Abstract: The present invention is directed to hemostatic wound dressings containing a fabric made from biocompatible, aldehyde-modified polysaccharide fibers; and a porous, polymeric matrix made from a biocompatible, water-soluble or water-swellable polymer, dispersed at least partially through the fabric, to methods of making such wound dressings and to methods of providing hemostasis to a wound.

Abstract: The present invention provides for a method and composition for treatment and prevention of Type II Diabetes Mellitus and its complications comprising the step of administering to a patient a therapeutically-effective amount of Rhamnan Sulphate, its functional analogs, or its physiologically acceptable salts, in therapeutic proportions. The anticoagulation activity in the blood plasma of a patient is not appreciably increased.

Abstract: The present invention provides methods for inducing, maintaining and expanding CTL (cytotoxic T cell) having an antigen-specific cytotoxic activity at a high level, which is useful in the adoptive immunotherapy, by using as an effective ingredient at least one compound selected from the group consisting of acidic polysaccharides, acidic oligosaccharides, acidic monosaccharides, and salts thereof. The above-mentioned compounds include fucoidans, heparins, alginic acid, chondroitin sulfate A, chondroitin sulfate B, pectic acid, hyaluronic acid, degradation products of fucoidans, sulfated glucose, sulfated fucose and salts thereof.

Abstract: The invention claimed is a method of predicting the structural integrity of a mammalian tissue comprising the steps of measuring an amount of a heparanoid-like substance in a mammalian bodily excretion then referring to a predictive chart showing a correlation between the amount of the heparanoid-like substance in the mammalian bodily excretion in relation to an amount of the heparanoid-like substance in said mammalian tissue and then predicting the amount of heparanoid-like substance in said mammalian tissue from the amount of heparanoid-like substance measured in the mammalian bodily excretion.

Abstract: The invention described is a method and composition for inducing cell surface anti-thrombotic activity in endothelial cells comprising administering to a patient a therapeutically-effective amount of Rhamnan Sulphate. The dose of Rhamnan Sulphate is equivalent to between approximately 8,000 IU and 12,000 IU of heparin activity daily on variable schedule or optionally at single dosage of 7.5 mg/kg, that is repeated on a daily basis as needed, to lower the incidence of thrombus formation or to lower the incidence of hard clot formation.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: An aqueous solution for prophylactic treatment of teats of lactating mammals, comprising as a first component at least partially deacetylated chitosan, or an acid addition salt thereof, in a concentration of up to about 2% by weight of chitosan, the solution having a pH of from about 4 to about 6.8, and said first component having a molecular weight such that the viscosity of the solution is less than about 50 mPas; and a method of prophylactic treatment of teats of lactating mammals.

Abstract: The present invention provides for compositions and methods for the preservation of tissues and organs ex vivo and in situ. In addition, the present invention provides for kits that may be used in the preparation of the solutions of the present invention. The present invention also provides a device for perfusing tissues and organs with the solutions of the present invention.

Abstract: The present invention relates to improved methods for reducing pain and organ dysfunction using bioadhesive, bioresorbable, anti-adhesion compositions made of intermacromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other, and are then either dried into membranes or sponges, or are used as gels, fluids or microspheres. Compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions. The compositions are designed to breakdown in-vivo, and thus be removed from the body. Membranes are inserted during surgery either dry or optionally after conditioning in aqueous solutions.

Abstract: Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0.5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6.4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6.4 or less and unstable at pH of greater than 6.4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6.4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

Abstract: The invention as described comprises a method and composition for enhanced absorption of arginine in mammals, for the treatment of the cellular environment in cardiovascular diseases comprising the step of administering to a patient a therapeutically-effective amount of polyarginine and co-administering a therapeutically-effective amount of heparin or its functional analog or their physiologically acceptable salt. The dose of polyarginine administered to the patient is between approximately 100 mg to 6000 mg daily. Optionally, the dose of polyarginine administered to the patient is between approximately 200 mg to 1900 mg daily. Optionally, the dose of polyarginine administered to the patient is between approximately 400 mg to 1800 mg daily.

Abstract: The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels.

Abstract: The invention provides a novel composition and methods of its preparation and uses. The composition comprises as main components serum and a gelling agent and is useful in various medical applications. The composition may be used to coat a medical device, as a biological glue, or as dressings, membranes, scaffolding or hydrogel useful in bioengineering applications. One or more therapeutic products may be added to the composition and the composition is also a vehicle for delivery of therapeutic products.

Abstract: The invention features methods and products associated with non-invasive delivery of polysaccharide preparations.

Abstract: Disclosed are methods of conjugating biologically active substances, particularly, alpha-interferon, with a hyaluronan or a mixture of a hyaluronan with at least one other hydrophilic polymer having a functional group capable of reacting with divinyl sulfone. Also disclosed are stable intermediates formed by partially reacting a hyaluronan with divinyl sulfone and stopping the reaction before completion to leave free, or reactive vinyl groups on the hyaluronan molecule available for conjugation with the biologically active substance.

Abstract: This invention is a prosthetic device generally placed on the outside surface of the vessel or graft which then elutes antiproliferative drugs or agents from a drug-eluting matrix material. Methods of perivascular antiproliferative drug administration also are disclosed.

Abstract: A carrier and a method for preparing it are provided for use in the delivery of therapeutic agents. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent oxime linkages with a second polysaccharide and each of the first and second polysaccharide is selected from the group consisting of hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate and alginate.

Abstract: New biomaterials essentially constituted by esterified derivatives of hyaluronic acid or by cross-linked derivatives of hyaluronic acid for use in the surgical sector, particularly for use in the prevention of post-surgical adhesion.

Abstract: Matrices that support cell adhesion and growth are disclosed that deliver low heparin-binding affinity growth factor protein peptides in a controlled manner. These matrices comprise covalently or non-covalently bound heparin or heparin-like polymers, which serve to sequester the low heparin-binding affinity growth factor protein peptides within the matrix. The controlled release of some low heparin-binding affinity growth factor or peptides thereof occurs by degradation of some matrix component or dissociation of the low heparin-binding affinity growth factor protein peptides from the bound heparin. This differs from many controlled delivery devices in that release is not controlled solely by diffusion, and the rate of release may therefore be regulated by altering the rate of degradation of the matrix component or the amount of heparin bound within the matrix. The controlled release of such low heparin-binding affinity growth factor proteins such as NGF-&bgr;, NT-3 and BDNF, is demonstrated.

Abstract: The invention relates to compounds that are capable of modulating CD154 mobilization and that are useful for stabilizing the thrombotic and/or coagulation process and/or reducing the activation of cells involved in an inflammatory response. The invention also relates to methods useful for identifying such compounds. The invention also relates to the treatment of platelets for transfusion with metalloproteinase inhibitors to treat or prevent inflammation. The present invention also includes compositions and methods to treat injury and disease related to such biological processes.

Abstract: A method of preventing pain in a sickle cell patient is disclosed. The method includes orally administering to the patient, an amount of an active agent effective on oral administration to inhibit binding of the patient's sickle erythrocytes to P-selectin on the patient's vascular endothelium. The inhibition may be evidenced in a number of ways. The active agent administration inhibits the adhesion of sickle erythrocytes to vascular endothelium in the patient, thereby preventing patient pain associated with vascular occlusion. Also disclosed are compositions useful in practicing the method.

Abstract: The invention provides compositions and methods for cell separation. These reagents and techniques specifically agglutinate cells via surface antigen recognition and can be used to recover even rare cell types in high yield.

Abstract: A procedure for the manufacture of contact lenses for eye treatment, eye protection and eye-care wherein the lenses are impregnated with a suitable composition, a composition for the impregnation of a contact lens for the treatment and/or care and/or protection of the eye, and a kit containing such a composition and one or more contact lenses are disclosed herein. A method for the treatment and/or car and/or protection of the eye comprising wearing contact lenses impregnated with a suitable composition and a composition for disinfection and/or conservation of eye care products is also disclosed herein.

Abstract: The invention provides a method of inhibiting tumor growth in a mammal, by administering to the mammal composition containing taurolidine, taurultam, or a biologically active derivative thereof. The composition is administered to directly contact a tumor cell at a dose sufficient to induce cell death by apoptosis.

Abstract: The present invention relates to a composition and a method for treatment of injury caused or complicated by infections such as pneumonia, injuries in the respiratory organs caused by burns and/or infections and infected chronic leg ulcers in the patients suffering from diabetes, venous or combined venous/arterial insufficiency, wherein a therapeutically active amount of HGF (hepatocyte growth factor) and at least antibiotic agent, to which the infection in question respond, are administered to a mammal suffering from such injury. The present invention also relates to analysis of excrement with regard to HGF, as well as a kit for carrying out the analysis for the diagnosis of certain illness conditions where HGF has turned out to be an important factor.

Abstract: Modified amino acid compounds useful in the delivery of active agents are provided. The active agents can be peptides. Methods of administration, such as oral, subcutaneous, sublingual, and intranasal administration and methods of preparation of the modified amino acid compounds are also provided.

Abstract: An especially useful fibrin glue composition comprises a biocompatible, bioabsorbable hyaluronic acid derivative material, upon which are applied or chemically bonded fibrinogen and thrombin, along with other optional constituents, such as additional coagulation factors, anti-fibrinolytics, stabilizers and biologically active substances. The fibrinogen, thrombin and other components can take the form of a dry preparation, an aqueous or nonaqueous preparation, or as a combination thereof. Such a fibrin glue composition can be placed directly on a wound site and is fully reabsorbed into the body.

Abstract: Drug eluting coating compositions are composed of at least one therapeutic agent dispersed in modified, biologically active binders. The therapeutic agents included in the coating composition are paclitaxel, sirolimus, tacrolimus, everolimus, actinomycin-D, dexamethasone, mycophenolic acid, cyclosporins, estradiol, and derivatives and analogs thereof. These therapeutic agents are applied to the surface of the medical device by a modified, biologically active binders. By using these biologically active binders, the therapeutic agents can be applied to at least one surface of a medical implant without using inert polymer carriers.

Abstract: A lignocaine or a salt, ester or metabolite thereof for use in initiating the natural capacity of regeneration of collateral blood vessels.

Abstract: The present invention provides methods and compositions for delivering a therapeutic agent across a membrane that has limited permeability for the therapeutic agent. The method includes delivering the therapeutic agent to the membrane in a composition which includes a sulphated chitinous polymer as a primary carrier.

Abstract: The invention concerns the use of low molecular weight heparin for preventing and/or treating motor neuron diseases.

Abstract: The invention concerns a method applied to a substance treated to exhibit a biological activity, for example a coagulating or anticoagulation activity. The treated substance has been obtained from a source substance having the biological activity, after a treatment such that the treated substance does not contain any molecule of the source substance in significant amount. The treatment can in particular consist in using a high dilution process of the same type used for producing homeopathic solutions or granules. The method is designed to protect the treated substance from external factors to which it is subjected and is characterised in that it comprises the step which consists in placing the treated substance in a chamber (19), sheltered from electromagnetic fields. The chamber (19) is enclosed with a magnetic shield (19a) made in particular of soft iron or mumetal.

Abstract: The invention relates generally to compositions and methods for preventing or inhibiting thrombin generation or activity.

Abstract: The object of the present invention is to provide a composition which exerts a higher effect on recovering health from articular disorders than that attained by amino sugars and glycosaminoglycans. The present invention solves the object by providing an agent for treating articular disorders, comprising an amino sugar and trehalose as effective ingredients.

Abstract: A charged liposome or micelle encapsulated therapeutic agent or medicament for the treatment of an obstruction in blood vessel. The present method comprises the steps of advancing a delivery catheter with a distal expansion member to the obstruction in a vessel, expanding the expansion member to a configuration wherein the expansion member dilates the obstruction and the expansion member delivers the charged liposomes or micelles with encapsulated therapeutic agents or medicaments to the obstruction. Electrical energy is applied to enhance tissue and cell penetration.

Abstract: Disclosed are methods for a treating a disease or condition relating to blood coagulation and fibrinolysis using p38 MAP kinase inhibitors.

Abstract: Treatment with magnesium produces a inhibition of acute stent thrombosis under high-shear flow conditions without any hemostatic or significant hemodynamic complications.

Abstract: The present invention provides methods for administering an active agent to an animal in need of the agent by the pulmonary route. This method comprises administering via the pulmonary route, a composition comprising (a) an active agent and (b)(i) an acylated amino acid, (ii) a sulfonated amino acid, or (iii) a combination of (i) and (ii). Administration of the compositions of the present invention provide improved pulmonary delivery and greater bioavailability of the active agent than administration of the active agent alone. As a result, lesser amounts of the active agent may be administered to obtain a desired result when contained in the composition of the present invention than when administered alone.

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: A carrier and a method for preparing it are provided for use in the delivery of therapeutic agents. A polysaccharide is reacted with an oxidizing agent to open sugar rings on the polysaccharide to form aldehyde groups. The aldehyde groups are reacted to form covalent oxime linkages with a second polysaccharide and each of the first and second polysaccharide is selected from the group consisting of hyaluronic acid, dextran, dextran sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan, heparan sulfate and alginate.

Abstract: The present invention provides tangible means and methods for stimulation of angiogenesis via enhanced endothelial expression of core proteins having a syndecan-4 cytoplasmic region intracellularly. The tangible means include a prepared DNA sequence fragment having separate and individual DNA sequenced portions coding for an heparan sulfate binding extracellular domain, a central transmembrane domain, and a cytoplasmic domain coding for the syndecan-4 polypeptide. The prepared DNA sequence unitary fragment may be delivered to endothelial cells in-situ, both under in-vivo and/or in-vitro conditions, using suitable expression vectors including plasmids and viruses. The resulting transfected endothelial cells overexpress heparan sulfate binding, core proteins; and the resulting overexpression of these proteoglycan entities causes stimulation of angiogenesis in-situ.

Abstract: The present invention is directed to use of an agent which is able to prevent pathological overexpression of TGF-&bgr; gene in vivo for the preparation of a medicament for the treatment of disorders connected with AP-1 mediated TGF-&bgr; gene expression, except use of sulodexide, low molecular weight heparin derivatives obtained by chemical or enzymatic depolymerization, chemically modified heparin derivatives and low molecular weight dermatan sulfates obtained by chemical or enzymatic depolymerization for the treatment of diabetic nephropathy. Further, the invention provides convenient, fast in vitro methods to assess the value of agents useful for the said disorders.

Abstract: The present invention relates generally to sulfated oligosaccharides, and in particular to the use of certain sulfated oligosaccharides as agents for lowering blood levels of triglycerides such as, for example in treatment of hypertriglyceridaemia.

Abstract: The invention concerns the use of low molecular weight heparin for preventing and/or treating motor neuron diseases.

Abstract: The description relates to a process for the production of esters of heparin, wherein from 0.1 to 2 g of a halogenated reagent having the formula R—CH2—X, where R is a phenyl group which is non-substituted or substituted by a halogen atom or by a nitro group, and X is a halogen atom, preferably chlorine, are reacted with from 2 to 20 g of one of the quaternary ammonium salts of heparin in from 30 to 250 ml of N,N-dimethylformamide and/or N,N-dimethylacetamide.

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: The present invention is directed to a stabilized cross-linked hydrogel matrix comprising a first high molecular weight component and a second high molecular weight component that are covalently linked, and at least one stabilizing or enhancing agent, wherein the first high molecular weight component and the second high molecular weight component are each selected from the group consisting of polyglycans and polypeptides. This stabilized hydrogel matrix may be prepared as bioactive gels, pastes, slurries, cell attachment scaffolds for implantable medical devices, and casting or binding materials suitable for the construction of medical devices. The intrinsic bioactivity of the hydrogel matrix makes it useful as a gel or paste in multiple applications, including as a cell attachment scaffold that promotes wound healing around an implanted device, as gels and pastes for induction of localized vasculogenesis, wound healing, tissue repair, and regeneration, as a wound adhesive, and for tissue bulking.

Abstract: The present invention provides storage stable liquid sealer protein complexes containing fibrinogen that are convenient to store and transport, that are stable over several months, and that do not have to be discarded if an intended surgical procedure is not carried out. The complexes of the invention comprise fibrinogen, an anti-proteolytic agent, an anti-gelling agent, and a physiologically acceptable carrier.

Abstract: Polysaccharides, which are widely used as an anticoagulation drugs, especially heparin, are clinically administered only by intravenous or subcutaneous injection because of their strong hydrophilicity and high negative charge. Amphiphilic heparin derivatives were synthesized by conjugation to bile acids, sterols, and alkanoic acids, respectively. These heparin derivatives were slightly hydrophobic, exhibited good solubility in water, and have high anticoagulation activity. These slightly hydrophobic heparin derivatives are efficiently absorbed in the gastrointestinal tract and can be used in oral dosage forms. Methods of using these amphiphilic heparin derivatives and similarly modified macromolecules for oral administration are also disclosed.

Abstract: Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.