Fibronectin solution suitable for use in humans and process for

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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424101, 514 21, 530380, 530386, 530392, A61K 3704, A61K 3516, C07K 1514

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active

047270594

DESCRIPTION:

BRIEF SUMMARY
CROSS REFERENCE TO RELATED APPLICATIONS

This application is a national phase application corresponding to PCT/AT86/00026 filed Mar. 28, 1986 and based, under the International Convention, on an Austrian application No. A 933/85 of Mar. 28, 1985.


FIELD OF THE INVENTION

The invention relates to a fibronectin solution suitable for use in humans and a process for the preparation thereof.


BACKGROUND OF THE INVENTION

Fibronectin is a high-molecular glycoprotein, consisting of two subunits, each having a molecular weight of approximately 220,000 and which is found in plasma in soluble form, in a concentration of about 0.3 mg/ml. In insoluble form, fibronectin is found in connective tissues and as associated with basement membranes. Soluble fibronectin interacts with collagen, heparin, fibrin and staphilococci; it has a function in cell adhesion, as for instance thrombocyte adhesion, the structuring of fibrin coagulation, and in the formation of connective tissue, but also particularly as one of the main opsonizing factors in the phagocytosis function of the reticuloendothelial system.
Fibronectin is cross-linked with fibrin under the action of factor XIII and stabilizes the fibrin coagulation, attracting fibroblasts in the process. Corresponding to its incorporation in the fibrin coagulum, the serum concentration of fibrin is lower by approximately 20.degree.-50.degree. than that of plasma.
Of particular clinical importance is the opsonin-function of fibronectin, and there are clear indications that, for the normal function of the reticuloendothelial systems in the spleen, the liver and the bone marrow, fibronectin is required. So, for instance, in research with laboratory animals it has been established that after artificial fibronectin depletion, phagocytosis capacity is massively inhibited. Further, fibronectin facilitates the bond between fibrin and macrophages and increases the phagocytosis in streptococci. A lower level of fibronectin is found in patients, after major surgery or trauma and in the case of advanced malignancies. The reduction of fibronectin is probably also related to the "shock lung" occuring in septicemia. In patients in intensive care it has been found that a higher level of fibronectin, established on arrival, could usually be connected to a significantly lower mortality rate, and that patient whose fibronectin level fell below 0.195 mg/ml during their stay, presented a mortality rate higher by 65% than that of patients whose fibronectin level did not fall below 0.195% during their stay.
Fibronectin is present in fresh plasma, fresh frozen plasma, antihemophilic plasma and cryoprecipitates, and has been used therapeutically in the form of cryoprecipitates, whereby in some of the patients dramatic improvements took place, particularly with regard to cardio-pulmonary functions. This mode of administrating fibronectin has however the disadvantage of a quite large volume and of the fact that these forms of administration can not be subjected to heat treatments analogous to those which make albumin safe from hepatitis.


OBJECT OF THE INVENTION

It is the object of this invention to create a preparation of fibronectin in the form of a solution containing fibronectin, which has been made virus-safe through heat inactivation of hepatitis and other possible viral contaminants.


DESCRIPTION OF THE INVENTION

In the process according to the invention for the preparation of this fibronectin solution inorganic in that the initial material containing fibronectin in the form of cryoprecipitate, fresh frozen plasma, outdated plasma, cryoprecipitate-poor plasma or fibronectin-containing human plasma fractions, or for instance made from plasma precipitated with organic precipitating agents, such as polyethyleneglycol, alcohols, ether, or with anorganic precipitating agents, such as ammonium sulfate, sodium sulfate, sodium chloride, or from chromatographically produced fibronectin-containing plasma fractions (for instance ion-exchange chromatography or affinity chromatography on gelatine-, heparin-

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patent: 4305871 (1981-12-01), Shanbrom
patent: 4315906 (1982-02-01), Gelder
patent: 4341764 (1982-07-01), Wallace et al.
patent: 4404187 (1983-09-01), Schwinn et al.
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patent: 4565651 (1986-01-01), Ohmura et al.
patent: 4585654 (1986-04-01), Landaburu et al.
patent: 4587122 (1986-05-01), Kagitani et al.
patent: 4623717 (1986-11-01), Fernandes et al.

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