27 results about "Insulin analog" patented technology

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.

In an aspect, the present disclosure provides a method comprising: (a) positioning an insulin delivery device on a body of a subject via a single puncture site in said body of said subject; (b) using said insulin delivery device to deliver an insulin or insulin analog formulation to said subject via said single puncture site; and (c) using a sensor of said insulin delivery device to measure a glucose concentration in said body of said subject via said single puncture site, wherein (b) and (c) are performed at substantially the same time for a time period of at least 1 hour subsequent to said positioning in (a), while maintaining a sensitivity of said sensor of at least 50% of an initial sensitivity of said sensor.

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 therapeutic use of a glucokinase activator in combination with insulin or an insulin analogue. Methods of using glucokinase (GK) activators, particularly in combination with insulin or insulin analogs, are generally disclosed herein. In certain aspects, the disclosure provides methods of treating type 1 diabetes mellitus comprising administering a GK activator in combination with insulin or an insulin analogue. Also disclosed herein are uses of GK activators as medicaments, and the preparation of medicaments for such uses.

The present invention relates to insulin formulations comprising polysorbate 80. The present invention provides, inter alia, aqueous liquid pharmaceutical formulations comprising insulin or an insulin analogue, ionic zinc, a chelating agent, and polysorbate 80.

This disclosure provides a composition containing a conjugate with a modified insulin molecule. The conjugate has an insulin molecule, which can be insulin or an insulin analog, glucagon, GLP-1, GLP-2 or a GLP-I agonist. The conjugate also contains one or more polymers. Each of the one or more polymers is covalently linked to the insulin molecule. Additionally, each of the one or more polymers is covalently linked to between 0 to 50 copies of a decoy ligand, and to between 0 to 50 copies of a glucose-binding agent, such that the combined total number of glucose-binding agents and decoy ligands covalently linked to each of the one or more polymers is at least 1. The conjugate can reversibly bind to soluble glucose and in which the extent of its glucose-binding controls the extent to which the modified insulin is able to bind to and activate the insulin receptor. Methods of making the conjugate, as well as use of the conjugate in treatment, are also provided.

The disclosure describes devices and methods for insertion and delivery of insulin or an insulin analog formulation and measurement of subcutaneous glucose concentration. A device for delivery of insulin or an insulin analog formulation and measurement of subcutaneous glucose concentration, may comprise: (a) a tube comprising a proximal end and a distal end, wherein the proximal end is in fluid communication with a source of the insulin or insulin analog formulation, and wherein the distal end is configured to deliver the insulin or insulin analog formulation subcutaneously; (b) a glucose sensor disposed along a central axis of the tube; and (c) a penetrating body disposed along the central axis of the tube, wherein the penetrating body comprises a cross-sectional area no more than a cross-sectional area of the glucose sensor.

A pharmaceutical formulation presented, comprising an insulin or an insulin analog, and at least one protective excipient, in high concentration, selected from: a protective osmolyte, a surfactant, and a phenolic preservative. In embodiments, the insulin or insulin analog is one or more of: regular human insulin, insulin lispro, insulin aspart, insulin glulisine, insulin glargine, insulin detemir, or insulin degludec. In some embodiments, at least one of: the concentration of the protective osmolyte confers an osmolarity greater than 250 mOsm / L, the concentration of the surfactant is greater than 0.1% w / v, or the concentration of the phenolic preservative is greater than 0.4% w / v. In some embodiments, insulin API is dissolved and incubated for 20 to 40 minutes at high pH before the protective excipients are added.

The invention relates to the technical field of biology, in particular to a method for treating insulin analogues through sequential enzyme digestion so as to improve the enzyme digestion yield. The method comprises the step of carrying out specific enzyme digestion on the proinsulin analogue by using recombinant double-base amino acid endopeptidase (Kex-2 enzyme) and recombinant trypsin in sequence, and comprises the following steps: firstly, adding the Kex-2 enzyme to perform enzyme digestion on double bases between Linker-A chains to generate an intermediate peptide 1, and then adding the recombinant trypsin to cut a guide peptide and a connecting peptide to obtain a target product. According to the method, the enzyme digestion yield can be remarkably increased by 25% or above, meanwhile, miscut impurities generated by single recombinant trypsin enzyme digestion are avoided, and the method is suitable for efficient enzyme digestion in insulin analogue production.

In an aspect, the present disclosure provides an insulin delivery device configured to be positioned on a body of a subject via a single puncture site in said body of said subject, wherein said insulin delivery device is configured to deliver an insulin or insulin analog formulation to said subject via said single puncture site, wherein said insulin delivery device comprises a sensor configured to measure a glucose concentration in said body of said subject via said single puncture site, and wherein said delivering and said measuring are performed at substantially the same time for a time period of at least 1 hour subsequent to said positioning, while maintaining a sensitivity of said sensor of at least 50% of an initial sensitivity of said sensor.

The present invention relates to insulin analogs, particularly insulin analogs having shortened B chains. The present invention also relates to the crystal structure of insulin from the venom of cone snails and to methods of using the crystal and related structural information to screen for and design insulin analogs that interact with or modulate the insulin receptor. The present invention also relates to therapeutic and prophylactic methods using insulin analogs.

The application belongs to the technical field of medical devices, and particularly relates to a double closed loop insulin delivery system, application thereof and a medical product. The application discloses a double closed loop insulin delivery system, and particularly comprises a dynamic blood glucose monitoring system, a double closed loop control algorithm, an insulin pump and specific sugar response insulin analogues. The application controls blood glucose in a double closed loop mode, can realize a high proportion of time of blood glucose in a target range, realizes more stable, safe and simple blood glucose control, and does not need human intervention in the use process of the system, and provides a more intelligent and humanized treatment scheme for diabetic patients.

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

The invention relates to an aqueous pharmaceutical formulation having insulin, an insulin analog, or an insulin derivative, and methionine; and to the production thereof, to the use thereof for treating diabetes mellitus, and to a medication for treating diabetes mellitus.

In an aspect, the present disclosure provides an insulin delivery device configured to be positioned on a body of a subject via a single puncture site in said body of said subject, wherein said insulin delivery device is configured to deliver an insulin or insulin analog formulation to said subject via said single puncture site, wherein said insulin delivery device comprises a sensor configured to measure a glucose concentration in said body of said subject via said single puncture site, and wherein said delivering and said measuring are performed at substantially the same time for a time period of at least 1 hour subsequent to said positioning, while maintaining a sensitivity of said sensor of at least 50% of an initial sensitivity of said sensor.

The subject matter of this invention is directed towards insulin analogs that are stable and glucose-responsive. An insulin analog can be a single chain insulin (SCI). The binding affinity of insulin to the insulin receptor can be controlled by the glucose-bound conformation of insulin. The invention further discloses methods for the recombinant expression, purification, and refolding of an insulin analog.

Provided herein are engineered insulin polypeptides that exhibit blocked cross-beta fibrosis, and pharmaceutical compositions comprising the polypeptides. The present disclosure also provides methods of making insulin polypeptides, and methods of treating diabetes and hyperglycemia using the pharmaceutical compositions.

The invention discloses a method for rapidly synthesizing an insulin derivative based on a carbon terminal temporary structure support strategy, which comprises the following steps: firstly, synthesizing a folding renaturation precursor of the insulin derivative of which the carbon terminal contains a temporary structure support through an N-fluorenylmethoxycarbonyl (Fmoc) solid-phase polypeptide synthesis method, and then forming three pairs of disulfide bonds through oxidative folding renaturation. And finally, removing the carbon terminal temporary structure support through a reduction acidolysis reaction to obtain the insulin derivative. The synthesis steps are all completed on the solid-phase resin, disulfide bond pairing can be completed only through one-step folding renaturation, then the insulin analogue can be obtained by removing a carbon terminal temporary structure support through a simple reduction acidolysis reaction, the steps are few, consumed time is short, and operation is easy.

The present disclosure describes devices and methods for inserting and delivering insulin or insulin analogue formulations and measuring subcutaneous glucose concentrations. A device for delivering an insulin or insulin analogue preparation and measuring subcutaneous glucose concentration may comprise: (a) a tube comprising a proximal end and a distal end, where the proximal end is in fluid communication with a source of the insulin or insulin analogue preparation, and where the distal end is configured to deliver the insulin or insulin analogue preparation subcutaneously; (b) a glucose sensor disposed along the central axis of the tube; and (c) a penetrating body disposed along a central axis of the tube, wherein the penetrating body includes a cross-sectional area that does not exceed a cross-sectional area of the glucose sensor.

A method for improving the solubility of a pharmaceutical compound is disclosed, wherein the pharmaceutical compound is insulin, a natural insulin variant, an insulin variant or insulin analog, a GLP-1 agonist, a GIP agonist, a glucagon agonist, an amylin agonist or an incretin mimic. The method involves using a non-nutritive sugar, such as raspberry glycoside, neohesperidin A, dulcitin B, dodecyl-β-D-maltodextrin (DDM), or carhariside, or any combination thereof, in the presence of a solvent such as ethanol or a mixture thereof, followed by removal of the solvent by drying and re-solubilization to generate a water-soluble complex. The complex formed using the disclosed method is also described.

The present disclosure describes devices and methods for inserting and delivering insulin or insulin analog formulations and measuring subcutaneous glucose concentrations. The device for delivering insulin or insulin analog formulations and measuring subcutaneous glucose concentrations may include: (a) a tube including a proximal end and a distal end, the proximal end being in fluid communication with a source of insulin or insulin analog formulation and the distal end being configured to subcutaneously deliver the insulin or insulin analog formulation; (b) a glucose sensor disposed along a central axis of the tube; and (c) a penetrator disposed along the central axis of the tube, the penetrator comprising a cross-sectional area equal to or less than the cross-sectional area of ​​the glucose sensor.

Compositions and methods for oral and / or mucosal administration of a biologically active agent are provided according to aspects of the present disclosure which include: a plurality of particles, wherein each particle has an exterior surface, the exterior surface defining a particle interior, the exterior surface having at least one type of zwitterionic polymer and / or zwitterionic copolymer disposed thereon and / or extending therefrom; and a biologically active agent disposed on the exterior surface and / or in the particle interior, wherein the biologically active agent is or includes a protein, peptide, or dietary supplement. According to particular aspects, compositions and methods for oral and / or mucosal administration of an anti diabetes biological agent, such as insulin and / or an insulin analog.

A device for delivery of an insulin or insulin analog formulation and measurement of subcutaneous glucose concentration may comprise a hollow tube, and an amperometric glucose sensor located proximal to a distal end of the hollow tube. The amperometric glucose sensor may comprise a redox mediator and an enzyme comprising glucose oxidase or glucose dehydrogenase. An applied bias potential may allow an electrode layer of the amperometric glucose sensor to undergo substantially no electropolymerization of an excipient of the insulin or insulin analog formulation during continuous operation of amperometric glucose sensor. A sensitivity of the amperometric glucose sensor to the subcutaneous glucose concentration may be maintained in presence of the insulin or insulin analog formulation.

A device for delivery of an insulin or insulin analog formulation and measurement of subcutaneous glucose concentration may comprise a hollow tube, and an amperometric glucose sensor located proximal to a distal end of the hollow tube. The amperometric glucose sensor may comprise a redox mediator and an enzyme comprising glucose oxidase or glucose dehydrogenase. An applied bias potential may allow an electrode layer of the amperometric glucose sensor to undergo substantially no electropolymerization of an excipient of the insulin or insulin analog formulation during continuous operation of amperometric glucose sensor. A sensitivity of the amperometric glucose sensor to the subcutaneous glucose concentration may be maintained in presence of the insulin or insulin analog formulation.

The disclosure described herein provides compositions and uses of insulin analogs for the stable and effective treatment of metabolic diseases or disorders in a subject. In some embodiments, the insulin analog is a derivatized native insulin peptide (comprising an A chain and a B chain) that includes a difference of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids from native insulin. In typical embodiments, the insulin analogs described herein include a substitution at the N-terminus, the C-terminus, or both, comprising a hydrophobic moiety. The insulin analogs described herein exhibit potent receptor binding and extended plasma half-life. Pharmaceutical compositions of the insulin analogs described herein are described for the treatment of metabolic diseases or disorders, such as diabetes, in a subject.

The invention is a pharmaceutical composition of human insulin or an insulin analog comprising citrate, treprostinil and stabilizing agents, which has a faster pharmacokinetic and / or pharmacodynamic effect than commercial formulations of existing insulin analog products and which is stable for commercial use.

Provided are an ultra-long-acting insulin analog, a preparation method therefor, and a use thereof. The present invention comprises modification of an amino acid sequence of natural human insulin, and by means of dual fatty acid modification at a suitable site, prolongs the acting time of an insulin analog, thereby improving patient compliance. The present invention solves the technical problem in the prior art that the drug acting time of insulin analogs is unsatisfactory, uses a recombinant expression-based preparation method, and has a simple process route and low costs.