【０００１】[0001]
【産業上の利用分野】本発明は、炭酸水素イオンを含有
する透析液、すなわち重曹透析液を調製するための固形
製剤に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid preparation for preparing a dialysate containing hydrogen carbonate ions, that is, a sodium bicarbonate dialysate.
【０００２】[0002]
【従来の技術】近年、下記のような重曹透析液の需要が
増加している。Ｎａ+ １２０〜１５０ ｍＥｑ／ｌＫ+ ０．５〜３．０ ｍＥｑ／ｌＣａ++ １．５〜４．５ ｍＥｑ／ｌＭｇ++ ０〜２．０ ｍＥｑ／ｌＣｌ- ９０〜１３５ ｍＥｑ／ｌＨＣＯ3- ２０〜 ３５ ｍＥｑ／ｌＣＨ3 ＣＯ2- ５〜 １０ ｍＥｑ／ｌブドウ糖 ０〜２．５ ｇ／ｌしかし、このような組成の透析液は、１人１回の血液透
析に大量（約３５０リットル）使用され、しかも製剤的
に不安定なことから、使用直前に調製せざるを得ず、各
種電解質の正確な秤量、溶解、ｐＨ調整など煩雑な作業
を要するものであった。2. Description of the Related Art In recent years, the demand for the following sodium bicarbonate dialysate has been increasing.Na + 120~150 mEq / l K + 0.5~3.0 mEq / l Ca ++ 1.5~4.5 mEq / l Mg ++ 0~2.0 mEq / l Cl - 90~135 mEq/ l HCO 3 - 20~ 35 mEq / l CH 3 CO 2 - 5~ 10 mEq / l glucose 0 to 2.5 g / l, however, dialysate having such a composition is the one single hemodialysis Since a large amount (about 350 liters) was used and the formulation was unstable, it had to be prepared just before use, and required complicated work such as accurate weighing, dissolution, and pH adjustment of various electrolytes. .
【０００３】そこで前記作業を軽減するものとして、１
人１回分の包装単位で、必要な成分中炭酸水素ナトリウ
ムを別にした濃厚原液（約１１リットル）が市販される
ようになった。しかし、運搬、保管場所、透析液調製時
の取り扱い等において十分改良されたとは言えず、その
後も種々の提案がなされている。例えば、特開平３−７
４３３１号公報には、重曹透析液調製に必要な成分を、
カルシウム成分を含み炭酸水素ナトリウムを含まない群
と炭酸水素ナトリウムを含みカルシウム成分を含まない
群とに分け、前者にはｐＨ調整製剤としての酢酸を含ま
せ、両群をそれぞれ造粒して混合した透析用剤が開示さ
れている。この発明は、所定量の透析用剤を単に計算量
の水に溶解するだけで重曹透析液の調製ができるように
したものであるが、ｐＨ調整剤として液体の酸が使用さ
れているため、たとえ少量であっても経時的に酸と炭酸
水素ナトリウムの反応が進み、炭酸水素イオン含量の減
少をもたらす虞があり、さらには、長期保存中に造粒物
の凝集が生じ、取り扱いに不便を来す可能性があるなど
の問題点を有している。To reduce the above work, therefore, 1
A concentrated stock solution (about 11 liters) from which sodium hydrogen carbonate as a necessary component has been removed has been put on the market in a packaging unit for one person. However, it cannot be said that it has been sufficiently improved in transportation, storage location, handling during preparation of dialysate, and various proposals have been made since then. For example, Japanese Patent Laid-Open No. 3-7
No. 4331 discloses components necessary for preparation of sodium bicarbonate dialysate,
It was divided into a group containing calcium component and no sodium hydrogen carbonate and a group containing sodium hydrogen carbonate and no calcium component. The former was mixed with acetic acid as a pHadjusting preparation, and both groups were granulated and mixed. A dialysis agent is disclosed. This invention is a sodium bicarbonate dialysate can be prepared by simply dissolving a predetermined amount of dialysis agent in a calculated amount of water, but since a liquid acid is used as a pH adjusting agent, Even if the amount is small, the reaction between the acid and sodium hydrogencarbonate may proceed over time, resulting in a decrease in the hydrogencarbonate ion content.Furthermore, agglomeration of the granulated product may occur during long-term storage, which makes handling inconvenient. There is a problem that it may come.
【０００４】[0004]
【発明が解決しようとする課題】本発明の課題は、重曹
透析液を調製するために必要な電解質とｐＨ調整剤とし
ての酸を含む固形製剤であって、安定性に優れ、取り扱
い易く、用時に水に速やかに溶ける透析用剤を提供する
ことにある。The object of the present invention is a solid preparation containing an electrolyte necessary for preparing a sodium bicarbonate dialysate and an acid as a pHadjusting agent, which is excellent in stability, easy to handle, and easy to use. Sometimes it is to provide a dialysis agent that dissolves rapidly in water.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、透析用剤
に必要な各電解質、さらには必要に応じて添加するブド
ウ糖の安定性及び吸湿性について考慮しながら、ｐＨ調
整剤をも含めた安定な固形製剤の可能性について鋭意研
究した。その結果、ｐＨ調整剤として薬理学的に許容さ
れる固体の有機酸を使用し、相互に反応し易い成分を群
分けしてそれぞれ顆粒剤とし、両者を混合することによ
って前記課題を解決できることを見出した。本発明はそ
の知見に基づいて完成したものである。Means for Solving the Problems The present inventors have taken into consideration each electrolyte necessary for a dialysis agent, and further the stability and hygroscopicity of glucose added as necessary, while adjusting the pHadjustment.
It was intensively studied the possibility of stable solid formulations including theinteger agents. As a result, it is possible to solve the above-mentioned problems by using a solid organic acid that is pharmaceutically acceptable as a pHadjuster , grouping components that easily react with each other into granules, and mixing the two together. I found it. The present invention has been completed based on the findings.
【０００６】すなわち、本発明は、少なくともＮａ+、
Ｃａ++、Ｃｌ-及びＨＣＯ3-を含有する透析液の調製
に必要な電解質のうち、重炭酸塩以外の１種以上及びｐ
Ｈ調整剤としての薬理学的に許容される固体の有機酸を
含有する第１顆粒剤と、重炭酸塩及び前記で使用された
残りの電解質を含有する第２顆粒剤との混合物である透
析用剤を提供するものである。That is, the present invention provides at least Na+ ,
Among the electrolytes necessary for the preparation of a dialysate containing Ca++ , Cl− and HCO3− , one or more kinds other than bicarbonate and p
Dialysis, which is a mixture of a first granule containing a pharmaceutically acceptable solid organic acid as an H-adjusting agent and a second granule containing a bicarbonate and the remaining electrolyte used above. It is intended to provide an agent.
【０００７】前記固体の有機酸として、クエン酸、酒石
酸、マレイン酸、オキサロ酢酸、イソクエン酸、リンゴ
酸等を挙げることができ、なかでもクエン酸が好まし
い。これらの有機酸は１種のみならず２種以上使用する
ことができる。Examples of the solid organic acid include citric acid, tartaric acid, maleic acid, oxaloacetic acid, isocitric acid, malic acid and the like, with citric acid being preferred. These organic acids may be used alone or in combination of two or more.
【０００８】本発明に用いられる電解質は薬理学的に許
容されるものでなければならない。例えば、従来の技術
の項に記載した重曹透析液の成分を与えるものとして、
炭酸水素ナトリウム、炭酸水素カリウム、塩化ナトリウ
ム、塩化カリウム、塩化カルシウム、塩化マグネシウ
ム、酢酸ナトリウム、酢酸カリウム、グルコン酸カルシ
ウム等を挙げることができる。本発明を構成する顆粒剤
は、上記のような電解質と共に、血液中に含まれるその
他の成分、例えばブドウ糖等を含むことができる。The electrolyte used in the present invention must be pharmacologically acceptable. For example, as giving the ingredients of the baking soda dialysate described in the section of the prior art,
Examples thereof include sodium hydrogen carbonate, potassium hydrogen carbonate, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate, potassium acetate, calcium gluconate and the like. The granules constituting the present invention can contain other components contained in blood, such as glucose, in addition to the electrolyte as described above.
【０００９】本発明の第２顆粒剤に含まれる成分として
は、炭酸水素ナトリウムと、塩化ナトリウム、塩化カリ
ウム、酢酸ナトリウム、酢酸カリウム及びブドウ糖から
なる群から選ばれた１種又は２種以上との組合せが、安
定性に優れ、好ましい。The components contained in the second granule of the present invention include sodium hydrogen carbonate and one or more selected from the group consisting of sodium chloride, potassium chloride, sodium acetate, potassium acetate and glucose. The combination is preferable because of its excellent stability.
【００１０】本発明の透析用剤に含まれる成分の好まし
い配合範囲を、透析液調製後の組成範囲で示せば下記の
如くであり、そのｐＨは７.０〜８.０、より好ましくは
７.２〜７.６である。 Ｎａ+ １２０ 〜１５０ ｍＥｑ／ｌ Ｋ+ ０ 〜 ４ ｍＥｑ／ｌ Ｃａ++ １ 〜 ６ ｍＥｑ／ｌ Ｍｇ++ ０ 〜 ２ ｍＥｑ／ｌ Ｃｌ- ９０ 〜１３５ ｍＥｑ／ｌ ＣＨ3ＣＯＯ- ２ 〜 １５ ｍＥｑ／ｌ ＨＣＯ3- １０ 〜 ４０ ｍＥｑ／ｌ クエン酸（ｐＨ調整剤） １ 〜 ５ ｍＥｑ／ｌ ブドウ糖 ０ 〜 １０ ｇ／ｌThe preferred blending range of the components contained in the dialysis agent of the present invention is shown below in terms of the composition range after preparation of the dialysate, and its pH is 7.0 to 8.0, more preferably 7 .2 to 7.6.Na + 120 ~150 mEq / l K + 0 ~ 4 mEq / l Ca ++ 1 ~ 6 mEq / l Mg ++ 0 ~ 2 mEq / l Cl - 90 ~135 mEq / l CH 3 COO - 2 ~ 15 mEq/ l HCO 3 - 10 ~ 40 mEq / l of citric acid (pHadjusting agent) 1 ~ 5 mEq / l dextrose 0 ~ 10 g / l
【００１１】本発明の透析用剤を製造するに当り、電解
質ないしブドウ糖等の配合量、あるいは第１顆粒剤と第
２顆粒剤との混合比は、例えば前記範囲内の各溶質濃度
を設定し、それらを供給する電解質等の組合せを決める
ことにより逆算することができる。In producing the dialysis agent of the present invention, the amount of electrolyte or glucose or the like, or the mixing ratio of the first granule and the second granule, is set so that each solute concentration is within the above range. , Can be calculated back by determining the combination of the electrolytes that supply them.
【００１２】本発明に係る顆粒剤の造粒方法は、特に限
定されず、乾式造粒法、押し出し造粒法又は流動層造粒
法の何れでもよいが、押し出し造粒法と流動層造粒法は
乾燥工程を要し、乾燥工程中に炭酸水素ナトリウムやブ
ドウ糖が分解する虞があること、また、乾燥が不充分な
場合、保存中若しくは輸送中に顆粒剤の固結や炭酸水素
ナトリウムの分解が生じる可能性があることから、乾式
造粒法が好ましい。なお、配合する電解質等は造粒前に
粉砕し、粒子径が約１００μｍ以下の粉末にして使用す
るのがよい。粉末の粒子径が２５０μｍを超えると、機
械的強度が不充分な造粒物が得られ、輸送中に粉化し易
く、さらには水に対する溶解速度が遅くなるので好まし
くない。また、塩化マグネシウムを使用する場合、吸湿
性、潮解性が強いため、塩化カルシウムや塩化ナトリウ
ム等と混合した後、粉砕するとよい。The granulation method of the granules according to the present invention is not particularly limited, and may be any of dry granulation method, extrusion granulation method or fluidized bed granulation method, but extrusion granulation method and fluidized bed granulation method. The method requires a drying step, and sodium hydrogen carbonate and glucose may be decomposed during the drying step. Also, if the drying is insufficient, the granules are hardened or sodium hydrogen carbonate is contaminated during storage or transportation. The dry granulation method is preferable because decomposition may occur. It is preferable that the electrolyte or the like to be blended is pulverized before granulation to be used as a powder having a particle diameter of about 100 μm or less. When the particle size of the powder exceeds 250 μm, a granulated product having insufficient mechanical strength is obtained, which is easily pulverized during transportation, and the dissolution rate in water becomes slow, which is not preferable. In addition, when magnesium chloride is used, it has good hygroscopicity and deliquescent, so it is advisable to mix it with calcium chloride, sodium chloride or the like and then pulverize it.
【００１３】乾式造粒法により本発明の透析用剤を製造
する場合、例えば、それぞれ計算量の塩化カルシウム、
塩化マグネシウム、塩化ナトリウム（計算量の一部）、
塩化カリウム、酢酸ナトリウム、クエン酸及びブドウ糖
を品川式混合機（三英製作所製）に供給して撹拌し、こ
の混合末をサンプルミル（不二パウダル社製粉砕機）に
より微粉化した後、再度混合し、ローラコンパクター
（ターボ工業株式会社製乾燥造粒機）で造粒後、篩にか
けて大粒子及び小粒子を除き第１顆粒剤とすればよい。
また、計算量の炭酸水素ナトリウム及び前記で使用した
残りの塩化ナトリウムを同様にして第２顆粒剤とし、次
いで計算量の第１顆粒剤及び第２顆粒剤を混合すればよ
い。When the dialysis agent of the present invention is produced by a dry granulation method, for example, calculated amounts of calcium chloride,
Magnesium chloride, sodium chloride (part of the calculation amount),
Potassium chloride, sodium acetate, citric acid and glucose are supplied to a Shinagawa mixer (manufactured by Sanei Seisakusho) and stirred, and the mixed powder is pulverized by a sample mill (a pulverizer manufactured by Fuji Paudal) and then mixed again. Then, after granulating with a roller compactor (dry granulator manufactured by Turbo Kogyo Co., Ltd.), the particles are passed through a sieve to remove the large particles and the small particles to obtain the first granules.
Further, the calculated amount of sodium hydrogen carbonate and the remaining sodium chloride used above may be similarly used as the second granule, and then the calculated amounts of the first granule and the second granule may be mixed.
【００１４】第１及び第２顆粒剤の混合は、必ずしも均
一にする必要はない。例えば、成人１人１回の透析分を
包装容器にそれぞれ充填し、密封すればよい。The mixing of the first and second granules does not necessarily have to be uniform. For example, a dialysis dose for each adult may be filled in a packaging container and sealed.
【００１５】しかし、複数の患者に対し同時に血液透析
をする場合、透析液調製の自動化が望ましく、両剤が均
一に混合されていれば好都合である。そこで医療現場に
均一に混合されたものを提供するには、その製造工程に
おいて均一に混合し、なお、保存中あるいは輸送中に偏
析しないようにする必要がある。そのためには、第１顆
粒剤と第２顆粒剤をそれぞれ実質的に同一メッシュの篩
で分級した後、均一に混合すれば良い。なお、分級後の
粒子径は、通常１２〜１５０メッシュ、好ましくは１２
〜８０メッシュ、さらに好ましくは１２〜４８メッシュ
の範囲内である。However, when performing hemodialysis on a plurality of patients at the same time, it is desirable to automate the preparation of dialysate, and it is convenient if both agents are mixed uniformly. Therefore, in order to provide a uniformly mixed product to the medical field, it is necessary to uniformly mix it in the manufacturing process and to prevent segregation during storage or transportation. For that purpose, the first granule and the second granule may be classified with a sieve having substantially the same mesh, and then mixed uniformly. The particle size after classification is usually 12 to 150 mesh, preferably 12
-80 mesh, and more preferably 12-48 mesh.
【００１６】本発明の透析用剤は、実質的に酸素ガスが
存在しない状態で保存すれば、より安定である。その包
装にあたっては、例えば窒素気流中あるいは炭酸ガス中
で酸素ガスバリヤー性の高い容器に充填し、密封すれば
よい。The dialysis agent of the present invention is more stable when stored in a state where oxygen gas does not substantially exist. For packaging, a container having a high oxygen gas barrier property may be filled in a nitrogen stream or carbon dioxide gas and sealed.
【００１７】[0017]
【作用】従来ｐＨ調整剤として使用されていた液体の酢
酸若しくは乳酸に代えて固体の有機酸を用いることによ
り、ｐＨ調整剤を含有する顆粒剤と炭酸水素ナトリウム
を含有する顆粒剤を混合しても変質や含量変化を来すこ
とのない安定な重曹透析用剤が得られ、したがって使用
に際し必要な全ての成分を含む製剤として提供でき、取
り扱い易く、しかも長期保存が可能である。また、顆粒
剤としたことから、水に速やかに溶解する。By using a solid organic acid instead of liquid acetic acid or lactic acid, which has been conventionally used as a pH adjuster, a granule containing a pH adjuster and a granule containing sodium hydrogen carbonate are mixed. Also, a stable sodium bicarbonate dialysis agent that does not deteriorate or change in content can be obtained. Therefore, it can be provided as a preparation containing all the components necessary for use, is easy to handle, and can be stored for a long period of time. In addition, since it is a granule, it dissolves quickly in water.
【００１８】[0018]
【実施例】以下の実施例に記載する「％」は重量によ
る。実施例１塩化ナトリウム３２１７ｇ、塩化カリウム１４９ｇ、塩
化カルシウム・２水和物２２１ｇ、塩化マグネシウム・
６水和物１０２ｇ、酢酸ナトリウム４９１ｇ、クエン酸
２００ｇ及びブドウ糖１０００ｇを万能ミキサー（小平
製作所製、ＡＣＭ２０／１０ＬＪ型）に供給して撹拌し
た。次いでサンプルミル（不二パウダル製、粉砕機ＫII
Ｗ−１型）にて粉砕し、さらに万能ミキサーで撹拌し
た。得られた混合物をローラコンパクター（ターボ工業
株式会社製、乾式造粒機ＷＰ９０×３０型）により造粒
した後、ロールグラニュレータ（日本グラニュレータ
製、ＧＲＮ−１０３１型）で破砕し、篩で分級して１２
〜４８メッシュの第１顆粒剤を得た。この組成物の粒度
分布及び比容積は下記のとおりであった。粒度分布 １２〜１８メッシュ ７．９％１８〜２４メッシュ ２０．０％２４〜３０メッシュ ４０．１％３０〜４８メッシュ ３２．０％比容積 ０．８４７ｇ／ｍｌEXAMPLES "%" in the following examples is by weight. Example 1 3217 g of sodium chloride, 149 g of potassium chloride, 221 g of calcium chloride dihydrate, magnesium chloride
102 g of hexahydrate, 491 g of sodium acetate, 200 g of citric acid and 1000 g of glucose were supplied to a universal mixer (manufactured by Kodaira Seisakusho, ACM20 / 10LJ type) and stirred. Sample mill (made by Fuji Paudal, crusher KII
W-1 type) was crushed and further stirred with a universal mixer. The obtained mixture is granulated by a roller compactor (manufactured by Turbo Kogyo Co., Ltd., a dry granulator WP90 × 30 type), crushed by a roll granulator (manufactured by Nippon Granulator, GRN-1031 type), and classified by a sieve. Then 12
~ 48 mesh of the first granule was obtained. The particle size distribution and specific volume of this composition were as follows. Particle size distribution 12-18 mesh 7.9% 18-24 mesh 20.0% 24-30 mesh 40.1% 30-48 mesh 32.0% Specific volume 0.847 g / ml
【００１９】次に、炭酸水素ナトリウム２５２０ｇと塩
化ナトリウム２８６０ｇを前記と同様にして１２〜４８
メッシュの第２顆粒剤を得た。この組成物の粒度分布は
下記のとおりであった。粒度分布 １２〜１８メッシュ １７．２％１８〜２４メッシュ ２４．５％２４〜３０メッシュ ３２．０％３０〜４８メッシュ ２６．３％比容積 １．０１８ｇ／ｍｌNext, 2520 g of sodium hydrogen carbonate and 2860 g of sodium chloride were added in the same manner as above to 12 to 48 g.
A second mesh granule was obtained. The particle size distribution of this composition was as follows. Particle size distribution 12-18 mesh 17.2% 18-24 mesh 24.5% 24-30 mesh 32.0% 30-48 mesh 26.3% Specific volume 1.018 g / ml
【００２０】得られた第１顆粒剤２０００ｇと第２顆粒
剤２０００ｇをロッキングミキサー（愛知電機株式会社
製、ＲＭＨ−１０型）に入れ、２０分間混合した後、分
級し、１２〜４８メッシュの混合物（透析用剤）を得
た。この透析用剤の粒度分布及び比容積は下記のとおり
であった。粒度分布 １２〜１８メッシュ １２．０％１８〜２４メッシュ ２３．０％２４〜３０メッシュ ３６．１％３０〜４８メッシュ ２８．９％比容積 ０．９３０ｇ／ｍｌ2000 g of the first granules and 2000 g of the second granules thus obtained were placed in a rocking mixer (RMH-10 type, manufactured by Aichi Denki Co., Ltd.), mixed for 20 minutes and then classified to obtain a mixture of 12 to 48 mesh. (Dialysis agent) was obtained. The particle size distribution and specific volume of this dialysis agent were as follows. Particle size distribution 12-18 mesh 12.0% 18-24 mesh 23.0% 24-30 mesh 36.1% 30-48 mesh 28.9% Specific volume 0.930 g / ml
【００２１】実施例２実施例１と同様にして、塩化ナトリウム４２１７ｇ、塩
化カリウム１４９ｇ、塩化カルシウム・２水和物２２１
ｇ、塩化マグネシウム・６水和物１０２ｇ、酢酸ナトリ
ウム４９１ｇ及びクエン酸２００ｇから１２〜４８メッ
シュの第１顆粒剤を、また、炭酸水素ナトリウム２５２
０ｇ、塩化ナトリウム１８６０ｇ及びブドウ糖１０００
ｇから１２〜４８メッシュの第２顆粒剤をそれぞれ得、
第１顆粒剤２０００ｇと第２顆粒剤２０００ｇを均一に
混合し、ポリ容器に充填して密栓した。なお、この混合
物（透析用剤）の粒度分布は下記のとおりであった。粒度分布 １２〜１８メッシュ ８．０％１８〜２４メッシュ １８．５％２４〜３０メッシュ ４２．０％３０〜４８メッシュ ３１．５％比容積 ０．９０５ｇ／ｍｌExample 2 In the same manner as in Example 1, 4217 g of sodium chloride, 149 g of potassium chloride, calcium chloride dihydrate 221
g, magnesium chloride hexahydrate 102 g, sodium acetate 491 g and citric acid 200 g, the first granule of 12 to 48 mesh, sodium bicarbonate 252
0 g, sodium chloride 1860 g and glucose 1000
g to obtain 12-48 mesh second granules,
2000 g of the first granules and 2000 g of the second granules were uniformly mixed, filled in a plastic container and sealed. The particle size distribution of this mixture (dialysis agent) was as follows. Particle size distribution 12-18 mesh 8.0% 18-24 mesh 18.5% 24-30 mesh 42.0% 30-48 mesh 31.5% Specific volume 0.905 g / ml
【００２２】実施例３実施例１と同様にして、塩化ナトリウム３７０８ｇ、塩
化カリウム１４９ｇ、塩化カルシウム・２水和物２２１
ｇ、塩化マグネシウム・６水和物１０２ｇ、クエン酸２
００ｇ及びブドウ糖１０００ｇから１２〜４８メッシュ
の第１顆粒剤を、また、炭酸水素ナトリウム２５２０
ｇ、塩化ナトリウム２３６９ｇ及び酢酸ナトリウム４９
１ｇから１２〜４８メッシュの第２顆粒剤をそれぞれ
得、第１顆粒剤２０００ｇと第２顆粒剤２０００ｇから
１２〜４８メッシュの均一混合物（透析用剤）を得た。
この透析用剤の粒度分布は下記のとおりであった。粒度分布 １２〜１８メッシュ １０．５％１８〜２４メッシュ ２０．０％２４〜３０メッシュ ３７．６％３０〜４８メッシュ ３１．９％比容積 ０．９０５ｇ／ｍｌExample 3 In the same manner as in Example 1, 3708 g of sodium chloride, 149 g of potassium chloride, calcium chloride dihydrate 221
g, magnesium chloride hexahydrate 102 g, citric acid 2
The first granules of 12 to 48 mesh from 00 g and glucose 1000 g, sodium hydrogen carbonate 2520
g, sodium chloride 2369g and sodium acetate 49
Second granules of 1 to 12 to 48 mesh were obtained, respectively, and a uniform mixture (dialysis agent) of 2000 g of the first granules and 2000 g of the second granules of 12 to 48 mesh was obtained.
The particle size distribution of this dialysis agent was as follows. Particle size distribution 12-18 mesh 10.5% 18-24 mesh 20.0% 24-30 mesh 37.6% 30-48 mesh 31.9% Specific volume 0.905 g / ml
【００２３】実施例４実施例１と同様にして、塩化ナトリウム３８５７ｇ、塩
化カルシウム・２水和物２２１ｇ、塩化マグネシウム・
６水和物１０２ｇ、クエン酸２００ｇ及びブドウ糖１０
００ｇから１２〜４８メッシュの第１顆粒剤を、また、
炭酸水素ナトリウム２５２０ｇ、塩化ナトリウム２２２
０ｇ、塩化カリウム１４９ｇ及び酢酸ナトリウム４９１
ｇから１２〜４８メッシュの第２顆粒剤をそれぞれ得、
第１顆粒剤２０００ｇと第２顆粒剤２０００ｇから１２
〜４８メッシュの均一混合物（透析用剤）を得た。この
透析用剤をアルミ製ボトルに充填し、ボトル内の空間部
を窒素ガスで置換して密栓した。粒度分布 １２〜１８メッシュ １１．２％１８〜２４メッシュ ２２．５％２４〜３０メッシュ ３５．７％３０〜４８メッシュ ３０．６％比容積 ０．９１４ｇ／ｍｌExample 4 In the same manner as in Example 1, 3857 g of sodium chloride, 221 g of calcium chloride dihydrate, and magnesium chloride.
Hexahydrate 102 g, citric acid 200 g and glucose 10
1st granule of 12 to 48 mesh from 00g,
2520 g sodium hydrogen carbonate, 222 sodium chloride
0 g, potassium chloride 149 g and sodium acetate 491
g to obtain 12-48 mesh second granules,
2000g of the first granule and 2000g of the second granule to 12
A uniform mixture of ~ 48 mesh (dialysis agent) was obtained. This dialysis agent was filled in an aluminum bottle, the space in the bottle was replaced with nitrogen gas, and the bottle was sealed. Particle size distribution 12-18 mesh 11.2% 18-24 mesh 22.5% 24-30 mesh 35.7% 30-48 mesh 30.6% Specific volume 0.914 g / ml
【００２４】〔参考例〕比較試験のための透析用剤を次
のようにして調製した。クエン酸を除いた他は実施例１
の第１顆粒剤の製造と同じにして顆粒剤を得、その２０
００ｇをバーチカルグラニュレータ（富士産業株式会社
製、ＦＭ−ＶＧ−２５型）に入れ、撹拌しながら酢酸４
８．３ｇを加え、さらに実施例１の第２顆粒剤２０９６
ｇを加えて均一に混合した。Reference Example A dialysis agent for a comparative test was prepared as follows. Example 1 except that citric acid was omitted
Granules were obtained in the same manner as in the production of the first granules of
00 g was placed in a vertical granulator (Fuji Sangyo Co., Ltd., FM-VG-25 type), and acetic acid 4 was added while stirring.
8.3 g was added, and the second granule 2096 of Example 1 was further added.
g was added and mixed uniformly.
【００２５】〔試験例１〕実施例１〜４及び参考例の透
析用剤をそれぞれガラス瓶に入れ、密栓して４０℃にて
３か月間保存し（実施例４で製造した透析用剤のみ、ガ
ラス瓶内の空間部を窒素ガスで置換）、１か月経過毎に
対照との色差（ΔＥ）、凝集の有無、水に溶解後の炭酸
水素イオン濃度及びｐＨを測定した。前記溶解に際し、
何れの試料も数分以内に溶解した。なお、色差は、対応
する実施例又は参考例の透析用剤を５℃にて同様に保存
して対照とし、色差計（日本電色工業株式会社製、Σ８
０型）を用いて測定した。炭酸水素イオン濃度及びｐＨ
は、試料１０．７６ｇを蒸留水に溶かして１０００mlと
し、それぞれイオンクロマトグラフィー（横河電機株式
会社製、ＩＣ−５００Ｓ型）及びｐＨメータ（堀場製作
所製、Ｆ−１６型）を用いて測定した。それらの結果を
表１に示した。[Test Example 1] The dialysis agents of Examples 1 to 4 and Reference Example were placed in glass bottles, sealed and stored at 40 ° C. for 3 months (only the dialysis agents produced in Example 4, The space in the glass bottle was replaced with nitrogen gas), and the color difference (ΔE) from the control, the presence or absence of aggregation, the hydrogen carbonate ion concentration after dissolution in water and the pH were measured every one month. Upon dissolution,
Both samples dissolved within minutes. The color difference was measured by storing the dialysis agent of the corresponding Example or Reference Example at 5 ° C. in the same manner as a control and using a color difference meter (manufactured by Nippon Denshoku Industries Co., Ltd., Σ8).
0 type). Bicarbonate ion concentration and pH
Was dissolved in distilled water to make 1000 ml, and measured using ion chromatography (Yokogawa Electric Co., Ltd. IC-500S type) and pH meter (Horiba Seisakusho F-16 type). . The results are shown in Table 1.
【００２６】[0026]
【表１】[Table 1]
【００２７】表１より、本発明透析用剤は、長期保存後
も外観（色）と炭酸水素ナトリウム含量が殆ど変化せ
ず、水に速やかに溶け、凝集物は生じないことが分か
る。一方、ｐＨ調整剤として酢酸を用いた参考例は、各
項目について変化が著しく、長期保存ができないことが
分かる。From Table 1, it can be seen that the dialysis agent of the present invention hardly changes in appearance (color) and sodium hydrogencarbonate content even after long-term storage, dissolves rapidly in water, and does not generate aggregates. On the other hand, in the reference example using acetic acid as the pHadjuster , it can be seen that each item is remarkably changed and cannot be stored for a long period of time.
【００２８】〔試験例２〕実施例１の透析用剤を１００
０mlのポリエチレン容器に８００ｇ入れ、密栓して振と
う機にて7 日間振とうした後、容器内の上部、中部、下
部の３か所より試料を採取し、それぞれ１０．７６ｇを
蒸留水に溶かして１０００mlとし、炭酸水素イオン濃度
及びカルシウムイオン濃度を測定した。それらの結果を
表２に示した。Test Example 2 100 parts of the dialysis agent of Example 1 was used.
Place 800 g in a 0 ml polyethylene container, seal tightly and shake on a shaker for 7 days, then collect samples from the upper, middle and lower parts of the container and dissolve 10.76 g of each in distilled water. The total amount was 1000 ml, and the hydrogen carbonate ion concentration and the calcium ion concentration were measured. The results are shown in Table 2.
【００２９】[0029]
【表２】[Table 2]
【００３０】表２より、本発明透析用剤は、振とうによ
って偏析が生じないことが分かる。From Table 2, it can be seen that the dialysis agent of the present invention does not cause segregation by shaking.
【００３１】[0031]
【発明の効果】本発明の透析用剤は、長期保存が可能な
顆粒剤であり、取り扱い易く、その所定量又は計算量を
水に溶かすことにより重曹透析液が速やかに調製でき
る。The dialysis agent of the present invention is a granule that can be stored for a long period of time, is easy to handle, and a sodium bicarbonate dialysate can be rapidly prepared by dissolving a predetermined amount or calculated amount thereof in water.
─────────────────────────────────────────────────────フロントページの続き (56)参考文献 特開 平４−257522（ＪＰ，Ａ) 特開 平３−74331（ＪＰ，Ａ) 特公 昭63−52009（ＪＰ，Ｂ１) (58)調査した分野(Int.Cl.7，ＤＢ名) A61M 1/14 A61K 9/08─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-4-257522 (JP, A) JP-A-3-74331 (JP, A) JP-B-63-52009 (JP, B1) (58) Field (Int.Cl.7 , DB name) A61M 1/14 A61K 9/08
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18080893AJP3398184B2 (en) | 1993-03-30 | 1993-06-25 | Dialysis agent |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9685493 | 1993-03-30 | ||
| JP5-96854 | 1993-03-30 | ||
| JP18080893AJP3398184B2 (en) | 1993-03-30 | 1993-06-25 | Dialysis agent |
| Publication Number | Publication Date |
|---|---|
| JPH06335528A JPH06335528A (en) | 1994-12-06 |
| JP3398184B2true JP3398184B2 (en) | 2003-04-21 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18080893AExpired - Fee RelatedJP3398184B2 (en) | 1993-03-30 | 1993-06-25 | Dialysis agent |
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| JP (1) | JP3398184B2 (en) |
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