JP2003088582A - Peritoneal dialysate and storage vessel - Google Patents
Peritoneal dialysate and storage vesselInfo
- Publication number
- JP2003088582A JP2003088582A JP2001284260A JP2001284260A JP2003088582A JP 2003088582 A JP2003088582 A JP 2003088582A JP 2001284260 A JP2001284260 A JP 2001284260A JP 2001284260 A JP2001284260 A JP 2001284260A JP 2003088582 A JP2003088582 A JP 2003088582A
- Authority
- JP
- Japan
- Prior art keywords
- liquid
- alkaline
- acidic
- peritoneal
- peritoneal dialysate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- External Artificial Organs (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は腎不全患者の腹腔内
に貯留・排液することによって、透析を行う腹膜透析に
関し、特に安全性に考慮した腹膜透析液および該透析液
を収容した容器に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to peritoneal dialysis in which dialysis is carried out by storing and draining in the abdominal cavity of a patient with renal failure, and more particularly to peritoneal dialysis fluid in consideration of safety and a container containing the dialysate. .
【0002】[0002]
【従来の技術】近年の報告によると、酸性の腹膜透析液
は、腹膜機能低下の原因の1つに挙げられている。ま
た、酸性の腹膜透析液によって、腹膜機能の低下だけで
なく、腹腔内リンパ球の免疫能が低下し、腹膜炎が発生
し易くなるという説もある。このように、酸性の腹膜透
析液は生体にとって好ましくないと考えられているにも
関わらず、浸透圧調整剤のブドウ糖を中性域で滅菌・保
存すると、分解してしまうため、酸性側領域に調整して
いるという事情があった。2. Description of the Related Art According to recent reports, an acidic peritoneal dialysis solution has been cited as one of the causes of decreased peritoneal function. There is also a theory that an acidic peritoneal dialysis solution not only lowers the peritoneal function, but also lowers the immunopotency of intraperitoneal lymphocytes, which easily causes peritonitis. Thus, even though acidic peritoneal dialysis fluid is considered to be unfavorable to the living body, if glucose, which is an osmotic pressure adjusting agent, is sterilized and stored in a neutral region, it will be decomposed, so that the acid side region will be decomposed. There was a situation that I was adjusting.
【0003】しかし、生体適合性や上記弊害改善の点か
ら、中性腹膜透析液が注目されており、調製方法や保存
容器や薬液組成を工夫することによって、上記ブドウ糖
の分解を抑制する研究も広く行われている。例えば、ブ
ドウ糖やカルシウム、マグネシウムや乳酸塩を含有する
酸性濃縮液と、重炭酸塩を含有するアルカリ側濃縮液の
2液に分けて収容保存し、使用時に混合する方法などで
ある。それによって、ブドウ糖の分解を防止し、且つカ
ルシウムやマグネシウムの不溶塩の生成を防止できる。However, from the viewpoint of biocompatibility and improvement of the above-mentioned harmful effects, neutral peritoneal dialysis fluid has been attracting attention, and researches for suppressing the above-mentioned decomposition of glucose by devising a preparation method, a storage container and a chemical solution composition have been conducted. It is widely practiced. For example, there is a method in which an acidic concentrated liquid containing glucose, calcium, magnesium, or a lactate and an alkaline concentrated liquid containing bicarbonate are separately stored, stored, and mixed at the time of use. Thereby, the decomposition of glucose can be prevented, and the formation of insoluble salts of calcium and magnesium can be prevented.
【0004】このような調製方法や薬液組成を開示した
ものとして、特開平9−87182号がある。或いは、
乳酸塩を含まない酸性濃縮液と、重炭酸塩を含むアルカ
リ側濃縮液の2液を混合する方法が特許第278144
7号に開示されている。また、ブドウ糖やカルシウム、
マグネシウムを含有する酸性濃縮液と乳酸塩を含有する
液を混合する方法を開示したものとしては、特開平8−
131542号がある。さらに、特開平8−16419
9号に記載されているように、1剤によって中性腹膜透
析液を調製しているものもある。Japanese Patent Application Laid-Open No. 9-87182 discloses such a preparation method and a chemical composition. Alternatively,
Patent No. 278144 is a method of mixing two liquids, an acidic liquid concentrate containing no lactate and an alkaline liquid concentrate containing bicarbonate.
No. 7 is disclosed. Also, glucose and calcium,
As a method for mixing an acidic concentrated liquid containing magnesium and a liquid containing lactate, JP-A-8-
There is 131542. Furthermore, JP-A-8-16419
As described in No. 9, there is also one in which a neutral peritoneal dialysate is prepared with one agent.
【0005】[0005]
【発明が解決しようとする課題】ところが、上記の方法
や製剤は、投与時の安全性の点で満足できるものではな
かった。既述したように、ブドウ糖の分解を防止するた
めに、腹膜透析液を2液に分割して保存し、投与前に2
液を混合する方法を採ったのであるが、2液に分割した
ために生じる問題点もあった。つまり、患者腹腔に投与
する際に、誤って混合前のいずれか一方の液(酸性濃縮
液、或はアルカリ性濃縮液)のみを注入した場合に予想
される腹腔へのダメージである。However, the above methods and preparations have not been satisfactory in terms of safety during administration. As described above, in order to prevent the decomposition of glucose, the peritoneal dialysis fluid is divided into two fluids and stored.
Although the method of mixing the liquids was adopted, there was a problem caused by the division into two liquids. In other words, it is the damage to the abdominal cavity that would be expected if only one of the solutions before mixing (acidic concentrated solution or alkaline concentrated solution) was mistakenly injected into the abdominal cavity of a patient.
【0006】また、上記の誤操作(未混合の単独の液の
注入)に限らず、混合後の注入であっても、何らかの事
情により、両液が充分に混ざらずに腹腔内に注入される
可能性もある。このような場合に予想される問題点つい
て、以下に記載する。先ずpHが5以下の酸濃縮液や、
pHが10以上のアルカリ性溶液のみを腹腔内に注入す
ると、細胞障害や腹痛が起きる。Further, not only the above-mentioned erroneous operation (injection of unmixed single liquid), but also injection after mixing, for some reason, both liquids can be injected into the abdominal cavity without being sufficiently mixed. There is also a nature. The problems expected in such a case are described below. First, an acid concentrate with a pH of 5 or less,
Injecting only an alkaline solution having a pH of 10 or more into the abdominal cavity causes cell damage and abdominal pain.
【0007】さらに分割した液の浸透圧が異なる場合
で、浸透圧の低い、または高い一方の液のみを腹腔に注
入したときには、以下のような問題が予想される。浸透
圧の程度に依るが、低浸透圧の場合には細胞が破裂し、
逆に高浸透圧の場合には細胞が収縮する。いずれにして
も、腹膜の正常な機能を行うためには好ましくない状況
である。場合によっては、腹痛を伴うと考えられる。従
来の2液分割型の腹膜透析液、または腹膜透析液保存容
器は上記のような場合の安全性、即ち Fail Safe機構に
関して、充分配慮されているとは言えなかった。Further, when the osmotic pressures of the divided liquids are different and only one of the low or high osmotic pressure is injected into the abdominal cavity, the following problems are expected. Depending on the osmotic pressure, cells rupture at low osmotic pressure,
Conversely, in the case of high osmotic pressure, cells contract. In any case, it is a situation that is not preferable for performing the normal function of the peritoneum. In some cases, it may be associated with abdominal pain. It cannot be said that the conventional two-liquid split type peritoneal dialysate or the peritoneal dialysate storage container has been sufficiently considered with regard to the safety in the above case, that is, the Fail Safe mechanism.
【0008】[0008]
【課題を解決するための手段】上記課題を解決するため
に、本発明は以下のような手段を講じたことを特徴とす
る。第1に、腹膜透析液の調製に誤操作があった場合、
または前記透析液が混合不充分な状態にあった場合で
も、患者腹腔内に(注入時に腹腔のダメージがより大き
い)酸性濃縮液が注入されるのを防止する手段を講じた
事である。言い換えれば、腹膜透析液保存容器におい
て、酸性濃縮液が単独で生体に注入されるのを防止する
防止手段を設けたことである。第2に、アルカリ性濃縮
液が単独で患者腹腔内に投与された場合でも、生体への
ダメージが少ないように、前記アルカリ性濃縮液の特
性、即ちpHまたは浸透圧を所定の範囲にしたことであ
る。In order to solve the above problems, the present invention is characterized by the following means. First, if there is an error in the preparation of peritoneal dialysate,
Alternatively, even if the dialysate is in an insufficiently mixed state, measures have been taken to prevent the injection of the acidic concentrated solution into the abdominal cavity of the patient (which causes a greater damage to the abdominal cavity at the time of injection). In other words, the peritoneal dialysate storage container is provided with a preventive means for preventing the acidic concentrated liquid from being independently injected into the living body. Secondly, the characteristics of the alkaline concentrate, that is, the pH or the osmotic pressure is set within a predetermined range so that the damage to the living body is small even when the alkaline concentrate is administered alone into the abdominal cavity of a patient. .
【0009】上記構成によって、混合せずに単独液を注
入した場合でも、アルカリ性濃縮液が注入されること
で、酸性濃縮液が腹腔内に注入されることで起こる、よ
り大きい腹腔へのダメージは避けられる。また、アルカ
リ性濃縮液の単独の注入においても、(腹腔内)貯留液
のpHや浸透圧が短時間で緩衝されるため、生体へのダ
メージは軽減される。With the above structure, even if a single solution is injected without being mixed, the alkaline concentrated solution is injected, and therefore, the acidic concentrated solution is injected into the abdominal cavity, which causes a larger damage to the abdominal cavity. can avoid. Further, even when the alkaline concentrated liquid is injected alone, the pH and osmotic pressure of the (intraperitoneal) stored liquid are buffered in a short time, so that the damage to the living body is reduced.
【0010】そして、前記アルカリ性濃縮液の物理的特
性を所定範囲になるように、pH調整剤の種類や濃度、
液比を特定したことも、二義的ではあるが、本発明の特
徴の1つである。これらの構成によって、アルカリ性濃
縮液の物理的特性を生体適合性を保持できる範囲に留め
ることができ、その結果、アルカリ性濃縮液を単独で注
入した場合の生体へのダメージを軽減できる。Then, the kind and concentration of the pH adjusting agent are adjusted so that the physical characteristics of the alkaline concentrate are within a predetermined range.
The fact that the liquid ratio is specified is one of the features of the present invention, although it is secondary. With these configurations, the physical characteristics of the alkaline concentrate can be kept within a range where biocompatibility can be maintained, and as a result, damage to the living body when the alkaline concentrate is injected alone can be reduced.
【0011】即ち、本発明の第1は以下のような構成で
ある。第1に、血液アルカリ化剤を含有せず、且つグル
コースを含有する酸性濃縮液と、グルコースを含有せ
ず、且つpH調整成分と血液アルカリ化剤を含有するア
ルカリ性濃縮液の2液に分離して収容された腹膜透析液
であって、前記アルカリ性濃縮液のpHが7〜9の範囲
にあり、且つ該濃縮液の浸透圧が280〜460mOs
mの範囲にあることを特徴とする腹膜透析液である。That is, the first aspect of the present invention is as follows. First, it is separated into two liquids, an acidic concentrated liquid that does not contain a blood alkaline agent and contains glucose, and an alkaline concentrated liquid that does not contain glucose and contains a pH adjusting component and a blood alkaline agent. Stored in a peritoneal dialysis solution, wherein the pH of the alkaline concentrate is in the range of 7 to 9, and the osmotic pressure of the concentrate is 280 to 460 mOs.
It is a peritoneal dialysate characterized by being in the range of m.
【0012】また、前記pH調整成分が、1〜5mM濃
度の炭酸水素ナトリウムである前記腹膜透析液である。[0012] The pH adjusting component is the peritoneal dialysis solution, which is sodium hydrogen carbonate having a concentration of 1 to 5 mM.
【0013】また、前記血液アルカリ化剤が、乳酸化合
物(無機塩)である前記腹膜透析液である。The blood alkalinizing agent is the peritoneal dialysate, which is a lactic acid compound (inorganic salt).
【0014】また、前記酸性濃縮液のpHが3〜4の範
囲にある前記腹膜透析液である。The peritoneal dialysis solution has a pH of the acidic concentrated solution in the range of 3 to 4.
【0015】また、前記酸性側濃縮液と前記アルカリ性
濃縮液の2つの液量の割合(液比)が、1:1.5〜
1:2の範囲にある前記腹膜透析液である。In addition, the ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to
The peritoneal dialysate in the range of 1: 2.
【0016】さらに、本発明の第2は以下のような構成
である。腹膜透析液を、グルコースを含有する酸性濃縮
液と、グルコースを含有せず、且つpH調整成分と血液
アルカリ化剤を含有するアルカリ性濃縮液の2液に分離
して収容した容器であって、該容器は前記酸性濃縮液を
収容する第1収容部と前記アルカリ性濃縮液を収容する
第2収容部とを有し、両液(酸性濃縮液、アルカリ性濃
縮液)の混合前は前記両収容部(第1収容部、第2収容
部)が遮断され、混合時に両収容部が連通可能となる連
通手段を有し、さらに患者体内に投与する際に、実質的
に当該収容容器からの唯一の液流出手段となる液出口部
を第2収容部に設けたことを特徴とする腹膜透析液保存
容器である。Further, the second aspect of the present invention is as follows. A container in which a peritoneal dialysate is separated and stored into two liquids, an acidic concentrated liquid containing glucose and an alkaline concentrated liquid containing no glucose and containing a pH adjusting component and a blood alkalizing agent, The container has a first storage part for storing the acidic concentrated liquid and a second storage part for storing the alkaline concentrated liquid, and both the storage parts before mixing both liquids (acidic concentrated liquid and alkaline concentrated liquid) ( The first container, the second container) are shut off, and the container has a communication means that allows the two containers to communicate with each other at the time of mixing, and when administered into the patient's body, substantially the only liquid from the container. A peritoneal dialysis solution storage container is characterized in that a liquid outlet serving as an outflow means is provided in the second container.
【0017】また、前記アルカリ性濃縮液のpHが7〜
9の範囲にある前記腹膜透析液保存容器である。The pH of the alkaline concentrate is 7 to 7.
The peritoneal dialysate storage container in the range of 9.
【0018】また、前記酸性濃縮液のpHが3〜4の範
囲にある前記腹膜透析液保存容器である。Further, the peritoneal dialysate storage container has a pH of the acidic concentrated liquid in the range of 3 to 4.
【0019】また、前記pH調整成分が、1〜5mM濃
度の炭酸水素ナトリウムである前記腹膜透析液保存容器
である。Further, in the container for storing the peritoneal dialysate, the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM.
【0020】また、前記アルカリ性濃縮液の浸透圧が2
80〜460mOsmの範囲にある前記腹膜透析液保存
容器である。The osmotic pressure of the alkaline concentrate is 2
The container for storing the peritoneal dialysate in the range of 80 to 460 mOsm.
【0021】また、前記酸性側濃縮液と前記アルカリ性
濃縮液の2つの液量の割合(液比)が、1:1.5〜
1:2の範囲にある前記腹膜透析液保存容器である。Further, the ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to
The storage container for the peritoneal dialysate in the range of 1: 2.
【0022】また、前記第2収容部において、前記連通
手段を設けた側と反対側の領域に前記液出口を形成した
前記腹膜透析液保存容器である。Further, the peritoneal dialysate storage container has the liquid outlet formed in a region opposite to the side where the communication means is provided in the second container.
【0023】また、前記収容容器の出口部に患者腹腔内
に、容器に収容した液を注入するための回路セットを連
結した前記腹膜透析液保存容器である。Further, the peritoneal dialysate storage container has a circuit set for injecting the liquid contained in the container into the abdominal cavity of the patient at the outlet of the container.
【0024】また、前記血液アルカリ化剤が、乳酸化合
物(無機塩)である前記腹膜透析液保存容器である。Further, in the container for storing peritoneal dialysate, the blood alkalizing agent is a lactic acid compound (inorganic salt).
【0025】[0025]
【発明の実施の形態】以下、図と共に本発明の1つの実
施態様、および好ましい実施態様について述べる。図1
は本発明の腹膜透析液保存容器1である。保存容器1
は、酸性濃縮液を収容する第1収容部2と、アルカリ性
濃縮液を収容する第2収容部3とを有する。保存容器1
はまた、前記両収容部2、3とを混合前には遮断し、混
合時に両収容部を連通することができる連通手段4を有
する。連通手段4としては、図1に示すような両収容部
を連絡する連通路5とそれに装着したクランプ6であっ
ても良いし、図2に示すような、混合時に両収容部の隔
壁7を破断するイージーピール(easy peel)型のもの
であっても良い。そして、図示しないが、両収容部に保
存された各液の採取や、各液への混注を行うためのポー
トを設けるのは、特に制限されない。BEST MODE FOR CARRYING OUT THE INVENTION One embodiment and a preferred embodiment of the present invention will be described below with reference to the drawings. Figure 1
Is the peritoneal dialysate storage container 1 of the present invention. Storage container 1
Has a first storage part 2 for storing an acidic concentrated liquid and a second storage part 3 for storing an alkaline concentrated liquid. Storage container 1
Further, it has a communication means 4 capable of shutting off the two accommodation parts 2 and 3 before mixing and communicating the both accommodation parts at the time of mixing. The communication means 4 may be a communication passage 5 for connecting both storage portions as shown in FIG. 1 and a clamp 6 attached thereto, or a partition wall 7 of both storage portions at the time of mixing as shown in FIG. It may be of the easy peel type that breaks. Although not shown, provision of a port for collecting each of the liquids stored in both of the storage parts and providing a mixed injection into each liquid is not particularly limited.
【0026】しかし、患者腹腔に投与する際に、腹膜透
析液保存容器1から透析液が流出する実質的な液出口8
は第2収容部3のみに設ける。液出口部8が第1収容部
2ではなく、第2収容部3のみに設けられておれば、そ
の形成位置、形態や数は特に限定されるものではなく、
必要に応じて自由に設計することができる。但し、液出
口部8が隔壁7や連通路5の傍に設けられていると、混
合不充分な場合に酸性濃縮液が直接流出する恐れが無い
とは言えないため、隔壁や連通路の形成された部位とは
反対側に、液出口部8を設けるのが好ましい。However, when administered to the peritoneal cavity of a patient, a substantial fluid outlet 8 through which the dialysate flows out from the peritoneal dialysate storage container 1.
Is provided only in the second storage portion 3. If the liquid outlet portion 8 is provided only in the second storage portion 3 instead of in the first storage portion 2, the formation position, the form and the number thereof are not particularly limited,
It can be freely designed as needed. However, if the liquid outlet portion 8 is provided near the partition wall 7 or the communication passage 5, it cannot be said that the acidic concentrated liquid will not directly flow out when the mixing is insufficient, so that the formation of the partition wall or the communication passage is performed. It is preferable to provide the liquid outlet portion 8 on the side opposite to the formed portion.
【0027】例えば、図1に示すように連通路5が左側
上方に形成されている場合は、液出口部8を右側端部下
方に形成し、図2に示すように、隔壁7が左側全域に形
成されている場合は、液出口部8を右側端部の領域のい
ずれかに形成する。液出口8の数としては、製造の際の
負担やその効果の点から、せいぜい1〜2が実質的であ
る。また、液出口の大きさは保存される透析液量から流
入速度を逆算し、そのために必要な出口部面積を有する
ように設計できる。For example, when the communication passage 5 is formed on the upper left side as shown in FIG. 1, the liquid outlet portion 8 is formed below the right end portion, and as shown in FIG. In the case of being formed at 1, the liquid outlet portion 8 is formed at any of the right end portions. The number of the liquid outlets 8 is practically 1 to 2 at most from the viewpoint of the burden in manufacturing and the effect thereof. Further, the size of the liquid outlet can be designed so that the inflow velocity is calculated back from the amount of dialysate stored and the outlet area required for that purpose is obtained.
【0028】次に透析液の組成や物理的特性について、
述べる。先ず2液を混合後に調製される腹膜透析液、即
ち患者腹腔内に投与される液であるが、pHが6.5〜
7.5の範囲にあるのが望ましい。また、除水の必要性
に応じて、2液混合後に280〜480mOsm、或は
それよりやや広い範囲の浸透圧のものが選択できる。上
記の最終的に調製される腹膜透析液の物理的特性や各液
に要求される事項を考慮して、各液の組成や物理的特性
が決定される。Next, regarding the composition and physical characteristics of the dialysate,
Describe. First, the peritoneal dialysate prepared after mixing the two solutions, that is, the solution to be administered intraperitoneally to a patient, has a pH of 6.5 to 5.
It is preferably in the range of 7.5. Further, depending on the necessity of removing water, it is possible to select one having an osmotic pressure of 280 to 480 mOsm after mixing the two liquids or a slightly wider range than that. The composition and physical properties of each liquid are determined in consideration of the physical properties of the finally prepared peritoneal dialysate and the requirements for each liquid.
【0029】先ず酸・塩基平衡の観点から述べると、混
合前の酸性濃縮液に含まれるグルコースの分解を防止す
るために、酸性濃縮液のpHは3〜4の範囲にあるのが
望ましい。となれば、アルカリ性濃縮液のpHは、該濃
縮液側に添加する緩衝剤、即ちpH調整成分の種類とそ
の添加量によって影響される。つまり、緩衝能の小さい
水酸化ナトリウムなどをpH調整成分として選ぶと、ア
ルカリ性濃縮液のpHを高くしなければならないが、中
性よりややアルカリ側の領域で緩衝能力の高い炭酸水素
ナトリウムをpH調整成分として選ぶと、アルカリ性濃
縮液のpHを低めに抑えることができる。First, from the viewpoint of acid-base equilibrium, the pH of the acidic concentrate is preferably in the range of 3 to 4 in order to prevent the decomposition of glucose contained in the acidic concentrate before mixing. Then, the pH of the alkaline concentrate is affected by the type of buffering agent added to the concentrate side, that is, the pH adjusting component, and the amount of addition thereof. In other words, if you select sodium hydroxide, which has a low buffering capacity, as the pH-adjusting component, you must raise the pH of the alkaline concentrate, but adjust the pH of sodium bicarbonate that has a high buffering capacity in the slightly alkaline region rather than neutral. When selected as a component, the pH of the alkaline concentrate can be suppressed to a low level.
【0030】また、アルカリ性濃縮液を直接体内に注入
した場合に、生体が有する緩衝機能によって、短時間に
復元される範囲のpHとして、およそ7〜9と見込み、
その範囲のpHを実現するため、濃度1〜3mMの炭酸
水素ナトリウムを添加するのが好ましい。When the alkaline concentrated solution is directly injected into the body, the pH of the range that is restored in a short time by the buffer function of the living body is expected to be about 7-9.
In order to realize the pH within the range, it is preferable to add sodium hydrogencarbonate having a concentration of 1 to 3 mM.
【0031】次に浸透圧の観点から、腹膜透析液の好ま
しい実施形態について、述べる。酸性濃縮液に含有され
るグルコースの安定性を考慮すると、酸性側濃縮液にな
るべく他の成分を添加しないのが望ましい。そのため、
従来の透析液の中には酸性濃縮液の浸透圧を低くし、逆
にアルカリ性濃縮液の浸透圧を高くすることで、混合後
の腹膜透析液の浸透圧を生体が許容できる範囲にするも
のもある。しかし、一方の液の浸透圧を極端に高くし、
逆にもう一方の液の浸透圧を低くした場合に、既述した
ような誤操作による注入、或は混合不充分な際の注入が
なされると、腹腔に対して少なからぬダメージを与え
る。特に低浸透圧の液が腹腔内に注入されると、腹膜中
皮細胞を損傷するため、好ましくない。Next, from the viewpoint of osmotic pressure, a preferred embodiment of the peritoneal dialysate will be described. Considering the stability of glucose contained in the acidic concentrate, it is desirable to add no other component to the acidic concentrate as much as possible. for that reason,
In the conventional dialysate, the osmotic pressure of the acidic concentrate is reduced and the osmotic pressure of the alkaline concentrate is increased to make the osmotic pressure of the peritoneal dialysate after mixing within a range that the living body can tolerate. There is also. However, making the osmotic pressure of one of the liquids extremely high,
On the contrary, when the osmotic pressure of the other liquid is lowered, if the injection is performed by the erroneous operation as described above or the injection is performed when the mixing is insufficient, it causes considerable damage to the abdominal cavity. In particular, when a solution having a low osmotic pressure is injected into the abdominal cavity, the peritoneal mesothelial cells are damaged, which is not preferable.
【0032】従って、2液分割型の腹膜透析液、または
その液を収容した透析液保存容器では、一方の側の濃縮
液が単独で腹腔内に注入される危険性、2液が混合不充
分のまま注入される危険性を想定した場合、注入される
可能性のある液側の浸透圧を280〜460mOsmの
範囲にするのが好ましい。本実施態様で言うならば、ア
ルカリ側濃縮液において、上記範囲の浸透圧に設定する
のが好ましい。腹腔内に注入される透析液の浸透圧が上
記範囲にあれば、腹膜中皮や腹腔内の細胞等への損傷や
影響を軽減できる。Therefore, in a two-liquid split type peritoneal dialysis fluid or a dialysis fluid storage container containing the fluid, there is a risk that the concentrated fluid on one side is independently injected into the abdominal cavity and the two fluids are not sufficiently mixed. When assuming the risk of being injected as it is, it is preferable to set the osmotic pressure on the liquid side, which may be injected, in the range of 280 to 460 mOsm. In the present embodiment, it is preferable to set the osmotic pressure in the above range in the concentrated solution on the alkaline side. When the osmotic pressure of the dialysate injected into the abdominal cavity is within the above range, damage or influence on the peritoneal mesothelium or cells in the abdominal cavity can be reduced.
【0033】さらに、上記の浸透圧の調整、また滅菌時
の各分割液への熱負荷の影響から、酸性側濃縮液とアル
カリ側濃縮液との液比は、1:1.5〜1:2の範囲に
するのが好ましい。即ち、液比が大きすぎたり、小さす
ぎると、2液混合後の浸透圧の予測に誤差がおき易くな
り、また液量によって、濃縮液にかかる熱負荷が異なる
ため、2つの濃縮液に対して均等に熱滅菌することが困
難となる。Furthermore, the liquid ratio of the concentrated liquid on the acidic side to the concentrated liquid on the alkaline side is 1: 1.5 to 1: 1 due to the above-mentioned adjustment of the osmotic pressure and the influence of the heat load on each divided liquid during sterilization. A range of 2 is preferable. That is, if the liquid ratio is too large or too small, it is easy to make an error in the prediction of the osmotic pressure after mixing the two liquids, and the heat load applied to the concentrated liquid differs depending on the liquid amount. It becomes difficult to heat sterilize evenly.
【0034】本発明でいう血液アルカリ化剤とは、患者
の腹膜を介して、患者の血液の酸・塩基平衡調節を行う
ものを言い、例えば乳酸ナトリウム等の乳酸化合物であ
る。The blood alkalinizing agent referred to in the present invention refers to an agent that adjusts the acid-base balance of the blood of a patient through the peritoneum of the patient, and is, for example, a lactic acid compound such as sodium lactate.
【0035】[0035]
【実施例】実験1.
腹膜透析液の調製例
本発明の一例である腹膜透析液の混合前の各液の組成,
pH,浸透圧と、混合後の透析液のpH、浸透圧を以下
に示す。EXAMPLES Experiment 1. Example of preparation of peritoneal dialysate Composition of each fluid before mixing of peritoneal dialysate, which is an example of the present invention,
The pH and osmotic pressure and the pH and osmotic pressure of the dialysate after mixing are shown below.
【0036】(1)酸性濃縮液
グルコース : グルコース濃度を変更した下記の3種
類のものを調製した。
a.239.2mmol/l, b.350.2mmol/
l, c.522.7mmol/l
塩化カルシウム : 5.56mmol/l
塩化マグネシウム : 1.41mmol/l
3.5%塩酸 : 0.3ml/l
上記の組成にて調製された酸性濃縮液は、pHが3.4
6、浸透圧はグルコース濃度によって、それぞれ270
mOsm(a),393mOsm(b),565mOs
m(c)を示した。(1) Acidic Concentrated Solution Glucose: The following three types of glucose having different glucose concentrations were prepared. a.239.2 mmol / l, b.350.2 mmol /
l, c. 522.7 mmol / l calcium chloride: 5.56 mmol / l magnesium chloride: 1.41 mmol / l 3.5% hydrochloric acid: 0.3 ml / l The acidic concentrate prepared with the above composition has a pH of Is 3.4
6. The osmotic pressure is 270 depending on the glucose concentration.
mOsm (a), 393mOsm (b), 565mOs
m (c) was shown.
【0037】(2)アルカリ性濃縮液(pH:8.1、浸
透圧 :392mOsm)
塩化ナトリウム : 151.6mmol/l
乳酸ナトリウム : 54.9mmol/l
炭酸水素ナトリウム : 2.0mmol/l(2) Alkaline concentrated solution (pH: 8.1, osmotic pressure: 392 mOsm) Sodium chloride: 151.6 mmol / l Sodium lactate: 54.9 mmol / l Sodium hydrogen carbonate: 2.0 mmol / l
【0038】上記の酸性濃縮液720mlとアルカリ性
濃縮液1280mlを2つの隔室にそれぞれ収容した
後、115℃で30分間オートクレーブ滅菌を行い、隔
室を連通して、上記2液を混合した。混合後の腹膜透析
液のpHは7.1〜7.3を示し、同じく浸透圧は34
0〜470 mOsm[異なるグルコース濃度による混
合後の各透析液の浸透圧平均値は350 mOsm
(a),394 mOsm(b),460 mOsm
(c)]を示し、それぞれ生理的な領域にあることが示
された。After 720 ml of the above acidic concentrate and 1280 ml of the above alkaline concentrate were respectively housed in two compartments, autoclave sterilization was performed at 115 ° C. for 30 minutes, the compartments were communicated, and the two solutions were mixed. The pH of the peritoneal dialysate after mixing was 7.1 to 7.3, and the osmotic pressure was 34
0-470 mOsm [The average osmotic pressure of each dialysate after mixing with different glucose concentrations is 350 mOsm.
(A), 394 mOsm (b), 460 mOsm
(C)] is shown, and each is shown to be in a physiological region.
【0039】実験2.培養細胞を用いた生体適合性の評
価
(1)概要
混合前の酸性濃縮液、またはアルカリ性濃縮液が直接腹
腔内に投与された場合の生体への影響をシミュレーショ
ンするものとして、本実験を行った。以下に示す各被験
液をV79細胞(ハムスター肺由来の繊維芽細胞)に3
0分間暴露して、暴露後の細胞活性をWST-1試薬
(宝酒造)を用いて評価した。本実験系では、溶液のp
Hのみならず浸透圧の生細胞に与える影響を比較した。Experiment 2. Evaluation of biocompatibility using cultured cells (1) Outline This experiment was conducted as a simulation of the effect on the living body when an acidic concentrate before mixing or an alkaline concentrate was directly administered intraperitoneally . Each test solution shown below was added to V79 cells (hamster lung-derived fibroblasts)
After exposure for 0 minutes, the cell activity after the exposure was evaluated using WST-1 reagent (Takara Shuzo). In this experimental system, the p
The effect of not only H but also osmotic pressure on living cells was compared.
【0040】(2)各被験液
細胞に対する、pHと浸透圧の影響を確認するために、
以下に示す7種の被験液を用いた。ネガティブコントロ
ールには、臨床で使用されている腹膜透析液を用いた。
酸性、低浸透圧の溶液
酸性、高浸透圧の溶液
炭酸水素ナトリウムを使用した弱アルカリ性、低浸透
圧の溶液
炭酸水素ナトリウムを使用した弱アルカリ性、高浸透
圧の溶液
水酸化ナトリウムを使用した強アルカリ性、低浸透圧
の溶液
水酸化ナトリウムを使用した強アルカリ性、高浸透圧
の溶液
コントロール(中性腹膜透析液、生体適合性良)
各被験液は表1の成分分量とpH及び浸透圧になるよう
に調製した。(2) In order to confirm the influence of pH and osmotic pressure on each test solution cell,
The following seven test liquids were used. The peritoneal dialysate used clinically was used as a negative control. Acidic, low osmotic solution Acidic, high osmotic solution Weak alkaline using sodium bicarbonate, low osmotic solution Weak alkaline using sodium bicarbonate, high osmotic solution Strong alkaline using sodium hydroxide , Low osmotic solution solution Strongly alkaline and high osmotic solution control using sodium hydroxide (neutral peritoneal dialysis solution, good biocompatibility) Each test solution should have the component content, pH and osmotic pressure of Table 1. Was prepared.
【0041】[0041]
【表1】 [Table 1]
【0042】(3)方法及び結果
98穴プレートにV79細胞を10,000個づつ播種
して、1晩培養した。この培養プレートに各被験液を分
注して、細胞に30分間暴露した。その後、WST−1
試薬を加えて細胞生存率(培養用培地に暴露したものに
対する吸光度比)を測定した。図3に結果を示す。コン
トロールの中性腹膜透析液の暴露では、87%の細胞の
生存が確認された。これに対して、各被験液では、67
〜80%の生存率に低下していたが、被験液,の酸
性溶液や、,の強アルカリ性溶液に比べると、,
の弱アルカリ性溶液の方が高く維持されていることが
分かる。また、被験液とを比較すると、高浸透圧の
の溶液の方が高い細胞生存率を示した。(3) Method and Results 10,000 V79 cells were seeded on a 98-well plate and cultured overnight. Each test solution was dispensed into this culture plate and exposed to the cells for 30 minutes. Then WST-1
The cell viability (absorbance ratio to that exposed to the culture medium) was measured by adding a reagent. The results are shown in FIG. Upon exposure to a control neutral peritoneal dialysate, 87% cell survival was confirmed. On the other hand, in each test solution, 67
Although the survival rate was reduced to ~ 80%, compared to the acidic solution of test solution, or the strong alkaline solution of,
It can be seen that the weak alkaline solution of 1 is maintained at a higher level. Further, when compared with the test solution, the hyperosmolarity solution showed higher cell viability.
【0043】[0043]
【発明の効果】腹膜透析液の液(バッグ)交換の際に、
患者の誤操作等によって、未混合のまま、或いは混合不
充分で患者腹腔内に液を注入することがあっても、生体
の受けるダメージをより軽減することができる。[Effects of the Invention] When exchanging the peritoneal dialysis fluid (bag),
Even if the liquid is injected into the abdominal cavity of the patient due to an erroneous operation by the patient or due to insufficient mixing, the damage to the living body can be further reduced.
【図1】本発明の腹膜透析液保存容器の一実施態様の全
体的概要を示す模式図。FIG. 1 is a schematic diagram showing an overall outline of one embodiment of a peritoneal dialysate storage container of the present invention.
【図2】腹膜透析液保存容器の別の実施態様の概要を示
す模式図。FIG. 2 is a schematic view showing the outline of another embodiment of a peritoneal dialysate storage container.
【図3】各被験液(或はコントロール)の細胞生存率に
与える影響を示すグラフ。FIG. 3 is a graph showing the effect of each test solution (or control) on cell viability.
1.腹膜透析液保存容器 2.第1収容部 3.第2収容部 4.連通手段 5.連通路 6.クランプ(遮断器具) 7.隔壁 8.液出口部 1. Peritoneal dialysate storage container 2. First storage part 3. Second storage section 4. Communication means 5. Communication passage 6. Clamp (blocking device) 7. Partition 8. Liquid outlet
Claims (14)
ースを含有する酸性濃縮液と、グルコースを含有せず、
且つpH調整成分と血液アルカリ化剤を含有するアルカ
リ性濃縮液の2液に分離して収容された腹膜透析液であ
って、前記アルカリ性濃縮液のpHが7〜9の範囲にあ
り、且つ該濃縮液の浸透圧が280〜460mOsmの
範囲にあることを特徴とする腹膜透析液。1. An acidic concentrated liquid which does not contain a blood alkalizing agent and contains glucose, and does not contain glucose,
A peritoneal dialysis fluid which is separately stored in two solutions of an alkaline concentrate containing a pH adjusting component and a blood alkalizing agent, wherein the pH of the alkaline concentrate is in the range of 7 to 9 and A peritoneal dialysate characterized in that the osmotic pressure of the fluid is in the range of 280 to 460 mOsm.
る請求項1記載の腹膜透析液。2. The peritoneal dialysis solution according to claim 1, wherein the pH of the acidic concentrated solution is in the range of 3 to 4.
酸水素ナトリウムである請求項1または2のいずれかの
項に記載の腹膜透析液。3. The peritoneal dialysis solution according to claim 1, wherein the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM.
の2つの液量の割合(液比)が、1:1.5〜1:2の
範囲にある請求項1〜3のいずれかの項に記載の腹膜透
析液。4. The ratio (liquid ratio) of the two liquid amounts of the acidic side concentrated liquid and the alkaline concentrated liquid is in the range of 1: 1.5 to 1: 2. The peritoneal dialysis solution according to the item.
機塩)である請求項1〜4のいずれかの項に記載の腹膜
透析液。5. The peritoneal dialysis solution according to claim 1, wherein the blood alkalizing agent is a lactic acid compound (inorganic salt).
濃縮液と、グルコースを含有せず、且つpH調整成分と
血液アルカリ化剤を含有するアルカリ性濃縮液の2液に
分離して収容した容器であって、該容器は前記酸性濃縮
液を収容する第1収容部と前記アルカリ性濃縮液を収容
する第2収容部とを有し、両液(酸性濃縮液、アルカリ
性濃縮液)の混合前は前記両収容部(第1収容部、第2
収容部)が遮断され、混合時に両収容部が連通可能とな
る連通手段を有し、さらに患者体内に投与する際に、実
質的に当該収容容器からの唯一の液流出手段となる液出
口部を第2収容部に設けたことを特徴とする腹膜透析液
保存容器。6. A container in which the peritoneal dialysate is separated and contained into two liquids, an acidic concentrated liquid containing glucose and an alkaline concentrated liquid containing no glucose and containing a pH adjusting component and a blood alkalinizing agent. The container has a first storage part for storing the acidic concentrate and a second storage part for storing the alkaline concentrate, and before mixing both liquids (acidic concentrate, alkaline concentrate) Both of the accommodating parts (first accommodating part, second accommodating part)
(Accommodation part) is cut off, and has a communication means capable of communicating both the storage parts at the time of mixing, and further, when administered into the patient's body, is a liquid outlet part which is substantially the only liquid outflow means from the storage container. A container for storing peritoneal dialysate, characterized in that the container is provided in the second container.
囲にある請求項6記載の腹膜透析液保存容器。7. The peritoneal dialysate storage container according to claim 6, wherein the pH of the alkaline concentrate is in the range of 7-9.
る請求項6または7のいずれかの項に記載の腹膜透析液
保存容器。8. The peritoneal dialysate storage container according to claim 6, wherein the acidic concentrated liquid has a pH in the range of 3 to 4.
酸水素ナトリウムである請求項6〜8のいずれかの項に
記載の腹膜透析液保存容器。9. The peritoneal dialysate storage container according to claim 6, wherein the pH adjusting component is sodium hydrogen carbonate having a concentration of 1 to 5 mM.
〜460mOsmの範囲にある請求項6〜9のいずれか
の項に記載の腹膜透析液保存容器。10. The osmotic pressure of the alkaline concentrate is 280.
The storage container for peritoneal dialysate according to any one of claims 6 to 9, which is in the range of 460 mOsm to 460 mOsm.
液の2つの液量の割合(液比)が、1:1.5〜1:2
の範囲にある請求項6〜10のいずれかの項に記載の腹
膜透析液保存容器。11. The ratio (liquid ratio) of the two liquid amounts of the concentrated liquid on the acidic side and the concentrated liquid on the alkaline side is 1: 1.5 to 1: 2.
The peritoneal dialysate storage container according to any one of claims 6 to 10, which is in the range of.
を設けた側と反対側の領域に前記液出口を形成した請求
項6〜11のいずれかの項に記載の腹膜透析液保存容
器。12. The peritoneal dialysis solution storage container according to claim 6, wherein the liquid outlet is formed in a region of the second storage portion opposite to the side where the communication means is provided.
容器に収容した液を注入するための回路セットを連結し
た請求項6〜12のいずれかの項に記載の腹膜透析液保
存容器。13. The patient's abdominal cavity at the outlet of the container,
The peritoneal dialysate storage container according to any one of claims 6 to 12, wherein a circuit set for injecting the liquid contained in the container is connected.
ましくは乳酸塩である請求項6〜13のいずれかの項に
記載の腹膜透析液保存容器。14. The peritoneal dialysate storage container according to claim 6, wherein the blood alkalinizing agent is an organic acid salt, preferably a lactate salt.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001284260A JP2003088582A (en) | 2001-09-19 | 2001-09-19 | Peritoneal dialysate and storage vessel |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001284260A JP2003088582A (en) | 2001-09-19 | 2001-09-19 | Peritoneal dialysate and storage vessel |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2003088582A true JP2003088582A (en) | 2003-03-25 |
Family
ID=19107613
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2001284260A Pending JP2003088582A (en) | 2001-09-19 | 2001-09-19 | Peritoneal dialysate and storage vessel |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2003088582A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004108059A1 (en) * | 2003-06-06 | 2004-12-16 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
JP2006000482A (en) * | 2004-06-18 | 2006-01-05 | Jms Co Ltd | Biocompatible liquid preparation, method for its production and method for its preservation |
JP2006174988A (en) * | 2004-12-22 | 2006-07-06 | Jms Co Ltd | Package of medical system and its thermal sterilization method |
JP2010252641A (en) * | 2009-04-22 | 2010-11-11 | Mitsubishi Rayon Co Ltd | Method for producing polysaccharide derived from lactic bacterium |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2781447B2 (en) * | 1989-05-26 | 1998-07-30 | フレゼニウス アクチエンゲゼルシャフト | Non-precipitated dialysis solution |
JP2000245826A (en) * | 1999-02-26 | 2000-09-12 | Jms Co Ltd | Neutral peritoneal dialysate |
-
2001
- 2001-09-19 JP JP2001284260A patent/JP2003088582A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2781447B2 (en) * | 1989-05-26 | 1998-07-30 | フレゼニウス アクチエンゲゼルシャフト | Non-precipitated dialysis solution |
JP2000245826A (en) * | 1999-02-26 | 2000-09-12 | Jms Co Ltd | Neutral peritoneal dialysate |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004108059A1 (en) * | 2003-06-06 | 2004-12-16 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
JPWO2004108059A1 (en) * | 2003-06-06 | 2006-07-20 | 株式会社大塚製薬工場 | Aseptic formulation |
CN100471480C (en) * | 2003-06-06 | 2009-03-25 | 株式会社大塚制药工场 | Aseptic combination preparation |
KR101168848B1 (en) * | 2003-06-06 | 2012-07-26 | 가부시키가이샤 오츠까 세이야꾸 고죠 | Aseptic combination preparation |
US8404274B2 (en) | 2003-06-06 | 2013-03-26 | Otsuka Pharmaceutical Factory, Inc. | Aseptic combination preparation |
JP2006000482A (en) * | 2004-06-18 | 2006-01-05 | Jms Co Ltd | Biocompatible liquid preparation, method for its production and method for its preservation |
JP2006174988A (en) * | 2004-12-22 | 2006-07-06 | Jms Co Ltd | Package of medical system and its thermal sterilization method |
JP2010252641A (en) * | 2009-04-22 | 2010-11-11 | Mitsubishi Rayon Co Ltd | Method for producing polysaccharide derived from lactic bacterium |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100367942C (en) | Bicarbonate-based solutions for dialysis therapies | |
JP3034303B2 (en) | Histidine buffered peritoneal dialysis solution | |
EP1585531B1 (en) | Biocompatible dialysis fluids containing icodextrins | |
EP1753437B1 (en) | Bicarbonate-based peritoneal dialysis solutions | |
JP5329420B2 (en) | Stable bicarbonate-containing chemicals | |
JP4135849B2 (en) | Solution, in particular a solution for hemodialysis or peritoneal dialysis and method for its preparation | |
KR20020008145A (en) | Method, apparatus and components of dialysis systems | |
CN1336825A (en) | Bicarbonate-based solution in two parts for peritoneal dialysis or substitution in continuous renal replacement therapy | |
MXPA06000973A (en) | Dialysis solutions with reduced levels of glucose degradation products. | |
MXPA04012299A (en) | A stable bicarbonate-based solution in a single container. | |
JPWO2004108059A1 (en) | Aseptic formulation | |
JP4284737B2 (en) | Neutral peritoneal dialysis solution | |
JP2003088582A (en) | Peritoneal dialysate and storage vessel | |
JP3871442B2 (en) | Peritoneal dialysate | |
JP3909063B2 (en) | In-use mixed chemicals with improved safety | |
EP2962683A1 (en) | Low sodium solution | |
JP2008119509A (en) | Solution set for preparation of peritoneal dialysis fluid | |
US20060079464A1 (en) | Peritoneal dialysate containing taurine | |
JP2004154558A (en) | Multi-chamber container for storing fluid replacement for filtration type artificial kidney | |
US20200338117A1 (en) | Method and system for providing peritoneal dialysis fluids with variable potassium concentrations | |
WO2019086318A1 (en) | "method and system for providing peritoneal dialysis fluids with varying sodium concentrations" | |
JP4533351B2 (en) | In-use mixed chemicals with improved safety |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080805 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20101228 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110118 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20111004 |