Adsorbent for immunoglobulins and complexes thereof, adsorption

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Separation or purification

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210660, 210674, 4241401, 604 501, 604 502, A61K 3900, C07K 1700

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active

061334316

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to an adsorbent and an adsorption device for adsorbing immunoglobulins and/or immunoglobulin complexes, and a method for adsorbing and removing immunoglobulins and/or immunoglobulin complexes.


BACKGROUND ART

In recent years, it has become clear that, in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematoses, Guillain-Barre syndrome, and idiopathic thrombocytopenic purpura, or in diseases such as glomerular nephritis, rejection of transplanted organs, tumor, and infectious disease, immunoglobulins and/or immunoglobulin complexes present in the blood have a close relationship with the cause or progress of diseases and/or phenomena.
Under the above-mentioned circumstance, several adsorbing and removing materials have been utilized in the hope of preventing the progress of the above-mentioned diseases, relieving the conditions, and furthermore promoting healing by specifically adsorbing and removing immunoglobulins and/or immunoglobulin complexes from the body fluid such as the blood and the plasma. For example, an immune adsorbent (Japanese Laid-open Publication No. 62-242628) in which protein A capable of binding to immunoglobulins is immobilized onto a silica matrix is known as an adsorbent which is highly specific to immunoglobulin G and immunoglobulin complexes thereof. Furthermore, an adsorbent (Japanese Laid-open Publication No. 57-122875) for immunoglobulins and/or immunoglobulin complexes in which a hydrophobic compound is immobilized onto an insoluble carrier has already been clinically applied in Japan.
However, the adsorbent which has been used (e.g., the above-mentioned adsorbent for protein A) has disadvantages. Specifically, protein A, which is a functional group, is a heterogenous protein having a molecular weight of about 42,000 daltons derived from Staphylococcus aureus, so that when the adsorbent is used in contact with the body fluid, protein A is eluted and its antigenicity may cause side effects. Also there is a problem of stability during sterilization of the adsorbent, therefore sterilization method is limited. Additionally, storage stability is not sufficient after protein A is immobilized onto a silica matrix; and the like. Furthermore, the adsorbent for immunoglobulins and/or immune complexes thereof described in Japanese Laid-open Publication No. 57-122875 has the disadvantages of poor adsorbing characteristics such as adsorption specificity to a substance of interest and adsorbing capacity (I. Amano et al., "Blood purification therapy, 1st part", Japanese Journal of Clinical Medicine, Vol. 49, pp. 649-654 (1991 sup.). Accordingly, in terms of the safety, stability, adsorbing specificity, adsorbing capacity, and the like, the conventionally known adsorbent for adsorbing immunoglobulins and/or immunoglobulin complexes is not necessarily suitable for use in treating diseases caused by the presence of the above-mentioned pathogenic immunoglobulins and/or immunoglobulin complexes in the body fluid.


DISCLOSURE OF THE INVENTION

The objective of the present invention is to provide an adsorbent with high stability and safety which has high adsorbing specificity to immunoglobulins and/or immunoglobulin complexes and whose adsorbing characteristics decrease less during sterilization or storage, an adsorption device using the adsorbent, and a method for adsorbing and removing immunoglobulins and/or immunoglobulin complexes.
The inventors of the present invention considered the factors that (1) various proteins are known to be immunoglobulin binding proteins, such as protein A, protein G, protein H, protein L, and a rheumatoid factor (N. Tsuchiya, Clinical Immunology, Vol. 23, pp. 896-903 (1991); P. Akesson et al., Mol. Immunol., Vol. 27, pp. 523-531 (1990); and L. Bjorck, J. Immunol., pp. 1194-1197 (1988)) have substantially high adsorbing specificity to immunoglobulins and/or immunoglobulin complexes, (2) a peptide having tens of amino acid residues or about ten or less amino acid residues has antigenicity to a livin

REFERENCES:
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patent: 5108894 (1992-04-01), Bjorck et al.
patent: 5306812 (1994-04-01), Zanetti et al.
patent: 5312901 (1994-05-01), Fahnestock
Affinity Chromatography Principles and Methods, Pharmacia Fine Chemicals, 1974, p. 6.
Akesson, P. et al., Mol. Immunol., vol. 27, pp. 523-531 (1990).
Bjorck, L., J. Immunol., vol. 140, pp. 1194-1197 (1988).
Fahnestock, S.R. et al., J. Bacteriol., vol. 167, pp. 870-880 (1986).
Guss, B. et al., Embo J., vol. 5, pp. 1567-1575 (1986).
Sjobring, U. et al., J. Biol. Chem., vol. 266, pp. 399-405 (1991).

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