254 results about "PEGylation" patented technology

The invention relates to the technical field of bioactive peptides, in particular to an antioxidant peptide based on mussel byssus, a preparation method, a preparation and application of the antioxidant peptide based on mussel byssus, the antioxidant peptide is designed and synthesized by referring to the structural characteristics of mussel byssus proteins mfp-3, mfp-5 and mfp-6, the antioxidant peptide comprises four sequences of MFP3-AP1, MFP5-AP2, MFP6-AP3 and MFP-Hybrid, tyrosine in the peptide is modified into DOPA through enzymatic modification, and the antioxidant peptide is prepared through enzymatic modification. The stability and activity of the antioxidant peptide are enhanced through disulfide bond formation, metal ion coordination, PEGylation and other modifications, and the antioxidant peptide has high DPPH free radical scavenging activity, ABTS free radical scavenging activity, hydroxyl free radical scavenging activity and iron ion reducing capacity, has a protective effect on the cellular level, can be prepared into a liquid preparation, a freeze-dried preparation or a micro-capsule preparation, and can be used for preparing the antioxidant peptide. The compound is expected to be applied to the fields of antioxidant health care products, cosmetics and medicines.

The invention belongs to the technical field of bionic nano-drugs, and particularly relates to a bionic vesicle preparation as well as a preparation method and application thereof. The bionic vesicle preparation disclosed by the invention is prepared from the following raw materials: mesenchymal stem cell outer vesicles, nintedanib and DSPE-PEG-HA (hyaluronic acid modified pegylated phospholipid); the nintedanib is loaded in the mesenchymal stem cell outer vesicle, and the DSPE-PEG-HA is coupled to the surface of the mesenchymal stem cell outer vesicle. The bionic vesicle preparation disclosed by the invention can be used for directly delivering a drug to a pulmonary fibrosis injury part through inhalation type drug delivery, and acting on a focus part at a higher local concentration, meanwhile, the exposure of the drug in whole-body circulation is remarkably reduced, the occurrence of side effects is reduced, and the specific targeting intervention and regulation on fibroblasts are realized.

The invention relates to a pegylated cellulose nanocrystal and a preparation method and application thereof, in particular to the technical field of nanomaterials, the preparation method comprises the following steps: modifying polyethylene glycol into chlorinated polyethylene glycol; carrying out alkaline treatment on the cellulose nanocrystal to enhance the activity of the cellulose nanocrystal; then mixing and reacting the polyethylene glycol cellulose nanocrystal and the polyethylene glycol cellulose nanocrystal to obtain a polyethylene glycol cellulose nanocrystal; according to the invention, polyethylene glycol is grafted on the surface of the cellulose nanocrystal through chemical reaction, so that the action mechanism of the cellulose nanocrystal is changed and enhanced, on one hand, the grafting of polyethylene glycol not only exerts the steric hindrance effect, but also enhances the characteristics (crystallinity, thermal stability and dispersity) of the cellulose nanocrystal; on the other hand, due to the existence of polyethylene glycol, the short-circuit diffusion effect and the nucleation effect can be enhanced, so that the cement hydration degree is improved; and polyethylene glycol has an internal curing effect, so that the self-constriction of the cement-based material can be reduced.

Provided herein are PEGylated liposomes, and methods of making and using thereof. The PEGylated liposomes comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less. The PEGylated liposomes are stable and capable of delivery of an agent for the generation of an immune response, for example an agent for vaccine, therapeutic, or diagnostic uses. Compositions and methods related to making the PEGylated liposomes and using the PEGylated liposomes for stimulating an immune response are also provided.

The disclosure provides method of treating cancer in a patient with ATM-deficient or ATR-deficient tumors, comprising safely and efficaciously administering to the patient PLXO38, a long lasting-PEGylated prodrug of the topoisomerase I inhibitor. The disclosure further provides combination therapies of PLXO38 with inhibitors of the DNA damage response (DDR).

The present invention provides synthetic peptide compounds and uses thereof for therapy and diagnostics of complement-mediated diseases, such as inflammatory diseases, autoimmune diseases, and microbial and bacterial infections; and non-complement-mediated diseases, such cystic fibrosis and various acute diseases. The invention is directed to modifications of a synthetic peptide of 15 amino acids from the Polar Assortant (PA) peptide, which is a scrambled peptide derived from human Astrovirus protein. In some embodiments, the invention is directed to peptide compounds that are peptide mimetics, peptide analogs and / or synthetic derivatives of PA (e.g., sarcosine derivatives) having, for example, internal peptide substitutions, and modifications, including PEGylation at the N-terminus and C-terminus. The invention further provides methods of selecting at least one synthetic peptide for treating various conditions.

The invention belongs to the field of biological medicine, and particularly relates to lipid nanoparticles, application thereof and a drug delivery carrier. The lipid nanoparticle comprises an ionizable lipid, cholesterol, phospholipid, a pegylated lipid and a sterol substitute, and is characterized in that the ionizable lipid is Lipid 5, the phospholipid is DSPC, the pegylated lipid is 18: 0 mPEG2000 PE, and the sterol substitute is one or more of beta-sitosterol, stigmasterol or stigmasterol or a derivative thereof; the molar ratio of the ionizable lipid to the cholesterol to the phospholipid to the pegylated lipid to the sterol substitute is (40-60): (5-38.5): (5-30): (1-2): (5-38.5). According to the invention, the LNP with unique physicochemical properties is constructed through high synergy of the components, the technical problems of low delivery efficiency and poor specificity of hematopoietic stem progenitor cells in the prior art are solved, and high-efficiency and high-specificity drug delivery of HSPCs in vivo and in vitro is realized. The invention also provides a drug delivery carrier containing the lipid nanoparticles and a preparation method thereof.

Provided herein are PEGylated liposomes, and methods of making and using thereof. The PEGylated liposomes comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less. The PEGylated liposomes are stable and capable of delivery of an agent for the generation of an immune response, for example an agent for vaccine, therapeutic, or diagnostic uses. Compositions and methods related to making the PEGylated liposomes and using the PEGylated liposomes for stimulating an immune response are also provided.

A method and kit are provided for detecting anti-drug antibodies (ADAs) against self-assembling trimeric biologics, such as XPro1595, a pegylated variant of soluble human Tumor Necrosis Factor, in biological samples, particularly human serum. The method employs an Affinity Capture Elution-Protein A / G (ACE-AG) assay that overcomes non-specific reagent interactions inherent in conventional bridging and standard ACE assays due to the biologic's dynamic monomer exchange. The assay utilizes a two-plate system: a streptavidin-coated plate with biotinylated trimeric biologic captures ADAs, which are eluted, neutralized, and transferred to a protein A / G-coated plate for specific immunoglobulin capture and detection with a sulfo-tagged trimeric biologic via electrochemiluminescence. The kit includes pre-coated plates, labeled biologics, elution and neutralization solutions, assay buffer, confirmatory reagent, and instructions. The assay offers a robust, specific, and sensitive solution for immunogenicity testing of trimeric biologics.

Described are methods for producing recombinant Arginase, such as PEGylated, cobalt-substituted recombinant human Arginase 1. Also described are pharmaceutical compositions comprising such recombinant Arginase, as well as methods of treatment and uses of such recombinant Arginase.

The invention discloses a preparation method of a pegylation acoustic catalysis effect black phosphorus loaded biological enzyme nano particle, which is a novel nano composite material based on material chemistry and pharmaceutical chemistry, and bacterial keratitis is treated by using the unique acoustic catalysis property of the nano particle. Nanoparticle synthesis mainly comprises the following steps: 1) pretreatment of commercial black phosphorus; (2) uploading biological enzyme iron-curcumin to black phosphorus in situ; and (3) synthesizing hyaluronic acid coupled phospholipid polyethylene glycol (DSPE-coated PEG2000-HA) and modifying the biological enzyme black phosphorus nanoparticles. The finally obtained nano composite material has good biocompatibility, ocular surface adhesion, biological enzyme activity and acoustic catalytic treatment effect on bacterial biofilm infection of eyes.

The invention relates to lipid nanoparticles for fish in-vivo skin gene editing and application of the lipid nanoparticles, and belongs to the technical field of fish gene editing. The lipid nanoparticle for fish in-vivo skin gene editing comprises a gene editing element and a lipid layer, wherein the lipid layer wraps the surface of the gene editing element; the gene editing element is a CRISPR (clustered regularly interspaced short palindromic repeats) / Cas9 (CRISPR associated protein 9) ribonucleoprotein compound or nucleic acid for coding the compound; the lipid nanoparticle carrier comprises ionizable cationic lipid, auxiliary lipid, cholesterol, pegylated lipid and permanent cationic lipid, and the lipid nanoparticle carrier comprises the following components in parts by mole: 15 parts of ionizable cationic lipid, 25-30 parts of auxiliary lipid, 30 parts of cholesterol, 3 parts of pegylated lipid and 7 parts of permanent cationic lipid. The formula is high in pertinence, high in editing efficiency, simple, convenient and safe to operate and wide in application prospect.

The present invention relates to an improved method for separating and detecting of free or residual polyethylene glycol (PEG) in pegylated protein mixture. In particular, the method improves sensitivity, effective separation, and robustness of the quantification of free or residual PEG and related substance present in pegylated protein mixture which obtained as drug substance or drug product.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles include a novel ionizable lipid as well as additional lipids such as cationic lipids, phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles further including therapeutic and / or prophylactic agents such as RNA are useful in the delivery of therapeutic and / or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

This description provides formulations for a pharmaceutical product comprising a PEGylated CBS protein having the amino acid sequence SEQ ID NO: 1. Dosages and dosage regimens are provided for the treatment of homocystinuria in a subject in need. In addition, dosages and dosage regimens are also provided for reducing homocysteine ​​(Hcy) levels or increasing cysteine ​​(Cys) and / or cystathionine (Cth) levels in a subject in need.

The present disclosure provides compositions which facilitate preferential targeting or delivery of a therapeutic agent to a particular organ, cell, or tissue. The presently disclosed compositions comprise lipid nanoparticles formed from a covalent-bond forming lipid, a cationic lipid, and, in some embodiments, a steroid or sterol, a phospholipid, and a PEG lipid.

The invention discloses an application of pegylated irinotecan in preparation of a medicine for preventing and / or treating triple-negative breast cancer brain metastasis diseases, which is shown by in-vivo imaging observation and lifetime observation of high, medium and low dose groups of pegylated irinotecan with a specific structure. The high-dose group, the medium-dose group and the low-dose group all have a definite anti-tumor effect, bioluminescence signal values are inhibited to different degrees, the lifetime is prolonged, and the lifetime of the high-dose group and the lifetime of the medium-dose group are remarkably longer than that of the NKTR-102 group.

Formulations of gas-filled microvesicles comprising a ligand, which may advantageously be used in methods for separating cells or biological materials. The formulations comprise a phospholipid and a suitable mixture of a pegylated phospholipid and of a pegylated phospholipid comprising a ligand.

The disclosure relates to methods of delivering a gene therapy agent to a subject, treating an individual in need of a gene therapy agent, increasing expression of a gene therapy agent, reducing an immune response to a gene therapy agent, and preventing immune-related adverse events in a subject by administering a gene therapy agent and an IL-2 conjugate to the subject. The IL-2 conjugate has at least one amino acid residue replaced by an unnatural amino acid linked to a conjugating moiety. The disclosure further relates to methods of selecting a subject for treatment with a gene therapy agent and an IL-2 conjugate.

The present invention relates to a functionalized artificial cell based on a composite coacervate, preparation and application thereof, and relates to the field of biomedicine technology. The preparation method is as follows: a positively charged solution and a negatively charged solution are mixed, the positively charged solution being a polylysine solution or an ε-polylysine hydrochloride solution, and the negatively charged solution being a deoxyribonucleic acid solution; a coacervate droplet suspension containing functional components is obtained by liquid-liquid phase separation; phospholipids and PEGylated phospholipids are dissolved in an organic solvent and then subjected to vacuum rotary evaporation until the organic solvent evaporates to obtain a lipid membrane; the coacervate droplet suspension is added to the lipid membrane for hydration until the lipid membrane is completely dissolved, thereby obtaining a functionalized artificial cell; at least one of the positively charged solution, the negatively charged solution and the phospholipid solution contains a functional component. The functionalized artificial cell based on the composite coacervate constructed by the present invention has a cell membrane-like and cytoplasm-like structure, and has good physiological stability and biocompatibility.

Provided herein is an antibody-drug conjugate (ADC) especially a PEGylated mono- or bispecific antibody hydroxyl-bearing drug conjugate prepared with site-specific conjugation to provide homogeneous conjugate with high potency and low toxicity. The disclosure also relates to a method for the preparation of the antibody hydroxyl-bearing drug conjugate, a composition comprising the antibody hydroxyl-bearing drug conjugate, and the use thereof in treating diseases.

This invention relates to the field of biomedical technology, specifically to a polyethylene glycol-modified liposome loaded with dimethylcurcumin and its preparation method. First, cholesterol is reacted with succinic anhydride to obtain cholesterol monosuccinate. Then, the cholesterol monosuccinate is coupled with polyethylene glycol via an ester bond to synthesize polyethylene glycol-cholesterol. Using polyethylene glycol-cholesterol, polyethylene glycol monostearate, and lecithin as the main components, and dimethylcurcumin as the model drug, polyethylene glycol-modified dimethylcurcumin liposomes are prepared using a thin-film hydration method. These liposomes exhibit high encapsulation efficiency. In vitro simulated drug release experiments show that these liposomes can improve the sustained-release effect of dimethylcurcumin. Cytotoxicity experiments also demonstrate that the polyethylene glycol-modified dimethylcurcumin liposomes possess good antitumor activity.

Provided is a method for improving the stability of urate oxidase. The inventors have discovered that combining an active ingredient urate oxidase or chemically modified urate oxidase with a stabilizer xanthine through a non-covalent bond can significantly improve the in vivo and in vitro stability of urate oxidase and chemically modified urate oxidase in the form of a tetramer, thereby effectively improving the stability of urate oxidase.

Provided herein are targeting compounds (e.g., a compound of Formula I, a stereoisomer thereof, a tautomer thereof, and / or a pharmaceutically acceptable salt thereof), lipid nanoparticle (LNP) compositions comprising such targeting compounds and the use thereof. The LNP compositions described herein may further comprise one or more selected from ionizable lipids, PEG-lipids, phospholipids, and structural lipids.

A drug delivery vehicle comprising a vesicle conjugated to one or more targeting groups, wherein the targeting groups comprise an oligosaccharide which is Lewis A or Lewis B or a mimetic thereof, or a pharmaceutically acceptable salt or PEGylated form of the oligosaccharide:wherein R represents the point of attachment to the vesicle.

The present invention discloses a PEGylated asparaginase and its application in drug preparation and clinical treatment. In the PEG-modified asparaginase of the present invention, one molecule of asparaginase is coupled with 13-45 molecules of polyethylene glycol, wherein the polyethylene glycol is a linear polyethylene glycol with an average molecular weight of 2-20 kDa. The asparaginase after PEG modification prepared by the present invention. The PEGylated asparaginase provided by the present invention has the advantages of reducing immunogenicity and significantly extending half-life, and the coupling of polyethylene glycol and asparaginase is more stable. Compared with the original research drug and generic drug products of the PEGylated asparaginase sold on the market, the PEGylated asparaginase provided by the present invention has a more stable structure, a firm PEG bond, is not easy to fall off, and has higher homogeneity and activity.

The invention belongs to the field of biological medicine, and particularly relates to a mass spectrum tag probe for a rapid drug sensitive test as well as preparation and application thereof, and the mass spectrum tag probe mainly comprises three parts, namely a gold nanoparticle carrier, a pegylated antibiotic target head and a mass spectrum tag peptide fragment. The probe disclosed by the invention is low in preparation cost, good in stability and high in detection speed (only 4 hours), and compared with a traditional drug sensitive test, the probe disclosed by the invention can be used for directly detecting a complex bacterial sample and does not need to be purified and cultured; compared with biosensing and mass spectrometry technologies, the probe provided by the invention has higher detection sensitivity and is not easily influenced by a matrix; compared with a qPCR technology, the method does not need to know the sequence information of the drug-resistant gene in advance, can directly detect the apparent sensitivity / drug resistance of bacteria, and is wider in detection range; compared with biosensing, mass spectrometry, qPCR and other methods, the probe provided by the invention can realize detection of various pathogenic bacteria and detection of sensitivity of multiple antibiotic drugs.

This invention relates to lipid nanoparticles for in vivo skin gene editing in fish and their applications, belonging to the field of fish gene editing technology. The lipid nanoparticles for in vivo skin gene editing in fish comprise: a gene editing element and a lipid layer, wherein the lipid layer coats the surface of the gene editing element; the gene editing element is a CRISPR / Cas9 ribonucleoprotein complex or a nucleic acid encoding the complex; the lipid nanoparticle carrier comprises ionizable cationic lipids, auxiliary lipids, cholesterol, polyethylene glycol-modified lipids, and permanently cationic lipids, and by molar weight, the proportions are 15 parts ionizable cationic lipids, 25-30 parts auxiliary lipids, 30 parts cholesterol, 3 parts polyethylene glycol-modified lipids, and 7 parts permanently cationic lipids. The formulation of this invention is highly targeted, has high editing efficiency, is simple and safe to operate, and has broad application prospects.