46 results about "Insulin glargine" patented technology

Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

A basal insulin formulation composed of insulin, preferably insulin glargine, injectable zinc and injectable iron compounds as precipitating and / or stabilizing agents has been developed for subcutaneous, intradermal or intramuscular administration. The formulation is designed to form a precipitate of insulin following injection, creating a slow releasing “basal insulin” over a period of 12 to 24 hours.

The invention relates to methods of separation and / or purification of impurities yielding a purified heterologous protein product devoid of related impurities or with substantially minimal quantities of such glycosylated impurities. More specifically, the invention relates to the identification of glycosylated forms of insulin analogues such as glargine impurities characterized post expression in yeast based systems such as Pichia pastoris. The invention also relates to methods used to clone gene encoding the protein insulin glargine; inserting the related gene in a suitable yeast host; producing culture of the recombinant strain, stimulating expression of the heterologous polypeptide, its secretion and purification post fermentation and related enzymatic conversions.

The invention provides a preparation method of an insulin glargine injection and the insulin glargine injection prepared by using the preparation method. The preparation method comprises the following steps: dissolving glycerol into part of water for injection to prepare a glycerol solution, then dividing the glycerol solution into three parts, and respectively adding insulin glargine, metacresol and zinc chloride; firstly uniformly mixing an insulin glargine-glycerol solution and a metacresol-glycerol solution to obtain a mixed solution I; then adding a hydrochloric acid solution into the mixed solution I until the pH value is equal to 3.0 to 3.5, then adding a zinc chloride-glycerol solution, uniformly stirring, and then adding a sodium hydroxide solution until the pH value is equal to 3.5 to 4.5; and finally stabilizing the volume to reach a final volume by using the water for injection. By adopting the preparation method provided by the invention, insulin glargine and other auxiliary materials can be rapidly dissolved, the preparation cycle time can be significantly shortened, process impurities produced in a preparation process can be reduced, the quality of the insulin glargine injection can be improved, the process energy consumption can also be reduced, and the production efficiency can be improved; and the preparation method can be more suitable for the requirements of large-scale production.

A basal insulin formulation composed of insulin, preferably insulin glargine, injectable zinc and injectable iron compounds as precipitating and / or stabilizing agents has been developed for subcutaneous, intradermal or intramuscular administration. The formulation is designed to form a precipitate of insulin following injection, creating a slow releasing “basal insulin” over a period of 12 to 24 hours.

The invention relates to a method for preparing a recombinant glycine-arginine insulin crystal. The method specifically comprises the following steps of (1) dissolving recombinant glycine-arginine insulin, a phenol derivative, a zinc-containing substance and organic acid in water so as to obtain crystal fluid; and (2) taking a pH regulating agent for regulating the pH value of the crystal fluid to 4.5-7.0, performing stirring for 3-9 hours, and performing separation so as to obtain the recombinant glycine-arginine insulin crystal, wherein the concentration of the recombinant glycine-arginine insulin in the crystal fluid is 1-3.5g / L, the mass / volume percentage of the phenol derivative is 0.01-1.00%, the mass / volume percentage of the zinc-containing substance is 0.005-1.5%, and the mass / volume percentage of the organic acid is 0.01-2.0%. The crystal fluid prepared by the method does not contain organic solvents, the operation process is safe, the technology is simple and easy to control, poisonous and harmful substances in chromatography in the previous step can be effectively removed, the time for filtration, collection, crystal washing and freeze drying of products is shortened, the cost is reduced, and the method is suitable for industrialized production of the recombinant glycine-arginine insulin.

Disclosed is a method for preparing an insulin glargine (GlyA21-ArgB31-AryB32-human insulin) crystal, comprising crystallizing the insulin glargine at pH 7.0-9.0 and in a crystallization solution containing a recombinant insulin glargine, an organic solvent of a 10-30% concentration by volume, a zinc compound, a phenol derivative, a salt and an organic acid.

The invention provides a preparation method of insulin glargine injection and the prepared insulin glargine injection. The preparation method comprises: dissolving glycerin with part of water for injection, preparing a glycerol solution, and then dividing it into three parts, adding insulin glargine, m-cresol and zinc chloride respectively; Glycerin solution is mixed evenly to obtain mixed solution I; then hydrochloric acid solution is added to the mixed solution I to pH=3.0~3.5, then zinc chloride-glycerin solution is added, stirred evenly, then sodium hydroxide solution is added to pH= 3.5-4.5; finally dilute to the final volume with water for injection. The preparation method of the present invention can rapidly dissolve insulin glargine and other auxiliary materials, significantly shorten the preparation cycle time, reduce process impurities generated during the preparation process, improve the quality of insulin glargine injection, reduce process energy consumption, and improve production efficiency , more suitable for large-scale production needs.

The invention relates to the field of biochemistry and discloses an extraction method of an insulin glargine precursor protein. The extraction method comprises the following steps of adding an acid into an insulin glargine precursor protein fermentation broth to adjust a pH value to 1-4, carrying out centrifugation and collecting a supernatant so that the insulin glargine precursor protein is obtained. Before bacterium centrifugation, the acid is used to adjust a pH value of the insulin glargine precursor protein fermentation broth to 1-4 so that after extraction, insulin glargine precursor protein content is improved, target protein loss caused by direct centrifugation removal of the bacteria is avoided and an insulin glargine yield is improved.

The invention provides a preparation method of insulin glargine and insulin glargine prepared by the same. With an insulin glargine solution as a raw material, the method comprises the following steps: mixing the insulin glargine solution, an organic acid, a phenol derivative, a zinc salt and water to obtain crystalline liquid; adjusting pH to 3-4 and preserving heat for 1-8 hours at 25-35 DEG C; adjusting pH to 7.0-8.0 and cooling to 2-8 DEG C; standing for 3-5 hours; centrifuging; and separating the solid and supernate. Compared with prior art, the preparation method provided by the invention realizes higher production efficiency and product quality so as to better guarantee the long-term medication safety of the patients.

The invention provides a method for improving the efficiency in preparation of insulin and the like. The method comprises the step of conducting chromatography on a precursor of insulin glargine by use of a hydroxyapatite medium. The invention further provides a preparation method for active insulin glargine. The preparation method comprises the step of conducting enzyme digestion on a recombinant expression precursor of insulin glargine by use of a Kex-2p enzyme. In a preferred embodiment of the invention, the preparation method comprises the following steps: obtaining the recombinant expression precursor of insulin glargine; conducting enzyme digestion on the recombinant expression precursor of insulin glargine by use of the Kex-2p enzyme; conducting further chromatographic purification on the enzyme digestion product, so as to obtain active insulin glargine.

The invention relates to the technical field of insulin crystallization, in particular to a method for preparing insulin glargine crystals. The method for preparing insulin glargine crystals adopts the gas-phase diffusion hanging drop method, comprising the following steps: (1) preparing a crystallization solution containing the following components: Tris 0.2-1.0M, citric acid 0.2-1.0M; the pH of the crystallization solution is 8.0 to 11.0; (2) Mix the insulin glargine solution with the crystallization solution to obtain a mixed crystallization solution; (3) Hang the mixed crystallization solution above the mother liquor pool filled with the crystallization solution, and let it stand for cultivation . The method can be used to obtain insulin glargine crystals with regular shape and suitable size in the form of single crystals, and the resolution of X-ray diffraction is high, and the crystal structure of insulin glargine can be correctly analyzed.