Polysaccharide including carboxyl functional groups. The polysaccharide being chosen from the group of anionic synthetic polysaccharides including 1,6 bonds obtained from neutral polysaccharides of which at least one of a carboxyl functional groups is esterified by a hydrophobic alcohol (-Ah) (residue of a hydrophobic alcohol). The hydrophobic alcohol (Ah) being grafted or bonded to the anionic polysaccharide by a function F (ester function), which results from coupling between the carboxylate function of the anionic polysaccharide and hydroxyl function of the hydrophobic alcohol. Carboxyl functions of anionic polysaccharide, which are not substituted, are in the form of carboxylate of a cation. The polysaccharide including carboxyl functional groups are amphiphilic at neutral pH. It also relates to its use for the preparation of pharmaceutical compositions and the pharmaceutical compositions comprising a polysaccharide and at least one active principle.

Abstract: The various embodiments provide a composition that provides local control over inflammation. The composition localizes the activities of the cytokine-neutralizing antibodies to the site of inflammation through covalent attachment to hydrophilic matrices. The various embodiments including a hydrophilic polymer, a ligand binding moiety covalently attached to the polymer, and optionally, a cellular adhesion peptide covalently attached to the polymer. The hydrophilic polymer may be a glycosaminoglycan such as hyaluronan. The cellular adhesion peptide may be a linear RGD peptide sequence covalently attached to the polymer. The ligand binding moiety may be a monoclonal antibody covalently attached to the polymer. The antibody may be selected from the group consisting of an anti-IL-1?, an anti-IL-6, an anti-TNF-?, and combinations thereof. The polymer functions as a substrate or matrix for cell migration and tissue regeneration.

Abstract: The present invention provides polymeric prodrugs including an intracellular releasable disulfide linker for the delivery of oligonucleotides. Methods of making the compounds as well as methods of delivering nucleic acids to tumor cells in a mammal using the same are also provided.

Abstract: A process for producing a polysaccharide sponge comprises the steps of (A) freezing a photoreactive polysaccharide solution, and (B) irradiating the frozen photoreactive polysaccharide solution with light to crosslink the photoreactive polysaccharide, thereby obtaining the polysaccharide sponge. The process includes simplified steps requiring no removal of solvent, and has such an advantage that impurities are easily removed therefrom.

Abstract: A hyaluronic acid derivative in which an anti-inflammatory drug is bound to hyaluronic acid through a covalent bond via a spacer having a biodegradable region, and a production process thereof.

Abstract: Described herein is the synthesis of alkylated and semi-synthetic glycosaminoglycosan ethers, referred to herein as “SAGEs.” The synthesis of sulfated alkylated SAGEs is also described. The compounds described herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of inflammatory diseases and skin disorders.

Abstract: Pharmaceutical formulations containing (i) an amphiphilic drug and (ii) a short-chain sphingolipid are described and provided herein along with methods of making and using same.

Abstract: The invention relates to novel amidines and quanidines, the production and use thereof and the use thereof as trypsine-type serine protease competitive inhibitors, especially thrombine and compliment proteases CIs and C1r. The invention also relates to pharmaceutical compositions which contain said compounds as active ingredients, in addition to the use of the compounds as thrombine inhibitors, anticoagulants, compliment inhibitors and anti-inflammatory agents. The novel compositions are characterised by the linkage of a serine protease inhibitor having amidine or guanidine functions with an alkyl radical having two or more hydroxyl functions, whereby said alkyl radical is derived from sugar derivates. Several sugar structural components or components derived from sugar can therefore be linked to each other. Said principle of linking sugar derivates enables oral active compounds to be obtained.

Abstract: One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.

Abstract: The present invention is directed to human influenza virus binding substance containing at least one oligosaccharide chain, which comprises a terminal NeuNAc?6 linked to: (a) a linear or branched polylactosamine type structure consisting of at least three lactosamine residues, a linear sequence optionally containing one or two ?3-linked fucose residues in a non-sialylated lactosamine, a branched structure optionally carrying one or more additional NeuNAc?-residues at a terminal position in a branch, and/or (b) a linear or branched structure with two lactosamine and one lactose residue, a linear structure in addition containing one or two ?3-linked fucose residues in a non-sialylated lactosamine or lactose, a branched structure optionally carrying one additional NeuNAc?-residue in a terminal position of the branch, or an analog or derivative of said oligosaccharide chain for use in binding of human influenza virus.

Abstract: A bone growth-promoting composition is provided comprising hyaluronic acid and a growth factor. The composition has a viscosity and biodegradability sufficient to persist at an intra-articular site of desired bone growth for a period of time sufficient to promote the bone growth. Preferably hyaluronic acid is used in a composition range of 0.1–4% by weight and preferred growth factor is bFGF, present in a concentration range of about 10?6 to 100 mg/ml.

Abstract: The present invention provides a method for enzymatically producing uridine 5?-diphospho-N-acetylgalactosamine (UDP-GalNAc) (which is an important substrate for oligosaccharide synthesis) from uridine 5?-triphosphate (UTP) and N-acetylgalactosamine 1-phosphate (GalNAc 1-P), the method including using, as an enzyme, uridine 5?-diphospho-N-acetylglucosamine pyrophosphorylase (UDP-GlcNAc pyrophosphorylase) derived from a microorganism (exclusive of a pathogenic microorganism). The GalNAc 1-P employed can be prepared from N-acetylgalactosamine and a phosphate donor in a reaction system by use of N-acetylgalactosamine kinase. According to the present invention, uridine 5?-diphospho-N-acetylgalactosamine can be efficiently produced by use of a relatively inexpensive substrate.

Abstract: The present invention relates to water-soluble taxanes covalently bounded to hyaluronic acid or hyaluronic acid derivatives, and in particular to paclitaxel and docetaxel, useful for the preparation of pharmaceutical compositions to be used in the field of oncology, in the treatment of autoimmune disorders and of restenoisis. The invention also relates to the process for preparing taxanes covalently bounded to hyaluronic acid or hyaluronic acid derivatives by direct synthesis between molecules of hyaluronic acid and of taxane or by indirect synthesis by the introduction of a spacer between the hyaluronic acid or hyaluronic acid derivative and the taxane.

Abstract: Methods and compositions are provided for the reduction of fouling of objects present in marine environments. The methods and compositions include anticoagulants, such as, for example, glycosaminoglycans, coumarin-type molecules, metal chelators, plasminogen activators and platelet inhibitors. The methods include reducing marine fouling, comprising incorporating an anticoagulant compound into a marine coating. In addition, the methods include identifying compounds useful for reducing marine fouling, comprising measuring either blood coagulation or barnacle cement polymerization in the presence and absence of the compound, wherein a reduction in the blood coagulation or the barnacle cement polymerization in the presence of the compound identifies the compound as useful for reducing marine fouling. The coagulation or the polymerization can be measured by a serine protease activity or a transglutaminase activity.

Abstract: An isolated polysaccharide has the structure [-?(1,3)-D-GalpNAc-?(1,4)-D-Glcp-]n The polysaccharide may be from a Bifidobacterium strain NCIMB41003. The polysaccharide exhibits immunomodulatory activity.

Abstract: A novel process which can simply prepare a crosslinked hyaluronic acid gel having a small crosslinking agent content and exhibiting excellent viscoelasticity is provided. A process for preparing a crosslinked hyaluronic acid gel, comprising stirring and mixing a mixture containing 10 W/V % or more of hyaluronic acid, a crosslinking agent and water under acidic or alkaline condition.

Abstract: The present invention provides an immunogenic conjugate comprising biologically deacylated gram-negative bacterial moieties linked to D. discoideum proteinase 1, as well as novel subunits thereof, and methods of making and using the conjugates in vaccines to treat sepsis and other infectious complications.

Abstract: The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH3 to form an alkoxyamine linkage.

Abstract: Methods are disclosed for preparing novel biodegradable cross-linked nanoparticles based on covalently cross-linking modifications of hyaluronic acid. The final products of the present invention are stable in aqueous media, and may be used as detergents and as additives for pharmaceutical compositions for drug delivery, DNA carrier system and other applications. The nanoparticles made from the biopolymers of the present invention may also be used in controlled release applications, super-absorbent materials as well as biomaterials like enzyme immobilization.

Abstract: The present invention relates to compounds which activate the p53 response, and find use in, for example, hyperproliferative diseases such as cancer treatment and potentially other diseases/conditions (involving sirtuin function).

Abstract: A resin connected by amide bond to pyridyl sulfide or methylthiosulfonate can be conjugated to a post traditionally modified protein/peptide to allow determination of presence and kind and optionally location of cysteine modification(s).

Abstract: Various methods for altering surface characteristics of a microsphere are provided. One method includes coupling an enolic acid to the microsphere to modify the surface characteristics of the microsphere. The surface characteristics may include charge density and/or pKa. A reagent can be coupled to the microsphere via the enolic acid. The reagent may include a biomolecule. The modified surface characteristics may increase a stability of the reagent when the reagent is coupled to the microsphere. The modified surface characteristics may also improve performance of an assay carried out with the microsphere. Another embodiment relates to a microsphere that includes an enolic acid coupled to a polymer core of the microsphere such that the enolic acid modifies surface characteristics of the microsphere. A reagent can be coupled to the microsphere via the enolic acid.

Abstract: The present invention concerns amide derivatives of hyaluronic acid (HA) and biomaterials made of amide derivatives of hyaluronic acid (HA), particularly the hexadecylamide of HA, administered by the intra-articular route as a partial/total substitute for synovial fluid to treat joints affected by osteoarthrosis (OA) as well as cases of joint inflammation and/or trauma that cause damage to the cartilage and/or synovia (associated with pain). Lastly, we describe and claim their use in the treatment of joints where the entire structure shows signs of wear due to physiological aging.

Abstract: The invention provides injection vehicles suitable for administering particulate suspensions, such as polymer-based formulations, as well as associated pharmaceutical formulations, articles of manufacture, and kits. Other aspects of the invention included methods for producing and administering pharmaceutical formulations. The injection vehicles of the invention are superior to conventional injection vehicles in that they include a pseudoplastic composition that improves injectability, which facilitates delivery of the desired dose. The injection vehicles of the invention also allow the use of smaller-bore needles than are usually necessary to inject polymer-based formulations, reducing the pain associated with injection of such formulations.

Abstract: Described herein are composites produced by reacting a first thiolated macromolecule with at least one compound having at least one thiol-reactive electrophilic functional group. The methods described herein permit the cross-linking of a variety of different thiolated macromolecules with one another. The composites described herein have a variety of biomedical and pharmaceutical applications, which are also described herein.

Abstract: Modified capsular saccharides comprising a blocking group at a hydroxyl group position on at least one of the monosaccharide units of the corresponding native capsular saccharide, wherein the blocking group is of the formula (Ia) or (Ib): —OX—Y (Ia) or —O—R1 (Ib) wherein X is C(O), S(O) or SO2; Y is NR1R2 or R3; R1 is C1-6 alkyl substituted with 1, 2 or 3 groups independently selected from hydroxyl, sulphydryl and amine; R2 is H or C1-6 alkyl; and R3 is C1-6 alkyl; processes for modifying a capsular saccharide with the blocking groups; saccharide-protein conjugates comprising the modified capsular saccharide; processes for making the saccharide-protein conjugates, pharmaceutical compositions comprising the modified capsular saccharides and/or saccharide-protein conjugates; and methods and uses of the same.

Abstract: The present application discloses methods for identifying inhibitors with high binding-affinity for the carbonic anhydrase-IX (CA-IX) enzyme using click chemistry and uses the candidates thereof as positron emission tomography (PET) imaging agents.

Abstract: Described herein is the synthesis of alkylated and semi-synthetic glycosaminoglycosan ethers, referred to herein as “SAGEs.” The synthesis of sulfated alkylated SAGEs is also described. The compounds described herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of inflammatory diseases and skin disorders.

Abstract: A silver nanocomposite, a formation method for forming the silver nanocomposite, and an application method utilizing the silver nanocomposite. The silver nanocomposite includes a silver nanoparticle conjugated to a glycosaminoglycan (GAG) or glucose. The formation method includes chemically reacting silver nitrate with a reducing agent to form a silver nanoparticle conjugated to the reducing agent of a GAG or glucose. The application method may include topically applying the silver nanocomposite to a wound or burn as an anti-microbial with respect to an antibiotic-resistant genotype in the wound or burn, wherein the silver nanocomposite topically applied includes the silver nanoparticle conjugated to the GAG of 2,6-diaminopyridinyl heparin (DAPHP) or hyaluronan (HA). The application method may include applying the silver nanocomposite as a coating to plastic, a catheter, or a surgical tool, wherein the silver nanocomposite applied as the coating includes the silver nanoparticle conjugated to the GAG of DAPHP.

Abstract: The invention provides a biodegradable hyaluronic acid derivative including at least one modified hyaluronic acid repeating unit represented by the formula (HA)-[O(C?O)NH-M]p, wherein HA is a unit including N-acetyl-D-glucosamine and D-glucuronic acid, M is a modifying moiety containing a C2-16 hydrocarbyl group, and p is an integer of 1 to 4.

Abstract: Implant that is injectable by a sub-cutaneous or intradermal route in the form of a monophasic hydrogel comprising a gel made up of cross-linked hyaluronic acid and one of its physiologically acceptable salts.

Abstract: The present invention relates to methods of producing crosslinked hyaluronic acid microbeads, as well as the produced microbeads, said method comprising the steps of: (a) mixing an aqueous alkaline solution comprising hyaluronic acid, or a salt thereof, with a solution comprising a crosslinking agent; (b) forming microdroplets having a desired size from the mixed solution of step (a) in an organic or oil phase to form a water in organic or water in oil (W/O) emulsion; (c) continuously stirring the W/O emulsion, whereby the reaction of hyaluronic acid with divinylsulfone takes place to provide crosslinked hyaluronic acid microbeads; and (d) purifying the crosslinked hyaluronic acid microbeads.

Abstract: The present invention relates to reagents and methods used in virus isolation and analysis.

Abstract: Disclosed is a boron adsorbent having an excellent adsorbing ability against boron contained in a solution, which is inexpensive and has high general versatility. Also disclosed is a boron removal method which can remove boron efficiently in a simple manner. An amide derivative represented by the general formula (1) is added to a boron-containing water under alkaline conditions to cause the adsorption of boron to the amide derivative. Then, a cation source having two or more valencies is added to the water to cause the aggregation of the amide body. The aggregated amide body is removed from the water. In the general formula (1), m represents 1 or 2; X represents —CH2OH, —CHO or —COOH; n represents an integer of 2 to 5; X are independent from each other and n are independent from each other when m represents 2; and Y represents a monovalent hydrocarbon group having 6 to 16 carbon atoms when m is 1, and represents a divalent hydrocarbon group having 8 to 18 carbon atoms when m is 2.

Abstract: Acid polysaccharides characterised by the concomitant presence of partial esters with non-polysaccharide carboxylic acids and esters between the acid groups of the initial polysaccharide and the alcohol groups of the repetitive units, with the formation of crosslinking among the polysaccharide chains. Process for the preparation of these derivatives comprising the reaction, in homogenous phase in the protic, polar solvent formamide, of the salt of a monovalent inorganic cation of the selected carboxylated polysaccharide with an anhydride of an alkylcarboxylic acid in the presence of a basic catalyst containing an atom of trisubstituted nitrogen. The formamide hydrolysis leads to the formation of a formate ester.

Abstract: An object of the present invention is to provide a chondroitin sulfate having a decreased molecular weight which has utilization as an inhibitor of peritoneal disorder caused by long-term use of a peritoneal dialysis fluid containing glucose or a polysaccharide thereof as an osmotic agent, utilization as an osmotic agent in a peritoneal dialysis fluid, and the like. The chondroitin sulfate having a decreased molecular weight of the present invention as a means for achieving the object is characterized by having a weight average molecular weight of from 1000 to 20000 and containing a constituent disaccharide unit represented by the following structural formula in an amount of from 65 o to 100% (molar ratio) of the total.

Abstract: The present invention relates to methods of producing crosslinked hyaluronic acid microbeads, as well as the produced microbeads, said method comprising the steps of: (a) providing an aqueous alkaline solution comprising hyaluronic acid, or a salt thereof; (b) forming microdroplets having a desired size from the mixed solution of step (a) in an organic or oil phase to form a water in organic or water in oil (VWO) emulsion, wherein the amount of oil phase used is of from 20 to less than 50% by weight based on the sum of oil phase and water; (c) adding a solution comprising a crosslinking agent to the emulsion, whereby the reaction of hyaluronic acid with the crosslinking agent takes place to provide crosslinked hyaluronic acid microbeads; and (d) optionally working up the dispersion of crosslinked hyaluronic acid microbeads obtained in step (c).

Abstract: The present application discloses novel glycoproteins and a related glycosylcarbamoylation methodology suitable for the preparation of glycopeptides (in particular glycoproteins and glycosylated cells), as well as the use of such glycoproteins in medicine, e.g. as pharmaceuticals and diagnostics or in diagnostic kits. The method for the preparation of a carbohydrate-peptide conjugate comprises reacting a cyclic carbamate (1) (wherein R3 and R4 are hydroxyl, acetamido, or a carbohydrate moiety; and R5 is hydrogen, methyl, hydroxymethyl, acetamidomethyl, carboxyl, or X—(CH2)r—, wherein X is a carbohydrate moiety and r is an integer selected from 0, 1, 2 and 3) with a peptide comprising at least one primary amino group.

Abstract: Beta-mimetic compositions and methods of making and using such compositions in preparing bioactive peptides, such as antimicrobial peptides, are disclosed. In particular, spirocyclic proline hybrids are provided that may be used to alter the cis/trans isomerization of proline in a peptide, and which may replace a residue, for example, the i+2 residue, of a beta-turn in a peptide of known sequence, thereby retaining or modifying the structure of the peptide.

Abstract: Disclosed are polysaccharides containing residues of glucosamine or galactosamine in the repetitive unit, characterised by the presence of esters on the hydroxyls or amides on the amine functions, with lipoic acid or with mixtures of lipoic acid and formic acid.

Abstract: The invention is directed to novel synthetic C-glycolipids that selectively induce a ThI-type immune response characterized by enhanced IL-12 secretion and increased activation of dendritic cells. The compounds of the invention are thereby useful in treating infections, cancers, cell proliferative disorders, and autoimmune diseases, both directly and as adjuvants.

Abstract: Compounds and pharmaceutical compositions comprising them are disclosed that may be useful for the treatment of diseases and disorders such as diabetes and obesity.

Abstract: The invention relates to compositions and methods useful in the labeling and identification of proteins. The invention provides for highly soluble zwitterionic dye molecules where the dyes and associated side groups are non-titratable and maintain their net zwitterionic character over a broad pH range, for example, between pH 3 and 12. These dye molecules find utility in a variety of applications, including use in the field of proteomics.

Abstract: A cationized hyaluronic acid and/or a salt thereof includes a quaternary ammonium group-containing group, and has a degree of cationization of 0.15 to 0.6.