177results about "Insulins" patented technology

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 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.

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 invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions relating to diabetes. The insulin derivatives are glucose sensitive and display glucose-sensitive albumin binding. The insulin derivatives have a long half-life. The invention also relates to novel intermediates. Finally, the invention provides a pharmaceutical composition comprising the insulin derivatives of the invention and the use of such a composition in the treatment or prevention of medical conditions relating to diabetes.

Provided herein are engineered insulin polypeptide that exhibit disrupted cross-β fibrillation and pharmaceutical compositions comprising the polypeptides. The disclosure also provides are methods for making the insulin polypeptide. Also included are methods of using the pharmaceutical compositions to treat diabetes and hyperglycemia.

The present disclosure relates to toxin-derived delivery constructs, in particular isolated non-naturally occurring delivery constructs, for oral delivery, comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering a bioactive cargo through epithelial cells via endocytotic transport; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

Provided herein are methods for generating a protein product, comprising: providing a plant seed; contacting said plant seed with a protein expression vector that encodes for a protein; transiently expressing said protein in said plant seed using said protein expression vector, and isolating said protein from said plant seed to obtain a protein product.

To provide neoantigens and uses thereof.SOLUTION: Disclosure herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. The use of immunotherapeutic compositions is also disclosed. Novel immunotherapeutic agents and uses thereof are disclosed herein based on the finding of neoantigens generated from individual tumor-specific mutations. Thus, the disclosure provides peptides, polynucleotides encoding the peptides and peptide binding agents that may be used for stimulating immune response toward tumor associated antigen or neoepitopes, or for creating immunogenic compositions or cancer vaccines for use in disease treatment.SELECTED DRAWING: None

This application provides an insulin analogue and its use, the insulin analogue comprising an A chain and a B chain; the sequence of the A chain includes: GIVEQCCTSICSLX aa14 QLENYCN, the B-chain sequence contains: FVNQHLCGSHLVEALY aa16 LVCGEY aa22 GF Y aa25 YTPY aa29 Y aa30 ; where X aa14 Selected from E, Y, K, or D, Y aa16 Selected from Y or H, Y aa22 Selected from Q, S, T, Y, or N, Y aa25 Selected from F, H, or K, Y aa29 Let R and Y be... aa30 It does not exist; the condition is: X aa14 and Y aa25 There is only one K in the insulin analogue. The insulin derivative obtained by the above-mentioned insulin analogue has significantly better in vitro INSR phosphorylation activity and glucose uptake activity than the control drug Icodec. The efficacy (PD) was evaluated using a type 1 diabetic rat model. It has the potential to be administered once a week or less frequently and has a significant hypoglycemic effect.

Provided herein are compositions, systems, kits, devices, and methods comprising peptides of interest, mixture of individual amino acids, an aqueous solution, and uses thereof. The methods comprising peptides of interest may be characterized as methods of synthesizing a peptide. These peptides of interest may be characterized as hydrophobic or partially hydrophobic. These individual amino acids may be characterized as natural amino acids or unnatural amino acids. The aqueous solution may be characterized as pure or substantially pure water. Various compositions, systems, kits, devices, or methods of the present disclosure may involve synthesizing a peptide of interest from a template peptide.

The disclosure relates to novel compounds that include one or more aromatic boron-containing groups, including diboronates, and methods of making the disclosed compounds. The present disclosure further relates to pharmaceutical compositions comprising the disclosed compounds, and their use in prevention and treatment of diseases and disorders, such as hyperglycemia, type 2 diabetes, impaired glucose tolerance, type 1 diabetes, obesity, metabolic syndrome X, or dyslipidemia, diabetes during pregnancy, pre-diabetes, Alzheimer's disease, MODY 1, MODY 2 or MODY 3 diabetes, mood disorders, and psychiatric disorders.

The invention relates to a composition, in particular solid, comprising a permeation enhancer, said permeation enhancer being an acylated aminoacid substituted on the amine function, also called AC-aa-NS, said composition comprising in particular a peptide or a protein, the AC-aa-NS compounds, their methods of preparation and their use in medicine.

Provided are compositions and methods for treating diabetes in a canine or feline. A canine or feline insulin-serum albumin fusion protein is administered to a subject.

The present invention relates to a composition comprising: an insulin derivative comprising at least one arylboronic acid or arylboroxol; and methionine, and to the use of the composition in the treatment of diabetes mellitus, including type 1 diabetes mellitus and type 2 diabetes mellitus.

The present invention belongs to the technical field of insulin derivatives. Disclosed are a phenylboronic-acid-based insulin derivative, and a preparation method therefor and the use thereof. The provided phenylboronic-acid-based insulin derivative has a good glucose-responsive release function, wherein the phenylboronic acid group binds to a glycosyl protein to generate a phenylboronic acid ester bond, thereby generating an insulin and glycosyl protein complex in situ in blood. When the concentration of glucose in the blood is high, the glucose specifically cleaves the phenylboronic acid ester bond, thereby releasing the insulin. The provided phenylboronic-acid-based insulin derivative achieves stable and rapid glucose-responsive insulin release, which can steadily and persistently maintain the blood glucose of a diabetic subject within the normal range with almost no occurrence of hypoglycemia.

To provide dosing regimens of GLP-1 analogs for the treatment of fat, obese, overweight, nonalcoholic fatty liver disease (NAFLD), and / or nonalcoholic steatohepatitis (NASH).SOLUTION: Administering to the subject a first effective amount of one or more first active ingredients selected from the group consisting of GLP-1 and GLP-1 analogs; A dosing regimen is provided, comprising: a first effective amount administered continuously, or intermittently at an interval between two consecutive administrations of six hours or less; and one or more second active ingredients selected from the group consisting of a second effective amount of GLP-I and a GLP-1 analog, administered to said subject once daily, twice daily, three times daily, or four times daily.SELECTED DRAWING: None

Provided herein are pharmaceutical dosage forms for delivering peptide therapeutics to a mucosal surface. The pharmaceutical dosage forms comprise a mucoadhesive layer; a peptide loading layer; and a water impermeable layer, wherein the peptide loading layer is between the mucoadhesive layer and the water impermeable layer, such that the water impermeable layer facilitates unidirectional movement of the an encapsulated peptide through the mucoadhesive layer and to the target mucosal surface. The pharmaceutical dosage form is suitable for delivery of the encapsulated peptide therapeutic to buccal mucosa; sublingual mucosa; palate mucosa; and tongue mucosa. The peptide therapeutic may be an insulin; an insulin derivative; an insulin analog; a pre-insulin; a pro-drug of insulin; a glucagon-like peptide 1 (GLP-1); a GLP-1 analog; a pre- GLP-1; a pro-drug of GLP- 1; or a combination thereof and may be suitable for the treatment of diabetes.

The invention relates to an application of a fatty acid-containing side chain in the aspects of improving the activity, activity selectivity and oral availability of a polypeptide derivative, a method for realizing the application and the polypeptide derivative modified by the side chain.

Provided herein are the use of fatty acid-containing side chains in improving the activity, activity selectivity, and oral availability of polypeptide derivatives, methods for achieving such use, and polypeptide derivatives modified by such side chains.

This invention relates to drug-device core-shell microneedle devices containing anti-diabetes and anti-obesity medications, and transdermal delivery of said medications. The microneedle drug-device system comprises: (a) a two-dimensional array of conical bilayer containing an inner layer with the base diameter ranging from about 100 mm to about 500 mm and the height ranging from about 100 mm about 1200 mm capable of accommodating a known amount of anti-diabetes and / or anti-obesity medications, and a suitable, photostable chromophore or a fluorophore whose absorption and / or emission occurring in the range of 400-900 nm; (b) a larger outer layer that adheres to and encapsulates the inner layer, and protects the inner layer, and (c) a two-dimensional array of cylindrical 'cap layer' that aligns with and adheres to the basal surface of core shell bilayer and seals the bilayer to prevent leakage of said medication(s). The apical (i.e., sharp) ends of the conical bilayer array inserts into the skin and are programmed to allow the said medications to effuse out of the bilayer and into the skin in a controlled fashion and to be monitored by photodetection devices.

Discloses herein are conjugates of a protein and one or more reducing sugars, wherein one, two, three or more target amino groups of the protein are glycated. Also disclosed are methods for the preparation of the glycated protein. Conjugates having one or more ketoamine linkages are efficiently prepared through the reaction between the protein and reducing sugars and exhibit desirable pharmaceutical properties.

The present disclosure relates to, inter alia, compositions and pharmaceutical composition s, including heterologous chimeric proteins that find use, inter alia, in the treatment of diabetes, obesity, or metabolic syndrome.

The invention relates to a TCEP-based recombinant proinsulin inclusion body denaturation and renaturation method, according to the method, TCEP is added as a reducing agent in the denaturation and renaturation process, compared with the prior art, the yield of proinsulin denaturation and renaturation is increased, and the yield of insulin is remarkably increased. Besides, TCEP is high in reducibility, wide in applicable pH range and extremely low in toxicity, so that the production efficiency and the process stability of the recombinant insulin production process can be remarkably improved, the harm to operators and the environment is reduced, and the requirements of green chemistry and safe production are met.

The present invention provides polypeptides comprising a NH-1,2,3-triazole, two alternative methods for synthesizing such polypeptides and a method for preparing a polypeptide being a stabilized variant of a protein having a certain function, which method comprises introducing at least one 1H-1,2,3-triazole moiety into said protein, thereby providing a polypeptide having increased stability and substantially the same biological function. Furthermore, the invention provides a metal affinity chromatographic method for purifying a polypeptide being NH-1,2,3-triazole functionalized.

Disclosed herein are insulin analogues containing a pairwise substitution of cysteine at positions A6 and A11 with selenocysteine residues such that a diselenide bridge forms between these positions. The disleenide bridge of the [SecA6, SecA11] insulin analogues stabilizes the analogue relative to its [CysA6, CysA11] parent structure, providing formulations with extended shelf life at or above room temperature. Also provide are methods of treating diabetes mellitus using the [SecA6, SecA11] insulin analogue.

The application discloses a recombinant protein, a DNA fragment, an expression vector, a preparation method of a transgenic lettuce and an oral hypoglycemic drug, relates to the technical field of biological medicines, and the amino acid sequence of the recombinant protein is shown as SEQ ID NO:1.The recombinant protein, i.e., a human transferrin-proinsulin fusion protein, can utilize the natural combination of the human transferrin-transferrin receptor to mediate the endocytosis transport of proinsulin after being orally taken, pass through the intestinal tract to enter the blood system, and reduce blood sugar.According to animal experiments, the effect of the recombinant protein is close to that of natural insulin, and the recombinant protein realizes oral delivery of insulin.

The invention belongs to the field of biological medicine preparation. The green synthesis method comprises the following steps: adjusting the pH value to 10.0-10.5, and reacting a main chain 50AA and a side chain (deprotected active ester) of the Ekoinsulin in a reaction solvent to obtain the Ekoinsulin. According to the invention, by controlling reaction conditions, such as adjusting a reaction solvent and a reaction pH value, directional conversion of the reaction between the main chain 50AA and the side chain of the Ekebainsulin is realized, the industrial operation difficulty is reduced, the reaction yield is greatly improved, the total reaction yield is not less than 85.7%, and the HPLC purity is greater than 99%.

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

Disclosed are a device, system, methods and computer-readable medium products that provide techniques for evaluating and modifying a duration of insulin action setting usable by an automatic medication delivery algorithm, such as an artificial pancreas application.