Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-08-29
1995-07-11
Cintins, Marianne M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
426656, A61K 3800, C07K 506
Patent
active
054321603
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP94/00101 filed Jan. 26, 1994.
TECHNICAL FIELD
The present invention relates to .beta.-alanyl-L-glutamine-containing nutrient compositions such as infusions and nutrient preparations.
PRIOR ART
As a means for supplementing nutrients to mammals including humans, it is known to supplement amino acids singly or in combination with proteins, vitamins and the like orally or through injection. For example, L-glutamine must be supplemented to a patient in post-operative catabolic condition since the quantity of L-glutamine in the muscle of such a patient seriously decreases. However, because of its heat instability in solution, L-glutamine itself cannot be contained in a nutrient composition which should be sterilized by heating.
It is known L-glutamine, which is thermally unstable in solution, is supplied in the form of a nutrient composition for mammals by converting L-glutamine into a dipeptide. For example, there are known a nutrient composition containing L-alanyl-L-glutamine (DE3206784A), a nutrient composition containing glycyl-L-glutamine (JPA-61-247354), a nutrient composition containing L-aspartyl-L-glutamine (JPA-62-151156), and a nutrient composition containing L-glutamyl-L-glutamine (WO90/11024, U.S. Pat. No. 5,134,125).
In the nutrient compositions containing dipeptides of L-glutamine such as L-alanyl-L-glutamine, glycyl-L-glutamine, L-aspartyl-L-glutamine and L-glutamyl-L-glutamine, heat stability is improved in comparison with L-glutamine. Still, under sterilizing conditions, the depeptides are not satisfactory in heat stability, and therefore, it has been desired to be developed an L-glutamine-containing substance which is superior in heat stability.
DISCLOSURE OF THE INVENTION
The present invention relates to .beta.-alanyl-L-glutamine-containing nutrient compositions having improved solubility in water and excellent heat stability.
Examples of nutrient compositions include amino acid infusions and nutrient preparations.
Amino acid infusions of the present invention contain .beta.-alanyl-L-glutamine, and at least one of essential amino acids such as glycine and L-isomers of isoleucine, leucine, lysine, phenylalanine, methionine, threonine, tryptophane, valine, arginine, histidine, alanine, aspartic acid, cysteine, glutamic acid, proline, serine and tyrosine and salts of those essential amino acids. If necessary, the amino acid infusions may additionally contain carbohydrates such as glucose, fructose, xylitol, sorbitol and maltose, polyhydric alcohols such as glycerol, lipids such as soy bean oil, cotton seed oil, sesame oil, yolk lecithin and soy bean lecithin, vitamins such as vitamin A, vitamin B1, vitamin B2, vitamin B6, nicotinic acid, pantothenic acid, vitamin C, vitamin D, vitamin E, biotin and folic acid, electrolytes such as sodium chloride, sodium acetate, potassium chloride, magnesium sulfate, magnecium chloride, calcium chloride, dipotassium hydrogenphosphate and sodium dihydrogenphosphate, halogens such as iodine, and metals such as iron, zinc, manganese, copper and cobalt.
.beta.-Alanyl-L-glutamine used in the present invention is a known compound, and it can be synthesized according to a known process described, e.g., in CA, Vol.70, 38090n(1969).
An amino acid infusion can be obtained in the following manner: (a) To .beta.-alanyl-L-glutamine and at least one of the above-mentioned amino acids and additives is added 33 to 10,000 times as much distilled water for injection or aqueous solution such as physiological saline solution as .beta.-alanyl-L-glutamine by weight, followed by thorough stirring to completely dissolve solids; or (b) To a solution containing at least one of the above-mentioned amino acids is added 0.001 to 30 wt % of .beta.-alanyl-L-glutamine, followed by dissolving. The dissolving of .beta.-alanyl-L-glutamine and amino acids can be carried out, if necessary, with heating at 25.degree. to 50.degree. C. The pH of the obtained solution is adjusted at 4.0 to 7.5 with acetic acid, hydrochloric acid, lactic acid, malic acid, ci
REFERENCES:
patent: 4024286 (1977-05-01), Cornelius et al.
patent: 4340592 (1982-07-01), Adibi
patent: 5034377 (1991-07-01), Adibi et al.
patent: 5102871 (1992-04-01), Furukawa et al.
patent: 5134125 (1992-07-01), Hara et al.
Hara Takahiro
Yokoo Yoshiharu
Cintins Marianne M.
Kyowa Hakko Kohyo Co., Ltd.
Weddington K.
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