34 results about "Ziconotide" patented technology

The present invention is direct to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivicaine, clonidine, hydromorphone, baclofen, fentanyil, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ω-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivicaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

The invention relates to a polypeptide capable of passing through hemato encephalic barrier. According to the invention, the polypeptide capable of passing through hemato encephalic barrier is acquired by connecting C end of ziconotide with N end of cell penetrating peptide through a glycine. The polypeptide provided by the invention is suitable for vein, enterocoelia or nasal delivery, is convenient for operation and has small clinic risks. Through vein, enterocoelia or nasal delivery, the polypeptide has the characteristics of long acting time in human body, excellent analgesic effect, smallside effect of peptide and suitability for large-scale clinical application. The polypeptide provided by the invention is simply prepared, the preparation technology and the quality during the preparation process are controllable and the polypeptide is suitable for large-scale industrialized production.

The invention discloses a method for preparing ziconotide. The technical scheme of the invention comprises the following steps: (1) obtaining an Fmoc-Cys(Acm)-amino resin from Fmoc-Cys(Acm)-OH and an amino resin; (2) obtaining a linear-ziconotide-amino resin of which a Cys side chain comprises Acm by performing the solid phase synthesis on the Fmoc-Cys(Acm)-amino resin and an amino acid adopting Fmoc group protection; (3) obtaining a linear crude peptide of which the Cys side chain comprises the Acm by performing cracking on the linear-ziconotide-amino resin of which the Cys side chain comprises the Acm, and obtaining linear ziconotide by removing the Acm, purifying and freeze-drying; (4) and obtaining the ziconotide by performing cyclization, purifying and freeze-drying on the linear ziconotide. The method for preparing ziconotide has the characteristics of simple reaction operation, easy subsequent treatment, low raw material investment, low cost, high yield and the like, and has considerable economic and practical value, and also has wide application prospect in the field of design synthesis of polypeptide drugs.

The invention relates to a solid phase synthesis method for ziconotide, which comprises the following steps: an Fmoc-Rink Amide-MBHA resin is taken as a solid phase carrier for program reaction; condensation reactions are orderly performed to link 25 amino acids with protecting groups to obtain a linear peptide complete-protection resin of the 25 amino acids,wherein in three groups of Cyses which form a disulfide bond, the Cyses in the same group are simultaneously linked with one of a Trt, Acm or Mob protecting group, and different groups of the Cyses are linked with different protecting groups; the protecting groups of the three groups of the Cyses are orderly removed; a cyclization reaction is performed to form a disulfide ring bond; a side chain protecting group is removed; and the resin is cut to obtain the ziconotide containing three disulfide rings. The method has the main advantages of few side products, high directive efficiency, simplicity, convenience, high yield of products, and favorability for the purification of the products.

The invention discloses a solid-phase synthesis method of ziconotide, and the method comprises the following steps: with Fmoc(9-fluorenylmethyloxycarbonyl)-amino resin as a solid-phase carrier, successively carrying out condensation reaction for connecting 25 protected amino acids to obtain linear fully-protected peptide resin, wherein three groups of Cys (cysteine) with disulfide bond formed areseparately connected with Trt (triphenylmethyl), Acm (acetamidomethyl), or tBu (t-butyl) protecting group; cutting resin, and simultaneously removing all amino acid protecting groups except for Acm and tBu to obtain a linear peptide containing Acm and tBu; oxidizing the linear peptide to form a first pair of disulfide bonds, and simultaneously removing Acm and forming a second pair of disulfide bonds to obtain bicyclic peptide resin; and removing tBu of the bicyclic peptide resin, and simultaneously carrying out cyclization to form a third pair of disulfide bonds and to obtain ziconotide. In the method disclosed by the invention, Trt, Acm and tBu are selected to protect the three groups of Cys, thereby improving the formation accuracy of the disulfide bonds; and after resin is cut off, three pairs of disulfide bonds are sequentially formed through two-step reaction, thereby simplifying steps and improving productivity.

The invention relates to an LHRH (luteinizing hormone releasing hormone) analogue and ziconotide composition sustained-release microsphere preparation and a preparation method thereof. The LHRH analogue and ziconotide composition sustained-release microsphere preparation comprises sustained-release microspheres, wherein the sustained-release microspheres comprise an LHRH analogue, ziconotide and a pharmaceutically acceptable high polymer material. The LHRH analogue and ziconotide composition sustained-release microsphere preparation can effectively bring synergistic effect of the LHRH analogue and the ziconotide into play; experiments prove that the LHRH analogue and ziconotide composition sustained-release microsphere preparation has a sustained-release effect, has a better curative effect in treating cancers, is capable of achieving an analgesic effect at the same time, is administrated by regular injection, and can be used for solving a problem that the ziconotide is inconvenient for clinical administration.