Abstract: The disclosure relates to methods for detecting PNH Type II cell populations in biological samples as well as methods for determining whether a patient is at an increased risk for developing thrombocytopenia or thrombosis based on the percentage of PNH Type II cells in the patient's blood. The disclosure also features reagents and conjugates for use in the methods.

Abstract: The invention provides methods of immobilizing an active agent to a substrate surface, including the steps of, depositing a primer compound on a substrate, thereby forming a primed substrate, contacting the primed substrate with a solution of a compound including a trihydroxyphenyl group, thereby forming a trihydroxyphenyl-treated primed substrate, and contacting the trihydroxyphenyl-treated primed substrate with a solution of an active agent, thereby immobilizing the active agent on the substrate. Further provided are methods of immobilizing an active agent on a substrate, including the steps of providing a substrate, combining a solution of a compound including a trihydroxyphenyl group with a solution of an active agent, thereby forming a solution of an active agent-trihydroxyphenyl conjugate, and contacting the primed substrate with the solution of the active agent-trihydroxyphenyl conjugate, thereby immobilizing the active agent on the substrate.

Abstract: Aspects of the invention include methods for treating or preventing a thromboembolic disease in a subject. In practicing methods according to certain embodiments, an amount of a low molecular weight heparin (LMWH) and a synergistically effective combination of two or more gastrointestinal epithelial barrier permeation enhancers is orally administered to a subject in a manner sufficient to treat the thromboembolic disease in the subject. Compositions and kits for practicing methods of the invention are also described.

Abstract: A medical implant device having a substrate with an oxidized surface and a silane derivative coating covalently bonded to the oxidized surface. A bioactive agent is covalently bonded to the silane derivative coating. An implantable stent device including a stent core having an oxidized surface with a layer of silane derivative covalently bonded thereto. A spacer layer comprising polyethylene glycol (PEG) is covalently bonded to the layer of silane derivative and a protein is covalently bonded to the PEG. A method of making a medical implant device including providing a substrate having a surface, oxidizing the surface and reacting with derivitized silane to form a silane coating covalently bonded to the surface. A bioactive agent is then covalently bonded to the silane coating. In particular instances, an additional coating of bio-absorbable polymer and/or pharmaceutical agent is deposited over the bioactive agent.

Abstract: Procedure for the synthesis of deprotected pentasaccharides from a protected precursor pentasaccharide through a reaction procedure having five stages whereamong is included an N-sulphation of amino groups and a hydrogenolysis of benzyl groups. Through this procedure a drastic reduction is achieved in the total synthesis time in comparison with the process traditionally employed, together with increased reproducibility thereof, permitting the standardization thereof.

Abstract: The present invention relates to the use of heparin derivatives for the prevention and/or treatment of cancer and/or cancer metastasis. The heparin derivatives are substantially 2-O and/or 6-O desulphated heparins which function as inhibitors of galectin-3 activity.

Abstract: The present invention relates to compositions and methods for the treatment of Alzheimer's disease and related disorders. More specifically, the present invention relates to novel combinatorial therapies of Alzheimer's disease and related disorders. In particular, the invention concerns compounds which, alone or in combination(s), can effectively modulate synapse function and/or angiogenesis and/or cell stress response. The invention also relates to methods of producing a drug or a drug combination for treating Alzheimer's disease and to methods of treating Alzheimer's disease or a related disorder.

Abstract: The invention relates to a preparation for restenosis prevention. The preparations for restenosis prevention known as yet do not reach sufficient active agent concentrations in the affected sections of the vascular walls as higher doses cause undesirable side effects. The present invention is a preparation to which at least one antihyperplastic agent is added that has a distribution ratio between butanol and water .gtoreq.0.5. The lipophilic active agent is absorbed by the vascular wall fast and in sufficient quantity. The preparation may be a liquid that can pass through capillaries and may contain a contrast agent so that the active agent is transferred into the vascular wall without any additional effort while the usually required contrast radiograms are taken. The preparation may also be applied to a catheter.

Abstract: The invention relates to a preparation for restenosis prevention. The preparations for restenosis prevention known as yet do not reach sufficient active agent concentrations in the affected sections of the vascular walls as higher doses cause undesirable side effects. The present invention is a preparation to which at least one antihyperplastic agent is added that has a distribution ratio between butanol and water .gtoreq.0.5. The lipophilic active agent is absorbed by the vascular wall fast and in sufficient quantity. The preparation may be a liquid that can pass through capillaries and may contain a contrast agent so that the active agent is transferred into the vascular wall without any additional effort while the usually required contrast radiograms are taken. The preparation may also be applied to a catheter.

Abstract: The invention relates to a preparation for restenosis prevention. The preparations for restenosis prevention known as yet do not reach sufficient active agent concentrations in the affected sections of the vascular walls as higher doses cause undesirable side effects. The present invention is a preparation to which at least one antihyperplastic agent is added that has a distribution ratio between butanol and water .gtoreq.0.5. The lipophilic active agent is absorbed by the vascular wall fast and in sufficient quantity. The preparation may be a liquid that can pass through capillaries and may contain a contrast agent so that the active agent is transferred into the vascular wall without any additional effort while the usually required contrast radiograms are taken. The preparation may also be applied to a catheter.

Abstract: Porous polymers having a plurality of openings or chambers that are highly convoluted, with each chamber being defined by multiple, thin, flat partitions are produced by a new gel enhanced phase separation technique. In a preferred embodiment, a second liquid is added to a polymer solution, the second liquid causing the solution to increase in viscosity. With sufficient polymer and second liquid present, the increase in viscosity can be up to that of a gel. The gel can then be shaped as needed. Subsequent solvent extraction leaves the porous polymeric body of defined shape. The porous polymers have utility as medical prostheses, the porosity permitting ingrowth of neighboring tissue. A second material may be incorporated into the chambers, thereby creating a microstructure filling the voids of the macrostructure.

Abstract: The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

Abstract: The invention provides methods and compositions for treating, preventing and/or remedying psoriasis, based on compounds that have a calcitonin-related gene peptide (CGRP) antagonistic effect. Methods are also disclosed for identifying compounds with CGRP antagonist activity which thereby are suitable candidate compounds for treating psoriasis.

Abstract: Compositions and methods of using the compositions are provided for forming an embolus within a region of an anatomical lumen for a transitory period in order to achieve a therapeutic effect.

Abstract: A method for determining the risk, severity or progression of cardiovascular disease, such as cardiac heart failure. A method for determining the likelihood of admission to the hospital for cardiac heart failure. The methods include determining the concentration of ET-1 and the concentration of one or more of biomarkers selected from the group consisting of cardiac troponin (e.g., cTnI, cTnT), VEGF, BNP, NT-proBNP, and IL-6 in a blood, serum or plasma sample from the patient.

Abstract: The present invention relates to liquid application for skin rejuvenation created from specific amino acids, lipids, nucleic acids and vitamins. This collection of molecules delivers precisely the factors necessary to a specific site requiring healing; a direct intervention system to most expeditiously remodel skin with building blocks. This delivery is a transdermal topical delivery and healing is via specific molecules that engender a false autocoid reaction rapidly followed by an incremental healing-anti-inflammatory response augmented by very specific GRAS ingredients in the invention and also recruited from the body to this needy site. Energy is brought to site by transdermally delivered protons and enhanced by the local vascular flow initiated by transdermal molecules. This delivery system bypasses digestion and dilution. Key is a lipophilic carrier with nuclear and mitochondrial ligands that rapidly penetrate and permeate all membranes and truncates the inflammatory site quickly manifesting curation.

Abstract: A peptide-POD with ability to penetrate and deliver fluorophores, siRNA, DNA and quantum dots to cells in culture and retinal and ocular tissues in vivo is provided herein. POD couples to adenovirus vectors, enhancing tropism for certain cells, potentially providing a safer and more efficacious method to deliver molecules to ocular and other tissues in vivo. POD constructs are therapeutic delivery vehicles for treating cells and tissues, including ocular cells and tissues suffering from retinal degeneration.

Abstract: An improved method for preparing a composition including a heparinoid, a local anesthetic, and a buffer for treatment of a lower urinary tract disease or condition can comprise either: (A) (i) providing a heparinoid in solid form or liquid form; (ii) providing a local anesthetic in solid form or liquid form; (iii) adding a liquid buffer to the heparinoid in solid form or liquid form; (iv) adding the local anesthetic to the mixture of the liquid buffer and the heparinoid; and (v) if necessary, adjusting the pH of the mixture of the liquid buffer, the local anesthetic, and the heparinoid so that a pH is achieved of from about 6.8 to about 8.

Abstract: The invention relates to a pharmaceutical or nutraceutical formulation comprising a core, comprising an active pharmaceutical or nutraceutical ingredient, a penetration promoter and a bioavailability promoting agent, and a polymeric coating for the gastrointestinal targeted release of the active ingredient, characterized in that the bioavailability promoting agent is a pharmaceutically acceptable inhibitor of proteolytic enzymes, which increases the oral bioavailability of the active ingredient by a factor of at least five, compared to a corresponding formulation without the bioavailability promoting agent.

Abstract: The present invention relates to a method of modulating a release of biomolecules having heparin-binding affinity, and more specifically, to a method of modulating a release of biomolecules having heparin-binding affinity, using thiolated heparin adsorbed on metal surface. According to the present invention, it is possible to modulate various biomolecules having heparin-binding affinity such as growth factors spatiotemporally by external electrical stimulations, without causing cytotoxicity and having deteriorating effects on cell activity. Thus, the present invention can be applied for various biomedical and biotechnical fields including drug delivery, biosensor, and cell culture.

Abstract: This invention relates to oral and intra-articular formulations based on sulphated hyaluronic acid which are effective in the treatment of degenerative osteoarthritis.

Abstract: In various embodiments methods are provided for identifying a mammal having an elevated risk for an adverse cardiac event (e.g. an MI) and/or determining the prognosis for the mammal. In certain embodiments the methods comprise determining, or causing to be determined, the presence and/or level of antibodies that bind a malondialdehyde-acetaldehyde adduct (MAA adduct) in a biological sample from the mammal, where an elevated level of anti-MAA adduct antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions and/or is at elevated risk for a myocardial infarction.

Abstract: This invention is in the field of medical treatment, in particular the invention provides a method for the prevention and treatment for sepsis or septic shock. The invention provides a novel use of a known medicament, i.e. pentasaccharide-depleted heparin for use in the treatment or prevention of sepsis, SIRS, severe sepsis or septic shock.

Abstract: The present invention is in the field of coagulation diagnostics and relates to a kit and method for preparing controls for use in test methods for determining thrombocyte function.

Abstract: The present invention relates to methods and kits for determining heparanase procoagulant activity in a biological sample. The invention also relates to diagnostic methods for the detection and/or monitoring of a coagulation-related pathologic disorder in a mammalian subject. The invention further relates to compositions comprising heparanase and at least one tissue factor, uses and methods based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions. The invention still further relates to methods for screening a coagulation modulatory compound, methods and uses based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions.

Abstract: According to one aspect of the disclosure, medical devices are provided which have a negatively charged surface and a lubricous hydrophilic coating comprising a sulf(on)ated species disposed on the negatively charged surface. In various embodiments, the sulf(on)ated species is ionically crosslinked with itself and with the negatively charged species by a multivalent cationic species. In other aspects, medical devices are provided which have a polymeric surface and a lubricous hydrophilic layer comprising a covalently crosslinked sulf(on)ated species disposed on the surface. Still other aspects of the invention pertain to methods of forming such devices and methods of using such devices.

Abstract: Oral pharmaceutical compositions for the controlled release of heparin or derivatives thereof, for example dalteparin, salts and/or derivatives thereof, comprising (a) a matrix consisting of amphiphilic compounds and lipophilic compounds with melting point lower than 90° C. in which the active ingredient is at least partially dispersed; (b) an outer hydrophilic matrix in which the lipophilic/amphiphilic matrix is dispersed; (c) optionally, other excipients suitable for solid pharmaceutical forms. The treatment of inflammatory bowel diseases (IBD) by administering to a patient in need thereof an effective amount of dalteparin, salts and/or derivatives thereof is also disclosed.

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.

Abstract: Methods, kits and compositions are described that include a non-naturally occurring kallikrein inhibitor and an anti-thrombolytic agent, e.g., an anti-fibrinolytic agent, for preventing or reducing blood loss and/or ischemia, e.g., ischemia associated with perioperative blood loss and cerebral ischemia, the onset of systemic inflammatory response, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia or a focal brain ischemia, e.g., in patients subjected to invasive surgical procedures, especially procedures requiring cardiopulmonary bypass.

Abstract: Compositions containing one or more active agents, one or more bioadhesives elements, and one or more charge masking agents are described herein. In some embodiments, the one or more active agents are biomolecules or macromolecules, such as polysaccharides, proteins, peptides, or nucleic acids, which are charged at physiological pH. The one or more charge masking agents are selected based on the nature of the charge on the active agent. The compositions may also contain one or more controlled release materials, such as extended or sustained release materials or delayed release materials, in order to modify release of the active agent.

Abstract: The present invention relates to the use of hydroxymethyl-group-containing glycosaminoglycans, such as in particular hydroxymethyl-hyaluronic acid, for the treatment and prevention of infectious diseases or malignant or premalignant diseases, in particular of the skin or mucosa. The invention additionally provides a preparation method for glycosaminoglycans modified with hydroxymethyl groups.

Abstract: The invention concerns novel biotinylated hexadecasaccharides of general formula (I) wherein: Biot is a biotin derivative; R, R1 and R2, represent independently of one another a C1-C6 alkoxy or and —OSO3; R3 represents a C1-C6 alkoxy or an —OSO3, or R3 constitutes a —O—CH2— bridge; Pe represents a saccharide concatenation; as well as their pharmaceutically acceptable salts, and their use as medicines.

Abstract: A catheter lock solution which is a catheter lock preparation having a bacteriostatic property at physiological osmotic pressure without practically containing a bacteriostatic component such as a preservative, an antimicrobial agent, or an antibiotic and having high safety, characterized in that the preparation contains a weak acid having an acid dissociation constant (pKa) of 3.0 to 6.5 as a buffer, a pH of the solution is less than 6.0, preferably from 3.0 to about 5.5, an osmotic pressure ratio is from 0.5 to 3.0, and a pH change (variation) can be suppressed to less than the 6.0 with the weak acid, and a container containing the catheter lock solution.

Abstract: High molecular weight heparosan polymers are described, as are methods of producing and using the high molecular weight heparosan polymers.

Abstract: Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking and methods of making and using thereof.

Abstract: Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Abstract: Drug-eluting rotational spun coatings that include one or more therapeutic agents may be used to coat a medical device. The medical devices include, for example, balloon catheters, vascular grafts and stents, which are coated with drug-eluting rotational spun materials that may be used to deliver a therapeutic agent to a target tissue or body lumen.

Abstract: An injector system for delivery of a pharmacological agent to biological tissue having a plurality of needles arranged in an array, a plurality of reservoirs configured to receive a pharmacological composition therein, the reservoirs being in fluid communication with a respective one of the plurality of needles, a pneumatic pressure source, a pneumatic drive system that is configured to induce a first discharge of the pharmacological composition out of the reservoirs and needles in a plurality of delivery modes, agent delivery volume control means for controlling volume of the pharmacological composition discharged from the needles, and a control system having actuation control means for controlling said pneumatic drive system. The control system is programmed to control the delivery modes.

Abstract: A method for inhibiting cellular proliferation of fibroblasts and/or glioma cells in a mammal includes administering a composition to a mammal wherein the composition includes an amount of an anionic polymer and an anti-platelet agent effective to inhibit cellular proliferation of fibroblasts and gliomas in the mammal.

Abstract: A pharmaceutical composition for use in the prevention and/or treatment of a neurodegenerative disorder comprising a compound comprised of one or more disaccharide units, the or each disaccharide unit comprising a uronate moiety linked to a glucosamine moiety, wherein the 2-O atom of the uronate moiety is substituted with a hydrogen atom, the 6-O atom of the glucosamine moiety is substituted with a sulphate group and the 2-N atom of the glucosamine moiety is substituted with an atom or group other than a sulphate group. The composition is particularly preferred for use in the prevention and/or treatment of Alzheimer's disease.

Abstract: Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric form of thyroid hormone, or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

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: One embodiment of the present invention is a pharmaceutical composition comprising at least one specific 2-iminopyrrolidine derivative and at least one other compound (B). Another embodiment of the present invention is a pharmaceutical composition comprising at least one specific 2-iminopyrrolidine derivative, which is to be used in combination with at least one other compound (B). According to the present invention, there are provided pharmaceutical compositions capable of treating or ameliorating diseases, such as heart diseases, effectively.

Abstract: A method of factor X1-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor X1-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor X1; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor X1-dependent manner.

Abstract: Disclosed herein are methods of inducing neuronal outgrowth of a neuron. The methods comprise contacting the neuron with an agent that binds receptor protein tyrosine phosphatase ? (RPTP?), to thereby induce neuronal outgrowth of the neuron. The agent may induces clustering of RPTP? and/or inhibit binding of chondroitin sulfate proteoglycan (CSPG) to RPTP?. Examples of suitable agents are heparan sulfate proteoglycan, heparan sulfate, heparan sulfate oligosaccharides, or heparin oligosaccharides. Additional agents are also disclosed. The neuron can be a CNS neuron or peripheral neuron. Also disclosed herein are methods of treating neuronal injury in a subject comprising, administering to the subject an agent that binds RPTP?. Administration may be to a site of neuronal injury, to thereby induce neuronal outgrowth at the site of neuronal injury.

Abstract: Pharmaceutical compositions suitable for the oral administration of heparin or derivatives thereof, particularly controlled-release oral pharmaceutical compositions containing heparin with different molecular weight, for the treatment of inflammatory bowel diseases and related conditions, are disclosed.

Abstract: The invention relates to sulphated polysaccharides which have the general structure of the constituent polysaccharides of heparin and which have a molecular weight of less than 8000 Daltons, comprising two antithrombin III-binding hexasaccharide sequences corresponding to formula (I) in which: R1 represents an OH group when the hexasaccharide of formula (I) is located at the reducing end of the polysaccharide, or else R1 represents a bond with another saccharide unit of said polysaccharide; R2 represents a hydrogen atom when the hexasaccharide of formula (I) is located at the non-reducing end of the polysaccharide, in which case the bond between carbon atoms 4 and 5 of the first saccharide unit of said hexasaccharide is a double bond, or else R2 represents a bond with another saccharide unit of said polysaccharide, in which case the bond between carbon atoms 4 and 5 of the first saccharide unit is a single bond.

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 non-psychoactive derivatives of tetrahydrocannabinol, which are useful in treating interstitial cystitis and relieving symptoms thereof. The invention uses (6aR,10aR)-?8-tetrahydrocannabinol-11-oic acids (hereinafter referred to as (6aR,10aR)-?8-THC-11-oic acid), as well as pharmaceutical compositions containing the (6aR,10aR)-?8-THC-11-oic acids, for treatment of interstitial cystitis in a mammal. The invention further covers methods of formulating and administering the compounds and pharmaceutical compositions as therapeutic agents in the treatment of interstitial cystitis, with particularly preferred administration routes being oral and via intravesicular instillation.

Abstract: Provided herein are methods of treating, suppressing, inhibiting, or preventing bronchitis in a subject comprising the step of administering to a subject a compound comprising a lipid or phospholipid moiety bond to a physiologically acceptable monomer, dimer, oligomer, or polymer, and/or a pharmaceutically acceptable salt or a pharmaceutical product thereof.