Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-04-03
1996-08-06
Schain, Howard E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 6, 514 12, 514 21, A61K 3840, A61K 3818, A61K 3814
Patent
active
055433928
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a digestive tract cell activating agent. More particularly, the present invention relates to a digestive tract cell activating agent which contains an epidermal growth factor, lactoferrins and/or a hydrolysate of lactoferrin, and is useful widely in the medical treatment area including prevention and therapy of digestive tract diseases, promotion of digestive tract functions and activation thereof.
BACKGROUND ART
The Epidermal growth factor (hereinafter sometimes referred to as "EGF") is a peptide having a molecular weight of about 6,000, has proliferation-stimulating function for a wide variety of mammalian cells, and is contained in body fluid of all mammals. Since EGF is contained in breastmilk in a relatively high concentration, general attention is attracted by the relationship between EGF and growth and development of a newborn (neonate in the case of an animal), and among others, the effect of EGF on the development of digestive tract of neonatal rat and mouse has been studied. For example, it has been clarified that feeding a neonatal rat with an artificil milk added with EGF accelerate synthesis of DNA in the small intestine [C. L. Berseth: American Journal of Physiology, Vol. 253, p. G662, 1987], and that it increases the wet weight of stomach [J. Falconer: Biology of the Neonate, Vol. 52, p. 347, 1987, and E. V. O'Loughlin, et al: American Journal of Physiology, Vol. 249, p. G674, 1985]. It has also been demonstrated that administration of EGF to a neonatal rat accelerates development functions of the small intestine and mucosa thereof [C. Malo, et al: Gastroenterology, Vol. 83, p. 23, 1982, and Y. Oka, et al: Endocrinology, Vol. 112, p. 940, 1983].
There are known some cases of application of EGF for therapy of digestive tract diseases in accordance with the findings as described above. A recent case is reported where administration of EGF to an eight month old infant suffering from necrotic inflammation of small intestine (necrotinsing enteritis) led to recovery of fataldamages to the digestive tract [P. E. Sullivan, et al: Lancet, Vol. 338, p. 53, 1991], demonstrating clinical effectiveness of EGF.
The effect and the action mechanism of EGF on cultured cells have widely been studied to date since discovery of EGF in 1962. Regarding digestive tract cells, it has now been clarified that DNA synthesis in intestine apithelial cells is accelerated by EGF, and this action is caused via an EGF receptor presentin the cytoplasmic membrane [M. E. Forgue Lafite, et al: FEBS Letter, Vol. 114, p. 243, 1980; and N. Gallo-payet, et al: Endocrinology, Vol. 116, p. 194, 1985].
Sice usefulness of EGF for activating the digestive trtact has been revealed, blending of EGF into powder milk for infant was proposed (Japanese Patent Provisional Publication No. 62-228,225; and Japanese Patent Provisional Publication No. 1-148,146). More specifically, because digestive tract cells are not matured, a newborn is susceptible to easy entry of various bacteria and antigens through the digestive tract, and furthermore because of an incomplete immunological function, a newborn is sensible to infectious diseases. Therefore, with a view to promoting growth or proliferation of digestive tract cells, accelerating development of the digestive tract functions, and preventing ingression of bacteria, it was proposed to blend EGF into powder milk for infant.
Breastmilk contains, in addition to EGF, other substances showing proliferation stimulating function. Lactoferrin (hereinafter sometimes referred to as "Lf") is an iron-binding protein having a molecular weight of about 80,000 contained in a very large quantity in breastmilk, and has been known to exhibit an antimicrobial activity against detrimental micro-organisms such as Escherichia coli, candida, clostridium and Staphylococcus [Journal of Pediatrics, Vol. 91, p. 1, 1979; and Journal of Dairy Science, Vol. 67, p. 60, 1981]. The known functions of Lf and its hydrolysate thereof include antimicrobial activity and inhibition of
REFERENCES:
patent: 4820690 (1989-04-01), Gregory et al.
patent: 4977137 (1990-12-01), Nichols et al.
patent: 5214028 (1993-05-01), Tomita et al.
Fukuwatari Yasuo
Shimamura Seiichi
Shinoda Ichizo
Tomita Mamoru
Morinaga Milk Industry Co. Ltd.
Schain Howard E.
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