Abstract: The present invention discloses a cross-linked hyaluronic acid/collagen formulation which has improved composition for dermal filling and higher persistence than cross-linked collagen or HA alone. Also disclosed are methods for preparing cross-linked hyaluronic acid/collagen formulations and using such for augmenting soft tissues in mammals.

Abstract: Disclosed herein are an in situ-forming, bioadhesive hydrogel and the medical uses thereof. Being formed by in situ crosslinking through an enzymatic reaction, the hydrogel has an advantage over conventional bioadhesive hydrogels in terms of biocompatibility. In addition, the in situ-forming bioadhesive hydrogel has excellent biocompatibility and mechanical strength and has excellent tissue adhesiveness thanks to modification with/without dopa derivatives. The hydrogel finds a variety of applications in the biomedical field, including bioadhesives or hemostats, implant substances for tissue regeneration and augmentation, carriers for delivering biologically active materials or drugs, etc.

Abstract: This disclosure relates to particles (e.g., nanoparticles and microparticles) that display multiple functionalized surface domains in a controlled mosaic pattern. The disclosure also provides simple methods to create various particles that have multiple functionalized surface domains while allowing the use of a wide variety of diverse core structures. The multiple functionalized domains provide controllable particle binding and orientation, and controlled and sustained drug release profiles.

Abstract: The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.

Abstract: Provided are crosslinked polymer compositions that include a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer, which contains or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further include other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents.

Abstract: Compositions are described comprising a of a block copolymer having an overall ionic charge and in which one of the blocks has pendant zwitterionic groups and a biologically active compound having a charge opposite that of the polymer. The polymer is preferably a linear diablock copolymer, preferably having a low polydispersity, such as a (tertiary amine group containing monomer) block-(zwitterionic monomer) copolymer. Suitable cationic monomers are dialkyl aminoalkyl(alk)acrylates and -acrylamides and suitable zwitterionic monomers are phosphorylcholine group containing acrylate monomers such as 2-methacyloyloxyetyl-21-trimethyl ammonium ethyl phosphate liner salt. The biologically active compound is generally polyionic and is for instance a nucleic acid, such as DNA, especially plasmid DNA.

Abstract: IL-28A, IL-28B, IL-29, and certain mutants thereof have been shown to have antiviral activity on a spectrum of viral species. Of particular interest is the antiviral activity demonstrated on viruses that infect liver, such as hepatitis B virus and hepatitis C virus. In addition, IL-28A, IL-28B, IL-29, and mutants thereof do not exhibit some of the antiproliferative activity on hematopoietic cells that is observed with interferon treatment. Without the immunosuppressive effects accompanying interferon treatment, IL-28A, IL-28B, and IL-29 will be useful in treating immunocompromised patients for viral infections.

Abstract: The invention provides biodegradable polymeric hydrogel matrices having excellent durability and swellability. The matrices are formed from a combination of poly-?(1?4)glucopyranose macromer and a biocompatible biostable hydrophilic macromer. The matrices can be used in association with a medical device or alone. In some methods the polymeric matrix is placed or formed at a target site in which the matrix swells and occludes the target area, and is able to be degraded at the target site after period of time.

Abstract: A polymer having a number average molecular weight (Mn) of about 10 000 g/mol comprising a monomeric rigid moiety R and a monomeric flexible moiety F, wherein R comprises a main-chain polycyclic core and F has a main chain comprising a number of atoms sufficient for the transition temperature of the polymer to be lower than the degradation temperature of the polymer is provided. A method of manufacturing of same is also provided. Biomedical devices, scaffolds and supports for tissue engineering, delivery devices, textiles, moulds, vehicle parts, tubes, active disassembly devices, microactuators, toys and inflatable membranes comprising same are also described.

Abstract: The present invention relates to conjugates of small-interfering nucleic acids (siNA). Compositions of siNA suited for administration to a patient are described. Methods for delivering the compositions are also described.

Abstract: Compositions of dendrimer-photosensitizer complexes including therapeutic molecules, and methods for their synthesis and use are disclosed. The therapeutic molecules and the photosensitizers are each covalently attached to the dendrimer at its end-groups, essentially randomly. Upon exposure to radiation of a suitable wavelength, the photosensitizers are activated to break up the dendrimer structure and thus release the therapeutic molecules. In a preferred embodiment, the end-groups of the dendrimer are replaced with or covalently connected to therapeutic molecules and photosensitizers. In a further preferred embodiment, targeting molecules may also be attached to the dendrimer to create a more accurate treatment.

Abstract: Compositions, methods and kits to be used as a lubricant and for treatment of a cavity pathology including joint pathology are provided. The composition comprises therapeutically effective amounts of at least one bioactive agent, such as magnesium compound, at least one lubricating agent, such as hyaluronic acid, and at least one cell membrane repairing agent, such as polyethylene glycol. The components of these compositions may be administered by a direct application, an application through a cannula, an intra-articular injection, as a flush fluid during an arthroscopy of the affected area, as a post-arthroscopy injection, or as part of a lavage of the area affected by the intra-articular pathology. In addition, the composition of the present invention may be administered to the patient from a pump or a depot.

Abstract: The present invention relates, in general, to materials and methods for the preparation of modified blood factors which have low levels of water soluble polymer molecules conjugated to the blood factor but exhibit biological activity similar to or better than molecules having a higher number of water soluble polymer moieties.

Abstract: Therapeutic particles contain metal ions and are characterized by the use of unique ligand sets capable of making the metal ion complex soluble in biological media to induce selective toxicity in diseased cells. The particles may comprise a polymeric base particle, at least one pharmaceutically active metal ion, including metal ions from more than one metal element, a ligand that is covalently attached to the polymeric base particle and attached to the metal ion via a stimuli-responsive bond, and a cell targeting component. When the metal ion-containing particle enters a pre-defined environment, the ligands binding the metal to the particle are broken, triggering release of the free metal ion while the original ligands remain covalently bound to the particle.

Abstract: Compositions comprising anti-fibrotic agent(s) and/or polymeric compositions can be used in various medical applications including the prevention of surgical adhesions, treatment of inflammatory arthritis, treatment of scars and keloids, the treatment of vascular disease, and the prevention of cartilage loss.

Abstract: This invention provides a method of inactivating non-enveloped virus particles. The method includes the step of contacting the virus with a virucidally-enhanced alcoholic composition that includes an alcohol, and an enhancer selected from the group consisting of cationic oligomers and polymers, proton donors, chaotropic agents, and mixtures thereof.

Abstract: The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutic when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands the polymers present methods for controlled delivery of the therapeutic agents. The invention also relates to methods of treating subjects with the therapeutic compositions described herein. The invention further relates to methods for conducting pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the polymeric compounds described herein.

Abstract: Provided herein are a method, which comprises implanting in a patient an implantable device comprising a coating that includes a PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid biocompatible polymer and the methods of use thereof.

Abstract: The present invention relates to conjugate comprising a carrier substituted with one or more occurrences of a moiety having the structure (I): wherein each occurrence of M is independently a modifier having a molecular weight ?10 kDa; denotes direct of indirect attachment of M to linker LM; and each occurrence of LM is independently an optionally substituted succinamide-containing linker, whereby the modifier M is directly or indirectly attached to the succinamide linker through an amide bond, and the carrier is linked directly or indirectly to each occurrence of the succinamide linker through an ester bond. In another aspect, the invention provides compositions comprising the conjugates, methods for their preparation, and methods of use thereof in the treatment of various disorder, including, but not limited to cancer.

Abstract: The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Abstract: The site-specific expression of selectins on endothelial cells of blood vessels during angiogenesis provides an opportunity to target anti-cancer drugs to the vascular endothelium to extend the range of the therapeutic effect. This invention describes an innovative drug targeting strategy for the selective delivery of the anticancer drugs to endothelial cells by means of polymer-drug conjugates modified with a carbohydrate ligand for the vascular selectins. A model chemotherapeutic drug, doxorubicin, and the E-selectin ligand, sLex, are attached to a biocompatible polymer (HPMA). The selective binding, cellular uptake, intracellular fate, and cell cytotoxicity of the polymer-bound drug are investigated in human endothelial cells.

Abstract: Novel compounds of the general formula (I): in which X represents a polymer; Q represents a linking group; W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety; each of R1 and R2 independently represents a hydrogen atom or a C1-4alkyl group; and either Z1 represents a protein or a peptide linked to CR2 via a nucleophilic moiety, and Z2 represents a molecule linked to CR2 via a nucleophilic moiety, or Z1 and Z2 together represent a single group derived from a protein or peptide linked to CR via two nucleophilic moieties.

Abstract: The present invention describes compositions and methods for trapping/capturing and/or destroying dangerous substances such as chemical and biological warfare agents. The present invention relates to dendritic polymers, specifically, to quaternary ammonium functionalized dendritic polymers and N-Halamine functionalized dendritic polymers. Such dendrimers are useful for the capture and neutralization of biological and chemical warfare agents.

Abstract: The invention provides methods for making copolymers and multi-arm block copolymers useful as drug delivery vehicles. The multi-arm block copolymers comprise a central core molecule, such as a residue of a polyol, and at least three copolymer arms covalently attached to the central core molecule, each copolymer arm comprising an inner hydrophobic polymer segment covalently attached to the central core molecule and an outer hydrophilic polymer segment covalently attached to the hydrophobic polymer segment, wherein the central core molecule and the hydrophobic polymer segment define a hydrophobic core region. The solubility of hydrophobic biologically active agents can be improved by entrapment within the hydrophobic core region of the block copolymer. The invention further includes pharmaceutical compositions including such block copolymers, pharmaceutical compositions, and methods of using the block copolymers as drug delivery vehicles.

Abstract: Methods for preparing water soluble, non-peptidic polymers carrying carboxyl functional groups, particularly carboxylic acid functionalized poly(ethylene glycol) (PEG) polymers are disclosed, as are the products of these methods. In general, an ester reagent R(C?0)OR?, wherein R? is a tertiary group and R comprises a functional group X, is reacted with a water soluble, non-peptidic polymer POLY-Y, where Y is a functional group which reacts with X to form a covalent bond, to form a tertiary ester of the polymer, which is then treated with a strong base in aqueous solution, to form a carboxylate salt of the polymer. Typically, this carboxylate salt is then treated with an inorganic acid in aqueous solution, to convert the carboxylate salt to a carboxylic acid, thereby forming a carboxylic acid functionalized polymer.

Abstract: A novel multi-arm polyethylene glycol (PEG) (I) and preparation method thereof. Active derivatives (II) based on the multi-arm PEG. Gels formed of the active derivatives. Drug conjugates formed of the active derivatives and drug molecules and uses thereof in medical preparation. The multi-arm PEG is formed by polymerizing ethylene oxide with pentaerythritol oligomers as initiator, wherein PEG is the same or different and is a —(CH2CH2O)m-, the average value of m is an integer of 3-1000, l is an integer more than or equal to 2. An 8-arm PEG is preferred, wherein l is equal to 3. The active derivatives (II) comprise link groups X attached to PEG and active end groups F attached to X.

Abstract: Conjugates of a polymer having attached thereto an angiogenesis targeting moiety and a therapeutically active agent such as an anti-cancer agent or anti-angiogenesis agent, and processes of preparing same are disclosed. Pharmaceutical compositions containing these conjugates and uses thereof in the treatment of angiogenesis-related medical conditions such as cancer and cancer metastases are also disclosed.

Abstract: The present invention relates to conjugates of biologically active compounds, preferably therapeutically active compounds, with polymeric moieties having low polydispersity, as well as controlled polymerisation processes for producing the conjugates. An initiation for a controlled radical polymerisation process comprises a biologically active, usually therapeutically active, moiety and the monomer includes zwitterionic monomer for instance 2-methacryloyloxyethyl -2?-trimethylammonium ethyl phosphate inner salt. The process allows close control of the molecular weight and polydispersity of the polymeric moiety and the possibility of optimizing the delivery characteristics of the active agent.

Abstract: The present invention is directed a method comprising administering a composition to an individual, wherein the composition comprises a plurality of conjugates, each conjugate in the plurality a protein derivatized with a water-soluble polymer, wherein the polymer is coupled to the protein via succinimide groups covalently attached to either cysteine sulfhydryl groups or lysine amino groups, and substantially all of the succinimide groups present in the composition are present in a ring-opened form.

Abstract: Provided is a thermosensitive composition preventing tissue adhesion and a method for preparing the same, and, more particularly, a thermosensitive composition preventing tissue adhesion which further contains a drug selectively inhibiting inflammatory response and a method for preparing the composition, in which the composition is produced through a chemical reaction by adding a cross-linking agent to an aqueous solution which contains a block copolymer containing a polyethyleneoxide block having the ability to suppress tissue adhesion, and a polymer with 10,000 to 1,000,000 g/mol of molecular weight which can be mixed with the copolymer; the composition is characterized in that the difference of viscosity, absorbance of visible rays region, and stability between the upper and lower liquid layers are within 10% when centrifuging the composition; and also the method for preparing the composition enhances cross-linking homogenization and viscosity stability through simultaneous spraying and stirring methods wi

Abstract: Provided are crosslinked polymer compositions that include a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer, which contains or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further include other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents.

Abstract: A polymeric material, methods of making the polymeric material, articles that include the polymeric material, and compositions that contain the polymeric material are provided. The polymeric material has a plurality of different pendant groups that include a first pendant group containing a —COOH group or a salt thereof, a second pendant group containing a poly(alkylene oxide) group, a third pendant group containing a silicon-containing group, and a fourth pendant group containing a quaternary amino group. The polymeric material can be used, for example, to provide coatings that can be antifouling, antimicrobial, or both.

Abstract: Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric Nanoparticle form of thyroid hormone agonist, partial agonist or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

Abstract: Methods for delivering a biologically active agent into the body of a mammal are provided, the method comprising administering a carbamate-containing conjugate to the mammal.

Abstract: The invention relates to a coating composition comprising an antimicrobial hydrophilic copolymer consisting of a macromer and a comonomer, the use of said coating composition in medical applications and, in particular in a medical device and to a medical device comprising the coating composition, preferably selected from catheters, endoscopes, laryngoscopes, tubes for feeding or drainage or endotracheal use or oesophageal use. The coating composition can further comprise a hydrophilic polymer, a polyelectrolyte and a photo-initiator.

Abstract: The present disclosure provides novel functional polyoxazoline derivatives prepared by terminating polyoxazoline polymerization with inert chemical groups. In addition, the present disclosure demonstrates the synthesis of novel electrophilic initiators with protected functional groups capable of initiating oxazoline polymerization and capable of surviving the conditions of polymerization. These initiators are used to synthesize the above inert-terminal polyoxazoline derivatives as well as other poly-oxazolines with active terminal groups. Furthermore, the present disclosure provides for polyoxazoline-lipid conjugates and liposomal compositions prepared using such polyoxazoline-lipid conjugates. Methods of using the foregoing to prepare conjugates with target molecules are also disclosed.

Abstract: The present invention provides a polymer-metal complex composite, which comprises a block copolymer capable of serving as a constituent member of a polymeric micelle and a metal complex having MRI contrast ability, accumulates in a tumor-specific manner, achieves high image contrast even in a small amount, and has reduced side effects and a long retention time in blood. The polymer-metal complex composite of the present invention comprises a block copolymer (A) represented by general formula (a) and a metal complex (B) having MRI contrast ability, wherein the composite comprises a structure in which a carboxyl anion of poly(carbo) in the copolymer (A) is attached to the metal complex (B) via a metal atom (M).

Abstract: Compositions and methods for tissue repair are provided including cell binding peptides and growth factor binding peptides. The cell binding peptides bind to one or more of stem cells, fibroblasts, or endothelial cells. The growth factor binding peptides include platelet derived growth factor (PDGF) binding peptides and growth differentiation factor (GDF) binding peptides. The tissue for repair includes tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, or dermis. Implantable devices for tissue repair are provided to which the cell and growth factor binding peptides are attached, such as acellular extracellular matrix having attached binding peptide.

Abstract: Compositions and methods for tissue repair are provided including cell binding peptides and growth factor binding peptides. The cell binding peptides bind to one or more of stem cells, fibroblasts, or endothelial cells. The growth factor binding peptides include platelet derived growth factor (PDGF) binding peptides and growth differentiation factor (GDF) binding peptides. The tissue for repair includes tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, or dermis. Implantable devices for tissue repair are provided to which the cell and growth factor binding peptides are attached, such as acellular extracellular matrix having attached binding peptide.

Abstract: The invention relates to a static copolymer of linear polyethylenimine that comprises two monomer units of the following formulas I and II, in which R1 is a hydrogen atom or a C1-C6 alkyl radical, R2 is a hydrogen atom, a C1-C6 alkyl, aryl or aralkyl group, wherein the alkyl group is a C1-C6 one, n is a number between 1 and 99% of the total monomers, m is a number between 1 and 99% of the total monomers, and advantageously m+n=100%. The invention also relates to complexes of this copolymer with a nucleic acid, and to the use thereof in in vivo, in vitro or ex vivo gene transfection.

Abstract: The invention provides nucleic acid therapeutics and methods for using these nucleic acid therapeutics in the treatment of complement-related disorders.

Abstract: The present inventors have developed a novel composition and method for inhibiting inflammation and treating of symptoms of tissue ischemia, including that associated with peripheral and cardiac vascular disease by local administration of a pharmaceutical composition including an effective amount of a poloxamer.

Abstract: The present invention relates to compositions and methods for treating and preventing skeletal muscle deficiencies. In particular, the present invention provides compositions comprising poloxamers (e.g., poloxamer 188-P188) and methods of using the same for treating and preventing skeletal muscle deficiencies and injuries (e.g., dystrophin-deficient skeletal muscle; skeletal muscle having a contraction force deficit; skeletal muscle having a Ca2+ imbalance; skeletal muscle having microtears).

Abstract: Provided are crosslinked polymer compositions that include a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (—NH2) or thiol (—SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer, which contains or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further include other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents.

Abstract: Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.

Abstract: The present disclosure provides copolymers of 2-substituted-2-oxazolines possessing two or three reactive functional groups which are also chemically orthogonal. The copolymers described may be random copolymers, block copolymers or a mixture of random and block copolymer configurations. Furthermore, the present disclosure provides novel methods for synthesizing the above polymers and for conjugating to molecules such as targeting, diagnostic and therapeutic agents.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.

Abstract: The present invention provides a combination product which comprises: (1) a polyaldehyde obtained by introducing an aldehyde group into a branched glucose in a ?-1,3-glucan, and (2) a polyamine obtained by increasing the molecular weight of a poly-L-lysine. The combination product according to the present invention is useful as a material for a tissue adhesive hydrogel which can be used as a hemostatic agent or the like which exhibits low risks for viral infections and the like, high biodegradability and biocompatibility, excellent safety, a good adhesion rate and a good adhesion strength.

Abstract: A method for treatment of a disease caused by aggregation of misfolded proteins including subjecting a body fluid of a patient to a separation of an aggregated misfolded protein which includes contacting both the misfolded and normal protein with a conjugated polyelectrolyte (CPE) and separating the CPE/protein complex from the other constituents of the sample.

Abstract: A method for separation of an aggregated misfolded protein from an environment including a non-aggregating normal form of the protein includes contacting both the misfolded and normal protein with a conjugated polyelectrolyte (CPE) and separating the CPE/protein complex from the other constituents of the sample.