151 results about "Semaglutide" patented technology

The invention provides a solid-phase synthesis method of semeglutide, and belongs to the technical field of synthesis of medical intermediates, and the method specifically comprises the following steps: segmenting a semeglutide main chain into three shorter polypeptide fragments, namely a fragment 4, a fragment 5 and a fragment 2, which are 7-14 sites, 15-22 sites and 23-37 sites; and respectively synthesizing and then assembling fragments to obtain a target product. The method specifically comprises the following steps: a) synthesizing a 7-14 peptide fragment and a 15-22 peptide fragment, and assembling the 7-14 peptide fragment and the 15-22 peptide fragment into a 7-22 peptide fragment, namely a fragment 1; b) synthesizing a 23-37 peptide fragment, selectively removing a protecting group A11oc on Lys26, and connecting with a side chain to form a fragment 3; c) connecting the peptide fragment 7-22 with the peptide fragment 23-37, and removing a protecting group to obtain a crude product; and d) separating and purifying to obtain a finished product. According to the invention, the purpose of high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug can be achieved.

The invention relates to the technical field of oral membranes, in particular to a multilayer oral membrane and a preparation method thereof. The invention provides an oral membrane composition, which comprises semeglutide and pharmaceutically acceptable auxiliary materials, and is characterized in that the composition is formed by combining a drug-containing biological adhesion layer and a backing layer, and the backing layer mainly comprises a membrane forming material, a solvent and a plasticizer; the drug-containing biological adhesion layer mainly comprises semeglutide, a film-forming material, an adhesive, a pH regulator, a flavoring agent and a solvent. By preparing the double-layer oral membrane, the semeglutide is administrated through the oral cavity, and after the insoluble or slowly eroded / dissolved backing layer (preventing saliva from dissolving the medicine) and the adhesive layer containing the main medicine are combined together, the one-way delivery of the main medicine can be realized; through experiments, it is accidentally found that when temperature-sensitive materials such as poloxamer are added to be combined with a conventional adhesive for use, the residence time of the medicine in the oral mucosa can be remarkably prolonged, the curative effect of the medicine is improved, and the main mechanism is that after the medicine is administered, in the oral temperature environment, after the medicine makes contact with mucus on the surface of the oral mucosa, the oral mucosa does not adhere to the oral mucosa. And after the entanglement and piling effects among poloxamer micelles are intensified to form gel, the gel and a conventional adhesive are cooperated to improve the adhesion between the oral membrane and the oral mucosa. Besides, the medicine can be removed at any time, blood sugar can be better controlled, T2DM complications can be better reduced, a more ideal taking mode is provided for weight loss patients, and a new administration mode is provided for reducing blood sugar and reducing weight. The prepared oral cavity membrane is small in size, light in weight, thin, convenient to apply, carry and transport, safe and environmentally friendly to use and capable of meeting the requirements of old people and travelers.

Pharmaceutical compositions of semaglutide or salts thereof for intranasal administration for the treatment of diabetes, obesity, non-alcoholic fatty liver disease (NAFLD) or neurodegenerative diseases. The method of delivering semaglutide through the intranasal route avoids repeated injections and improves systemic absorption of semaglutide as compared to oral pastilles.

The invention provides semeglutide, which is synthesized by adopting the following method, and the specific steps are as follows: 1) segmenting the main chain of semeglutide into three polypeptide fragments: 7-14 sites, 15-22 sites and 23-37 sites; (2) respectively preparing the 7-14-site fragments, the 15-22-site fragments and the 23-37-site fragments through solid-phase synthesis; 3) connecting the 7-14-site fragment with the 15-22-site fragment to form a 7-22-site fragment, and activating the C end of the fragment into active ester; (4) selectively removing an Alloc protecting group of Lys26 in the 23-37-site fragment, and then carrying out fatty acid modification to obtain a modified 23-37-site fragment; 5) in a liquid phase system, coupling the activated 7-22-site fragment and the modified 23-37-site fragment according to a molar ratio of 1: (0.6-1.4) to form a complete polypeptide chain; and 6) removing the protecting group and purifying to obtain a semaglutide finished product. The method provided by the invention can effectively realize high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug.

The present invention is related to oral dispersible film of semaglutide for treating diabetes. The oral dispersible film of semaglutide comprising semaglutide, taste masking agent, permeation enhancer, film forming polymer, plasticizer, and other pharmaceutically acceptable excipients. The oral dispersible film of Semaglutide can be prepared by casting dispersion of semaglutide which is prepared in suitable solvent.

Disclosed herein are semaglutide formulations that comprise lower quantities of semaglutide compared to commercially available products; as well as their methods of making and methods of using.

The application relates to application of semaglutide in preparation of a medicine for treating or delaying ovarian aging, and through a natural aging mouse model, a cell aging model and transcriptome analysis, it is first proved that semaglutide can significantly increase the number of follicles and reduce the level of aging markers, and from a molecular level, it is revealed that the mechanism of realizing multi-target point delay of ovarian aging is that semaglutide realizes multi-target point delay of ovarian aging through regulating an adipocyte cytokine signal pathway, inhibiting excessive cell division and regulating an NF-kappa B signal pathway. As a marketed drug, semaglutide has clear safety, a long half-life and high patient compliance, and has a significant clinical conversion prospect. The application breaks through the limitation that existing hormone replacement therapy and assisted reproductive technology can only treat symptoms or solve the problem of fertility, provides a first drug intervention strategy which can fundamentally delay the process of follicle depletion, and fills the blank in the field of ovarian aging treatment.

Provided herein are compounds comprising an ionic form of a GLP-1 receptor agonist, such as semaglutide, and a counterion thereof, additional esters and prodrug derivatives of semaglutide, and methods of use thereof.

A preparation method for semaglutide. The method comprises: producing a semaglutide resin by means of a solid-phase synthesis, producing crude semaglutide by cleavage and deprotection, producing refined semaglutide by purification and freeze-drying, comprising the solid-phase synthesis of a semaglutide 1-6 peptide fragment resin, which is cleaved and purified to serve as a first peptide fragment; and synthesizing a lysine having a sidechain group at locus 20 of semaglutide to serve as a second peptide fragment. In the method, prepared is a semaglutide loci 1-6 fully protected peptide fragment, which serves as a key starting material applied in the solid-phase synthesis of semaglutide, thus reducing the generation of D-His, D-Glu, D-Thr, D-Phe racemic impurities and +Gly impurities, reducing the difficulty of coarse product purification, increasing the purity and yield of semaglutide, reducing synthesis costs, and favoring industrialized large-scale production.

The invention discloses sodium caprylate and a preparation method and application thereof, the sodium caprylate is 8-(2-(2-hydroxyethoxy) benzamido) sodium caprylate, the 8-(2-hydroxybenzamido) sodium caprylate and 2-iodoethanol are subjected to a reaction in an organic solvent containing inorganic base to prepare the sodium caprylate, and the sodium caprylate can be used as a penetration enhancer in an oral administration system. And when the semeglutide oral soluble film is used for preparing the semeglutide oral soluble film, the semeglutide oral soluble film shows a very good in-vitro disintegration effect and a very good permeation promoting effect in animal experiments. The preparation method of the 8-(2-(2-hydroxyethoxy) benzamido) sodium caprylate is simple, does not involve expensive reactants, is convenient for post-treatment, and is beneficial to large-scale production.

The present disclosure provides, among other things, methods and compositions for the oral administration of semaglutide polypeptides. The present disclosure provides methods and compositions that include a semaglutide polypeptide formulation, e.g., tablet formulation suitable for oral administration, where the formulation includes a crystallized polypeptide composition and a pharmaceutically acceptable carrier.

The present disclosure provides methods for treating an inflammatory disease or disorder, wherein the inflammatory disease or disorder is a metabolic disease or disorder, comprising administration of a GLP-1 receptor agonist (e.g., semaglutide, exendin-4), and an IL-2 protein (e.g., aldesleukin) to a subject. Also presented herein are compositions for use with the methods disclosed herein and kits for administering a GLP-1 receptor agonist (e.g., semaglutide, exendin- 4), and an IL-2 protein (e.g., aldesleukin).

The present invention relates to the GLP-1 receptor agonist semaglutide for use in medicine.

The invention discloses a preparation rich in polygonatum sibiricum polypeptide and application of the preparation in diabetes mellitus. The composition is prepared from rhizoma polygonati polypeptide, semeglutide, astaxanthin, an active agent and a ferroptosis mixture. Pharmacodynamic experiments show that in a diabetic mouse model, fasting blood glucose can be remarkably reduced, the serum insulin level can be increased, renal function indexes can be improved, and expression of NLRP3 inflammation pathway related proteins (NLRP3, Caspase-1 and IL-1beta) in pancreatic tissue can be remarkably inhibited. By integrating multiple mechanisms of blood glucose reduction, oxidation resistance, inflammation resistance, ferroptosis resistance and the like, multi-target collaborative intervention is realized, the pharmaceutical composition is remarkably superior to a single component in the aspects of blood glucose reduction, pancreas islet function protection and complication alleviation, and a new clinical strategy is provided for treatment of diabetes mellitus, especially type 1 diabetes mellitus.

Dry powder formulations of GLP-1 receptor agonists, such as semaglutide, dosage forms containing the same, and liquid feedstocks for preparing dosage forms, such as dry powers, that contain GLP-1 receptor agonists, are disclosed. Also disclosed are liquid formulations of GLP-1 receptor agonists, such as semaglutide.

The present invention relates to the general field of amino acids and peptides. In particular, the present invention relates to solid metal complex salts of amino acids or peptides, to processes for preparing such solid metal complex salts and to the use of such salts in the preparation of semeglutide, tiall and pharmaceutically acceptable salts thereof.

A computer implemented method for determining a dosage of semaglutide for administering to a patient for the treatment of obesity includes receiving patient data relating to a patient, wherein the patient data includes patient weight data; processing the patient data with a dosage calculator to determine the dosage of semaglutide for administering to the patient; and administering the dosage.

Disclosed herein are therapeutic uses of myostatin-selective inhibitors, such as myostatin-selective inhibitors, for treating metabolic disorders, such as obesity. Data presented herein support the notion that selectively targeting myostatin without inhibiting Activin A can achieve equivalent or enhanced efficacy when used in conjunction with a GLP-1 receptor agonist in improving body composition, as compared to broadly antagonizing the ActRII pathway in conjunction with a GLP-1 receptor agonist. Administration of a myostatin-selective inhibitor can prolong the effect of semaglutide on fat mass loss. Moreover, administration of a myostatin-selective inhibitor can elicit positive effects on bone in all parameters evaluated, indicating that diet- or inflammation-induced bone atrophy may be prevented by selective inhibition of the myostatin pathway.

The invention relates to the technical field of polypeptide synthesis, and provides a preparation method of semaglutide, which comprises the following steps: gradually coupling a liquid phase and a solid phase to obtain a fragment 1: Boc-His (trt)-Aib and a fragment 3: tBuO-Ste-Glu (AEEA-AEEA-OH)-OtBu, activating the fragment 3, carrying out coupling reaction on the fragment 3 and lysine side chain amino in a fragment 2: Arg34GLP-1 (9-37) protected by a terminal glutamic acid amino group, namely deprotecting P = FMOC to obtain an intermediate I, and purifying to obtain the semaglutide. Coupling the fragment 1 with the intermediate II to obtain an intermediate II, cutting, precipitating, separating, purifying and freeze-drying to obtain a semaglutide product; according to the present invention, based on the reaction rate of the different combination modes of the three fragments and the preparation of the recombinant main chain GLP-1 (9-37), the reaction process of the semaglutide is short, the yield is high, the purity is good, the semaglutide is green and environmentally friendly, and the industrial preparation of the semaglutide is easily achieved.

The present invention is related to oral dispersible film of semaglutide for treating diabetes. The oral dispersible film of semaglutide comprising semaglutide, taste masking agent, permeation enhancer, film forming polymer, plasticizer, and other pharmaceutically acceptable excipients. The oral dispersible film of Semaglutide can be prepared by casting dispersion of semaglutide which is prepared in suitable solvent.

The invention belongs to the technical field of biological medicine, and relates to a brain-targeted delivery system of semeglutide as well as a preparation method and application of the brain-targeted delivery system of semeglutide, the delivery system comprises yeast microcapsules and a semeglutide-cationic polymer; the delivery system takes a yeast microcapsule as a delivery carrier, and a semeglutide-cationic polymer is encapsulated in the yeast microcapsule. By simulating a natural way that microorganisms are recognized by macrophages through digestive tracts, active uptake is realized by utilizing specific binding of yeast microcapsules and Dectin-1 receptors on the surfaces of the macrophages, the semeglutide is accurately delivered to the brain by virtue of the cross-blood-brain-barrier migration ability of the macrophages, a central GLP-1 receptor pathway is activated to regulate metabolism, and meanwhile, the semeglutide can be used for preparing a medicine for treating liver cancer. According to the system, the oral bioavailability of the semeglutide can be improved, and non-specific distribution of the whole body is reduced.

The application belongs to the technical field of hydrogel preparation, and particularly relates to a hydrogel loaded with semaglutide and a preparation method and application thereof. The preparation method comprises the following steps: adding ferulic acid modified chitosan into deionized water to obtain a modified chitosan solution, adding oxidized dextran into deionized water, ultrasonic dissolving to obtain an oxidized dextran solution, adding semaglutide into the oxidized dextran solution to obtain an oxidized dextran mixed solution, and mixing the modified chitosan solution and the oxidized dextran mixed solution to obtain the hydrogel loaded with semaglutide. The hydrogel loaded with semaglutide has the advantages of short gelation time, good injection performance, non-toxicity and good biocompatibility. The hydrogel can significantly reduce myocardial interstitial fibrosis after myocardial infarction and improve the ejection capacity of the heart after myocardial infarction. The hydrogel can be used for preparing drugs for treating myocardial infarction.

The present disclosure relates to a pharmaceutical composition useful for the prevention or treatment of diabetes, preservation of beta-cell function, hypertension, hyperlipidemia, obesity, non-alcoholic steatohepatitis, or neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, which includes a sustained-release microsphere containing semaglutide or a pharmaceutically acceptable salt thereof, a bioavailability enhancer and a biodegradable polymer, so that the pharmaceutical composition do not have a high initial burst of drug, contain a high content of drug relative to the particle size and have a high bioavailability, and thus, can minimize pain and inflammatory response of patient that may occur when administered to the human body.

The present invention relates to a sustained-release pharmaceutical composition using a GLP-1 receptor agonist. Specifically, microparticles comprising semaglutide are prepared using a 5-hydroxydopamine-modified self-crosslinkable hyaluronic acid derivative (SAMH) as a carrier, and the semaglutide is gradually released over a long period of time upon injection into the body, thereby providing excellent effects on blood glucose control and weight management. The sustained-release pharmaceutical composition according to the present invention maintains a low viscosity before administration to the human body, thus being easily administered by injection, and is self-crosslinked and hydrogelated after administration to the human body, and thus can maintain the pharmacological effect of the semaglutide for a long period of time with only a single administration.

The present invention provides a microneedle array containing semaglutide and a manufacturing method therefor, the microneedle array increasing the stability of a drug in a solution and minimizing the influence of enzymes in the skin, thereby enabling excessive use of the drug during manufacture of the microneedle to be reduced and skin permeability to be improved.

The present invention relates to a process for preparing Semaglutide by solid phase peptide synthesis (SPPS). It describes a convergent synthesis by using different fragments including pseudoprolines in one or more of the fragments bound to a solid support.

The invention relates to the technical field of medicines, and provides a semeglutide coated tablet and a preparation method thereof. The chip-coated sheet comprises a chip core layer and a shell layer, the tablet core layer comprises a first absorption enhancer; the shell layer comprises a second absorption enhancer; the first absorption enhancer and the second absorption enhancer are selected from the group consisting of sodium 8-(2-hydroxybenzamido) caprylate, Tween 80, lauryl sodium sulfate, sodium caprate, polyglycerol-3 diisostearate, oleic acid, lauric acid, sodium deoxycholate, sodium cholate, polyoxyethylene (35) castor oil, PEG-vitamin E succinate, PEG-vitamin D3 succinate and pluronic. The invention relates to a preservative which is prepared from the following raw materials: polyethylene glycol, a methoxy polyethylene glycol-polycaprolactone copolymer, sucrose fatty acid ester, 15-hydroxystearic acid polyethylene glycol ester and caprylic / capric acid polyethylene glycol glyceride. The coated tablet provided by the invention adopts a double-layer structure consisting of the tablet core layer and the shell layer, so that the bioavailability of the preparation can be remarkably improved, the oral dosage can be hopefully and greatly reduced, and the medication cost is reduced.

Disclosed herein are an aqueous pharmaceutical formulation comprising cagrilintide and an aqueous formulation comprising semaglutide. The compositions of these two pharmaceutical formulations allow for their presentation in, and administration using, the dual-chamber medical device disclosed herein. Individuals with diseases, such as diabetes and / or obesity and / or related co-morbidities, may benefit from the co-administration of semaglutide and cagrilintide, and / or of the two liquid pharmaceutical formulations disclosed herein, using the medical device disclosed herein.

The invention relates to the field of drug synthesis, and discloses a method for preparing semeglutide through fragment condensation, which comprises the following steps: taking 1-4 amino acids of a semeglutide amino acid sequence as a fragment I, 1-16 amino acids of the amino acid sequence as a fragment II, 17-29 amino acids of the amino acid sequence as a fragment III, and 30-31 amino acids of the amino acid sequence as a fragment IV; preparing the first fragment, the second fragment, the third fragment and the fourth fragment into a semeglutide product by adopting a solid-liquid combination method; the fragment I of the method can effectively inhibit racemization impurities of His; the C-terminal amino acids of the second fragment, the third fragment and the fourth fragment in the method are all Gly, and racemization impurities cannot be generated when the three fragments are condensed. In addition, the fragment synthesized by the fragment II, the fragment III and the fragment IV is high in purity and good in solubility, the condensation reaction efficiency of the polypeptide fragment is high, the fragment utilization rate is high, the cost is low, the unutilized fragment can be extracted and separated, and the post-treatment is simple.

The present invention relates to a depot composition comprising calcium chloride in the interior of microspheres. The depot composition according to the present invention can control the excessive release of the effective ingredient contained in the interior of the microspheres at the initial stage of the depot injection by using calcium chloride as a cationic salt. In addition, the composition has excellent suspendability and a very small amount of residual solvent, and thus the effect of the effective ingredient can be uniformly and continuously obtained even if the user administers it in the form of an injection. In addition, an improved medical therapy of semaglutide can be provided by adjusting the dose of semaglutide or tirzepatide through the depot dosage form.