DESCRIPTION
Technical Field
[0001] The present invention relates to a dialysis agent-filled body that
is used to prepare an artificial perfusion fluid for hemodialysis.
Background Art
[0002] Hemodialysis therapy (hereinafter referred to as “hemodialysis”),
which is also called artificial dialysis therapy, is a method of purifying
blood that is most commonly used for patients with chronic renal failure
and the like. In hemodialysis, in order to avoid uremia, waste products
in the blood are removed, and also the concentration of serum
electrolytes and water content are maintained.
[0003] Hemodialysis is performed on a single patient for 3 to 4 hours,
and the amount of dialysis perfusion fluid that is needed is as large as
100 liters to 300 liters, for example, per dose per patient. Also, it has
been pointed out that bacteria are likely to grow in such perfusion fluids,
and long-term storage of a perfusion fluid has been considered difficult.
Therefore, in actual dialysis facilities, it is a common practice to prepare
a desired artificial perfusion fluid by dissolving a powdered hemodialysis
agent in dialysis water immediately before dialysis.
[0004] As this artificial perfusion fluid, dialysis fluids in which acetic
acid is used as an ingredient serving as an alkaline agent have been
widely used, but in recent years are coming to be replaced by dialysis
fluids using bicarbonate (sodium bicarbonate) in order to significantly
reduce unpleasant conditions during dialysis.
[0005] Furthermore, recently, acetate-free dialysis agents that do not
use acetate are coming into use because acetate has a vasodilatory effect
3
and a cardiac function inhibitory effect. Known examples thereof
include techniques in which the mixing ratio or pH of citric acids that
are ingredients are set to predetermined ranges (Patent Documents 1
and 2).
[0006] However, it has been pointed out that bicarbonate ions forming
the sodium hydrogen carbonate react with calcium ions and magnesium
that are other ingredients of the hemodialysis agent and generate
insoluble compounds (metal carbonate) such as calcium carbonate or
magnesium carbonate. Accordingly, a conventional hemodialysis agent
is divided into an agent A containing ingredients other than sodium
hydrogen carbonate and an agent B containing sodium hydrogen
carbonate, which are respectively contained in different containers.
[0007] Furthermore, it has also been pointed out that a filled body in
which a container is filled with such an agent A for hemodialysis
generates hydrogen chloride gas when citric acid is brought into contact
with a chloride salt (e.g., sodium chloride), and, for example, a technique
is also known in which sodium chloride is taken as a core particle and is
coated by another chloride (Patent Document 3).
[0008] Meanwhile, the number of patients who need such hemodialysis
is considered to continuously increase on a worldwide scale also in the
future. Accordingly, in order to increase the versatility of such a
hemodialysis agent-filled body on a worldwide scale, it is necessary to
increase the production efficiency. Furthermore, in order to allow the
filled body to be stored for a long period of time, it is necessary to avoid
decomposition of ingredients and generation of by-products.
Furthermore, it is also required for such a hemodialysis agent-filled body
to have superior handleability because the artificial perfusion fluid is
prepared therefrom in dialysis facilities.
4
Prior Art Documents
Patent Documents
[0009] Patent Document 1: Japanese Patent Laid-Open publication No.
2003-104869
Patent Document 2: Japanese Patent Laid-Open publication No.
2008-246209
Patent Document 3: WO 2005/094918
Summary of Invention
Problem to be Solved by Invention
[0010] The present invention solves the above-described problems, and it
is an object thereof to provide a dialysis agent-filled body having
superior handleability in response to a future increase in the number of
hemodialysis patients on a worldwide scale and demand for hemodialysis
agents associated therewith.
Means for Solving the Problem
[0011] The present invention provides a dialysis agent A-filled body for
preparing an artificial perfusion fluid for bicarbonate hemodialysis,
comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the citric acid ingredient and the plurality of electrolyte
ingredients are isolated from each other by the container filled with the
agent A.
[0012] In one embodiment, the container filled with the agent A is
configured by a container (A-1) that contains the citric acid ingredient
and a container (A-2) that contains the plurality of electrolyte
5
ingredients.
[0013] In a further embodiment, an electrolyte having a greatest content
among the plurality of electrolyte ingredients is located closest to an
opening slit provided in the container (A-2).
[0014] In a still further embodiment, the electrolyte having the greatest
content is a sodium salt.
[0015] In one embodiment, the citric acid ingredient is a citric acid
anhydride.
[0016] The present invention also provides a dialysis agent-filled body
for preparing an artificial perfusion fluid for hemodialysis, comprising:
the above dialysis agent A-filled body; and
a dialysis agent B-filled body including an agent B containing
bicarbonate, and a container filled with the agent B.
[0017] The present invention also provides a dialysis agent A-filled body
for preparing an artificial perfusion fluid for bicarbonate hemodialysis,
comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the citric acid ingredient is a citric acid anhydride.
[0018] In one embodiment, the citric acid ingredient and the plurality of
electrolyte ingredients are isolated from each other by the container
filled with the agent A.
[0019] In a futher embodiment, the container filled with the agent A is
configured by a container (A-1) that contains the citric acid ingredient
and a container (A-2) that contains the plurality of electrolyte
ingredients.
[0020] In a still further embodiment, an electrolyte having a greatest
content among the plurality of electrolyte ingredients is located closest to
an opening slit provided in the container (A-2).
6
[0021] In another embodiment, the electrolyte having the greatest
content is a sodium salt.
[0022] The present invention also provides a dialysis agent-filled body
for preparing an artificial perfusion fluid for hemodialysis, comprising:
the above dialysis agent A-filled body; and
a dialysis agent B-filled body including an agent B containing
bicarbonate, and a container filled with the agent B.
[0023] The present invention also provides a dialysis agent A-filled body
for preparing an artificial perfusion fluid for bicarbonate hemodialysis,
comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the container filled with the agent A is configured by a
container (A-1) that contains the citric acid ingredient and a container
(A-2) that contains the plurality of electrolyte ingredients, and
an electrolyte having a greatest content among the plurality of
electrolyte ingredients is located closest to an opening slit provided in
the container (A-2).
[0024] In one embodiment, the electrolyte having the greatest content is
a sodium salt.
[0025] In one embodiment, the citric acid ingredient is a citric acid
anhydride.
[0026] The present invention also provides a dialysis agent-filled body
for preparing an artificial perfusion fluid for hemodialysis, comprising:
the above dialysis agent A-filled body; and
a dialysis agent B-filled body including an agent B containing
bicarbonate, and a container filled with the agent B.
Effects of Invention
7
[0027] According to the present invention, a hemodialysis agent-filled
body can be produced more easily than in conventional examples. In
the hemodialysis agent-filled body of the present invention, not only a
deterioration in its ingredients due to long-term storage but also
generation of harmful substances during storage can be suppressed. In
the hemodialysis agent-filled body of the present invention, even if some
of the ingredients fall out of the filled body during preparation of an
artificial perfusion fluid, the concentration of the ingredients after the
preparation are not likely to significantly change in the artificial
perfusion fluid. Accordingly, the handleability in dialysis facilities
becomes superior. Thus, it is possible to provide a hemodialysis
agent-filled body that can sufficiently cope with a future increase in the
number of hemodialysis patients on a worldwide scale and demand for
hemodialysis agents associated therewith.
Brief Description of Drawings
[0028] Fig. 1 is a diagram schematically showing an example of a
dialysis agent-filled body of the present invention.
Fig. 2 is a schematic diagram illustrating an example of a dialysis
agent A-filled body constituting the dialysis agent-filled body of the
present invention.
Fig. 3 is a schematic diagram illustrating an example of a
container (A-1) constituting the dialysis agent A-filled body, wherein Fig.
3(a) is a front view of the container (A-1), and Fig. 3(b) is a vertical
cross-sectional view of the container (A-1).
Fig. 4 is a schematic diagram illustrating an example of a
container (A-2) constituting the dialysis agent A-filled body, wherein Fig.
4(a) is a front view of the container (A-2), and Fig. 4(b) is a vertical
8
cross-sectional view of the container (A-2).
Fig. 5 is a schematic diagram illustrating other examples of the
dialysis agent A-filled body constituting the dialysis agent-filled body of
the present invention, showing front views and vertical cross-sectional
views of the container (A-2) of the dialysis agent A-filled body.
Fig. 6 is a schematic diagram illustrating other examples of the
dialysis agent A-filled body constituting the dialysis agent-filled body of
the present invention, wherein Fig. 6(a) is a diagram showing the
dialysis agent A-filled body in which the container (A-1) and the
container (A-2) are secured to each other at some of their upper ends,
and Fig. 6(b) is a diagram showing the dialysis agent A-filled body in
which the container (A-1) and the container (A-2) are molded into one
piece such that they are aligned with each other at their upper sides and
are arranged side by side.
Fig. 7 is a schematic diagram illustrating an example of the
dialysis agent B-filled body shown in Fig. 1, wherein Fig 7(a) is a front
view of the filled body, and Fig. 7(b) is a vertical cross-sectional view of
the filled body.
Mode for Carrying Out the Invention
[0029] Hereinafter, the present invention will be described in detail.
[0030] Dialysis Agent-Filled Body
Fig. 1 is a diagram schematically showing an example of a
dialysis agent-filled body of the present invention.
[0031] The dialysis agent-filled body of the present invention is a group
of a plurality of containers (filled bodies) that are filled with a
hemodialysis agent for preparing an artificial perfusion fluid for
hemodialysis. A dialysis agent-filled body 100 shown in Fig. 1 includes
a dialysis agent A-filled body 110 and a dialysis agent B-filled body 180.
9
[0032] In a first embodiment of the present invention, the dialysis agent
A-filled body 110 mainly contains an agent A (i.e., a citric acid ingredient
and a plurality of electrolyte ingredients) necessary to prepare, for
example, an artificial perfusion fluid for bicarbonate hemodialysis from
among artificial perfusion fluids, and the dialysis agent B-filled body 180
mainly contains an agent B (i.e., bicarbonate) necessary to prepare an
artificial perfusion fluid for dialysis. Display sections 112 and 182 of
the filled bodies 110 and 180 display remarks such as the type of
ingredient contained in each filled body, the contents, and the usage
method, descriptions as defined by laws and ordinances, and the like,
according to the country and situation.
[0033] The dialysis agent A-filled body 110 includes, for example, an
exterior member 111 made of a resin molded body (e.g., the filled body
has a structure in the shape of a bag or obtained by heat-sealing four
sides thereof). Examples of the resin molded body include those made of
films of thermoplastic resins such as polyethylene (PE) or polyethylene
terephthalate (PET), aluminum-metallized plastic films (e.g., VM-PET),
and aluminum pouches, and layered bodies thereof. There is no
particular limitation on the size of the exterior member 111 constituting
the dialysis agent A-filled body 110, and the size can be freely designed
by those skilled in the art such that the exterior member 111 can be
properly filled with an agent A-filled container (described later) or
ingredients.
[0034] The dialysis agent B-filled body 180 includes, for example, an
exterior member (container) 181 made of a resin molded body (e.g., the
filled body has a structure in the shape of a bag or obtained by
heat-sealing four sides thereof). The resin molded body may be the
same resin molded body as that of the dialysis agent A-filled body 110,
but examples thereof include those made of films of thermoplastic resins
10
such as polyethylene (PE) or polyethylene terephthalate (PET), and
layered bodies thereof. There is no particular limitation on the size of
the exterior member 181 constituting the dialysis agent B-filled body 180,
and the size can be freely designed by those skilled in the art such that
the exterior member 181 can be properly filled with bicarbonate
(described later) and the like.
[0035] Dialysis Agent A-Filled Body
As described above, the dialysis agent A-filled body contains a
citric acid ingredient and a plurality of electrolyte ingredients as the
agent A. All of the citric acid ingredient and the plurality of electrolyte
ingredients are preferably in the form of powders. In the first
embodiment of the present invention, the dialysis agent A-filled body
includes an agent A-filled container, and the citric acid ingredient and
the plurality of electrolyte ingredients are isolated from each other by
the agent A-filled container. The agent A-filled container can store the
citric acid ingredient and the plurality of electrolyte ingredients
separately such that they are not mixed with or brought into contact
with each other by dividing (separating) them. In the present invention,
such isolation of the citric acid ingredient and the plurality of electrolyte
ingredients from each other using the agent A-filled container can be
realized, for example, by causing at least two containers, preferably in
two containers (A-1) and (A-2), to be separately filled with these
ingredients, or by dividing the interior portion of the exterior member
111 constituting the dialysis agent A-filled body 110 shown in Fig. 1 by
means of heat-sealing or the like into at least two, preferably two
sections, and causing these sections to be separately filled with these
ingredients.
[0036] Examples of the citric acid ingredient include citric acid that may
11
be any of a hydrate, an anhydride, and a combination thereof.
Furthermore, as the citric acid ingredient, citrate (e.g., sodium citrate,
etc.) other than chloride salts may also be contained in the citric acid.
[0037] Examples of the plurality of electrolyte ingredients include
chloride salts (e.g., sodium chloride, magnesium chloride, potassium
chloride, calcium chloride, combinations thereof, etc.) other than citric
acid. Furthermore, as the plurality of electrolyte ingredients, citrate
such as sodium citrate may also be contained.
[0038] Fig. 2 is a schematic diagram illustrating an example of the
dialysis agent A-filled body constituting the dialysis agent-filled body of
the present invention.
[0039] As shown in Fig. 2, the dialysis agent A-filled body 110 includes
an agent A-filled container 125 constituted by a container (A-1) 122 and
a container (A-2) 124. In Fig. 2, the container (A-1) 122 contains a citric
acid ingredient that can be used to prepare an artificial perfusion fluid
for hemodialysis. The container (A-2) 124 contains a plurality of
electrolyte ingredients that can be used to prepare the artificial
perfusion fluid. In the present invention, such a combination between
the containers (A-1) 122 and (A-2) 124 and the citric acid ingredient and
the electrolyte ingredients is merely an example, and, for example, the
container (A-1) 122 may contain the plurality of electrolyte ingredients
and the container (A-2) 124 may contain the citric acid ingredient.
[0040] Display sections 126 and 128 of the container (A-1) 122 and the
container (A-2) 124 display the type of ingredient contained in each
container, the content, and descriptions as defined by laws and
ordinances according to the country.
[0041] Ingredients of Dialysis Agent A-Filled Body
In the present invention, examples of the citric acid ingredient
12
contained in the dialysis agent A-filled body include citric acid hydrates
and citric acid anhydrides. In the embodiment of the present invention,
the citric acid ingredient may be contained in, for example, the container
(A-1), but the container (A-1) may contain some of the later-described
electrolyte ingredients (e.g., some of the amount of sodium citrate used)
together with the citric acid ingredient. In this case, a citric acid
anhydride is preferably used as the citric acid ingredient.
[0042] In a second embodiment of the present invention, the dialysis
agent A-filled body may be configured such that the citric acid ingredient
and the electrolyte ingredients are combined in one agent A-filled
container, without causing the agent A-filled container to isolate the
citric acid ingredient and the plurality of electrolyte ingredients from
each other (e.g., without dividing the interior portion with the
above-described containers (A-1) and (A-2)). In the case where the citric
acid ingredient and the plurality of electrolyte ingredients are combined
in one agent A-filled container, for example, the exterior member 111 of
the dialysis agent A-filled body 110 as shown in Fig. 1 may be used as it
is as the agent A-filled container. Note that, in this case, in order to
suppress generation of hydrogen chloride through a reaction with
chloride contained in the electrolyte ingredients, a citric acid anhydride
is used as the citric acid ingredient.
[0043] In the present invention, there is no particular limitation on the
content of the citric acid ingredient contained in the dialysis agent
A-filled body because it varies depending on the contents of the
above-described electrolyte ingredients used, a desired concentration of
the artificial perfusion fluid to be prepared, and the like, but the content
may be set by those skilled in the art, for example, to a content that
gives 1.5 to 5 mEq/L and preferably 2 to 3 mEq/L with respect to the
content of citric acid ions in the artificial perfusion fluid that is prepared.
13
When the citric acid ingredient has such a content, the artificial
perfusion fluid can be prepared, for example, so as to have a pH of 7 to
8.5 and preferably 7.5 to 8.
[0044] Furthermore, when preparing an artificial perfusion fluid
concentrate, for example, the content is set to a content that gives 35 to
45 times the concentration of the artificial perfusion fluid according to
the situation.
[0045] In the present invention, the plurality of electrolyte ingredients
contained in the dialysis agent A-filled body are electrolytes that may be
commonly used in preparation of an artificial perfusion fluid for
hemodialysis. Examples of such electrolytes include sodium chloride,
potassium chloride, calcium chloride (e.g., calcium chloride hydrate),
magnesium chloride (e.g., magnesium chloride hydrate), and sodium
citrate (e.g., sodium citrate hydrate).
[0046] There is no particular limitation on the contents of the plurality
of electrolytes because they vary depending on the content of the
above-described citric acid ingredient used, desired concentrations of the
artificial perfusion fluid to be prepared, the amount of the artificial
perfusion fluid to be prepared, and the like, and the contents may be
freely set by those skilled in the art. Note that, in the present invention,
sodium chloride preferably has the greatest content among those of the
plurality of electrolytes when compared with the other electrolytes (i.e.,
potassium chloride, calcium chloride, and magnesium chloride). The
reason for this is that the contents of the electrolytes are set to match
the concentration of electrolytes in the blood.
[0047] In the present invention, there is no particular limitation on the
content of sodium chloride that may be contained in the dialysis agent
A-filled body because it varies depending on the content of the citric acid
ingredient used, the contents of other electrolyte ingredients, a desired
14
concentration of the artificial perfusion fluid to be prepared, and the like,
but the content may be set by those skilled in the art, for example, to a
content that gives, for example, 75 to 150 mEq/L and preferably 80 to
145 mEq/L with respect to the content of sodium ions in the artificial
perfusion fluid that is prepared.
[0048] The dialysis agent A-filled body may further contain ingredients
other than the above-described citric acid ingredient and electrolyte
ingredients. Examples of other ingredients include a pH adjuster. An
example of the pH adjuster is an organic acid. Examples of the organic
acid include citric acid, oxalic acid, tartaric acid, maleic acid, ascorbic
acid, oxaloacetic acid, gluconic acid, isocitric acid, malic acid, and
pyruvic acid, and combinations thereof. The amount of such other
ingredients in the above-described dialysis agent A-filled body may be
selected as appropriate by those skilled in the art to a proper amount as
long as the amount does not inhibit the function of the dialysis agent A
achieved by the citric acid ingredient and the plurality of electrolyte
ingredients.
[0049] Form of Dialysis Agent A-Filled Body
Fig. 3 is a schematic diagram illustrating an example of the
container (A-1) constituting the dialysis agent A-filled body, wherein Fig.
3(a) is a front view of the container (A-1), and Fig. 3(b) is a vertical
cross-sectional view of the container (A-1).
[0050] The container (A-1) 122 has a structure, for example, in the shape
of a bag or obtained by heat-sealing four sides thereof. Examples of the
materials of which the container (A-1) can be made include films of
thermoplastic resins such as polyethylene (PE) or polyethylene
terephthalate (PET), and aluminum-metallized plastic films (e.g.,
VM-PET), and layered bodies thereof. There is no particular limitation
15
on the size of the container (A-1) 122, and the size can be freely designed
by those skilled in the art such that the container (A-1) 122 can be
properly filled with ingredients.
[0051] When the above-described citric acid ingredient is contained in
the container (A-1) 122, it is preferable that, as shown in Fig. 3(b), the
container (A-1) 122 is filled with a predetermined amount of a citric acid
ingredient layer 142 to a point near an opening slit 132 provided in the
container (A-1) 122. In other words, the interior portion of the
container (A-1) 122 is preferably designed to have a size that allows a
slight space portion 144 to be provided near the opening slit 132 in the
arrangement as shown in Fig. 3(b) (the arrangement in which the
display section 126 faces the front as shown in Fig. 3(a)) even when the
container (A-1) 122 is filled with the citric acid ingredient layer 142. In
this case, the space portion 144 has a reduced spatial volume, or is filled
with inert gas such as nitrogen gas as necessary. In the present
invention, since the space portion 144 is provided inside the container
(A-1) 122 (i.e., the container (A-1) 122 is not completely filled with the
citric acid ingredient layer 142), it is possible to reduce the possibility
that the citric acid ingredient layer 142 that is an ingredient is
accidentally dispersed out of the container (A-1) 122 when a person tears
the opening slit 132 with his or her hands.
[0052] Fig. 4 is a schematic diagram illustrating an example of the
container (A-2) constituting the dialysis agent A-filled body, wherein Fig.
4(a) is a front view of the container (A-2), and Fig. 4(b) is a vertical
cross-sectional view of the container (A-2).
[0053] The container (A-2) 124 has a structure, for example, in the shape
of a bag or obtained by heat-sealing four sides thereof. Examples of the
materials of which the container (A-2) can be made include films of
thermoplastic resins such as polyethylene (PE) or polyethylene
16
terephthalate (PET), and aluminum-metallized plastic films (e.g.,
VM-PET), and layered bodies thereof. There is no particular limitation
on the size of the container (A-2) 124, and the size can be freely designed
by those skilled in the art such that the container (A-2) 124 can be
properly filled with ingredients.
[0054] When the above-described plurality of electrolyte ingredients are
contained in the container (A-2) 124, it is preferable that, as shown in
Fig. 4(b), the container (A-2) 124 is filled with a predetermined amount
of electrolyte ingredients (a sodium citrate layer 152, a potassium
chloride layer 154, a calcium chloride layer 156, a magnesium chloride
layer 158, and a sodium chloride layer 160) to a point near an opening
slit 134 provided in the container (A-2) 124. In other words, the interior
portion of the container (A-2) 124 is preferably designed to have a size
that allows a slight space portion 146 to be provided near the opening
slit 134 in the arrangement as shown in Fig. 4(b) (the arrangement in
which the display section 128 faces the front as shown in Fig. 4(a)) even
when the container (A-2) 124 is filled with the electrolyte ingredients.
In this case, the space portion 146 has a spatial volume that has been
reduced as much as possible, for example, by removing air therefrom, or
is filled with inert gas such as nitrogen gas as necessary. In the present
invention, since the space portion 146 is provided inside the container
(A-2) 124 (i.e., the container (A-2) 124 is not completely filled with the
electrolyte ingredients), it is possible to reduce the possibility that the
electrolyte ingredients that are ingredients are accidentally dispersed
out of the container (A-2) 124 when a person tears the opening slit 134
with his or her hands.
[0055] The layers of the electrolyte ingredients (the sodium citrate layer
152, the potassium chloride layer 154, the calcium chloride layer 156, the
magnesium chloride layer 158, and the sodium chloride layer 160) with
17
which the container (A-2) 124 is filled may be in the form in which the
ingredients are layered as shown in Fig. 4(b), or in which the ingredients
are substantially uniformly mixed in advance.
[0056] Furthermore, in the present invention, it is preferable that, as
shown in Fig. 4(b), the electrolyte having the greatest content among the
above-described plurality of electrolyte ingredients with which the
container (A-2) 124 is filled is located closest to the opening slit provided
in the container (A-2). The electrolyte having the greatest content is
preferably sodium chloride. Alternatively, the electrolyte having the
greatest content may be divided into two substantially equal portions
that are isolated from each other as an upper layer and a lower layer in
the container (A-2), so that the container (A-2) is filled with these layers
together with other ingredients sandwiched therebetween.
[0057] In the present invention, these methods for filling a container
such that the electrolyte having the greatest content is located as
described above or is divided into an upper layer and a lower layer that
are isolated from each other to sandwich other ingredients therebetween
may be applied not only to the case of filling the container (A-2) but also
to the case of filling the container (A-1) and the container B.
[0058] The dialysis agent-filled body of the present invention is opened
by various medical workers such as nurses in order to prepare an
artificial perfusion fluid for hemodialysis. Opening should always be
carried out carefully, but some of the ingredients may be accidentally
dispersed at the time of opening. In this case, for example, if the
above-described plurality of electrolyte ingredients are substantially
uniformly mixed, a minuscule or small amount of an electrolyte from
among the electrolytes forming the above-described plurality of
electrolyte ingredients is dispersed as well. Accordingly, if an artificial
perfusion fluid for hemodialysis is prepared from the filled body out of
18
which some of the ingredients were dispersed, the concentration of that
minuscule or small amount of electrolyte significantly changes in the
perfusion fluid.
[0059] On the other hand, if the electrolyte having the greatest content
(the sodium chloride layer 160) is located near the opening slit 134 as
shown in Fig. 4(b), even if some of the electrolyte ingredients are
scattered and lost at the time of opening, the lost material is
substantially only a part of the electrolyte having the greatest content.
As a result, in the prepared perfusion fluid, the concentrations of the
electrolytes other than the electrolyte having the greatest content do not
change, and a change in the concentration of the electrolyte having the
greatest content is substantially small (because it has the greatest
content from the beginning).
[0060] Such an advantage of the layered structure can be more clearly
described, for example, by way of the following simulation.
[0061] The types and amounts of the plurality of electrolyte ingredients
that are to be contained in the container (A-2) are, for example, sodium
citrate 14 g, potassium chloride 55 g, calcium chloride 81 g, magnesium
chloride 38 g, and sodium chloride 1830 g. In this example, the
electrolyte having the greatest content is sodium chloride (1830 g). If
such a plurality of electrolyte ingredients are layered in the container
(A-2) 124 in the order shown in Fig. 4(b), the sodium chloride layer 160
having the greatest content is located closest to the opening slit 134 of
the container (A-2) 124.
[0062] It is assumed that 30 g of electrolyte ingredients is scattered and
lost when the opening slit 134 is opened. Clearly, it is natural that all
of the lost 30 g is typically sodium chloride because the uppermost layer
located near the opening slit 134 of the container (A-2) is constituted by
sodium chloride. In this case, if the partially scattered ingredients of
19
the dialysis agent A-filled body are dissolved, as they are, in water to
prepare 10 liters of artificial perfusion fluid, the concentrations of the
ions forming the respective electrolytes in the artificial perfusion fluid
are as shown in Table 1 in comparison with the case without such
scattering.
[0063]
[Table 1]
Ion Concentration
（when an artificial
perfusion fluid is
prepared without
scattering electrolyte
ingredients）
Ion Concentration
（when a sodium
chloride layer is
located near the
opening slit 134 and
an artificial perfusion
fluid is prepared with
scattering 30g of
electrolyte ingredients）
Ion Concentration
（when a magnesium
chloride layer is located
near the opening slit 134
and an artificial
perfusion fluid is
prepared with scattering
30g of electrolyte
ingredients）
mmol/L mEq/L mmol/L mEq/L mmol/L mEq/L
Na+ 140.406 140 139.012 139 140.406 140
K+ 2.003 2.0 2.003 2.0 2.003 2.0
Ca2+ 1.496 3.0 1.496 3.0 1.496 3.0
Mg2+ 0.507 1.0 0.507 1.0 0.107 0.2 (80%
reduced)
Citrate ion 0.680 2.0 0.680 2.0 0.680 2.0
Cl- 111.014 111 109.620 110 110.213 110
[0064] It is seen from Table 1 that, if the electrolyte having the greatest
content (the sodium chloride layer 160) is located near the opening slit
134 in the container (A-2) 124 as shown in Fig. 4(b), even when an
amount as much as 30 g is scattered, the concentrations of the ions in
the artificial perfusion fluid prepared after the scattering are not
lowered to a level that the application to hemodialysis is inhibited,
although the sodium ion concentration and the chloride ion concentration
are slightly lowered.
[0065] On the other hand, if the electrolyte having the greatest content
(the magnesium chloride layer 158) is located near the opening slit 134
in the container (A-2) 124, when an amount as much as 30 g is scattered,
80% of the magnesium ion concentration is lost from among the
20
concentrations of the ions in the artificial perfusion fluid prepared after
the scattering, that is, the magnesium ion concentration is lowered to a
level that the application to hemodialysis is significantly inhibited.
[0066] Although Fig. 4(b) shows an example in which the plurality of
electrolytes contained in the container (A-2) are arranged in the order of
the sodium citrate layer 152, the potassium chloride layer 154, the
calcium chloride layer 156, the magnesium chloride layer 158, and then
the sodium chloride layer 160, from the bottom of the container such that
the sodium chloride layer 160 having the greatest content is located
closest to the opening slit 134, the present invention is not necessarily
limited to this layering order. That is to say, in the present invention,
as long as the electrolyte having the greatest content (e.g., the sodium
chloride layer 160) is located closest to the opening slit, there is no
particular limitation on the layering order of the layers of the other
electrolytes, and some or the entirety of the other electrolytes may be
substantially uniformly mixed, or the other electrolytes may be layered
in any order.
[0067] Although Fig. 4 shows an example in which the opening slit 134
is arranged in the form of a V-notch in a side of an upper portion of the
container (A-2) 124, the present invention is not necessarily limited to
this arrangement and form. The opening slit may be, for example,
merely a printed mark for guiding scissors or a cutter to cut therealong,
or may be, for example, in the following forms:
(1) as shown in shown in Fig. 5 in which an opening portion 162
that is a perforated opening mark or groove in a side of an upper portion
of the container (A-2) is provided so as not to reach the space portion 146
inside the container (A-2) (Figs. 5(a) and 5(b));
(2) in which an opening portion 164 that is a perforated opening
mark or groove in a side of an upper portion of the container (A-2) is
21
provided so as to reach the space portion 146 inside the container (A-2)
(Figs. 5(c) and 5(d)); or
(3) in which an opening portion 166 that is an opening mark or
groove is provided starting from an upper end of the container (A-2)
toward a side of an upper portion so as not to reach the space portion 146
inside the container (A-2) (Figs. 5(e) and 5(f)).
[0068] Furthermore, in the present invention, for example, as shown in
Figs. 6(a) and 6(b), the container (A-1) 122 and the container (A-2) 124
may be in one piece to form the dialysis agent A-filled body 110 (or the
agent A-filled container).
[0069] In Fig. 6(a), the container (A-1) 122 and the container (A-2) are
secured to each other, for example, by heat-sealing or an adhesive at a
portion of their upper ends 127, and the opening portion 166 is provided
commonly for the container (A-1) 122 and the container (A-2) 124 as an
opening slit from an upper end toward a side of an upper portion. With
this configuration, the container (A-1) 122 and the container (A-2) 124
can be opened simultaneously along the opening portion 166.
[0070] Meanwhile, in Fig. 6(b), the container (A-1) 122 and the container
(A-2) 124 are molded into one piece such that they are aligned with each
other at their upper sides from which the containers are to be opened.
Furthermore, a side of an upper portion of the container (A-1) 122 and a
side of an upper portion of the container (A-2) 124 are respectively
provided with V-notches 163 and 165. Furthermore, a perforated
opening portion 129 is provided as necessary between the container (A-1)
122 and the container (A-2) 124. With this configuration, the container
(A-1) 122 and the container (A-2) 124 can be opened in one motion from
either the V-notch 163 or 165. Furthermore, the container (A-1) 122
and the container (A-2) 124 can be isolated from each other as necessary
along the opening portion 129.
22
[0071] Dialysis Agent B-Filled Body
The dialysis agent B-filled body includes an agent B containing
bicarbonate, and a container filled with the agent B.
[0072] In the present invention, examples of the bicarbonate contained
in the dialysis agent B-filled body include sodium hydrogen carbonate.
[0073] Fig. 7 is a schematic diagram illustrating an example of the
dialysis agent B-filled body shown in Fig. 1, wherein Fig 7(a) is a front
view of the filled body, and Fig. 7(b) is a vertical cross-sectional view of
the filled body.
[0074] It is preferable that, as shown in Fig. 7(b), in the dialysis agent
B-filled body 180, the container (B) (exterior member) 181 is filled with a
bicarbonate layer 174 located at the bottom of the container (B) 181 and
a sodium chloride layer 172 located at a point near an opening slit 136.
In other words, the interior portion of the container (B) 181 is preferably
designed to have a size that allows a slight space portion 148 to be
provided near the opening slit 136 in the arrangement as shown in Fig.
7(b) (the arrangement in which the display section 182 faces the front as
shown in Fig. 7(a)) even when the container (B) 181 is filled with the
bicarbonate layer 174 and the sodium chloride layer 172. In this case,
the space portion 148 has a reduced spatial volume, or is filled with inert
gas such as nitrogen gas as necessary. In the present invention, since
the space portion 148 is provided inside the container (B) 181 (i.e., the
container (B) 181 is not completely filled with the bicarbonate layer 172
and the sodium chloride layer 174), it is possible to reduce the possibility
that an ingredient (mainly the bicarbonate layer 174) accidentally
scattered out of the container (B) 181 when a person tears the opening
slit 136 with his or her hands.
[0075] In the present invention, there is no particular limitation on the
23
content of the bicarbonate contained in the dialysis agent B-filled body
because it varies depending on the contents of the above-described citric
acid ingredient and electrolyte ingredients used, a desired concentration
of the artificial perfusion fluid to be prepared, the amount of the
artificial perfusion fluid to be prepared, and the like, but the content
may be set by those skilled in the art, for example, to a content that
gives 15 to 45 mEq/L and preferably 25 to 40 mEq/L in the artificial
perfusion fluid that is prepared.
[0076] Furthermore, if the sodium chloride layer 174 is provided in the
above-described configuration, the content thereof may be selected as
appropriate by those skilled in the art such that the total of this content
and the content of the sodium chloride that may be contained in the
dialysis agent A-filled body is an amount that satisfies the amount of
sodium chloride required for the dialysis agent-filled body of the present
invention.
[0077] Preparation of Artificial Perfusion Fluid for Hemodialysis
The dialysis agent-filled body of the present invention is stored,
for example, in a dark place away from high humidity until immediately
before use. When preparing an artificial perfusion fluid for dialysis, for
example, the ingredients of the dialysis agent A-filled body are added to
and dissolved in dialysis water whose endotoxin concentration is less
than a predetermined concentration, meanwhile, the ingredients of the
dialysis agent B-filled body are added to and dissolved in other dialysis
water. Subsequently, these solutions are diluted to reach
predetermined concentrations, and are mixed at a predetermined ratio,
so that an artificial perfusion fluid is prepared.
[0078] The prepared artificial perfusion fluid is carefully applied to a
dialysis patient at a dose that varies depending on the dialysis time but
24
may be 100 liters to 300 liters, for example, using a method known to
those skilled in the art.
Examples
[0079] Hereinafter, the present invention will be more specifically
described by means of examples. It is to be understood that the present
invention is not limited to the examples below.
[0080] Example 1: Production of Agent A-Filled Body Using Citric Acid
Anhydride
A resin bag obtained by layering a polyethylene terephthalate
film, an aluminum-metallized polyethylene terephthalate film, and a
polyethylene film (about 0.3 liters) was filled with layers respectively
constituted by 14 g of sodium citrate, 55 g of potassium chloride, 81 g of
calcium chloride, 38 g of magnesium chloride, and 39 g of citric acid
anhydride arranged in this order from the bottom, and the opening
portion was heat-sealed to obtain an agent A-filled body (1).
[0081] The obtained agent A-filled body (1) was allowed to stand for one
week under accelerated conditions at 40C and 75%RH. Subsequently,
the hydrogen chloride concentration inside the agent A-filled body (1)
was measured using a gas detector (14M manufactured by Gastec
Corporation) including a gas detector tube (GV-100S manufactured by
Gastec Corporation) (first time). Similar operations and measurements
were performed a second time. Table 2 shows results obtained the first
time and the second time.
[0082] Comparative Example 1: Production of Agent A-Filled Body Using
Citric Acid Hydrate
A plurality of agent A-filled bodies (2) were obtained as in
25
Example 1, except that 42 g of citric acid hydrate was used instead of
citric acid anhydride.
[0083] One of the obtained agent A-filled bodies (2) was allowed to stand
for one week under accelerated conditions at 40C and 75%RH.
Subsequently, the hydrogen chloride concentration inside the agent
A-filled bodies (2) was measured as described above (first time). Similar
operations and measurements were performed a second time. Table 2
shows results obtained the first time and the second time.
[0084] Example 2: Production of Separately Packed A-1 Filled Body
Using Citric Acid Anhydride
A resin bag made of polyethylene (about 0.1 liters) was filled with
39 g of citric acid anhydride, and the opening portion was heat-sealed to
obtain an A-1 agent-filled body (3).
[0085] Furthermore, a resin bag made of polyethylene (about 0.2 liters)
was filled with layers respectively constituted by 14 g of sodium citrate,
55 g of potassium chloride, 81 g of calcium chloride, and 38 g of
magnesium chloride arranged in this order from the bottom, and the
opening portion was heat-sealed to obtain an A-2 agent-filled body (3).
[0086] The A-1 agent-filled body (3) and the A-2 agent-filled body (3)
were placed in a resin bag obtained by layering a polyethylene
terephthalate film, an aluminum-metallized polyethylene terephthalate
film, and a polyethylene film (about 0.3 liters), and the opening portion
was heat-sealed to obtain an agent A-filled body (3). The obtained agent
A-filled body (3) was allowed to stand for one week under accelerated
conditions at 40C and 75%RH. Subsequently, the hydrogen chloride
concentrations respectively inside the agent A-filled body (3) bag, the A-1
agent-filled body (3) bag, and the A-2 agent-filled body (3) bag were
measured using a gas detector (14M manufactured by Gastec
26
Corporation) including a gas detector tube (GV-100S manufactured by
Gastec Corporation) (first time). Similar operations and measurements
were performed a second time. Table 2 shows results obtained the first
time and the second time.
[0087]
[Table 2]
Types of
Citric Acid
Concentration of produced
hydrogen chloride (ppm)
Allowed to stand for one week
under accelerated conditions
Example 1 Citric acid
Anhydride
Agent A-filled body (1)
(1st time) 9.5
(2nd time) 0.4
Example 2
Citric acid
anhydride
other container
(A-1)
Agent A-filled body (3)
(1st time) <0.05
(2nd time) <0.05
A-1 agent-filled body (3)
(1st time) <0.05
(2nd time) <0.05
A-2 agent-filled body (3)
(1st time) <0.05
(2nd time) <0.05
Comparative
Example 1
Citric acid
anhydride
Agent A-filled body (2)
(1st time) 90
(2nd time) 70
[0088] It can be seen from Table 2 that, if citric acid anhydride is used
as the citric acid ingredient as the agent A-filled body, the concentration
of hydrogen chloride that is generated during storage of the agent
A-filled body is significantly reduced. Furthermore, it can be seen that,
if the citric acid ingredient and the plurality of electrolyte ingredients
are isolated from each other, the generation of hydrogen chloride gas is
suppressed.
Industrial Applicability
[0089] According to the present invention, it is possible to provide a
hemodialysis agent-filled body that can be produced more easily, and
from which an acceptable artificial perfusion fluid for hemodialysis can
27
be prepared even after long-term storage or when ingredients are
accidentally dispersed at the time of opening. That is to say, mass
production at a lower cost becomes possible, and time for transfer and
storage can be extended. Accordingly, the hemodialysis agent-filled
body is useful in that a proper artificial perfusion fluid for hemodialysis
can be provided for use not only by domestic dialysis patients but also by
a larger number of dialysis patients in foreign countries.
References Signs List
[0090] 100 dialysis agent-filled body
110 dialysis agent A-filled body
111 dialysis agent A exterior member
112,126, 128, 182 display section
122 container (A-1)
124 container (A-2)
125 agent A-filled container
142 citric acid ingredient layer
132, 134, 136 opening slit
144, 146, 148 space portion
152 sodium citrate layer
154 potassium chloride layer
156 calcium chloride layer
158 magnesium chloride layer
160, 174 sodium chloride layer
162, 164, 166 opening portion
172 bicarbonate layer
180 dialysis agent B-filled body
181 container (B) (exterior member)

WE CLAIM:
1. A dialysis agent A-filled body for preparing an artificial perfusion
fluid for bicarbonate hemodialysis, comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the citric acid ingredient and the plurality of electrolyte
ingredients are isolated from each other by the container filled with the
agent A.
2. The dialysis agent A-filled body of claim 1, wherein the container
filled with the agent A is configured by a container (A-1) that contains
the citric acid ingredient and a container (A-2) that contains the
plurality of electrolyte ingredients.
3. The dialysis agent A-filled body of claim 2, wherein an electrolyte
having a greatest content among the plurality of electrolyte ingredients
is located closest to an opening slit provided in the container (A-2).
4. The dialysis agent A-filled body of claim 3, wherein the
electrolyte having the greatest content is a sodium salt.
5. The dialysis agent A-filled body of any one of claims 1 to 4,
wherein the citric acid ingredient is a citric acid anhydride.
6. A dialysis agent-filled body for preparing an artificial perfusion
fluid for hemodialysis, comprising:
the dialysis agent A-filled body of any one of claims 1 to 5; and
a dialysis agent B-filled body including an agent B containing
29
bicarbonate, and a container filled with the agent B.
7. A dialysis agent A-filled body for preparing an artificial perfusion
fluid for bicarbonate hemodialysis, comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the citric acid ingredient is a citric acid anhydride.
8. The dialysis agent A-filled body of claim 7, wherein the citric acid
ingredient and the plurality of electrolyte ingredients are isolated from
each other by the container filled with the agent A.
9. The dialysis agent A-filled body of claim 8, wherein the container
filled with the agent A is configured by a container (A-1) that contains
the citric acid ingredient and a container (A-2) that contains the
plurality of electrolyte ingredients.
10. The dialysis agent A-filled body of claim 9, wherein an electrolyte
having a greatest content among the plurality of electrolyte ingredients
is located closest to an opening slit provided in the container (A-2).
11. The dialysis agent A-filled body of claim 10, wherein the
electrolyte having the greatest content is a sodium salt.
12. A dialysis agent-filled body for preparing an artificial perfusion
fluid for hemodialysis, comprising:
the dialysis agent A-filled body of any one of claims 7 to 11; and
a dialysis agent B-filled body including an agent B containing
bicarbonate, and a container filled with the agent B.
30
13. A dialysis agent A-filled body for preparing an artificial perfusion
fluid for bicarbonate hemodialysis, comprising:
an agent A containing a citric acid ingredient and a plurality of
electrolyte ingredients, and a container filled with the agent A,
wherein the container filled with the agent A is configured by a
container (A-1) that contains the citric acid ingredient and a container
(A-2) that contains the plurality of electrolyte ingredients, and
an electrolyte having a greatest content among the plurality of
electrolyte ingredients is located closest to an opening slit provided in
the container (A-2).
14. The dialysis agent A-filled body of claim 13, wherein the
electrolyte having the greatest content is a sodium salt.
15. The dialysis agent A-filled body of claim 13 or 14, wherein the
citric acid ingredient is a citric acid anhydride.
16. A dialysis agent-filled body for preparing an artificial perfusion
fluid for hemodialysis, comprising:
the dialysis agent A-filled body of any one of claims 13 to 15; and
a dialysis agent B-filled body including an agent B containing
bicarbonate, and a container filled with the agent B.