38 results about "Terlipressin" patented technology

The invention describes compositions of peptide analogs exemplified by peptides derived from vasopressin, terlipressin, and GLP1 and others that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm)x-Peptide, wherein A is a hydrophobic moiety or a metal binding moiety, and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. A may be linked to Cm by a linker group. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

The invention discloses a Telis-vasophysin preparing method of solid-phase polypeptide, which comprises the following steps: adopting Rink Amide resin (concluding Rink Amide MBHA resin, Rink AmideAM resin) as original material, Fmoc protective amino acid as monomer, TBTU or HBTU-to-HOBt as condensing agent to connect amino sequently; using Boc-Gly-OH for the last peptide chain; adding peptide cutting agent to cut peptide; adding ether to deposit to obtain crude product; adding alkali material to oxidate at 7.5-10.0 pH value to generate oxide crude product; proceeding separation and purifying through C18 (or C8) pillar to produce object product. The method possesses low manufacturing cost, simple technology, high obtaining rate and low environmental pollution, which is convenient to do industrial construction.

The present invention relates to the field of polypeptide purification, and particularly to a method for purifying terli. According to the method, a terli crude product is pre-treated, and then purification and salt conversion are performed to obtain the terli with purity more than 99.5%. The method of the present invention has the following advantages that: the operation is simple and easy to perform; the terli prepared by the method of the present invention has characteristics of high purity (the purity can be more than 99.5%, and the maximum single impurity is less than 0.1%) and high yield (the purification yield can be more than 85%, and the total yield can be more than 50%); and the method meets requirements of industrialization, and more than 1000 g of the refined peptide can be obtained in one batch.

The invention belongs to the technical field of medicines, and particularly relates to a related substance analysis method for terlipressin for injection. The content detection method for the terlipressin for injection includes the following steps: (Step 1) preparation of test solvent: the terlipressin for injection is prepared into the test solvent; (Step 2) preparation of self-control solvent: the test solvent is diluted, so that the self-control solvent is prepared; (Step 3) related substance content calculation: the control solvent and the test solvent are respectively injected into high-performance liquid chromatographs, so that chromatograms are obtained, and the related substance content in the test solvent is obtained by calculation.

The invention discloses a method for synthesizing terlipressin by solid-phase oxidization and cyclization. The method comprises the following steps: (1) obtaining Fmoc-Gly-amino resins by using Fmoc-Gly-OH and amino resins; (2) coupling the Fmoc-Gly-amino resins one by one to obtain linear terlipressin-amino resins; (3) synthesizing the linear terlipressin-amino resins into terlipressin-amino resins by adopting iodine solid-phase oxidized cyclization; (4) cracking and cutting the terlipressin-amino resins to obtain raw peptides of the terlipressin; and (5) carrying out purification, salt conversion and freeze-drying on the raw peptides to obtain terlipressin acetate. The invention has the key innovations that solid-phase oxidization reduces a large amount of waste liquid brought by liquid-phase oxidization, accelerates the reaction time, belongs to process greening reformation and greatly improves the total yield.

The invention relates to a purifying method for terlipressin. The method is characterized by comprising the following steps: step 1, dissolving a crude terlipressin product with water and adjusting a pH value to 3 to 4; step 2, flushing a C18 reversed-phase filled column by using an ion pair mobile phase A containing surfactant; step 3, loading a solution obtained in the step 1 into a C18 reversed-phase filling material; step 4, carrying out gradient procedures, wherein the initial-state mobile phase B of an elution gradient is 5% which is maintained for 5 min, then the proportion of the mobile phase B is increased to 30% within 60 min, and a part of target peak elution fraction is collected; and step 5, carrying out nanofiltration membrane desalination and then freeze drying so as to obtain pure terlipressin.

The invention discloses a method for detecting and analyzing high-molecular polymers in terlipressin for injection, which belongs to the technical field of compound detection and analysis. As follows: Chromatographic column: TSKgel G2000SWXL, size 7.8mm×300mm, 5um; mobile phase: 0.1mol / L sodium sulfate solution prepared with 0.1mol / L phosphate buffer; detection wavelength: 274nm; flow rate: 0.5ml / min; Temperature: 25°C; Injection volume: 20μl; Elution method: Isocratic elution. The invention can accurately detect the content of high molecular polymer in the terlipressin for injection, can effectively control the content of high molecular polymer in the product, and the detection method of the invention has the advantages of simple method and strong operability.

The disclosure provides pharmaceutical compositions comprising terlipressin having increased concentration with long term storage stability.

The invention discloses a fragment condensation method of terlipressin. The fully protected first peptide fragment sequence resin of terlipressin is prepared in solid phase, cyclized to form a disulfide bond, and then the cyclized fully protected first peptide is cyclized. The peptide fragment sequence is cleaved from the resin; the cyclized fully protected first peptide fragment sequence is condensed with H-Gly-NH2 in the liquid phase to obtain the cyclized fully protected second peptide fragment sequence; liquid phase or solid phase preparation of terlipress The third peptide fragment sequence of the protein; the cyclized fully protected second peptide fragment sequence is de-protected at the amino terminal and condensed with the third peptide fragment sequence, and then removes all protecting groups to obtain the crude terlipressin, which is purified and converted to salt to obtain the product Terlipressin acetate; the first peptide fragment sequence is the 4-11th amino acid in the terlipressin sequence, the second peptide fragment sequence is the 4-12th amino acid in the terlipressin sequence, the The tripeptide fragment sequence is the 1-3 amino acid in the terlipressin sequence.