Abstract: A non-anticoagulant (NAC) form of heparin which shows antiproliferative activity with respect to smooth muscle cells is useful in the prevention of restenosis and other conditions benefited by antiproliferative activity with respect to smooth muscle cells. This NAC form of heparin is prepared by oxidizing heparin/heparan sulfate to a desired level with periodate followed by reduction of the resulting aldehyde groups; all under conditions which prevent depolymerization of the heparin.

Abstract: A method of treating thrombosis with a pharmaceutical formulation comprising an endo-beta-glucuronidase, preferably leech-derived, heparin and a pharmacologically acceptable diluent, carrier or excipient which does not prevent the interaction between the heparin and the endo-beta-glucuronidase is disclosed. The formulation, which is disclosed, can also comprise a clot-lytic agent such as tissue plasminogen activator. Endo-beta-glucuronidase, unlike other hyaluronidases, has been found not to be inhibited by heparin.

Abstract: Various peptides having affinity for sulfated polysaccharides such as heparin, dextran sulfate and Pentosan polysulfate are bound to resins and used in affinity chromatography to prepare anti-HIV sulfated polysaccharides.

Abstract: Disclosed is an anticoagulant material comprising a polymer obtained from an ionically bonded composite synthesized from i) a basic compound having a copolymerizable functional group and ii) a heparin salt. Disclosed is also a process for preparing the anticoagulant material. The anticoagulant material of the present invention can maintain excellent anticoagulant properties or antithrombotic properties over a long period of time and is capable of being applied as a component material for various medical articles such as artificial internal organs and artificial blood vessels, and a process for preparing it.

Abstract: Salts of glycosaminoglycans (heparin, its fractions or fragments which are supersulfated, dermatan sulfate, heparan sulfate, and modified heparins) with bases of formula (I), ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, and R.sub.4 represent H, alkyl, or cycloalkyl; R.sub.5 and R.sub.6 represent H, or alkyl; R.sub.7 and R.sub.8 represent H or alkyl; n and m are integers from 1-4 and X is --O--CO--O--, which salts have the pharmacological properties of the glycosaminoglycans themselves, and are orally and rectally administrable.

Abstract: The present invention comprises a method for impeding the formation of tumor metastasis or tumor invasiveness in a host. Such inhibition comprises administration to the host of a glycosaminoglycan derivative substantially devoid of anticoagulation activity and is an effective inhibitory of heparanase activity. Such a glycosaminoglycan derivative may be provided by purchase or synthesis as directed herein. Parenteral administration to a tumor-bearing host of the glycosaminoglycan derivative results in the exposure of host-borne tumor cells thereto. Such exposure to effective levels of the derivative results in the inhibition of tumor heparanase activity and a lessening of invasiveness and metastatic spread.Heparin, a glycosaminoglycan particularly effective as a heparanase inhibitor and an anti-clotting agent, is a preferred glycosaminoglycan for derivatization.

Abstract: A non-anticoagulant (NAC) form of heparin which shows antiproliferative activity with respect to smooth muscle cells is useful in the prevention of restenosis and other conditions benefited by antiproliferative activity with respect to smooth muscle cells. This NAC form of heparin is prepared by deacetylating and then oxidizing heparin/heparan sulfate substantially to completion with periodate followed by reduction of the resulting aldehyde groups under conditions which prevent depolymerization of the heparin.

Abstract: Heparanase activity in a patient may be inhibited by administering an effective heparanase-inhibiting amount of heparin or an effective chemically modified derivative of heparin which inhibits heparanase activity. Such derivatives are preferably N-desulfated, N-acetylated heparin or O-desulfated, N-acetylated heparin. By means of this invention, allograft rejection may be prevented or delayed and autoimmune diseases such as arthritis may be alleviated and treated.

Abstract: A process for the depolymerization and supersulfation of heparin and the so obtained supersulfated heparins are disclosed. The process comprises treating heparin with oleum containing from 2 to 6% free sulfuric anhydride at a temperature from -10.degree. to +20.degree. C. The obtained heparins have molecular weights from 2000 to 5000 and a sulfation degree from 3.4 to 4.3. All of them are endowed with a remarkable antithrombotic activity.

Abstract: A thermoplastic polyurethane having prolonged biostability has tertiary amino groups in the polymer chain. Protonation of the amino groups with an aqueous acid causes the polymer to absorb up to 1,700% by weight of water and swell. The protonated amino groups form a complex with an antithrombogenic agent to give an antithrombogenic polyurethane. The invention includes a shaped article of the polyurethane.

Abstract: A thermoplastic polyurethane has tertiary amino groups in the polymer chain. Protonation of the amino groups with an aqueous acid causes the polymer to absorb up to 1,000% by weight of water and swell. The protonated amino groups form a complex with an antithrombogenic agent to give an antithrombogenic polyurethane. The invention includes a shaped article of the polyurethane. The shaped article may be antithrombogenic.

Abstract: The present invention includes an image-enhancing agent comprising a biodegradable, water-soluble polymer, synthetic or naturally derived and having repeating hydrophilic monomeric units with amino or hydroxyl groups. This agent also includes chelating agents comprising functional groups bound to an amino or bydroxyl group of the monomeric units. These chelating agents have a formation constant for divalent or trivalent metal cations of at least about 10.sup.8 at physiological temperature and pH. This image-enhancing agent is biodegradable to intermediary metabolites, excretable chelates, oligomers, monomers or combinations thereof of low toxicity.These image-enhancing agents may further comprise a paramagnetic metal ion for enhancement of the image arising from induced magnetic resonance signals.Images resulting from scanning of gamma particle emissions may be enhanced when the image-enhancing agent of the present invention comprise radioisotopic metal ions emitting gamma particles.

Abstract: A porous medium having a positive surface change removes heparin from a heparin-containing liquid, without removing other proteinaceous components from the liquid. Methods and devices are disclosed.

Abstract: Method for the treatment of arthritis, rheumatism and inflammation of connective tissue in which a multivalent metal ion substantially pure complex of xylan polysulphate, wherein the multivalent metal ion is selected from the group consisting of Ca.sup.2+, Mg.sup.2+, Cu.sup.2+ and Zn.sup.2+ is administered to a patient in need of such treatment.

Abstract: Disclosed is a method of providing a substrate with a layer comprising a polyvinyl base hydrogel and a biochemically active material by photolithograhy, comprising coating the substrate by centrifugal force with an aqueous solution of a photosensitive hydrogel forming polymer, a crosslinking agent and a biochemically active material, drying said coating, exposing the coated substrate through a photomask to ultraviolet radiation and developing said exposed coating, which is characterized by applying to the substrate an aqueous solution comprising as the cross-linking agent a polyazonium compound and glutardialdehyde. Because of this specific combination of cross-linking agents superior properties with respect to the binding of the biochemically active material are obtained.

Abstract: A composition for thrombolytic therapy includes a tissue-type plasminogen activator (t-PA) and a low affinity heparin fraction. The composition is administered intravenously to allow the t-PA to dissolve blood clots while the low affinity heparin fraction prevents reocculsion without the harmful side effects observed for unfractionated heparin, such as, stimulation of and interference with t-PA activity in the circulatory system, as well as, interference with fibrinolytic activity which can cause hemorrhaging in the mammalian circulatory system.

Abstract: Probe cocktails contain a nucleic acid probe and a sulfated polysaccharide as a volume excluding polymer to speed up hybridization rates. Exemplary sulfated polysaccharides are chondroitin sulfate A and C, which can be extracted from cartilage and similar tissues. Compared to synthetic anionic polymers such as dextran sulfate, the probe cocktails can have reduced viscosities and surface tensions, as well as reduced water loss when the cocktail is heated to denature DNA before rehybridization. The reduced viscosity and surface tension are of particular value when entering and exiting narrow spaces, as in some automated analyzers and in capillary gap methodologies.

Abstract: A process for the preparation of a material for affinity chromatography is described, in which a sulfated polysaccharide is bonded to a carrier material which has amino groups.For this purpose, a sulfated polysaccharide is treated with an oxidizing agent which oxidizes glycols to aldehydes, with cleavage of the carbon chain, and this modified sulfated polysaccharide is allowed to react with a carrier which has amino groups.It is possible using the described affinity material to adsorb proteins which bind to sulfated polysaccharides from solutions of these proteins and, where appropriate, then to desorb them, for example antithrombin III from blood plasma.

Abstract: A process for preparing dermatan sulphate (DS) of pharmaceutical purity from animal organs rich in micropolysaccharides (MPS), by: a) stabilizing the fresh organs by freezing them either as such or in the form of powder, b) micronizing the material containing the MPS with an aqueous CaCl.sub.2 solution, c) digesting the homogenate comprising the raw material and the CaCl.sub.2 with proteolytic enzyme at alkaline pH and at low temperature, d) acidifying, heating and filtering the lysate, e) treating the filtrate with quaternary ammonium salts able to undergo complexing with and thus precipitate either the DS alone or all the MPS selectively, f) recovering and purifying the DS either directly from the ammonium salt complex containing it or from the complex obtained from the mixture of ammonium salt complexes of all the MPS by fractional solubilization with acetone.

Abstract: Heparins, heparin fractions or fragments, optionally salified with pharmaceutically acceptable cations, having molecular weight ranging from 1.000 to 30.000 D, characterized by an EDTA content lower than 0.1%, by the absence, in the .sup.1 H--NMR spectra, of the signals due to EDTA between 2.50 and 4.00 p.p.m. and substantially free from bleeding effect and optionally free from signals, in the .sup.13 C--NMR spectrum, from 80 to 86 ppm.

Abstract: A method is provided for controlling production of low molecular weight heparin (LMW-heparin) when depolymerizing heparin with heparinase in a reaction mixture in a reactor. Depolymerization to a desired average molecular weight is monitored by measuring an increase in UV-absorption (preferably at 230-235). When the absorption has reached a value for a desired molecular weight, the depolymerization is stopped or LMW-heparin having the desired molecular weight is continuously removed from the reaction mixture. In a preferred embodiment, the reaction mixture is subjected to ultrafiltration to produce a filtrate containing LMW-heparin, and a retentate which is recycled to the reactor. UV-absorption and refractive index of the filtrate are measured, and depolymerization is controlled in accordance with the measured absorption and refractive index to produce a filtrate containing a LMW-heparin of low polydispersity and predetermined molecular weight.

Abstract: New heparinic derivatives having anticalculous activity, devoid of the anticoagulant and antithrombotic activity characteristic of the heparins, obtained by treating commercial or purified or low molecular weight heparins in a basic medium, optionally in the presence of alkali metal salts and of a reducing agent. The heparinic derivatives obtained through this treatment show significant chemical-physical characteristics, in particular they present a .sup.13 C-NMR spectrum different from that of the starting heparins especially in the zone between 102 and 92 p.p.m. with a characteristic signal at 101.3 p.p.m., a specific rotatory power at 546 nm between about +15.degree. and about +40.degree. in aqueous solution, a sulfur content between about 6% and about 9%, a sulfate/carboxyl ratio between about 1.20 and about 1.70 and a content of free amino groups between about 0.4% and about 2.1%. These heparin derivatives can be useful in the treatment of the nephrolithiases.

Abstract: Various variants of photoprotein aequorin (pAQ440), useful for elucidating the mechanism of its luminescence and thereby extending the possibility of concrete applications of aequorin protein, and a process for producing variant aequorin proteins are provided, which variants are obtained by converting base(s) in a specified order of the base arrangement of aequorin gene into other base(s), or by deleting a certain bases in specified continued orders thereof, according to site-specific mutagenesis method.

Abstract: Fecal leakage and contamination from the vent opening of an animal carcass during slaughtering and processing methods is reduced or eliminated by applying a curable adhesive composition to the vent opening and permitting the applied curable composition to cure to form a cured firmly adherent vent seal after slaughtering but prior to other processing steps. In a preferred embodiment, the curable adhesive comprises a cyanoacrylate adhesive which cures in a matter of seconds under processing conditions to form a cured vent seal which retains its sealing integrity even upon exposure to high temperature and high humidity environments encountered at downstream processing stations. The curable sealing compositions are safe in the fully-cured state and do not liberate undesirable materials during curing.

Abstract: Anti-thrombobenic, anti-microbial compositions containing heparin reacted with quaternary ammonium components and bound with water-insoluble polymers are disclosed. Such compositions may also contain additional quaternary ammonium compounds not reacted with heparin and may also contain quaternary ammonium compound(s) reacted with antibiotics.

Abstract: A novel complex of (a) a metal ion selected from copper, calcium, manganese, iron, and zinc ions, and (b) a fraction of heparin, heparan sulfate, low molecular weight heparin, low molecular weight heparan sulfate, heparin fragments, heparan sulfate fragments, and oligosaccharides derived from heparin or from heparan sulfate, or a salt of such fractions which fractions bind to the said metal ion, said complex containing from 5 to 1,000 nmole metal of component (a) per .mu.mole of component (b).

Abstract: The oligosaccharides of the invention are composed essentially of chains:possessing a specific affinity for the anionic and cationic cell growth factor which recognize herparin,comprising at least one sequence of 5 residues matching those present in naturally occurring heparin and possessing a strongly anionic character such as that indicated in the NMR spectrum shown in FIG. 1, as well as their pharmacologically acceptable salts.

Abstract: A glycosaminoglycoside (GAG) composition predominantly of tetrasacchardie units derived from heparin/heparan sulfate has enchanced activity in preventing the proliferation of smooth muscle cells. This GAG preparation is useful in the treatment of diseases characterized by unwanted smooth muscle cell proliferation and activity.

Abstract: Method for obtaining biologically active mucopolysaccharides by controlled depolymerization of heparin, wherein the quantity of products generating nitrous acid is selected so that those products are totally consumed when the desired depolymerization degree is reached.

Abstract: According to the process of the invention, a glycosaminoglycan is used in the form of a salt soluble in an organic medium and is subjected to the action of a given sulfation agent.

Abstract: The present invention relates to modified heparins having antithrombotic activity.The invention also relates to a process of preparing such modified heparins starting from water insoluble heparin ammonium quaternary complexes.Finally, the invention relates to pharmaceutical compositions containing the above modified heparins.

Abstract: New heparin derivatives having antithrombotic activity, also endowed with reduced hemorrhagic and anticoagulant activity, obtained by treating in a basic medium heparins of various origin, optionally in the presence of alkali metal salts and of a reducing agent.The heparin derivatives obtained through this treatment show peculiar chimico-physical characteristics, like new signals at about 53 and 54 p.p.m. in the .sup.13 C-NMR spectrum and an increase of the specific rotatory power, compared to that of the starting heparins, to values between +50.degree. to +90.degree..Said structural modifications produce an improvement of the biological properties of the heparin, substantially keeping the antithrombotic activity while diminishing the hemorrhagic effect in vivo and the anticoagulant activity in vitro.

Abstract: The compositions of the invention are composed of fragments of heparin consisting essentially of repeated disaccharide sequences corresponding to the regular regions of heparin and possessing a MW between 4,800 and 9,000. These compositions can be used for the regulation of physiological systems.

Abstract: A process for the controlled preparation of low molecular weight glucosaminoglycans by treating conventional high molecular weight glucosaminoglycans in the solid state or in solution form with a rectilinear gamma ray beam at doses within the range of 2.5 to 20 Mrad supplied by successive irradiation stages with cooling intervals between one irradiation stage and the next in the dynamic phase.The mixture obtained is subjected to fractionation, purification, neutralization and lyophilization. The glucosaminoglycans obtained have a molecular weight of between 1000 and 35,000 daltons and are used for the preparation of pharmaceutical compositions possessing antithrombotic, fibinolytic, antiatherogenic and heparin cofactor II activation activity.

Abstract: A method of depolymerizing heparin to obtain a heparin with low molecular weight provided with antithrombotic activity comprises treating a quarternary ammonium salt of heparin with a quarternary ammonium hydroxide.

Abstract: A process for controlled chemical depolymerization of naturally occurring linear polysaccharides, more specifically glycosaminoglycans. Depolymerized glycosaminoglycans, such as heparins which are obtained according to the process and pharmaceutical compositions which contain such depolymerized heparins. In the process, the polysaccharides are subjected to the action of atomic oxygen which, preferably, is derived from hypochlorous acid.

Abstract: Process for the preparation of oligosaccharides by a controlled chemical depolymerization of natural polysaccharides, such as heparins, heparan sulfates, dermatan sulfates, chondroitinsulfates, hyaluronic acid, by a radicalic reaction in an aqueous solution, at a temperature ranging between 20.degree. and 70.degree. C., in the presence of a catalyst selected in the group consisting of Cu++, Fe++, Cr+++, Cr.sub.2 O.sub.7 - as well as the resulting oligosaccharides and their related pharmaceutical compositions. The products exhibit high antithrombotic activity, little or no anticoagulant activity, high fibinolytic activity an antiinflammatory activity.

Abstract: Method of crosslinking carboxyl-containing polysaccharides in that the polysaccharide is at first activated with a bi- or polyfunctional reagent, and then after removal of any potential excess of activating reagent the crosslinking is performed during drying. The invention also comprises a material produced according to this method.

Abstract: Process for the depolymerization and sulfation of polysaccharides by reaction of said polysaccharides with a sulfuric acid/chlorosulfonic acid mixture.

Abstract: An epithelium-derived inhibitor of the growth of smooth muscle cells is disclosed along with methods for purifying this substance. As initially isolated, the inhibitor comprises a heparan sulfate proteoglycan having a buoyant density of less than 1.4 g/ml which releases a glycosaminoglycan chain having a molecular weight of about 55,000 to 75,000 on protease cleavage. Growth inhibiting activity is found in the glycosaminoglycan chain and in glycosaminoglycan fragments derived therefrom. Use of a dialyzable detergent in purification steps greatly aids in the handling and purification of the inhibitor. The inhibitor can be used in a variety of techniques for inhibiting the growth of smooth muscle cells, both in vivo and in vitro.

Abstract: Novel processes for synthesizing acid mucopolysaccharide fragments having from 2-12 saccharides and substantially pure products of a single structure produced thereby. Condensation are disclosed between a first protected saccharide and a second protected saccharide to form a protected condensation product having units linked in the manner found in chondroitin sulfate and dermatan sulfate and having protecting groups thereon which allow selective positioning of functional groups, in particular sulfate, at desired positions. Other condensations are disclosed in which a protected condensation product is formed which can be elongated, and has protecting groups thereon which allow selective positioning of functional groups, in particular sulfate, at desired positions. Also disclosed is a process for selectively positioning functional groups on a protected acid mucopolysaccharide having from 2-12 units.

Abstract: Ester derivatives of low molecular weight heparin are disclosed. These derivatives exhibit improved Anti-Xa activity in relation to global anticlotting activity.

Abstract: A process for the specific adsorption of heparin and other heparin-like substances which comprises flowing a buffered solution of whole blood, from which corpuscular blood constituents have been removed, plasma and/or solutions containing whole blood or plasma through an adsorber capsule containing a medium that adsorbs heparin and other heparin-like substances at an acid pH, preferably in the range of 4.0 to 5.5. Preferably, the process is carried out in a closed, extracorporeal circulation and the medium possesses anion exchange resin properties.

Abstract: Heparin fractions which are a mixture of oligosaccharides containing 6-12 monosaccharides are described. The oligosaccharides contain reducing end groups composed of iduronic acid 2-sulfate or glucosamine N, 6-disulfate. The end group monosaccharides contain the reducing anomeric carbons. The SO.sub.3.sup.- /COO.sup.- ratio is essentially the same as in heparin. The method of preparation is a depolymerization initiated by free radicals. One fraction is a heparin fragment with a molecular weight (MWw) of 2,100 daltons (+10%). The compound contains 6-8 monosaccharides, has the same SO.sub.3.sup.- /COO.sup.- ratio as the parent heparin and has platelet anti-aggregating activity, arterial and venous antithrombotic action, fibrinolytic and antiatherosclerotic activity. It exhibits poor anti factor Xa activity and no anticoagulant action.

Abstract: There is disclosed oligosaccharide compounds having heparin-like anticomplement activity and reduced anticoagulant activity as compared with heparin on a weight or molar basis. The oligosaccharide compounds have at least 5 and no greater than 25 saccharide units. The oligosaccharides can have an even nuber of saccharide units with a terminus nonreducing sugar, or an odd number of saccharide units without a terminus nonreducing sugar. There is also disclosed anticomplement pharmaceutical compositions with reduced anticoagulant side effect activity and a process for preparing the oligosaccharide compounds.

Abstract: A method is provided for preventing or reducing deep vein thrombosis and/or pulmonary embolism by administering a thromboxane A.sub.2 receptor antagonist in conjunction with heparin. A combination of thromboxane A.sub.2 receptor antagonist and heparin is also provided.

Abstract: The invention relates to pharmaceutical compositions intended to decrease the incidence of tumor metastasis in patients who suffer from malignant diseases.The pharmaceutical compositions of the invention contain as active ingredient heparin or a suitable derivative thereof. Amongst suitable derivatives are N-desulfated and N-acetylated heparin.The dosage of the administered heparin or heparin derivative is quite critical and will generally be in the range of from 0.05 mg/kg/day to about 0.5 mg/kg/day. A preferred range is between about 0.1 mg/kg/day to about 0.5 mg/kg/day.

Abstract: New uses for heparin, or heparin-like compounds are described that encompass preserving and healing of cells and cell functions arising from transplantations, circumcisions, dermatitides, fissures, fistulas, stimulation of epithelial growth, keloid prevention, cold injuries, pathology and forensic diagnosis, myocardium, trauma, decubitus ulcers, psoriasis, poisonings, insect and snake bites, corrosive ingestions, the "bends," space-travel sickness, brain and heart nerve conduction electrical dysrhythmias, pulmonary respiratory distress, blood and blood products, ulcerative colon lesions, interstitial cystitis, and related cosmetic uses. The uses are realized by applying the compounds either in solution, or in the form of a cream or aerosol, preferably at a pH of about 5.5, in an effective amount and for a time sufficient to effect treatment. Generally, the concentration of heparin or heparin-like compounds will be in the range of 1500 to 5000 international units per milliliter.

Abstract: A non thrombogenic quarternary ammonium/heparin complex coating for a medical article is disclosed where the organic cationic salt is an alkylbenzyldimethyl ammonium ion present in an amount of at least 50% by weight and having the following formula: ##STR1## where R is a uniform alkyl group containing between 16 to 18 carbon atoms.

Abstract: A process for preparing dermatan sulphate (DS) of pharmaceutical purity from animal organs rich in mucopolysaccharides (MPS), by: (a) stabilizing the fresh organs by freezing them either as such or in the form of powder, (b) micronizing the material containing the MPS with an aqueous CaCl.sub.2 solution, (c) digesting the homogenate comprising the raw material and the CaCl.sub.2 with proteolytic enzymes at alkaline pH and at low temperature, (d) acidifying, heating and filtering the lysate, (e) treating the filtrate with quaternary ammonium salts able to undergo complexing with and thus precipitate either the DS along or all the MPS selectively, (f) recovering and purifying the DA either directly from the ammonium salt complex containing it or from the complex obtained from the mixture of ammonium salt complexes of all the MPS by fractional solubilization with acetone.