Adsorption material for the selective removal of LDL and/or vLDL

Liquid purification or separation – Processes – Ion exchange or selective sorption

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2101982, 2105021, 210656, 422 70, 436 71, 436161, 502405, 530413, 530417, B01D 1500, B01D 1508, C07K 318, C07K 320

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active

054014158

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BRIEF SUMMARY
DESCRIPTION

The invention concerns an adsorption material and a process for removing LDL cholesterol or/and vLDL cholesterol or/and Lp(a) lipoprotein from aqueous liquids such as plasma or serum, a method for the determination of the concentration of LDL cholesterol or/and vLDL cholesterol or/and Lp(a) lipoprotein in liquids as well as a device for the said methods.
The selective elimination of LDL or/and Lp(a) lipoprotein and/or fibrinogen from human blood is desirable for medical reasons in particular for treating a severe familial hypercholesterolaemia and atherosclerosis (Trans. Am. Soc. Artig. Intern. Organs. (1986) 17, 104-107). The familial hypercholesterolaemia is the most dangerous type of hyperlipidaemia. When present in its homozygotic form the affected persons are already in danger of becoming diseased in their youth (and even at a child's age) and dying from severe and rapidly progressing coronary angiopathy (Plasma Sep. and Plasma Frac. 272-280 (Karger Basel, 1983)).
Previous treatments for severe hypercholesterolaemia have proven to be unsatisfactory. This applies to the various types of diet as well as to drug therapy. Therefore one has tried to tackle the severe metabolic disorders by means of extracorporeal removal of atherogenic lipoprotein fractions (very low density and low density lipoproteins, vLDL and LDL) from blood. The aim of an extracorporeal method of treatment is to achieve a total cholesterol level and LDL cholesterol level in the range <200 mg/dl and <130 mg/dl respectively (Klin. Wochenzeitschrift (1987) 69, 161-168; GIT Labor Medizin (1989) 9, 386-395).
The elimination of LDL cholesterol is at present carried out with three different extracorporeal methods. Apart from a cascade filtration (Artherosclerosis 60, 23-37 (1988), Artherosclerosis 73, 197-202 (1988), LDL cholesterol can be eliminated by precipitation with heparin in an acidic pH range (HELP method=heparin induced extracorporeal LDL precipitation) (Klin. Wochenschrift 65, 161-168 (1987), EP 0 166 324, DE 33 10 727) .
The third method of eliminating LDL cholesterol from blood or plasma is adsorption to suitable carrier materials. Thus for example monoclonal and/or polyclonal antibodies which specifically bind the LDL cholesterol can be coupled to a porous polyanionic carrier material (J. Clin. Apheresis 4, 59-65 (1988), Proc. Natl. Acad. Sci. USA 78, 611-615 (1981), JP 60239425). In addition to antibodies, porous polyanions such as heparin (DE 36 17 672, U.S. Pat. No. 4,637,944, U.S. Pat. No. 4,103,685) and synthetic oligoanions or polyanions such as sulfated polysaccharides (EP 0 110 409, EP 0 225 867, EP 143 369, U.S. Pat. No. 4,096,136, U.S. Pat. No. 4,603,010) have been bound to carrier materials and investigated for specific LDL adsorption from plasma or blood. Cellulose, organic polymerisates, coated silica gels and agarose have been described as a carrier matrix for binding the described substances.
The results attained up to now with the described adsorption materials are, however, inadequate for the purpose of adsorbing LDL to a matrix in an extracorporeal perfusion system in a medical and therapeutic context since either the binding capacity and/or the selectivity of these materials for LDL does not meet the practical requirements and/or physiological protective mechanisms (e.g. coagulation system, complement system) are activated. (Artheriosclerosis 73, 143-148 (1988), "Schweiz. med. Wschr." 119, 55-58 . (1989)).
The object of the present invention was therefore to provide materials which enable the removal of artherogenic lipoprotein fractions from aqueous liquids, in particular from whole blood, plasma and serum, and at the same time fulfil the requirements for a simple and safe application in an extracorporeal perfusion system for humans. These requirements are for example capability of sterilization with steam, heat or .gamma.rays, minimal release of particles in the micrometre range, no release of toxic constituents and a sufficiently high flow rate through the materials in the range up to 20

REFERENCES:
patent: 4650784 (1987-03-01), Ramsden et al.
patent: 4773994 (1988-09-01), Williams
patent: 4775483 (1988-10-01), Mookerjea et al.
patent: 4814077 (1989-03-01), Furuyoshi et al.
patent: 4828695 (1989-05-01), Yamamura et al.
patent: 5203991 (1993-04-01), Kutsuna et al.

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