528results about "Insulins" patented technology

To provide methods for treating a subject having or at risk of developing a neurocognitive disorder, such as frontotemporal lobar degeneration or neuronal ceroid lipofuscinosis.SOLUTION: Provided is a method comprising administering, to a subject diagnosed as having a neurocognitive disorder (NCD), a composition comprising a population of cells comprising a transgene encoding a progranulin (PGRN) or a granulin (GRN).SELECTED DRAWING: Figure 1A

Disclosed is an acylated insulin, a pharmaceutical formulation thereof, a pharmaceutical composition thereof with a long-acting GLP-1 compound, and a medical use of the acylated insulin, the pharmaceutical formulation and the pharmaceutical composition. Compared with insulin degludec or other insulin derivatives, the acylated insulin has an unexpected, significantly increased drug effect, a longer duration of action, a longer in vivo half-life, an excellent bioavailability, as well as better physical and chemical stabilities.

Most therapeutic treatments require the adjustment of the prescribed dose following initiation of treatment. Dose adjustment is important to ensure an optimal safety and efficacy profile of a treatment. Gene therapy is inherently limited by its inability to adjust the dose following initial administration. This invention describes genetic elements that enable dose adjustment following initial dosing with a gene therapy. Enablement of dose adjustment allows for the ability of single-injection gene therapy to replace multi-injection subcutaneous protein regiments improving pharmacokinetics, safety / efficacy profile, medication adherence, and reducing healthcare costs.

The present invention relates to an improved process for producing a product comprising a protein of interest (TP) capable of crystallizing under salt soluble conditions by crystallization of said TP. The present invention uses at least two different TP-containing protein feeds, which are mixed to produce a supersaturated protein solution in which TP crystallizes. One of the protein feeds must have a pH at least plus 0.1 to the pH (pHMCY, TP) providing the maximum crystallization yield of the TP, and one of the protein feeds must have a pH at most minus 0.1 to the pHMCY, TP.

The invention discloses a crystallization method of recombinant human insulin, which belongs to the technical field of biological medicine, and comprises the following steps: taking a sample containing recombinant human insulin, carrying out column chromatography salt conversion to obtain a salt conversion eluent, then adding purified water, adjusting the pH value to prepare a solution to be crystallized, and adding an acid solution, a zinc salt solution and arginine to obtain a crystallization solution; and adjusting the pH value and temperature of the crystallization liquid, and crystallizing to obtain the hexahedral crystal. According to the method, the to-be-crystallized solution is prepared from the purified and prepared qualified eluent containing the human insulin in a chromatography salt conversion mode, and the preparation mode of the to-be-crystallized solution is simple, efficient and easy to operate; the crystallization liquid system is simple, only acid, zinc salt and arginine need to be added into the to-be-crystallized solution, phenols and organic solvents do not need to be added, and chemical substance residues are avoided. The residual salt and the organic solvent in the salt conversion concentrated solution are fully utilized to participate in the crystallization reaction, the solvent does not need to be repeatedly added, the reagent is saved, and the process time is shortened.

The present application relates to the field of biomedicine, and specifically provides an acylated human insulin analogue, a pharmaceutical composition thereof and a preparation method therefor, and a method for using the acylated human insulin analogue or the pharmaceutical composition thereof to treat metabolic diseases.

The present invention proposes a method for purifying polypeptides, which uses a high-precision high-performance liquid chromatography system and is also equipped with a control cabinet, an axially pressurized liquid chromatography column (DAC), an eluent delivery system, a sample loading device, an online detection device, and an automatic fraction collection system; the flow error of the pump of the eluent delivery system is within 1.5%; the chromatographic column filler is a spherical mesoporous silica matrix reversed-phase chromatography filler, which is a type of specially constructed silica gel, and has undergone special bonding modification, which effectively improves the effect and yield of polypeptide separation and purification, increases the sample loading amount of the filler, and solves the technical problems existing in the polypeptide purification process such as the large number of micropores, low lifespan, and alkali resistance of traditional silica gel. At the same time, through a closed-loop fully automatic chromatographic purification method that integrates online solvent recovery, online liquid preparation, and UHPLC online detection / automatic fraction collection, the problems of purification, fraction collection, and solvent recovery of large molecular weight polypeptides are solved.

Relaxin (RLN) analogs are disclosed that include modifications that increase half-life compared to native human RLN, maintain selectivity for the RXFP1 receptor, and provide stability in vitro and in vivo, improving druggability and reducing immunogenicity. Pharmaceutical compositions are also disclosed that include one or more of the RLN analogs described herein in a pharmaceutically acceptable carrier. Methods of making and using the RLN analogs are also disclosed, particularly for treating cardiovascular, pulmonary, and / or renal conditions, diseases, or disorders.

The invention discloses a synthesis method of an insulin analogue, which comprises the following steps of: firstly, obtaining A-chain peptide resin by using a solid-phase synthesis method, constructing a disulfide bond between A6 and A11 on a solid phase, and cracking the A-chain peptide resin by using a cracking solution containing a sulfydryl activator to obtain a peptide chain with an activated sulfydryl group and a protected sulfydryl group; then a solid-phase synthesis method is used for obtaining B-chain peptide resin, Lys side chain protecting groups are removed on a solid phase in a fixed-point mode, side chain fatty acid modification is completed, and a peptide chain with an exposed sulfydryl group and a protected sulfydryl group is obtained after cracking is conducted through a cracking solution; and mixing the products in a solution according to a certain proportion to form a first pair of intermolecular disulfide bonds, and constructing and purifying the last pair of disulfide bonds to obtain the insulin analogue. The method disclosed by the invention has the advantages of convenience in synthesis, low cost, simple process and the like, can be used for research on amino acid mutation of insulin compounds, and has important practical significance on development of insulin drugs.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

Provided are β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

Described herein are particles comprising a first compartment, a second compartment, and a compound of Formula (I), as well as compositions and methods of making and using the same. The particles may comprise a cell capable of expressing a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.

Provided are a new acylated insulin, a pharmaceutical preparation thereof, a pharmaceutical composition thereof containing a long-acting GLP-1 compound, and the medical use of the acylated insulin, the pharmaceutical preparation and the pharmaceutical composition.

Compositions and methods for treating diabetes in dogs or cats are provided. A viral particle comprising a polynucleotide encoding a canine or feline insulin-serum albumin fusion polypeptide is administered to a subject.

This disclosure provides a method of preventing, alleviating, or treating a condition (i.e., neutropenia) in a patient in need thereof, the condition characterized by compromised white blood cell production in the patient. The method includes administering to the patient a therapeutically effective amount of a protein complex comprising a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

Provided are β-eliminative linkers suitable for the conjugation of small molecule, peptide, and protein and compounds comprising the linkers.

The invention provides a preparation method and application of a long-acting insulin analogue, and the preparation method comprises the following steps: taking eicosandioic acid A as a starting raw material, carrying out unilateral esterification with trimethylsilyl ethanol to obtain an intermediate B, reacting the intermediate B with Hosu to obtain an active intermediate C, reacting the intermediate C with L-glutamic acid-1-trimethylsilyl ethyl ester to obtain an intermediate D, and carrying out condensation reaction on the intermediate D to obtain the long-acting insulin analogue. The intermediate D reacts with Hosu to obtain an active intermediate E, the intermediate E reacts with AEEA-AEA to obtain an intermediate F, the intermediate F reacts with Hosu to obtain an active intermediate G, and trimethylsilylethyl is removed from the intermediate G through tetrabutylammonium fluoride trihydrate to obtain the Ecobainsulin side chain. The route of the method has the following advantages that related raw materials are simple and easy to obtain, the reaction condition is mild, the yield is high, and the method is suitable for industrial production. The preparation method is simple and easy to implement, large-scale production is easy, the prepared side chain of the Ekoinsulin and A14E, B16E, B25H and DesB30 insulin precursors are coupled with lysine at the B29 site under the alkaline condition to obtain a crude Ekoinsulin product, and the crude product is subjected to two-step purification to obtain the Ekoinsulin with the purity of 99.0% or above.

The invention relates to in vivo generation of beneficial molecules using genetically modified, nonpathogenic microorganisms. The invention has application to various fields, such as medicine, human performance, and veterinary medicine. In various embodiments, the use of transgenic Trypanosoma rangeli, a nonpathogenic microorganism may be purposefully engineered, altered, and designed to be a blood symbiont in humans and animals after genetic modification to express foreign nucleic acid sequences that encode proteins, polynucleotides, and / or pathways to treat disease or enhance specific aspects of host physiology to include metabolic dominance to correct or augment homeostatic imbalances when suitable. The foreign nucleic acid sequences may be used to generate enzymes, scavenger molecules, peptides and hormones, antibodies, nanobodies, signaling ligands, and other therapeutic or novel synthetic agents.

The present invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions associated with diabetes. The insulin derivatives are glucose-sensitive and exhibit glucose-sensitive albumin binding. The present invention also relates to novel intermediates. Finally, the present invention provides pharmaceutical compositions comprising the insulin derivatives of the present invention and the use of such compositions in the treatment or prevention of medical conditions associated with diabetes.

The invention relates to the field of medicines, and particularly discloses a fusion protein with a GIP and GLP-1 dual receptor agonist function and application of the fusion protein. A specifically designed GLP-1 / GIP targeting polypeptide is fused with the N end of an IgG4 heavy chain constant region and the N end of a light chain constant region or the N end of Fc to obtain the GLP-1 / GIP targeting polypeptide. A research result shows that the fusion protein with the GIP and GLP-1 dual receptor agonist function has an obvious effect of reducing the weight of a mouse, the weight of the liver of the mouse is also reduced, the blood sugar of the mouse is also remarkably reduced, and the total cholesterol in serum is reduced to a certain extent. Therefore, the compound can be applied to medicines or products for slimming, reducing blood sugar and treating fatty liver.

The present invention provides an aggregate, a preparation method thereof, and an oral insulin formulation. Specifically, an aggregate formed by the assembly of a chalcogen heterocyclic compound and insulin is provided. The aggregate can be further prepared into an oral insulin formulation. The oral formulation can be used to lower the blood glucose level of mammals and is used as part of a diabetes treatment regimen. The chalcogen heterocyclic compound in the oral insulin formulation prepared by this method can effectively protect insulin from overcoming the three major physiological barriers of the oral intake route, is stable in the gastrointestinal environment, and undergoes a dynamic chemical exchange reaction with the sulfhydryl groups of intestinal mucin in intestinal fluid and the proteins on the inner and outer sides of the epithelial cell membrane through the surface poly-chalcogen molecular bond, entering the circulatory system from intestinal epithelial cells and playing a role in lowering blood glucose. When the oral insulin formulation is administered orally, it has high bioavailability and good blood glucose lowering effect in mammals and can be used for the treatment of diabetes.

Provided herein, inter alia, are methods and compositions for engineering T cells. The methods include culturing T cells with insulin during engineering of the T cells. The methods provided herein contemplate to increase cell viability, expansion and gene editing efficiency, allowing for an increase in the total number of engineered T cells.

The present invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions associated with diabetes. The insulin derivatives are glucose sensitive and show glucose sensitive albumin binding. The present invention also relates to novel intermediates. Finally, the present invention provides pharmaceutical compositions comprising the insulin derivatives of the present invention, and the use of such compositions in the treatment or prevention of medical conditions associated with diabetes.

Disclosed herein are compositions that are useful for targeting a signaling pathway modulator to a muscle cell. In some instances, such compositions may be useful in treating a muscle disorder, such as muscular dystrophy.

A method of increasing lipid synthesis or accumulation in and optionally secretion from a mammary epithelial cell (MEC) culture is provided. The method contacts the MEC with an LXR agonist in the presence of a fatty acid to increase lipid synthesis or accumulation and optionally increase lipid secretion. Also provided is a method of producing synthetic fat globules, the method comprising: (a) isolating lipid droplets from cultured cells; (b) encapsulating the droplets with a lipid bilayer, thereby producing synthetic fat globules. Compositions thus produced are also provided.

Aspects of the disclosure include an implantable composition / medical device encapsulating insulin-producing cells for use in the treatment and management of diabetes, generally comprising a multilayer lattice structure fabricated from a continuously bioprinted cell-laden core / shell fiber, the lattice structure having a defined infill density and at least coating applied to the lattice post-printing, and preferably at least one conformal coating. In this way, multilayer lattice structures are provided with improved stability, retrievability, and functionality.

The present disclosure provides recombinantly manufactured ultra-long acting insulin-Fc fusion proteins for use in treating canine and feline diabetes. The insulin-Fc fusion proteins comprise an insulin polypeptide linked via a peptide linker to an Fc-fragment of canine or feline origin. Based on the results obtained, creating a treatment that is amenable to low cost manufacturing, exhibits sufficient in vivo bioactivity, displays extended duration of bioactivity, does not induce anti-drug antibodies, and substantially retains is potency over multiple administrations, requires a non-obvious combination of insulin polypeptide, peptide linkers, and species-specific Fc fragment, in addition to selective mutations on one or more of these components. Exemplary ultra-long acting insulin-Fc fusion proteins, polynucleotides encoding these insulin-Fc fusion proteins, and pharmaceutical formulations of exemplary insulin-Fc fusion proteins are provided, in addition to methods of use and preparation.

A two-chain insulin analogue contains a modified A-chain polypeptide and a modified B-chain polypeptide. The A-chain polypeptide comprises one or more of: a His or Glu substitution at position A8, a Glu substitution at position A14; and a Gln or Arg substitution at position A17. The B-chain polypeptide comprises one or more of: a deletion of the amino acids at position B1, B1-B2, B1-B3, B30 or a combination thereof; an Ala or Glu substitution at position B2; a Glu substitution at position B3. The analogue exhibits thermodynamic stability in a zinc-free solution, decreased self-association, maintains biological potency, and no increased mitogenicity. The analogue exhibits resistance to chemical degradation and physical degradation. A method of treating a patient with diabetes mellitus or obesity comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.

The invention discloses a synthesis method of insulin degludec, and belongs to the technical field of chemical pharmacy. The preparation method comprises the following steps: adding a reaction solvent into 50-peptide and a side chain serving as raw materials, adjusting the pH value, and reacting to obtain an insulin degludec crude product; the fifty peptide is an insulin degludec main chain; the side chain is a deprotected active ester; and carrying out preparative liquid phase separation and freeze drying on the insulin degludec crude product to obtain the insulin degludec. In the synthesis method provided by the invention, directional conversion is achieved through a reaction solvent and pH value control, the industrial operation difficulty is reduced, and the reaction yield is greatly improved; the total reaction yield is not less than 82%, and the HPLC purity is not less than 99%. The insulin degludec synthesis method provided by the invention has the advantages of simple operation, high directional conversion rate, environmental friendliness, high yield and high purity.

Disclosed is an acylated insulin, a pharmaceutical formulation thereof, a pharmaceutical composition thereof with a long-acting GLP-1 compound, and a medical use of the acylated insulin, the pharmaceutical formulation and the pharmaceutical composition. Compared with insulin degludec or other insulin derivatives, the acylated insulin has an unexpected, significantly increased drug effect, a longer duration of action, a longer in vivo half-life, an excellent bioavailability, as well as better physical and chemical stabilities.