Medical compositions containing ghrelin

Abstract

It is provided a pharmaceutical composition stably containing ghrelin or its derivative, which is an endogenous growth hormone secretagogue (GHS) to a growth hormone secretagogue-receptor (GHS-R), comprising a aqueous solution containing the ghrelins having pH range of 2 to 7, wherein the aqueous solution having pH range of 2 to 7 is a buffer solution, especially, glycine hydrochloride buffer, acetate buffer, citrate buffer, lactate buffer, phosphate buffer, citric acid-phosphate buffer, phosphate-acetate-borate buffer or phthalate buffer, and the concentration of the ghrelins in the solution is from 0.03 nmol/mL to 61 μmol/mL.

Description

TECHNICAL FIELD [0001] The present invention relates to a pharmaceutical composition containing ghrelin or derivative thereof, which is an endogenous growth hormone secretagogue (GHS) to a growth hormone secretagogue-receptor (GHS-R) in a stable state, as well as to a method for preventing degradation of modifying hydrophobic group of ghrelin or its derivative in an aqueous solution dissolved ghrelin or its derivative therein. BACKGROUND ART [0002] Ghrelin, an endogenous growth hormone secretagogue (GHS) to growth hormone secretagogue receptor (GHS-R) which is one of orphan receptors, is a physiologically active peptide first isolated and purified from rat in 1999 (Kojima, et al., Nature, 402: 656-660, 1999). Thereafter, some ghrelins having same chemical structure of rat ghrelin have been isolated from vertebrates other than rat, such as human, mouse, pig, chicken, eel, bovine, equine, ovine, frog, trout and canine. The chemical structures of these ghrelins are listed in the follow...

AI Technical Summary

Benefits of technology

[0036] (20) A method according to (19), wherein one or more pH adjuster selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, boric acid, carbonic acid, bicarbonic acid, gluconic acid, sodium hydroxide, potassium hydroxide, aqueous ammonia, citric acid, monoethanolamine, lactic acid, acetic acid, succinic acid, fumaric acid, maleic acid, phosphoric acid, methanesulfonic acid, malic acid, propionic acid, trifluoroacetic acid and salt thereof is contained.

[0037] (21) A method according to (19), wherein one or more buffer agent selected from the group consisting of glycine, acetic acid, citric acid, boric acid, phthalic acid, phosphoric acid, succinic acid, lactic acid, tartaric acid, carbonic acid, hydrochloric acid, sodium hydroxide and the salt thereof is contained.

Problems solved by technology

However, due to the non-existence of peptides like ghrelin having the modifying hydrophobic group in molecule at the hydroxyl group of side chain of specific amino acid residue, the stability of these peptides for development as medicines have never been studied.

Incidentally, the compound to be developed as medicines has the various kinds of chemical structures, and because of these chemical structures, the compounds may easily degrade in the formulation process or in the storage process thereafter.

The physiologically active peptides or physiologically active proteins are inactivated and degraded by protease existing in the digestive organ, and it is difficult to develop the oral administrable composition containing these peptides or proteins.

Though the stability of ghrelin in the aqueous solution is very important for preparation of the pharmaceutical composition, there has never been any study of the stability of ghrelin in the aqueous solution.

That is, it is unknown about the stability, the chemical structure of degradation product and the mechanism of production of the degradation product of ghrelin.

Further, it is unknown about the mechanism of degradation of modifying hydrophobic group of ghrelin, as well as the secondary degradation from the degradation product of ghrelin.

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