Iron lactoferrin complexes and preparation thereof

Details Iron lactoferrin complexes and preparation thereof Iron lactoferrin complexes and preparation thereof

1995-04-24

1997-02-25

Nazario-Gonzalez, Porfirio

Organic compounds -- part of the class 532-570 series

Organic compounds

Heavy metal containing

556147, 556148, 530394, 530395, 530400, C07F 1502

Patent

active

056060866

DESCRIPTION:

BRIEF SUMMARY
This application was filed under 35 U.S.C. .sctn.371 as a request for U.S. examination of International application No. PCT/JP94/00233 filed on Feb. 16, 1994 and published as WO94/19375 Sep. 1, 1994.


FIELD OF THE INVENTION

This invention relates to thermally stable and heat resistant iron lactoferrin complexes bound with a large quantity of and preparation thereof.
The heat resistant lactoferrin complexes of the present invention contain a large quantity of iron, show no iron specific astringent taste, and prevent the acceleration of peroxide formation by iron. Thus, the complexes are useful as raw materials of foods, medicines, feeds, cosmetics and so forth for the prevention and treatment of anemia, the enrichment of iron content, or the prevention of the infection by pathogenic microorganisms.


BACKGROUND OF THE INVENTION

Various physiological activities of lactoferrin (hereinafter abbreviated as Lf) such as acceleration of iron absorption, prevention of lipoperoxide formation, antibacterial and antiviral activity, cell proliferation, and control of immune system have been known. Therefore, Lf has been used in the production of foods, medicines, feeds and cosmetics. These products are generally pasteurized thermally, or treated with boiled water before use.
However, Lf has an essential drawback of instability against heat. Heat treatment causes precipitation of Lf due to thermal denaturation, and loss of iron binding property which leads to a physiologically inactive state. Investigation for the stabilization of Lf against heat was carried out and revealed that heating at pH 4 does not affect the binding property of Lf to iron (Davidson and Lonnerdal. Am. J. Physiol., 257: G930-G934, 1989). However, heat treated Lf at pH 4 gradually degenerates and loses its physiological properties. Additionally, heat treated of Lf under low ionic strength maintained its physiological activity (Japanese Laid-open Patent Application No. 108629/1992). However, practical ionic strength in commonly used products is not necessarily low. The relative effect on heat stability of Lf to pH and electric conductivity, .OMEGA., was investigated to develop a method of preparation of heat resistant of Lf and showed stabilization of Lf solutions against heat by adjusting log .OMEGA. to satisfy the following equations (Japanese Laid-open Patent Application No. 8269/1992). pasteurization of Lf solutions and the other raw material solutions followed by aseptic mixing of the pasteurized solutions. Japanese Regulations demand single pasteurization by heating after mixing, and does not allow separate pasteurization and mixing.


DISCLOSURE OF THE PRESENT INVENTION

The inventors have been investigating to solve the problems mentioned above for the stabilization of Lf against heat and concluded that it is necessary to modify Lf itself to give heat resistance while maintaining iron binding property. The inventors have prepared heat resistant iron-Lf complexes by reacting of iron salt solution containing carbonic acid or hydrogencarbonic acid ion with Lfs solutions. The iron salt solution must have pH.ltoreq.4 when dissolved in water to give the heat resistant complexes with Lf and carbonic acid or hydrogencarbonic acid ion. Therefore, one object of the present invention is to provide heat resistant carbonate- and/or hydrogen-carbonate-iron-Lf complexes. One other object of the present invention is to provide processes for the preparation of heat resistant carbonate- and/or hydrogen-carbonate-iron-Lf complexes.
That is, the present invention relates to heat resistant iron-Lf complexes in which Lfs are bound with iron via carbonic acid and/or hydrogencarbonic acid.
Additionally, the present invention relates to processes for the preparation of heat resistant iron-Lf complexes. An aqueous solution of Lf is mixed with iron salt, which shows pH.ltoreq.4 when dissolved in water, or an aqueous solution in which are dissolved Lf together with the iron salt. The aqueous solution is made pH.ltoreq.7 by adding salt(s) containing carbonic acid ion

REFERENCES:
patent: 4946944 (1990-08-01), Frankinet et al.
patent: 5116953 (1992-05-01), Dosako et al.
patent: 5141743 (1992-08-01), Schryvers

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