552 results about "Protein drug" patented technology

The invention discloses a chewable composition for oral delivery of bioactive agents having nanoparticles that are composed of chitosan, poly-glutamic acid, and at least one protein drug or bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular protein drug and bioactive agent delivery.

A preparation method for porous microspheres of a biodegradable polymer is provided. The method comprises the following steps: (a) dissolving a biodegradable polymer in an organic solvent to form an oil phase of 1-30% (g / ml) concentration; (b) selecting a pore-forming agent 1-50% of the biodegradable polymer in the step (a) and dissolving the pore-forming agent in water to form an internal water phase; (c) adding dropwise the internal water phase into the oil phase at a volume ratio of (1-30):100, and stirring to form a primary emulsion; (d) preparing a polyvinyl alcohol aqueous solution of 0.5-10% (g / ml) concentration, which serves as an external water phase; (e) pouring the primary emulsion into the external water phase at a volume ratio of (3-30):100, stirring or performing ultrasonic treatment to form a double-emulsion, and allowing the polymer in the double-emulsion to solidify, thereby forming microspheres; (f) freeze-drying the microspheres to obtain the final product. The obtained porous microspheres of the biodegradable polymer have high porosity, large specific surface area and good adsorption and encapsulation properties; and are used for the adsorption and encapsulation of unstable protein drugs, polypeptide drugs and growth factors and can retain pharmaceutical activity and effectiveness thereof.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class Mof chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect

The present invention relates to immunoglobulin Fc variants having an increased binding affinity for FcRn, which is characterized by including one or more amino acid modifications selected from the group consisting of 307S, 308F, 380S, 380A, 428L, 429K, 430S, 433K and 434S (this numbering is according to the EU index) in the constant region of a native immunoglobulin Fc fragment. Owing to the high binding affinity for FcRn, the immunoglobulin Fc variants according to the present invention show more prolonged in vivo half-life, and thus can be used for the preparation of a long-acting formulation of protein drugs.

One aspect of the invention provides a degradable / biocompatible elastomer. The elastomer comprises a degradable cross-linked network of a hydrophobic, hydrolysable amorphous star polymer and a hydrophilic, biocompatible polymer. The network may be crosslinked thermally or by irradiation. In a preferred embodiment, the elastomer is used for a drug delivery system, and is particularly useful for delivery of peptide and protein drugs.

The invention discloses the nanoparticles composed of chitosan, poly-γ-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

A solid lipophilic microparticle having an average particle size ranging from 0.1 to 200 μm, comprising a lipophilic substance, hyaluronic acid or an inorganic salt thereof and an active ingredient selected from the group consisting of a protein or peptide drug, retains the full activity of the active ingredient, and when formulated in the form of an oil dispersion or oil-in-water emulsion, it releases in an in vivo environment the active ingredient in a controlled manner over a long period.

The present invention provides a polysaccharide-functionalized nanoparticle, a drug delivery system for controlled release comprising the nanoparticle and a preparation method thereof. In particular, the nanoparticle of the present invention comprises a core of a biodegradable polymer, an outer hydrogel layer of a biocompatible polymer emulsifier and a polysaccharide physically bound to the core and the hydrogel layer, thus enabling to significantly enhance stability and controlled release of a protein drug such as a growth factor.

The present invention provides for a method of simultaneously treating both cancer and the Multidrug Resistance Phenotype via inhibition of cellular thiols, such as Glutathione S-Transferase (GST). This enzyme is overproduced in leukemia and solid tumor cells and is one of the main pathways involved in the Multidrug Resistance phenotype. The treatment provides for the administration of a chemically inert pro-drug, designed to be a specific substrate for the GST enzyme that, once cleaved, liberates the bioactive toxin Nitric Oxide (NO) intracellularly at the site of a malignant growth. NO then acts to inhibit the growth of the malignant cells and to induce cellular differentiation and apoptosis therein, effectively treating an existing cancerous condition. Additionally, once NO is liberated from the pro-drug, the remaining structure acts to inhibit further GST activity, providing a treatment for the Multidrug Resistant phenotype.

The invention provides modular antibody-therapeutic agent conjugates and antibody-detectable-agent conjugates, and methods of using said conjugates in therapeutic and diagnostic procedures.

A transdermal system for sustained delivery of high molecular weight hydrophilic drugs, especially peptide-, polypeptide- or protein-drugs, and methods of use thereof, are provided. The system includes an apparatus that generates micro-channels in the skin of a subject in combination with a transdermal patch comprising at least one drug reservoir layer comprising a polymeric matrix and a therapeutic or immunogenic peptide, polypeptide, or protein. The system provides sustained delivery of therapeutic or immunogenic agents, thereby achieving sustained therapeutic blood concentrations of these agents.

The invention discloses the nanoparticles composed of chitosan, poly-γ-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

The present invention relates to a nanoparticle-protein-hydrogel composite comprising (1) a polysaccharide-functionalized nanoparticle comprising a core composed of a biodegradable polymer, a hydrogel surface layer composed of a biocompatible polymer emulsifier, and a polysaccharide physically bound to the core and / or the hydrogel layer; (2) a protein forming a specific binding with the polysaccharide; and (3) a hydrogel matrix composed of a biocompatible polymer as a matrix for the nanoparticle. The present also relates to a drug delivery system and a bone defect replacement matrix comprising the composite for sustained release, and the preparation method thereof. Further, the present invention also provides a method for controlling the release rate of a protein drug by changing the content of the polysaccharide in a unit mass of the nanoparticle and / or by changing the content of the nanoparticle in a unit mass of the composite.

The invention relates to the technical field of biological medicines, which is an application of a small polypeptide molecule in preparing a drug for preventing ischemic cerebrovascular disease. The research of the invention finds out that polypeptide bioactive molecules and polypeptide spliceosomes extracted from the secretion of amoeba histolytica have the pharmacological action of preventing ischemic cerebrovascular disease. The pentapeptide and tripeptide are proved to be capable of remarkably reducing the brain damage to the mouse caused by ischemia-reperfusion and remarkably improving the neuro behavioral of the mouse after ischemia by the results of pharmacological experiment on mouse models with focal cerebral ischemia. Compared with the kindred protein drugs, the small polypeptide molecule has strong brain protection effects; in addition, molecular weight is small, thereby being easy to permeate blood-brain barrier and having remarkable advantage of brain permeability. Therefore, the small polypeptide molecule provided has good application prospect in preparing the drug for preventing the ischemic cerebrovascular disease.

The invention aims at providing a method for preparing a multi-drug multi-coating eluting intravascular stent through ultrasonic atomizing and spraying, wherein VEGF, SZ-21 and other protein drugs, taking chitosan as a drug carrier, form a first coating; the second layer is a shielding layer, which adopts a polymer poly L lactic acid (PLLA) and can be added with polyethylene glycol (PEG) in different proportions to control release speed of drug; the third layer is lipid soluble medicine, such as rapamycin, which uses PLLA as a drug carrier; and a coating at the top end of the fourth layer, same as the second layer, is a shielding layer. Two uniform drug polymer coatings can simultaneously load multiple drugs, and the release speed of the drug can be regulated and controlled by regulating a mixing proportion of the PEG and the polymer, so as to inhibit restenosis and to reduce formation of thrombus simultaneously.

The present invention relates to improved pharmaceutical formulations, uses and methods for the oral delivery of peptide or protein drugs with advantageously high bioavailability, safety and cost-effectiveness. In particular, the invention provides a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa for use as a medicament, wherein said peptide or protein drug is to be administered orally in combination with a pharmaceutically acceptable copper salt / complex and / or a pharmaceutically acceptable zinc salt / complex, and with a pharmaceutically acceptable reducing agent. The invention also provides a pharmaceutical composition comprising a peptide or protein drug having a molecular weight of equal to or less than about 50 kDa; a pharmaceutically acceptable copper salt / complex and / or a pharmaceutically acceptable zinc salt / complex; and a pharmaceutically acceptable reducing agent.

Disclosed herein is a hinge antibody capable of being selectively activated in a target cell or tissue to treat a condition therein. The hinge antibody includes a functional antibody, two inhibitory domains and four cleavable linkers. The functional antibody is capable of treating the condition in an activated state, and has two light chains and two heavy chains. Each inhibitory domain includes a hinge domain of an immunoglobulin and consists of two peptide arms. Each cleavable linker includes a peptide substrate cleavable by an enzyme specifically or highly expressed in the target cell or tissue, and connects one of the peptide arms of the inhibitory domains to the N-terminal of one of the light chains and heavy chains of the functional antibody. Also disclosed herein are methods for preparing and using this hinge antibody.

The invention discloses a nano graphene oxide protein complex, a preparation method of the nano graphene oxide protein complex and applications of the nano graphene oxide protein complex. The complex is of a complex structure that protein is absorbed on the surface of the nano graphene oxide. The nano graphene oxide protein complex is prepared as follows: conducting fluorescence labeling on protein drugs, modifying the nano graphene oxide protein by polyethylene glycol (PEG), and combining and gathering the protein drugs on the nano graphene oxide through a physical adsorption mode. The nano graphene oxide protein complex designed by the invention has extremely high loading efficiency and stability; in an in-vitro physiological environment, the protein physically absorbed on the surface of the graphene oxide can be released gradually, the enzyme digestion and the hydrolysis to the protein, caused by the protease can be avoided effectively, and simultaneously, in the cells, the protein can be effectively delivered into the cells from the surface of the graphene oxide. According to the invention, the effects of regulating and controlling the physiological activities of the cells can be improved, the powerful guaranteeing can be provided for the medical application under the physiological conditions; and according to the preparation method provided by the invention, the method is simple and convenient, the cost is low and the volume production is facilitated.

The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one protein drug or bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular protein drug and bioactive agent delivery.

The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

The present invention relates to probiotic microorganisms producing chimeric human growth hormone for oral use and methods for preparing them. The invention provides probiotic Lactobacillus or yeast transformant expressing chimeric protein which is human growth hormone fused with Fc fragment of human IgG, in which the transformants are safely delivered into intestine though oral route. Also, the invention provides a chimeric protein-expressing vector which can induce transcytosis in intestine epithelial cells. Accordingly, the invention demonstrates that the chimeric protein for oral delivery system can be absorbed in intestine, and delivery of the chimeric protein by oral route using Lactobacillus has very excellent efficiency in vivo test in rats. Accordingly, the Lactobacillus of the present invention is an excellent deliverer of protein drugs.

The invention discloses a preparation method of silk fibroin nanospheres, which comprises the following steps: dispersing a silk fibroin solution into nanometer liquid drops by an inverse emulsion method, adding polyols under ultrasonic oscillation to promote silk fibroin in the nanometer liquid drops to form a structure insoluble in water, adding high water-absorbing resins to dry and cure the silk fibroin in a microemulsion state so as to obtain silk fibroin nanospheres which are insoluble in water. The silk fibroin nanospheres have good biocompatibility, are nontoxic and harmless for human body, and have no immunogenicity; the preparation process adopts mild technology with a normal temperature, a normal pressure, and no chemical cross-linking agents; therefore, the product can be used as a carrier with biologically-active substances to load enzymes, nucleic acids, polypeptides, protein drugs, and the like; the obtained silk fibroin spheres have small particle sizes, good dispersibility, do not adhere, and can be prepared into various cosmetics, skin care products, sunscreen creams and the like; the silk fibroin spheres have small particles which can run freely in blood, thus can be used as injections and have wide application in fields of disease diagnosis and treatment.

The invention relates to a method for restraining enveloped virus infection, relative polypeptide and protein drug, belonging to biological medicine technical field. The invention comprises a method for restraining influenza virus, particularly for restraining highly pathogenic influenza virus and human influenza virus (as H1N1 hypotype and H3N2 hypotype), relative polypeptide and protein, relative nucleic acid encoding the polypeptide and protein, and relative carriers and cells for representing the polypeptide and protein.

The invention belongs to the technical field of medicines, and relates to a redox sensitive albumin binding prodrug with a series of tumor tissue specific responses. The albumin binding prodrug is ananti-tumor drug-maleimide molecule prodrug particularly including three docetaxel-maleimide small molecule prodrugs; by utilizing a maleimide ring in a prodrug structure as a target head of plasma albumin 34-bit free sulfydryl in a binding body, so that after a drug enters into a body through intravenous injection, the drug is quickly and specifically bound with albumin to form an albumin-drug composition; therefore, the drug stability is enhanced, the circulation time of the drug in the boy is obviously prolonged, and accumulation of the drug on tumor tissues is realized by utilizing an EPR (Enhanced Permeability and Retention) effect. In addition, in the prodrug structure, by using a redox sensitive key as a binding key, quick release of the drug in tumor cells is promoted, a toxic effect of the drug on normal cells also can be alleviated, the prodrug has high selectivity, the aims of increasing an effect and reducing the toxicity of docetaxel are fulfilled, and a greater market application prospect is achieved.

The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.

The invention discloses a cross-linkable amphiphilic natural polysaccharide and application thereof. Specifically, in particular, a double-bond and a hydrophobic chain are employed for dual modification of a natural polysaccharide polymer to obtain cross-linkable amphiphilic natural polysaccharide, and the cross-linkable amphiphilic natural polysaccharide is applied to loading and delivery of protein drugs. The amphiphilic natural polysaccharide provided by the invention can self-assemble into nanogel with protein loading capacity in an aqueous solution, and then an initiator is employed to activate the double-bond modifying natural polysaccharide to generate a free radical, thus triggering mutual crosslinking of the double-bond to form a new covalent bond, and the stable action force of the covalent bond is utilized to obtain the preparation so as to achieve efficient delivery of protein drugs.

This invention belongs to chemistry pharmaceutical field and relates to a medication transfer system, especially relates to an agglutinin masked medication-load transfer mechanism transferring from nose to brain. This invention comprises medication carrier nanograin, vesicle or lipid body surface finish agglutinin. By using the transfer system, resort time of medication-load system on nasal mucosa can be prolonged, dielectric mucosa absorb the medication-load system and selectively deliver small molecular chemistry medication, diagnosis medication, polypeptide proteins and gene medication into brain. This invention can deliver more medication into brain and relatively decrease medication in outer tissue, so it can depress toxic action at every pore while toning up prevention, cure and diagnosis effect of backbone diseases.

The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.