Abstract: Methods of evaluating heparin preparations, e.g., for suitability for use as a drug or for use in making a drug, by determining the absence, presence or amount of a structural signature that is indicative of the methods used to make the heparin preparation.

Abstract: The present invention relates to mixtures of polysaccharides derived from heparin having a mean molecular weight of 1500 to 3000 Daltons and an anti-Xa/anti-IIa ratio greater than 30, their method of preparation and pharmaceutical compositions containing them.

Abstract: The invention relates to a composition of glycosaminoglycans for the treatment of diabetic foot ulcer, it specifically relates to low molecular weight heparins (LMWHs) and very low molecular weight heparins (VLMWHs) in the treatment of chronic ulcers, particularly of diabetic foot ulcers, and more specifically in the manufacture of a medicinal product for the treatment of chronic ulcers, and particularly diabetic foot ulcers and pressure ulcers.

Abstract: The present invention relates to a heparin fraction comprising constituents having molecular weights of from about 2,000 to about 4,000 daltons, wherein from about 1% to about 100% of hydroxyl residues of the constituents are oxidized. The present invention also relates to methods of inhibiting angiogenesis and treating an angiogenesis-mediated disorder in a subject by administering a heparin fraction comprising constituents having molecular weights of from about 2,000 to about 30,000 daltons, wherein from about 1% to about 100% of hydroxyl residues of the constituents are oxidized. Another aspect of the present invention relates to compositions including the heparin fractions of the present invention.

Abstract: The present invention relates to mixtures of polysaccharides derived from heparin having a mean molecular weight of 1500 to 3000 Daltons and an anti-Xa/anti-IIa ratio greater than 30, their method of preparation and pharmaceutical compositions containing them.

Abstract: Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide-reactive group and/or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan.

Abstract: A compound of the following formula or a salt, solvate or formula (I) and a pharmaceutical composition containing said compound. It concerns also its use in the treatment of cancer and/or of pathological angiogenesis and/or in promoting the mobilisation of stem cells, in particular hematopoietic stem cells.

Abstract: The use of Herapan Sulphate 2 (HS-2) in therapeutic bone growth and regeneration is described. Herapan Sulphate 2 was identified as a variant of Heparan Sulphate purified from embryonic day (E10) of murine neuroepithelia.

Abstract: Alkali and alkali-earth metal salts of polysaccharides derived from heparin, their method of preparation and the pharmaceutical compositions containing them.

Abstract: Manufactured hyaluronic acid products are used in numerous surgical applications including viscoelastic supplementation for the treatment of osteoarthritis, however, traditional sterilization techniques result in the breakdown of such high molecular weight viscoelastic biopolymers and are thus unsuitable. Disclosed are processes for obtaining concentrated sterile solutions of high molecular weight biopolymers such as hyaluronic acid. The processes include filter sterilization with a dilute preparation of the biopolymer, and concentration of the dilute filter sterilized biopolymer by ultrafiltration to a desired concentration.

Abstract: This invention provides low molecular weight lipid-GAG and phospholipids-GAG conjugates and methods of use thereof in suppressing, inhibiting, preventing, or treating a pathogenic effect on a cell, including, inter alia, infection with intracellular pathogens.

Abstract: Methods and apparatus for the separation of polysaccharides, particular heparin products, and glycosylated molecules are provided. The separation is based on the molecular weight and charge, by application of an electric field across a low-friction matrix, modified with a charged separation agent comprising charged regions ordered in a monotonous sequence distributed throughout the matrix, to generate a charge density gradient formed when an external electric field is applied. Saccharides of different charges migrate differently across the porous matrix and immobilized by charge neutralization in different charge regions of the matrix.

Abstract: The present invention is directed to a multistep process for the physical depolymerization of heparin wherein heparin is subjected to at least two ?-ray irradiations and wherein between two irradiation steps the depolymerised heparin is subjected to a separation step and only a fraction of the depolymerised heparin obtained from the first irradiation is subjected to the second irradiation step. It is also directed to heparin-derived oligosaccharide fractions obtainable by the process of the invention.

Abstract: The present invention relates to mucoactive agents, such as heparin which are useful in the treatment of diseases where excess mucus is present in the respiratory tract, such as cystic fibrosis and chronic obstructive pulmonary disease. In particular, the invention relates to pharmaceutical compositions for administration by pulmonary inhalation. It also relates to methods for producing particles suitable for pulmonary inhalation, such as spray drying or jet milling.

Abstract: Methods of making LMWH compositions are provided to provide the LMWH compositions at a yield of at least about 10%.

Abstract: Using digital microfluidics, recombinant enzyme technology, and magnetic nanoparticles, a functional prototype of an artificial Golgi organelle is described. Analogous to the natural Golgi, which is responsible for the enzymatic modification of glycosaminoglycans immobilized on proteins, this artificial Golgi enzymatically modifies glycosaminoglycans, such as heparan sulfate (HS) chains, immobilized onto magnetic nanoparticles. Sulfo groups were transferred from adenosine 3?-phosphate 5?-phosphosulfate to the 3-hydroxyl group of the D-glucosamine residue in an immobilized HS chain using D-glucosaminyl 3-O-sulfotransferase. After modification, the nanoparticles with immobilized HS exhibited increased affinity for fluorescently labeled antithrombin III as detected by confocal microscopy. Since the biosynthesis of HS involves an array of specialized glycosyl transferases, epimerase, and sulfotransferases, this approach should mimic the synthesis of HS in vivo.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

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: 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: Methods and compositions for treating disease are provided. More particularly, methods and compositions of inhibiting pathogenic interferon production are prevented, which may be useful in the treatment of various diseases. In other embodiments, therapeutic compounds and methods for the treatment of autoimmune diseases and chronic inflammatory diseases are provided. One such method is a method for inhibiting pathogenic interferon production or inhibiting activation of plasmacytoid dendritic cells or treating an autoimmune or chronic inflammatory disease, which comprises inhibiting one or more of LL-37 and hCAP18.

Abstract: A new method is described for the oversulfation of epiK5-N-sulfate to obtain an epiK5-amine-O-oversulfate with very high sulfation degree which, by subsequent N-sulfation, provides new epiK5-N,O-oversulfate-derivatives with a sulfation degree of at least 4, basically free of activity on the coagulation parameters and useful in the cosmetic or pharmaceutical field. Also described are new low molecular weight epiK5-N-sulfates useful as intermediates in the preparation of the corresponding LMW-epiK5-N,O-oversulfate-derivatives.

Abstract: Polysaccharide preparations lacking substantial anticoagulant activity are provided herein. Methods of making and using such preparations are provided.

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: Polysaccharide preparations lacking substantial anticoagulant activity are provided herein. Methods of making and using such preparations are provided.

Abstract: The present invention relates to novel heparin-nitroxide derivatives comprising heparin and at least two and more nitroxides/polynitroxide radicals that are covalently coupled to heparin by derivatisation of glycosaminoglycan carboxyl or amino groups. The heparin-nitroxide derivatives are useful as therapeutic or diagnostic agents. This invention further concerns novel methods for the production of the heparin-nitroxide agents, and methods of their uses for specifically targeting and labelling of biological vessels. The inventions also suggest the uses of the heparin-nitroxide derivatives for treatment of oxidative stress-mediated diseases. Furthermore, the heparin-nitroxide derivatives according to the present invention are in particular useful for electron paramagnetic resonance imaging (EPRI), for magnetic resonance imaging (MRI), and for preservation of biological transplants.

Abstract: The invention relates to salts of the active ingredient clopidogrel with polyanions. The salts are predominantly in amorphous form, and the polyanions have at least 4 negative charges.

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

Abstract: A new method is described for the oversulfation of epiK-N sulfate to obtain an epiK5-amine-O-oversulfate with very high sulfation degree which, by subsequent N-sulfation, provides new epiK5-N,O-oversulfate-derivatives with a sulfation degree of at least 4, basically free of activity on the coagulation parameters and useful in the cosmetic or pharmaceutical field. Also described are new low molecular weight epiK5-N-sulfates useful as intermediates in the preparation of the corresponding LMW-epiK5-N,O-oversulfate-derivatives.

Abstract: Provided herein are methods and compositions for the in vitro formation of tetracycline conjugates, for example, tetracycline conjugated to anti-coagulants. The present invention also provides methods for preventing or treating plaque-related diseases or disorders such as atherosclerosis using tetracycline alone, or the tetracycline conjugates of the present invention.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patent who is then diagnosed or treated using the effector molecule.

Abstract: The present disclosure provides polymer compounds binding with lipoamide produced by the reaction of the primary amine group of lipoamide with the carboxy group of polysaccharide compounds such as chondroitin sulfates, carboxymethyl celluloses, or hyaluronic acids; functional compounds such as peptides, proteins, growth factors; or drugs; or biocompatible polymers such as poly(ethylene oxide), poly(vinyl alcohol), or poly(vinyl pyrrolidone). The present disclosure also provides their synthesis methods, products of hydrogels and films using the same as and methods for manufacturing the products.

Abstract: Thermosetting polymeric compositions, such as polyurethane compositions, and related methods are provided. The invention relates to coating and polymer compositions and related methods derived from a biodegradable natural polysaccharide compound such as chitosan, pectin, heparin, and combinations thereof reacted to a cyclic oxide compound, such as an oxetane, oxolane or oxepane compound. The compositions and methods of the present invention exhibit self-repairing properties upon exposure to ultraviolet (UV) light. The compositions and methods of the present invention can be used in many coating applications, such as the transportation, packaging, fashion, and biomedical industries.

Abstract: This invention provides a method of treating a subject suffering from an obstructive respiratory disease, including the step of administering to a subject a compound comprising a lipid or phospholipid moiety bound to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof, in an amount effective to treat the subject suffering from an obstructive respiratory disease.

Abstract: Alkali and alkali-earth metal salts of polysaccharides derived from heparin, their method of preparation and the pharmaceutical compositions containing them.

Abstract: Partially desulfated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives exhibit antiangiogenic activity and are devoid of anticoagulant activity.

Abstract: Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Abstract: This invention provides a method of treating a subject suffering from a dermatologic condition, including, inter alia, psoriasis, contact dermatitis, and seboreic dermatitis, the method includes the step of administering to a subject a compound comprising a lipid or phospholipid moiety bound to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof, in an amount effective to treat the subject suffering from a dermatologic condition.

Abstract: The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

Abstract: The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

Abstract: The present invention is directed to conjugates for biorecognition comprising (i) an carbohydrate backbone structure (PO) of 5 to 20 monosaccharide units, (ii) oligosaccharide biorecognition groups (Bio) of 1 to 10 monomer units, (iii) a bifunctional spacer groups of the formula -(y)p-(S)q-(z)r-, wherein S is a spacer group, p, q and r are each 0 or 1, whereby at least one of p and r is different from 0, and y and z are chemoselective ligation groups, which covalently link a said Bio group to said backbone structure, and the degree of conjugation, indicating the average number of covalently attached Bio biorecognition groups per monomer unit of the backbone, being from 0.2 to 1. The invention is also directed to processes for their preparation, intermediates for use in the process as well as use of said conjugates, especially for inhibiting pathogenic bacteria.

Abstract: The invention relates to biotinylated heparins comprising constituent polysaccharides having at their reducing ends at least one covalent bond with biotin or a biotin derivative, and also to the process for preparing them, to pharmaceutical compositions containing them and to their therapeutic use. The biotinylated polysaccharides are of the formula (I) with the variables as defined herein.

Abstract: The present invention relates to polymeric derivatives, which can be conjugated to an amino-containing drug to improve its in vivo properties. The polymeric derivative can subsequently be released to yield the drug in its native form. Methods of preparing and using these polymeric derivatives and drug conjugates are described.

Abstract: Novel carbosilane dendrimers, their preparation and their uses. The dendrimers of the invention have secondary, tertiary and quaternary amino groups at their branch ends. Their possible uses include vehicles for carrying anionic-charged molecules in the blood, such as nucleic acids, among them ODN and RNAi, and other anionic drugs with which they have the capacity of interacting, protecting them from interaction with plasma protein and/or increasing their penetration rate in target cells. In the cases where the bond is long-lasting, the dendrimers of the invention can be used to fix anionic molecules to surfaces. Their uses also include their administration as active ingredients to prevent or treat diseases caused by micro-organisms with whose structure and/or life cycle they interfere.

Abstract: Orthogonally protected disaccharide building blocks for synthesis of heparin saccharide are disclosed. The disaccharide building block has a formula (I), in which L is a leaving group, P1, P2, P3 and P4 are different, and of them P1 is an ester-type protecting group, P2 is a hydroxyl protecting group that could be oxidized to a carboxylic acid, P3 is a hydroxyl protecting group, and P4 is a hydroxyl protecting group which allows chemoselective deprotection with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Acting as an elongation unit, the disaccharide building block of formula (I) may react with a starting unit of formula (II) to synthesize a heparin saccharide of desired size.

Abstract: The invention relates to a process for the depolymerization of glycosaminoglycanes characterized by the use of UVC radiation. The invention also relates to the intermediate depolymerized heparin obtained by the process. The intermediate depolymerized heparin can be dissolved in a buffer solution and fractionated by gel permeation for obtaining the desired molecular weight.

Abstract: A prodrug comprising a heparin and a drug is provided. The prodrug can be used to form a coating on a medical device. The prodrug can also be used with a polymeric material to form a coating on a medical device. The polymeric material can be a hydrophobic polymer, a hydrophilic polymer, a non-fouling polymer, or combinations thereof. The medical device can be implanted in a human being for the treatment of a disease such as atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, or combinations thereof.

Abstract: In an affinity-type purification, ligands dissociated from the stationary phase that would otherwise leach into the species being purified are captured by a second ligand that is also incorporated into the stationary phase, the second ligand exhibiting an affinity-type interaction with the dissociated first ligand with sufficient specificity to avoid the undesired retention by the second ligand of species from the liquid sample or source liquid other than the species sought to be purified in the affinity column.

Abstract: This invention provides a method for inhibiting or preventing the abnormal growth of cells, including transformed cells, by administering an effective amount of O-acylated heparin derivative. Abnormal growth of cells refers to cell growth independent of normal regulatory mechanism (e.g. loss of contact inhibition). This includes the abnormal growth of: (1) tumor cells (tumors); (2) benign and malignant cells of other proliferative disease in which aberrant cellular proliferation occurs; (3) aberrant smooth muscle cell proliferation, such as might occur following treatment for coronary atherosclerosis such as angioplasty or the insertion of a stent into an occluded vessel.

Abstract: Orthogonally protected disaccharide building blocks for synthesis of heparin oligosaccharide. The disaccharide building block has a formula (I), in which L is a leaving group, P1, P2, P3 and are different, and of them P1 is an ester-type protecting group, P2 is a hydroxyl protecting group that could be oxidized to a carboxylic acid, P3 is a hydroxyl protecting group, and P4 is a hydroxyl protecting group which allows chemoslective deprotection with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Acting as an elongation unit, the disaccharide building block of formula (I) may react with a starting unit of formula (II) to synthesize a heparin oligosaccharide.

Abstract: The invention relates to methods and products associated with analyzing and monitoring heterogeneous populations of sulfated polysaccharides. In particular therapeutic heparin products including low molecular weight heparin products and methods of analyzing and monitoring these products are described.