U.S. patent application number 11/402024 was filed with the patent office on 2006-08-31 for method and a device for preparing a medical liquid.
This patent application is currently assigned to Gambro Hospal (Schweiz) AG. Invention is credited to Antonio Bosetto, Francesco Paolini.
Application Number | 20060191850 11/402024 |
Document ID | / |
Family ID | 11418189 |
Filed Date | 2006-08-31 |
United States Patent
Application |
20060191850 |
Kind Code |
A1 |
Bosetto; Antonio ; et
al. |
August 31, 2006 |
Method and a device for preparing a medical liquid
Abstract
A method for preparing a medical liquid from a liquid, such as
water, and two concentrated solutions comprises the following
steps: circulating the liquid in a conduit (15), at a flowrate Q0;
injecting into the conduit (15), at a flowrate Q1, a first
concentrated solution containing a first ionic substance A and a
second ionic substance B, the ionic substances A and B having,
respectively, in the first concentrated solution, a concentration
[Asol] and a first concentration [B1sol]; injecting into the
conduit (15), at a flowrate Q2, a second concentrated solution
containing the first ionic substance A and the second ionic
substance B, the first ionic substance A having, in the second
concentrated solution, the same concentration [Asol] as in the
first concentrated solution, and the second ionic substance B
having, in the second concentrated solution, a second concentration
[B2sol] different than the first concentration [B1sol] in the first
concentrated solution; regulating the injection flowrate Q1 and the
injection flowrate Q2 of the first and second concentrated
solutions in such a way that at any given time the diluted solution
resulting from the mixing of the liquid and the concentrated
solutions has a desired concentration [Ades] of first substance A
and a desired concentration [Bdes] of second substance B.
Inventors: |
Bosetto; Antonio;
(Mirandola, IT) ; Paolini; Francesco; (Modena,
IT) |
Correspondence
Address: |
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER;LLP
901 NEW YORK AVENUE, NW
WASHINGTON
DC
20001-4413
US
|
Assignee: |
Gambro Hospal (Schweiz) AG
|
Family ID: |
11418189 |
Appl. No.: |
11/402024 |
Filed: |
April 12, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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|
10844422 |
May 13, 2004 |
7067061 |
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11402024 |
Apr 12, 2006 |
|
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09869712 |
Oct 9, 2001 |
6793827 |
|
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PCT/IB00/01588 |
Nov 2, 2000 |
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10844422 |
May 13, 2004 |
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Current U.S.
Class: |
210/647 ;
210/101; 210/321.71 |
Current CPC
Class: |
A61M 1/1666 20140204;
Y10S 210/929 20130101; A61M 1/1656 20130101; B01F 3/088 20130101;
A61M 1/167 20140204 |
Class at
Publication: |
210/647 ;
210/321.71; 210/101 |
International
Class: |
B01D 61/26 20060101
B01D061/26 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 2, 1999 |
IT |
TO99A000949 |
Claims
1-17. (canceled)
18. An extracorporeal blood treatment apparatus comprising: a
preparation conduit with a first end configured to receive a liquid
and a second end for delivering a treatment liquid; a circulation
device for circulating the liquid in the preparation conduit; a
first concentrated solution containing at least sodium, potassium,
and calcium and/or magnesium; a first injection means for injecting
into the preparation conduit, at a first injection flowrate Q1, the
first concentrated solution; a second concentrated solution having,
with respect to the first concentrated solution, the same
concentration of sodium and of calcium and/or magnesium and a
different concentration of potassium; a second injection means for
injecting into the preparation conduit, at a second injection
flowrate Q2, the second concentrated solution; a control means for
adjusting the first injection flowrate Q1 and the second injection
flowrate Q2 such that at any given time a diluted solution
resulting from a mixing of the liquid and the first and second
concentrated solutions has a desired concentration of sodium and of
calcium and/or magnesium and a desired concentration of potassium;
and a supply conduit connected to the second end of the preparation
conduit and to an inlet of a membrane exchanger.
19. An apparatus according to claim 18, further comprising a
removal conduit for removing spent liquid, the removal conduit
being connected to an outlet of the membrane exchanger.
20. An apparatus according to claim 18, wherein the control means
controls, over the course of time, the first injection flowrate Q1
and the second injection flowrate Q2 of the first and second
concentrated solutions, respectively, such that the concentration
of potassium in the diluted solution varies over the course of time
in accordance with a predetermined profile.
21. An apparatus according to claim 18, wherein the control means
controls, over the course of time, the first injection flowrate Q1
and the second injection flowrate Q2 of the first and second
concentrated solutions, respectively, in such a way that the
concentration of sodium in the diluted solution varies over the
course of time in accordance with a predetermined profile.
22. An apparatus according to claim 21, wherein the control means
maintains a sum of the injection flowrates Q1 and Q2 of the first
and second concentrated solutions, respectively, constant such
that, for a constant flowrate of the liquid in the preparation
conduit, the concentration of sodium in the diluted solution
remains substantially constant.
23. An apparatus according to claim 18, further comprising an
infusion device configured to infuse a patient with a third
solution containing at least bicarbonate, which is absent from the
treatment liquid.
24. An apparatus according to claim 18, wherein said control means
comprises a control unit.
25. An apparatus according to claim 18, wherein said first
injection means further comprises a first pump arranged on a first
subsidiary conduit connecting the first concentrated solution with
the preparation conduit.
26. An apparatus according to claim 18 or 25, wherein said second
injection means further comprises a second pump arranged on a
second subsidiary conduit connecting the second concentrated
solution with the preparation conduit.
Description
[0001] The present invention relates to a method and a device for
preparing a medical liquid.
[0002] The invention has an application in particular in the
treatment of renal insufficiency, where it can be used for
preparing a dialysis liquid. In this context, the invention is
particularly suitable for treating patients whose internal medium
presents an excess of potassium.
[0003] The kidneys perform many functions, including elimination of
water, excretion of catabolites (or waste products of metabolism,
such as urea and creatinine), regulation of the concentration of
electrolytes in the blood (sodium, potassium, magnesium, calcium,
bicarbonates, phosphates, chlorides), and regulation of the
acid-base balance of the internal medium, which balance is obtained
in particular through the elimination of weak acids (phosphates,
monosodium acids) and through the production of ammonium salts.
[0004] In persons who have lost the use of their kidneys, since
these excretory and, regulatory mechanisms no longer function, the
internal medium becomes charged with water and waste products of
metabolism and presents an excess of electrolytes (sodium in
particular), and, in general, acidosis, with the pH of the blood
plasma shifting towards 7.
[0005] To remedy kidney dysfunction, the conventional practice is
to treat the blood by extracorporeal circulation in a semipermeable
membrane exchanger (hemodialyzer) with circulation, on either side
of the membrane, of the patient's blood and of a dialysis liquid
comprising the main electrolytes of the blood. (chlorides,
bicarbonates, sodium, calcium, potassium, magnesium) in
concentrations close to those of the blood of a healthy subject. As
a result of the physical phenomenon called dialysis, the molecules
migrate from the liquid in which their concentration is highest to
the liquid in which their concentration is lowest.
[0006] A significant electrolytic change in uremic patients is the
increase in the potassium concentration of the plasma. Now,
hyperkalemia (too high a concentration of potassium) is associated
with incidents linked to hyperpolarization of the membrane of the
neuromuscular cells, which can result in hypokinetic arrhythmia and
complete atrioventricular block. One of the objectives of dialysis
treatment is therefore to eliminate the excess potassium
accumulated by the patients between two treatment sessions. In
accordance with the physical principle cited above, the quantity of
potassium eliminated during treatment depends directly on the
difference between the concentration of the potassium in the plasma
and the concentration of the potassium in the dialysis liquid,
which is generally fixed at a constant level, less (approximately 2
mEq/l) than the physiological level (approximately 3.5 mEq/l).
[0007] At the start of conventional dialysis treatment, a patient
with hyperkalemia (whose plasma potassium concentration can be as
high as 10 mEq/l) is exposed to the undesirable effects resulting
from the considerable difference between the potassium
concentration of his plasma and that of the dialysis liquid: this
increased gradient in fact causes a substantial diffusive flow of
potassium across the membrane of the hemodialyzer, which in turn
causes a substantial flow of potassium across the membrane of the
cells, which affects the electric potential of the membrane at rest
and, consequently, the cellular excitability. As this mechanism
also influences the cardiac pacemaker cells, the patent runs the
risk of cardiac arrhythmia during the dialysis treatment. This
phenomenon is naturally heightened in cases of cardiac weakness and
can lead to a reduction in the ejection volume affecting the
cardiovascular circulation.
[0008] A particular object of the invention is therefore to modify
the conditions of conventional dialysis treatment, without however
affecting its effectiveness, in such a way that patients with
hyperkalemia are no longer exposed to the risks mentioned above. A
general object of the invention is to conceive a device and a
method for preparing a treatment liquid which can be used for
extracorporeal treatment of blood, and by means of which the
concentration of two ionic substances can be adjusted separately,
in particular sodium and potassium (or calcium, or magnesium).
[0009] According to the invention, this object is achieved by means
of a method for preparing a medical liquid from a liquid, such as
water, and two concentrated solutions, comprising the following
steps:
[0010] circulating the liquid in a conduit, at a flowrate Q0;
[0011] injecting into the conduit, at a flowrate Q1, a first
concentrated solution containing a first ionic substance A and a
second ionic substance B, the ionic substances A and B having,
respectively, in the first concentrated solution, a concentration
[Asol] and a first concentration [B1sol];
[0012] injecting into the conduit, at a flowrate Q2, a second
concentrated solution containing the first ionic substance A and
the second ionic substance B, the first ionic substance A having,
in the second concentrated solution, the same concentration [Asol]
as in the first concentrated solution, and the second ionic
substance B having, in the second concentrated solution, a second
concentration [B2sol] different than the first concentration
[B1sol] in the first concentrated solution;
[0013] regulating the injection flowrate Q1 and the injection
flowrate Q2 of the first and second concentrated solutions in such
a way that at any given time the diluted solution resulting from
the mixing of the liquid and the concentrated solutions has a
desired concentration [Ades] of first substance A and a desired
concentration [Bdes] of second substance B.
[0014] According to one characteristic of the invention, the
injection flowrate Q1 and the injection flowrate Q2 of the
concentrated solutions A and B are varied over the course of time
in such a way that the concentration of the second substance B in
the diluted solution varies over the course of time in accordance
with a predetermined profile. According to another characteristic
of the invention, the flowrate Q0 of the liquid in the conduit is
constant, and the sum of the injection flowrates Q1+Q2 of the
concentrated solutions A and B is maintained constant in such a way
that the concentration of the first substance A in the diluted
solution remains substantially constant.
[0015] According to yet another characteristic of the invention,
the injection flowrate Q1 and the injection flowrate Q2 of the
concentrated solutions A and B are varied over the course of time
in such a way that the concentration of the first substance A in
the diluted solution varies over the course of time in accordance
with a predetermined profile.
[0016] The invention also relates to a device for preparing a
treatment liquid from a liquid, such as water, and two concentrated
solutions, comprising:
[0017] a conduit with a first end intended to be connected to a
source of liquid, such as water, and a second end for delivering a
treatment liquid;
[0018] first injection means for injecting into the conduit, at a
flowrate Q1, a first concentrated solution containing a first ionic
substance A and a second ionic substance B, the ionic substances A
and B having, respectively, in the first concentrated solution, a
concentration [Asol] and a first concentration [B1sol];
[0019] second injection means for injecting into the conduit, at a
flowrate Q2, a second concentrated solution containing the first
ionic substance A and the second ionic substance B, the first ionic
substance A having, in the second concentrated solution, the same
concentration [Asol] as in the first concentrated solution, and the
second ionic substance B having, in the second concentrated
solution, a second concentration [B2sol] different than the first
concentration [B1sol] in the first concentrated solution;
[0020] regulating means for regulating the first and second
injection means and for adjusting the injection flowrate Q1 and the
injection flowrate Q2 of the first and second concentrated
solutions in such a way that at any given time the diluted solution
resulting from the mixing of the liquid and the concentrated
solutions has a desired concentration [Ades] of first substance A
and a desired concentration [Bdes] of second substance B.
[0021] In one embodiment of the invention, the device for preparing
treatment liquid is incorporated in a hemodialysis system, the
substance A is sodium and the substance B is potassium, calcium, or
magnesium. As the sodium concentration in a dialysis liquid is much
higher than the potassium (calcium or magnesium) concentration, the
potassium concentration can be very precisely regulated by
measuring the conductivity of the mixture forming in the conduit
immediately downstream of the site of injection of the first
concentrated solution into the conduit, and of the mixture forming
in the conduit immediately downstream of the site of injection of
the second concentrated solution into the conduit (there is an
excellent correlation between the conductivity of a solution and
its sodium concentration).
[0022] Moreover, there is no danger of influencing the plasma
potassium or calcium concentration of a patient using a very dilute
dialysis solution prepared and administered by a system equipped
with reliable means for measuring concentrations, which would not
be the case if this objective were achieved by injection of more
concentrated solution.
[0023] The invention also relates to a kit of solutions for
extracorporeal treatment of blood, comprising two concentrated
solutions and a bag with two compartments intended to contain each
of the solutions from the kit. Each of the solutions contains at
least two ionic substances A and B, the ionic substance A having
the same concentration in the two solutions and the ionic substance
B having different concentrations in two solutions.
[0024] According to one characteristic of the invention, the two
solutions are identical except for one ionic substance whose
concentration differs from one solution to the other.
[0025] Other characteristics and advantages of the invention will
become more apparent on reading the following description.
Reference will be made to the attached drawings, in which:
[0026] FIG. 1 is a diagram showing a device for treatment of
blood;
[0027] FIG. 2 shows a bag with two compartments for containing the
two concentrated solutions from a treatment kit; and
[0028] FIG. 3 is a graph showing several profiles of variation in
the potassium concentration of a dialysis liquid.
[0029] The hemodialysis system shown in FIG. 1 comprises a
hemodialyzer 1 with two compartments 2, 3 separated by a
semipermeable membrane 4. A first compartment 2 has an inlet
connected to a blood withdrawal conduit 5 on which a circulation
pump 6 is arranged, and an outlet connected to a blood return
conduit 7 on which a bubble trap 8 is interposed.
[0030] An infusion device comprising a pump 10 and a balance 11 is
provided for injecting into the bubble trap 8 the contents of a bag
9 of infusion liquid containing sodium bicarbonate. The bag 9 is
suspended from the balance 11 and it is connected to the bubble
trap 8 via a conduit 12 on which the infusion pump 10 is arranged.
The balance 11 serves to control the pump 10 so that the flowrate
of the infusion liquid is equal to a reference flowrate.
[0031] The second compartment 3 of the hemodialyzer 1 has an inlet
connected to a conduit 12 for supply of fresh dialysis liquid, and
an outlet connected to a conduit 13 for removal of spent liquid
(dialysis liquid and ultrafiltrate).
[0032] The supply conduit 12 connects the hemodialyzer 1 to a
device 14 for preparing dialysis liquid, comprising a main conduit
15 whose upstream end is intended to be connected to a source of
running water. First and second subsidiary channels 16, 17 are
connected to this main conduit 15.
[0033] According to the invention, the free end of the first
subsidiary conduit 16 is intended to be immersed in a container 18
for a first concentrated saline solution containing sodium
chloride, calcium chloride, magnesium chloride and potassium
chloride. This first conduit 16 is equipped with a pump 19 for
metering the first concentrated solution into the dialysis liquid,
which is controlled as a function of the comparison between 1) a
first reference value of conductivity for the solution forming at
the junction of the main conduit 15 and the first subsidiary
conduit 16, and 2) the value of the conductivity of this solution
measured by means of a first conductivity probe 20 arranged on the
main conduit 15 immediately downstream of the junction between the
main conduit 15 and the first subsidiary conduit 16.
[0034] According to the invention, the free end of the second
subsidiary conduit 17 is intended to be immersed in a container 21
for a second concentrated saline solution containing sodium
chloride, calcium chloride, magnesium chloride and potassium
chloride. This second solution contains the same ionic substances
as the first solution and in the same concentrations, except for
potassium whose concentration is different. The second conduit 17
is equipped with a pump 22 for metering the second concentrated
solution into the dialysis liquid, which is controlled as a
function of the comparison between 1) a second reference value of
conductivity for the solution forming at the junction of the main
conduit 15 and the second subsidiary conduit 17, and 2) the value
of the conductivity of this solution measured by means of a second
conductivity probe 23 arranged on the main conduit 15 immediately
downstream of the junction between the main conduit 15 and the
second subsidiary conduit 17.
[0035] The conduit 12 for supply of dialysis liquid forms the
continuation of the main conduit 15 of the device 14 for
preparation of dialysis liquid. Arranged on this supply conduit 12,
in the direction of circulation of the liquid, are a first
flowmeter 24 and a first circulation pump 25.
[0036] The downstream end of the conduit 13 for removal of spent
liquid is intended to be connected to the drain. Arranged on this
conduit, in the direction of circulation of the liquid, are a probe
26 for measuring the potassium concentration, a second circulation
pump 27, and a second flowmeter 28. An extraction pump 29 is
connected to the removal conduit 13 upstream of the second
circulation pump 27.
[0037] The hemodialysis system represented in FIG. 1 also comprises
a calculation and control unit 30. This unit is connected to a
screen 31 and to a keyboard 32 via which the user inputs various
reference values: flowrate reference values (blood flowrate Qb,
dialysis liquid flowrate Qd, infusion solution flowrate Qinf),
reference values for concentration of ionic substances in the
dialysis liquid, reference value for the duration of treatment T,
reference value for loss of weight WL. Moreover, the calculation
and control unit 30 receives information emitted by the measurement
elements of the system, such as the flowmeters 24, 28, the
conductivity probes 20, 23, and the probe 26 for measuring
potassium concentration. As a function of the instructions received
and of programmed operating modes and algorithms, it controls the
drive elements of the system, such as the pumps 6, 10, 19, 22, 25,
27, 29.
[0038] According to the invention, the concentration of sodium and
the concentration of potassium in the dialysis liquid can be
adjusted independently of one another: for a constant flowrate Q0
of water, the concentration of sodium depends on the sum of the
flowrate Q1 of the first concentrated solution injected via the
pump 19 into the main conduit 15 and the flowrate Q2 of the second
concentrated solution injected via the pump 22 into the main
conduit 15, while the concentration of potassium depends on the
ratio of the flowrates Q1, Q2 of the first and second concentrated
solutions. The concentration of sodium and of potassium in the
dialysis liquid is chosen as a function of each individual patient.
It can be set at a fixed value. According to the invention, for
patients with hyperkalemia, the potassium concentration of the
dialysis liquid is modified continuously during the treatment
session according to a predetermined profile of variation.
EXAMPLE
[0039] The hemodialysis system described above is equipped with a
bag 50 made of flexible transparent plastic, as is represented in
FIG. 2, and comprising two compartments 51 and 52 corresponding
respectively to the containers 18 and 21 in FIG. 1. The bag 50 is
provided in its upper part with eyelets 53 by which it can be
suspended vertically from a suitable support. Each compartment 51,
52 is equipped at its base with an access tube 54, 55 provided at
its end with a connection element 56, 57 intended to cooperate with
a complementary connection element fixed to the end of the
subsidiary conduits 16, 17 of the device 14 for preparation of
dialysis liquid. A clip 58, 59 is arranged on each of the tubes 54,
55.
[0040] The compartment 51 (container 18) contains the following
substances, in the following concentrations: [0041] NaCl: 284.31
g/l [0042] KCl: 19.57 g/l [0043] CaCl2: 10.29 g/l [0044] MgCl2:
2.63 g/l [0045] Anhydrous glucose: 35 g/l.
[0046] The compartment 52 (container 21) contains the following
substances, in the following concentrations: [0047] NaCl: 284.31
g/l [0048] KCl: 0 g/l [0049] CaCl2: 10.29 g/l [0050] MgCl2: 2.63
g/l [0051] Anhydrous glucose: 35 g/l.
[0052] By means of these two solutions it is possible, according to
the invention, to prepare a dialysis liquid having a sodium
concentration of between approximately 130 mEq/l and approximately
155 mEq/l, and a potassium concentration varying, during a
treatment session, from between an initial value of approximately
2.5 mEq/l and approximately 5.5 mEq/l and a final value of between
approximately 1 mEq/l and approximately 2 mEq/l.
[0053] FIG. 3 shows four profiles of variation of the potassium
concentration of a dialysis liquid, which profiles can be obtained
using the device 14 for preparation of dialysis liquid connected to
the bag 50 with two compartments containing the concentrated
solutions which have just been described. In this figure, the
broken line shows the constant potassium concentration of a
conventional dialysis liquid, that is to say 2 mEq/l.
[0054] The hemodialysis apparatus which has just been described
functions in the following manner.
[0055] An operator inputs to the control unit 30, via the keyboard
32, conventional reference values corresponding to the various
parameters of treatment (prescription), namely the blood flowrate
Qb, the dialysis liquid flowrate Qd, the infusion flowrate Qinf of
the bicarbonate solution, the total weight loss WL (quantity of
plasma water to be withdrawn from patient by ultrafiltration), the
total duration T of the session, and the sodium concentration of
the dialysis liquid.
[0056] According to the invention, the operator also inputs, to the
control unit, an information item or a series of information items
concerning the potassium concentration of the dialysis liquid,
which can be either a fixed reference value or one of the variation
profiles stored beforehand in the control unit, corresponding for
example to one of the graphs in FIG. 3. The operator can also
create and store a profile appropriate to an individual client.
[0057] According to an alternative embodiment of the invention, the
potassium concentration of the dialysis liquid is adjusted via the
control unit 30 in the following manner: a dialysis liquid having a
potassium concentration corresponding to a predetermined reference
value is initially circulated in the hemodialyzer 1, and this
reference value is compared with the value of the potassium
concentration in the spent liquid, measured by the probe 26. The
control unit 30 subsequently controls the pumps 19, 22 of the
device 14 for preparation of treatment liquid in such a way that
the difference between the reference value and the measured value
remains substantially equal to a given value, corresponding to a
difference, acceptable for the patient, between the potassium
concentration of the plasma and that of the dialysis liquid.
[0058] After a kit of concentrated solutions, such as the bag
described above, has been connected to the conduits 16, 17 of the
device 14 for preparation of dialysis liquid, the dialysis liquid
circuit is filled with dialysis liquid. To do this, the main
conduit 15 is connected to a source of running water and the pumps
19, 22, 25, 27 are started up. The pumps 19 and 22 are regulated
via the control unit 30 in such a way that the potassium
concentration and the sodium concentration of the dialysis liquid
are equal to the corresponding reference values. The pumps 25, 27
for circulating dialysis liquid are regulated via the control unit
30 in such a way that the flowrate of the pump 25 situated upstream
of the hemodialyzer 1 is equal to the reference flowrate Qd (500
ml/min, for example) and so that the flowrate of the pump 27
situated downstream of the hemodialyzer 1 is such that the
flowrates measured by the flowmeters 24, 28 are equal.
[0059] At the same time as the dialysis liquid circuit is filling
with the dialysis liquid according to the prescription, the circuit
for extracorporeal blood circulation is rinsed and filled with
sterile physiological liquid.
[0060] When priming of the dialysis liquid circuit and of the blood
circuit is completed, the blood circuit is connected to the patient
and the treatment proper can commence: the pumps 19, 22 of the
device 14 for preparation of dialysis liquid, and the pumps 25, 27
for circulating the dialysis liquid, continue functioning, while
the blood pump 6, the extraction pump 29 and the infusion pump 10
are started up. The blood pump 6 is set at the reference flowrate
Qb (for example 200 ml/mn), the infusion pump 10 is set at the
reference flowrate Qinf, and the extraction pump 29 is set at a
flowrate QUF calculated by the control unit 30 on the basis of the
reference values for total weight loss WL, infusion flowrate Qinf
and total duration of treatment T.
[0061] The invention which has just been described is open to
variants.
[0062] In the same way as the potassium concentation, the calcium
or magnesium concentration can be adjusted to the needs of each
individual patient.
[0063] With the preparation device according to the invention, it
is possible to simultaneously adjust the potassium concentration of
a dialysis liquid according to a first defined variation profile
and the sodium concentration of the same dialysis liquid according
to a second defined variation profile.
[0064] A probe for measuring the potassium concentration can be
mounted on the supply conduit 12 in order to provide a measured
value of the potassium concentration which will be used, for
example, to calculate the difference between this value and the
value measured downstream of the hemodialyzer 1 by the probe
26.
* * * * *