22 results about "Long acting insulin" patented technology

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.

The present invention relates to the field of pharmaceutical synthesis. A long-acting insulin compound is disclosed. The long-acting insulin compound of the present invention for preparing a pharmaceutical composition for treating disease, and use of the pharmaceutical composition in treating various diseases, including type-I diabetes, type-II diabetes, and gestational diabetes.

Fixed doses and administration regimens for long-acting insulin receptor agonists suitable for once-weekly administration, such as weekly basal insulin-Fc (BIF), are described herein.

The present disclosure provides recombinantly manufactured ultra-long acting insulin-Fe fusion proteins for use in treating canine and feline diabetes. The insulin-Fe fusion proteins comprise an insulin polypeptide linked via a peptide linker to an Fe-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-dmg antibodies, and substantially retains is potency over multiple administrations, requires a non-obvious com- bination of insulin polypeptide, peptide linkers, and species-specific Fe fragment, in addition to selective mutations on one or more of these components. Exemplary ultra-long acting insulin-Fe fusion proteins, polynucleotides encoding these insulin-Fe fusion proteins, and pharmaceutical formulations of exemplary insulin-Fe fusion proteins are provided, in addition to methods of use and preparation. 20 24 28 71 86 23 D ec 2 02 4 1 0 0 5 6 8 8 4 5 4 A B S T R A C T 2 0 2 4 2 8 7 1 8 6 2 3 D e c 2 0 2 4

The invention provides a method for preparing a long aliphatic chain diacid derivative and application of the long aliphatic chain diacid derivative, and the method comprises the following steps: carrying out acylating chlorination reaction on long aliphatic chain diacid with a structure as shown in a formula (A), and reacting with tert-butyl alcohol to obtain long aliphatic chain diacid-tert-butyl ester; the preparation method comprises the following steps: sequentially carrying out esterification reaction, nucleophilic addition amidation reaction with a compound as shown in a formula (B), hydrogenation reaction, nucleophilic addition amidation reaction with a compound as shown in a formula (E), esterification reaction with N-hydroxysuccinimide and nucleophilic addition amidation reaction with a compound as shown in a formula (H) on long aliphatic chain diacid tert-butyl ester; and carrying out esterification reaction with N-hydroxysuccinimide, and finally carrying out deprotection reaction to obtain the compound as shown in the formula (K). The method has the advantages of simplicity and convenience in operation, low content of related impurities in the product, easiness in purification of an intermediate, high yield, simplicity in purification of the product, commercialization and the like, and a new idea is provided for preparation of long-acting insulin.

This disclosure provides a recombinantly prepared ultralong-acting insulin-Fc fusion protein for the treatment of diabetes. The insulin-Fc fusion protein comprises an insulin polypeptide linked to a human Fc fragment via a peptide linker. Based on the results obtained, a therapeutically appropriate combination of insulin polypeptide, peptide linker, and Fc fragment, exhibiting adequate in vivo biological activity, demonstrating an extended duration of biological activity, and not exhibiting immunogenicity, is created, requiring a non-obvious combination of these components, including the insulin polypeptide, peptide linker, and Fc fragment, and selective mutations in one or more of these components. In addition to the uses and methods of preparation, exemplary ultralong-acting insulin-Fc fusion proteins, polynucleotides encoding these insulin-Fc fusion proteins, and pharmaceutical formulations of exemplary insulin-Fc fusion proteins are also provided.

Providing modified insulin and glucokinase nucleic acids for treating diabetes SOLUTION: Reducing hyperglycaemia and maintaining euglycaemia are the goals of all therapeutic approaches to the T1DM and T2DM. Current therapy for most diabetics is based on regular subcutaneous injections of both short-acting and long-acting insulin preparations. The present disclosure relates to modified nucleic acid sequences encoding insulin and glucokinase, expression cassettes and delivery vectors comprising the same, and methods for their delivery to treat diabetes.SELECTED DRAWING: None

A liquid composition comprising a GLP-1 agonist or / and a pharmacologically tolerable salt thereof and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin and / or with long-acting insulin / insulin derivates where appropriate.

The application relates to an aqueous pharmaceutical formulation comprising 200-1000 U / mL [equimolar to 200-1000 IU human insulin] of insulin glargine.

The invention discloses application of a hydrogel-loaded long-acting insulin receptor antagonist in establishment of a gestational diabetes animal model, 12-week-old C57BL / 6J female mice are divided into two groups, the female mice and male mice are caged and copulated in a ratio of 2: 1, and the gestational condition is observed; from 7 days of pregnancy of a C57BL / 6J female mouse, 60 nmol / kg of an insulin receptor antagonist loaded by phenylboronic acid-hyaluronic acid hydrogel is subcutaneously injected every two days, and the gestational diabetes animal model is established. Different from the characteristics of long modeling time, low success rate, high animal death rate, embryotoxicity in modeling mode, short half-life period of modeling medicine and the like of the conventional gestational diabetes mouse or rat model, the invention establishes a stable and reliable mouse model similar to human pathogenesis, the success rate is high, no obvious toxic effect is generated on a female mouse and an embryo, and the model has a good application prospect. The medicine has a long half-life period and accords with the characteristics of human gestational diabetes.

This invention relates to the field of cell culture technology, and more particularly to a culture medium additive for mesenchymal stem cells and its application. The culture medium additive of this invention, using water as a solvent, comprises the following components at the following concentrations: 0.5-1.5 mg / L rhTXNDC5 protein, 10-20 mg / L vascular endothelial cadherin 5, 10-20 mg / L vascular endothelial cadherin 11, 10-20 mg / L recombinant human long-acting insulin-like growth factor-1, 400-600 mg / L dextran, 200-400 mg / L riboflavin, 300-500 IU / L superoxide dismutase, 10-20 mg / L ethanolamine, and 1-3 mg / L progesterone. Adding this culture medium additive to serum-free culture medium can increase the yield of mesenchymal stem cells and accelerate the emergence time of umbilical cord mesenchymal stem cells.

The invention relates to a novel administration regime useful in the treatment of diseases or conditions where administration of insulin will be of benefit. In particular, the invention relates to a long-acting or ultra-long acting insulin for use in treating a disease or condition where administration of insulin will be of benefit, wherein the administration of said insulin includes or consists of one or more of the following steps: (a) obtaining a first data set of the subject, (b) obtaining a second data set of the subject, (c) obtaining a first data structure of the subject, and (d) obtaining a second data structure of the subject. When a determination is made that the at least first data structure, second data structure, first data set, and second data set collectively do contain the set of evaluation information, the device further includes providing the long-acting or ultra-long-acting insulin dose guidance recommendation.

The application discloses an amphoteric ion polymer-insulin conjugate and a preparation method and application thereof. 2-bromoisobutyric acid N-hydroxysuccinimide ester is reacted with INS to introduce an ATRP reaction site at the Lys B29 position of the INS, so that INS-Br is obtained; the INS-Br, MPC and a catalyst are mixed, deoxygenated, CuBr is further mixed, and full polymerization reaction is carried out, so that CuBr and PMDETA are used as a catalytic system, INS-Br is used to initiate polymerization of the amphoteric ion monomer MPC, and through dialysis and cation chromatographic column purification technology, INS-PMPC is obtained. Compared with INS and INS-PEG, the INS-PMPC has a longer blood glucose control time under the same dose, and can significantly reduce the risk of hypoglycemia, has high stability under room temperature and mechanical stirring, is resistant to storage, is suitable for areas where cold chain facilities are lacking, and is a long-acting insulin drug with higher safety.

The present disclosure relates to compositions of insulin-Fc fusion proteins and their use to treat feline diabetes.

The invention relates to a preparation method of amino acid selectively protected Fmoc-His (Mmt) containing side chain amino groups, and belongs to the technical field of polypeptide synthesis. The preparation method comprises the following steps: protecting carboxyl of amino acid, a main chain and amino groups of side chains, removing under specific conditions to obtain a corresponding product with protected amino groups of the side chains, and protecting amino groups of the main chain to realize synthesis of the high-purity histidine derivative. According to the method, the total yield can reach 78%, the product purity is larger than 99.8%, the chiral integrity is larger than 99.95%, the COD value of process wastewater is reduced by 62% compared with that of a traditional method, and the method is suitable for industrial production of polypeptide drugs such as long-acting insulin analogues. The amino acid preparation method provided by the invention is also suitable for lysine / histidine / ornithine / 2.3-diaminopropionic acid / tryptophan and the like.

The present disclosure provides methods for lowering the blood glucose of a target subject, including for treating diabetes, by administering recombinantly manufactured ultra-long acting insulin-Fc fusion proteins.

The present invention provides long-acting insulin-Fc fusion proteins, which have reduced insulin receptor affinity, increased growth factor receptor selectivity, and a prolonged half-life in the body, which can extend the duration of blood glucose reduction in the body, shorten the interval between insulin doses, and reduce side effects such as the risk of hypoglycemia.

The present invention relates to a composition for preventing or treating diabetes mellitus comprising a long-acting insulin conjugate and a long-acting insulinotropic peptide conjugate, and a method for treating diabetes mellitus. More specifically, the combined administration of a long-acting analogue conjugate and a long-acting insulinotropic peptide conjugate inhibits weight gain due to the administration of insulin and vomiting and nausea due to the administration of insulinotropic peptide, and also reduces the required dose of insulin, thereby significantly enhancing drug compliance. The invention also relates to the administration of a pharmaceutical composition comprising a long-acting insulin analogue conjugate and a long-acting insulinotropic peptide analogue conjugate for reducing the side effects of pancreatic beta cells in a diabetic patient, and to a method for reducing the side effects of pancreatic beta cells in a diabetic patient, comprising the step of administering the composition. Specifically, the present invention is characterized by reducing side effects such as pancreatic beta cell dysfunction, pancreatic beta cell amount reduction, lipotoxicity, or glucotoxicity associated with the progression of diabetes mellitus.

The present invention relates to the field of pharmaceutical synthesis. A long-acting insulin compound is disclosed. The long-acting insulin compound of the present invention for preparing a pharmaceutical composition for treating disease, and use of the pharmaceutical composition in treating various diseases, including type-I diabetes, type-II diabetes, and gestational diabetes.

The present invention belongs to the technical field of biological genetic engineering, and specifically relates to a long-acting recombinant canine insulin fusion protein and its preparation method and application. The fusion protein formed by connecting proinsulin and 7p has high biological activity, and the recombinant canine long-acting insulin is co-expressed in an Escherichia coli expression system using a molecular chaperone, and a high-purity soluble target protein is obtained through denaturation, renaturation and purification. The target protein is mainly located in the supernatant, avoiding the formation of inclusion bodies, simplifying the purification process, and optimizing the induced expression conditions, so that the proportion of soluble protein is significantly increased, and the protein is mainly located in the supernatant. The high expression amount and high purity fusion protein obtained by final purification have good biological activity, which solves the problems of difficulty in obtaining animal insulin, short half-life in vivo and easy to cause immune response. The long-acting recombinant canine insulin expressed by the present invention provides a more suitable treatment plan for canine diabetes treatment, and has industrialization prospects.

The present disclosure relates to compositions of insulin-Fc fusion proteins and their use to treat feline diabetes.