Fresenius Kabi Deutschland Gmbh

Fresenius Ag

Other

Supramol Parenteral Colloids Gmbh

Fresenius Kabi Austria Gmbh

501 Fresenius Ag

Klaus Sommermeyer

Wolfram Eichner

Michele Orlando

Jurgen Hemberger

Klaus Henning

Cornelius Jungheinrich

Katharina Lutterbeck

Roland Scharpf

Burghard Weidler

Sven Frie

Norbert Zander

Harald Conradt

Ronald Frank

Frank Hacket

Martin Schimmel

Elmar Kraus

Klaus Langer

Reinhold Herbert

Frank Bepperling

Franz Cech

Michael Gorg

Jutta Passlick-Deetjen

Peter Mayser

Thomas Hey

Friedrich Grimminger

Norbert Feichtinger

Ewald Schlotzer

Jürgen Hemberger

Karin Schaupp

Udo Eggenreich

Andreas Meyer Zu Vilsendorf

Gerald Hofer

Eckart Grabenhorst

Anneliese Wurm

Eckhard Nagel

Jens Opitz

Jurgen Koenig

Franziska Hauschild

Helmut Knoller

Martin Thomas

Werner Seeger

Bernd W Mueller

Thomas Maul

Hans-Jorg Muller

Bernd Eschenbach

Harald S Conradt

Bernd-W Müller

The invention relates to a method for coupling proteins to a starch-derived modified polysaccharide. The binding interaction between the modified polysaccharide and the protein is based on a covalent bond which is the result of a coupling reaction between the terminal aldehyde group or a functional group of the modified polysaccharide molecule resulting from the chemical reaction of this aldehyde group and a functional group of the protein which reacts with the aldehyde group or with the resulting functional group of the polysaccharide molecule. The bond directly resulting from the coupling reaction can be optionally modified by a further reaction to the aforementioned covalent bond. The invention further relates to pharmaceutical compositions that comprise conjugates formed in this coupling process and to the use of conjugates and compositions for the prophylaxis or therapy of the human or animal body.

Coupling proteins to a modified polysaccharide

For cooling organs and tissues in transplantation medicine, only ice preparations are used so far which are not soft like a gel and are brought to the necessary degree of comminution by mechanically comminuting frozen, sterile, pyrogen-free isotonic infusion solutions, such as 5% glucose or 0.9% saline, with great effort. The lack of gel-like consistency of the preparations and the expensive production process are very disadvantageous. Therefore, it was necessary to produce a cooling preparation for transplantation medicine, which in a temperature range from &#x2212;5&#xb0; C. to 4&#xb0; C. is gel-like and soft, transparent and sufficiently mechanically stable and yet remains formable. In accordance with the invention, such preparation can be produced from gelatin solutions in the concentration range of 3-20 wt-%, which are isotonized or adjusted to 280-650 mosmol/kg and are almost pH-neutral, by simple cooling and/or freezing.

Method for cooling an organ with a transparent cooling gel

Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a covalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Conjugates of hydroxyalkyl starch and a protein

The invention relates to a method for coupling low-molecular weight substances to a starch-derived modified polysaccharide. The binding interaction between the modified polysaccharide and the low-molecular weight substance is based on a covalent bond which is the result of a coupling reaction between the terminal aldehyde group or a functional group of the modified polysaccharide molecule resulting from the chemical reaction of this aldehyde group and a functional group of the low-molecular weight substance which reacts with this aldehyde group or with the resulting functional group of the polysaccharide molecule. The bond directly resulting from the coupling reaction can be optionally modified by a further reaction to the aforementioned covalent bond. The invention further relates to pharmaceutical compositions that comprise conjugates formed in this coupling process and to the use of said conjugates and compositions for the prophylaxis or therapy of the human or animal body.

Coupling low-molecular substances to a modified polysaccharide

The invention relates to a method for the preparation of a hydroxyalkyl starch derivative which comprises reacting hydroxyalkyl starch (HAS) via the optionally oxidized reducing end of the HAS with the amino group M of a crosslinking compound which, apart from the amino group, comprises a specifically protected carbonyl group, namely an acetal group or a ketal group.

Hydroxyalkyl starch derivatives and process for their preparation

Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a convalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

A molecular complex of a high molecular weight carrier substance and of a medicinal substance. The carrier substance has functional groups whereby the carrier substance and the medicinal substance are bound non-covalently. The medicinal substance is insoluble or slightly soluble in water and the carrier substance is readily soluble in water. The carrier substance can be starch or a starch derivative and can have only one functional group for non-covalent binding of the medicinal substance in each molecule.

Complexing of medicinal substances with high-molecular carriers and injection and infusion solutions containing said complexes

The invention relates to compounds, comprising a conjugate of hydroxyalkyl starch (HAS) and an active agent, whereby the hydroxyalkyl starch is either directly covalently bonded to the active agent, or by means of a linker. The invention further relates to methods for the production of a covalent HAS-active agent conjugate, whereby HAS and an active agent are reacted in a reaction medium, characterised in that the reaction medium is water or a mixture of water and an organic solvent, comprising at least 10 wt. % water.

Conjugates of hydroxyalkyl starch and an active agent

The invention relates to the use of hyperbranched amylopectin which has an average branch degree of between &#x3e;10 and 25 mol % and a molecular weight (Mw) ranging from 40.000-800.000 Dalton and the derivatives thereof in methods for surgical or therapeutic treatment of human or animal bodies or in a diagnostic method, preferably as a plasma volume expander. Plasma volume expanders based on hydroxy-ethylated amylopectin have, as a result of hydroxy ethylation, hitherto exhibited the disadvantage of incomplete metabolism and thus temporary tissue storage which is linked to side-effects. According to the invention, novel plasma expanders based on polysaccharides which do not exhibit the same disadvantages as the former are provided. Improved, completely metabolised plasma expanders based on hyperbranched amylopectin which can be obtained therefrom so that native plant-amylopectins are altered-by transglycosylation in such a way the adjustable, high degree of branching enables control of the serum-&#x3b1;-amylase decomposition so that no or only a very insignificant degree of hydroxy ethylation is necessary.

Hyperbranched amylopectin for use in methods for surgical or therapeutic treatment of mammals or in diagnostic methods, especially for use as a plasma volume expander

The invention relates to starch derivatives of formula (I), in which: X represents a bromine or iodine atom; R&#x2033; represents a straight-chain or branched alkyl group, aryl group or aralkyl group, and; R&#x2014;CO&#x2014; represents an oxidized substituted or unsubstituted starch radical that is oxidized on the reducing terminal group to form a carboxylic acid. Starch derivatives of formula (I) can selectively couple to active substances containing SH groups and have a prolonged half-life period in the human body. The invention also relates to coupling products of compound (I) with active substances, to methods for the production thereof, and to their use as medicaments 

Starch derivatives, starch active substance conjugates, method for the production thereof and their use as medicaments

The invention relates to novel pharmaceutical forms for antibiotics containing amino sugar, amphotericin B, daunorubicin and doxorubicin, in which the known side effects are reduced and which can be used in a simple manner. The antimycotic agent B is nephrotoxic. The cytostatic agents daunorubicin and doxorubicin are highly cardiotoxic. The novel pharmaceutical forms are antibiotic-starch conjugates, wherein the antibiotic is combined with the polysaccharide at the reducing end thereof by means of a peptide bond. According to the invention, said bond is carried out by means of Joxidation of the starch derivative at the reducing end thereof in an aqueous alkaline solution, and by coupling the starch derivative oxidised thereby to the antibiotic in an organic solution. The conjugates obtained are less toxic. The polysaccharide part can be decomposed by serum-&#x3b1;-amylase and the peptide bond can be accessed by an enzymatic attack.

Water-soluble antibiotic comprising an amino sugar, in the form of a polysaccharide conjugate

The invention relates to a method for the continuous production of hydrolytically broken down starch or hydrolytically broken down substituted starch products such as hydroxyethyl- or hydroxypropyl starch. The invention essentially consists of carrying out most of the hydrolytic breakdown in a pipe-shaped, temperature-controlled reactor having no mixing elements. The remaining breakdown is carried out in one or more reactors fitted with mixing elements (fine hydrolysis). The product obtained can be used both in the food industry and for medical purposes, especially as plasma diluent.

Method for the continuous production of hydrolytically broken down and possibly substituted starch, use of hydrolytically broken down starch and device for producing same

To produce a two-chamber arrangement having a first chamber, which is filled with a first component, and a second chamber, which is filled with a second component, two separate bags are sterilized and filled independently of each other with the first/second component. Only after the bags have been sterilized and filled are they connected to each other in such a way that the component contained in one chamber can be transferred into the other chamber so as to be able to mix the two components together. Once they have been filled, the first and second bags are preferably sealed with an openable peel seam, after which the bag ends are welded together.

Method for producing a two-chamber arrangement, and such a two-chamber arrangement

The invention relates to an oil-in-water emulsion comprising, as an active ingredient, &agr;-tocopherol or the stereoisomers thereof and comprising, as an emulsifier, phospholipids. The inventive emulsion is used in order to attain a protective action against damages to human organs resulting from peroxidation. The emulsion contains a &agr;-tocopherol content, with regard to action, of 1.48 g/l to 30 g/l RRR-g(a)-tocopherol, 0-25 g/l of an oil which is compatible with I.V. administration, and 0.25 g/l to 3 g/l of a phospholipid. The emulsion is preferably administered as an infusion and is especially used to reduce damages resulting from peroxidation due to ischemia and /or reperfusion and, among other things, during an organ transplantation.

Oil-in-water emulsion for protecting human organs against peroxidation

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Rosbach v.d.H., Germany

Klaus Sommermeyer