Surgery – Blood drawn and replaced or treated and returned to body – Constituent removed from blood and remainder returned to body
Reexamination Certificate
1999-04-19
2002-07-09
Sykes, Angela D. (Department: 3762)
Surgery
Blood drawn and replaced or treated and returned to body
Constituent removed from blood and remainder returned to body
C422S044000, C210S679000, C210S905000, C502S402000
Reexamination Certificate
active
06416487
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a method of removing beta-2 microglobulin from blood, plasma and other physiological liquids of organism.
Beta-2 microglobulin, a protein, is found in abnormally high concentrations in physiological fluids of patients with chronic renal failure and on chronic dialysis. Beta-2 microglobulin is removed by the kidneys in the proximal tubes by endocytosis in a healthy individual. The molecule is the co-dimer in the dimeric structure of Class-1 HLA antigens. These antigens are found in high concentration on lymphocytes and are found on all nucleated mammalian cells. In patients with malfunctioning kidney, beta-2 microglobulin accumulates to 40 to 60 multiples of normal. The accumulation of beta-2 microglobulin is basis of the initiation of Dialysis-Associated Amyloidosis. This is a clinical entity that causes arthropathy and neuropathy. The primary effect is severe joint destruction and pain. Many patients require corrective surgery such as Carpal-Tunnel Laminectomies and Cervical Spine Laminectomy. In addition, they require use of analgesics and anti-inflammatory medications to treat the symptoms of DRA.
Attempts to remove beta-2 microglobulin have been made, as disclosed for example in A New Therapeutic Approach to Dialysis Amyloidosis: Intensive Removal of &bgr;
2
-Microglobulin with Adsorbent Column by Fumitake Geijyo, Noriyuki Homma, Shin Hasegawa, and Massaaki Arakawa published in Department of Internal Medicine (II), Niigata University School of Medicine, Niigata, Japan. A method of removing beta-2 microglobulin from blood is also disclosed in our U.S. patent application Ser. No. 08/902,727 filed on Jul. 30, 1997, now U.S. Pat. No. 5,909,663. This method can be further amplified and improved.
SUMMARY OF THE INVENTION
Accordingly, it is an object of present invention to provide a method of removal of beta-2 microglobulin, which is a further improvement of existing methods.
In keeping with these objects and with others which will become apparent hereinafter, one feature of present invention resides, briefly stated, in a method of removal of beta-2 microglobulin in accordance with which a blood is passed through an adsorbent material which has a pore size and a structure selected so as to remove beta-2 microglobulin from blood, and the blood from which the beta-2 microglobulin is removed is reentered into the patient.
In accordance with a preferable embodiment of the present invention, the passing of the blood through the adsorbent material can take place simultaneously with the conventional hemodialysis procedure, where the blood is forced to pass in sequence through the adsorbent material and through the hemodialysis membrane cartridge.
In accordance with still a further feature of the present invention, the adsorbent material is a porous polydivinylbenzene or polystyrene-co-polydivinylbenzene polymer with an enhanced proportion of mesopores.
In accordance with still a further feature of the present invention, the passing includes passing through the adsorbent material which is a porous polydivinylbenzene or polystyrene-co-polydivinylbenzene polymer with an enhanced proportion of mesopores and with a surface of the beads and of macropores modified so as to prevent absorption of large proteins and platelets and to minimize activation of blood complement system without affecting noticeably accessibility of an inner absorption space of the beads for beta-2 microglobulin and middle-sized toxicant molecules.
The novel features which are considered as characteristic for the present invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
DESCRIPTION OF PREFERRED EMBODIMENTS
In accordance with present invention, a method of removing beta-2 microglobulin from blood, plasma and other physiological liquid of organism is proposed. A patient's blood is withdrawn from an arterial blood circulatory access point, and passed through an adsorbent material—polymer.
In accordance with the present invention, the passing of the blood through the adsorbent material can take place simultaneously with the conventional hemodialysis procedure, where blood is forced to pass through the adsorbent material and then through a hemodialysis membrane cartridge, or vice versa.
The adsorbent material through which the blood passes can be a porous polydivinylbenzene or polystyrene-co-polydivinylbenzene polymer with an enhanced proportion of mesopores.
Also, the adsorbent material can be a porous polydivinylbenzene or polystyrene-co-polydivinylbenzene polymer with an enhanced proportion of mesopores and with a surface of the beads and of macropores modified so as to prevent adsorption of large proteins and platelets and to minimize activation of blood complement system without affecting noticeably accessibility of an inner adsorption space of the beads for beta-2 microglobulin and middle-sized toxicant molecules.
In accordance with this invention sorbents prepared in accordance with the invention are charged to a column or cartridge for service. The column should preferably be provided with an inlet and an outlet designed to allow easy connection with the blood circuit, and with two porous filters set between the inlet and the sorbent layer, and between the sorbent layer and the outlet. The column may be made of a biocompatible material, glass, polyethylene, polypropylene, polycarbonate, polystyrene. Of these, polypropylene and polycarbonate are preferred materials, because the column packed with the sorbent can be sterilized (e.g., autoclave and gamma-ray sterilization) before use.
The column or cartridge is then filled with a 1% solution of human serum albumin in normal saline and stored at 4° C. When ready for use, the column is washed with 0.9% NaCl solution to which has been added a suitable anticoagulant, such as ACD-A containing heparin in an effective amount. For a 250 ml cartridge, this is approximately 1 l of the sodium chloride solution to which 150 ml of ACD-A containing 6,000 units of heparin has been added.
As usual the following two typical extracorporeal blood circulation systems can be employed:
(I) Blood taken from a blood vessel of a patient is forced to pass through a column packed with the sorbent of this invention, and the clarified blood is returned to the blood vessel of the patient.
(ii) Blood taken from a patient is first separated through a separation membrane, by centrifugation or the like into hemocytes and plasma, the plasma thus separated is then forced to pass through the column packed with the sorbent of this invention to remove toxicants from the plasma; then, the clarified plasma from the column is mixed with the hemocytes separated above, and the mixture is returned to the blood vessels of the patient.
The preparation of the adsorbent material can be performed as follows:
REFERENCES:
patent: 5051185 (1991-09-01), Watanabe et al.
patent: 5073265 (1991-12-01), Johnson et al.
patent: 5403750 (1995-04-01), Braatz et al.
patent: 5773384 (1998-06-01), Davankov et al.
patent: 5904663 (1999-05-01), Braverman et al.
Braverman Andrew
Davankov Vadim
Bianco Patricia
Renal Tech International LLC
Sykes Angela D.
Zborovsky I.
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