Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1986-11-07
1989-02-21
Schain, Howard E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
514 12, 514 21, 530309, 530324, C07K 732, A61K 4900, A61K 3724
Patent
active
048063363
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to human intestinal hormone, namely the hormone secretin which stimulates pancreatic secrection.
Secretin is an intestinal hormone formed by the mucosa of the upper portion of the small intestine, which stimulates the secretion of water and bicarbonate from the pancreas. The structure of porcine secretin has been known for some time and it has been isolated from porcine intestine and has been found to be constituted by a peptide composed of 27 amino acid residues (Mutt, V., Jorpes, J. E. and Magnusson, S. (1970) Eur. J. Biochem., 15, 513-519). Moreover, it has been found that bovine and porcine secretins are identical but that they are markedly different from chicken secretin (Carlquist, M., Jornvall, H. and Mutt, V. (1981) FEBS Lett., 127, 71-74).
Although bovine and porcine secretins behave identically with human secretin in some respects they are not structurally identical. In accordance with the instant invention it has now been found that amino acids number 15 and 16 differ in that the human secretin at said positions contains the residues of glutamic acid (Glu) and glycine (Gly), respectively. Thus, the human intestinal hormone of this invention has the peptide structure: His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-Arg-Glu-Gly-Ala-Arg-Le u-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val-NH.sub.2.
In the instant disclosure the abbreviations used for characterizing the amino acids and their residues are the traditional ones as found for example in the textbook Organic Chemistry, second edition, Ralph J. Fessenden & Joan S. Fessenden, Willard Grant Press, Boston, Mass., pages 852 and 853.
In the same way as the known secretins find diagnostic uses the human secretin according to this invention is highly useful in determining pancreatic and gallbladder functions. According to this aspect of the invention a composition for diagnostic use in this respect comprises an effective diagnostic amount of the secretin of this invention in combination with a carrier which does not interfere with the diagnostic procedure used.
The human secretin of this invention is in addition therapeutically useful in that it stimulates pancreatic secretion in man if administered in a suitable manner. According to this aspect of the invention a composition for such use is provided comprising an effective therapeutic amount of the human secretin of the invention in combination with a non-toxic, pharmaceutically acceptable carrier. In this context the invention also covers a method of treating gastro-intestinal disorders comprising administering a therapeutically effective amount of the hormone of this invention or a composition of this invention on a patient to be treated.
The present invention thus includes within its scope pharmaceutical compositions, which comprise the human intestinal hormone according to this invention in association with a pharmaceutically acceptable carrier. In clinical practice the compositions of the present invention will normally be administered parenterally due to the fact that being a peptide the hormone is sensitive to biologically active environments. Oral or rectal administration may, however, be conceivable using compositions of the slow release type making it possible for the active ingredient to reach the site of primary interest, namely the small intestine.
Preparations according to the invention for the preferred parenteral administration includes sterile aqueous or non-aqueous solutions, suspensions or emulsions. Examples of non-aqueous solvents or suspending media are propylene glycol, vegetable oils, such as olive oil, and injectible organic esters, such as ethyl oleate. These compositions may also contain adjuvants, such as preserving, wetting, emulsifying and dispersing agents. They may be sterilized, for example, by filtration through a bacteria-retaining filter, by incorporation of sterilizing agents in the composition, by irradiation or by heating. They may be also be manufactured in the form of sterile solid compositions, which can be dissolved in a sterile inject
REFERENCES:
patent: 3940480 (1976-02-01), Suenaga et al.
patent: 4533494 (1985-08-01), Uchiyama et al.
Nilsson et al, Eur. J. Biochem., vol. 112, pp. 383-388 (1980).
Carlquist et al., Febs Letters, vol. 127, pp. 71-74 (1981).
Muckadell et al., Chem Abstr., vol. 96, No. 80352m (1982).
Carlquist et al, Chem. Abstr., vol. 103, No. 65113d (1985).
Carlquist et al., "Human Secretin is not Identical to the Porcine/Bovine Hormone", IRCS Med. Sci., vol. 13, pp. 217-218 (1985).
Abstract Presented at the Sixth International Symposium on Gastrointestinal Hormones, No. 148, Jul. 6-10, 1986.
Chem. Pharm. Bull., vol. 33, pp. 2000-2005, 1985, Uchiyama, M. et al, Studies on Secretin II, Synthesis of Secretin with High Activity.
Carlquist Mats
Forssmann Wolf-Georg
Johansson Catja
Jornvall Hans
Mutt Viktor
Chan Christina
KabiGen AB and Skandigen AB
Schain Howard E.
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