56 results about "GLP-1 Analogue" patented technology

The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefor comprising said analogues.

The invention relates to a derivative or pharmaceutically-acceptable salt of a GLP-1 analogue containing an amino acid sequence shown in a formula (I). The derivative of the GLP-1 analogue has the function of human GLP-1 analogue, and compared with the human GLP-1 analogue, the derivative has a longer half-life period in vivo. The derivative or pharmaceutically-acceptable salt of the GLP-1 analogue, or the pharmaceutical composition of derivatives containing the GLP-1 analogue or pharmaceutically-acceptable salts thereof can be widely used for treating non-insulin-dependent diabetes mellitus,insulin-dependent diabetes mellitus and obesity. The formula (1) is as follows: X1-X2-Glu-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-X12-X13-X14-Glu-X16-X17-Ala-X19-X20-X21-Phe-Ile-X24-Trp-Leu-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37-X38-X39-Lys (I).

Provided are a glucagon-like peptide-1 (GLP-1) analogue monomer and dimmer, a preparation method thereof, and an application thereof. The GLP-1 analogue monomer comprises one cysteine; and the dimer is formed by two monomer molecules connected via an intermolecular disulfide bond formed by the cysteine. The GLP-1 monomer comprising cysteine has the following general formula: 7HAEX10TFTSX15VSSYLEX22X23AAKEFIX30WLX33KGRG37, wherein X10 is glycine or cysteine, X15 is aspartate or cysteine, X22 is glycine or cysteine, X23 is glutamine or cysteine, X30 is alanine or cysteine, and X33 is valine or cysteine; and only one of X10, X15, X22, X23, X30, and X33 is cysteine. The glucagon-like peptide-1 analogue dimer of the present invention has an in vivo half-life of more than 8 to 96 hours, thus facilitating clinical promotion and application.

The present invention relates to a peptide analogue of glucagon-like peptide-1 (7-36), which is useful to prophylactically prevent, improve, or reverse the diminished cognitive function associated with these types of disorders, by increasing (or sustaining) the LTP of synaptic transmission. Moreover, sustaining LTP may find utility in the prophylaxis of neurological disease by delaying the onset of impaired cognitive processes, and could serve as a treatment, not only for the diminished cognitive function caused by neurodegeneration, but also for the dysfunctional cognitive processes associated with trauma or age.

The invention relates to new type GLP-1 analogues and a microwave promotive solid phase synthesis process of the same. GLP-1 analogues with longer pharmacological action time can be obtained by modifying 8, 9, 16, 22, 27 or 37 sites of natural GLP-1, the chemical synthesis is highly effectively and rapidly realized by microwave promotive solid phase synthesis process, the crude product is purified by highly effective liquid phase, and GLP-1 analogues is obtained after lyophilized.

Disclosed is a glucagon-like peptide-1 (GLP-1) analogue which is obtained by ameliorating a highly antigenic GLP-1 analogue so that the GLP-1 analogue has reduced antigenicity without being lowered in the blood glucose suppressing activity. Specifically disclosed is a glycosylated form of an antigenic GLP-1 analogue, which has GLP-1 activity and is obtained by substituting at least one amino acid of an antigenic GLP-1 analogue with a glycosylated amino acid.

The invention relates to long-acting glucagon-like peptide 1 (GLP-1) analogues and a synthesis method thereof. GLP-1 analogues with longer pharmacological action time are obtained through adding a modified 37th amino acid to natural GLP-1, the synthesis of target polypeptides is quickly realized through a microwave-promoted solid-phase synthesis method, and crude products are purified and freeze-dried to obtain the GLP-1 analogues.

The invention relates to truncated GLP-1 analogues, in particular a GLP-1 analogue which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogues and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

Novel GLP-1 agonists which are protracted by coupling to a protraction protein.

The invention relates to the field of polypeptide solid-phase synthesis and provides a method for synthesizing glucagon-like peptide (GLP)-1 analogue in a solid-phase mode. The method for synthesizing the GLP-1 analogue in the solid-phase mode solves the problems that in the process of synthesizing the GLP-1 analogue in the solid-phase mode, peptide deficiency products and by-products are generated because of difficult or incomplete amino acid sequence connection, and the by-products are resulted to be difficulty to separate in subsequent purification. The peptide deficiency products and by-products are quite same in properties. According to the method for synthesizing the GLP-1 analogue in the solid-phase mode, a segment convergent synthesis method and a substituent-introduced method are adopted in difficult-connection points and polypeptide synthesis yield coefficient is improved.

The invention comprises a process for the purification of a GLP-1 peptide analogue applying reversed phase high performance liquid chromatography (RP-HPLC).

The invention relates to truncated GLP-1 analogues, in particular a GLP-1 analogue which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogues and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

The invention relates to a class of long-acting glucagon-like peptide-1 (GLP-1) analog and a synthesis method thereof. The GLP-1 analogue with longer pharmacological action time is obtained by modifying GLP-1. The synthesis of target polypeptide is quickly achieved by a orthogonal protection strategy solid phase synthesis method. The crude product is purified and lyophilized to obtain the GLP-1 analog.

GLP-1 analogues are disclosed. The general formula A of the GLP-1 analogues is shown as follows: <7>HAEGT FX<13>SDV SSY X<20>E X<22>QAA X<26>EFIAW LVKGR G<37>. In the general formula A, the X<13> is threonine or side-chain-modified lysine (K-nX), the X<20> is leucine or the side-chain-modified lysine (K-nX), the X<22> is glycine or the side-chain-modified lysine (K-nX), the X<26> is lysine (K-NH2) free of side chain modification or the side-chain-modified lysine (K-nX), just only one of the X<13>, the X<20>, the X<22> and the X<26> is the lysine (K-nX), the n is 4-10, and the X is the glycine, alanine or valine. The GLP-1 analogues effectively prolong the blood half-life period of GLP-1, overcome the current situation that the GLP-1 cannot be used in clinic due to the short half-life period of the GLP-1, and have an application prospect in the field of medicines treating diabetes and obesity. A preparing method of the GLP-1 analogues and applications of the GLP-1 analogues are also disclosed.

The invention discloses a glucagon-like peptide-1 analogue sustained release microsphere as well as a preparation method and an application thereof. The sustained release microsphere mainly includes 1-10 parts by weight of the glucagon-like peptide-1 analogue and 90-99 parts by weight of a polylactic acid-glycollic acid copolymer and is 0.5-100 [mu]m in range of average particle size. The invention also discloses the preparation method and the application of the sustained release microsphere and also inspects appearance, particle size, in-vitro releasing and in-vivo pharmacodynamic experimentof the microsphere. The sustained release microsphere supporting GLP-1 analogue has uniform particle size and has significant treatment effect on diabetes, can effectively control blood glucose for 14days and has the effect as a slow-effect preparation. The sustained release microsphere greatly reduces dosing frequency and increases compliance of patients, and also can inhibit food intake. The preparation method has simple process and gentle conditions, and is low in influence on activities of polypeptides.

A GLP-1 analogue composition for microneedle devices, which contains a GLP-1 analogue and at least one kind of solvent that is selected from the group consisting of water, glycerol, propylene glycol, ethylene glycol, 1,3-butylene glycol and polyethylene glycol.

The invention discloses a stable liquid preparation containing GLP-1 analogue fusion protein and preparation thereof. The stable liquid preparation is prepared from the effective components of: the GLP-1 analogue fusion protein, a pharmaceutical buffering agent, an osmotic-pressure regulating agent, a protective agent, a surface active agent, sodium caprylate and the like. The stable liquid preparation can be used for treating the diabetes and relevant diseases thereof.

This invention discloses GLP-1 analogues and their pharmaceutical salts, wherein the GLP-1 analogue comprises an amino acid sequence of general formula (I), wherein Lys represents a modified lysine with a lipophilic acid. The GLP-1 analogues provided by this invention have the function of human GLP-1, and a longer half-life in vivo compared with the human GLP-1. Uses of such compounds and compositions include treating non-insulin-dependent diabetes, insulin-dependent diabetes, and obesity.(I)   X1-X2-Glu-Gly-Thr-Phe-Thr-Ser-Asp-X10-Ser-X12-X13-X14-Glu-X16-X17-Ala-X19-X20-X21-Phe-Ile-X24-Trp-Leu-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37-X38-X39-Lys                                 

The invention belongs to the technical field of medicine preparation, and discloses a pharmaceutical composition containing a therapeutically effective amount of a glucagon-like peptide-1 (GLP-1) analogue and a dipeptidyl peptidase-4 (DPP-4) inhibitor and a preparation method thereof. The composition can effectively prevent, retard and treat type II diabetes, especially can effectively control the blood glucose concentration, and also can be used for treating diseases related to rising of the blood glucose concentration. In addition, the composition can reduce the use dosage of the GLP-1 analogue and the DPP-4 inhibitor, so as to effectively reduce side effects of the GLP-1 analogue and the DPP-4 inhibitor and improve the patient tolerance level.

A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.

The present invention provides a GLP-1 analogue having a high association-aggregability or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition to be used for preventing or treating diabetes, hyperglycemia, a diabetic complication caused by diabetes or hyperglycemia, or obesity, using the same.

The invention relates to an Xenopus laevis GLP-1 analogue, a synthesis method and applications thereof. According to the present invention, the side chain and the C terminal of Xenopus laevis GLP-1 are subjected to structure modification to obtain the Xenopus laevis GLP-1 analogue with advantages of high blood glucose lowering activity and long pharmacological action time; and the Xenopus laevis GLP-1 analogue has significantly improved biological activity, and further has effects of strong long-acting blood glucose lowering and strong weight reducing.

The invention provides novel GLP-1 analogues and compositions comprising such analogues. The compounds of the invention are useful in treating diabetes mellitus and related disorders.

The invention belongs to the technical field of medicine and particularly provides a long-acting GLP-1 (glucagon-like peptide-1) analogue dimer. The dimer is formed by two GLP-1 analogue monomers which are represented as the general formula HAX1GTFTSDVSSYLEGQAAKEFIX2WLVK X3RZ, wherein Z is NH2, G, GNH2, -GCG or -GCA; X1 is Leu, Pro, Phe or Tyr; X2 is Ala or Cys; X3 is Gly or Aib; when X2 is Ala, Z is -GCG or -GCA; when X2 is Cys, Z is NH2, G or GNH2. The long-acting GLP-1 analogue dimer has a long-acting hypoglycemic effect and is highly homologous with endogenous GLP-1(7-37), thereby being capable of avoiding safety risks, and clinical medication compliance can be improved.

The invention relates to a GLP-1 analogue and ziconotide composite slow-release microsphere preparation and a preparation method thereof. The slow-release microsphere preparation is prepared from a GLP-1 analogue, ziconotide, a biodegradable high polymer material with biocompatibility, a stabilizing agent and a freeze drying protection agent. The preparation method comprises the following steps of (1) adding water for preparing the GLP-1 analogue and the ziconotide into a medicine solution A; adding an organic solvent for preparing the biodegradable high polymer material with biocompatibility into a solution B; (2) mixing the solution A and the solution B; performing ultrasonic processing to form primary emulsion; adding the primary emulsion into a stabilizing agent water solution saturated by an organic mixed solvent; performing homogenizing emulsification to obtain secondary emulsion; (3) performing room-temperature stirring on the secondary emulsion for 1 hour; then, raising the temperature to 40 DEG C to 45 DEG C; maintaining the temperature for one hour; then, lowering the temperature to 10 DEG C; adding the freeze drying protection gent; screening and collecting particles; performing freeze drying; performing radiation sterilization. By using a related technology, the effect of treating diabetes and PDN (painful diabetic neuropathy) complications for a long time can be achieved; the pain of a patient is reduced; the medicine compliance of the patient is improved; the clinic practical significance is realized.

The invention relates to a long-acting African clawed frog glucagon-like peptide-1 (GLP-1) analogue as well as a synthesis method and application thereof. An African clawed frog glucagon-like peptide-1 is subjected to PEG (Polyethylene Glycol) modification to obtain the African clawed frog GLP-1 analogue which can keep blood glucose lowering activity and has longer pharmacological action time. The African clawed frog GLP-1 analogue provided by the invention is high in synthesis yield and low in cost; and the half-life period of the analogue is remarkably prolonged and the biological activity is remarkably improved.

The invention relates to long-acting glucagon-like peptide 1 (GLP-1) analogues and a synthesis method thereof. GLP-1 analogues with longer pharmacological action time are obtained through replacing the 34th amino acid of natural GLP-1, the synthesis of target polypeptides is quickly realized through a microwave-promoted solid-phase synthesis method, and crude products are purified and freeze-dried to obtain the GLP-1 analogues.

Novel GLP-1 agonists which are protracted by coupling to a protraction protein.

Provided herein are oral pharmaceutical compositions containing a GLP-1 analogue and / or insulin for treating and reducing the incidence of nonalcoholic fatty liver disease (NAFLD), hepatic steatosis, and sequelae thereof, and methods of utilizing same.