Abstract: Crosslinked glycosaminoglycans or salts thereof prepared by crosslinking glycosaminoglycan or salts thereof with a polyfunctional epoxy compound wherein a crosslinking index is 0.005 or more per 1 mole of repeating disaccharides in glycosaminoglycan, and having various medical and cosmetic uses.

Abstract: Method of treatment of diseases caused by retroviruses which comprises administering therapeutically effective amount of a natural or synthetic oligo- or polysaccharide having at least one S-oxoacid group attached to the saccharic carbon atom through a linking group of lower molecular weight or a pharmaceutically acceptable salt thereof to a subject in need of such treatment.

Abstract: A method is provided for reducing the occurrence of anastomotic intimal hyperplasia in grafts of artery, vein, biologic or synthetic conduits having end-to-side distal anastomosis. The method includes administering a regimen of fractionated heparin to the subject. Administration of the fractionated heparin can be either intravenously, intraperitoneally, subcutaneously or orally. Preferred dosage is 50-80 mg./kg. body weight per day.

Abstract: Short chained ligosaccharides of high structural homogeneity constituted essentially by hexasaccharides of the formula: ##STR1## in which R represents a hydrogen atom or the --SO.sub.3.sup.31 group. These hexasaccharides have a highly selective activity on certain steps in blood coagulation and are useful as anti-thrombotic medicaments.

Abstract: A complex of a therapeutic agent is disclosed in which the therapeutic agent is complexed to an ammonium ion selected from the group consisting of ##STR1## where R.sup.1 and R.sup.2 are the same or different and are alkyl or hydroxy substituted alkyl containing 1 to 6 carbon atoms; andR, R' and R" are the same or different and are saturated or unsaturated aliphatics containing at least 10 carbon atoms, ##STR2## where R.sup.1, R.sup.2 and R" are as defined above, ##STR3## where R.sup.3 is independently alkyl or hydroxy substituted alkyl containing at least 10 carbon atoms; and R.sup.1, R.sup.2, R.sup.3 and R' having the meanings given above; and ##STR4## where R.sup.1, R.sup.2 and R.sup.3 have the meanings given above. The therapeutic agent is heparin, a biologically active peptide or protein or an antineoplastic drug. The therapeutic agent may also be covalently bonded to a triglyceride type backbone to form a compound.

Abstract: The invention comprises heparin derivative compounds which possess a low density lipoprotein lowering action without a significant anticoagulent effect, and are therefore useful in the treatment of disturbances of fat metabolism, especially hyperlipidemia. The heparin derivatives of the invention are derived from natural heparin, and are prepared by the hydrolysis of heparin and optionally, subsequent acylation at free amine groups of the hydrolyzed heparin.

Abstract: A process to produce by covalent binding conjugates of a substance containing a 2-amino-2-deoxyglycopyranosyl residue the NH.sub.2 -function of which in its most stable conformation is equatorially oriented, and a substrate containing a primary amino group. This is done by subjecting the substrate to degradation by diazotation to form a substance fragment having a free terminal aldehyde group, said fragment through its aldehydo group being reacted with the amino group of the substrate to form a Schiffs base which is then by reduction converted to a secondary amine.The substance is preferably selected from oligo and polysaccharides containing glucosamine or galactose amine units. The substrate is suitably selected from surface-aminated plastic objects, aminated gels and proteins.The conjugate described consists of an 1-deoxy-2,5-anhydrohexitol unit which constitutes terminal unit in an oligo or polysaccharide and which in 1-position is covalently bound to an amino group associated with a substrate.

Abstract: Mucopolysaccharides biologically active and more specific than heparin, particularly with respect to the blood factor Xa. These mucopolysaccharides may be obtained by partial depolymerization, under controlled conditions, of heparin, by the action of a chemical agent such as nitrous acid. The conditions implemented allow the preparation of mucopolysaccharides having a USP titer lower than that of the starting heparin and a Yin-Wessler titer at least equal to that of said heparin. These products may be used particularly as antithrombotic drugs.

Abstract: Novel oligosaccharide fractions with valuable pharmacological properties are obtained from heparin. They have the same structural characteristics of heparin. The heparin fraction consists of oligosaccharides which contain end groups consisting of iduronic acid 2-sulfate, or glucosamine N, 6-disulfate. Further the oligosaccharides contain and monosaccharide endowed with reducing anomeric carbon, and are constituted by multiples of monosaccharide units.

Abstract: The oligosaccharidic fractions of the invention are soluble in an hydro-alcoholic mixture 50/50 (v/v) in which is added 0.5% NaCl, at pH 3.8, are constituted by chains the majority of which have 2 to 14 sugar units, are terminated by end units with a 2,5-anhydromanno structure and are devoid or practically devoid of anti-thrombotic activity.

Abstract: A process for producing natural heparan sulphate and dermatan sulphate for mixtures of proteoglycans from the aorta, myocardium and particularly vascularized organs, based on a series of precipitation and purification steps which enable the protein part of the proteoglycan to be eliminated and the two products to be obtained in substantially pure form, without any chemical or enzymatic degradation.When administered orally or parenterally, the heparan sulphate obtained exerts activation effects on antithrombin III and on the fibrinolytic process.The dermatan sulphate obtained exerts an inhibiting effect on Factor Xa and also possesses the property of activating the fibrinolytic effect of heparan sulphate.

Abstract: The medicaments of the invention contain in their active principle, oligosaccharides of low molecular weight corresponding to or including heparin fragments.

Abstract: Esterified oligosaccharides particularly estersified disaccharides containing a uronic acid residue and a hexosamine residue joined through a glycosidic linkage. Such as useful in cosmetic and pharmaceutical compositions.

Abstract: Anticoagulant products are constituted by polymers (homopolymers or copolymers) including in their chain substitutable groups on which are fixed statistically, groups X and/or Y and/or V, where X denotes the group --SO.sub.3 R.sub.1 or --R.sub.3 --SO.sub.3 R.sub.1, R.sub.1 being a hydrogen atom or a physiologically compatible metal, R.sub.3 being a --CH.sub.2 --CO--NH--R.sub.4 group in which R.sub.4 represensts an alkyl aryl or alkylaryl radical, which may or may not be substituted, or substituted or unsubstituted --CH.sub.2 --; Y denotes the group --SO.sub.2 --R.sub.2 or --R.sub.3 --SO.sub.2 --R.sub.2, R.sub.2 being the residue of an amino acid connected to the --SO.sub.2 bridge through its amine function and V denotes the group --CH.sub.2 --CO--NH--CHR--COOH, R being the side chain of an amino acid it being understood that: (a) if X is --SO.sub.3 R.sub.1 it is necessarily accompanied by Y and/or by V, and (b) V is always accompanied by X and/by Y.

Abstract: Low molecular weight heparin derivatives containing hydrophobic groups and exhibiting improved permeability are disclosed. Said derivatives exhibit anticoagulant activity and improved solubility in organic solvents.

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

Abstract: Acetyl ester derivatives of heparin are disclosed. These derivatives exhibit improved Anti-Xa activity in relation to their global anticlotting activity.

Abstract: Heparin derivatives containing hydrophobic groups and exhibiting improved permeability are disclosed. Said derivatives exhibit anticoagulant activity and improved solubility in organic solvents.

Abstract: Novel depolymerized and supersulfated heparin having a molecular weight comprised between 2000 and 9000 and a sulfation degree of at least 2.5, in which all of the primary hydroxy groups are sulfated; a process for its preparation by reacting a heparin of natural origin, or a fraction thereof with a sulfuric acid/chlorosulfonic acid mixture; and pharmaceutical compositions containing it as active ingredient, having potential antithrombotic, hypolipemic and fibrinolytic activity and useful in the prevention of thrombosis and for the treatment of atherosclerosis.

Abstract: There is provided, in accordance with practice of this invention, a process for separating Factor IX and/or Factor X from an impure protein fraction containing protein in addition to Factors IX and X. A silica resin coupled with a ligand capable of binding Factor IX and/or Factor X is provided. An aqueous solution of the impure protein fraction is applied to the ligand-coupled silica resin to thereby bind the Factor IX and/or Factor X to the resin. The Factor IX and/or Factor X is then recovered from the resin by elution.

Abstract: Water-soluble aminated .beta.-1,3-bound D-glucan and macrophage-stimulating composition containing as an active constituent such glucan.

Abstract: The invention provides novel orally active salts of the formula ##STR1## in which .circle. is the skeleton of a polyol, n is the number of OH's in the polyol (3 to 24); p is .gtoreq.3 and .ltoreq.n; r is the available valence of the heparin unit and .gtoreq.3 and .ltoreq.7; sr is equal to pv; and R.sup.+ is ##STR2## in which R.sup.iv is C.sub.1 -C.sub.3 alkyl; R' and R" are C.sub.1 -C.sub.7 alkyl, the same or different, or combined so that --NR'R" represents the residue of a saturated monocyclic secondary amine; R"' is identical to the corresponding portion of a natural amino acid; the alkylene groups contain 1 to 3 carbon atoms; and R.sup.v is H, --CONH.sub.2 or --COO(C.sub.1 -C.sub.7 alkyl). The salts are stable lipoidal "ion pairs" or complexes which can be absorbed through the gastrointestional wall and which slowly release heparinic acid to achieve long-lasting anticoagulant activity. Novel quaternary salts which are intermediates to the heparin salts of the invention are also disclosed.

Abstract: This invention relates to new xylane sulfates having an apparent molar weight comprised between 7000 and 12000.This invention relates also to a process for their preparation by fractionation, and to the therapeutic application thereof as anti-thrombosis and hypolipemic agents.

Abstract: New angiogenic factors of low molecular weight (under 1000), useful as treatment agents for wound healing and for biological assaying, made from in vitro cultures of a wide variety of tumor cells by a treatment which breaks up the proteinaceous tumor angiogenesis factors ("TAF") in them and liberates the more mobile low molecular weight factors. The treatment can be applied to cell extracts or the aqueous portion of the culture, and the proteinaceous part may be rendered insoluble or captured chemically so as to release the new factor. Separation techniques which can be used include solvent extraction of dried liquid fractions, using polar solvents such as ethanol, and the liberated factor can be purified chromatographically using adsorbents for which the factor has affinity, especially a basic adsorbent and preferably polysaccharide-based, followed by elution.

Abstract: The invention pertains to a mucopolysaccharide fraction obtainable from heparin or from fractions including heparinic constituents of molecular weights from 2000 to 50,000, which has a Yin-Wessler titer which is high relative to the USP titer. It contains components whose molecular weights are less than 10,000, particularly oligosaccharides in the area of 2000-3000, comprising from 8 to 12, notably 10 monosaccharide units, among which glucosamine units whose primary positions are sulphated. The last mentioned oligosaccharides include one N-acetyl-glucosamine unit per two units of 2-O-sulphate iduronic acid and per two N-sulphate-glucosamine units, the other saccharide units being of a different nature and including distinct substituents.

Abstract: There is disclosed a process for producing a convalently bound heparin--antithrombin-III complex useful for anticoagulant therapy, a covalently bound heparin--antithrombin-III complex produced by the process, a composition thereof in a pharmaceutically acceptable carrier, and a method for preventing and treating thromboembolisms by administering to a human patient a therapeutically effective amount of the complex or preparation.

Abstract: The invention relates to a process for preparing mucopolysaccharides having high anti-thrombotic activity compared to heparin. The mucopolysaccharides are obtained from a mucopolysaccharide composition having high anti-thrombotic activity and a ratio of YW/USP Titer higher than that of heparin by fractionation to remove, selectively, the mucopolysaccharide chains having less than six saccharide units.

Abstract: Conjugates are provided which are covalently bonded conjugates of an anticoagulant and protein that are prepared in the presence of a coupling agent that forms amide linkages between the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These conjugates are useful for enhancing the blood compatibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra-corporeal medical device.

Abstract: An enterally absorbable heparin or heparinoid preparation contains a non-ionic surfactant.

Abstract: A complex of a therapeutic agent is disclosed in which the therapeutic agent is complexed to an ammonium ion selected from the group consisting of ##STR1## where R.sup.1 and R.sup.2 are the same or different and are alkyl or hydroxy substituted alkyl containing 1 to 6 carbon atoms; andR, R' and R" are the same or different and are saturated or unsaturated aliphatics containing at least 10 carbon atoms, ##STR2## where R.sup.1, R.sup.2 and R" are as defined above, ##STR3## where R.sup.3 is independently alkyl or hydroxy substituted alkyl containing at least 10 carbon atoms; and R.sup.1, R.sup.2, R.sup.3 and R and R' have the meanings given above; and ##STR4## where R.sup.1, R.sup.2 and R.sup.3 have the meanings given above. The therapeutic agent is heparin, a biologically active peptide or protein or an antineoplastic drug. The therapeutic agent may also be covalently bonded to a triglyceride type backbone to form a compound.

Abstract: This invention relates to oxalate-free preparations of heparin, particularly in the form of calcium salts of heparin, which can be used for the preparation of injectable solutions of heparin which have long storage life.The invention is also directed to a process for freeing heparin from its oxalate content, such as by fractional precipitations by alcohol in the presence of adjusted amounts of mineral salt, until the heparin precipitated contains less than about 70 ppm of oxalate but may contain less than about 30 ppm, preferably even less than 20 ppm.

Abstract: Conjugates are provided which are covalently bonded conjugates of an anticoagulant and protein that are prepared in the presence of a coupling agent that forms amide linkages between the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These conjugates are useful for enhancing the blood compatibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra-corporeal medical device.

Abstract: Process for the preparation of oligosaccharides and oligosaccharide fractions by degradation of heparin, which comprises submitting to incubation an aqueous solution of heparin containing from 5 to 30 g of heparin/liter in the presence of 4-50 m.moles/l of cupric acetate and 50-300 m.moles/l of hydrogen peroxide, at a temperature of 40.degree.-50.degree. C., for 20-24 hours and keeping the pH at a value of 7.8 by means of sodium acetate.The obtained products show a high inhibiting property of the Xa factor, a high antithrombotic activity and a very modest anticoagulant activity; therefore they are very interesting for a possible utilization as drugs in the antithrombotic treatment, practically free from any risk of haemorrhages.

Abstract: Novel chemical compounds which are heparin fragments with a molecular weight of from 2,000 to 5,500 covalently bound to antithrombin III, and their use in medicine.

Abstract: A process to produce by covalent binding conjugates of a substance containing a 2-amino-2-deoxyglycopyranosyl residue the NH.sub.2 -function of which in its most stable conformation is equatorially oriented, and a substrate containing a primary amino group. This is done by subjecting the substance to degradation by diazotation to form a substance fragment having a free terminal aldehydo group, said fragment through its aldehydo group being reacted with the amino group of the substrate to form a Schiffs base which is then by reduction converted to a secondary amine.The substance is preferably selected from oligo and polysaccharides containing glucosamine or galactose amine units. The substrate is suitably selected from surface-aminated plastic objects, aminated gels and proteins.The conjugate described consists of a 1-deoxy-2,5-anhydrohexitol unit which constitutes terminal unit in an oligo or polysaccharide and which in 1-position is covalently bound to an amino group associated with a substrate.

Abstract: A complex of a therapeutic agent is disclosed in which the therapeutic agent is complexed to an ammonium ion selected from the group consisting of ##STR1## where R.sup.1 and R.sup.2 are the same or different and are alkyl or hydroxy substituted alkyl containing 1 to 6 carbon atoms; andR, R' and R" are the same or different and are saturated or unsaturated aliphatics containing at least 10 carbon atoms, ##STR2## where R.sup.1, R.sup.2 and R" are as defined above, ##STR3## where R.sup.3 is independently alkyl or hydroxy substituted alkyl containing at least 10 carbon atoms; and R.sup.1, R.sup.2, R.sup.3 and R and R' have the meanings given above; and ##STR4## where R.sup.1, R.sup.2 and R.sup.3 have the meanings given above. The therapeutic agent is heparin, a biologically active peptide or protein or an antineoplastic drug. The therapeutic agent may also be covalently bonded to a triglyceride type backbone to form a compound.

Abstract: A highly discriminating technique utilizing Concanavalin A, immobilized on a solid substrate, e.g. sepharose 4B, for the fractionation of heparin is disclosed. The heparin to be fractionated is incubated with antithrombin whereby a fraction complete with the antithrombin and the whole is then either passed through a column of the immobilized Concanavalin A or slurried with same. In both modes that fraction of the heparin complexed with the antithrombin is selectively absorbed by the immobilized Concanavalin A and constitutes the anticoagulant active fraction. That heparin which complexes with the antithrombin can be further fractionated to yield yet more highly active fractions by complexing the heparin in stages, adding an increment of a molar amount of antithrombin in each stage.

Abstract: The object of the invention is to provide a new antithrombotic agent.Coagulation of blood acts through a cascade of stages, the mechanisms and interaction of which have not been fully clarified. The present invention provides a derivative of heparin which can be administered orally, topically, or parenterally to antagonize the effect of factor Xa to a greater extent than commercial porcine heparin. In addition, the derivative has insignificant USP anticoagulant and platelet aggregating activities.The heparin derivative according to the invention, has a molecular weight of from about 2,500 to about 4,000 daltons, gives a positive metachromatic test for sulfated polysaccharides. Preferably, when isolated as the sodium salt, the derivative contains by elemental analysis about 26.2% carbon, 4.33% hydrogen, 1.98% nitrogen, 7.1% sulfur, and 9.8% sodium, the molar ratio C:N:S:Na being about 10:1.5:2:4.

Abstract: Conjugates are provided which are covalently bonded conjugates of an anticoagulant and protein that are prepared in the presence of a coupling agent that forms amide linkages between the anticoagulant and the protein. Such amide linking coupling agents exclude highly toxic coupling agents such as CNBr. These conjugates are useful for enhancing the blood compatibility of certain surfaces of a prosthetic device, a surgical apparatus, or an extra-corporeal medical device.

Abstract: A pledget of biological material of predetermined unit dosage is formed by a lyophilizing process. The lyophilizing process involves establishing a specific batch volume of sterile water, dissolving a preestablished amount of biological material in the batch volume of water, filling at least one container with a portion of the solution of water and dissolved material, and lyophilizing the solution in the container into the pledget. The amount of biological material to be dissolved in the water is established in relation to the volume and number of containers, the desired predetermined unit dosage of each pledget, and the desired number of pledgets to be formed at a time.

Abstract: A heparin-enriched material capable of long-term storage and particularly adapted for use as a raw material in processes for the extraction of heparin is produced by storing the animal organ material for a period of 0.5 to 15 hours (preferably 4 to 6 hours) at a temperature of 10.degree. to 50.degree. C. (preferably 30.degree. to 50.degree. C.), then injecting steam to effect a heat treatment at a temperature between 75.degree. and 100.degree. C. The heat treatment precipitates heparin-containing aggregate which is filtered from the aqueous phase and dried to a dry substance content of 90 to 95%.

Abstract: An orally administrable heparin comprising: a complex of heparin with (1) a protonated tertiary organic ammonium ion having the formula: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 each independently represent a branched or unbranched alkyl group of 1 to 12 carbon atoms, which may be unsubstituted or substituted with hydroxy or alkoxy groups, or R.sup.1 and R.sup.3 together with the N atom can form a pyrrolidine, imidazole or morpholine ring; or (2) an ester-containing quaternary ammonium ion having the formula: ##STR2## wherein R.sup.4, R.sup.5 and R.sup.6 each independently represent a branched or unbranched alkyl group of 1 to 12 carbon atoms, which may be unsubstituted or substituted with hydroxy or alkoxy groups, or R.sup.4 and R.sup.6 together with the N atom can form a pyrrolidine, imidazole or morpholine ring;R.sup.7 represents an alkyl group of 4 to 16 carbon atoms; andR.sup.8 represents a hydrogen atom or a methyl group.

Abstract: Mucopolysaccharides biologically active and more specific than heparin, particularly with respect to the blood factor Xa. These mucopolysaccharides may be obtained by partial depolymerisation, under controlled conditions, of heparin, by the action of a chemical agent such as nitrous acid. The conditions implemented allow the preparation of mucopolysaccharides having a USP titer lower than that of the starting heparin and a Yin-Wessler titer at least equal to that of said heparin. These products may be used particularly as antithrombotic drugs.

Abstract: The invention relates to an oligosaccharide which contains 4-8 monosaccharide units and which is characterized in that it contains at least one glucosamine unit which is 3-0-sulfated, and at least one additional glucosamine unit, whereby these units are linked via an intermediate monosaccharide unit, which is bound to the reducing end of the 3-0-sulfated glucosamine unit. The invention further relates to a pharmaceutical composition containing one or more such oligosaccharides, and to a process for the preparation of these oligosaccharides.

Abstract: An arterial polysaccharide complex of anionic character consisting of hexosamine glycanmonosulphates (FAPA) derived from the aorta of young mammals and a process for its preparation.

Abstract: The invention pertains to a mucopolysaccharide fraction obtainable from heparin or from fractions including heparinic constituents of molecular weights from 2,000 to 50,000, which has a Yin-Wessler titer which is high relative to the USP titer. It contains components whose molecular weights are less than 10,000, particularly oligosaccharides in the area of 2,000-3,000, comprising from 8 to 12, notably 10 monosaccharide units, among which glucosamine units whose primary positions are sulphated. The last mentioned oligosaccharides include one N-acetyl-glucosamine unit per two units of 2-0-sulphate iduronic acid and per two N-sulphate-glucosamine units, the other saccharide units being of a different nature and including distinct substituents.

Abstract: Oligosaccharides obtainable from heparin including heparinic constituents of molecular weights ranging from 2000 to 50,000. Said fractions have a Yin-Wessler titer and a U.S.P. titer in a ratio of at least 30.They consist of chains constituted by no more than 8 saccharidic moities. They possess a strong antithrombotic activity and are then useful as antithrombotic drugs.

Abstract: A concentrate of blood coagulation Factor VIII:C is obtained in high yield by fractionation of blood plasma with a sequence of adsorption steps employing two different water-insoluble, cross-linked polyelectrolyte copolymers, each in the presence of exogenous heparin.

Abstract: A polyphosphazene-bound heparin complex comprising a polymeric phosphozine backbone, a quaternary ammonium ion covalently attached to the backbone through a bivalent organic radical attached at one end to the nitrogen atoms of the ion and at the other end to a phosphorus atoms of the backbone, and heparin ionically bound to said quaternary ammonium ion is disclosed along with methods for preparing such complexes.

Abstract: A lectin-containing, water-insoluble gel matrix with a glycoprotein reversibly bound thereto can be used for fractionating a polysaccharidic substance capable of being separated into components of differing activity by virtue of differing affinity for the glycoprotein. In this manner, heparin can be fractionated into high activity and low activity components.