WO2016063811A1

WO2016063811A1 - Dialysis agent-filled body

Info

Publication number: WO2016063811A1
Application number: PCT/JP2015/079350
Authority: WO
Inventors: 俊成高橋; 勇樹山田
Original assignee: ニプロ株式会社
Priority date: 2014-10-23
Filing date: 2015-10-16
Publication date: 2016-04-28
Also published as: JPWO2016063811A1; JP6931266B2

Abstract

Disclosed is a dialysis agent-filled body which can be used in the preparation of an artificial perfusion solution for hemodialysis use. The dialysis agent-filled body according to the present invention comprises: an agent A-filled body for dialysis use which comprises an agent A containing a citric acid component and multiple electrolyte components and a container to be filled with the agent A, wherein the citric acid component and the multiple electrolyte components are isolated from each other by the container to be filled with the agent A; and an agent B-filled body for dialysis use which comprises an agent B containing a bicarbonate salt and a container to be filled with the agent B. According to the present invention, a dialysis agent-filled body can be provided, which can meet the possible future increase in hemodialysis patients on a global scale and the demand for dialysis agents for hemodialysis use associated with the aforementioned possible future increase in hemodialysis patients and has superior versatility.

Description

Dialysis agent filler

The present invention relates to a dialysis agent filler used in preparing an artificial perfusate for hemodialysis.

Hemodialysis therapy (hereinafter referred to as hemodialysis) is also called artificial dialysis therapy and is the most commonly used blood purification method for patients with chronic renal failure. In hemodialysis, in order to avoid uremia, in addition to the removal of waste products in the blood, the concentration of serum electrolyte and the amount of water are maintained.

Hemodialysis is performed for 3 to 4 hours per patient, and the amount of perfusate for dialysis required per patient is, for example, 100 to 300 liters. In addition, it has been pointed out that such a perfusate easily propagates bacteria, and long-term storage has been considered difficult. For this reason, in an actual dialysis facility, it is common practice to prepare a desired artificial perfusate by dissolving a powdered hemodialysis agent in dialysis water immediately before dialysis.

As this artificial perfusate, dialysate using acetic acid, which has been considered as one of the components as an alkalinizing agent, has been widely used. In recent years, sodium bicarbonate (sodium bicarbonate) that drastically reduces unpleasant symptoms during dialysis. Have been replaced by those using.

Furthermore, in recent years, acetic acid-free dialysis fluid solvents that do not use acetate have been used because acetate has an effect of suppressing vasodilation and cardiac function. As such an example, a technique for setting a blending ratio and pH of citric acids as constituent components within a predetermined range is known (Patent Documents 1 and 2).

However, the bicarbonate ions that make up the sodium bicarbonate react with calcium ions and magnesium, which are other components of hemodialysis agents, to produce insoluble compounds (metal carbonates) such as calcium carbonate and magnesium carbonate. It has been pointed out to do. For this reason, the conventional hemodialysis agent is divided into A agent containing components other than sodium hydrogen carbonate and B agent containing sodium hydrogen carbonate, and each is filled in different filling containers.

In addition, it has been pointed out that the filling body filled with such a hemodialysis agent A also generates hydrogen chloride gas due to contact between citric acid and a chloride salt (for example, sodium chloride). For example, a technique in which sodium chloride is used as a core particle and the periphery thereof is coated with another chloride is also known (Patent Document 3).

On the other hand, it is believed that the number of patients requiring such hemodialysis will continue to increase on a global scale. For this reason, in order to improve the versatility of the blood agent filling body on a global scale, it is necessary to further improve the production efficiency. In consideration of enabling long-term storage of the packing, decomposition of constituent components and generation of by-products must also be avoided. Furthermore, since such a blood agent filler is prepared as an artificial perfusate at each dialysis facility, it is desired that the blood product filler is further excellent in handleability.

JP 2003-104869 A JP 2008-246209 A International Publication No. 2005/094918

An object of the present invention is to solve the above-mentioned problems, and the object of the present invention is to make it more versatile in line with the future increase in hemodialysis patients worldwide and the accompanying demand for hemodialysis agents. An object of the present invention is to provide a dialysis agent filler excellent in properties.

The present invention is a dialysis agent A filler for preparing an artificial perfusion solution for bicarbonate hemodialysis,
A dialysis agent A comprising an A agent containing a citric acid component and a plurality of electrolyte components, and an A agent-filled container, wherein the citric acid component and the plurality of electrolyte components are separated by the A agent-filled container It is a filler.

In one embodiment, the agent A filling container is composed of a container (A-1) containing the citric acid component and a container (A-2) containing the plurality of electrolyte components.

In a further embodiment, the maximum amount of electrolyte constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit arranged in the container (A-2).

In yet a further embodiment, the maximum content of electrolyte is a sodium salt.

In one embodiment, the citric acid component is citric acid anhydride.

The present invention also provides a dialysis agent filler for preparing an artificial perfusion solution for hemodialysis, comprising the dialysis agent A filler; and a B agent containing a bicarbonate and a B agent filling container. A dialysis agent filler comprising: a dialysis agent B filler.

The present invention is also a dialysis agent A filler for preparing an artificial perfusion solution for bicarbonate hemodialysis,
A dialysis agent A filling body comprising an A agent containing a citric acid component and a plurality of electrolyte components, and an A agent-filled container, wherein the citric acid component is citric acid anhydride.

In one embodiment, the citric acid component and the plurality of electrolyte components are separated by the A agent-filled container.

In a further embodiment, the agent A filled container is composed of a container (A-1) containing the citric acid component and a container (A-2) containing the plurality of electrolyte components.

In a still further embodiment, the maximum amount of electrolyte constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit arranged in the container (A-2).

In yet another embodiment, the maximum content of electrolyte is a sodium salt.

The present invention is also a dialysis agent A filler for preparing an artificial perfusion solution for bicarbonate hemodialysis,
An agent A containing a citric acid component and a plurality of electrolyte components; and an agent A-filled container, and the agent A-filled container comprises a container (A-1) containing the citric acid component and the plurality of electrolyte components. A container (A-2) containing, and
A dialysis agent-A filling material in which the electrolyte of the maximum content constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit disposed in the container (A-2).

In one embodiment, the maximum content of electrolyte is a sodium salt.

In one embodiment, the citric acid component is citric acid anhydride.

According to the present invention, it is possible to manufacture a hemodialysis agent filler more easily than in the prior art. The hemodialysis agent-filled body of the present invention can also suppress the generation of harmful substances during storage as well as the denaturation of components due to long-term storage. In the preparation of an artificial perfusate, the hemodialysis agent filler of the present invention also has a large concentration of each component after preparation in the artificial perfusate even if a part of the components spills out when opened. Change is unlikely to occur. As a result, handling at each dialysis facility is further improved. As a result, it is possible to provide a hemodialysis agent filling material that can be sufficiently accommodated for the future worldwide increase in hemodialysis patients and the accompanying demand for hemodialysis agents.

It is a figure which represents typically an example of the dialysis agent filler of this invention. It is a schematic diagram for demonstrating an example of the dialysis agent A filling body which comprises the dialysis agent filling body of this invention. FIG. 2 is a schematic diagram for explaining an example of a container (A-1) constituting a dialysis agent A filler, (a) is a front view of the container (A-1), and (b) FIG. 3 is a longitudinal sectional view of the container (A-1). FIG. 2 is a schematic diagram for explaining an example of a container (A-2) constituting a dialysis agent A filler, (a) is a front view of the container (A-2), and (b) FIG. 4 is a longitudinal sectional view of the container (A-2). FIG. 9 is a schematic diagram for explaining another example of the dialysis agent-A filling body constituting the dialysis agent-packing body of the present invention, including a front view of the dialysis agent-A filling body container (A-2); It is longitudinal direction sectional drawing. FIG. 6 is a schematic diagram for explaining still another example of a dialysis agent-A filling body constituting the dialysis agent-packing body of the present invention, wherein (a) shows a container (A-1) and a container (A-2). ) Represents a dialysis agent A filling body fixed at a part of each upper end, and (b) is a height above the containers (A-1) and (A-2). It is a figure showing the A agent filling body for dialysis which arrange | positions and arrange | positions sideways and is shape | molded integrally. It is a schematic diagram for demonstrating an example of the B agent filling body for dialysis shown in FIG. 1, (a) is a front view of the said filling body, and (b) is a longitudinal cross-sectional view of the said filling body. is there.

Hereinafter, the present invention will be described in detail.

(Dialyzing agent filler)
FIG. 1 is a diagram schematically showing an example of the dialysis agent filler of the present invention.

The dialysis agent filler of the present invention is an assembly of a plurality of containers (fillers) filled with a hemodialysis agent for preparing an artificial perfusion solution for hemodialysis. A dialysis agent filler 100 shown in FIG. 1 includes a dialysis agent A filler 110 and a dialysis agent B filler 180.

In the first embodiment of the present invention, the dialysis agent A filler 110 is used to prepare, for example, an artificial perfusate for bicarbonate hemodialysis. The dialysis agent B filling body 180 mainly contains the agent B (ie, bicarbonate) required for preparing the dialysis artificial perfusate. To do. In the display fields 112 and 182 of the

fillers

110 and 180, the types, contents, usage instructions, etc. of the constituents contained in the respective fillers, the description items stipulated by laws and regulations, etc. are shown in each country and situation. It is also described.

The dialysis agent A filling body 110 is constituted by, for example, an exterior body 111 made of a resin molded body (for example, a bag-like structure or a filling body in which four sides are heat-sealed). Examples of the resin molded body include a thermoplastic resin film such as polyethylene (PE) and polyethylene terephthalate (PET), an aluminum vapor-deposited plastic film (for example, VM-PET), an aluminum pouch, and a laminate thereof. Things. The size of the exterior body 111 constituting the dialysis agent A filling body 110 is not particularly limited, and can be arbitrarily designed by those skilled in the art so that it can be appropriately filled with the agent A filling container or components described later. Can do.

The dialysis B agent filling body 180 is constituted by, for example, an exterior body (container) 181 made of a resin molded body (for example, a bag-like structure or a filling body in which four sides are heat-sealed). Examples of the resin molded body may be the same resin molded body as the dialysis agent A filler 110, but a thermoplastic resin film such as polyethylene (PE) and polyethylene terephthalate (PET), and a laminate thereof. The thing comprised from is mentioned. The size of the exterior body 181 that constitutes the dialysis B agent filling body 180 is not particularly limited, and can be arbitrarily designed by those skilled in the art so that it can be appropriately filled with a bicarbonate or the like to be described later.

(A-dialysis filler for dialysis)
As described above, the dialysis agent A filler contains a citric acid component and a plurality of electrolyte components as the A agent. Both the citric acid component and the plurality of electrolyte components preferably have a powder form. Here, in 1st embodiment of this invention, the A agent filling body for dialysis is equipped with the A agent filling container, The said citric acid component and several electrolyte component are isolate | separated by the said A agent filling container. . According to the A-agent-filled container, the citric acid component and the plurality of electrolyte components can be divided (divided), that is, stored separately without being mixed or brought into contact with each other. In the present invention, the separation of the citric acid component and the plurality of electrolyte components in the A agent-filled container is performed by, for example, separating these components into at least two containers, preferably two containers (A-1) and (A- 2) separately, or at least two, preferably two compartments are provided by heat sealing or the like in the exterior body 111 constituting the dialysis agent A filling body 110 shown in FIG. It can be achieved by filling separately.

Examples of the citric acid component include citric acid, which may be a hydrate, an anhydride, or a combination thereof. Further, as a citric acid component, citric acid may contain a citrate other than a chloride salt (for example, sodium citrate).

The plurality of electrolyte components include chloride salts other than citric acid (for example, sodium chloride, magnesium chloride, potassium chloride, calcium chloride, and combinations thereof). Furthermore, citrates such as sodium citrate may be contained as a plurality of electrolyte components.

FIG. 2 is a schematic diagram for explaining an example of the dialysis agent A filler constituting the dialysis agent filler of the present invention.

As shown in FIG. 2, the A-agent filling body 110 for dialysis includes an A-agent-filling container 125 including a container (A-1) 122 and a container (A-2) 124. In FIG. 2, a container (A-1) 122 contains a citrate component that can be used to prepare an artificial perfusate for hemodialysis. The container (A-2) 124 contains a plurality of electrolyte components that can be used for preparing the artificial perfusate. In the present invention, such a combination of the containers (A-1) 122 and (A-2) 124 with the citric acid component and the electrolyte component is merely an example. For example, a plurality of containers (A-1) 122 It may contain an electrolyte component, and the container (A-2) 124 may contain a citric acid component.

In the display fields 126 and 128 of the container (A-1) 122 and the container (A-2) 124, the types and contents of the components contained in the respective containers, the description items stipulated by the laws and regulations in each country, etc. Is described.

(Constituent component of dialysis agent A filler)
In the present invention, examples of the citric acid component contained in the dialysis agent A filler include citric acid hydrate and citric acid anhydride. In the above embodiment of the present invention, the citric acid component can be contained, for example, in the container (A-1), but the container (A-1) contains a part of the electrolyte component described later together with the citric acid component (for example, Part of the amount used such as sodium citrate) may be included. In such a case, it is preferable to use citric acid anhydride as the citric acid component.

In the second embodiment of the present invention, the citric acid component and the plurality of electrolyte components are separated by the agent A-filled container (for example, divided by the containers (A-1) and (A-2)). It is also possible to construct a dialysis agent A filling body by combining the citric acid component and the electrolyte component in one A agent filling container. When combining a citric acid component and a plurality of electrolyte components in one A agent filling container, for example, the outer packaging 111 of the A agent filling body 110 for dialysis as shown in FIG. can do. However, in such a case, citric acid anhydride is used as the citric acid component in order to suppress the generation of hydrogen chloride by reacting with the chloride contained in the electrolyte component.

In the present invention, the content of the citric acid component contained in the dialysis agent A filler is not necessarily limited because it varies depending on the content of the electrolyte component used, the concentration desired for the artificial perfusate to be prepared, etc. In the artificial perfusate, the content of, for example, 1.5 mEq / L to 5 mEq / L, preferably 2 mEq / L to 3 mEq / L based on the citrate ion content can be set by those skilled in the art. Due to such a content of the citric acid component, the artificial perfusate can be prepared to have a pH of, for example, 7 to 8.5, preferably 7.5 to 8.

In the case of preparing as a concentrate for artificial perfusate, for example, a content that is 35 to 45 times the concentration of the artificial perfusate is set according to the situation.

In the present invention, the plurality of electrolyte components contained in the dialysis agent A filler are electrolytes that can be generally used in the preparation of an artificial perfusion solution for hemodialysis. Examples of such electrolytes include sodium chloride, potassium chloride, calcium chloride (eg, calcium chloride hydrate), magnesium chloride (eg, magnesium chloride hydrate), and sodium citrate (eg, sodium citrate water) Japanese).

The content of the plurality of electrolytes varies depending on the content of the citric acid component to be used, the concentration desired for the artificial perfusate to be prepared, the amount to be prepared, and the like. Can be set. In the present invention, among the plurality of electrolytes, sodium chloride preferably has a maximum content as compared with each of other electrolytes (that is, potassium chloride, calcium chloride, and magnesium chloride). This is because it is set according to the electrolyte concentration in the blood.

In the present invention, the content of sodium chloride that can be contained in the dialysis agent A filler varies depending on the content of the citric acid component to be used, the content of other electrolyte components, the concentration desired for the artificial perfusate to be prepared, and the like. Therefore, although not necessarily limited, in the prepared artificial perfusate, the content of, for example, 75 mEq / L to 150 mEq / L, preferably 80 mEq / L to 145 mEq / L can be set by those skilled in the art based on the sodium ion content. .

The dialysis agent A filler may also contain other components in addition to the citric acid component and the electrolyte component. Examples of other components include a pH adjuster. Examples of pH adjusters include organic acids. Further examples of organic acids 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. In the dialysis agent A filled body, those other components can be appropriately selected by those skilled in the art as long as they do not impair the function of the citrate component and the plurality of electrolyte components as the dialysis agent A.

(Form of A-filler for dialysis)
FIG. 3 is a schematic diagram for explaining an example of the container (A-1) constituting the dialysis agent A filler, (a) is a front view of the container (A-1), and (B) is a longitudinal sectional view of the container (A-1).

The container (A-1) 122 is, for example, a bag-like structure or one in which four sides are heat-sealed. Examples of materials that can constitute the container (A-1) include polyethylene (PE), thermoplastic resin films such as polyethylene terephthalate (PET), and aluminum-deposited plastic films (for example, VM-PET), and these A laminated body is mentioned. The size of the container (A-1) 122 is not particularly limited, and can be arbitrarily designed by those skilled in the art so as to have a size capable of appropriately filling the constituent components.

When the citric acid component is contained in the container (A-1) 122, the citric acid component layer 142 is opened in the container (A-1) 122 as shown in FIG. It is preferable that a predetermined amount is filled in the container (A-1) 122 up to the vicinity of the slit 132. In other words, even if the inside of the container (A-1) 122 is filled with the citric acid component layer 142, the arrangement as shown in FIG. 3B (the display column 126 as shown in FIG. It is preferable that the size is designed so that a small space 144 is provided in the vicinity of the opening slit 132. Here, the space part 144 is filled with an inert gas such as nitrogen gas or the volume of the space part 144 is reduced as necessary. In the present invention, since the space 144 is formed in the container (A-1) 122 (that is, the container (A-1) 122 is not filled with the citric acid component layer 142), When the tear slit 132 is torn by hand, the possibility that the constituent citric acid component layer 142 is accidentally scattered outside the container (A-1) 122 can be reduced.

FIG. 4 is a schematic view for explaining an example of a container (A-2) constituting the dialysis agent A filler, (a) is a front view of the container (A-2), and (B) is a longitudinal sectional view of the container (A-2).

The container (A-2) 124 is, for example, a bag-like structure or one in which four sides are heat-sealed. Examples of materials that can constitute the container (A-2) include polyethylene (PE), thermoplastic resin films such as polyethylene terephthalate (PET), and aluminum-deposited plastic films (for example, VM-PET), and these A laminated body is mentioned. The size of the container (A-2) 124 is not particularly limited, and can be arbitrarily designed by those skilled in the art so as to have a size capable of appropriately filling the constituent components.

When the plurality of electrolyte components are contained in the container (A-2) 124, as shown in FIG. 4B, the electrolyte components (sodium citrate layer 152, potassium chloride layer 154, calcium chloride layer 156, Each of the magnesium chloride layer 158 and the sodium chloride layer 160) is filled in a predetermined amount in the container (A-2) 124 in the vicinity of the opening slit 134 provided in the container (A-2) 124. preferable. In other words, even if the inside of the container (A-2) 124 is filled with the electrolyte component, the arrangement as shown in FIG. 4B (the display field 128 as shown in FIG. It is preferable that the size is designed so that a slight space 146 is provided in the vicinity of the opening slit 134. Here, the space portion 146 is filled with, for example, an inert gas such as a nitrogen gas, or the space volume is reduced as much as possible by removing air. In the present invention, since the space portion 146 is formed in the container (A-2) 124 (that is, the container (A-2) 124 is not filled with the electrolyte component), the person can open the slit. When tearing 134 by hand, it is possible to reduce the possibility that the electrolyte component as a constituent component is accidentally scattered outside the container (A-2) 124.

The electrolyte component layers (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) filled in the container (A-2) 124 are shown in FIG. As shown in (b), the components may be stacked and filled, or the components may be filled in advance so as to be substantially uniform.

Furthermore, in the present invention, as shown in FIG. 4 (b), among the plurality of electrolyte components filled in the container (A-2) 124, the maximum amount of electrolyte is disposed in the container (A-2). It is preferable to fill and laminate in the vicinity of the opened slit. The maximum content of electrolyte is preferably sodium chloride. Furthermore, the electrolyte of the maximum content may be divided into approximately two equal parts, separated into the upper layer and the lower layer of the container (A-2), and the other components may be stacked in these layers.

In the present invention, not only the container (A-2) but also the container (A-1) can be filled with an electrolyte having such a maximum content or a method for laminating other components by separating them into an upper layer and a lower layer. It can also be applied when filling the container B.

The dialysis agent filler of the present invention is opened by various medical personnel such as nurses for the preparation of an artificial perfusion solution for hemodialysis. Opening should always be performed carefully, but it is also assumed that some components may be accidentally scattered during opening. In this case, for example, if the plurality of electrolyte components are substantially uniformly mixed, a minute amount or a small amount of the electrolyte among the electrolytes constituting the plurality of electrolyte components will be scattered together. For this reason, even if an artificial perfusate for hemodialysis is temporarily prepared from a filler partially scattered, the concentration of the trace amount or a small amount of electrolyte in the perfusate varies significantly.

However, when the maximum content of electrolyte (sodium chloride layer 160) is laminated in the vicinity of the opening slit 134 as shown in FIG. 4 (b), it is assumed that some electrolyte components are scattered and lost by opening. However, only a portion of the substantially maximum content of electrolyte will be lost. As a result, in the prepared perfusate, there is no variation in the concentration of each electrolyte other than the maximum content of electrolyte, and the concentration of the maximum content of electrolyte itself (because it originally had the maximum content) is substantial. There will be less fluctuation.

The merit of such lamination can be explained more clearly through, for example, the following simulation.

The plurality of electrolyte components to be contained in the container (A-2) and the amounts thereof are, for example, 14 g of sodium citrate, 55 g of potassium chloride, 81 g of calcium chloride, 38 g of magnesium chloride and 1830 g of sodium chloride. In this example, the maximum content of electrolyte is sodium chloride (1830 g). When such a plurality of electrolyte components are laminated on the container (A-2) 124 in the order shown in FIG. 4B, the maximum content of sodium chloride layer 160 becomes the opening slit of the container (A-2) 124. It is arranged closest to 134.

Here, it is assumed that the opening slit 134 is opened and 30 g of the electrolyte component is scattered and lost. Since the uppermost layer arranged in the vicinity of the opening slit 134 of the container (A-2) is composed of sodium chloride, it is clear that the 30 g is usually all sodium chloride. In that case, when the constituents of the dialysis agent A filling body partly scattered are dissolved in water and 10 liters of artificial perfusate is prepared as it is, the concentration of ions constituting each electrolyte in the artificial perfusate is Compared to the case where such scattering is not performed, it can be expressed as shown in Table 1.

As shown in Table 1, when the maximum amount of electrolyte (sodium chloride layer 160) is laminated in the vicinity of the opening slit 134 in the container (A-2) 124 as shown in FIG. Even if a large amount of splattering occurs, the concentration of each ion in the artificial perfusate prepared later decreases slightly to the sodium ion concentration and chloride ion concentration, but to a level that prevents application to hemodialysis. I understand that it is not.

On the other hand, when a maximum amount of electrolyte (magnesium chloride layer 158) is laminated in the vicinity of the opening slit 134 in the container (A-2) 124, an artificial perfusate prepared thereafter is produced even if as much as 30 g of scattering occurs. Of each ion concentration in the above, the magnesium ion concentration is lost by 80%, and it is lowered to such an extent that the application to hemodialysis is largely prevented.

In FIG. 4B, the plurality of electrolytes contained in the container (A-2) are separated from the bottom of the container by a sodium citrate layer 152, a potassium chloride layer 154, a calcium chloride layer 156, and a magnesium chloride layer. The example in which the sodium chloride layer 160 having the maximum content is arranged in the vicinity of the opening slit 134 in the order of 158 and the sodium chloride layer 160 has been described, but the present invention is not necessarily limited to such a stacking order. That is, in the present invention, as long as the maximum amount of electrolyte (for example, the sodium chloride layer 160) is disposed in the vicinity of the opening slit, the stacking order of the layers constituting the other electrolyte is not particularly limited. All or a part of the electrolyte may be mixed so as to be substantially uniform, or may be laminated in an arbitrary order.

In the present invention, the example in which the opening slit 134 is provided in the form of a V-notch on the upper side of the container (A-2) 124 has been described with reference to FIG. 4, but the present invention is not necessarily limited to such an arrangement and form. . The opening slit may only be marked by printing, for example, so that it can be cut with scissors or a knife, for example:
(1) As shown in FIG. 5, an opening 162 having a perforation opening mark or groove is provided on the upper side of the container (A-2), and the opening is placed inside the container (A-2). Those not reaching the space 146 (FIGS. 5A and 5B);
(2) An opening 164 provided with a perforation opening mark or groove on the upper side of the container (A-2) is provided until it reaches the space 146 inside the container (A-2) (see FIG. (C) and (d)); and (3) an opening portion 166 provided with an opening mark or a groove from the upper end of the container (A-2) toward the upper side portion is provided. That does not reach the space 146 inside the container (A-2) ((e) and (f) of FIG. 5);
It may be.

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 are integrated into a dialysis agent A. The filling body 110 (or A agent filling container) may be comprised.

In FIG. 6 (a), the upper ends 127 of the container (A-1) 122 and the container (A-2) are fixed to each other by, for example, heat sealing or adhesive, and the container (A-1) In common with 122 and the container (A-2) 124, an opening portion 166 is provided as an opening slit from the upper end toward the upper side portion. In such a configuration, the container (A-1) 122 and the container (A-2) 124 can be simultaneously opened through the opening portion 166.

On the other hand, in FIG. 6B, the container (A-1) 122 and the container (A-2) 124 are integrally formed with the same height at the upper position where opening is planned. Furthermore,

V notches

163 and 165 are provided on the upper side of the container (A-1) 122 and the upper side of the container (A-2) 124, respectively. Further, a perforation opening part 129 is provided between the container (A-1) 122 and the container (A-2) 124 as necessary. In such a configuration, the container (A-1) 122 and the container (A-2) 124 can be opened at once through either the V-

notches

163 or 165. In addition, the container (A-1) 122 and the container (A-2) 124 can be separated along the opening portion 129 as necessary.

(B-dialysis filler for dialysis)
The B agent filling body for dialysis includes a B agent containing bicarbonate and a B agent filling container.

In the present invention, sodium bicarbonate is an example of bicarbonate contained in the dialysis B agent filler.

FIG. 7 is a schematic view for explaining an example of the dialysis B agent filling body shown in FIG. 1, wherein (a) is a front view of the filling body, and (b) is a longitudinal view of the filling body. FIG.

As shown in FIG. 7 (b), in the B-dialysis filler 180, the bicarbonate layer 174 is disposed on the bottom side of the container (B) (exterior body) 181 and the sodium chloride layer 172 is It is preferable that the container (B) 181 is filled in the vicinity of the opening slit 136. In other words, even if the inside of the container (B) 181 is filled with the bicarbonate layer 174 and the sodium chloride layer 172, the arrangement as shown in FIG. 7B (as shown in FIG. 7A) It is preferable that the size is designed so that a slight space portion 148 is provided in the vicinity of the opening slit 136 in the arrangement when the display column 182 is directed to the front. Here, the space portion 148 is filled with an inert gas such as nitrogen gas or the volume of the space portion 148 is reduced. In the present invention, the space 148 is formed in the container (B) 181 (that is, the entire container (B) 181 is not filled with the bicarbonate layer 172 and the sodium chloride layer 174). When a person tears the opening slit 136 by hand, the possibility that the component (mainly the bicarbonate layer 174) is accidentally scattered outside the container (B) 181 can be reduced.

In the present invention, the content of bicarbonate contained in the dialysis agent B filler is determined according to the content of the citric acid component and the electrolyte component used, the concentration desired for the artificial perfusate to be prepared, the amount to be prepared, and the like. Although not necessarily limited due to changes, the content of the artificial perfusate to be prepared can be set by those skilled in the art, for example, 15 mEq / L to 45 mEq / L, preferably 25 mEq / L to 40 mEq / L.

Moreover, when the sodium chloride layer 174 is provided in the above, the content is the total of sodium chloride that can be contained in the dialysis agent A filler, and the sodium chloride required for the dialysis agent filler of the present invention. The amount can be appropriately selected by those skilled in the art so as to satisfy the above amount.

(Preparation of artificial perfusate for hemodialysis)
The dialysis agent filler of the present invention is stored, for example, in a dark place avoiding high humidity until just before use. In preparing an artificial perfusate for dialysis, for example, the components of the dialysis agent A filling material are added to and dissolved in dialysis water having a concentration lower than a predetermined endotoxin concentration, while dialysis B agent is filled in other dialysis water. It is dissolved by adding body components. Thereafter, dilution to a predetermined concentration and mixing of both solutions at a predetermined ratio are performed to prepare an artificial perfusate.

Although the prepared artificial perfusate varies depending on the dialysis time, it is carefully treated using means known to those skilled in the art, for example, at a dose of 100 L to 300 L for dialysis patients.

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

<Example 1: Production of agent A packing material using citric acid anhydride>
In order from the bottom, 14 g of sodium citrate, 55 g of potassium chloride, 81 g are placed on a resin bag (about 0.3 liter) obtained by laminating a polyethylene terephthalate film, an aluminum-deposited polyethylene terephthalate film, and a polyethylene film. Of calcium chloride, 38 g of magnesium chloride, and 39 g of citric acid anhydride were stacked while being laminated, and the opening was heat sealed to obtain an agent A filled body (1).

The obtained A agent filling body (1) was left for 1 week under accelerated conditions of 40 ° C. and 75% RH. Thereafter, the hydrogen chloride concentration in the A agent filling body (1) was measured by a gas detector (14M manufactured by Gastec Co., Ltd.) equipped with a gas detector tube (GV-100S manufactured by Gastec Co., Ltd.) (first time). The same operation and measurement were performed for the second time. The obtained first and second results are shown in Table 2, respectively.

<Comparative Example 1: Preparation of agent A filler using citric acid hydrate>
Except having used 42 g of citric acid hydrate instead of the citric acid anhydride, it carried out similarly to Example 1, and obtained the several A agent filling body (2).

Another one of the obtained A agent filling body (2) was left for 1 week under accelerated conditions of 40 ° C. and 75% RH. Thereafter, the hydrogen chloride concentration in the A agent filler (2) was measured in the same manner as described above (first time). The same operation and measurement were performed for the second time. The obtained first and second results are shown in Table 2.

<Example 2: Preparation of citric anhydride separate package A-1>
A polyethylene resin bag (about 0.1 liter) was filled with 39 g of citric anhydride, and the opening was heat-sealed to obtain an A-1 agent-filled body (3).

Also, in a polyethylene resin bag (about 0.2 liter), in order from the bottom, 14 g of sodium citrate, 55 g of potassium chloride, 81 g of calcium chloride, and 38 g of magnesium chloride are stacked while being stacked, and the opening is opened. Heat sealing was performed to obtain an A-2 agent filler (3).

A resin bag (about 0.000) obtained by laminating a polyethylene terephthalate film, an aluminum-deposited polyethylene terephthalate film, and a polyethylene film with the A-1 agent filler (3) and the A-2 agent filler (3). 3 liters), and the opening was heat-sealed to obtain an A-agent filler (3). The obtained A agent filling body (3) was left to stand under accelerated conditions of 40 ° C. and 75% RH for one week. Thereafter, the hydrogen chloride concentrations in the A agent filling body (3) bag, the A-1 agent filling body (3) bag, and the A-2 agent filling body (3) bag were measured with gas detector tubes (Gas Corporation). Measurement was performed with a gas detector (14M manufactured by Gastec Co., Ltd.) equipped with GV-100S manufactured by Tech (first time). The same operation and measurement were performed for the second time. The obtained first and second results are shown in Table 2, respectively.

As shown in Table 2, when citric acid anhydride was used for the citric acid component as the A agent packing, the concentration of hydrogen chloride generated during storage of the A agent packing could be significantly reduced. Recognize. Moreover, it turns out that generation | occurrence | production of hydrogen chloride gas was able to be suppressed by isolate | separating a citric acid component and a some electrolyte component.

According to the present invention, a hemodialysis agent filler can be more easily produced, and can be used for long-term storage and artificial perfusion for hemodialysis that can be tolerated even in the unlikely event that the components are scattered during opening. A liquid can be prepared. In other words, mass production is possible at a lower price, and the time for transportation and storage can be extended. This is useful in that an appropriate artificial perfusion solution for hemodialysis can be provided not only for use in domestic dialysis patients but also for a larger number of foreign dialysis patients.

100 dialysis agent filling body 110 dialysis A agent filling body 111 dialysis A agent

exterior body

112, 126, 128, 182 display column 122 container (A-1)
124 Container (A-2)
125 A agent filling container 142 Citric

acid component layer

132, 134, 136 Opening slit 144, 146, 148 Space 152 Sodium citrate layer 154 Potassium chloride layer 156 Calcium chloride layer 158

Magnesium chloride layer

160, 174

Sodium chloride layer

162, 164 , 166 Unsealed part 172 Bicarbonate layer 180 Filler B for dialysis 181 Container (B) (exterior body)

Claims

A preparation for dialysis A preparation for preparing an artificial perfusion solution for bicarbonate hemodialysis,
A dialysis agent A comprising an A agent containing a citric acid component and a plurality of electrolyte components, and an A agent-filled container, wherein the citric acid component and the plurality of electrolyte components are separated by the A agent-filled container Filling body.
The dialysis according to claim 1, wherein the A-agent-filled container is composed of a container (A-1) containing the citric acid component and a container (A-2) containing the plurality of electrolyte components. A agent filling body.
The dialysis agent A filling according to claim 2, wherein the electrolyte of the maximum content constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit arranged in the container (A-2). body.
The dialysis agent A filler according to claim 3, wherein the maximum content of electrolyte is a sodium salt.
The dialysis agent A filling material according to any one of claims 1 to 4, wherein the citric acid component is citric acid anhydride.
A dialysis agent filler for preparing an artificial perfusate for hemodialysis,
A dialysis agent A filling body according to any one of claims 1 to 5; and a dialysis B agent filling body comprising a B agent containing bicarbonate and a B agent filling container;
A dialysis agent filling body.
A preparation for dialysis A preparation for preparing an artificial perfusion solution for bicarbonate hemodialysis,
A filling agent for dialysis for dialysis comprising an A agent containing a citric acid component and a plurality of electrolyte components, and an A agent-filled container, and the citric acid component is citric acid anhydride.
The dialysis agent A filling body according to claim 7, wherein the citric acid component and the plurality of electrolyte components are separated by the agent A filling container.
The dialysis according to claim 8, wherein the A agent-filled container comprises a container (A-1) containing the citric acid component and a container (A-2) containing the plurality of electrolyte components. A agent filling body.
The filling of the A agent for dialysis according to claim 9, wherein the electrolyte with the maximum content constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit disposed in the container (A-2). body.
The dialysis agent A filler according to claim 10, wherein the maximum content of electrolyte is a sodium salt.
A dialysis agent filling body for preparing an artificial perfusate for hemodialysis, the dialysis agent A filling body according to any one of claims 7 to 11; and B agent and B agent filling container containing bicarbonate A dialysis B agent filler comprising:
A dialysis agent filling body.
A preparation for dialysis A preparation for preparing an artificial perfusion solution for bicarbonate hemodialysis,
An agent A containing a citric acid component and a plurality of electrolyte components; and an agent A-filled container, and the agent A-filled container comprises a container (A-1) containing the citric acid component and the plurality of electrolyte components. A container (A-2) containing, and
A filling agent for dialysis for dialysis, in which the electrolyte of the maximum content constituting the plurality of electrolyte components is stacked and filled in the vicinity of the opening slit arranged in the container (A-2).
The dialysis agent A filler according to claim 13, wherein the maximum content of electrolyte is a sodium salt.
The dialysis agent A filler according to claim 13 or 14, wherein the citric acid component is citric acid anhydride.
A dialysis agent filler for preparing an artificial perfusate for hemodialysis,
A dialysis agent A filling body according to any one of claims 13 to 15; and a dialysis B agent filling body comprising a B agent containing bicarbonate and a B agent filling container;
A dialysis agent filling body.