U.S. patent application number 10/997096 was filed with the patent office on 2005-05-26 for water purification pack.
Invention is credited to Taylor, Michael A..
Application Number | 20050113796 10/997096 |
Document ID | / |
Family ID | 23060912 |
Filed Date | 2005-05-26 |
United States Patent
Application |
20050113796 |
Kind Code |
A1 |
Taylor, Michael A. |
May 26, 2005 |
Water purification pack
Abstract
An apparatus and methods are disclosed for purifying fluid, such
as potable water, to quality levels suitable for medical
application, particularly to applications involving injection of
the fluid into a human body. The apparatus comprises a portable
purification pack constructed for a single use. The pack houses
depth filtration, activated carbon, mixed bed ion exchange resins
and terminal filtration stages in series. The terminal filter
comprises a fine (microfiltration or ultrafiltration), permeable
membrane, treated with an endotoxin-binding chemistry. In contrast
with semi-permeable osmotic membranes, the permeable membrane
produces high flow rates at relatively low pressures, while still
safely purifying fluid to injection quality.
Inventors: |
Taylor, Michael A.; (Napa,
CA) |
Correspondence
Address: |
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE
CA
92614
US
|
Family ID: |
23060912 |
Appl. No.: |
10/997096 |
Filed: |
November 9, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10997096 |
Nov 9, 2004 |
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10339702 |
Jan 8, 2003 |
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6814724 |
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10339702 |
Jan 8, 2003 |
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09364631 |
Jul 30, 1999 |
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6719745 |
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09364631 |
Jul 30, 1999 |
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09277448 |
Mar 26, 1999 |
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6274103 |
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Current U.S.
Class: |
604/500 ;
210/600 |
Current CPC
Class: |
C02F 1/42 20130101; C02F
9/005 20130101; C02F 1/444 20130101; Y02A 20/214 20180101; A61M
1/1668 20140204; C02F 1/688 20130101; Y10S 210/908 20130101; A61M
1/28 20130101; A61M 1/1656 20130101; B01D 61/00 20130101; C02F
2103/026 20130101; B01F 15/0254 20130101; A61M 1/1666 20140204;
B01F 1/0022 20130101; B01D 67/0093 20130101; C02F 2001/425
20130101; Y02A 20/208 20180101; Y10S 210/90 20130101; C02F 1/283
20130101; C02F 2103/04 20130101; B01F 1/0033 20130101; C02F
2001/422 20130101; B01F 2215/0034 20130101; B01D 61/002 20130101;
B01D 61/18 20130101 |
Class at
Publication: |
604/500 ;
210/600 |
International
Class: |
A61M 031/00 |
Claims
I claim:
1. A method of producing injectable quality fluid, comprising:
providing a housing surrounding a plurality of purification
elements, the housing having a fluid flow path through the
purification elements from an inlet to an outlet; supplying
non-sterile fluid to the inlet under a feed pressure of less than
about 20 psi; flowing the fluid through the plurality of
purification elements to form purified fluid; and outputting the
purified fluid from the outlet, wherein the purified fluid has an
organic content, conductivity, pH level and particulate
contamination level suitable for medical injection.
2. The method of claim 1, further comprising injecting the purified
fluid into a human body.
3. The method of claim 1, further comprising dissolving reagents in
the purified fluid.
4. The method of claim 3, wherein dissolving reagents in the
purified fluid comprises passing the purified fluid from the outlet
into a reagent cartridge containing dry reagents to form a medical
solution.
5. The method of claim 4, wherein the medical solution comprises
peritoneal dialysate.
6. The method of claim 1, wherein the purified fluid outputted from
the outlet has a flux rate of greater than about 30 mL/min.
7. The method of claim 6, wherein the purified fluid outputted from
the outlet has a flux rate of greater than about 90 mL/min.
8. The method of claim 7, wherein the feed pressure is between
about 5 psi and 10 psi.
9. The method of claim 1, wherein the plurality of purification
elements comprises a filter having a porosity of no more than about
0.5 .mu.m.
10. The method of claim 1, wherein the purified fluid has a total
organic content of less than about 500 ppb; conductivity of less
than about 2.0.mu. Siemens; pH between about 4.5 and 7.5; fewer
than about 12 particles/mL of particles greater than 10 .mu.m;
fewer than about 2 particles/mL of particles greater than 25 .mu.m;
and lower than about 0.025 ng/mL of endotoxins.
11. A method for producing fluid for medical injection, comprising:
providing a portable housing containing purification elements;
flowing non-sterile fluid through the purification elements;
retaining particulate contamination, organic matter, dissociated
ions, and endotoxins from the fluid within the purification
elements to produce purified fluid; and outputting the purified
fluid from the housing after retaining particulate contamination,
organic matter, dissociated ions, and endotoxins from the fluid,
the purified fluid being suitable for medical injection.
12. The method of claim 11, wherein the purification elements
comprise a bed of ion-exchange resins.
13. The method of claim 11, wherein the purification elements
comprise a depth filtration stage and an organic filtration
stage.
14. The method of claim 11, wherein retaining endotoxins comprises
passing the fluid through a permeable membrane treated with a
quaternary amine exchange chemistry.
15. The method of claim 11, wherein retaining endotoxins comprises
passing the fluid through a permeable ultrafiltration membrane
having a nominal cut-off porosity of between about 10,000 and
30,000 molecular weight.
16. A method of producing injectable quality fluid, comprising:
feeding non-sterile fluid into an inlet of a housing comprising a
plurality of purification elements, the housing having a length of
less than or equal to about six inches and a width of about less
than or equal to about five inches; flowing the fluid through the
plurality of purification elements; retaining within the housing
particulate, ionic, and organic contaminants from the fluid as the
fluid flows through the plurality of purification elements; and
outputting purified fluid from the housing after flwing the fluid
through the plurality of purification elements, wherein the
purified fluid is suitable for intravenous use.
17. The method of claim 16, further comprising dissolving dry
reagents in the purified fluid.
18. The method of claim 16, wherein the plurality of purification
elements comprises a filter having a permeable membrane chemically
treated for binding residual endotoxins.
19. The method of claim 18, wherein the permeable membrane has a
porosity of about 0.22 .mu.m or less.
20. The method of claim 16, wherein the plurality of purification
elements further comprises an organic filtration stage comprising a
bed of granular carbon configured to adsorb organic contaminants in
the fluid.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of co-pending U.S.
application Ser. No. 10/339,702, filed Jan. 8, 2003, which is a
divisional of U.S. application Ser. No. 09/364,631, filed Jul. 30,
1999, now U.S. Pat. No. 6,719,745, issued Apr. 13, 2004, which is a
continuation-in-part of U.S. application Ser. No. 09/277,448 filed
Mar. 26, 1999, now U.S. Pat. No. 6,274,103, issued Aug. 14,
2001.
FIELD OF THE INVENTION
[0002] The invention generally relates to water purification, and
more particularly to devices and methods for purifying water to a
quality suitable for medical applications.
BACKGROUND OF THE INVENTION
[0003] Various medical conditions require treatments that call for
the injection of fluids into the human body. For example, severe
trauma to the human body often involves significant loss of bodily
fluids. Additionally, illnesses often cause diarrhea followed by
dehydration and ion imbalance. In order to rehydrate the
individual, injection of an intravenous saline or dextrose solution
is required. Other medical applications (e.g., wound irrigation)
require similar fluid purity levels.
[0004] An example of the need for injection of fluids into the body
is in the area of dialysis. Treatments for patients having
substantially impaired renal function, or kidney failure, are known
as "dialysis." Either blood dialysis ("hemodialysis") or peritoneal
dialysis methods may be employed. Both methods essentially involve
the removal of toxins from body fluids by diffusion of the toxins
from the body fluids into a toxin free dialysis solution.
Peritoneal dialysis can be performed without complex equipment and
in a patient's home. In the peritoneal dialysis process, the
patient's peritoneal cavity is filled with a dialysate solution.
Dialysates are formulated with a high concentration of the
dextrose, as compared to body fluids, resulting in an osmotic
gradient within the peritoneal cavity. The effect of this gradient
is to cause body fluids, including impurities, to pass through the
peritoneal membrane and mix with the dialysate. By flushing the
dialysate from the cavity, the impurities can be removed.
[0005] Due to indirect contact with bodily fluids through bodily
tissues, rather than direct contact with blood, the dextrose
concentration needs to be considerably higher in peritoneal
dialysis than in hemodialysis, and the treatment is generally more
prolonged. Peritoneal dialysis may be performed intermittently or
continuously. In an intermittent peritoneal dialysis (IPD)
procedure, the patient commonly receives two liters of dialysate at
a time. For example, in a continuous ambulatory peritoneal dialysis
(CAPD) procedure, the peritoneal cavity is filled with two liters
of dialysate and the patient is the free to move about while
diffusion carries toxins into the peritoneal cavity. After about
4-6 hours, the peritoneum is drained of toxified dialysate over the
course of an hour. This process is repeated two to three times per
day each day of the week. Continuous Cycle Peritoneal Dialysis
(CCPD) in contrast, involves continuously feeding and flushing
dialysate solution through the peritoneal cavity, typically as the
patient sleeps.
[0006] Because peritoneal dialysates are administered directly into
the patient's body, it is important that the dialysis solution
maintains the correct proportions and concentrations of reagents.
Moreover, it is impractical to formulate and mix dialysis solutions
on site at the typical location of administration, such as the
patient's home. Accordingly, peritoneal dialysates are typically
delivered to the site of administration in pre-mixed solutions.
[0007] Unfortunately, dialysis solutions are not stable in
solutions over time. For example, dextrose has a tendency to
caramelize in solution over time, particularly in the
concentrations required in the peritoneal dialysis context. To
prevent such caramelization, peritoneal dialysis solutions are
typically acidified, such as with hydrochloric acid, lactate or
acetate, to a pH between 4.0 and 6.5. The ideal pH level for a
peritoneal dialysate, however, is between 7.2 and 7.4. While
achieving the desired goal of stabilizing dextrose in solution, the
pH of acidified peritoneal dialysis solutions tends to damage the
body's natural membranes after extended periods of dialysis.
Additionally, the use of acidified peritoneal dialysates tends to
induce acidosis in the patient.
[0008] Bicarbonates introduce further instability to dialysis
solutions. The most physiologically compatible buffer for a
peritoneal dialysate is bicarbonate. Bicarbonate ions react
undesirably with other reagents commonly included in dialysate
solutions, such as calcium or magnesium in solution, precipitating
out of solution as insoluble calcium carbonate or magnesium
carbonate. These insolubles can form even when the reactants are in
dry form. When occurring in solution, the reactions also alter the
pH balance of the solution through the liberation of carbon dioxide
(CO.sub.2). Even in the absence of calcium or magnesium salts,
dissolved sodium bicarbonate can spontaneously decompose into
sodium carbonate and CO.sub.2, undesirably lowering the solution's
pH level.
[0009] Accordingly, a need exists for improved methods and devices
for formulating solutions for peritoneal dialysis. Desirably, such
methods and devices should avoid the problems of non-physiologic
solutions and incompatibility of dialysate reagents, and also
simplify transportation, storage and mixing of such dialysates. One
aspect of this problem is the need for mechanisms for safely and
completely mixing constituents of dialysates in diluent at the
point of administration. Another aspect of this problem is the need
for producing injectable quality water or other diluent at the
point of administration.
[0010] It is often advantageous to provide purified fluid
independently of other constituents in the injected fluid. In many
situations, independent provision of purified water simplifies
transport and storage of solution constituents. In the case of
peritoneal dialysis, preparing dialysate solution from dry reagents
and independently provided pure water also minimizes the time for
which unstable solutions must be stored prior to administration.
Similarly, many other unstable solutions should be prepared soon
before administration, preferably at the site of
administration.
[0011] On site purification of fluids is also advantageous in a
number of other medical applications, including intravenous
injection, intramuscular injection, orally administered fluids,
wound irrigation, use in instrument cleaning solutions, and general
employment by immuno-compromised individuals (e.g., AIDS patients,
geriatrics, etc.).
[0012] While separating provision of injectable quality fluid from
other constituents can simplify transportation and delay production
of unstable solutions, transporting purified water to the site of
administration, even if produced and shipped separately from dry
reagents, can represent considerable costs, as well as introducing
opportunities for contamination. Transportation costs and
contamination are particularly problematic when fluids are to be
administered outside of a controlled hospital or clinic
environment. Problems are even further exacerbated in
lesser-developed countries, such as in the Indian subcontinent and
Africa. Even in a hospital setting, the ability to convert
available water into injectable quality water on site can reduce
transportation and storage costs as well as avoiding the risk of
contamination during transportation and storage.
[0013] Therefore, a need exists for a method and apparatus that
allow preparation of injectable quality fluid from available fluid.
Desirably, the apparatus should be transportable and convenient for
on-site use in remote locations.
SUMMARY OF THE INVENTION
[0014] In satisfying the aforementioned needs, the embodiments
described herein provide a portable apparatus and method for
purifying fluid to levels suitable for medical applications,
including injection into the human body.
[0015] In accordance with one aspect of the present invention, a
portable apparatus is provided for producing injectable quality
fluid. The apparatus includes a housing that defines a fluid flow
path from an inlet port to an outlet port. A depth filtration
stage, an organic filtration component, a deionization resin bed
and a permeable membrane are held within the housing along the
fluid flow path. The permeable membrane has a porosity of less than
about 0.5 .mu.m and is configured to retain endotoxins.
[0016] In accordance with another aspect of the present invention,
a water purification pack for producing injectable quality water
includes a container. The container defines a flow-through path
from an inlet to an outlet with an average cross-sectional area of
less than about 20 square inches. The container houses purification
elements within the path, including a permeable membrane having a
porosity of no more than about 0.5 .mu.m. The purification elements
provides a back-pressure low enough to allow fluid flow greater
than about 30 L/min under a feed pressure of between about 5 psi
and 10 psi.
[0017] In accordance with another aspect of the invention, a method
is provided for producing injectable quality of water. The method
includes providing a portable purification pack with a housing
surrounding purification elements in series. Non-sterile water is
provided to an inlet of the housing under a feed pressure of less
than about 20 psi. The water passes through the purification
elements. Purified water exits from an outlet of the housing. The
purified water has an organic content, conductivity, pH level and
particulate contamination level suitable for injection into the
human body.
[0018] In accordance with another aspect of the invention, a method
is provided for producing fluid for medical applications. The
method includes providing a portable housing. Non-sterile fluid
passes through the housing. Particulate contamination, organic
matter, dissociated ions, microbes and endotoxins from the feed
fluid are retained within purification elements in the housing.
Fluid suitable for medical applications is then output from the
housing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] These and other aspects of the invention will be apparent to
the skilled artisan in view of the Detailed Description and claims
set forth below, and in view of the appended drawings, which are
meant to illustrate and not to limit the invention, and
wherein:
[0020] FIG. 1 is a schematic side perspective view of a system for
producing peritoneal dialysate or other medical solutions;
[0021] FIG. 2 is a schematic side sectional view of a fluid
purification pack, constructed in accordance with one aspect of the
present invention;
[0022] FIG. 3 is a schematic side sectional view of a reagent
cartridge for housing reagents of peritoneal dialysate;
[0023] FIG. 4 shows the reagent cartridge of FIG. 3 after partial
dissolution of the reagents housed therein;
[0024] FIG. 5 shows the reagent cartridge of FIG. 3 after complete
dissolution of the reagents housed therein;
[0025] FIG. 6 is a schematic side sectional view of a reagent
cartridge for housing reagents of peritoneal dialysate;
[0026] FIG. 7 shows the reagent cartridge of FIG. 6 after complete
dissolution of the reagents housed therein;
[0027] FIGS. 8A and 8B illustrate side sectional and plan views,
respectively, of a downstream end of the water purification pack of
FIG. 2;
[0028] FIGS. 9A and 9B illustrate side sectional and plan views,
respectively, of an upstream end of the reagent cartridge of FIG.
3, configured to irreversibly connect with the water purification
pack; and
[0029] FIG. 10 is a side sectional view of a coupling between the
water purification pack and reagent cartridge of FIGS. 8 and 9.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0030] While the illustrated embodiments are described in the
context of a particular application, i.e., peritoneal dialysis, the
skilled artisan will find application for the apparatus and methods
for producing injectable quality fluid in a variety of medical
applications. Moreover, the apparatus and methods for producing
"injectable quality" fluids will have applications beyond the
medical field, wherever similarly pure water is desirable. The
fluid purification unit described herein has particular utility
when connected in series upstream of fluid collection/delivery
devices, such as the illustrated mechanism for mixing dry reagent
as purified diluent flows through.
[0031] System for Preparing Peritoneal Dialysis Solution
[0032] FIG. 1 illustrates a system 10 for producing solutions
suitable for injection into the human body. A diluent or fluid
purification pack 12, as described in more detail below, is
connected upstream of a reagent cartridge 14. The cartridge 14, in
turn, is in fluid communication with a solution reservoir 16 via a
tube 18. As also set forth in more detail below, purified diluent
is provided from the pack 12 to the reagent cartridge 14, wherein
the dry reagents are dissolved and solution is delivered to the
reservoir 16. Alternatively, the solution can be delivered directly
to the patient's body.
[0033] In the illustrated embodiment, the solution comprises
peritoneal dialysis solution. The cartridge 14 advantageously
houses dry or lyophilized formulations of reagents suitable for
peritoneal dialysis. Desirably, the solution is formed immediately
prior to delivery to the patient's peritoneal cavity, such that the
dialysate need not be stored in solution form for extended periods,
and little opportunity exists undesirable reactions within the
solution prior to delivery.
[0034] The cartridge 14 defines fluid flow paths through the dry
reagents, by way of porous elements therebetween, enabling dry
storage in confined reagent beds while also enabling dissolution
simply by passing diluent through the housing. Two preferred
versions of the cartridge 14 are described in more detail with
respect to FIGS. 3-7, below.
[0035] The diluent purification pack 12 of the illustrated
embodiment is capable of on-site purification of locally available
fluid, such as tap water from a municipal water source. The
preferred water purification pack is described in more detail with
respect to FIG. 2 below.
[0036] Water Purification Pack
[0037] Referring to FIG. 2, the preferred fluid purification pack
12 is capable of purifying water or other liquid diluent to the
standards required for injection into a patient, e.g., for
peritoneal dialysis applications. Advantageously, available water,
preferably potable water, can be introduced to the system, and is
purified as it flows through the pack. The purified water can be
delivered, for example, directly to the reagent cartridge 14 (FIG.
1), to a storage or collection container for short-term storage or
transportation or direct connection to another delivery device,
such as a wound irrigation pump. Accordingly, bulky purified water
need not be stored long in advance of its need or transported great
distances to the point of administration. Complex machinery for
purifying water is also obviated.
[0038] In order to serve as a diluent for injection into the human
body, or for similar applications, the independently provided water
must be highly purified. The U.S. Pharmacopoeia provides processes
for producing sterile water for injection. The preferred water pack
12 also produces water of a quality suitable for injection,
preferably equivalent to or surpassing the quality produced by the
U.S. Pharmacopoeia processes. Water purified through the pack thus
preferably meets or exceeds the U.S. Pharmacopoeia's standards for
Sterile Water for Injection, including sterility, pH, ammonia,
calcium, carbon dioxide, chloride, sulfate and oxidizable
substances tests. In particular, injectable quality water or other
fluid produced by the illustrated water purification pack 12
exhibits the following characteristics: a very low level of total
organic carbon, preferably less than about 1 ppm and more
preferably less than about 500 ppb; low conductivity, preferably
less than about 5.0.mu. Siemens (2.5 ppm) and more preferably less
than about 2.0.mu. Siemens (1 ppm); near neutral pH, preferably
between about 4.5 and 7.5, and more preferably between about 5.0
and 7.0; very low particulate concentration, preferably fewer than
less than about 12 particles/mL of particles.gtoreq.10 .mu.m, more
preferably less than about 6 particles/mL of such particles, and
preferably less than about 2 particles/mL of particles.gtoreq.25
.mu.m, more preferably less than about 1 particle/mL of such
particles; and low endotoxin levels, preferably less than about
0.25 endotoxin units (EU) per mL (0.025 ng/mL), more preferably
less than about 0.125 EU/mL (0.0125 ng/mL) with a 10:1 EU/ng
ratio.
[0039] Conventionally, purifying non-sterile fluid to such
stringent quality standards, particularly for introduction into the
human body, has called for extensive mechanical filtration and/or
distillation, pumping, distribution and monitoring systems. These
complex mechanisms can safely and economically produce large
volumes of sterile water to injectable quality. Such mechanisms,
however, occupy considerable space at a central location and
necessitate even more space for storing purified water closer to
the site of administration. Moreover, conventional water
purification mechanisms are not conducive to employment in a
portable apparatus for use in the field.
[0040] U.S. Pat. No. 5,725,777 to Taylor discloses a portable
apparatus for purifying water to injectable quality. The apparatus
includes several stages for purification, including multistage
depth prefiltering, ultrafiltration fibers, reverse osmosis fibers,
ion exchange resin and activated carbon in that order.
[0041] The reverse osmosis stage of Taylor '777 effectively
purifies water to a high degree. Unfortunately, because reverse
osmosis involves diffusing input water across a semi-permeable
membrane, the rate of water production is very slow relative to the
cross-section of the membrane. Even with the use of multiple
reverse osmosis fibers with a high overall membrane surface area,
diffusion is slow. In order to fully realize the advantages of
portability, purified diluent should be rapidly produced at the
time of administration. For acceptable rates using the apparatus of
Taylor '777, however, high pressures (e.g., 40 to 75 psi) are
applied across the semi-permeable membrane. Pumps and restrictor
means for realizing these pressures reduce the versatility and
portability of the overall system.
[0042] In the illustrated embodiment, the water or fluid
purification pack 12 comprises a housing 20 with an axial inlet 22
and outlet 24. The housing 20 defines a flow path between the inlet
22 and outlet 24, with multiple purification stages along the flow
path. The pack 12 is thus designed to purify fluid in the course of
traveling, preferably in a linear path, through the housing 20.
[0043] The housing 20 is preferably formed of a suitable polymer,
particularly polycarbonate, which aids in purifying water by
binding endotoxins through charge interactions. Endotoxins are the
organic byproduct of dead microorganisms, particularly the outer
cell wall of bacteria. Although the term endotoxin is occasionally
used to refer to any "cell-associated" bacterial toxin, it
primarily refers to the lipopolysaccharide complex associated with
the outer envelope of Gram-negative bacteria such as E. coli,
Salmonella, Shigella, Pseudomonas, Neisseria, Haemophilus, and
other leading pathogens. In high enough concentrations,
particularly in critical applications such as intravenous
injection, this organic matter can be toxic.
[0044] The pack 12 is configured for convenient portability. The
skilled artisan will appreciate the fact that different sizes will
safely produce different amounts of purified water. Thus, for an
embodiment optimized for safely purifying 10 L of water, the
outside dimensions of the housing 20 preferably include a length of
less than or equal to about 6 inches from inlet 22 to outlet 24,
and a width (diameter in the illustrated embodiment) of less than
or equal to about 5 inches. The illustrated housing 20, designed
for safely purifying 2 L of water, has a length of about 3 inches
and a diameter of about 2.25 inches. Preferably, therefore, the
fluid purification pack 12 has a cross-sectional area of less than
about 20 sq. inches, more preferably less than about 4 sq. inches.
Despite this small cross-section, the illustrated pack 12 can
achieve high flux rates under pressures as low as about 5-10
psi.
[0045] The fluid purification pack 12 is also preferably configured
to deliver a unit dose of purified fluid. The pack 12 thus is
preferably designed for one-time use and to be discarded
thereafter. As such, the sterility of the pack 12 can be assured,
since the pack 12 will not be reused after seals at the inlet 22
and outlet 24 are broken. Several of the features described
hereinbelow discourage or prevent recharging the water pack 12 for
repeated use, as will be understood by the skilled artisan.
[0046] Downstream of the inlet 22 is a depth filter 26. The
porosity limit of the illustrated depth filter 26 preferably ranges
from about 1 micron (.mu.m) to 10 .mu.m, most preferably about 1
.mu.m. The depth filter 26 is preferably formed of a porous
polypropylene mesh in multiple layers, particularly two to four
layers. Alternatively, the commercially available cellulose-based
depth filters can be employed, as will be understood by one of
ordinary skill in the art. In still other arrangements, ceramic or
other known particle filtration material can be employed. Most
preferably, the depth filter 26 comprises a series of depth filters
(not shown) that successively filter out smaller and smaller
particles. In the illustrated embodiment, four successive depth
filters are included within the depth filtration stage 26, having
porosities of about 100 .mu.m, 40 .mu.m, 10 .mu.m and 1 .mu.m in
sequence from upstream end to downstream end.
[0047] Downstream of the depth filter 26 is an organic filtration
stage 28, which can comprise a bed of granular carbon. In the
illustrated embodiment, the organic filtration stage comprises a
resin bed treated for retention of organic contaminants. The
illustrated embodiment incorporates a form of styrene
divinylbenzene commercially available from Rohm & Haas of
Philadelphia, Pa. under the trade names Ambersorb 563. This
component removes certain residual organic contaminants, such as
endotoxins, as well as commonly used additives placed in
municipally treated waters (e.g., chlorine, trihalomethanes and
chloramine).
[0048] Adjacent to the downstream end of the organic filtration
stage 28 is a restraint 30. The restraint 30 is a filter of
controlled porosity, preferably also comprising a polypropylene
mesh with a porosity of about 1-10 microns, more preferably about 1
micron. This component prevents passage of particulates shed by the
organic filtration component 28, as well as providing a secondary
assurance that insoluble particulates do not pass further through
the water purification pack.
[0049] Adjacent to the downstream side of the restraint 30 is a
deionization stage, preferably comprising a bed 32 of deionization
resin beads. The resin bed 32 more preferably comprises a mixture
of pharmaceutical grade resins with strong anion exchanger
(cation-impregnated) and strong cation exchanger
(anion-impregnated) chemistries, binding dissociable ions and other
charged particles with a very high affinity. In the illustrated
embodiment, the resin bed 32 comprises mixed anion- and
cation-impregnated resin beads with weakly associated hydrogen or
hydroxyl groups, respectively. The ion exchange resins of the
preferred embodiment comprise styrene divinyl benzene. Such resins
are available, for example, from Rohm & Haas of Philadelphia,
Pa. under the trade name IRN 150, or from Sybron of Birmingham,
N.J. under the trade name NM60. Cation exchangers exchange
hydrogens for any dissolved cations in the diluent. Common
dissolved cations include sodium (Na.sup.+), calcium (Ca.sup.2+)
and aluminum (Al.sup.3+). The anion exchange resins exchange
hydroxyl ions for any anions present in an aqueous solution. Common
anions include chloride (Cl.sup.-) and sulfides (S.sup.2-). The
resin bed 32 additionally retains some endotoxins that escape the
upstream filtration components. The skilled artisan will recognize
other types of ion-exchange resins that could also be utilized in
this stage.
[0050] The preferred mixed resin bed 32 simplifies and provides a
more compact pack 12 than more conventional ion exchange columns,
wherein anion and cation exchangers are separated. Moreover, the
mixed bed 32 arrangement prevents recharging the ion exchange resin
by back-flushing, thus discouraging re-use and maintaining
sterility of the unit.
[0051] Downstream of the deionization resin bed 32 are a
deionization bed restraint 34 and a terminal filter element 36, in
sequence. The restraint 34 preferably comprises the same
polypropylene mesh utilized for the illustrated depth filter 26 and
carbon bed restraint 30. The resin bed restraint 34 serves to
prevent passage of deionization bed fragments or fines, as well as
any other particulates that have escaped the upstream filters 26,
30. The restraint 34 also serves to protect the filter element 36
downstream of the restraint 34.
[0052] The terminal filter element 36 comprises a permeable
membrane, preferably a microfiltration or ultrafiltration membrane,
depending upon the application. The term "terminal," as utilized in
this context, refers to the filtration element with the lowest
porosity, and not the physical location. Typically, however, the
terminal filter will be immediately adjacent the outlet, as shown,
such that large particulates are filtered out by courser filtration
elements upstream of the terminal filter. The terminal filter 36
preferably has a porosity of at most about 0.5 .mu.m, and none
preferably less than about 0.22 .mu.m.
[0053] For applications in remote locations where water is
untreated or insufficiently treated, an ultrafiltration membrane is
most preferable. Nominal porosity of between about 10,000 and
30,000 molecular weight cut-off desirably filters out viruses
prevalent in such locations, such as hepatitis, rota virus, polio,
etc. Nominal cut-off for the illustrated embodiment is between
about 15,000 and 25,000 MW. While endotoxins (complex
lipopolysaccaride) generally aggregate into complexes of greater
than about 1,000,000 molucular weight, an ultrafiltration membrane
can retain even a single unit of endotoxin (about 15,000 molecular
weight).
[0054] For employment in more developed locations, where treated
water is available (e.g., municipal water in most American cities),
the water purification pack 12 need not filter out pathogenic
viruses. Accordingly, for such uses the terminal filter 36
comprises a microfiltration membrane. Advantageously, the higher
porosity of a microfiltration membrane allows a greater flow rate
for a given feed pressure or a lower feed pressure for a given flow
rate. The microfiltration membrane preferably has a porosity of
lower than about 0.5 .mu.m, and more preferably comprises a 0.22
.mu.m or finer filter, and most preferably has a porosity of about
0.20 .mu.m or finer. Desirably, the terminal filter 36 has enhanced
endotoxin binding characteristics and is preferably chemically
treated to incorporate a quaternary amine exchanger (QAE) to bind
endotoxins. Such endotoxin binding membranes are available under
the trade name HP200 from the Pall Specialty Materials Co. Most
preferably, the terminal filter 36 comprises two successive
QAE-treated 0.20 .mu.m permeable membranes, ensuring adequate
endotoxin retention. Despite a high flux rate compared to
ultrafiltration membranes, therefore, the terminal filter 36
incorporating a microfiltration membrane removes endotoxins as well
as microbes and particulate matter of less than 1 .mu.m from
diluent passing therethrough. In fact, challenge water with
endotoxin levels as high as 1,000 ng/mL have been purified through
the illustrated pack 12 to below the current detection limit (0.006
ng/mL).
[0055] The purification stages within the water purification pack
are thus such that water passing through the pack 12 and exiting
the housing outlet 24 is of a purity level safe for injection into
the human body (following the addition of appropriate salts for
physiologic solutions). Preferably, effluent water conforms to the
purity levels set forth above. It will be understood, of course,
that while safe enough for injection, the fluid may actually be
employed for alternative medical applications, such as wound
irrigation, use in instrument cleaning solutions, and general
employment by immuno-comprised individuals (e.g., AIDS patients,
geriatrics, etc.).
[0056] Desirably, the water purification pack 12 includes an
upstream cap 38 over the housing inlet 22, and a downstream cap 40
over the housing outlet 24. The sterility of the purification
elements housed within the housing 20 is thus maintained until use.
As will be understood in the art, the inlet 22 and outlet 24 can be
provided with threads or Luer-type fittings (see FIGS. 8-10) to
mate with upstream and downstream elements in the peritoneal
dialysate delivery system 10 (FIG. 1).
[0057] The sterility and efficacy of the water purification pack 12
is also reinforced by features discouraging re-use of the water
pack. As previously noted, the resin bed 32 preferably comprises a
mixed bed of anion- and cation-exchangers. Thus, the mixed bed 32
cannot be recharged by traditional backflushing techniques, since
regeneration of the cation-exchanger would result in exhaustion of
the anion exchanger and vice versa.
[0058] Additionally, the water purification pack is preferably
configured to irreversibly connect with a downstream collection
device. In one preferred arrangement, the housing outlet 24 is
welded or otherwise integrally connected with a collection tube
leading to a collection bag or other container. When water is
purified by passing through the housing 22 and fills the downstream
collection container, the preferred plastic tubing is
simultaneously cut and cauterized to seal the tube downstream of
the outlet 24, preventing re-use of the water pack 12.
[0059] With reference to FIGS. 8 and 9, in another preferred
arrangement, the outlet 24 is irreversibly connectable with the
downstream reagent cartridge 14. The water pack outlet 24 and the
reagent cartridge inlet 52 thus have interlocking mechanisms that
are irreversible without damage to the mechanisms.
[0060] In the illustrated embodiment, the water pack housing 20
includes a cylindrical collar 42 surrounding the outlet 24, the
collar having outer ratcheting teeth 44. The reagent pack 14
includes a similar cylindrical collar 46 surrounding the inlet 52,
and the collar 46 includes internal ratchet teeth 48. The outer
collar 46 of the reagent pack 14 is sized to fit over the outer
collar 42 of the water pack 12. The ratcheting teeth 44, 46 are
sloped to slide past each other during clockwise rotation to
tighten the inner Luer lock mechanism. The teeth 44, 46 engage one
another, however, to prevent counter-clockwise rotation, such that
the Luer lock cannot be loosened.
[0061] Accordingly, the locking mechanism must be broken or
otherwise damaged to separate the used water pack 12 from the
reagent cartridge 14. Such damage or breakage minimizes the risk of
accidentally re-using a spent water pack 12. The skilled artisan
will readily appreciate that similar irreversible locking
mechanisms can be utilized with other collection or delivery
devices downstream of the water purification pack. The skilled
artisan will also recognize other suitable irreversible locking
mechanisms for discouraging re-use.
[0062] Single-Bed Reagent Cartridge
[0063] FIGS. 3-5 illustrate a single-bed reagent cartridge 14 for
use with the water purification pack. The figures illustrate
various stages of dissolution, as will be better understood from
the methods of operation discussed hereinbelow.
[0064] FIG. 3 shows a fully charged reagent cartridge 14, in
accordance with the first embodiment. The cartridge 14 comprises
rigid walled housing 50 with an inlet port 52 at an upstream end,
and an outlet port 54 at a downstream end. Within the housing, a
number of porous elements define a fluid flow path between the
inlet port 52 and the outlet port 54.
[0065] The housing 50 is preferably transparent or translucent,
advantageously enabling the user to observe the operation of the
device and complete dissolution of reagents prior to use of a
produced solution, as will be apparent from the discussion of the
method of operation, discussed hereinbelow. Examples of translucent
and transparent polymers are polypropylene, polycarbonate and many
other well-known materials.
[0066] Within the housing 50, immediately downstream of the inlet
port 52, is an inlet frit 56, which serves as a safety filter to
contain any reagent which escapes the restraints described below.
An outlet frit 58 serves a similar function immediately upstream of
the outlet 54. Desirably, the inlet frit 56 and the outlet frit 58
comprise porous elements having a porosity smaller than the
smallest particle of the reagents housed within the cartridge 14.
The frits 56, 58 thus serve as filters to ensure that no reagent
escapes the cartridge prior to dissolution, as will be described
below. An exemplary frit is a multilayered polypropylene laminate,
having a porosity between about 1 .mu.m and 100 .mu.m, more
preferably between about 10 .mu.m to 50 .mu.m. Further details on
the preferred material are given below, with respect to the reagent
restraints.
[0067] Downstream of the inlet frit 56 is an upstream reagent
compression component 60. Similarly, upstream of the outlet frit 58
is a downstream reagent compression component 62. The compression
components 60, 62 preferably comprise materials that have
sponge-like elasticity and, as a result of compression, exert axial
pressure while trying to return to its original, expanded form. The
compression components 60, 62 preferably comprise compressible,
porous, open cell polymer or foam, desirably more porous than the
frits, to avoid generation of back pressure. An exemplary material
for the compression components is a polyurethane foam. Desirably,
the compression components 60, 62 and surrounding housing 50 are
arranged such that the compression components 60, 62 exert a
compressive force on the reagent bed regardless of the size of the
reagent bed. In other words, the compression components 60 and 62
would, if left uncompressed, together occupy a greater volume than
that defined by the housing 50. Desirably, the pressure exerted is
between about 50 grams per sq. inch and 2,000 grams per sq. inch,
more preferably between about 300 grams per sq. inch and 900 grams
per sq. inch.
[0068] It will be understood that, in other arrangements, metal or
polymer coiled springs and porous plates can serve the same
function. Such alternative compression components are disclosed,
for example, with respect to FIGS. 12-15; Col. 9, lines 8-53 of
U.S. Pat. No. 5,725,777, the disclosure of which is incorporated
herein by reference. Another preferred compression component is
disclosed in U.S. provisional application No. 60/132,088, filed
Apr. 30, 1999, the disclosure of which is hereby incorporated by
reference. It will also be understood, in view of the discussion
below, that a single compression component can serve the function
of the illustrated two compression components. Two components
exerting pressure on either side of a reagent bed 64 (described
below), however, has been found particularly advantageous in
operation.
[0069] A single reagent bed 64 is situated between the compression
components 60, 62. The reagent bed 64 is desirably sandwiched
between an upstream reagent restraint 66 and a downstream reagent
restraint 68. The upstream reagent restraint 66 is thus positioned
between the reagent bed 64 and the upstream compression component
60, while the downstream reagent restraint 68 is positioned between
the reagent bed 64 and the downstream compression component 62.
[0070] The restraints 66, 68 desirably prevent the passage of
reagent particles in their dry formulation. The porosity of the
restraints is therefore selected to be less than the size of the
smallest particles within the reagent bed, depending upon the
particular reagent formulations and physical particle size desired.
Desirably, the pores are large enough to avoid excessive pressure
drop across the restraints. Preferably, the restraint porosity in
the range between about 1 .mu.m and 100 .mu.m, more preferably
between about 10 .mu.m to 50 .mu.m. An exemplary restraint,
suitable for the illustrated peritoneal dialysis application,
comprises the same material as the frits 56, 58, and consists of a
non-woven polymer, particularly polypropylene with a porosity of
about 20 microns. Another exemplary restraint comprises sintered
polyethylene with a porosity of about 30 microns.
[0071] Additionally, the restraints 66, 68 are sized and shaped to
extend completely across the housing 50, forming an effective seal
against reagent particulates escaping around the restraints 66,
68.
[0072] The reagent bed 64 comprises a complete formulation of dry
or lyophilized reagents required to produce a peritoneal dialysis
solution. In the illustrated single-bed embodiment, the reagent bed
65 is a mixture of compatible reagents, such as will not exhibit
spontaneous chemical reaction from prolonged contact in their dry
form. Accordingly, a buffering agent such as an acetate or lactate,
and particularly sodium lactate, is employed in place of a
bicarbonate. Further reagents include electrolytes, such as sodium
chloride, magnesium chloride, potassium chloride and calcium
chloride; a sugar, preferably dextrose; and an acid, particularly
citric acid. Advantageously, the acid component of the reagent bed
65 can be lower than conventional solutions, since storage in dry
form alleviates the tendency for dextrose caramelization.
[0073] The illustrated housing 50 holds reagents sufficient to
produce 2 liters of a typical peritoneal dialysate solution.
Accordingly, the reagent bed 64 holds the following reagents:
1 TABLE I Dry Reagent Constituents Mass Dry Volume Calcium chloride
514 mg Negligible Magnesium chloride 101.6 mg Negligible Sodium
lactate 8.96 g 24 mL Sodium chloride 10.76 g 22 mL Dextrose 50 g 70
mL Total 70 g 116 mL
[0074] The dry volume of the above-listed reagents, which can
produce 2 L of 2.5% dextrose peritoneal dialysate, is thus about
100 mL. The housing 50 for such a formulation need only be about
125% to 500% of the dry reagent volume, more preferably about 150%
to 200%, depending upon the selected compression components 60, 62.
The illustrated housing 50 is about 2" in diameter and about 3" in
height, thus occupying about 175 mL. The cartridge 14 thus
represents a much smaller and more stable form of dialysate for
storage and transport, compared to 2 L of prepared solution. If a
smaller or larger volume of solution is desired, the skilled
artisan can readily determine the proportionate weight and volume
of dry reagents required in the reagent bed 64, such as for
producing 1 L, 3 L, 6 L, 10 L, etc. Similarly, the skilled artisan
can readily determine the proportions of reagents desirable for
1.5% dextrose dialysate, 4% dextrose dialysate, etc.
[0075] An inlet port cover 70 and an outlet port cover 72 cover the
housing inlet port 52 and outlet port 54, respectively. The port
covers 70, 72 advantageously seal out moisture and prevent
destabilization of the dry reagents housed within during transport
and storage. As with the water purification pack, the inlet port 52
and outlet port 54 can be configured with threaded or Luer-type
connection fittings. In the illustrated embodiment, the inlet port
52 is configured to mate with the outlet 24 of the water
purification pack 12 (FIG. 2), while the outlet port 54 is
configured to mate with the downstream tube 18 (see FIG. 1).
[0076] Double-Bed Reagent Cartridge
[0077] FIGS. 6 and 7 illustrate a double-bed reagent cartridge 14'.
FIGS. 6 and 7 illustrate the cartridge 14' in fully charged and
fully depleted conditions, respectively, as will be better
understood from the methods of operation discussed hereinbelow.
[0078] With reference initially to FIG. 6, the housing 50 of the
double-bed reagent cartridge 14' is preferably similar to that of
the first embodiment, such that like reference numerals are used to
refer to like parts. Thus, the housing 50 defines an inlet port 52
and outlet port 54, and contains porous elements between the inlet
port 52 and outlet port 54, such as to define a fluid flow path
through the housing 50. Specifically, the housing 50 contains an
upstream frit 56, upstream compression component 60, upstream
reagent restraint 66, downstream reagent restraint 68, downstream
compression component 62 and downstream frit 58. Each of these
elements can be as described with respect to the previous
embodiment.
[0079] Unlike the single-bed cartridge 14 of FIGS. 3-5, however,
multiple reagent beds are confined between the upstream restraint
66 and downstream restraint 68. In particular, a primary reagent
bed 80 and a secondary reagent bed 82 are shown in the illustrated
embodiment, separated by at least one restraint. In the illustrated
embodiment, the reagent beds 80 and 82 are separated by a first
intermediate restraint 84 and second intermediate restraint 86, as
well as an intermediate compression component 88 between the
intermediate restraints 84 and 86.
[0080] Accordingly, the primary reagent bed 80 is confined between
upstream restraint 66 and the first intermediate restraint 84,
while the secondary reagent bed 84 is similarly confined between
the second intermediate restraint 86 and the downstream restraint
68. The intermediate reagent bed restraints 84, 86 desirably serve
to contain the reagents within the beds 80, 82 in their dry form,
while still being porous enough to allow diluent, along with any
dissolved reagents, to pass through. Accordingly, the intermediate
reagent restraints 84, 86 can have the same structure as the frits
56, 58 and upstream and downstream reagent restraints 66, 68, as
described above with respect to the single-bed embodiment.
Similarly, the intermediate compression component 88 can have the
same structure as the upstream and downstream compression
components 60, 62.
[0081] Each of the intermediate compression component 88 and the
intermediate reagent restraints 84, 86 are interposed between and
separate the primary reagent bed 80 from the second reagent bed 82.
Due to the selected porosity of the elements, particularly the
intermediate restraints 84, 86, constituents of the two reagent
beds 80, 82 therefore do not interact with one another in their dry
states.
[0082] The illustrated double-bed embodiment therefore enables
separate storage of different reagents within the same housing 50.
A complete formulation of the dry reagents required to produce a
peritoneal dialysis solution may contain reagents that react
undesirably when exposed to one other for prolonged periods of
time, in either dry or liquid forms, as noted in the Background
section. For example, bicarbonates are preferred, physiologically
compatible buffering agents for peritoneal dialysis, but tend to be
very reactive with typical salts in the dialysate formulation, such
as calcium chloride or magnesium chloride. The reactions form
insoluble calcium carbonate or magnesium carbonate, and also
liberate CO.sub.2. Because of the potential reactivity of
incompatible reagents, it is preferable to separately store these
reagents within the device housing 50.
[0083] Separate storage is accomplished by separating reagents into
compatible groupings, which are then placed in separate
compartments within the housing. The compartments are represented,
in the illustrated embodiment, by the primary reagent bed 80 and
the secondary reagent bed 82. The potentially reactive reagents are
thereby constrained from movement through the housing, when
maintained in their dry form, by reagent bed restraints 66, 84, 86,
68 at the upstream and downstream ends of each of the reagent beds
80, 82. As noted above, the reagent bed restraints 66, 84, 86, 68
have fine enough porosity to prevent the passage of reagent
particles in their dry form.
[0084] In the illustrated embodiment, the primary reagent bed 80 is
a reagent mixture, preferably comprising: electrolytes,
particularly sodium chloride, potassium chloride, calcium chloride
and magnesium chloride; a sugar, particularly dextrose. In other
arrangements, the primary reagent bed 80 can also comprise a
buffer.
[0085] The secondary reagent bed 82 can contain at least one
component that is unstable in the presence of at least one
component in the primary reagent bed 80. Advantageously, the
secondary reagent bed 82 contains a bicarbonate, such as sodium
bicarbonate. Because the bicarbonate is separated from calcium
chloride and magnesium chloride, the reagents do not react to form
insoluble precipitates.
[0086] The skilled artisan will readily appreciate that, in other
arrangements, the primary reagent bed 80 can contain the
bicarbonate if the secondary bed 82 contains calcium chloride
and/or magnesium chloride. In still other alternatives, other
incompatible reagents for medical solutions can be similarly
separated into reagent beds within the same housing. Moreover,
three or more reagent beds can be utilized to separate multiple
incompatible reagents.
[0087] The illustrated housing 50 holds reagents sufficient to
produce 2 liters of a typical peritoneal dialysate solution.
Accordingly, the reagent beds 80, 82 hold the following
reagents:
2 TABLE II Mass Dry Volume Primary Reagent Bed Calcium chloride 514
mg Negligible Magnesium chloride 101.6 mg Negligible Sodium
chloride 10.76 g 22 mL Dextrose 50 g 70 mL Subtotal 61 92 mL
Secondary Reagent Bed Sodium bicarbonate 6.64 g 6.1 mL Total 68 g
98 mL
[0088] The dry volume of the above-listed reagents, which can
produce 2 L of 2.5% dextrose peritoneal dialysate, is thus about 98
mL. As with the previously described single-bed embodiment, the
total volume of the cartridge 14' is preferably between about 125%
and 500%, and more preferably 150% and 200%, of the dry reagent
volume. As also noted above, the skilled artisan can readily
determine the proportionate weights and volumes of dry reagents
required for forming other peritoneal dialysate solutions, such as
1.5% dextrose dialysate, 4% dextrose dialysate, etc.
[0089] Notably, the double-bed cartridge utilizes bicarbonate as
the buffer, and omits the need for physiologically damaging acid by
enabling production of a physiologic solution.
[0090] Method of Operation
[0091] In operation, purified diluent is provided to a reagent
cartridge 14 or 14', which is fully charged with an appropriate
amount of dry reagent, as set forth above. Fluid to be purified
(e.g., municipal tap water) is provided to the system 10 of FIG. 1,
such that the purified diluent is produced on site and need not be
produced remotely and transported, significantly reducing the cost
of transportation.
[0092] Accordingly, with reference to FIG. 2, diluent in the form
of available water is first provided to water purification pack 12
of FIG. 2. Pressure commonly found in municipal water systems is
sufficient to feed the water through the purification pack 12.
Alternatively, a hand pump or large syringe can be supplied with a
measured volume of water, and water hand-pumped therefrom into the
purification pack 12. Feed pressure is preferably less than about
20 psi. Fluid flux through the purification pack 12 (with a feed
pressure of about 5-10 psi) is preferably at least about 30 mL/min,
and more preferably at least about 90 mL/min through the pack
12.
[0093] The diluent enters the inlet 22 and passes through depth
filter 26, where particulates larger than about 1 micron are
filtered out. The depth filter 26 retains insoluble particulates
and microbes greater than the pore sizes of the successive layers
in this component. Depth filtration is extremely effective in
removing contaminants such as asbestos fibers and similarly sized
particles.
[0094] Filtered diluent continues downward through organic
filtration stage 28, where residual organics such as endotoxins and
additives such as chlorine, chloramine and trihalomethanes are
adsorbed. Additionally, some inorganic materials are removed in the
process. Carbon is effective at adsorbing many types of chemicals,
it is especially known for its power in adsorbing organic
compounds. Carbon's particular affinity for organics is due to its
non-polar nature. Carbon is also somewhat effective in adsorbing
metals and other inorganics. The illustrated resin has similar
absorption characteristics.
[0095] After being additionally purified by the organic filtration
stage 28, the partially purified diluent passes through the
restraint 30 and into the ion-exchange resin bed 32. Dissociated
ions and other charged particulates in solution bind to the resins.
Some endotoxins that have escaped the upstream components are also
retained in the resin bed 32.
[0096] After passing through the resin bed restraint 34, which
retains the contents of the resin bed 34, the diluent is further
purified through the terminal filter element 36. In one embodiment,
as previously noted, the terminal filter 36 comprises an
ultrafiltration membrane with a nominal cut-off of between about
10,000 and 30,000 molecular weight. Depending upon the density of
pores, 5-10 psi feed pressure can produce a flux of between about
35 mL/min and 100 mL/min through such an ultrafiltration membrane.
In another embodiment, the filter 36 comprises at least one and
preferably two microfiltration membranes of a very fine porosity
(e.g., about 0.22 .mu.m or finer), each including chemical
treatment with a quaternary amine exchanger for binding residual
endotoxins. The flux rate for a device with the microfiltration
membrane can be more that twice that of an ultrafiltration membrane
with equivalent pore density.
[0097] The multiple filtration and chemical binding components of
the water purification pack 12 thus ensure removal of particulate,
ionic and organic contaminants from the diluent as it passes
through the pack 12. Endotoxins, including organic matter such as
cell walls from dead bacteria, can be particularly toxic. Highly
purified diluent, sufficient to comply with or exceed FDA and U.S.
Pharmacopoeia water quality standards for "sterile water for
injection," exits the outlet 24, but without the need for reverse
osmosis.
[0098] With reference to FIG. 1 again, purified diluent then passes
from the water purification pack 12 to a collection/delivery
device. As noted above, in one embodiment, the downstream device
can comprise a simply storage container, such as a plastic bag. In
the illustrated embodiment, the storage/delivery device comprises
the reagent cartridge 14. Desirably, the downstream
storage/delivery device is irreversibly fixed to the water pack
outlet 24, either integrally or through a locking mechanism.
[0099] FIGS. 3-5 illustrate dissolution of dry reagent 64 as
diluent passes through the single-bed reagent cartridge 14 for the
peritoneal dialysis. While illustrated cross-sectionally, it will
be understood that the preferred transparent or translucent housing
50 enables the user to similarly observe dissolution of the reagent
bed 64 as solvent or diluent passes therethrough. Additionally, the
user can observe whether insoluble precipitates are present within
the reagent bed, prior to employing the cartridge 14.
Advantageously, gravitational force is sufficient to draw the water
through the cartridge 14.
[0100] Referring initially to FIG. 3, purified diluent enters the
cartridge 14 through the inlet port 52. Preferably, purified
diluent is fed directly from the water purification pack 12.
"Directly," as used herein, does not preclude use of intermediate
tubing, etc, but rather refers to the fact that water is purified
on site immediately prior to solution formation, rather remotely
produced and shipped. It will also be understood, however, that the
illustrated reagent cartridge will have utility with other sources
of sterile diluent.
[0101] The diluent passes through the porous inlet frit 56 and the
upstream compression component 60. In the illustrated embodiment,
the compression component 60 is a porous, open-celled foam, which
readily allows diluent to pass therethrough. The diluent then
passes through the upstream reagent restraint 66 to reach the dry
reagent bed 64. In addition to retaining the dry reagents in the
bed 64, the frit 56 and restraint 66 facilitate an even
distribution of water flow across the sectional area of the housing
50.
[0102] As the solution passes through interstitial spaces in the
bed 64, the dry reagents are eroded, preferably dissolved, and
carried by the diluent through the downstream reagent restraint 68,
the downstream compression component 44 and the outlet frit 58,
exiting through outlet 24. The solution passes through the tube 18
into the collection reservoir 16 (see FIG. 1) and then into the
peritoneal cavity of a patient.
[0103] Referring to FIG. 4, as the reagents are dissolved, the
volume of the reagent bed 64 is reduced, as can be seen from a
comparison of FIG. 4 with FIG. 3. The compression components 60, 62
apply continuous compressive force on either side of the reagent
bed 64. As dry reagent is dissolved, the compressive force packs
the reagents close together. Such continuous packing prevents
expansion of interstitial spaces as the reagent particles are
dissolved. Without the compressive force, the interstitial spaces
between the reagent particles tend to expand into larger channels
within the reagent bed 64. These channels would serve as diluent
flow paths, which would permit a large volume of diluent to flow
through the bed 64 with minimal further dissolution. Significant
portions of the bed would be by-passed by these channels, and
dissolution would be slow and inefficient. Applying continuous
compression to the beds minimizes this problem by continuously
forcing the reagent particles together as the bed dissolves,
ensuring continuous, even exposure of the diluent to the reagents
of the bed 64.
[0104] Though two compression components 60, 62 are preferred, thus
compressing the reagent bed 64 from two sides, it will be
understood that a single compression component can also serve to
keep the regent beds 64 compacted. Moreover, though illustrated in
an axial arrangement, such that diluent flows through the
compression components 60, 62, it will be understood that the
compression components can exert a radial force in other
arrangements.
[0105] The compressive force of the preferred compression
components 60, 62, exerted evenly across the housing 50,
additionally aids in maintaining the planar configuration of the
reagent restraints 66, 68 on either side of the reagent bed 64,
even as the compression components 60, 62 move the restraints
inwardly. The restraints 66, 68 thus continue to form an effective
seal against the housing sidewalls, preventing dry reagent
particulates from escaping the bed 64 until dissolved.
[0106] With reference to FIG. 5, dissolution continues until the
reagent bed is depleted and the restraints 66, 68 contact one
another. Diluent can continue to flow through the housing 50 into
the reservoir 16 (FIG. 1) until the appropriate concentration of
peritoneal dialysate solution is formed. For example, in the
illustrated embodiment, 2 liters of diluent should be mixed with
the contents of the reagent bed 64. Accordingly, 2 liters of
diluent are passed through the housing 50. The contents are
typically fully dissolved by the time about 1.5 liters has passed
through the housing, but diluent can continue to flow until the
appropriate final concentration is reached in the reservoir.
Alternatively, a concentrate can be first formed and independently
diluted.
[0107] Advantageously, the illustrated apparatus and method can
form peritoneal dialysis solution simply by passing water through
the cartridge 50, without complex or time consuming mixing
equipment. The solution can thus be formed on-site, immediately
prior to delivery to the peritoneal cavity, such that the dialysate
need not be shipped or stored in solution form. Accordingly, a low
acid level is possible without undue risk of dextrose
carmelization. Conventionally, a pre-formed dialysis solution
formed has a pH between about 4.0 and 6.5, and the exemplary
reagent mix of Table I produces a conventional solution with pH of
about 5.2. Solution produced from the illustrated single-bed
cartridge of FIGS. 3-4, however, can have lower acidity, since
dextrose does not sit in solution for extended periods of time.
Accordingly the pH level is preferably between about 6.0 and 7.5,
more preferably about 7.0.
[0108] Referring to FIGS. 6 and 7, the double-bed reagent cartridge
14' operates in similar fashion. Purified diluent is fed to the
housing inlet 52, and passes through the inlet frit 56, the
upstream compression component 60, the upstream restraint 66, and
into the primary reagent bed 80. Dissolution of reagents in the
primary bed 80 forms a solution which passes on through the first
intermediate restraint 84, the intermediate compression component
88 and the second intermediate restraint 86. Reagents in the
secondary bed 82 then also dissolve into the diluent, and the
enriched solution continues on through the downstream reagent
restraint 68, the downstream compression component 62 and the
outlet frit 58. A complete solution thus exits the outlet port
54.
[0109] As in the previous embodiment, the regent beds 80, 82 are
continually compressed as the reagents dissolve. Use of three
compression components 60, 88, 62 has been found to improve
dissolution by compressing each bed 80, 82 from two sides. The
skilled artisan will understand, however, that two compression
components, in the positions of the upstream and downstream third
components, can adequately serve to keep the reagent beds
compressed enough to aid the rate of dissolution, particularly if
provided with a high degree of elasticity. Similarly, a single
intermediate compression component, in the position of the
illustrated intermediate compression component 88, can accomplish
this function, while advantageously also separating the
incompatible reagent beds. Additionally, the compression component
need not be axially aligned with the reagent beds, but could
instead surround or be surrounded by the reagent beds, in which
case the compression components would preferably be outside the
diluent flow path.
[0110] Advantageously, the illustrated embodiments provide stable,
dry forms of peritoneal dialysis solutions. Storage and transport
of the reagent cartridges of the illustrated embodiments represents
considerable cost savings over storage and transport of prepared
peritoneal dialysate solutions. Dry or lyophilized reagents are
moreover more stable than solution, and therefore less harmful to
the patient.
[0111] While the storage and transport of dry reagents is generally
recognized as advantageous, practical application has been
difficult. The described embodiments not only provide transport and
storage, but additionally provide integrated mechanisms to ensure
complete dissolution of the dry reagents. Continuous compression of
the reagent bed(s) during dissolution, combined with the
transparent windows allowing real time viewing of the dissolution,
ensure rapid, complete and verifiable dissolution of the reagents.
Thus, the preferred embodiments can be utilized on site, even in
the home, without requiring complex mixing and/or analytical
tools.
[0112] Moreover, the illustrated embodiments facilitate a wider
practicable range of reagents. For example, physiologically
compatible bicarbonate can be employed along with calcium and
magnesium. Separate storage and solution preparation only
immediately prior to administration enables this combination. High
dextrose solutions, as appropriate for peritoneal dialysis, can be
employed without acidic buffers, such that physiologically
compatible pH levels can be practically obtained, preferably
between about 4.0 and 7.5, and more preferably between about 6.0
and 7.5. The reagents listed in Table II produce a solution with a
pH of about 7.0.
[0113] The illustrated fluid purification pack 12 is also a
compact, conveniently transportable device that facilitates on-site
production of injectable quality fluid from available fluid.
Advantageously, despite a small size and low feed pressure, the
pack 12 rapidly provides on-site, injectable quality water as input
water flows linearly from inlet to outlet. A permeable terminal
filter 36, represents the lowest porosity element in the pack 12.
In contrast to semi-permeable, osmotic membranes, this element
facilitates this high flux at low pressures while still retaining
extremely fine particles and toxins.
[0114] Although the foregoing invention has been described in terms
of certain preferred embodiments, other embodiments will become
apparent to those of ordinary skill in the art in view of the
disclosure herein. Accordingly, the present invention is not
intended to be limited by the recitation of preferred embodiments,
but is intended to be defined solely by reference to the dependent
claims.
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