Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 6 to 7 amino acid residues in defined sequence
Patent
1986-02-05
1987-09-22
Phillips, Delbert R.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
6 to 7 amino acid residues in defined sequence
C07K 706
Patent
active
046956220
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to the art of organic chemistry and, more particularly, to a novel hexapeptide.
STATE OF ART
At the present time acute pancreatitis is one of the most widespread diseases of the abdominal cavity organs. Parallel to the increasing general number of patients with acute pancreatitis, frequency of destructive forms of the disease is also growing. Despite the achieved success in the treatment of acute pancreatitis, hitherto in the case of a progressive necrosis of pancreas lethality remains high and reaches 50-60% on the average.
Known in the art are substances of a peptide nature such as glucagon and somatistatin inhibiting the external secretion of pancreas. (Greutzfeldt W. Gastrointestinal peptides: role in pathophysiology and diseases. Scand J. Gastroenterol., 1982 Suppl. 77, p. 7-20; Arnold R., Lankisch P. G. Somatostatin and the gastrointestinal tract, Glin. Gastroenterol., 1980, v. 9, p. 733-353).
However, these peptides proved to be less effective in the treatment of acute pancreatitis.
Known are carbasates of peptides which are selective inhibitors of elastase (cf. U.S. Pat. Nos. 4,064,236; 4,029,772 C1. 424/177). However, this property of the compounds is not decisive in the treatment of acute pancreatitis, wherefore these substances have not enjoyed a wide clinical application.
At the present time for the treatment of acute pancreatitis antienzymatic preparations such as tracilol are used. However, these preparations are effective enough only in the case of an edematic (light) form of the diseases (cf. Nesterenko Yu. A., atanov Yu. P. Assessment of Antienzymatic Therapy of Destructive Pancreatitis, "Khirurgiya". 1981, No. 1, p. 84-88).
Basic preparations employed for the treatment of pancreatitis are cytostatics, for example 5-fluorouracyl (Laptev V. V. Treatment of Destructive Pancreatitis with 5)Fluorouracyl, "Khirurgiya", 1981, No. 1, p. 67-72). However, the use of cytostatics appears to be insufficiently effective; moreover, it is accompanied by undesirable side effects such as inhibition of processes of homopoiesis and suppression of immune reactions.
Known in the art are hexapeptides of various structures such as a hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH.sub.2 (Bowers C. Y. et al, Endocrinology, 1984, 114, No. 5, p. 1537-1545) or Tyr-D-Ala-Gly-Phe-Leu-Arg and the like (A. V. Waldman, O. S. Medvedev, Theoretical Prerequisits for Finding Novel Cardio-Vascular Agents Among Peptides, "Vestnik Akademii Meditsinskikh Nauk SSSR" (Newsletters of the USSR Academy of Medical Sciences), 1982, No. 5, p. 14-23).
However, an antipancreonecrotic activity for such compounds has been hitherto unknown.
DISCLOSURE OF THE INVENTION
The hexapeptide according to the present invention is novel and hitherto unknown from the literature.
The present invention is directed to the provision of a novel hexapeptide possessing a high antipancreonecrotic activity causing no side responses and useful in medicine.
This object has been accomplished by that a novel hexapeptide according to the present invention has the following structure: Tyr-Ala-Gly-Phe-Leu-Arg
The hexapeptide according to the present invention comprises a white powder, well soluble in distilled water, a physiological solution, ethanol; insoluble in ether, ethylacetate, benzene. The melting temperature is 173.degree.-176.degree. C. [.alpha]sub.D.sup.22 =-19.1 (c 0.33 H.sub.2 O).
BEST MODE FOR CARRYING OUT THE INVENTION
The biological activity of the hexapeptide according to the present invention has been studied in experiments on dogs using an experimental acute pancreatitis model.
To this end, a similar operation was performed on 10 dogs. Under hexenal narcosis upper-median laparotomy was made. Into the wound a loop of duodenum was introduced with pancreas, cannulated and Wirsung's duct was dressed on a drain Snatorini's duct was additionally dressed too. Then the gall-bladder was punctured, bile was extracted therefrom and injected under pressure into Wirsung's duct at the rate of 0.5 ml per kg
REFERENCES:
Article: Assessment of Antienzymatid Therapy of Destructive Pancreatitis, Yu A. Nesterenko, Yu P. Atano.
Bespalova Zhanna D.
Chazov Evgeny I.
Dzhikia Alexandr A.
Emelyanov Sergei I.
Giorgadze Alexandr K.
Phillips Delbert R.
Vsesojuzny Kardiologichesky Nauchny Tsentr Akademii Meditsinskik
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