U.S. patent application number 10/094001 was filed with the patent office on 2002-07-11 for device for removing toxins from blood or plasma.
Invention is credited to Murray, Daniel J., Strom, Robert M..
Application Number | 20020091231 10/094001 |
Document ID | / |
Family ID | 22888346 |
Filed Date | 2002-07-11 |
United States Patent
Application |
20020091231 |
Kind Code |
A1 |
Strom, Robert M. ; et
al. |
July 11, 2002 |
Device for removing toxins from blood or plasma
Abstract
A device for removing toxins from blood or plasma comprising a
cartridge containing a polymeric resin having a coating thereon
which renders the resin blood compatible. The resin comprises
divinylbenzene monomer which has a porosity, pore size, and surface
area suitable for absorption of unhealthy components of blood, such
as .beta.-2-microglobulin.
Inventors: |
Strom, Robert M.; (Midland,
MI) ; Murray, Daniel J.; (Midland, MI) |
Correspondence
Address: |
THE DOW CHEMICAL COMPANY
INTELLECTUAL PROPERTY SECTION
P. O. BOX 1967
MIDLAND
MI
48641-1967
US
|
Family ID: |
22888346 |
Appl. No.: |
10/094001 |
Filed: |
March 8, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10094001 |
Mar 8, 2002 |
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09965256 |
Sep 27, 2001 |
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09965256 |
Sep 27, 2001 |
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09861969 |
May 21, 2001 |
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6325939 |
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09965256 |
Sep 27, 2001 |
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09746810 |
Dec 22, 2000 |
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6338801 |
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09746810 |
Dec 22, 2000 |
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09483620 |
Jan 14, 2000 |
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6238795 |
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09483620 |
Jan 14, 2000 |
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09236153 |
Jan 22, 1999 |
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Current U.S.
Class: |
528/403 |
Current CPC
Class: |
B01J 20/28083 20130101;
Y10T 428/31855 20150401; B01J 20/264 20130101; B01J 20/26 20130101;
Y10T 428/3192 20150401; B01J 20/28057 20130101; Y10T 428/2967
20150115; B01J 20/28076 20130101; A61M 1/3615 20140204; A61M 1/3679
20130101; B01J 20/28016 20130101; Y10T 428/31 20150115; B01J 20/261
20130101; B01J 2220/58 20130101; B01J 20/28004 20130101; Y10T
428/2991 20150115; B01J 20/321 20130101; Y10T 428/31909 20150401;
Y10S 210/903 20130101; Y10T 428/2978 20150115; B01D 17/0202
20130101; B01J 20/327 20130101; Y10S 210/905 20130101 |
Class at
Publication: |
528/403 |
International
Class: |
C08G 059/00 |
Claims
What is claimed is:
1. A device for removing toxins from blood or plasma comprising a
cartridge containing a polymeric resin and having a fluid inlet and
outlet, wherein the resin is derived from more than 50 mole percent
of divinylbenzene and includes a hemocompatible coating on the
surface thereof, wherein toxins are removed from blood or plasma
passing through the cartridge from the fluid inlet, into contact
with the resin, and exiting out the fluid outlet.
2. The device of claim 1 wherein the cartridge is comprised of a
martial capable of withstanding sterilization.
3. The device of claim 1 wherein the resin is capable of removing
toxins having a molecular weight between about 100 to about 20,000
daltons.
4. The device of claim 1 wherein the resin is derived from 60 to 90
mole percent divinylbenzene.
5. The device of claim 1 wherein the surface of the resin is
rendered hemocompatible through reaction of vinyl reactive
hemocompatible monomers or polymers with unreacted vinyl groups of
the resin.
6. The device according to claim 1, wherein the hemocompatible
coating is selected from the group consisting of:
phosphatidylcholine, heparin, polyalkylene glycol,
polyalkoxyphosphazene, and polyvinylpyrrolindone.
7. The device according to claim 1, wherein the hemocompatible
coating is selected from the group consisting of: 2-vinylpyridine,
4-vinylpyridine, 2-methyl-5-vinylpyridine, 4-vinylimidazole,
N-vinyl-2-ethylimidazole, vinylpyrrolidone, and
N-vinyl-2-methylimidazole.
8. The device according to claim 1, wherein the hemocompatible
coating is selected from the group consisting of: acrylic and
methacrylic acid derivatives including: dimethylaminoethyl
(meth)acrylate, diethylaminoethyl (meth)acrylate,
dimethylaminopropyl (meth)acrylate, and
3-dimethylamino-2-hydroxypropyl (meth)acrylate); acrylamide and
methacrylamide derivative; acrylamide and methacrylamide including
N-dimethylaminoethyl (meth)acrylamide, N-diethylaminoethyl
(meth)acrylamide.
9. The device according to claim 1, wherein the hemocompatible
coating is an alkyl (meth)acrylate selected from the group
consisting of: 2-hydroxyethyl methacrylate, methyl (meth)acrylate,
ethyl (meth)acrylate, and n-butyl(meth)acrylate.
10. The device according to claim 1, wherein the hemocompatible
coating is selected from the group consisting of: N-methyl
(meth)acrylamide, N-vinylpyrrolidone, vinyl acetate, and
vinylpyridine.
11. The device according to claim 1, wherein the resin is in the
form of beads having a size from 25 to 2500 .mu.m.
12. The device according to claim 1, wherein the resin has a pore
size from 20 to 500 .ANG..
13. The device according to claim 1, wherein the resin has a pore
volume less than 2.5 cc/g.
14. The device according to claim 1, wherein the resin has a
surface area from 200 to 1600 m.sup.2/g.
15. The device of claim 12, wherein the resin has a pore volume of
less than 2.5 cc/g.
16. The device of claim 15, wherein the resin has a surface area
from 200 to 1600 m.sup.2/g.
17. The device according to claim 1, wherein the hemocompatible
coating is a polymer prepared from the group consisting of:
2-hydroxyethyl methacrylate, methyl(meth)acrylate,
ethyl(meth)acrylate, n-butyl (meth)acrylate, and
vinylpyrrolidone.
18. The device of claim 1 wherein blood or plasma is withdrawn from
a patient, contacted with said polymeric divinylbenzene resin to
remove .beta.-2-microglobulin, and returned to the patient.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of copending U.S. Ser.
No. 09/965,256 filed Sep. 27, 2001 which is a continuation of U.S.
Pat. Nos. 6,325,939 issued Dec. 4, 2001 and 6,338,801 issued Jan.
15, 2002, both of which are divisionals of U.S. Pat. No. 6,238,795
issued May 29, 2001, which is a continuation of U.S. Ser. No.
09/236,153, filed Jan. 22, 1999, now abandoned. All of the
aforementioned references are incorporated herein and are relied
upon for priority.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to adsorbents for removing
toxicants from blood or plasma, and also for a method of producing
such adsorbents.
[0003] Conventional procedures for the purification of blood
extracorporeally include membrane techniques (hemodialysis,
plasmapheresis, ultrafiltration), sorption techniques
(hemoperfusion, plasma perfusion) and combinations of these
methods. Hemodialysis, ultrafiltration and plasma pheresis separate
compounds according to their size and do not selectively remove
specified components. Sorption techniques, on the contrary, can be
both selective and non-selective.
[0004] Hemoperfusion involves the passage of the contaminated blood
over a solid surface of a detoxicant particulate mass that
separates the contaminant by sorption or by ion exchange. Another
procedure, plasma perfusion, involves separation of blood cells
prior to contacting plasma with the adsorbent. In any case, treated
blood, or both cells and treated plasma, have to be returned to the
patient's blood circulation system.
[0005] There are cases where the toxic components to be removed
from blood are well established. In these cases, selective
adsorbents can be employed which incorporate ligands specially
designed to attract and bind the target species. Exemplary of
potential applications of selective perfusion systems are: (1) the
removal of autoimmune antibodies, immunoglobulins and immune
complexes using adsorbents such as Protein-A; (2) removal of
circulating toxins and tumor antigens (e.g., a-fetoprotein
associated with hepatic cancer, carcinoembrionic antigen associated
with various carcinomas, thioesterase or cytokeratins associated
with breast cancer, and the like) using adsorbents such as
immobilized monoclonal antibodies and specific immobilized ligands;
(3) removal of protein bound toxins and drugs (e.g., in the case of
psychotomimetic or narcotic drug overdose) based on the antigenic
properties of these protein conjugates; (4) procedures using live
cells in the plasma chamber in the place of adsorbents such as
islet cells or liver tissue fragments for the treatment of
diabetes, hepatocytes for the treatment of hepatic failure and the
like; (5) selective removal of plasma components using immobilized
enzymes as adsorbents; (6) removal of cholesterol [low density
lipoproteins (LDL)] using adsorbents specific to LDL; (7) removal
of excess phosphate on the MgO/TiO complex deposited on active
carbons; (8) adsorption of triglycerides, cholesterol and fatty
acids on hydrophobic polymer materials; (9) removal of human
immunodeficiency virus using calcinated
hydroxyapatite-silica-alumina adsorbing materials; (10) absorbing
free hemoglobin from plasma on polyphenylalanine,
polyalkylene-oxide or mineral or polymeric porous materials bearing
groups of tyramine, tyrosine, phenylalanine and aminophenol on the
surface.
[0006] Not less frequent are cases where several toxic compounds
appear in blood simultaneously, often unidentified or even unknown.
These are mainly toxins of low or middle-range molecular weights.
Here, selective immunoadsorbents can not be prepared in a
reasonable period of time and non-selective adsorbents are needed
which readily adsorb a variety of relatively small toxic molecules.
Preferential adsorption is mainly caused by smaller polarity of
these toxins as compared to that of natural amino acids and
saccharides which are useful conventional small components of
normal blood. Hydrophobic adsorbing materials, in particular
activated carbon, are used as the non-selective adsorbents in these
cases.
[0007] Hemoperfusion and plasma perfusion on non-specific activated
carbon-type sorbents was shown to be helpful in treatment of
schizophrenia (Kinney, U.S. Pat. No. 4,300,551, 1981), pulmonary
hypertension (SU 1507-397-A, 1989), multiple sclerosis (SU
1466-754-A, 1989), treatment of rhesus-conflict in obstetrics (SU
1533-697-A, 1989), for detoxication of organism of patients who
have undergone extensive surgery (SU 1487-909-A, 1989).
[0008] A technique for cancer treatment is described by Bodden
(U.S. Pat. No. 5,069,662, December, 1991), by which high
concentrations of anti-cancer agents can be perfused through a body
organ containing a tumor and then removed from the organ with
effluent blood. The contaminated blood is then transported to an
extracorporeal circuit, purified from contaminations and returned
to the body. This permits safe infusion of greater than usual
concentrations of chemotherapeutic agents and delivering lethal
doses of the agents to the tumor while preventing toxic levels of
the agents from entering the body's general circulation. The
process is applicable to the treatment of a number of tumors such
as those of kidney, pancreas, bladder, pelvis and, in particular,
the liver. Illustrative of suitable chemotherapeutic agents for use
in the practice are Adriamycin (doxorubicin), fluorinated
pyrimidines (5-fluorouracyl 5-FU or floxuridine FURD), cisplatin,
Mytomycin C, cyclophosphamide, methotrexate, vincristine,
Bleomycin, FAMT, and any other anti-cancer agent. Blood
detoxication most effectively can be achieved by hemoperfusion
through a cartridge with a non-specific sorbent, for example,
activated carbon, able to clear the blood from the above
antineoplastic agents.
[0009] In a hemoperfusion system, whole blood comes into direct
contact with the sorbent, such as active carbon, which leads to two
kinds of serious problems: first, fine carbon particles tend to be
released into the blood stream to become emboli in blood vessels
and organs such as lungs, spleen and kidneys; second, the
biological defense system of blood may be activated and react in
several ways: the blood may coagulate to form a clot, or thrombus,
the immune system may respond unfavorably, and white blood cells
may act to encapsulate the artificial device.
[0010] Therefore, many attempts have been done to prevent release
of fines and to enhance the biocompatibility of the sorbents. Clark
(U.S. Pat. No. 4,048,064, September 1977) describes formation of a
semipermeable polymeric coating on the carbon particles by
polymerization of various hydrophilic monomers, in particular
hydroxyethylmethacrylate (HEMA) and acrylamide. Moreover, he
includes heparin into the coating polymer, in order to minimize
complement activation and aggregation of platelets. Nakashima, et
al. (U.S. Pat. No. 4,171,283, October 1979) suggests to add an
epoxy moiety containing comonomer, which allows post-crosslinking
of the polymeric coat formed, thus enhancing the mechanical
stability of the coating. However, thin hydrophilic polymeric
coatings were found to "fall apart", whereas thick coatings
retarded diffusion and deteriorated sorption properties of the
carbon.
[0011] Maxid discloses (U.S. Pat. No. 5,149,425, September 1992;
U.S. Pat. No. 5,420,601, August 1993), thin integral membranes on
the surface of the adsorbent can be better prepared from
hydrophobic, insoluble in water polymer, in turn coated by a
second, but water-soluble polymer.
[0012] Alternatively, activated carbon was coated with a
polyelectrolyte complex prepared from a polycation (DEAE-cellulose)
and heparin and precipitated on the surface of carbon beads
(Valueva, et al., SU 844-569, 1981).
[0013] Polymeric hydrophobic materials may serve as non-selective
adsorbents.
[0014] Endotoxins were observed to adsorb on porous polypropylene
and polyethylene (Harris, U.S. Pat. No. 4,059,512, November 1977).
Macroporous styrene-divinylbenzene copolymers were shown to be
useful for blood detoxication from barbiturates and glutethimides
(Kunin, et al., U.S. Pat. No. 3,794,584, February 1974).
[0015] Polystyrene polymers prepared by an extensive crosslinking
of polystyrene chains with rigid bi-functional cross-linking
reagents such as dichlorodimethyl ether are taught by U.S. Pat. No.
5,773,384.
[0016] While polystyrene-type adsorbents are useful to adsorb small
and middle-size organic molecules, the hemocompatibility of the
material required additional improvement. An effort to render such
adsorbents hemocompatible is taught in WO 97/35660, or U.S. Pat.
No. 5,773,384.
[0017] The foregoing efforts are not efficient means of preparing
sufficient quantities of hemocompatible absorbent resin as the
cross-linked adsorbents contain from 0.5 to 7 percent by weight of
unreacted chloromethyl groups (U.S. Pat. No. 5,773,384, Col. 6,
Line 52).
[0018] U.S. Pat. No. 5,051,185 discloses a double-layered structure
comprising a water-insoluble core coated with a blood compatible
polymer. As a water-insoluble core there is disclosed a spherical
or particulate polymer having a particle size from 25 to 2500 .mu.m
having a specific surface area from 5 to 55 m.sup.2/g. The
water-insoluble core is preferably porous, displaying an average
pore size of from 20 to 5,000 .ANG..
[0019] The present invention has as an objective to provide an
adsorbent for removing toxicants from blood or plasma, which is
rendered hemocompatible through reaction of hemocompatible monomers
or polymers with pendant vinyl groups on the adsorbent resin. The
resin may be shaped to a convenient physical dimension for use.
Bead form and fiber form are physical shapes convenient for
exposure to blood or plasma for removal from blood of an absorbable
component thereof.
[0020] In keeping with these objects and with others which will
become apparent hereinafter, one feature of the present invention
resides, in an adsorbent for removing toxicants from blood or
plasma, of resin prepared from monomeric reactants of aromatic
compounds, which resin has a surface and pore structure modified so
as to prevent adsorption of large proteins and platelets and to
minimize activation of blood complement system, without affecting
noticeably the accessibility of the inner adsorption space of the
beads for small and middle-size toxicant molecules.
[0021] It is another feature of the present invention to provide a
method of producing the new adsorbent, which includes coating of
the surface of the beads, particles, spheres, fiber or other
convenient shape for resin, such that adsorption of large proteins
and platelets is prevented and activation of blood complement
system is minimized without blocking access by blood toxicants to
the inner adsorption space of the resin for small and middle-size
toxicant molecules. Preparation of the polymeric resin beads useful
for this invention may follow known methods of addition
polymerization. Helfferich. F., Ion Exchange, McGraw-Hill Book
Company, Inc., 1962, p. 34-36 to produce resin heads of known
sizes: 25 to 2500 .mu.m, preferably from 50 to 1500 .mu.m.
[0022] As monomeric starting materials for preparation of the
inventive polymeric resin, divinylbenzene (DVB) is the preferred
material. As noted by Helfferich, pure divinylbenzene is not
readily accessible. Commercially available sources are mixtures of
divinylbenzene isomers (about 40 to 60 percent) and ethylstyrene
(about 60 to 40 percent). Nominal DVB content is referenced as the
mole percent of pure divinylbenzene monomer in the polymerization
starting materials. The monomeric starting materials are combined
with an addition type catalyst such as benzoyl peroxide, lauroyl
peroxide, t-butyl hydroperoxide, or asobisisobutyronitrile present
from 0.5 to 5 percent by weight of the monomeric reactants present.
The hydrophobic monomeric starting materials are formed into small
droplets, such as by agitation in water to which a suspension
stabilizer such as: geletin, polyvinyl alcohol, an oleate salt, or
a methacrylate salt has been added. The aqueous phase including the
droplets of catalyzed monomer of DVB and divinylbenzene are
maintained at a temperature (40 to 110.degree. C., preferably from
60 to 90.degree. C.) sufficient for polymerization. Of course
pressurization will be necessary to polymerize the monomers in
liquid water at temperatures greater than 100.degree. C.
Alternatively, the beads can be externally sized in order to
provide a more narrow particle size distribution as described in
U.S. Pat. No. 4,444,961, incorporated herein by reference.
[0023] In contrast to the polymeric resin of U.S. Pat. Nos.
5,773,384 and 5,051,185, according to the instant invention resin
is formed from monomeric starting materials comprising DVB of 40
percent or more. Further, is not necessary or desirable to subject
the resin to a solvent swelling and subsequent cross-linking step
with a Lewis acid catalyst. Rather, DVB resin can be prepared with
porosity suitable for absorbing the contaminants in blood by
variation of the known parameters for preparation of DVB resins:
temperature, solvent amount and choice of catalyst, and reaction
time. Upgrading of the DVB monomer from commercially available
values to 65 to 90 mole % DVB can provide the skilled artisan
another parameter useful to benefit pore size, porosity, and
surface area.
[0024] Rendering DVB resin hemocompatible also varies from the
prior art of U.S. Pat. No. 5,773,384. Several approaches to
chemically modify the bead surface of an adsorbent are suggested to
render the resin hemocompatibile. These approaches include: the
formation of lipid-like layers on the surface of polystyrene beads
in an attempt to simulate the structure of biomembranes by forming
co-polymers of 2-methacryloyloxyethyl-phosphorylcholine with
n-butyl-methacrylate grafted on the surface of a polystyrene resin.
Groups of phosphatidylcholine are formed on the surface of
polystyrene beads, without a preliminary grafting of the
hydrophilic copolymer suggested by Ishihara, et al. Secondly,
heparin deposited on the surface of the polystyrene beads are
believed to inhibit activation of the blood complement system and
prevent formation of clots. Thirdly, long hydrophilic polymer
chains on the surface are believed to prevent contacts between
blood proteins and cells with the hydrophobic polystyrene surface.
A fourth approach is to deposit high molecular weight fluorinated
polyalkoxyphosphazene on the outer surface of the beads.
[0025] All the forgoing methods of rendering hemocompatible the
cross-linked polystyrene resin require the presence of unreacted
functional groups remaining after crosslinking polystyrene chains
with large amounts of bifunctional compounds, in particular, those
bearing reactive chloromethyl groups. This process is limited to a
curiosity as it is not scaleable to commercial size manufacture. In
contrast, porous adsorbent prepared from divinylbenzene is not only
commercially scaleable, but such resins are presently available.
Suitable commercially available resins include Dowex.RTM. polymeric
resins available from The Dow Chemical Company, Midland, Mich.,
United States of America identified as Dowex product numbers
XUS-43520.01, XUS-43520.10, and XUS-40323.00.
[0026] In contrast to the polystyrene resins mildly cross-linked
with amounts of DVB disclosed from 0.5 to 4.5 percent having
negligible unreacted vinyl groups taught by U.S. Pat. No. 5,773,384
which polystyrene resins must be subsequently cross-linked with
bi-functional cross-linkers such as dichlorodimethyl ether, the DVB
resins of the instant invention are readily rendered hemocompatible
by coating the resin by reaction of vinyl reactive and
hemocompatible monomers and polymers with unreacted vinyl groups of
the DVB resins. Also in contrast to the water-insoluble carrier of
particulate or spherical form according to U.S. Pat. No. 5,051,185,
the inventive resins while having a surface area from 20 to 500
m.sup.2/g, a pore size from 20 to 500 .ANG., preferably from 20 to
300 .ANG., and a pore volume less than 2.5 cc/g, preferably less
than 2.0 cc/g, but more than 1.0 cc/g, the instant resins can be
manufactured having a surface area from 200 to 1,600 m.sup.2/g,
preferably from 500 to 1,200 m.sup.2/g, more preferably 700 to
1,000 m.sup.2/g.
[0027] Suitable hemocompatible coating may be prepared from a wide
variety of such reactants capable of reacting with vinyl groups.
Suitable nitrogen containing reactants include: primary amines,
secondary amines, tertiary amines, quaternary amines and
nitrogen-containing aromatic cyclic compounds such as pyridines,
and imidazols. Specific examples of aromatic cyclic compounds
include vinyl derivatives of such nitrogen containing compounds
such as 2-vinylpyridine, 4-vinylpyridine, 2-methyl-5-vinylpyridine,
4-vinylimidazole, N-vinyl-2-ethylimidazole, vinylpyrrolidinone,
N-vinyl-2-methylimidazole. Also useful are acrylic or (meth)acrylic
acid derivatives including: dimethylaminoethyl (meth)acrylate,
diethylaminoethyl (meth)acrylate, dimethylaminopropyl
(meth)acrylate, 3-dimethylamino-2-hydroxypropyl (meth)acrylate),
acrylamide or methacrylamide derivative. Acrylamide and
methacrylamide such as N-dimethylaminoethyl (meth)acrylamide,
N-diethylaminoethyl (meth)acrylamide. Useful alone, or as a
co-polymer with the above mentioned addition polymerizable nitrogen
containing monomers, are the alkyl (meth)acrylates i.e.,
2-hydroxyethyl methacrylate, methyl (meth)acrylate, ethyl
(meth)acrylate, and n-butyl(meth)acrylate. Also useful alone or as
a co-polymer as a hemocompatible coating are N-methyl
(meth)acrylamide, N-vinylpyrrolidone, vinyl acetate, and
vinylpyridine.
[0028] Reaction conditions for coating the DVB resin beads with a
vinyl reactive additive reactant are similar to the reaction
conditions for formation of the DVB resin: a suitable catalyst such
as are generally known, a suitable solvent, heating the DVB resin,
catalyst, solvent, and additive reactant to the reactive
temperature: generally from 40 to 110.degree. C., for a time
sufficient for reaction, from 8 hours to 1/2 hour.
[0029] By rendering such resins hemocompatible, effective
adsorbents for blood toxins can be provided. Such divinylbenzene
resins avoid cross-linking of styrene-divinylbenzene copolymers
with monochlorodimethyl ether as a bifunctional reagent, or
cross-linking of such resin using chloromethylation taught by U.S.
Pat. No. 5,773,384. Consequently, the concerns for removing
unreacted cross-linker can be avoided.
[0030] The adsorbents prepared in accordance with this invention
are charged to a column or cartridge for use to removal
contaminants from blood or plasma. 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 absorbent layer, and between the
absorbent 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 alpha-ray
sterilization) before use.
[0031] By adjusting the pore size of the DVB resin and rendering
the resin hemocompatible, the resin is useful to remove blood
components having molecular weights of between 100 and 20,000
daltons including proteins, glycosated proteins, including
degranulation inhibitory protein, advanced glycosylation
endproducts, hormones such as parathyroid hormone and endotoxins
such as those toxins which cause sepsis. Such compounds as
creatinine, barbiturate, phenobarbital, sodium salicylate,
amphetamines, morphine sulfate, meprobamate, glutethimide, etc. can
also be effectively and rapidly removed from the blood by the
disclosed resin rendered hemocompatible. Moreover, by adjusting the
reaction conditions as stated herein to generate proper pore sizes,
the hemocompatible resin will absorb cytochrome C,
.beta.-2-microglobulin (molecular weight of about 20,000 daltons),
as well as vitamin B.sub.12.
EXAMPLE 1
[0032] Divinylbenzene/ethyl vinylbenzene copolymer beads having a
ratio of DVB to EVB of 80 to 20 on a weight basis were dried at
70.degree. C. in a vacuum oven for 24 hours. 100 g of the resulting
beads were placed into a flask with 650 ml of methanol. The
reaction mixture was heated to 65.degree. C. and this temperature
maintained until 200 ml of distillate removed. 200 ml methanol was
then added to the flask. After cooling to ambient temperature,
1-vinyl-2-pyrrolidinone (1.0 g., 9.0 mMole) and 75 ml of methanol
is added, followed by 0.237 g. (0.9 mMole) of .alpha.-cumyl
peroxyneoheptanoate and 20 ml methanol, followed by heating to
64.degree. C. for 4 hours while stirring gently. The solvent is
removed from the resin beads by suction filtration. The beads were
rinsed with 400 ml methanol, followed by washing by 1 L methanol in
a column with methanol pumped through the column at a rate of 3
ml/min.
EXAMPLE 2
[0033] Divinylbenzene/ethyl vinylbenzene copolymer beads having a
ratio of DVB to EVB of 80 to 20 on a weight basis were dried at
70.degree. C. in a vacuum oven for 24 hours. 100 g of the resulting
beads were placed into a flask with 650 ml of ethanol. The reaction
mixture was heated to 78.degree. C. and this temperature maintained
until 200 ml of distillate removed. 200 ml ethanol was then added
to the flask. After cooling to ambient temperature,
polyvinylpyrrolidinone molecular weight, 10,000 (1.0 g., 9.0 mMole)
available from Aldrich P.O. 2060 Milwaukee, Wis. 53201 United
States solid was added, followed by 0.02 g. (0.18 mMole) of
(.alpha.-cumyl peroxyneoheptanoate, followed by heating to
78.degree. C. for 4 hours while stirring gently. The solvent was
removed from the resin beads by suction filtration. The beads were
rinsed with 400 ml ethanol, followed by washing by 1 L ethanol in a
column pumped through the column at a rate of 3 ml/min for 5.5
hours followed by a wash of 1 L of 2-propanol pumped through the
column at a rate of 3 ml/min for 5.5 hours.
[0034] The polymer beads when contacted with blood are compatible.
Blood does not clot on contact. The beads remove blood contaminants
such as .beta.-2-microglobulin.
* * * * *