Abstract: The disubstituted piperazine analogs (DPAs) derivative compound and DPAs amine complex compound disclosed in the present aspects have characterized by presented pharmaceutics having functions to improve lipolysis, such as inhibiting obesity hyperlipidemia, and atherosclerosis.

Abstract: A biocompatible tissue-bonding adhesive composition comprising a polyol of functionality N. The polyol being terminated has at least one polyisocyanate in solution with at least (N?1)% of the solution comprising free polyisocyanate. N may be in the range 1.5-8. The polyol may be a branched polypropylene/polyethylene oxide copolymer.

Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising an exendin linker conjugate D-L, wherein D represents an exendin moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I), wherein the dashed line indicates the attachment to one of the amino groups of the exendin moiety by forming an amide bond. The invention further relates to pharmaceutical compositions comprising said prodrugs as well as their use as a medicament for treating or preventing diseases or disorders which can be treated by exendin.

Abstract: The invention described herein provides a mixture comprising polymer molecules or salts thereof, wherein a polymer molecule in the mixture comprises covalently bound subunits L, K, and M wherein the average molecular weight of the polymer molecules in the mixture is about 50 kDa to about 200 kDa, wherein the mole percentage of subunit M, K and L, relative to the total amount of subunits in the mixture, is about 90.5 to about 96 mol %, about 2.8 to about 7.3 mol %, and about 1.2 to about 2.2 mol %, respectively.

Abstract: A camptothecin/polymer dual phase drug release system is described that is stable in both liquid and lyophilized states. The polymer contains acetals and/or ketals.

Abstract: A biological coating material that includes a polymerizable polyacrylate monomer; a volatile liquid; a polymer selected from a synthetic rubber, a natural rubber, and a thermoplastic elastomer. The biological liquid coating material forms a coating or bandage in the form of a film that when applied and adhered to a surface or to the skin of a user inhibits the application surface from adhering to another surface.

Abstract: Nanocells allow the sequential delivery of two different therapeutic agents with different modes of action or different pharmacokinetics. A nanocell is formed by encapsulating a nanocore with a first agent inside a lipid vesicle containing a second agent. The agent in the outer lipid compartment is released first and may exert its effect before the agent in the nanocore is released. The nanocell delivery system may be formulated in pharmaceutical composition for delivery to patients suffering from diseases such as cancer, inflammatory diseases such as asthma, autoimmune diseases such as rheumatoid arthritis, infectious diseases, and neurological diseases such as epilepsy. In treating cancer, a traditional antineoplastic agent is contained in the outer lipid vesicle of the nanocell, and an antiangiogenic agent is loaded into the nanocore. This arrangement allows the antineoplastic agent to be released first and delivered to the tumor before the tumor's blood supply is cut off by the antianiogenic agent.

Abstract: The present invention relates to novel particles comprising polyelectrolyte polymers which are transporters of active principle (AP), in particular protein and peptide active principle, and to novel modified-release pharmaceutical formulations comprising said AP microparticles. These novel particles loaded with AP release the AP over a prolonged period of time of several days, or even several weeks.

Abstract: A biocompatible controlled release form of complexed iodine is achieved by a complexation of polyvinyl alcohol based foam and characterized by a residual starch component to optimize iodine release profiles. The resulting iodine complexed polyvinyl alcohol foam may be utilized locally as an antimicrobial agent that releases controlled amounts of iodine sufficient to kill microbes for extended durations without excessive bulk and rigidity.

Abstract: Nanocells allow the sequential delivery of two different therapeutic agents with different modes of action or different pharmacokinetics. A nanocell is formed by encapsulating a nanocore with a first agent inside a lipid vesicle containing a second agent. The agent in the outer lipid compartment is released first and may exert its effect before the agent in the nanocore is released. The nanocell delivery system may be formulated in pharmaceutical composition for delivery to patients suffering from diseases such as cancer, inflammatory diseases such as asthma, autoimmune diseases such as rheumatoid arthritis, infectious diseases, and neurological diseases such as epilepsy. In treating cancer, a traditional antineoplastic agent is contained in the outer lipid vesicle of the nanocell, and an antiangiogenic agent is loaded into the nanocore. This arrangement allows the antineoplastic agent to be released first and delivered to the tumor before the tumor's blood supply is cut off by the antiangiogenic agent.

Abstract: This invention discloses ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a plurality of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, or disrupt, simultaneously and independently, the functional domain of a different disease causing protein.

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: To achieve, an in vivo repair of injured mammalian nerve tissue, an effective amount of a biomembrane fusion agent is administered to the injured nerve tissue. The application of the biomembrane fusion agent may be performed by directly contacting the agent with the nerve tissue at the site of the injury. Alternatively, the biomembrane fusion agent is delivered to the site of the injury through the blood supply after administration of the biomembrane fusion agent to the patient. The administration is preferably by parenteral administration including intravascular, intramuscular, subcutaneous, or intraperitoneal injection of an effective quantity of the biomembrane fusion agent so that an effective amount is delivered to the site of the nerve tissue injury.

Abstract: The present invention relates to biodegradable polymers (e.g., polyesters and polyester amides) derived from functionalized biologically active compounds that can provide site specific delivery of bioactive compounds upon biodegradation in a controlled manner.

Abstract: The invention provides peptides that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of peptide not attached to the water-soluble oligomer.

Abstract: Disclosed herein are polymer/fullerene nanoparticles that have selective uptake into cancer cells, and which, upon being taken into the cancer cells induce apoptosis. Induction of apoptosis can be controlled by activation of the nanoparticles. Activation can occur such as by photoactivation, or other means.

Abstract: Biodegradable triblock copolymer compositions are provided which are useful in tissue engineering and drug delivery. The copolymers are reverse thermal gels in that when heated from a lower temperature to a higher temperature, they gel. These gels are useful in drug delivery when complexed with an active agent. For example the compositions can be used for intraocular injection of active agents, such as anti-angiogenic agents for treatment of a maculopathy or retinitis.

Abstract: The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

Abstract: The invention relates to graftable polymers comprising biologically active agents and the use of such polymers in the manufacture of shaped articles, such as implantable medical devices and catheters. The graftable polymers are covalently grafted to a surface via one or more grafting moieties incorporated into the pharmaceutically-active graftable polymer. The coated articles of the invention can further comprise tie-coats, and the ratio of polymer:tie coat can be used to adjust the rate of drug elution.

Abstract: A method is provided for preparing water-soluble polymer derivatives bearing a terminal carboxylic acid or ester thereof. The method involves the hydrolyzing an ortho ester of a water-soluble polymer so as provide the corresponding acid. In addition, the invention provides water-soluble polymers bearing a terminal carboxylic acid or ester thereof, intermediates and reagents useful in carrying out the method, as well as gels, pharmaceutical formulations, conjugates related to the described water-soluble polymer derivatives.

Abstract: The present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a conjugate having a degradable linkage. The conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods for delivering such compositions are also provided.

Abstract: A pharmaceutical composition or combination drug, which contains, as active ingredients, (a) a coordination compound composed of a block copolymer represented by the following formula I or formula II and cisplatin, and (b) gemcitabine hydrochloride. In the formulae I and II, R1, A, R2, R3, m and n are as defined in the description.

Abstract: A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight?5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

Abstract: Amide compounds, amide polymers, compositions including amide compounds and amide polymers may be used to bind target ions, such as phosphorous-containing compounds in the gastrointestinal tract of animals. In some cases, amide compounds and amide polymers may include a core derived from an amide polyol and an organic polyacid or ester.

Abstract: A biobeneficial coating composition for coating an implantable device, such as a drug eluting stent, a method of coating the device with the composition, and an implantable device coated with the composition are provided.

Abstract: Provided herein are water-soluble polymer conjugates and polymer-based compositions of antimicrobial agents. Also provided are methods for synthesizing and administering such conjugates and compositions.

Abstract: A co-polyester which includes the reaction product of a polycondensation polyester and epsilon-caprolactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof and a diol. The co-polyester is injectable and absorbable into animal, such as human, tissue and can be used for facial cosmetic or reconstructive surgery of soft tissue. Another embodiment is directed to a method for preventing adhesion using a co-polyester comprising the reaction product of a polycondensation polyester and epsilon-caprolactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof and a diol, and the co-polyester comprises about 40 to 50% by weight of the polycondensation polyester based on the total weight of the co-polyester.

Abstract: This invention deals with a carboxyl-bearing, amphiphilic, solid copolyester stent coating composition for multifaceted prevention of vascular restenosis through a plurality of physicopharmacological modes. The composition includes one or more bioactive compounds and a copolymerization product of polyalkylene glycol, end-grafted with one or more cyclic monomer and treated further to introduce carboxyl-bearing end- or side-groups. The invention also deals with bioactive agents in an ionically conjugated form. The present coating may be applied to a metallic or an absorbable polymeric stent for use in preventing vascular restenosis.

Abstract: The invention relates to the use of Polycefin-LLL nanoconjugate as a means of cytoplasmic delivery of drugs. In one embodiment, the present invention provides a drug delivery molecule, comprising a polymerized carboxylic acid molecular scaffold covalently linked to L-leucylleucylleucine. In another embodiment, the Polycefin-LLL includes drug antisense morpholino oligos, targeting antibodies, and a pH-sensitive endosome escape unit. In addition, the drug could be siRNA, microRNA, and aptamer.

Abstract: The present disclosure provides a polymer comprising a derivative of chitosan, wherein the derivative is zwitterionic, as well as methods of using the polymer. In addition, the present disclosure provides a nanoparticle structure comprising a derivative of chitosan and a dendrimer, as well as methods of utilizing the nanoparticle structure.

Abstract: Cationic polymers hydrolyzable to zwitterionic polymers, monomers for making the cationic polymers, surfaces that include the polymers, therapeutic agent delivery systems that include the cationic polymers, methods for administering a therapeutic agent using the delivery systems, and methods for making and using the cationic polymers, monomers, surfaces, and therapeutic agent delivery systems.

Abstract: The invention provides compositions comprising a polyamidoamine (PAA) polymer comprising a pendant disulphide, sulphydryl, or activated sulphydryl moiety, and methods for their manufacture. The invention extends to the use of such polyamidoamine polymers to form cross-linked compositions, and hydrogels comprising the same, and the use of such compositions in various biological and non-biological applications, such as the delivery of biomolecules to target sites, and for tracking fluid flows. The invention also provides carrier particles, which may be used to deliver biomolecules, and to methods of treatment. The invention also provides a fluid tracking system for monitoring fluid flow.

Abstract: A novel process of manufacturing sevelamer carbonate from a polyallylamine carbonate or bicarbonate chloride salt. Process for manufacture of carbonate and/or bicarbonate salts of water insoluble polymers containing amino groups that are useful as anion binders in the gastrointestinal (GI) system. The process arranges the polyallylamine chain in a solution in such a way that the cross-linking reaction with epichlorohydrin can be controlled at a desired reaction rate.

Abstract: PEG and related polymer derivatives having weak, hydrolytically unstable linkages near the reactive end of the polymer are provided for conjugation to drugs, including proteins, enzymes, small molecules, and others. These derivatives provide a sufficient circulation period for a drug-PEG conjugate, followed by hydrolytic breakdown of the conjugate and release of the bound molecule. In some cases, drugs that demonstrate reduced activity when permanently coupled to PEG maintain a therapeutically suitable activity when coupled to a degradable PEG in accordance with the invention. The PEG derivatives of the invention can be used to impart improved water solubility, increased size, a slower rate of kidney clearance, and reduced immunogenicity to a conjugate formed by attachment thereto. Controlled hydrolytic release of the bound molecule into an aqueous environment can then enhance the drug's delivery profile by providing a delivery system which employs such polymers and utilizes the teachings provided herein.

Abstract: A nanoassembly includes a core protected by a biocompatible shell. The nanoassembly includes a plurality of block copolymers including drug-binding linkers and block copolymer cross-linkers. A first active agent is covalently conjugated to the plurality of block copolymers and a second active agent is physically entrapped in the core.

Abstract: Methods for making formulations of drugs and crystalline side chain polymers which formulations provide controlled and/or sustained release drug formulations.

Abstract: A composite material containing polymeric nanofibers, themselves containing NO-donor molecules, imbibed with an elastomer matrix is permeable to both water and gas so that dissociation reactions in the presence of water releases NO gas in a sustained manner. The NO-donor nanofibers may be formed by synthesizing acceptable NO-donor molecules, blending such molecules in solution with PVP, PCL or PVAc, electrospinning the blend at relatively high voltage for form fiber mats, applying PDMS rubber to the fiber mat and crosslinking it. The resulting NO-releasing electrospun fiber composite may be used in medical devices such as catheters, stents, or vascular grafts, with the purpose of releasing nitric oxide within a controlled rate and for a sustained period of time, as well as other known medical applications for NO.

Abstract: The invention relates to an amphiphilic-BMP polymer complex which is physically and chemically stable and soluble in water, characterized in that: the amphiphilic polymers comprise a hydrophilic polysaccharide skeleton functionalized with hydrophobic substituents and hydrophilic groups the BMP is selected from the group of therapeutically active BMPs (Bone morphogenetic Proteins), the polymer/BMP mass ratio is lower than or equal to 700. The invention also relates to the process for preparing the amphiphilic-BMP polymer complex in an aqueous medium and in the absence of organic solvents likely to denature the protein. The invention also relates to therapeutic compositions of an amphiphilic-BMP polymer complex according to the invention.

Abstract: Compositions and methods for the treatment of inflammation are provided.

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: 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: Coatings for implantable medical devices comprising non-fouling moieties or polymers chemically bonded to the surface of the device via chelating structures, and methods of fabricating the coatings are disclosed.

Abstract: Provided are combinations, compositions and kits containing a hyaluronan degrading enzyme, such as a soluble hyaluronidase, for treatment of hyaluronan-associated conditions, diseases and disorders. In one example, the products include an additional agent or treatment. Such products can be used in methods for administering the products to treat the hyaluronan-associated diseases and conditions, for example, hyaluronan-associated cancers, for example, hyaluronan-rich tumors. The methods include administration of the hyaluronan degrading enzyme composition alone or in combination with other treatments. Also provided are methods and compositions for providing sustained treatment effects in hyaluronan-associated diseases and conditions.

Abstract: One aspect of the invention relates to a hydrogel comprising a polymer comprising a plurality of pendent hydroxyl groups, a crosslinker, and a sclerosing agent. Another aspect of the invention relates to a method for reducing lung volume in a patient comprising the steps of advancing into a region of a patient's lung via said patient's trachea a multi-lumen catheter lumen through a bronchoscope; and co-administering, through the multi-lumen catheter, a first mixture comprising a first amount of a polymer containing a plurality of pendent hydroxyl groups; a second mixture comprising a second amount of a crosslinker; and a third mixture comprising a third amount of a sclerosing agent; thereby forming a hydrogel in said region. In certain embodiments, the compositions and methods described herein are intended for use in the treatment of patients with emphysema of the lung.

Abstract: A drug delivery system for the treatment of liver cancer that is based on interventional injection of a temperature and pH-sensitive hydrogel is provided. The drug delivery system is composed of a block copolymer applicable to hepatic arterial catheterization and a therapeutic agent is loaded inside the drug delivery system, and the drug delivery system is in the sol state outside, and undergoes a phase transition into the gel state inside the hepatic artery, thereby delaying or blocking blood supply of the hepatic artery, and slowly releasing the therapeutic agent during the phase transition into the gel state inside the hepatic artery.

Abstract: The invention features a method for treating a subject diagnosed with, or at risk of developing, a bacterial infection by administering to the subject a combination of biologically active agents.

Abstract: Delivery compositions are provided that include two or more active agents, wherein at least one active agent is conjugated to a polymer. The delivery compositions allow for controlled release of multiple active agents, including active agents with varying solubility, charge, and/or molecular weight.

Abstract: Described herein are polymer-agent conjugates and particles, which can be used, for example, in the treatment of cancer. Also described herein are mixtures, compositions and dosage forms containing the particles, methods of using the particles (e.g., to treat a disorder), kits including the polymer-agent conjugates and particles, methods of making the polymer-agent conjugates and particles, methods of storing the particles and methods of analyzing the particles.

Abstract: A polynucleotide delivery vehicle comprising a modified polymer is provided herein, the modified polymer having the following formula: in which W1, W2, W3, W4, W5, W6, Z1, Z2, Z3, Z4, Z5, Z9, R1, R2, R3, R4, R5, n1, n2, n3, n4, n5, and n6 are defined herein. Also disclosed are methods of delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type and methods of reducing expression of a gene in a cell or a subject in need thereof with the modified polymer.

Abstract: The invention provides polymer conjugates of opioid antagonists comprising a polymer, such as poly(ethylene glycol), covalently attached to an opioid antagonist. The linkage between the polymer and the opioid antagonist is preferably hydrolytically stable. The invention also includes a method of treating one or more side effects associated with the use of opioid analgesics, such as constipation, nausea, or pruritus, by administering a polymer conjugate of the invention.