Universiteit Gent

Gatt Technologies Bv

Vrije Universiteit Brussel

Bender Analytical Holding B.v.

Universiteit Hasselt

Bender Analytical Holdong B.v.

Richard Hoogenboom

Johannes Caspar Mathias Elizabeth Bender

Jan Cornelis Maria Van Hest

Victor Retamero De La Rosa

Annemieke Madder

Joachim Van Guyse

Bryn Monnery

Steven Ballet

Harry Van Goor

Gertjan Vancoillie

Chris Vervaet

Maarten Vergaelen

Aseel Samaro

Valérie Vanhoorne

Evelien Baeten

Ondrej Sedlacek

Tanja Junkers

Charlotte Martin

Bart Verbraeken

Patrick Andreas Anton Van Vliet

Johannes Caspar Bender

Jan Cornelis Van Hest

The present invention provides peptide hydrogelators capable of forming hydrogels as carriers of active ingredients and acting as sustained or controlled release drug delivery systems.

Hydrogel-forming composition for controlled release

The present invention, in general, relates to the field of poly(2-oxazolines) (PAOx), more in particular poly(2-methoxymethyl-2-oxazoline) (PMeOMeOX) and poly(2-dimethylamino-2-oxazoline) (PDMAOx). The present invention also provides methods for preparing these PAOx, as well as compositions and uses comprising said PAOx.

Poly(2-oxazoline)s and methods for preparing them

The present invention provides a post-fabrication modification approach for the fabrication of colored and chromic materials and sensors using plasma surface modification to covalently bind the coloring agent to the substrate, thus avoiding leaching of the dye. Advantageously, in said methods, said coloring agent is a dye or pigment linked to a radical sensitive functional group, such as an alkenyl or alkynyl functional group, and is applied to the substrate prior to the gas plasma treatment. The methods envisaged herein are generic in nature, which allow the covalent immobilization of various dyes on different materials. The covalently coated materials after plasma surface modification, particularly the covalently coated chromic materials and sensors, can be used in many different applications, such as protective textile and wound dressing applications.

Methods for obtaining colored or chromic substrates

The present invention relates to polyoxazoline polymers, polymer combinations and compositions comprising those polymers or combinations of polymers. The invention further relates to the use of said polyoxazoline polymers, said combinations and compositions comprising such polymers and combinations for the sustained release of one or more active ingredients, in particular one or more active pharmaceutical ingredients. It further relates to the use of polyoxazoline polymers or polymer combinations as drug carrier.

Drug formulations comprising polyoxazolines as matrix excipient

The invention entails the combination of basic catalysts, specifically guanidine-based catalysts, such as TBD, in conjunction with functionalized amines having a hydrogen bond donating or accepting functionality, to facilitate the accelerated transamidation of polymer compounds with non-activated ester side chains.

Amidation of polymers containing ester side chains using functionalized amines

A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-POX) with a nucleophilic cross-linking agent is disclosed. The EL-POX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m&#x2265;2, n&#x2265;2 and m+n&#x2265;5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m&#x2265;3; and wherein the EL-POX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked POX-polymers are also disclosed.

Cross-linked polymers and implants derived from electrophilically activated polyoxazoline

Cyclic imino ether polymers, such as polyoxazolines or polyoxazines, having a low polydispersity index can be obtained in a tubular flow reactor by applying a sufficiently high linear flow velocity of the reaction mixture in the tubular flow reactor, such as a flow velocity of least 100 cm/min or at least 120 cm/min. Also, methods to control the polydispersity of a cyclic imino ether polymer during polymerization are provided.

Methods for the preparation of cyclic imino ether polymers

The invention relates to invention relates to a statistical copolymer represented by the following formula (I): Ini-[Ox]-[Oz]-Nuc (I) wherein: Ini represents a residue of an initiator of cationic polymerization, Nuc represents a residue of a nucleophilic agent, Ox represents N(R)CHRCHR; each Rindependently represents H or C(O)R; and Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl; Oz represents N(R)CHRCHRCHR; each Rindependently represents C(O)Ror H; and Rindependently represents optionally substituted Calkyl, optionally substituted cycloalkyl, optionally substituted aralkyl or optionally substituted aryl; each Rindependently represents H, linear or branched Calkyl; m&#x2265;5; n&#x2265;5; m+n&#x2265;20; 3:97&#x2264;m:n&#x2264;97:3. The statistical copolymers of the present invention exhibit useful properties that can be exploited in the medical field, especially in polymer micelles for drug delivery and polyplexes for DNA delivery.

Poly(cyclic imino ether)s

A method for production of a uniform polymer of high molar mass is provides, the method comprising: (a) polymerizing cyclic imino ether monomer in a first reaction mixture by cationic ring opening polymerization to produce a polymerized first reaction mixture containing (i) polymerized material and (ii) solvent and/or unreacted cyclic imino ether monomer; (b) separating solvent and/or unreacted cyclic imino ether monomer from polymerized material contained in the polymerized first reaction mixture; (c) copolymerizing by cationic ring opening polymerization a second liquid reaction mixture containing cyclic imino ether monomer and solvent by combining the separated unreacted cyclic imino ether monomer and/or the separated solvent with other components. Also disclosed are polyoxazoline polymers comprising at least 50 wt. % of repeating units derived from a 2-substituted 2-oxazoline monomer selected from 2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, 2-n-propyl-2-oxazoline, 2-i-propyl-2-oxazoline and combinations thereof, said polymer having a DP of at least 250 and a very low dispersity.

Method for the preparation of uniform, high molar mass cyclic imino ether polymers

Provided are hydrogel-forming peptides that comprise at least one dyad of hydrophobic amino acid residues in which one is a &#x3b2;- or &#x3b2;-homo amino acid residue. The hydrogels derived from these peptides can be loaded with biological materials and can be used in physiological conditions.

Hydrogel-forming peptides

A biocompatible, covalently cross-linked, polymer that is obtained by reacting an electrophilically activated polyoxazoline (EL-PDX) with a nucleophilic cross-linking agent is disclosed. The EL-PDX comprises m electrophilic groups; and the nucleophilic cross-linking agent comprises n nucleophilic groups, wherein the m electrophilic groups are capable of reacting with the n nucleophilic groups to form covalent bonds; wherein m&#x2265;2, n&#x2265;2 and m+n&#x2265;5; wherein at least one of the m electrophilic groups is a pendant electrophilic group and/or wherein m&#x2265;3; and wherein the EL-PDX comprises an excess amount of electrophilic groups relative to the amount of nucleophilic groups contained in the nucleophilic cross-linking agent. Biocompatible medical products and kits comprising the cross-linked PDX-polymers are also disclosed.

A method for production of a uniform polymer of high molar mass is provides, the method comprising: (a) polymerizing cyclic imino ether monomer in a first reaction mixture by cationic ring opening polymerization to produce a polymerized first reaction mixture containing (i) polymerized material and (ii) solvent and/or unreacted cyclic imino ether monomer; (b) separating solvent and/or unreacted cyclic imino ether monomer from polymerized material contained in the polymerized first reaction mixture; (c) copolyerizing by cationic ring opening polymerization a second liquid reaction mixture containing cyclic imino ether monomer and solvent by combining the separated unreacted cyclic imino ether monomer and/or the separated solvent with other components. Also disclosed are polyoxazoline polymers comprising at least 50 wt. % of repeating units derived from a 2-substituted 2-oxazoline monomer selected from 2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, 2-n-propyl-2-oxazoline, 2-i-propyl-2-oxazoline and combinations thereof, said polymer having a DP of at least 250 and a very low dispersity.

Provided herein are fullerene compositions, and methods of preparing fullerene compositions. More particularly, the fullerene compositions include a fullerene-polymer complex having a fullerene and a non-conjugated hydrophilic or amphiphilic polymer. The non-conjugated polymer is substituted with a substituent having a functional group capable of forming intermolecular interactions with the fullerene via pi-stacking.

Fullerene compositions

One aspect of the invention relates to a biocompatible medical product comprising at least 1% by weight of dry matter of a covalently cross-linked polymer that is obtained by reacting a nucleophilically activated polyoxazoline (NU-PDX) with an electrophilic cross-linking agent other than an electrophilically activated polyoxazoline, said NU-PDX comprising m nucleophilic groups; and said electrophilic cross-linking agent comprising n electrophilic groups, wherein the m nucleophilic groups are capable of reaction with the n electrophilic groups to form covalent bonds; wherein m&#x2267;2, n&#x2267;2 and m+n&#x2267;5; and wherein the NU-PDX comprises at least 30 oxazoline units in case the electrophilic cross-linking agent is an isocyanate. Also provided is a kit for producing the aforementioned biocompatible cross-linked polymer. The biocompatible cross-linked polymers according to the invention have excellent implant and/or sealing characteristics.

Growing community of inventors

Terneuzen, Netherlands

Richard Hoogenboom