Targeting monomers and polymers having targeting blocks

Provided herein are monomers incorporating folate or other targeting agent, polymers prepared therefrom, polymers prepared therefrom having a therapeutic agent covalently coupled thereto, as well as micelles and therapeutic compositions thereof.

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 191-. (canceled)92. A composition comprising surface functionalized biodegradable particles comprising one or more encapsulated antigens or antigenic epitopes thereof , wherein the particles have a negative zeta potential of about −100 mV to about −30 mV , and wherein the antigen is associated with type-1 diabetes (T1D).93. The composition of claim 92 , wherein the particles are poly (lactic acid) (PLA) claim 92 , poly (glycolic acid) (PGA) claim 92 , or poly (lactic co-glycolic acid) (PLGA) particles.94. The composition of claim 92 , wherein the antigens are selected from the group consisting pancreatic beta-cell antigen claim 92 , insulin claim 92 , proinsulin claim 92 , islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) claim 92 , glutamic acid decarboxylase (GAD) claim 92 , zinc transporter 8 isoform a claim 92 , and protein tyrosine phosphatase receptor type N.95. The composition of claim 92 , wherein the antigens or antigenic epitopes are selected from the group consisting of SEQ ID: 1798 claim 92 , SEQ ID: 1987 claim 92 , SEQ ID: 4981 claim 92 , SEQ ID: 1971 claim 92 , SEQ ID: 2065 claim 92 , SEQ ID: 2240 claim 92 , SEQ ID: 2266 claim 92 , SEQ ID: 1839 claim 92 , SEQ ID: 1832 claim 92 , SEQ ID: 1841 claim 92 , SEQ ID: 1871 claim 92 , SEQ ID: 1994 claim 92 , SEQ ID: 2012 claim 92 , SEQ ID: 2070 claim 92 , SEQ ID: 2114 claim 92 , SEQ ID: 2249 claim 92 , SEQ ID: 1925 claim 92 , SEQ ID: 1961 claim 92 , SEQ ID: 2110 claim 92 , SEQ ID: 2421 claim 92 , SEQ ID NO: 2028 claim 92 , and SEQ ID NO: 2074.96. The composition of claim 95 , wherein the negative zeta potential of the particles is achieved by surface ...

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 124-. (canceled)25. A composition comprising particles having a negative surface charge and comprising one or more antigens or allergens conjugated to the surface of the particles or encapsulated within the particle , wherein the particles comprise polylactide-co-glycolide (PLGA) and a polyamino acid having a carboxyl group on the side chain , wherein the particles have a negative zeta potential ranging from about −100 mV to about −30 mV.26. The composition of claim 25 , wherein the polyamino acid having a carboxyl group on the side chain is poly(aspartic acid) or poly(glutamic acid).27. The composition of claim 26 , wherein the polyamino acid having a carboxyl group on the side chain is poly(gamma-glutamic acid) claim 26 , poly(L-glutamic acid) claim 26 , poly(D-glutamic acid) claim 26 , or poly(D claim 26 ,L-glutamic acid).28. The composition of claim 25 , wherein the particles are microparticles or nanoparticles.29. The composition of claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV claim 25 , or about −75 mV to −30 mV claim 25 , or about −50 mV to −30 mV claim 25 , or about −100 mV to −50 mV claim 25 , or about −75 mV to −50 mV claim 25 , or about −75 mV to −25 mV.30. The composition of claim 25 , wherein the particles have a zeta potential ranging from about −80 mV to −30 mV31. The composition of claim 25 , wherein the PLGA has a molecular weight of 1 claim 25 ,000 Da to 100 claim 25 ,000 Da.32. The composition of claim 31 , wherein the PLGA has a molecular weight of 12 claim 31 ,000 Da to 98 claim 31 ,000 Da.33. The composition of claim 32 , wherein the PLGA has a molecular weight of 12 claim 32 , ...

Acryloyloxyethylphosphorylcholine Containing Polymer Conjugates And Their Preparation

The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients. 140-. (canceled)42. The compound of wherein Q is methyl.43. The compound of wherein T is —CH—CH-phosphorylcholine.44. The compound of wherein m is about 100 to about 500.45. The compound of wherein m is about 500 to about 1000.46. The compound of wherein the polymer has 3 claim 41 , 4 claim 41 , 5 claim 41 , 6 claim 41 , 7 or 8 polymer arms.47. The compound of wherein the polymer has 3 arms.48. The compound of wherein the polymer has 6 arms.49. The compound of wherein the polymer has more than 8 arms.50. The compound of wherein the phosphorylcholine containing polymer is covalently bonded to at least an amino group claim 41 , a hydroxyl group claim 41 , a sulfhydryl group or a carboxyl group of the biologically active protein.51. The compound of wherein the biologically active protein is a human protein.52. The compound of wherein the human protein is obtained by heterologous gene expression in a cell selected from the group consisting of a bacterium claim 51 , a yeast cell claim 51 , a mammalian cell in culture claim 51 , an insect cell in culture claim 51 , a plant cell in culture claim 51 , an avian cell in culture claim 51 , a cell of a transgenic avian claim 51 , a cell of a transgenic mammal claim 51 , and a cell of a transgenic plant.53. The compound of wherein the biologically active protein is selected from the group consisting of a cytokine claim 41 , an enzyme claim 41 , an antibody and an antibody fragment.54. The compound of claim 41 , wherein the polymer portion of the compound is polydisperse.55. The compound of claim 54 , wherein the polymer portion has a polydispersity value in the range of about 1.4 to about 1.2.56. The compound of claim ...

SURFACES HAVING REDUCED NON-SPECIFIC BINDING AND ANTIGENICITY

Disclosed herein are compositions and methods for reducing the antigenicity of molecules. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone. 1. A surface having reduced antigenicity and non-specific binding comprising: a surface comprising a plurality of poly[oligo(ethylene glycol) methyl ether methacrylate (POEGMA) polymers comprising a poly(methyl methacrylate) backbone and a plurality of side chains covalently attached to the backbone , each side chain comprising 1 to 9 ethylene glycol monomers repeated in tandem and terminating with an alkoxy moeity.2. The surface of claim 1 , wherein the surface is not reactive with anti-PEG antibodies in a subject.3. The surface of claim 1 , wherein the surface does not bind proteins claim 1 , lipids claim 1 , or carbohydrates non-specifically.4. The surface of claim 1 , wherein the is non-antigenic and does not induce an immune response.5. The surface of claim 1 , wherein the side chain comprises 1 to 5 ethylene glycol monomers repeated in tandem.6. The surface of claim 1 , wherein the side chain comprises 1 to 3 ethylene glycol monomers repeated in tandem.7. The surface of claim 1 , wherein the side chain comprises 2 to 3 ethylene glycol monomers repeated in tandem.8. The surface of claim 1 , wherein the side chain comprises 2 ethylene glycol monomers repeated in tandem.9. The surface of claim 1 , wherein the side chain comprises 3 ethylene glycol monomers repeated in tandem.10. The surface of claim 1 , wherein the alkoxy is methoxy claim 1 , ethoxy claim 1 , or propoxy.11. The surface of claim 1 , wherein the alkoxy is methoxy.12. The surface of claim 1 , wherein the POEGMA comprises monomers of ethylene glycol methyl ether methacrylate (EG-1-OMe).13. The surface of claim 1 , wherein the ...

POLYMER-SUNITINIB CONJUGATES

The invention relates to (among other things) polymer-sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over sunitinib in unconjugated form. 1. A compound comprising a sunitinib residue covalently attached via a releasable linkage-containing spacer moiety to a water-soluble , non-peptidic polymer.6. The compound of any one of to , wherein the releasable linkage-containing spacer moiety includes a releasable linkage selected from the group consisting of thioether , carbamate , ester , carbonate , urea and enzyme-cleavable peptidic linkages.8. The compound of any one of to , wherein the water-soluble , non-peptidic polymer is a poly(alkylene oxide).9. The compound of claim 8 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).10. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer is linear.11. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer is branched.16. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has a molecular weight of less than 2000 Daltons.17. The compound of any one of to claim 8 , wherein water-soluble claim 8 , non-peptidic polymer has from about 1 to about 30 monomers.18. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has from about 1 to about 10 monomers.19. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has a molecular weight of from 2000 Daltons to about 150 claim 8 ,000 Daltons.20. The compound of any one of to claim 8 , wherein the water-soluble polymer claim 8 , non-peptidic polymer includes an alkoxy or hydroxy end-capping moiety.21. A composition comprising (i) a compound comprising a sunitinib residue covalently attached via a releasable linkage-containing spacer moiety to a water-soluble ...

MACROMOLECULAR CONJUGATES FOR VISUALIZATION AND SEPARATION OF PROTEINS AND CELLS

Macromolecular water-soluble conjugates based on synthetic copolymers to which at least one affinity tag, at least one imaging probe, and at least one targeting ligand are bound via covalent bonds. The macromolecular conjugate may be used in identification, visualization, quantification or isolation of proteins and/or cells. The targeting ligand may be attached to the synthetic copolymer via a flexible linker. 1: Synthetic macromolecular conjugate for selective interaction with proteins , characterized in that it contains a copolymer to which at least one affinity tag , at least one imaging probe and at least one targeting ligand are bound via covalent bonds.3: The macromolecular conjugate according to claim 1 , characterized in that the molecular weight of the conjugate is preferably in the range of 1000 to 500000 g/mol claim 1 , preferably in the range of 20000 to 150000 g/mol.4: The macromolecular conjugate according to claim 1 , characterized in that the targeting ligand is a moiety capable of selectively binding to the targeted protein or peptide sequence claim 1 , in particular the targeting ligand is selected from the group comprising an inhibitor or substrate of the targeted enzyme claim 1 , an agonist or antagonist of the targeted receptor claim 1 , a ligand of the targeted protein resin.5: The macromolecular conjugate according to claim 1 , characterized in that the targeting ligand may be attached to the synthetic copolymer via a flexible linker claim 1 , preferably via a flexible linker based on polyethylene glycol claim 1 , peptide claim 1 , preferably a peptide having a molecular weight from 100 to 5000 g/mol claim 1 , or nucleic acid claim 1 , preferably a nucleic acids comprising 1 to 40 nucleotides claim 1 , or oligosaccharide claim 1 , preferably an oligosaccharide containing 1 to 40 monosaccharides.6: The macromolecular conjugate according to claim 1 , characterized in that the affinity tag is selected from biotin claim 1 , His-tag claim 1 , FLAG ...

Protein-Polymer-Drug Conjugates

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L D -D, the protein based recognition-molecule being connected to the polymeric carrier by L P . Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L D and L P 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.

FORMULATION FOR PHOTODYNAMIC THERAPY

Photodynamic therapy of tumors such as bladder tumors includes photosensitizing with a photosensitizer that is a complex or a compound of hypericin and a polymeric complexing agent. The photosensitizer is formed from an alkali salt of hypericin and the polymeric complexing agent. The alkali salt of hypericin is a sodium salt or a potassium salt. The complexing agent is a polyethylene glycol or a poly-N-vinyl amide. 1. A formulation for photodynamic therapy , comprising:hypericin that is bonded or complexed to a polymeric complexing agent, wherein the hypericin is present as a salt.2. The formulation according to claim 1 , wherein the polymeric complexing agent is a polyethylene glycol or a poly-N-vinyl amide.3. The formulation according to claim 2 , wherein poly-N-vinyl amide is a polyvinylpyrrolidone (PVP) of various degrees of polymerization and cross-linking.4. The formulation according to claim 3 , wherein the polyvinylpyrrolidone is PVP k17 claim 3 , PVP k25 or PVP k30.5. The formulation according to claim 1 , wherein the hypericin salt is an alkali metal salt claim 1 , a potassium salt or a sodium salt.6. A formulation for photodynamic therapy claim 1 , comprising:a stable complex or a stable compound of a sodium or potassium salt of hypericin and a polymeric complexing agent selected from the group consisting of polethylene glycol and poly-N-vinyl amide, wherein the photosensitizer is obtained from a lyophilisate obtained from a solution of the sodium or potassium salt of hypericin, containing 0.0225 mg hypericin/g solution, the polymeric complexing agent and a buffer system comprising a phosphate buffer or a citric acid buffer.7. The formulation according to claim 6 , wherein the poly-N-vinyl amide is a polyvinylpyrrolidone (PVP) of various degrees of polymerization and cross-linking.8. The formulation according to claim 7 , wherein the polyvinylpyrrolidone is PVP k17 claim 7 , PVP k25 or PVP k30. The invention relates to a method for photodynamic therapy, a ...

METHOD FOR THE PRODUCTION OF A FORMULATION OF A HYPERICIN SALT

Photodynamic therapy of tumors such as bladder tumors includes photosensitizing with a photosensitizer that is a complex or a compound of hypericin and a polymeric complexing agent. The photosensitizer is formed from an alkali salt of hypericin and the polymeric complexing agent. The alkali salt of hypericin is a sodium salt or a potassium salt. The complexing agent is a polyethylene glycol or a poly-N-vinyl amide. 1. A method for the production of a formulation of a hypericin salt , comprising: 'adding sufficient of a buffer system comprising a phosphate buffer or a citric acid buffer to obtain a concentration of 0.0225 mg hypericin/g solution; and', 'bonding or complexing the hypericin salt to a polyethylene glycol, a poly-N-vinyl amide, or polyvinylpyrrolidone (PVP);'}lyophilizing the solution to obtain lyophilizate to yield 0.225 mg hypericin in each resulting obtained photosensitizer.2. The method according to claim 1 , wherein the complexing is performed in aqueous claim 1 , optionally buffered claim 1 , solution.3. The method according to claim 1 , wherein the formulation is prepared for intravenous claim 1 , intracavity claim 1 , inhalative claim 1 , oral claim 1 , intraperitoneal and topical administration claim 1 , in hydrophilic or hydrophobic vehicles claim 1 , or in the form of a solution claim 1 , a cream claim 1 , a gel claim 1 , an aerosol claim 1 , emulsions or as a patch.4. The method according to claim 2 , wherein the aqueous solution is decanted into injection flasks and freeze-dried.6. The method according to claim 5 , wherein the complexing is performed in aqueous claim 5 , optionally buffered claim 5 , solution.7. The method according to claim 5 , wherein the formulation is prepared for intravenous claim 5 , intracavity claim 5 , inhalative claim 5 , oral claim 5 , intraperitoneal and topical administration claim 5 , in hydrophilic or hydrophobic vehicles claim 5 , or in the form of a solution claim 5 , a cream claim 5 , a gel claim 5 , an ...

NANOSTRUCTURED ACTIVE INGREDIENT CARRIER SYSTEM

The invention relates to a nanostructured active ingredient carrier system, in particular for reducing cytotoxic properties owing to the use of sheath polymer and the transport resulting therefrom, for interactions with cell membranes during the transport of hydrophilic constituents and, in connection therewith, the generation of an early endosomal release of the interaction complex from the carrier system. The problem addressed by the present invention is that of specifying a nanostructured active ingredient carrier system which avoids the disadvantages of the prior art and in particular permits a reduction in cytotoxic properties owing to the use of a sheath polymer and the transport resulting therefrom. This problem is solved in that a nanostructured active ingredient carrier system is provided in the form of a particle consisting of a carrier sheath, wherein the carrier sheath comprises at least one or more hydrophobic sheath polymers, one or more charged complexing polymers and one or more hydrophilic active ingredients, wherein the complexing polymer interacts with the active ingredient. 1. A nanostructured active ingredient carrier system in the form of a particle containing a carrier shell , characterized in that the carrier shell comprises at least one or more hydrophobic shell polymers , one or more charged complexing polymers , and one or more hydrophilic active ingredients , wherein the complexing polymer interacts with the active ingredient.2. The nanostructured active ingredient carrier system according to claim 1 , characterized in that the interaction between the complexing polymer and the active ingredient is caused by one or more non-covalent interactions in the form of electrostatic bonds claim 1 , ionic bonds claim 1 , hydrogen bonds claim 1 , or van der Waals forces.3. The nanostructured active ingredient carrier system according to claim 1 , characterized in that the active ingredients belong to the following substance classes:nucleic acids in ...

SITE SPECIFIC CURCUMIN-POLYMER MOLECULAR COMPLEXES AND METHODS OF TREATING COLON DISEASES AND INFLAMMATION

Methods and materials relating to a medicament preparation comprising a curcuminoid component, such as curcumin, and a polymer component having a backbone comprising polymethacrylate or methyl methacrylate provided as a curcuminoid-polymer complex, which enhances the solubility, stability and bioavailability of the curcumin component and are useful for the treatment of various inflammatory diseases and conditions when delivered to the gastro-intestinal tract, including sepsis, mucositis, gastritis, infections, inflammatory bowel disease and cancers of GIT. The curcumin-polymer complex inhibiting the activation of TLR receptors and thereby reduce the release of inflammatory cytokines, such that the curcumin-polymer complexes are more potent than free curcumin in antagonizing on the activation of TLR4. 1. A method of inhibiting the stimulation of TLR receptors in a patient , the method comprising:providing a curcuminoid-polymer complex in a medicament, the curcuminoid-polymer 5 complex comprising at least one curcuminoid component selected from the group consisting essentially of curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydroxycurcumin, Bis-0-Demethyl curcumin (BDMC), or combinations thereof, at least one polymer or co-polymer component having a backbone comprising polymethacrylate or methyl methacrylate, and optionally a surfactant component; anddelivering the curcuminoid-polymer complex to a gastro-intestinal tract of said patient.2. The method of claim 1 , wherein the curcuminoid component comprises curcumin.3. The method of claim 2 , wherein the complex presents an aqueous solubility of the curcumin in an amount greater than about 1 μg/ml.4. The method of claim 3 , wherein the aqueous solubility is between about 1 μg/ml and about 100 mg/ml.5. The method of claim 1 , wherein the polymer or co-polymer component is chosen such that the aqueous solubility of the curcuminoid component is greater than about 1 μg/ml at a pH of 7.0 and above.6. The method ...

METHOD INVOLVING 1-BENZOTRIAZOLYL CARBONATE ESTERS OF POLY(ETHYLENE GLYCOL)

The invention provides for preparing a polymer-active agent conjugate, the method comprising the steps of reacting an amino acid derivative with a biologically active agent under conditions to form a polymer-active agent conjugate. 1. A method comprising:(i) reacting a water-soluble and non-peptidic polymer having two or more terminal hydroxyl groups with di(1-benzotriazolyl)carbonate to form a water-soluble and non-peptidic polymer having two or more 1-benzotriazolylcarbonate ester groups; and(ii) reacting the water-soluble and non-peptidic polymer having two or more 1-benzotriazolylcarbonate ester groups with a water-soluble and non-peptidic polymer having three or more primary amino groups under conditions effective to form a cross-linked polymer composition.2. The method of claim 1 , wherein the water-soluble and non-peptidic polymer within each of (a) the water-soluble and non-peptidic polymer having two or more terminal hydroxyl groups claim 1 , (b) the water-soluble and non-peptidic polymer having two or more 1-benzotriazolylcarbonate ester groups claim 1 , and (c) the water-soluble and non-peptidic polymer having three or more primary amino groups is independently selected from the group consisting of poly(alkylene glycol) claim 1 , poly(oxyethylated polyol) claim 1 , poly(olefinic alcohol) claim 1 , poly(vinylpyrrolidone) claim 1 , poly(hydroxypropylmethacrylamide) claim 1 , poly(α-hydroxy acid) claim 1 , poly(vinyl alcohol) claim 1 , polyphosphazene claim 1 , polyoxazoline claim 1 , poly(N-acryloylmorpholine) claim 1 , and copolymers claim 1 , terpolymers claim 1 , and mixtures thereof.3. The method of claim 1 , wherein the water-soluble and non-peptidic polymer within the water-soluble and non-peptidic polymer having three or more primary amino groups is selected from polyethylene glycol having a plurality of amino groups claim 1 , proteins claim 1 , aminocarbohydrates claim 1 , and poly(vinylamine).4. The method of claim 1 , wherein the water-soluble and ...

SARS-CoV-2 Subunit Vaccine and Microneedle Array Delivery System

A recombinant coronavirus vaccine is provided. Methods of making and delivering the coronavirus vaccine also are provided. A microneedle array is provided, along with methods of making and using the microneedle array. 1. A method of preventing infection with SARS-CoV-2 , vaccinating a patient for SARS-CoV-2 , or treating or reducing a symptom of a SARS-CoV-2 infection in a patient , comprising administering to the patient an amount of a composition , by a route of administration effective to induce an immune response to SARS-CoV-2 , wherein said composition comprises a polypeptide comprising an immunogenic amino acid sequence of a SARS-CoV-2 spike protein or a conservative derivative thereof able to elicit an immune response to a SARS-CoV-2 spike protein , and optionally an amino acid sequence not from SARS-CoV-2 , or a polypeptide having the sequence of SEQ ID NO: 2 , of amino acids 1-661 of SEQ ID NO: 2 , of a naturally-occurring variant thereof , or a derivative thereof having at least 95% sequence identity with amino acids 1-661 of SEQ ID NO: 2 , or with SEQ ID NO: 2 , and a pharmaceutically acceptable excipient.2. The method of claim 1 , wherein the composition is administered to the patient parenterally.3. The method of claim 1 , wherein the composition is administered to the patient by inhalation or intra-nasally.4. The method of claim 1 , wherein the composition is administered to or through the skin.5. The method of claim 1 , wherein the composition is administered to the patient more than once.6. A nucleic acid claim 1 , comprising a gene for expressing a polypeptide having the sequence of SEQ ID NO: 2 claim 1 , of amino acids 1-661 of SEQ ID NO: 2 claim 1 , of a naturally-occurring variant thereof claim 1 , or a derivative thereof having at least 95% sequence identity with amino acids 1-661 of SEQ ID NO: 2 claim 1 , or with SEQ ID NO: 2.7. The nucleic acid of claim 6 , encoding a recombinant viral vector comprising the gene.8. The nucleic acid of claim 6 ...

ZWITTERIONIC POLYMER BIOCONJUGATES AND RELATED METHODS

Zwitterionic polymer and mixed charge copolymer bioconjugates, methods for making and using the bioconjugates. 1. A mixed charge copolymer bioconjugate comprising one or more mixed charge copolymers covalently coupled to a biomolecule , wherein the mixed charge copolymer comprises a plurality of positively charged repeating units and a plurality of negatively charged repeating units , and wherein the mixed charge copolymer is substantially electronically neutral.3. The conjugate of claim 1 , wherein R-Rare independently selected from the group consisting of C1-C3 alkyl.4. The conjugate of claim 1 , wherein Lis selected from the group consisting of —C(═O)O—(CH)— and —C(═O)NH—(CH)— claim 1 , wherein n is 1-20.5. The conjugate of claim 1 , wherein Lis —(CH)— claim 1 , where n is an integer from 1-20.6. The conjugate of claim 1 , wherein the biomolecule is a protein claim 1 , a nucleic acid claim 1 , a carbohydrate claim 1 , a lipid claim 1 , a small molecule claim 1 , or a small molecule agent.7. A composition claim 1 , comprising the conjugate of and a pharmaceutically accepted carrier or diluent. This application is a division of U.S. application Ser. No. 14/526,846, filed Oct. 29, 2014 (now U.S. Pat. No. 10,130,716), which is a continuation of U.S. application Ser. No. 13/463,677, filed May 3, 2012 (now U.S. Pat. No. 8,877,172), which is a continuation of International Application No. PCT/US2010/055886, filed Nov. 8, 2010, which claims the benefit of U.S. Provisional Application No. 61/259,088, filed Nov. 6, 2009, each of which is expressly incorporated herein by reference in its entirety.This invention was made with Government support under Contract No. N000140910137 awarded by the Office of Naval Research and Contract No. DMR-0705907 awarded by the National Science Foundation. The Government has certain rights in the invention.The sequence listing associated with this application is provided in text format in lieu of a paper copy and is hereby incorporated by ...

TREATMENT FOR TUMORS DRIVEN BY METABOLIC DYSFUNCTION

The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating metabolically-driven diseases and disorders, such as certain cancers. 151.-. (canceled)53. The method of claim 52 , wherein the corresponding predetermined cutoff value for the HOMA score is the HOMA score of at least one lean subject54. The method of claim 52 , wherein the corresponding predetermined cutoff value for the HOMA score is a HOMA score that corresponds to a metabolically normal level.55. The method of claim 52 , wherein the corresponding predetermined cutoff value for BMI is a BMI that corresponds to at least one of overweightness claim 52 , obesity claim 52 , severe obesity claim 52 , morbid obesity or super obesity.56. The method of claim 52 , wherein the corresponding predetermined cutoff value for WHR is a WHR that corresponds to central obesity.57. The method of claim 56 , wherein the predetermined cutoff value is 0.85 if the subject is female or 0.9 if the subject is male.58. The method of claim 52 , further comprising administering to the subject at least one therapeutically effective amount of a second active agent.59. The method of claim 58 , wherein the second active agent comprises at least one kinase inhibitor.60. The method of claim 59 , wherein the at least one kinase inhibitor is a multi-kinase inhibitor; a serine/threonine kinase inhibitor; a tyrosine kinase inhibitor claim 59 , an MTOR inhibitor claim 59 , a PI3K inhibitor or any combination thereof.61. The method of claim 58 , wherein the second active agent comprises Fulvestrant.62. The method of claim 58 , wherein the at least one polymer conjugate claim 58 , or a pharmaceutically acceptable salt claim 58 , prodrug or analog thereof and the second active agent are administered sequentially or in a substantially simultaneous manner.63. The method of claim 62 , wherein the second active agent is administered at a time point after the ...

ANTIVIRAL CONJUGATES OF POLYANIONIC POLYMER AND ANTIVIRAL DRUG

A compound is provided, which comprise an anionic polymer carrier conjugated to an antiviral drug via a biodegradable linker. This compound is particularly useful as a broad-spectrum antiviral agent. 127-. (canceled)28. A compound comprising a polyanion carrier conjugated to an antiviral drug via a biodegradable linker , wherein the compound has antiviral activity by at least two modes of antiviral activities selected from: i) extracellular inhibition of virus cell entry due to the activity of polyanion carrier; ii) intracellular inhibition of the viral polymerases due to activity of the polyanion carrier; and iii) intracellular antiviral activity due to release of the antiviral drug from the carrier upon cell entry.291. The compound according to claim , wherein the biodegradable linker comprises a disulfide bond and a self-immolative spacer.301. The compound according to claim , wherein the linker is capable of releasing the antiviral drug via disulfide reshuffling in the presence of a thiol.311. The compound according to claim , wherein the antiviral drug is a broad-spectrum antiviral drug.321. The compound according to claim , wherein the antiviral drug is a nucleoside or ribonucleoside analogue.331. The compound according to claim , wherein said antiviral drug is a ribavirin , azdothymidine , lamivudine , favipiravir or a derivative thereof of any of the foregoing.341. The compound according to claim , wherein the polyanion carrier comprises monomers selected from the group consisting of: poly(acrylic acid) and poly(methacrylic) acid.351. The compound according to claim , for use in the treatment , amelioration or prevention of a retroviral infection.361. The compound according to claim , for use in the treatment , amelioration or prevention of one or more of influenza , HIV , hepatitis C virus , ebola , mumps , respiratory syncytial virus , dengue and measles.37. A compound comprising a polyanion carrier conjugated to an antiviral drug via a biodegradable ...

Acryloyloxyethylphosphorylcholine Containing Polymer Conjugates And Their Preparation

The present invention relates to polymeric reagents and conjugates thereof, methods for synthesizing the polymeric reagents and conjugates, pharmaceutical compositions comprising the conjugates and methods of using the polymer conjugates including therapeutic methods where conjugates are administered to patients. 140-. (canceled)42. The compound of wherein Q is methyl.43. The compound of wherein T is —CH—CH-phosphorylcholine.44. The compound of wherein m is about 100 to about 500.45. The compound of wherein m is about 500 to about 1000.46. The compound of wherein the polymer has 2 claim 41 , 3 claim 41 , 4 claim 41 , 5 claim 41 , 6 claim 41 , 7 or 8 polymer arms.47. The compound of wherein the polymer has 3 arms.48. The compound of wherein the polymer has 6 arms.49. The compound of wherein the polymer has more than 8 arms.50. The compound of wherein the phosphorylcholine containing polymer is covalently bonded to at least an amino group claim 41 , a hydroxyl group claim 41 , a sulfhydryl group or a carboxyl group of the biologically active protein.51. The compound of wherein the biologically active protein is a human protein.52. The compound of wherein the human protein is obtained by heterologous gene expression in a cell selected from the group consisting of a bacterium claim 51 , a yeast cell claim 51 , a mammalian cell in culture claim 51 , an insect cell in culture claim 51 , a plant cell in culture claim 51 , an avian cell in culture claim 51 , a cell of a transgenic avian claim 51 , a cell of a transgenic mammal claim 51 , and a cell of a transgenic plant.53. The compound of wherein the biologically active protein is selected from the group consisting of a cytokine claim 41 , an enzyme claim 41 , an antibody and an antibody fragment.54. The compound of claim 41 , wherein the polymer portion of the compound is polydisperse.55. The compound of claim 54 , wherein the polymer portion has a polydispersity value in the range of about 1.4 to about 1.2.56. The ...

POLYMERIC SYSTEMS AND USES THEREOF IN THERANOSTIC APPLICATIONS

Polymeric systems useful for theranostic applications are disclosed. The polymeric systems comprise a fluorescent or fluorogenic moiety and a therapeutically active agent, each attached to the same or different polymeric moiety. The polymeric systems are designed such that a fluorescent signal is generated in response to a chemical event, preferably upon contacting an analyte (e.g., an enzyme) that is over-expressed in a diseased tissue or organ. Probes useful for inclusion in such polymeric systems, processes of preparing such probes and the polymeric systems, and uses thereof in diagnostic and/or theranostic applications are also disclosed. 1. A polymeric system comprising a first polymeric moiety comprising a polymeric backbone composed of a plurality of backbone units and having attached to at least a portion of said backbone units a fluorogenic moiety , said fluorogenic moiety being attached to said backbone units via a first cleavable linking moiety such that upon cleavage of said linking moiety , a fluorescent signal is generated ,the system further comprising a therapeutically active agent, such that:(i) said fluorogenic moiety is attached to one portion of said backbone units and said therapeutically active agent is attached to another portion of said backbone units;(ii) said therapeutically active agent forms a part of said fluorogenic moiety;(iii) said therapeutically active agent is attached to said first cleavable linking moiety; or(iv) the system further comprises a second polymeric moiety comprising a second polymeric backbone composed of a plurality of backbone units and having attached to at least a portion of said backbone units a therapeutically active agent.2. The polymeric system of claim 1 , wherein upon said cleavage claim 1 , a fluorescent moiety is generated.3. The polymeric system of claim 2 , wherein said fluorescent moiety is or comprises a cyanine dye.4. The polymeric system of claim 1 , wherein said first cleavable linking moiety is a ...

Compositions Comprising Apoptotic Signaling and Methods for Induction of Antigen-Specific Tolerance

The present invention utilizes carrier particles to present antigen peptides and proteins to the immune system in such a way as to include antigen specific tolerance. The carrier particle is designed in order to trigger an immune tolerance effect. The invention is useful for treatment of immune related disorders such as autoimmune disease, transplant rejection and allergic reactions. 1. A composition for induction of antigen-specific tolerance comprising a carrier particle attached thereto an apoptotic signaling molecule and an antigenic peptide.2. The composition of claim 1 , wherein said composition induces antigen-specific tolerance in a subject.3. The composition of claim 1 , wherein the antigenic peptide is an autoimmune antigen claim 1 , a transplantation antigen or an allergen.4. The composition of claim 3 , wherein the antigenic peptide is myelin basic protein claim 3 , acetylcholine receptor claim 3 , endogenous antigen claim 3 , myelin oligodendrocyte glycoprotein claim 3 , pancreatic beta-cell antigen claim 3 , insulin claim 3 , glutamic acid decarboxylase (GAD) claim 3 , collagen type 11 claim 3 , human carticlage gp39 claim 3 , fp130-RAPS claim 3 , proteolipid protein claim 3 , fibrillarin claim 3 , small nucleolar protein claim 3 , thyroid stimulating factor receptor claim 3 , histones claim 3 , glycoprotein gp70 claim 3 , pyruvate dehydrogenase dehyrolipoamide acetyltransferase (PCD-E2) claim 3 , hair follicle antigen or human tropomyosin isoform 5.5. The composition of claim 1 , wherein the antigenic peptide is coupled to the carrier by a conjugate molecule.6. The composition of claim 5 , wherein the conjugate is ethylene carbodiimide (ECDI).7. The composition of claim 1 , wherein the apoptotic signaling molecule is annexin-1 claim 1 , annexin-5 claim 1 , phosphatidyl serine claim 1 , or milk fat globule-EGF-factor 8 (MFG-E8).8. The composition of claim 1 , wherein the apoptotic signaling molecule is Fas-ligand or TNF-alpha.9. The composition of ...

HYPOXIA-INDUCING CRYOGELS

The present disclosure relates to a hypoxia-inducing cryogel, comprising one or more polymer and one or more hypoxia-inducing agent. The present disclosure additionally relates to a hypoxia-inducing construct, comprising a cryogel and a support. Methods of reducing concentration of oxygen in a medium, comprising contacting the medium with a hypoxia-inducing cryogel (HIC) or a hypoxia-inducing construct are disclosed. Additionally, methods of inducing hypoxia in a cell, comprising contacting the cell with a medium, wherein the medium comprises a HIC or a hypoxia-inducing construct are disclosed. 1. A hypoxia-inducing cryogel , comprising one or more polymers; and one or more hypoxia-inducing agents.2. The cryogel of claim 1 , wherein the one or more polymers are biocompatible and/or hydrophilic.3. (canceled)4. The cryogel of claim 1 , wherein the one or more polymers are independently selected from the group consisting of a DNA strand claim 1 , a peptide claim 1 , a protein claim 1 , alginate claim 1 , hyaluronic acid claim 1 , chitosan claim 1 , heparin claim 1 , carboxymethyl cellulose claim 1 , cellulose claim 1 , carob gum claim 1 , hyaluronic acid glycidyl methacrylate (HAGM) claim 1 , methacrylated gelatin claim 1 , methacrylated alginate claim 1 , poly(ethylene glycol) (PEG) claim 1 , acrylate-PEG claim 1 , methacrylate-PEG claim 1 , PEG-co-poly(glycolic acid) claim 1 , PEG-co-poly(L-lactide) claim 1 , poly(2-hydroxyethyl methacrylate) (pHEMA) claim 1 , poly-2-hydroxyethylacrylate (polyHEA) claim 1 , polyacrylamide (PAAm) claim 1 , and poly(N-isopropylacrylamide) (PNIPAAm) claim 1 , and copolymers and combinations thereof.57.-. (canceled)8. The cryogel of claim 4 , wherein the peptide is selected from the group consisting of GRGDS claim 4 , GGGGRGDSP claim 4 , and GFOGER.9. The cryogel of claim 4 , wherein the peptide or the protein is covalently attached to at least one polymer of the one or more polymers.10. (canceled)11. The cryogel of claim 9 , wherein ...

FABRICATION OF MACROPOROUS POLYMERIC HYDROGEL MICROPARTICLES

A polymeric hydrogel microparticle that contains polyacrylamide and chitosan, the chitosan uniformly incorporated in a polyacrylamide matrix. The microparticle, having a coefficient variation of 0 to 2% and containing macropores with an average size of 1 to 60 nm, is capable of transporting biomolecules conjugated to it. Also disclosed are a method of fabricating such a micro-particle in a micromold via photo-induced radical polymerization and a one-pot method of conjugating biomolecules to polymeric hydrogel microparticles. 1. A polymeric hydrogel microparticle comprising polyacrylamide and chitosan , the chitosan uniformly incorporated in a polyacrylamide matrix , wherein the microparticle has a coefficient variation of 0 to 2% and contains macropores having an average size of 1 to 60 nm.2. The polymeric hydrogel microparticle of claim 1 , wherein the chitosan has an average molar mass of 4 claim 1 ,500-200 claim 1 ,000 Da.3. The polymeric hydrogel microparticle of claim 2 , wherein the chitosan contains primary amines each having a pKa value of 6.0-6.9.4. The polymeric hydrogel microparticle of claim 3 , wherein the microparticle has a total polymer content of 5 to 50 w/v %.5. The polymeric hydrogel microparticle of claim 3 , wherein the microparticle is capable of conjugating to a biomolecule that has a molecular weight greater than 120 claim 3 ,000 Da.6. The polymeric hydrogel microparticle of claim 5 , wherein the biomolecule has a molecular weight greater than 200 claim 5 ,000 Da.7. The polymeric hydrogel microparticle of claim 6 , wherein the biomolecule has a molecular weight of 240 claim 6 ,000 Da.8. The polymeric hydrogel microparticle of claim 1 , wherein the macropores have an average size greater than 11 nm.9. The polymeric hydrogel microparticle of claim 8 , wherein the microparticle is capable of conjugating to a biomolecule that has a molecular weight greater than 120 claim 8 ,000 Da.10. The polymeric hydrogel microparticle of claim 9 , wherein the ...

TREATMENT FOR TUMORS DRIVEN BY METABOLIC DYSFUCTION

The present disclosure relates to modified or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating metabolically-driven diseases and disorders, such as certain cancers. 151.-. (canceled)53. The method of claim 52 , wherein the second active agent comprises at least one kinase inhibitor.54. The method of claim 53 , wherein the at least one kinase inhibitor is a multi-kinase inhibitor; a serine/threonine kinase inhibitor claim 53 , a tyrosine kinase inhibitor claim 53 , an MTOR inhibitor claim 53 , a PI3K inhibitor claim 53 , an AKT inhibitor or any combination thereof.55. The method of claim 52 , wherein the second active agent comprises Fulvestrant56. The method of claim 52 , wherein the second active agent comprises a chemotherapeutic agent.57. The method of claim 52 , wherein the chemotherapeutic agent comprises an alkylating agent claim 52 , an antibiotic claim 52 , an anti-metabolite claim 52 , a detoxifying agent claim 52 , an interferon claim 52 , a polyclonal or monoclonal antibody claim 52 , an EGFR inhibitor claim 52 , an FGFR inhibitor claim 52 , a HER2 inhibitor claim 52 , a PI3K inhibitor claim 52 , an AKT inhibitor claim 52 , a histone deacetylase inhibitor claim 52 , a hormone claim 52 , a mitotic inhibitor claim 52 , an MTOR inhibitor claim 52 , a multi-kinase inhibitor claim 52 , a serine/threonine kinase inhibitor claim 52 , a tyrosine kinase inhibitor claim 52 , a VEGF/VEGFR inhibitor claim 52 , a taxane or taxane derivative claim 52 , an aromatase inhibitor claim 52 , an anthracycline claim 52 , a microtubule targeting drug claim 52 , a topoisomerase poison drug claim 52 , a cytidine analogue drug claim 52 , an anti-neoplastic agent claim 52 , an anti-proliferative agent claim 52 , eribulin or eribulin derivative or any combination thereof.58. The method of claim 52 , wherein the at least one polymer conjugate claim 52 , or a pharmaceutically acceptable salt claim 52 , prodrug or analog thereof claim 52 ...

POLYMERS AND POLYMERIC ASSEMBLIES FOR PEPTIDE AND PROTEIN ENCAOSULATION AND RELEASE, AND METHODS THEREOF

The invention provides polymers and polymeric nanogels that stably encapsulate peptides and proteins, which are controllably released upon degradable of the nano-structures in response to specific microenvironment, and compositions and methods of preparation and use thereof. 1. A crosslinked polymeric nanogel-protein conjugate adapted to stably transporting a protein across a cell membrane and then intracellularly releasing the protein with intact biological activity.2. The crosslinked polymeric nanogel-protein conjugate of claim 1 , wherein the protein is securely encapsulated inside an aggregate formed by the self-crosslinked polymeric nanogel.3. The crosslinked polymeric nanogel-protein conjugate of claim 1 , wherein the protein is securely conjugated on a surface of the nanoaggregate formed by the self-crosslinked polymeric nanogel.4. The crosslinked polymeric nanogel-protein conjugate of claim 2 , wherein the protein is encapsulated inside the nanoaggregate by one or more disulfide linkages.5. The crosslinked polymeric nanogel-protein conjugate of claim 3 , wherein the protein is conjugated to the surface of the nanoaggregate by one or more disulfide linkages.6. The crosslinked polymeric nanogel-protein conjugate of claim 1 , wherein the protein is a cytosolically active protein.7. The crosslinked polymeric nanogel-protein conjugate of claim 1 , wherein the protein is caspase.8. The crosslinked polymeric nanogel-protein conjugate of claim 1 , wherein the conjugate is further functionalized with a targeting ligand.9. The crosslinked polymeric nanogel-protein conjugate of claim 8 , wherein the targeting ligand is an antibody protein claim 8 , a peptide claim 8 , or a small molecule.10. The crosslinked polymeric nanogel-protein conjugate of claim 8 , wherein the targeting ligand is a peptide.11. The crosslinked polymeric nanogel-protein conjugate of claim 8 , wherein the conjugate is functionalized with a cell penetrating peptide.12. The crosslinked polymeric ...

COMPOSITIONS AND METHODS FOR INDUCING APOPTOSIS

In an aspect, the invention relates to compositions, method, and kits for inducing apoptosis. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 1. A method of inducing apoptosis , the method comprising:(i) contacting a population of cells with a first complex comprising a targeting moiety and a morpholino; and 'wherein the contacting of the cells with the first complex and the second complex induces apoptosis of the cells.', '(ii) contacting a population of cells with a second complex comprising a copolymer carrier and one or more morpholinos;'}2. The method of claim 1 , further comprising repeating step (i) and step (ii).3. The method of claim 1 , further comprising (iii) confirming apoptosis of the cells.4. The method of claim 1 , wherein the cells are B-cells.5. The method of claim 1 , wherein the cells are in a subject.6. The method of claim 5 , wherein the subject has non-Hodgkin's lymphoma.7. The method of claim 1 , wherein the targeting moiety is specific for a non-internalizing cell surface molecule or slowly internalizing cell surface molecule.8. The method of claim 7 , wherein the non-internalizing cell surface molecule or slowly internalizing cell surface molecule is a CD20 receptor claim 7 , a protein tyrosine phosphatase receptor type C claim 7 , a cell surface death receptor claim 7 , a prostate stem cell antigen receptor claim 7 , or a receptor belonging to the tumor necrosis factor receptor superfamily.9. The method of claim 7 , wherein the targeting moiety is a polysaccharide claim 7 , a peptide ligand claim 7 , an aptamer claim 7 , a Fab′ fragment claim 7 , or a single-chain variable fragment.10. The method of claim 9 , wherein the targeting moiety is a Fab′ fragment.11. The method of claim 10 , wherein the Fab′ fragment is derived from an anti-CD20 receptor antibody.12. The method of claim 11 , wherein the anti-CD20 receptor antibody is 1F5 ...

MEMBRANE-LYTIC BLOCK COPOLYMERS

Membrane-lytic block copolymers, micellar assemblies, pharmaceutical compositions, and related methods are described. 2. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of 2-(dimethylamino)ethyl methacrylate claim 1 , 2-dimethylaminoethyl acrylate claim 1 , (3-acrylamidopropyl)trimethylammonium chloride claim 1 , N-(3-aminopropyl) methacrylamide claim 1 , N claim 1 ,N-diethylacrylamide claim 1 , N claim 1 ,N-diethylmethacrylamide claim 1 , N claim 1 ,N-dimethylacrylamide claim 1 , N-[3-(dimethylamino)propyl]methacrylamide claim 1 , 2-aminoethyl methacrylate claim 1 , 2-(diethylamino)ethyl methacrylate claim 1 , 2-(dimethylamino)ethylmethacrylate claim 1 , [2-hydroxy-3-(2-aminoethyl) amino]propyl methacrylate claim 1 , [3methacryloylamino)propyl]trimethylammonium chloride claim 1 , and L-lysine.3. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of methacrylic acid claim 1 , acrylic acid claim 1 , dimethylmaleic anhydride modified N-(3-aminopropyl) methacrylamide claim 1 , and 2-aminoethyl methacrylate.4. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of oligo(ethylene glycol) claim 1 , hydroxypropylmethacrylamide claim 1 , 2-hydroxyethyl methacrylate claim 1 , N-isopropylacrylamide claim 1 , 3-glucanoamidopropyl methacrylamide claim 1 , 2-lactobionamidoethyl methacrylamide claim 1 , betaine claim 1 , phosphocholine claim 1 , sulfobetaine and carboxybetaine.5. The block copolymer of claim 1 , wherein A claim 1 , Aor Aindependently comprise repeating units selected from the group consisting of 2-diisopropylaminoethyl methacrylate claim 1 , 2-(pentamethyleneimino)ethyl methacrylate claim 1 , 2-(hexamethyleneimino)ethyl methacrylate claim 1 , 2-(dipropylamino) ethyl methacrylate claim 1 , 2-(dibutylamino) ethyl ...

Macromolecular Delivery Systems for Non-Invasive Imaging, Evaluation and Treatment of Arthritis and Other Inflammatory Diseases

This invention relates to biotechnology, more particularly, to water-soluble polymeric delivery systems for the imaging, evaluation and/or treatment of rheumatoid arthritis and other inflammatory diseases. Using modern MR imaging techniques, the specific accumulation of macromolecules in arthritic joints in adjuvant-induced arthritis in rats is demonstrated. The strong correlation between the uptake and retention of the MR contrast agent labeled polymer with histopathological features of inflammation and local tissue damage demonstrates the practical applications of the macromolecular delivery system of the invention. 166-. (canceled)67: A method for treating an inflammatory disease , comprising:administering to a subject in need thereof a pharmaceutical composition comprising a N-(2-hydroxypropyl) methacrylamide copolymer and a physiologically acceptable carrier,wherein said N-(2-hydroxypropyl)methacrylamide copolymer consists of N-(2-hydroxypropyl)methacrylamide and N-methacryloyl glycylglycyl hydrazone glucocorticoid or a pharmaceutically acceptable salt thereof, andwherein said glucocorticoid is dexamethasone.68: The method of claim 67 , wherein the pharmaceutically acceptable salt is dexamethasone palmitate.69: The method of claim 67 , wherein the inflammatory disease is arthritis.70: The method of claim 69 , wherein the arthritis is rheumatoid arthritis.71: The method of claim 67 , wherein the inflammatory disease is selected from the group consisting of temprormandibular joint syndrome claim 67 , inflamed nerve root claim 67 , Crohn's disease claim 67 , chronic obstructive pulmonary disease claim 67 , psoriasis diseases claim 67 , asthma claim 67 , colitis claim 67 , multiple sclerosis claim 67 , lupus claim 67 , erythematosus claim 67 , and atherosclerosis.72: The method of claim 67 , wherein the subject has an inflamed arthritic joint.73: The method of claim 72 , wherein the joint is an ankle joint.74: The method of claim 72 , wherein the joint is a knee ...

POLYMERIC NANOPARTICLES AND DERIVATIVES THEREOF FOR NUCLEIC ACID BINDING AND DELIVERY

The invention provides polymers and polymeric nanogels in which nucleic acid molecules can be stably entrapped or encapsulated and are controllably delivered and released upon degradation of the nano-structures in response to specific microenvironment triggers, and compositions and methods of preparation and use thereof. 3. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein X comprises a crosslinked group.4. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein X comprises a group capable of forming a crosslinking bond.5. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein the nucleic acid molecule is selected from the group consisting of single-stranded or double-stranded RNA or DNA claim 1 , and derivatives or analogs thereof.6. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein the nucleic acid molecule is selected from the group consisting of dsRNA claim 1 , siRNA claim 1 , mRNA claim 1 , ncRNA claim 1 , microRNA claim 1 , catalytic RNA claim 1 , guide RNA claim 1 , aptamers claim 1 , genes claim 1 , plasmids claim 1 , and derivatives or analogs thereof.711-. (canceled)12. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein the co-polymer is a random co-polymer.13. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein the co-polymer is a block co-polymer.1418-. (canceled)19. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein W comprises a charged group.2023-. (canceled)24. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein W is a charge-neutral group.27. (canceled)2932-. (canceled)33. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein Y is selected from a linear or branched C-Calkyl substituted with or without an aromatic moiety.34. The crosslinked polymeric nanogel-nucleic acid assembly of claim 1 , wherein the crosslinked network of ...

ENZYME-CATALYZED SYNTHESIS OF SITE-SPECIFIC AND STOICHIOMETRIC BIOMOLECULE-POLYMER CONJUGATES

Methods for producing polypeptide-polymer conjugates include attachment of an initiator agent to a polypeptide specifically at the C-terminus of the polypeptide using a sortase enzyme and in situ polymerization of a polymer from the C-terminus. The polypeptide-polymer conjugates may have desirable pharmacological properties and may be used therapeutically. 1. A method of making polypeptide-polymer conjugates having one or more altered pharmacological properties from a plurality of polypeptides having C-termini , the method comprising:(a) contacting the plurality of polypeptides with a sortase and an initiator agent under conditions that permit attachment of the initiator agent to the C-terminus to form a plurality of macroinitiators; and(b) incubating the plurality of macroinitiators with a monomer under conditions that permit free-radical polymerization to occur from the initiator agent to form polypeptide-polymer conjugates, such that at least about 25% of the polypeptides have a conjugated polymer initiated solely from the C-terminus,wherein the polypeptide-polymer conjugates have an altered pharmacological property selected from at least one of (i) an in vivo half-life that is at least 25% greater compared with the in vivo half life of the plurality of polypeptides; and (ii) an in vivo biodistribution to a tissue, organ or disease site that is at least 25% greater than the in vivo biodistribution of the plurality of polypeptides.2. The method of claim 1 , wherein the plurality of polypeptides comprise one or more peptides or protein therapeutic agents selected from an inteferon claim 1 , insulin claim 1 , monoclonal antibody claim 1 , blood factor claim 1 , colony stimulating factor claim 1 , growth hormone claim 1 , interleukin claim 1 , growth factor claim 1 , therapeutic vaccine claim 1 , calcitonin claim 1 , tumor necrosis factors (TNF) claim 1 , TNF-related apoptosis-inducing ligand (TRAIL) claim 1 , glucagon-like peptide-1 (GLP-1) claim 1 , vasoactive ...

POLYMER OF GAMMA-GLUTAMYL TRANSPEPTIDASE CATALYZING HYDROLYSIS-INDUCED CHARGE REVERSAL AND ITS APPLICATION IN THE FIELD OF DRUG DELIVERY

This present invention relates to a polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal. The polymer comprises a γ-glutamyl transpeptidase-responsive element represented by Formula (I). When the polymer is used as drug carrier for anticancer drug, it can have a long circulation time in the blood, and can realize a charge reversal from negatively charged or the neutral to positively charged around the tumor blood vessel region, so that the positively charged polymer effectively penetrates deep into the tumor tissue, fast entering into the tumor cells, and greatly improves the therapeutic effect of the drug on the tumor. This overcomes the problems of slow diffusion of traditional polymer drug carriers in tumors and weak interaction with tumor cells, and has great significance in the field of anticancer treatment in the medical field. 2. A method for preparing the polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal according to claim 1 , comprising: the polymer is obtained by direct polymerization of a monomer containing the γ-glutamyl transpeptidase responsive element.4. The method for preparing the polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal according to claim 3 , wherein the monomer containing the γ-glutamyl transpeptidase responsive element comprises an acrylamide-based monomer containing the γ-glutamyl transpeptidase responsive element claim 3 , an acrylate-based monomer containing the γ-glutamyl transpeptidase responsive element claim 3 , a methacrylamide-based monomer containing the γ-glutamyl transpeptidase responsive element claim 3 , or a methacrylate-based monomer containing the γ-glutamyl transpeptidase responsive element.6. A method for preparing the drug carrier prepared by the polymer of γ-glutamyl transpeptidase catalyzing hydrolysis-induced charge reversal according to claim 5 , comprising:the drug carrier is synthesized by random copolymerization or ...

HYPERICIN-PVP COMPLEX WITH HIGH HYPERICIN CONTENT

The invention relates to a complex that consists of hypericin or a hypericin salt and polyvinyl pyrrolidone (PVP), the average mass fraction of hypericin or hypericin salt in the entire complex being higher than 6% by weight. The invention further relates to a process for preparing said hypericin-PVP complex, according to which process a mixture of hypericin and PVP is heated to a temperature above the glass transition temperature of the PVP used. 1. A complex formed from hypericin or a hypericin salt and polyvinylpyrrolidone (PVP) , characterized in that the mean proportion by weight of hypericin or of hypericin salt with respect to the total complex is more than 6% by weight.2. The complex as claimed in claim 1 , characterized in that the mean molar ratio of hypericin to PVP in the complex is more than 2.5.3. The complex as claimed in claim 1 , characterized in that the PVP has a mean molar mass of 10 to 40 kD claim 1 , preferably from 12 to 25 kD.4. A pharmaceutical composition containing a complex as claimed in .5. The pharmaceutical composition as claimed in claim 4 , characterized in that the composition is provided for intravenous administration and in that the composition contains hypericin in a concentration of at least 25 mg/L.6. The method for the production of a complex as claimed in claim 1 , characterized in that a mixture of hypericin and PVP is heated to a temperature which is above the glass transition temperature of the PVP employed.7. The method as claimed in claim 6 , characterized in that a solvent or a mixture of solvents claim 6 , preferably water claim 6 , ethanol claim 6 , methanol claim 6 , pyridine claim 6 , acetone claim 6 , ethylmethylketone and/or ethyl acetate claim 6 , more preferably water claim 6 , ethanol claim 6 , methanol and/or pyridine claim 6 , more preferably water and/or ethanol claim 6 , is added to the mixture of hypericin and PVP.8. The method as claimed in claim 6 , characterized in that the mixture is maintained at a ...

Drug Carrier, Brain-targeting Nanodrug Based on CRISPR Gene Editing Technology and Preparation Method and Use thereof

The present disclosure provides a drug carrier, a brain-targeting nanodrug based on CRISPR gene editing technology and a preparation method and use thereof. The nanodrug contains nanoparticles prepared by coupling Cas9/sgRNA and drug carriers. The drug carrier includes a polymer mPEG-P (GPMA, FPMA) and a polymer Ang-PEG-PGPMA, wherein a structural formula of the mPEG-P (GPMA, FPMA) is: 2. The drug carrier according to claim 1 , wherein the polymer mPEG-P (GPMA claim 1 , FPMA) is mPEG-P (GPMA claim 1 , FPMA).3. The drug carrier according to claim 1 , wherein the polymer Ang-PEG-PGPMA is Ang-PEG-PGPMA.4. A brain-targeting nanodrug based on CRISPR gene editing technology claim 1 , comprising nanoparticles obtained by coupling a therapeutic drug with the drug carrier according to .5. The brain-targeting nanodrug according to claim 4 , wherein in the Cas9/sgRNA claim 4 , a ratio of the Cas9 protein to the sgRNA in mole part is 1:1-1:1.5.6. The brain-targeting nanodrug according to claim 4 , wherein the nanoparticles contain 1 part of Cas9/sgRNA claim 4 , 1-3 parts of mPEG-P (GPMA claim 4 , FPMA) and 4-12 parts of Ang-PEG-PGPMA claim 4 , in mole part.7. A method for preparing the brain-targeting nanodrug based on CRISPR gene editing technology according to claim 4 , comprising:Step a. dissolving the polymer mPEG-P (GPMA, FPMA) and the polymer Ang-PEG-PGPMA in a buffer solution to obtain a mixed solution A; andStep b. adding the Cas9/sgRNA to the mixed solution A, so as to obtain by reaction nanoparticles Ang-NP@Cas9/sgRNA.8. The method according to claim 7 , wherein the buffer solution is any one selected from the group consisting of a HEPES buffer solution and a PBS buffer solution.9. The method according to claim 7 , wherein the reaction in Step b is conducted in a condition of mixing well and standing at room temperature.10. The brain-targeting nanodrug according to claim 4 , wherein the therapeutic drug is Cas9/sgRNA claim 4 , wherein the Cas9/sgRNA is obtained by ...

Interpenetrating Polymer Network Hydrogel

A strain-hardened interpenetrating polymer network (IPN) hydrogel is provided. The interpenetrating polymer network hydrogel is based on two different networks. The first network is a non-silicone network of preformed hydrophilic non-ionic telechelic macromonomers chemically cross-linked by polymerization of its end-groups. The second network is a non-silicone network of ionizable monomers. The second network has been polymerized and chemically cross-linked in the presence of the first network and has formed physical cross-links with the first network. An aqueous salt solution having a neutral pH is used to ionize and swell the second network in the interpenetrating polymer network. The swelling of the second network is constrained by the first network, and this constraining effect results in an increase in effective physical cross-links within the interpenetrating polymer network, and, in turn, an increase its elastic modulus. The strain-hardened interpenetrating polymer network hydrogel is attractive and useful for medical, industrial, and personal hygiene purposes.

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 191-. (canceled)92. A composition comprising surface functionalized biodegradable poly(lactide-co-glycolide) (PLG) particles comprising encapsulated antigen or one or more antigenic epitopes , wherein the particle has a negative zeta potential of from about −30 mV to −80 mV.93. The composition of claim 92 , wherein said antigen comprises an autoimmune antigen claim 92 , an antigen expressed on a tissue to be transplanted into a subject claim 92 , or an enzyme for enzyme replacement therapy.94. The composition of claim 92 , wherein the antigen is one or more antigenic gliaden epitopes.95. The composition of claim 94 , wherein the one or more antigenic gliaden epitopes comprises one or more of the sequences set forth in SEQ ID NOS: 1295-1724 claim 94 , 1726-1766 claim 94 , and 4986-5440.96. The composition of claim 92 , wherein the PLG comprises a copolymer ratio of about 50:50 of polylactic acid:polyglycolic acid.97. The composition of claim 92 , wherein the negative zeta potential is achieved by surface functionalization.98. The composition of claim 92 , wherein the is surface functionalization is carboxylation.99. The composition of claim 98 , wherein the carboxylation is achieved by using poly(ethylene-maleic anhydride) (PEMA).100. The composition of claim 92 , wherein the particles have a zeta potential of about −50 mV to about −40 mV.101. The composition of claim 92 , wherein the particles have a zeta potential of about −60 mV to about −30 mV.102. The composition of claim 92 , wherein the particle has a diameter of between about 200 nm to about 2000 nm.103. The composition of claim 92 , wherein the particle has a diameter of about 400 to ...

POLYMER-SUNITINIB CONJUGATES

The invention relates to (among other things) polymer-sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over sunitinib in unconjugated form. 1. A compound comprising a sunitinib residue covalently attached via a releasable linkage-containing spacer moiety to a water-soluble , non-peptidic polymer.6. The compound of any one of to , wherein the releasable linkage-containing spacer moiety includes a releasable linkage selected from the group consisting of thioether , carbamate , ester , carbonate , urea and enzyme-cleavable peptidic linkages.8. The compound of any one of to , wherein the water-soluble , non-peptidic polymer is a poly(alkylene oxide).9. The compound of claim 8 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).10. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer is linear.11. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer is branched.16. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has a molecular weight of less than 2000 Daltons.17. The compound of any one of to claim 8 , wherein water-soluble claim 8 , non-peptidic polymer has from about 1 to about 30 monomers.18. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has from about 1 to about 10 monomers.19. The compound of any one of to claim 8 , wherein the water-soluble claim 8 , non-peptidic polymer has a molecular weight of from 2000 Daltons to about 150 claim 8 ,000 Daltons.20. The compound of any one of to claim 8 , wherein the water-soluble polymer claim 8 , non-peptidic polymer includes an alkoxy or hydroxy end-capping moiety.21. A composition comprising (i) a compound comprising a sunitinib residue covalently attached via a releasable linkage-containing spacer moiety to a water-soluble ...

PEGYLATED ENDOSTATIN ANALOGUE AND APPLICATION THEREOF

The present invention provides a polyethylene glycol-modified endostatin analogue and an application thereof. The endostatin analogue is coupled to polyethylene glycol at lysine away from a nucleolin binding domain, or is coupled to polyethylene glycol at lysine away from a nucleolin binding domain and amidogen at the N end. 1. An endostatin analogue-PEG coupled complex , wherein the endostatin analogue has a lysine residue at a position corresponding to position 96 of the amino acid sequence SEQ ID NO. 1 of naturally occurring endostatin , and no lysine residue at any other position; and the endostatin analogue is coupled to PEG only at the lysine residue or is coupled to PEG at N-terminus and the lysine residue.2. (canceled)3. The coupled complex according to claim 1 , wherein the endostatin analogue is formed by mutation of lysine residues at positions 76 claim 1 , 107 claim 1 , 118 and 184 of the amino acid sequence SEQ ID NO. 1 of naturally occurring endostatin.4. The coupled complex according to claim 1 , wherein the endostatin analogue is a functional variant of endostatin having an amino acid sequence inserted at its N-terminus.5. (canceled)6. The coupled complex according to claim 4 , wherein the endostatin analogue is formed by mutation of the lysine residues at positions 76 claim 4 , 107 claim 4 , 118 and 184 of the amino acid sequence SEQ ID NO. 1 of naturally occurring endostatin claim 4 , and insertion of GGSHHHHH (SEQ ID NO. 14) between methionine M and histidine H at its N-terminus.7. The coupled complex according to claim 4 , wherein the amino acid sequence inserted at N-terminus is MGGSHHHHH (SEQ ID NO. 15).8. The coupled complex according to claim 3 , wherein the lysine residues at positions 76 claim 3 , 107 claim 3 , 118 and 184 of the amino acid sequence SEQ ID NO. 1 of naturally occurring endostatin are mutated to X1 claim 3 , X3 claim 3 , X4 and X5 claim 3 , respectively claim 3 , wherein X1 claim 3 , X3 claim 3 , X4 or X5 is independently any ...

SIRNA COMPOSITIONS THAT SPECIFICALLY DOWN REGULATE EXPRESSION OF A VARIANT OF THE PNPLA3 GENE AND METHODS OF USE THEREOF FOR TREATING A CHRONIC LIVER DISEASE

The invention provides siRNA compositions that specifically downregulates expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD). 1. A composition comprising a small interfering RNA (siRNA) molecule that specifically downregulates expression of a rs738409 C>G variant of a patatin-like phospholipase domain-containing (PNPLA3) gene.2. The composition according to claim 1 , wherein the siRNA molecule is single stranded.3. The composition according to claim 2 , wherein the siRNA molecule comprises the nucleotide sequence of SEQ ID NO 1.4. The composition according to claim 1 , wherein the siRNA molecule is double stranded.5. The composition according to claim 4 , wherein the double stranded siRNA molecule comprises the nucleotide sequences of SEQ ID NOs 1 and 2.6. The composition according to claim 1 , wherein the siRNA molecule comprises a nucleotide sequence of at least one of SEQ ID NOs 278-552.7. The composition according to claim 1 , further comprising a nanoparticle to which the siRNA molecule is coupled.8. The composition according to claim 7 , wherein the nanoparticle comprises low molecular weight polyethyleneimine (LPEI) and a lipid.9. The composition according to claim 8 , wherein the lipid is a bile acid.10. The composition according to claim 1 , wherein the siRNA molecule does not downregulate expression of a wild-type isoform of the PNPLA3 gene.11. The composition according to claim 1 , wherein the siRNA molecule comprises one or more non-naturally occurring nucleotides.12. A method for treating a subject with a chronic liver disease or alcoholic liver disease (ALD) claim 1 , the methods comprising administrating a therapeutically effective amount of a composition comprising a small interfering RNA (siRNA) molecule that specifically downregulates expression of a rs738409 C>G variant of a patatin-like phospholipase domain-containing (PNPLA3) gene.13. The method according to ...

POLYMERS FOR DELIVERY OF FACTOR VIII AND/OR FACTOR IX

In some aspects, a composition comprising a pH-sensitive crosslinked copolymer of methacrylic acid and poly(ethylene glycol) monomethyl ether methacrylate and a therapeutic protein is provided. In some embodiments, the therapeutic protein is a high molecular weight protein such as factor VIII or factor IX. In some embodiments, the composition is orally administered to a patient to treat a disease or disorder such as, e.g., hemophilia. 1. A composition comprising:(A) a therapeutic protein; wherein the therapeutic protein is factor IX or factor VIII; and(B) a copolymer comprising methacrylic acid and poly(ethylene glycol) monomethyl ether monomethacrylate crosslinked with about 0.5-2.0% tetra(ethylene glycol) dimethacrylate (TEGDMA) or about 0.5-2.0% poly(ethylene glycol) dimethacrylate (PEGDMA) wherein the poly(ethylene glycol) component of the PEGDMA has an average molecular weight of about 100-1,000; or{'img': {'@id': 'CUSTOM-CHARACTER-00001', '@he': '7.53mm', '@wi': '135.93mm', '@file': 'US20190275162A1-20190912-P00999.TIF', '@alt': 'text missing or illegible when filed', '@img-content': 'character', '@img-format': 'tif'}, '.'}2. The composition of claim 1 , wherein the therapeutic protein is factor IX.3. The composition of claim 1 , wherein the therapeutic protein is factor VIII.4. The composition of claim 1 , wherein the composition is comprised in a pharmaceutical preparation formulated for oral administration.58-. (canceled)9. The composition of claim 1 , wherein the ratio of the molar percentage of methacrylic acid (MAA) to poly(ethylene glycol) monomethyl ether monomethacrylate is from about 1:1 to about 60:1.10. The composition of claim 9 , wherein the ratio of the molar percentage of methacrylic acid to poly(ethylene glycol) monomethyl ether monomethacrylate is from about 20:1 to about 40:1.1115-. (canceled)1615. The composition of claim claim 9 , wherein the average molecular weight is from about 200 to about 600.17. The composition of claim 16 , wherein ...

ENGINEERED CELLS AND AGENT COMPOSITIONS FOR THERAPEUTIC AGENT DELIVERY AND TREATMENTS USING SAME

Provided herein are engineered cells and methods for engineering cells to deliver a therapeutic agent, e.g., a small molecule, peptide or other drug, to a cell or tissue to be treated. 1. A composition comprising:a) a genetically engineered cell that expresses on its cell surface at least one heterologous ligand-binding polypeptide; andb) at least one copolymer drug composition, wherein each of the at least one copolymer drug composition comprises a ligand that specifically binds the heterologous ligand-binding polypeptide described in (a), such that the at least one copolymer drug composition is displayed on the surface of the genetically engineered cell,wherein the engineered cell further comprises a nucleic acid construct encoding a polypeptide, operably linked to a regulatory nucleic acid sequence that renders expression of the polypeptide modulated by the presence or absence of a drug comprised by the copolymer drug composition.2. The composition of claim 1 , wherein the at least one heterologous ligand-binding polypeptide comprises an antigen binding domain of an antibody that binds the ligand comprised by a copolymer drug composition.3. The composition of claim 1 , wherein the genetically-engineered cell further expresses a heterologous receptor that binds a cell-surface ligand on a target cell.4. The composition of claim 1 , wherein the genetically engineered cell is a T cell claim 1 , a macrophage or a stem cell.510.-. (canceled)11. The composition of claim 1 , wherein the drug comprised by the copolymer drug composition is required for the expression of the polypeptide.1215.-. (canceled)16. The composition of claim 1 , wherein the expression of the polypeptide is repressed by the drug comprised by the copolymer drug composition.17. The composition of claim 16 , wherein the polypeptide promotes the death of the genetically engineered cell.18. The composition of claim 1 , wherein the polypeptide modulates an activity of a target cell.1922.-. (canceled)23. ...

Stabilization of Glucagon by Trehalose Glycopolymer Nanogels

Trehalose-based nanogels for stabilizing and controlled releasing biomolecules such as glucagons are disclosed. Specifically, trehalose-based nanogels comprise (a) a copolymer comprising first methacrylate units and second methacrylate units, wherein (i) the first methacrylate units comprise trehalose side chains; and (ii) the second methacrylate units comprise disulfide side chains; (b) dithiol cross-linkers; wherein the dithiol cross-linkers cross link the copolymer through the disulfide side chains of the second methacrylate units. 1. A trehalose-based nanogel , the nanogel comprising: (i) the first units comprise trehalose side chains; and', '(ii) the second units comprise disulfide side chains; and, '(a) a copolymer comprising first units and second units, wherein'}(b) dithiol cross-linkers;wherein the dithiol cross-linkers cross-link the copolymer through the disulfide side chains of the second units.2. The trehalose-based nanogel of claim 1 , wherein(i) the first units are first methacrylate units comprising the trehalose side chains; and(ii) the second units are second methacrylate units comprising the disulfide side chains;wherein the dithiol cross-linkers cross-link the copolymer through the disulfide side chains of the second methacrylate units.3. The trehalose-based nanogel of claim 2 , wherein the nanogel further comprises one biomolecule.4. The trehalose-based nanogel of claim 3 , wherein the biomolecule is glucagon.5. The trehalose-based nanogel of claim 3 , wherein the biomolecule is covalently bonded with the copolymer.6. The trehalose-based nanogel of claim 3 , wherein the biomolecule is used as a cross-linker.7. The trehalose-based nanogel of claim 3 , wherein the nanogel is biocompatible.8. The trehalose-based nanogel of claim 3 , wherein the biomolecule is controlled-releasable.9. The trehalose-based nanogel of claim 2 , wherein the nanogel has an average in the range of 2-500 nm.10. (canceled)11. (canceled)12. (canceled)13. The trehalose-based ...

DRUG DELIVERY SYSTEM FOR TREATING DISEASE

The present invention relates to HPMA-CBz copolymers and methods for treating certain diseases comprising administering the copolymers to a subject in need thereof. 1. A composition comprising an N-(2-hydroxypropyl)methacrylamide-benzyl carbamate (HPMA-Cbz) monomer.2. The composition of claim 1 , wherein the PMA-Cbz monomer is synthesized from one or more acid-labile claim 1 , CBz derived linkers.3. The composition of claim 2 , wherein the linker is an activated linker.4. The composition of claim 3 , further comprising a therapeutic agent or drug.5. The composition of claim 4 , wherein the therapeutic agent or drug is a janus kinase inhibitor.6. The composition of claim 5 , wherein the therapeutic agent or drug is baricitinib claim 5 , ruxolitinib claim 5 , tofacitinib claim 5 , oclacitinib claim 5 , upadacitinib claim 5 , and/or peficitinib.7. The composition of claim 6 , wherein the therapeutic agent or drug is baricitinib.8. A method of synthesizing a polymer claim 6 , said method comprising polymerizing the composition of or under conditions sufficient to form a polymer.9. A co-polymer of HPMA and HPMA-Cbz-Drug.11. The copolymer of claim 9 , wherein the copolymer has a polydispersion index (PDI) between 1.1 and 1.6.12. The copolymer of claim 9 , comprising 0.1%-50% HPMA-link-Drug monomer.13. The copolymer of claim 9 , wherein its molecular weight is greater than 10 claim 9 ,000 MW and less than 60 claim 9 ,000.14. A pharmaceutical composition for the treatment of an inflammatory disease claim 9 , comprising the polymer of .15. The pharmaceutical composition of claim 14 , wherein the polymer comprises a drug that is baricitinib.16. A method for treating an inflammatory disease claim 14 , the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of .17. The method of claim 16 , wherein the inflammatory disease is arthritis.18. The method of claim 16 , wherein the inflammatory disease is osteoarthritis ...

Peptide Conjugated Particles

The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance). 191-. (canceled)92. A composition comprising surface functionalized biodegradable particles comprising one or more encapsulated antigens or antigenic epitopes thereof , wherein said particles have a negative zeta potential , and wherein said antigen is associated with an autoimmune disorder of the central nervous system.93. The composition of claim 92 , wherein said particles are poly (lactic acid) (PLA) claim 92 , poly (glycolic acid) (PGA) claim 92 , or poly (lactic co-glycolic acid) (PLGA) particles.94. The composition of claim 92 , wherein said antigen is associated with Multiple Sclerosis (MS) claim 92 , Neuromyelitis Optica (NMO) claim 92 , and/or autoimmune encephalomyelitis.95. The composition of claim 94 , wherein said autoimmune antigen is selected from the group consisting of myelin oligodendrocyte glycoprotein (MOG) claim 94 , myelin basic protein (MBP) claim 94 , proteolipid protein (PLP) claim 94 , myelin associated glycoprotein (MAG) claim 94 , and aquaporin-4 (AQP-4).96. The composition of claim 95 , wherein said autoimmune antigen is selected from the group consisting of SEQ. ID NO: 1 claim 95 , SEQ. ID NO: 14 claim 95 , SEQ. ID NO: 22 claim 95 , SEQ. ID NO: 23 claim 95 , SEQ. ID NO: 47 claim 95 , SEQ. ID NO: 69 claim 95 , SEQ. ID NO: 84 claim 95 , SEQ. ID NO: 87 claim 95 , SEQ. ID NO: 197 claim 95 , SEQ. ID NO: 388 claim 95 , SEQ. ID NO: 471 claim 95 , SEQ. ID NO: 549 claim 95 , SEQ. ID NO: 564 claim 95 , SEQ. ID NO: 1056 claim 95 , SEQ. ID NO: 1082 claim 95 , SEQ. ID NO: 1121 claim 95 , and SEQ. ID NO: 4979.97. The composition of claim 92 , wherein the negative zeta potential of said particles is achieved by surface ...

CLEAVABLE POLYMER DRUG CONJUGATES

This invention relates to polymer drug conjugates comprising a (meth)acrylate based polymer backbone with at least two types of side chains wherein one of the side chains is a PEG chain and the other side chain comprises at least one therapeutic agent covalently bonded to a cleavable linker, methods of preparing said polymer-drug conjugates and their use for treatment of diseases such as cancer. 122.-. (canceled)23. A polymer-drug conjugate for delivery of therapeutic agents comprising a (meth)acrylate based polymer backbone characterized in that the polymer comprises at least two types of side chains wherein one of the side chains is a PEG chain such as —CO—Z—CHCH(OCHCH)ORwherein n is a natural number between 1-200 and Ris selected from a group comprising H or —CH , Z is selected from —O or —NH and the other side chain is comprising at least one therapeutic agent covalently bonded to a cleavable linker.25. A polymer drug conjugate according to wherein linker is selected from a group comprising a poly(ethylene glycol) claim 23 , an amino acid claim 23 , poly(amino acid) claim 23 , polypeptide and short peptides.26. A polymer drug conjugate according to wherein the linker is a short peptide that is cathepsin B labile.27. A polymer drug conjugate according to wherein short peptide is selected from a group comprising Gly-Phe-Leu-Gly (SEQ ID NO: 1) claim 26 , Val-Cit (SEQ ID NO:2) claim 26 , Phe-Lys (SEQ ID NO: 3) claim 26 , Val-Ala (SEQ ID NO: 4) claim 26 , Ala-Leu-Ala-Leu (SEQ ID NO: 5).28. A polymer drug conjugate according to wherein claim 23 , the linker is a C-Chydrocarbon or C-Csubstituted or hetero substituted hydrocarbon claim 23 , which comprises a functional group that dissociates under physiological conditions claim 23 , preferably said functional group is selected from acetal claim 23 , ester claim 23 , imine claim 23 , amide claim 23 , disulfide claim 23 , carbonate claim 23 , hydrazine claim 23 , carbamate.29. A polymer-drug conjugate according to wherein ...

DYNAMIC USER-PROGRAMMABLE MATERIALS INCLUDING STIMULI-RESPONSIVE PROTEINS

The present disclosure features a protein-polymer conjugate, including a multivalent polymer building block, a stimuli-responsive protein covalently conjugated to the multivalent polymer building block to provide a protein-polymer conjugate, wherein the protein undergoes a modification upon exposure to a predetermined stimulus, and the protein modification triggers a physical and/or chemical response in the protein-polymer conjugate.

N-MALEIMIDYL POLYMER DERIVATIVES

The invention is directed to multi-functional N-maleimidyl polymer derivatives comprising a water soluble and non-peptidic polymer backbone having a terminal carbon, such as a poly(alkylene glycol), the terminal carbon of the polymer backbone being directly bonded to the nitrogen atom of a N-maleimidyl moiety without a linking group therebetween. The invention also provides two methods of preparing such linkerless N-maleimidyl polymer derivatives.

PROTEIN-POLYMER-DRUG CONJUGATES

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L-D, the protein based recognition-molecule being connected to the polymeric carrier by L. Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. Land Lare 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. 3. A polymeric scaffold useful for conjugating a protein based recognition-molecule (PBRM) claim 1 , the scaffold comprising a polymeric carrier and a compound of being connected to the polymeric carrier via a biodegradable bond.4. The scaffold of claim 3 , wherein the polymeric carrier is poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF).5. The scaffold of claim 3 , wherein the PBRM has a molecular weight of greater than 40 kDa.7. The scaffold of claim 6 , wherein the PHF has a molecular weight ranging from 6 kDa to 20 kDa claim 6 , mis an integer from 2 to 20 claim 6 , mis an integer from 1 to 9 claim 6 , and mis an integer from 1 to 75 claim 6 , and the sum of m claim 6 , m claim 6 , m claim 6 , and mranges from about 45 to about 150.8. The scaffold of claim 6 , wherein the PHF has a molecular weight ranging from 8 kDa to 15 kDa claim 6 , mis an integer from 2 to 15 claim 6 , mis an integer from 1 to 7 claim 6 , and mis an integer from 1 to 55 claim 6 , and the sum of m claim 6 , m claim 6 , m claim 6 , and mranges from about 60 to about 110.9. The scaffold of claim 6 , wherein the functional group of Lis selected from —SR claim 6 , —S—S-LG claim 6 , maleimido claim 6 , and halo claim 6 , in which LG is a leaving group and Ris H or a sulfur ...

Method and composition for a protein transduction technology and its applications

A protein transduction method for efficiently delivery of exogenous proteins into mammalian cells is invented, which has the capability of targeting different cellular compartments and protection from degradation of the delivered proteins from cellular proteases. A composition for treat proteins has cation reagents, lipids and enhancers in a carrier. The method can be used in a number of ways including: production of large quantities of properly folded, post-translationally modified proteins using mammalian cell machinery a in-cell fluorescence spectroscopy and imaging using small molecule fluorophores and a in-cell NMR spectroscopy using living mammalian cells. The method permits cell biology at atomic resolution that is physiologically and pathological relevant and permits protein therapy to treat human diseases. The method can also be used to deliver exogenous protein inside mammalian cells, wherein the exogenous proteins follow a similar secretion pathway as that of the endogenous protein.

Enzyme-catalyzed synthesis of site-specific and stoichiometric biomolecule-polymer conjugates

Methods for producing polypeptide-polymer conjugates include attachment of an initiator agent to a polypeptide specifically at the C-terminus of the polypeptide using a sortase enzyme and in situ polymerization of a polymer from the C-terminus. The polypeptide-polymer conjugates may have desirable pharmacological properties and may be used therapeutically.

CONTIGUITY PARTICLE FORMATION AND METHODS OF USE

Embodiments of systems, methods, and compositions provided herein relate to hollow beads encapsulating single cells. Some embodiments include performing multiple co-assays on a single cell encapsulated within a hollow bead, including nucleic acid sequencing, preparing nucleic acid libraries, determining methylation status, identifying genomic variants, or protein analysis. 1. A hollow bead encapsulating a single cell comprising:a polymer shell; anda single cell disposed within the polymer shell,wherein the polymer shell comprises pores that allow diffusion of a reagent through the polymer shell while retaining the single cell.2. The hollow bead of claim 1 , wherein an interior of the polymer shell comprises an aqueous environment.3. The hollow bead of claim 1 , wherein the single cell disposed within the polymer shell is free from interaction with the polymer shell and/or is not in contact with the polymer shell.4. The hollow bead of claim 1 , wherein the hollow bead has a diameter of about 20 μm to about 200 μm.5. The hollow bead of claim 1 , wherein the polymer shell comprises a four-arm polyethylene glycol (PEG).6. The hollow bead of claim 1 , wherein the polymer comprises claim 1 , PEG claim 1 , PEG-acrylate claim 1 , PEG-amine claim 1 , PEG-carboxylate claim 1 , PEG-dithiol claim 1 , PEG-epoxide claim 1 , PEG-isocyanate claim 1 , PEG-maleimide claim 1 , polyacrylic acid (PAA) claim 1 , poly(methyl methacrylate) (PMMA) claim 1 , alginate claim 1 , polystyrene (PS) claim 1 , polystyrene sulfonate (PSS) claim 1 , polyvinylpyrrolidone (PVPON) claim 1 , acrylamide claim 1 , N claim 1 ,N′-bis(acryloyl)cystamine claim 1 , polypropylene oxide (PPO) claim 1 , poly(hydroxyethyl methacrylate) (PHEMA) claim 1 , poly(N-isopropylacrylamide) (PNIPAAm) claim 1 , poly(lactic acid) (PLA) claim 1 , poly(lactic-co-glycolic acid) (PLGA) claim 1 , polycaprolactone (PCL) claim 1 , poly(vinylsulfonic acid) (PVSA) claim 1 , poly(L-aspartic acid) claim 1 , poly(L-glutamic acid) claim 1 ...

ANTIMICROBIAL PLATELET-LIKE PARTICLES

Disclosed herein are platelet-like particles incorporating antimicrobial metallic nanoparticles. The platelet-like particles include an ultra-low crosslinked polymeric microgel and fibrin targeting moiety. The antimicrobial metallic nanoparticles can be covalently or noncovalently incorporated into the platelet-like particles. The particles are useful to stop bleeding and to promote wound healing while at the same time suppressing bacterial infections that can accompany tissue damage. 1. A highly deformable microgel comprising at least one ultra-low crosslinked polymer , fibrin-binding moiety , and antimicrobial metallic nanoparticle.2. The microgel according to claim 1 , wherein the ultra-low crosslinked polymer comprises a polyacrylamide claim 1 , a poly(acrylic acid) claim 1 , a polyethylene glycol claim 1 , a polyvinyl alcohol claim 1 , polysaccharide claim 1 , a polyvinylpyrrolidone claim 1 , or a copolymer thereof.3. The microgel according to claim 1 , wherein the ultra-low crosslinked polymer comprises a poly(acrylamide/acrylic acid) copolymer.4. The microgel according to claim 1 , wherein the ultra-low crosslinked polymer comprises a poly(acrylamide/acrylic acid) copolymer prepared by a precipitation polymerization of a mixture of acrylamide and acrylic acid monomers claim 1 , in which the initial mixture comprises no more than 40% claim 1 , no more than 30% claim 1 , no more than 20% claim 1 , no more than 10% claim 1 , no more than 9% claim 1 , no more than 8% claim 1 , no more than 7% claim 1 , no more than 6% claim 1 , no more than 5% claim 1 , no more than 4% claim 1 , no more than 3% claim 1 , no more than 2% claim 1 , or no more than 1% by weight acrylic acid.5. The microgel according to claim 1 , wherein the ultra-low crosslinked polymer comprises a poly(N-isopropylacrylamide/acrylic acid) copolymer6. The microgel according to claim 1 , wherein the ultra-low crosslinked polymer has a crosslinking density no greater than 2.5%.79-. (canceled)10. The ...

Stomach acid-stable and mucin-binding protein-polymer conjugates

Provided herein are protein-polymer conjugates, pharmaceutical compositions including protein-polymer conjugates, and methods of using the same, e.g., in therapeutic and industrial applications.

Protein-polymer-drug conjugates

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L D -D, the protein based recognition-molecule being connected to the polymeric carrier by L P . Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L D and L P 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.

Protein-polymer-drug conjugates

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L D -D, the protein based recognition-molecule being connected to the polymeric carrier by L P . Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L D and L P 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.

Protein-polymer-drug conjugates

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.

Protein-polymer-drug conjugates

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L D -D, the protein based recognition-molecule being connected to the polymeric carrier by L P . Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L D and L P 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.

Protein-polymer-drug conjugates

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -L D -D, the protein based recognition-molecule being connected to the polymeric carrier by L P . Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. L D and L P 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.

NANOSTRUCTURED ACTIVE INGREDIENT CARRIER SYSTEM

The invention relates to a nanostructured active ingredient carrier system, in particular for reducing cytotoxic properties owing to the use of sheath polymer and the transport resulting therefrom, for interactions with cell membranes during the transport of hydrophilic constituents and, in connection therewith, the generation of an early endosomal release of the interaction complex from the carrier system. The problem addressed by the present invention is that of specifying a nanostructured active ingredient carrier system which avoids the disadvantages of the prior art and in particular permits a reduction in cytotoxic properties owing to the use of a sheath polymer and the transport resulting therefrom. This problem is solved in that a nanostructured active ingredient carrier system is provided in the form of a particle consisting of a carrier sheath, wherein the carrier sheath comprises at least one or more hydrophobic sheath polymers, one or more charged complexing polymers and one or more hydrophilic active ingredients, wherein the complexing polymer interacts with the active ingredient. 1. A nanostructured active ingredient carrier system comprising at least one hydrophobic shell polymer , at least one complexing polymer , and at least one hydrophilic active ingredient , wherein the complexing polymer interacts with the active ingredient , and the complexing polymer comprises primary amino groups , secondary amino groups , or a combination of primary and secondary amino groups.2. The nanostructured active ingredient carrier system according to claim 1 , wherein an interaction between the complexing polymer and the active ingredient is caused by one or more non-covalent interactions in the form of electrostatic bonds claim 1 , ionic bonds claim 1 , hydrogen bonds claim 1 , or van der Waals forces.3. The nanostructured active ingredient carrier system according to claim 1 , wherein the hydrophilic active ingredient includes a genetic material.4. The ...

Gene delivery in nano scale micelle form containing anti-oxidant substances

본 발명은 항산화 물질을 내부에 포함하는 나노미셀 형태의 유전자 전달체 및 이의 제조방법에 관한 것이다. 또한, 본 발명은 상기 유전자 전달체와 핵산물질을 혼합하여 핵산물질이 회합된 유전자 전달 복합체에 관한 것이다. 본 발명에 따른 유전자 전달 복합체는 미셀의 내부에 항산화 물질을 포함하는 구조를 가지며, 나노 크기의 유전자 복합체가 세포내로 유입시 유발되는 산화적스트레스와 미트콘드리아 막 손상은 감소되면서 비바이러스성 유전자 전달체의 유전자 전달 효율은 향상시킬 수 있다. The present invention relates to a nano micelle-type gene carrier containing an antioxidant therein and a method for producing the same. The present invention also relates to a gene delivery complex in which a nucleic acid material is associated by mixing the gene delivery material and a nucleic acid material. The gene delivery complex according to the present invention has a structure containing an antioxidant substance inside the micelle, and the non-viral gene carrier is reduced while the oxidative stress and mitochondrial membrane damage caused when the nano-sized gene complex is introduced into the cell is reduced. Gene transfer efficiency can be improved.

Targeting monomers and polymers having targeting blocks

Provided herein are monomers incorporating folate or other targeting agent, polymers prepared therefrom, polymers prepared therefrom having a therapeutic agent covalently coupled thereto, as well as micelles and therapeutic compositions thereof.

Zwitterionic polymer bioconjugates and related methods

Zwitterionic polymer and mixed charge copolymer bioconjugates, methods for making and using the bioconjugates.

Drugs delivery system for their being delivered simultaneously with other enzyme- and light-activated agents

Изобретение относится к соединениям для лечения раковых тканей у теплокровных животных, используемым в системе подачи лекарств для их одновременной подачи с лекарствами, активизируемыми ферментами и светом. Задачей изобретения является создание растворимых биоактивных сополимеров, содержащих дополнительное хемотерапевтическое вещество и дополнительные фотосенсибилизаторы, прикрепленные через ферментно-расщепляемые связи. Соединение содержит как противораковое лекарство, так и фотоактивизируемое лекарство, прикрепленные к сополимерным носителям. Носители выбраны из группы, состоящей из: а) сополимерного носителя, к которому прикреплены противораковое и фотоактивизируемое лекарства, б) смеси сополимерных носителей, к одному из которых прикреплено противораковое лекарство, а к другому - фотоактивизируемое лекарство, в) комбинации а и б носителей. Противораковое лекарство прикреплено к полимерному носителю посредством боковых цепочек, которые стабильны в кровотоке животного, однако поддаются внутриклеточному гидролизу лисосомными ферментами. Фотоактивизируемое лекарство прикреплено посредством либо той же самой расщепляемой боковой цепочки, либо нерасщепляемого соединения. После ввода соединения в пациента макромолекулы полимера входят в целевые раковые клетки с помощью пиноцитоза. После ввода соединения и возможной задержки для оптимального поглощения сополимеров в раковой ткани и начала действия противоракового лекарства приводят в действие соответствующие источники света. Комбинированное воздействие противоракового лекарства и фотоактивизированного лекарства разрушает раковые к�

Manufacturing method of macroporous bead polymer

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Pharmaceutical preparations comprising cation exchange resin adsorption compounds and treatment therewith

Pharmaceutical preparations comprising phosphorus containing cation exchange resins having a basic drug adsorbed thereon; and treatment therewith

Prolonged release pharmaceutical preparations

Prolonged release pharmaceutical preparations containing ion exchange resin drug complexes at least a substantial portion of which have been treated with a solvating agent and provided with a diffusion barrier coating.

Pharmaceutical products

PHARMACEUTICAL PREPARATION

Medicament in particulate form

The medicament in particulate form has one or more anionic or partially anionic active substances bound to a carrier material. The carrier material includes particulate copolymer or homopolymer of acrylic acid or acrylic acid ester or methacrylic acid esters. The carrier further includes oxygen in the ester group, a branched or unbranched alkyl chain with 2-10 carbon atoms, --NR 2 where R represents H and lower alkyl chains in any combination, and H or a lower alkyl chain. The grain size distribution of the carrier is 10-1000 nm.

Process for the preparation of a complexed drug

Compositions using microencapsulated neutralizing antibodies

Compositions useful in treating immune modulated disease comprising an anticytokine antibody or immune active drug capable of modifying cytokine activity or modulating the immune system microencapsulated with a biodegradable nonantigenic material, such as albumin or PLGA. When the composition is introduced into a subject, it is phagocytosed by the target organ, the target organ digests the microsphere, releasing the drug or an active form or fragment thereof intracellularly. The drug then modifies the target organ function, thereby modulating it's activity. A method is disclosed for preparation of the microencapsulated composition.

Process for making absorbable microparticles

The invention pertains to a process for making encased bound microparticles by nebulizing a dispersion of the bound microparticles into a solution of an encasing polymer and into a liquid, non-solvent of said encasing polymer.

Compositions using microencapsulated neutralizing antibodies.

Sustained release drug-resin complexes

Disclosed are oral pharmaceutical preparations which comprise a pharmacologically active drug bound to small particles of an ion-exchange resin to provide a drug-resin complex having a drug content above a specified value. The drug-resin complex is subsequently coated with a water-permeable diffusion barrier coating that is insoluble in gastrointestinal fluids thereby providing a controllable sustained release of drug under conditions encountered in the gastrointestinal tract.

Binding theophylline to ion exchange resins

In a method in which an ionizable pharmaceutical material, such as theophylline, having a pharmaceutically-active anionic group is bonded to an anion exchange resin having cationic groups bonded to displacable anionic groups by bringing said material and said resin into contact with each other under conditions such that the pharmaceutically-active anionic group of said material is bonded to the cationic group of said resin and replaces the anionic group thereof, the improvement comprising effecting said contact in an environment which is substantially free of carbon dioxide and/or bicarbonate ion, a pharmacologically active composition comprising said pharmaceutically active anion and said resin, including a composition in which at least about 40% of the binding capacity of the resin comprises said pharmaceutically active anion, and a sustained release pharmaceutical composition, including enteric coated particles of the composition, and stabilizing said composition by maintaining it in an environment substantially free of bicarbonate and/or carbon dioxide.

Compositions for controlled delivery of pharmaceutical compounds

Sustained release pharmaceutical compound delivery compositions and methods for their production are disclosed wherein ion exchange resin particles are loaded with releasably bound pharmaceutical compounds and incorporated in an aqueous reversibly gelling polymeric solution. The pores of the ion exchange resin are sufficiently small to lock in the pharmaceutical compound without exposure to the large polymer molecules. The pharmaceutical compound remains bound within the pores of the ion exchange resin particles until after administration to a target tissue site where small ions migrate into the pores and initiate an exchange reaction.

Pharmaceutical composition including sodium cromoglycate

Pharmaceutical compositions comprising microspheres incorporating sodium cromoglycate, wherein the microspheres comprise material having ion-exchange properties. There are also described aqueous suspensions of such microspheres and methods of treatment using them.

Pharmaceutical composition including sodium cromoglycate

Pharmaceutical compositions comprising microspheres incorporating sodium cromoglycate, wherein the microspheres comprise material having ion-exchange properties.

Sustained release oral suspensions

Stable sustained release wax- and polymer-coated drug-ion exchange resin complexes especially useful in preparing oral suspensions are disclosed.

Sustained release oral suspensions

Stable sustained release wax- and polymer-coated drug-ion exchange resin complexes especially useful in preparing oral suspensions are disclosed.

Zwitterionic polymer bioconjugates and related methods

Zwitterionic polymer and mixed charge copolymer bioconjugates, methods for making and using the bioconjugates.

Organic polymer compound and production thereof

A homopolymer of a (meth)acrylic acid derivative represented by general formula (I), a process for producing the same by mechanochemical polymerization, and polymer drug and prodrug containing the same: wherein R?1 represents hydrogen or methyl; R?2 represents a residue of a compound having a physiological activity in its chemical structure; X represents a residue of a compound having hydroxyl, amino or carboxyl groups at both terminals in its chemical structure; and n is such a number as to give a number-average molecular weight of 20,000 to 200,000.

Polymer treated ion exchange resin

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

N-maleimidyl polymer derivatives

The invention is directed to multi-functional N-maleimidyl polymer derivatives comprising a water soluble and non-peptidic polymer backbone having a terminal carbon, such as a poly(alkylene glycol), the terminal carbon of the polymer backbone being directly bonded to the nitrogen atom of a N-maleimidyl moiety without a linking group therebetween. The invention also provides two methods of preparing such linkerless N-maleimidyl polymer derivatives.

Patent JPS59500217A

(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。

Colonic-targeted oral drug-dosage forms based on crosslinked hydrogels containing azobonds and exhibiting ph-dependent swelling

Colonic-targeted oral drug dosage forms composed of a drug confined within a crosslinked hydrogel that exhibits pH-dependent swelling and is composed of an ionizable comonomer such as acrylic acid, a nonionizable comonomer such as an acrylamide, and a crosslinking agent that contains an aromatic azobond. Selective drug release in the colon occurs by a combination of pH-dependent swelling of the hydrogel and degradation of the hydrogel by enzymatic cleavage of the azobonds by azoreductases.

Drug delivery system for the simultaneous delivery of drugs activatable by enzymes and light

Compositions for the treatment of cancerous tissues in warm-blooded animals containing both an anticancer drug and a photoactivatable drug attached to copolymeric carriers are made up of a member selected from the group consisting of (a) a copolymeric carrier having attached thereto both an anticancer drug and a photoactivatable drug, (b) a mixture of copolymeric carriers wherein one copolymeric carrier has attached an anticancer drug and the other copolymeric carrier has attached a photoactivatable drug and (c) a combination of (a) and (b). The anticancer drug is attached to the polymeric carrier by side-chains which are stable in the blood stream of the warm-blooded animal but susceptible to hydrolysis by lysosomal enzymes intracellularly. The photoactivatable drug is attached by either the same degradable side-chain or by a non-degradable attachment. The polymer carrier may optionally contain a targeting moiety. Upon administration polymeric macromolecules enter targeted cancer cells by pinocytosis which reduces the side effects normally elicited by the free drugs. A time lag is allowed following administration for optimal uptake of the copolymers in the cancerous tissue for the anticancer agent to begin to take effect. Then a light sources of the appropriate wavelength and energy is to activate the photoactivatable drug. The combined effect of the anticancer agent and photoactivatable drug provides greater cell destruction at reduced dosages and side effects.

Nanocomposite for drug delivery and its manufacturing method

본 발명은 약물 전달용 나노 복합체 및 그 제조방법에 관한 것으로, 보다 상세하게는 물 또는 생리적 용액 내에서 우수한 용해성을 나타내면서도 가수분해가 발생하지 않아 우수한 안정성을 나타낼 수 있는 약물 전달용 나노 복합체에 관한 것이다. 또한, 낮은 pH 하에서 약물을 선택적으로 조절하여 방출할 수 있고, 온도에 따라 약물의 방출속도 및 방출량의 조절이 가능할 수 있다. 따라서 용해도가 낮은 약물들도 효과적으로 작용부위까지 전달하여 약물의 효과를 극대화할 수 있으며, 목표지점 이외에 다른 부위로 운반된 약물에 의한 부작용을 최소화할 수 있다.  The present invention relates to a nanocomposite for drug delivery and a method for producing the nanocomposite. More particularly, the present invention relates to a nanocomposite for drug delivery, which exhibits excellent solubility in water or a physiological solution, will be. In addition, the drug can be selectively controlled and released under a low pH, and the release rate and the release amount of the drug can be controlled depending on the temperature. Thus, drugs with low solubility can be effectively delivered to the site of action, maximizing the effect of the drug, and minimizing adverse effects due to drugs delivered to other sites other than the target site.

Conjugation of polymer to colony stimulating factor-1

A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.

PROCEDURE FOR THE SOLUBILIZATION IN WATER AND IN AQUEOUS VEHICLES OF PHARMACOLOGICALLY ACTIVE SUBSTANCES

siRNA compositions that specifically downregulate expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD)

The invention provides siRNA compositions that specifically downregulates expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD).

siRNA compositions that specifically downregulate expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD)

The invention provides siRNA compositions that specifically downregulates expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD).

Interpenetrating polymer network hydrogel

A strain-hardened interpenetrating polymer network (IPN) hydrogel is provided. The interpenetrating polymer network hydrogel is based on two different networks. The first network is a non-silicone network of preformed hydrophilic non-ionic telechelic macromonomers chemically cross-linked by polymerization of its end-groups. The second network is a non-silicone network of ionizable monomers. The second network has been polymerized and chemically cross-linked in the presence of the first network and has formed physical cross-links with the first network. An aqueous salt solution having a neutral pH is used to ionize and swell the second network in the interpenetrating polymer network. The swelling of the second network is constrained by the first network, and this constraining effect results in an increase in effective physical cross-links within the interpenetrating polymer network, and, in turn, an increase its elastic modulus. The strain-hardened interpenetrating polymer network hydrogel is attractive and useful for medical, industrial, and personal hygiene purposes.

Reversibly Masked Polymers

The present invention is directed to reversibly inactivation of membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.

Membrane active heteropolymers

The present invention is directed to a class of membrane active polymers useful for cellular delivery of compounds. Conjugation of the described membrane active polymers to targeting, anti-opsonization, and anti-aggregation agents provides polymers suitable for in vivo delivery. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.

Endosomolytic poly(vinyl ether) polymers

The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

Endosomolytic poly(acrylate) polymers

The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.

Enzyme-catalyzed synthesis of site-specific and stoichiometric biomolecule-polymer conjugates

Process for solubilizing pharmaceutically active ingredients in water and in aqueous vehicles

Supercritical carbon dioxide extraction method for capsaicinoids

FIELD: chemistry. SUBSTANCE: invention relates to the field of obtaining substances using supercritical media. A method is described for the extraction of capsaicinoids with supercritical carbon dioxide from pungent peppers in a supercritical fluid extraction unit, characterized in that the extraction is carried out in two stages, and in the first stage of extraction, carbon dioxide is used with the use of a co-solvent, which is used as distilled water, then the resulting extract, then the standard collection is replaced with a modified one, and the second stage is carried out, and liquefied carbon dioxide is used as a solvent for extraction in the second stage, after which the obtained extract is discharged into the collection. EFFECT: isolation of two extracts: at the first stage, the isolation of the extract containing: capsaicinoids - 0.8-3.0% (of the total extract), essential oils - 0.5%, dyes - 72.0%, fatty oils - 1.0%, unidentified impurities - 20.0%; at the second stage - the isolation of the extract containing: capsaicinoids - 14-21% (of the total extract), essential oils - 23.0%, dyes - 14.0%, fatty oils - 43.0%. 1 cl, 2 dwg РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 750 703 C1 (51) МПК A61K 47/58 (2017.01) A61K 36/81 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК A61K 47/58 (2021.05); A61K 36/81 (2021.05) (21)(22) Заявка: 2020133884, 14.10.2020 (24) Дата начала отсчета срока действия патента: Дата регистрации: 01.07.2021 (45) Опубликовано: 01.07.2021 Бюл. № 19 2 7 5 0 7 0 3 R U (56) Список документов, цитированных в отчете о поиске: SU 379258 A1, 20.04.1973. CN 107954889 A, 24.04.2018. SU 1622983 A1, 20.04.1995. SU 1121823 A1, 10.04.1995. CN 108276301 A, 13.07.2018. CN 109761840 A, 17.05.2019. (54) Способ экстракции капсаициноидов сверхкритическим диоксидом углерода (57) Реферат: Изобретение относится к области получения на второй стадии используется сжиженный веществ с использованием ...

Process for the manufacture of compounds intended to slowly and uniformly release an active substance in either an acidic or a basic medium