Preventives and remedies for intestinal mucosal disorder

Details Preventives and remedies for intestinal mucosal disorder Preventives and remedies for intestinal mucosal disorder

2000-10-02

2002-01-08

Seidel, Marianne C. (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Phosphorus containing other than solely as part of an...

C514S669000, C514S012200, C514S002600

Reexamination Certificate

active

06337322

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a drug for preventing and treating intestinal mucosal disorders.
BACKGROUND ART
Currently, pervenous nutrition and enteral nutrition are the predominant therapeutic methods used in the field of gastrointestinal surgery, and greatly contribute to therapeutic outcomes. However, these two methods have drawbacks. Pervenous nutrition and enteral nutrition are employed as a trophotherapy to treat invasion precipitated by surgery or grave infectious diseases; malignant tumors; chronic marasmic conditions; hepatic cirrhosis; chronic obstructive lung diseases; or similar conditions. Problems reported in relation to pervenous nutrition (introduction of hyperalimentation by transfusion via the central vein) include atrophy of the intestinal tract mucosa (Johnson, L. R. et al.: Gastroenterology. 68: 1177-1183, 1975), disturbance of intestinal flora (Winitz, M. et al.: Am. J. Nutrition. 23: 546-559, 1970), decrease in intestinal absorption (King, A. B.: Ed. Bounous, G. CRC Press, Florida, 1993), and a deterioration in the biological protection mechanism provided by intestinal tract barrier immunity (Alverdy, J. C.: Ed. Bounous, G. CRC Press, Florida, 1993). When enteral nutrition through the intestinal tract—which resembles peroral ingestion more closely than pervenous nutrition does—is carried out, aggravation of mucosal lesions and diarrhea can cause a reduction in the absorption of calorific elements and nutritional substances, thereby possibly exacerbating the conditions. For example, when enteral elemental nutrition of low residue content is administered over a long term, atrophy of the small intestine, reduced nutritional absorption, and diarrhea are possibly induced by the administration of a hyperosmolar solution.
Thus, there is demand for a preventive and therapeutic agent to treat disorders of the intestinal mucosa. Thus far, there have been known a drug for preventing atrophy of the intestinal mucosa (Japanese Patent Application Laid-Open (kokai) No. 5-9121) and a drug for preventing and treating disorders of the intestinal mucosa, which drug contains M-CSF as an active ingredient (Japanese Patent Application Laid-Open (kokai) No. 6-321801).
In addition, organic acids such as butyric acid and propionic acid are known to promote proliferation (Sakata, T.: British Journal of Nutrition. 58: 95-103, 1987) and assist the metabolism of epithelial cells in the intestinal tract (Scheppach, W.: Gut. 35: S35-S38, 1994). Amino acids such as glutamine are also known to promote proliferation and assist the metabolism of cells in the intestinal tract (Fox, A. D. et al.: J. Parenteral and Enteral Nutrition. 12: 325-331, 1988; Klimberg, V. S. et al.: Arch. Surg. 125: 1040-1045, 1990; Odweyer, S. T. et al.: J. Parenteral and Enteral Nutrition. 13: 579-585, 1989).
However, these drugs used in preventing and treating intestinal mucosal disorders are unsatisfactory with regard to effectiveness and dose.
Thus, an object of the present invention is to provide a substance effective in preventing and treating intestinal mucosal disorders which are caused by a variety of tissue disorder factors, inter alia, long-term administration of pervenous or enteral nutrition.
DISCLOSURE OF THE INVENTION
The present inventors have conducted careful research into substances effective in preventing and treating intestinal mucosal disorders, and have found that ethanolamine, phosphoethanolamine, phosphoglycerolethanolamine, or a salt thereof (hereinafter these compounds may be collectively referred to as “ethanolamines”)—contained in organisms and being safe—are effective in preventing and treating intestinal mucosal disorders. The present invention has been accomplished on the basis of this finding.
Accordingly, the present invention provides a drug for preventing and treating intestinal mucosal disorders or pathological conditions caused by the disorders, which drug contains as an active ingredient a member selected from the group consisting of ethanolamine, phosphoethanolamine, phosphoglycerolethanolamine, and salts thereof.
The present invention also provides use of a member selected from the group consisting of ethanolamine, phosphoethanolamine, phosphoglycerolethanolamine, and salts thereof in the manufacture of a drug for preventing and treating intestinal mucosal disorders or pathological conditions caused by the disorders.
Furthermore, the present invention provides a method for treating intestinal mucosal disorders or pathological conditions caused by the disorders, which method comprises administering to a patient in need thereof an effective amount of a member selected from the group consisting of ethanolamine, phosphoethanolamine, phosphoglycerolethanolamine, and salts thereof.


REFERENCES:
patent: 8-310944 (1996-11-01), None
R. Rao, et al., European Journal of Pharmacology, vol. 303, No. 3, pp. 209 to 212, “Epidermal Growth Factor Protects Mouse Ileal Mucosa from Triton X-100-Induced Injury”, 1996.
M. Sottili, et al., Gastroenterology, vol. 109, No. 1, pp. 24 to 31, “Up-Regulation of Transforming Growth Factor &agr; Binding Sites in Experimental Rabbit Colitis”, 1995.
“Changes in activity of alkaline and acid phosphatases in stomach mucous membranes and samll intestines under action of amino alcohols”, Mnatsakanyan et al, 1966, Bio. Zh. Arm.: Abstract.*
“Ethanolamine modulation of phospholipid metabolite levels in human B-cell malignancies”, Shedd et al, 1995, Proc Annu Meet Am Assoc Cancer Res: Abstract.

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