U.S. patent number 3,888,250 [Application Number 05/375,835] was granted by the patent office on 1975-06-10 for disposable hemoperfusion assembly for detoxification of blood and method therefor.
This patent grant is currently assigned to Becton, Dickinson and Company. Invention is credited to John B. Hill.
United States Patent |
3,888,250 |
Hill |
June 10, 1975 |
Disposable hemoperfusion assembly for detoxification of blood and
method therefor
Abstract
A disposable hemoperfusion assembly adapted for use in the
detoxification of blood includes a housing having an inlet opening
and an outlet opening which is adapted to be connected to a source
of blood to be detoxified is disclosed. Blood detoxification means
is disposed in the housing which includes an elongated base sheet
material having adhesive means disposed on at least one side
thereof, a layer or coating of chemically or physically reactive or
adsorbent particles bonded to the adhesive side of the base sheet
whereby substantially no fragmentation of the particles occurs when
blood is passed through the detoxification means.
Inventors: |
Hill; John B. (Chapel Hill,
NC) |
Assignee: |
Becton, Dickinson and Company
(East Rutherford, NJ)
|
Family
ID: |
23482565 |
Appl.
No.: |
05/375,835 |
Filed: |
July 2, 1973 |
Current U.S.
Class: |
604/6.06;
210/669; 210/694; 210/494.1; 604/28 |
Current CPC
Class: |
E05D
15/44 (20130101); A61M 1/3679 (20130101); Y10T
16/541 (20150115) |
Current International
Class: |
A61M
1/36 (20060101); A61m 005/00 (); A61m 001/03 () |
Field of
Search: |
;128/214R,214C,214.2
;210/24,27,494,500,502,DIG.23 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Andrade et al. - Trans. Amer. Soc. Artific. Inter. Orgs., Vol.
XVIII, 1972 (June), pp. 473-483. .
Chang et al. - Trans. Amer. Soc. Artific. Inter. Orgs., Vol. XVIII,
1972 (June) pp. 465-472..
|
Primary Examiner: Truluck; Dalton L.
Attorney, Agent or Firm: Kane, Dalsimer, Kane, Sullivan and
Kurucz
Claims
What is claimed is:
1. A hemoperfusion apparatus useful in the detoxification of blood
comprising:
a. a housing having spaced outlet and inlet openings, blood
transfering means connected thereto adapted to be connected to a
source of blood to be detoxified and having an interior passageway
for the blood extending between the inlet and outlet openings;
and,
b. a detoxification cartridge assembly disposed in the passageway
in the housing, said cartridge assembly including a base supporting
sheet having a coating of adhesive on at least one side thereof and
a uni-layer of individually spaced apart particles of adsorbent
material between 100 and 5,000 microns in size bonded by the
adhesive to the coated side of the sheet so that the major portion
of the particles are free from bonding material whereby to prevent
fragmentation of the adsorbent material said sheet being formed to
provide a cartridge having alternate layers of base sheet material
and adsorbent particles, said particles being in intimate contact
with said layers;
c. said sheet material, adhesive, adsorbent particles and portions
of the housing which the blood engages being inert to each other
and being nontoxic and inert to blood.
2. The assembly of claim 1 wherein the particles of adsorbent
material include chemically reactive material.
3. The assembly of claim 1 wherein the particles of adsorbent
material include physically reactive material.
4. The assembly of claim 1 further includes a filter means having a
porosity greater than the formed elements of blood is mounted in
the path of said outlet opening so that any particles having a size
greater than the formed elements of blood are removed from the
detoxified blood.
5. The assembly of claim 1 wherein the base sheet material is a
plastic film.
6. The assembly of claim 1 wherein the base sheet material is an
open web.
7. The assembly of claim 1 wherein the adhesive means is a pressure
sensitive adhesive.
8. The assembly of claim 1 wherein said particles are activated
carbon.
9. The assembly of claim 1 wherein said particles have a particle
size preferably of from 297 to 840 microns.
10. The assembly of claim 1 wherein said particles are macroscopic
beads derived from polysaccharide dextran.
11. The assembly of claim 8 wherein the carbon particles have a
mean pore diameter of 18-21 A and a total surface area of 1,150 to
1,250 sq. meters per gram.
12. The assembly of claim 1 wherein said adsorbent particles are
bonded to each side of said base sheet material.
13. The assembly of claim 1 wherein said detoxification means is
formed into a coil and is encased in a tubular sleeve formed of a
plastic film material.
14. The apparatus as set forth in claim 1 wherein said cartridge is
free of internal bypass channels and said cartridge is disposed in
the housing with its longitudinal axis extending in a direction
between the inlet and outlet openings and having engagement with
the wall portions of the housing surrounding the cartridge so as to
prevent bypassing around the cartridge whereby blood introduced
into the inlet opening passes between the layers of sheet material
in the cartridge in engagement with the adsorbent particles to the
outlet opening.
15. A method of detoxifying blood comprising the steps of:
a. providing a source of blood to be detoxified.
b. connecting a hemoperfusion apparatus to said blood source, said
apparatus including a detoxification cartridge assembly having a
base supporting sheet having a coating of adhesive on at least one
side thereof and a uni-layer of individual spaced apart particles
of adsorbent material between 100 and 5,000 microns in size bonded
by the adhesive to prevent fragmentation of the adsorbent material
to the coated side of the sheet so that the major portion of the
particles are free from bonding material, to said sheet being
formed to provide a cartridge having alternate layers of base sheet
material and adsorbent particles in intimate contact with said
layers;
c. connecting said apparatus to the blood source; and,
d. pumping said blood between the layers of the sheet material in
engagement with the adsorbent particles whereby to detoxify said
blood.
Description
BACKGROUND OF THE INVENTION
There have been attempts to provide hemoperfusion devices for the
detoxification of blood particularly where the blood may have
lethal quantities of drugs or poisons and it is necessary to remove
the toxic elements from the blood quickly, efficiently and
safely.
Some of the conventional methods which may be used to reduce toxic
levels of drugs after ingestion include gastric lavage and the use
of emetics such as syrup of ipecac and apomorphine. These
procedures, however, must be instituted before a potential lethal
quantity of the drug has gained entrance into the blood by way of
gastrointestinal adsorption. Other methods used are hemodialysis
and peritoneal dialysis to reduce adsorbed drugs to a non-lethal
level in the blood and tissue. These methods may be satisfactory
except where the drug penetrates the semipermeable membrane slowly
or not at all thereby preventing efficient dialysis. Investigators
have since embarked on the hemoperfusion of blood to detoxify it by
using an activated adsorbent type of material such as activated
charcoal or ion exchange resins.
Animal experiments have affirmed problems which can exist when
using these devices such as fragmentation of the adsorbent
material, compacting of the particle bed and loss of some formed
blood elements such as leucocytes and platelets. The fragmentation
of the adsorbent is considered the most serious effect since there
is a tendency to produce "adsorbent embolization." Thus, the term
"charcoal embolization" emerges since most of the adsorbents used
are activated carbons. Excess red blood cell destruction could lead
to anemia, hemoglobinemia or hemoglobinuria. The problems which
could arise due to loss of leucocytes and platelets are impairment
to the mechanisms for preventing infection and clotting. Many
devices employing these adsorbents have been used in the form of a
cartridge having loosely packed activated carbons or ion exchange
resins. However, fragmentation as noted above, occurs and there is
a substantial platelet loss. To overcome the charcoal embolization
problem some experimenters have embedded the charcoal in a
collodian membrane. However, coating of the charcoal retards rapid
removal of the toxic drug from the blood. Other experimenters have
suggested and tried the use of bonding the charcoal particles into
a solid mass by using a thermoplastic resin such as polyethylene
powder and have used the bonded charcoal mass to filter gases.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a disposable
hemoperfusion assembly for the detoxification of blood which
overcomes many of the difficulties and disadvantages heretofore
encountered when employing chemically or physically reactive
particles or activated adsorbent materials.
It is also an object of the invention to provide a disposable
hemoperfusion assembly employing such materials bonded to the
surface of a base sheet in fixed position wherein substantially all
of the surface area of the activated materials is exposed and is
capable of contacting the blood as it passes thereover to remove
the toxic materials therefrom while preventing compaction and
fragmentation and minimizing the pressure drop across the assembly.
It is also a further object of the invention to provide an
inexpensive assembly which is readily coupled to a blood source for
the detoxification of blood in mammals in which the assembly may be
included in existing hemodialysis or peritoneal dialysis equipment
to remove toxins therefrom.
My invention generally contemplates the provision of a disposable
hemoperfusion assembly for the detoxification of blood which
includes a housing having an inlet opening and an outlet opening
and being adapted to be connected to a source of blood to be
detoxified. Blood detoxification means is disposed in the housing
which includes an elongated base sheet material having adhesive
means disposed on at least one side thereof, a layer or coating of
chemically or physically reactive or adsorbent particles bonded to
the adhesive side of the base sheet whereby substantially no
fragmentation of the particles occurs when blood is passed through
the detoxification means.
The assembly may also include filter means positioned within the
path of the outlet opening and having a porosity of at least the
size of the formed elements of the blood so that fragments of the
bonded particles which may break loose from the base sheet are
prevented from entering the detoxified blood as it passes through
the disposable assembly.
Also disclosed is a method for making and using the disposable
hemoperfusion assembly of the invention herein. The assembly
comprises providing detoxification means including an elongated
base sheet material having adhesive means on at least one side
thereof; forming a layer or coating of chemically or physically
reactive or adsorbent particles and bonding the particles to the
side of the base sheet having the adhesive means thereon;
positioning the coated base sheet material into the housing in such
a manner so as to provide a path for blood to pass therethrough in
which the blood contacts substantially the entire free surface of
the bonded particles on the base sheet material. In applying the
layer of the particles care should be taken so that the major
portion of the particles is free from bonding material to insure
adequate adsorption.
Also, as the blood passes through the detoxification means the
blood may be further filtered by positioning a filter having a
porosity of at least the size of the formed elements of the blood
in the blood path so that fragments of the bonded particles which
may break loose are prevented from entering the detoxified blood as
it passes through the disposable assembly.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the use of the invention herein in
which a mammal, such as a dog, is being detoxified by passing blood
upwardly through the disposable hemoperfusion assembly of the
invention herein by means of a suitable pump.
FIG. 2 is a partial sectional elevational view of the disposable
hemoperfusion assembly as illustrated in FIG. 1.
FIG. 3 is a partial sectional view taken along the lines 3--3 of
FIG. 2.
FIG. 4 is a fragmentary elevational view of the base sheet material
illustrated as being coated on both sides thereof.
FIG. 5 is a partial sectional view of a disposable hemoperfusion
device employing the base sheet material of FIG. 4.
FIG. 6 is a fragmentary elevational view of an alternate form of
base sheet material and is illustrated as being an open web
material having a coating of adsorbent materials on both sides
thereof.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
For a better understanding of the invention herein reference is had
to FIGS. 2 and 3 which illustrate the disposable hemoperfusion
assembly. Disposable hemoperfusion assembly 10 includes a housing
or tubular member 12 preferably made of a high impact moldable
plastics material such as polycarbonate, polyvinylchloride,
polypropylene or polyethylene or any other type of material which
is inert to and is non-toxic to blood. Closure members 14 and 16
are mounted over the open ends of housing 12 and are generally
configured in the shape of a funnel to provide inlet opening 15 and
outlet opening 17, not shown. Closure members 14 and 16 are
preferably made of the same material as housing 12 and are
identical in configuration and structure so that a description of
closure member 14 will serve to describe the corresponding
configuration and structure of the closure member 16.
As illustrated in FIG. 2, end closure 14 is generally cylindrical
in shape having a flat base 18 and a wall 20 formed around the
periphery of base 18 so as to provide a recess. The diameter of the
closure member 14 is substantially equal to the external diameter
of housing 12 so that the open end closure of the housing will nest
in the recess formed in member 14. Closure member 14 when mounted
over the open end of housing 12 can be sealed by any appropriate
means, for example, by swage fitting, by employing a suitable
adhesive by threaded engagement or any other suitable means. Formed
in the base of closure member 14 is spout 26 which provides a
passageway for inlet opening 15. A suitable cap 30 is mounted over
the open end of spout 26. As depicted in FIG. 2, spout 26 is formed
centrally of base 18 so that inlet opening 15 is in axial alignment
with the central axis of housing 12. Base sheet material 34 may be
in the form of a film as illustrated in FIGS. 2 and 4 or may be in
the form of an opened web as illustrated in FIG. 6.
Base sheet 34 is coated with a suitable adhesive which is capable
of adhering to the base sheet and also capable of bonding adsorbent
particles 40 in fixed position thereto. It should be understood
that the base sheet material 34, adhesive 36 and the particles 40
should not interact in such a manner as to cause toxicity in
mammals. Also, all of the component parts of hemoperfusion assembly
10 must be compatible with and nontoxic to blood.
The chemically or physically reactive or adsorbent particles 40 may
include activated carbon, ion exchange resins, dextran gels such as
Sephadex which is a dry insoluble powder of macroscopic beads which
are synthetic organic compounds derived from polysaccharide
dextrans and is sold by Pharmacia Fine Chemicals Inc. Also, any
combination of the particles 40 may be employed either in admixture
or in separate compartments.
It has been found that the size of particles 40 may be up to about
5,000 microns and may be in the range of from 100 to 2,000 microns.
Preferably, particles 40 may range in size from 297 to 1,000
microns. Still more preferably, they may range in size from about
297 to 840 microns and most advantageously from about 500 to 600
microns.
The surface area of particles 40 may vary widely. However, it has
been found that where particles 40 are type PCB activated carbon
made by the Pittsburgh Activated Carbon Company, the surface area
of particles 40 may range from about 1,150 to 1,250 square meters
per gram.
Spout 26 is formed having a tubular tip 27 projecting from base 18
of end closure 14. Tip 27 has a conical or tapered exterior having
a bore 15 to provide the outlet passageway for hemoperfusion
assembly 10. A retaining collar 28 projects forwardly from base 18
of end closure 14 in concentric relationship with conical tip
portion 27. Retaining collar 28 is spaced from tip 27 a distance
sufficient to accommodate coupling means disposed on the end of the
flexible tubular members, not shown, connecting disposable
hemoperfusion assembly 10 to a blood source as seen in FIG. 1. The
interior surface of retaining collar 28 is formed having thread
means 29 such as is commonly referred to as a female LUER connector
and coupling means disposed on the ends of the flexible tubings of
FIG. 1 are commonly referred to as the male LUER coupling means or
male adaptors for a LUER connector. Spout 26 is constructed
similarly to the structure disclosed in U.S. Pat. No.
3,402,713.
As noted above, closure member 16 comprises identical structure as
that described in closure member 14 and like parts are similarly
numbered employing the primes of the corresponding portions.
Disposed in hemoperfusion assembly 10 is detoxification means 32
which comprises an elongated base sheet material 34 preferably in
the form of a plastic film such as is sold by DuPont Company under
the tradename MYLAR.
Adhesive material 36 is coated on one or both sides of base sheet
34 and is preferably pressure sensitive so as to readily bond
particles 40 thereto. It is preferable to have about .2 grams per
sq. inch of adsorbent material bonded to the base sheet material
40. Particles 40 are uniformly coated on base sheet 34 to form a
uni-layer of bonded particles 40 as illustrated in FIGS. 2 and
3.
Detoxification means 32 is wound about a central core 42 preferably
by employing adhesive material 36 to bond one end of elongated base
sheet material 34 thereto. Thereafter, base sheet material 34 is
wound about core 42 so as to form a coil of substantially uniformly
spaced concentric layers of adsorbent particles 40 spaced from each
layer by base sheet material 34 as illustrated in FIGS. 2 and 3. A
suitable adhesive material may be any one of the chloro sulfonated
polyethylene synthetic rubbers such as is sold under the tradename
HYPALON 20. It should be understood that any adhesive material may
be employed which is non-toxic and inert to blood and the other
components forming hemoperfusion assembly 10. Also, the adhesive
material 36 should effect a substantially permanent bond between
base sheet material 34 and adsorbent particles 40. In this
connection, particles 40 should be bonded to base sheet material 34
and have a bond strength sufficient to resist washings of the
adsorbent material prior to use so that they do not become loose
and pass into the detoxified blood when used. Since particles 40
are bonded the disadvantage of clogging of assembly 10 by
compaction is prevented. Also, the particles 40 should have a
hardness sufficient to withstand the mechanical pressures of
manufacture and handling and subsequent use.
As noted above, various types of particles 40 have been found
useful for practicing the invention herein. Particles 40 which are
preferred are formed of activated charcoal of the type having a
hardness sufficient to withstand mechanical pressures of
manufacture, handling and subsequent use. Such activated carbons
are made from cocoanut shell charcoal such as is sold under the
tradename PCB by the Pittsburg Activated Carbon Company. Also,
resins which have been found to be suitable are those such as are
sold under the tradename Amberlite XAD-2 made by the Rohm &
Haas Company and are insoluble cross linked polymers in the form of
beads. These ion exchange resins may be admixed with activated
carbon or may form separate elements of the detoxification means
32.
When detoxification means 32 is wound about coil 42 it is sealed in
tubular sleeve 46 which fits tightly about detoxification means 32
so as to prevent channelling or bypassing of blood therethrough
without first contacting particles 40. Tubular sleeve 46 is
preferably made of a plastic material such as polyester.
Detoxification means 32, after being fitted with tubular sleeve 46,
is positioned in housing 12 and sealed therein by suitable potting
material 47 such as an epoxy resin which immobilizes or fixes
detoxification means 32 in place as illustrated in FIGS. 2 and
3.
Before mounting end closure 14 and 16 on housing 12 it is preferred
to mount filters 50 at each end of tubular member 12. A suitable
filter material which is compatible with blood and the other
elements forming hemoperfusion assembly 10 is sold under the
tradename Dafab 120 which are monofilament polyester screens having
40 micron openings formed therein. The porosity of the filters is
sufficiently small but are large enough to permit the formed
elements of the blood to pass therethrough without effecting
cellular damage thereto. Also, filter elements 50 and
detoxification means 32 are such that the pressure drop between the
inlet opening 15' and the outlet opening 15 is less than 25
millimeters Hg gauge per three inches of length of detoxification
unit 32 at a flow rate of 100 ml. per min. It is necessary to
maintain a minimal pressure drop since excessive pressure exerted
against the formed elements of blood can cause cellular damage and
possibly hemolysis of the red blood cells.
In FIGS. 4, 5 and 6 alternative embodiments of detoxification means
32 are illustrated. Detoxification means 32' is illustrated in
FIGS. 4 and 5 as an elongated base sheet material 34' which has
applied to each side thereof adhesive material 36' so that each
side of base sheet material 34' is coated with a layer of particles
40'. Detoxification means 32' is wound about a central core 42' in
which a double layer of particles 40' are interposed between each
coil of base sheet material 34'. Detoxification means 32' is
encased in thermoplastic sleeve 46' and is mounted in hemoperfusion
assembly 10' by a suitable epoxy potting material 47'. The
hemoperfusion assembly 10' of FIG. 5 is constructed in accordance
with the embodiment of FIGS. 1 and 2 described above.
FIG. 6 is similar to FIG. 4 except that elongated base sheet
material 32" is made of an opened web material rather than a film
as shown in FIG. 4. Adhesive material 36" is applied to both
surfaces of elongated base sheet material 32" so that particles 40"
are bonded to the web portions of elongated base sheet material 32"
and is wound about central core 42' and fitted within hemoperfusion
assembly 10'.
In practicing the invention herein reference is had to FIG. 1 which
illustrates the use of the apparatus and hemoperfusion assembly of
the invention herein to detoxify a mammal such as a dog. The dog is
suitably restrained on a table and is administered anesthesia
through the mouth which is illustrated by tube T placed in its
mouth. The dog blood is anticoagulated in a well known manner with
a dose of a suitable anticoagulant as by intraveneously
administered heparin. A flexible conduit 60 is connected to pump P
at one end with its other end coupled to the femoral artery of the
dog. Tube 61 is connected to the inlet opening of hemoperfusion
assembly 10 and pump P. Toxic blood is pumped from the femoral
artery of the dog into pump P and through flexible conduit 61 where
the toxic blood passes through hemoperfusion assembly 10 through
conduit 62 and then through bubble trap B which removes any gases
which may be trapped in the system. The detoxified blood is
conducted downward through a third flexible tube 64 which is
coupled to the outlet opening of bubble trap B at one end and to
the femoral vein at its other end. Thus, a complete circuit is
provided in which toxic blood is pumped through hemoperfusion
assembly 10 in an upward direction and allowed to flow downwardly
through bubble trap B to remove any gases therefrom before the
detoxified blood is conducted back into the dog. It has been found
that many toxic substances which are adsorbed into the blood such
as barbituates, sodium salicylate, amphetamines, morphine sulphate,
meprobamate, glutethimide, etc., can be efficiently and rapidly
removed from the blood.
By way of example, hemoperfusion assembly 10 will be described
using activated carbon type PCB made by the Pittsburgh Activated
Carbon Company as the adsorbent material of detoxification means
32. Detoxification means 32 has bonded thereto about 73 grams of
adsorbent particles 40 which range in size of from 297 to 840
microns, a mean pore diameter of 18-21 A, a hardness of 92 and a
surface area of from 1,150 to 1,250 square meters per gram.
Hemoperfusion assembly 10 is washed with normal saline until less
than 0.2 micrograms of activated carbon per liter of saline is
collected on a 0.2 micron millipore filter. The washing procedure
performs a second function of removing substantially all entrapped
air in detoxification means 32. Then, caps 30 and 30" are mounted
in place to seal the inlet and outlet openings of hemoperfusion
assembly 10. When the hemoperfusion assembly 10 is connected into
the circuit as illustrated in FIG. 1, all of the saline solution
contained in hemoperfusion assembly 10 is removed by blood and
thereafter the detoxified blood is allowed to circulate through the
animal to be detoxified.
The animal, a dog, to be detoxified was administered 175 milligrams
per kilogram of body weight of sodium phenobarbital intravenously
and allowed to remain in this condition for approximately 1 hour
without further treatment. In previous experiments the dosage of
phenobarbital administered to the dog proved to be lethal. After
about 11/2 hours elapsed time, perfusion was started by pumping
blood from the femoral artery through hemoperfusion assembly 10.
Perfusion ceased after 5 hours. The hemoperfusion assembly was
disconnected from the dog and within approximately 30 minutes the
dog was able to rise on his front legs and subsequently went on to
full recovery.
An analysis of the perfused blood from the dog indicated no
significant hemolysis and no evidence of damage to the dog due to
"charcoal embolism" and removal of the drug from the blood to a non
lethal level.
From the foregoing description it is apparent that the
disadvantages and difficulties heretofore encountered have been
overcome. Further, the hemoperfusion assembly of the invention
herein provides an assembly which is readily and easily constructed
to achieve a uniform product design and performance.
* * * * *