JP2008007524A - Solid sodium bicarbonate dialysis agent - Google Patents
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本発明は固形重曹透析用剤、すなわち重曹含有透析液を調製するための固形製剤に関する。 The present invention relates to a solid sodium bicarbonate dialysis agent, that is, a solid preparation for preparing a sodium bicarbonate-containing dialysate .
腎機能が低下した患者に血液透析を実施する場合、患者の血液は人工腎臓中で浄化される。この人工腎臓の内部においては透析液が灌流し、透析膜を介して、該血液中の老廃物を透析液側に移行させることが一般に行われる。この透析液としては、酢酸透析液が広く使用されてきたが、近年、透析中の不快症状を激減させる重曹を使用するものに代替されてきている。 When hemodialysis is performed on a patient with impaired renal function, the patient's blood is purified in an artificial kidney. In general, the dialysate is perfused inside the artificial kidney, and the waste in the blood is transferred to the dialysate side through the dialysis membrane. As this dialysis solution, an acetic acid dialysis solution has been widely used, but in recent years, it has been replaced by one using baking soda that drastically reduces unpleasant symptoms during dialysis.
重曹を含む透析液は、通常、電解質成分（例えば塩化ナトリウム、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）およびｐＨ調整剤（例えば酢酸）を含む製剤（以下、Ａ剤という）、重曹を含む製剤（以下、Ｂ剤という）の２種類の透析液製剤から調製される。これらの透析液製剤にはブドウ糖などの糖が含まれる場合もあるし、別に糖を含む製剤を混合する場合もある。 The dialysate containing sodium bicarbonate usually contains an electrolyte component (for example, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium acetate) and a pH adjuster (for example, acetic acid) (hereinafter referred to as “agent A”), sodium bicarbonate. It is prepared from two types of dialysate preparations (hereinafter referred to as “agent B”). These dialysate preparations may contain sugars such as glucose, or may be mixed with preparations containing sugars separately.
従来、Ａ剤およびＢ剤は所定濃度に調製された濃厚液の状態で販売され、使用者が水で希釈して使用されてきた。しかし、一回の透析で患者一人あたり約３００Ｌの透析液を必要とするため、多数の患者に透析治療を行う場合、多量の濃厚液を使用し、水で希釈することになる。そこで、透析液を調製する人の負担を軽減し、省スペース化を計るため、粉末製剤化したＢ剤を使用する場合が多くなってきた。それに伴い、Ａ剤を粉末化した２剤からなる固形重曹透析用剤が開発されている。しかし、Ａ剤にブドウ糖が含まれている２剤の固形重曹透析用剤は、製造工程においてブドウ糖が加熱され、分解および着色するおそれがある。そのため、ブドウ糖を別包装にした３剤からなる固形重曹透析用剤に比べて、安定性が維持される時間が短くなる。 Conventionally, the A agent and the B agent are sold in the form of a concentrated liquid prepared to a predetermined concentration, and the user has been diluted with water and used. However, since approximately 300 L of dialysate is required per patient in one dialysis, a large amount of concentrated solution is used and diluted with water when dialysis treatment is performed on a large number of patients. Therefore, in order to reduce the burden on the person who prepares the dialysate and to save space, there are many cases where the B-form made into a powder formulation is used. Along with this, a solid baking soda dialysis agent comprising two agents obtained by pulverizing the agent A has been developed. However, in the two solid baking soda dialysis agents in which glucose is contained in the agent A, glucose may be heated and decomposed and colored in the production process. Therefore, compared with the solid baking soda dialysis agent which consists of 3 agents which packaged glucose separately, the time for which stability is maintained becomes short.
粉末化した固形重曹透析用剤として、重曹以外の電解質、ブドウ糖および液体酸よりなる粉末状のＡ剤と、重曹のみ、あるいは重曹および酢酸ナトリウムまたはブドウ糖よりなる粉末状のＢ剤、との二つの組成物よりなる透析用製剤が開示されている（特許文献１〜３）。これらの透析用製剤のＡ剤は、重曹以外の電解質およびブドウ糖を撹拌混合機で撹拌混合し、ついで粉砕機で粉砕したのち再び混合し、乾式造粒機で造粒したのち、液体酸を配合して混合する乾式法（Ａ）、および塩化ナトリウムおよびブドウ糖を撹拌混合機で混合し、流動層造粒機内で塩化ナトリウムと重曹以外の電解質を水に溶解させて得られる水溶液を噴霧しながら造粒したのち、液体酸を配合して混合する流動層法（Ｂ）のいずれかで製造されるものである。しかし、上記（Ａ）および（Ｂ）のいずれの方法で得られた透析用製剤も、製造工程中、ブドウ糖にかかる加熱時間が長いため、得られた製剤中のブドウ糖が分解および着色しているおそれがある。また、上記方法により得られる透析用製剤は、含量均一性を得ることが困難である。 As powdered solid baking soda dialysis agent, there are two types of powders, A agent consisting of electrolytes other than baking soda, glucose and liquid acid, and B agent powder consisting of baking soda alone or sodium bicarbonate and sodium acetate or glucose. A dialysis preparation comprising a composition is disclosed ( Patent Documents 1 to 3 ). These A preparations for dialysis are prepared by mixing electrolytes and glucose other than baking soda with a stirring mixer, then pulverizing with a pulverizer, mixing again, granulating with a dry granulator, and then adding a liquid acid. The dry method (A), in which sodium chloride and glucose are mixed with a stirring mixer, and an aqueous solution obtained by dissolving an electrolyte other than sodium chloride and sodium bicarbonate in water in a fluidized bed granulator is sprayed. After being granulated, it is produced by one of the fluidized bed methods (B) in which a liquid acid is blended and mixed. However, in the preparation for dialysis obtained by any of the above methods (A) and (B), since the heating time for glucose is long during the production process, the glucose in the obtained preparation is decomposed and colored. There is a fear. Moreover, it is difficult to obtain uniform content of the dialysis preparation obtained by the above method.
上記事情に鑑み、本発明はブドウ糖が分解および着色するおそれがなく、安定性および含量均一性に優れた固形重曹透析用剤を提供することにある。 In view of the above circumstances, an object of the present invention is to provide a solid baking soda dialysis agent that is excellent in stability and content uniformity without the risk of glucose decomposition and coloring.
本発明者らは、上記課題を解決するために種々鋭意検討した結果、転動攪拌流動層造粒装置を用いて固形重曹透析用剤を製造することにより、所期の目的が達成されることを見出し、本発明に到達した。 As a result of intensive studies to solve the above problems, the present inventors have achieved the intended purpose by producing a solid baking soda dialysis agent using a tumbling stirred fluidized bed granulator. And reached the present invention.
すなわち、本発明は塩化ナトリウムおよびブドウ糖を含む核粒子と、塩化カルシウム、塩化マグネシウム、塩化カリウム、酢酸ナトリウムおよび酢酸を含むコーティング層とからなり、該核粒子が該コーティング層により覆われたものである固形重曹透析用剤である。 That is, the present invention comprises a core particle containing sodium chloride and glucose and a coating layer containing calcium chloride, magnesium chloride, potassium chloride, sodium acetate and acetic acid, and the core particle is covered with the coating layer. It is a solid baking soda dialysis agent.
また、本発明は下記工程（１）および（２）により製造された固形重曹透析用剤である。
（１）転動攪拌流動層造粒装置を用いて、塩化ナトリウムおよびブドウ糖粉末を含む核粒子に、塩化カルシウム、塩化マグネシウム、塩化カリウムおよび酢酸ナトリウムを含む水溶液を噴霧し、乾燥させる工程、（２）工程（１）で得られた生成物に、酢酸を混合して固形重曹透析用剤を得る工程
Moreover, this invention is a solid baking soda dialysis agent manufactured by the following process (1) and (2) .
(1) A step of spraying and drying an aqueous solution containing calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing sodium chloride and glucose powder using a tumbling stirring fluidized bed granulator, (2 ) Step of obtaining solid sodium bicarbonate dialysis agent by mixing acetic acid with the product obtained in step (1)
本発明の固形重曹透析用剤は、転動攪拌流動層造粒装置を用いることにより、含量均一性に優れた固形重曹透析用剤を提供することが出来る。また、ブドウ糖が分解および着色するおそれがなく、長期保存安定性に富んだ固形重曹透析用剤が得られる。さらに、酢酸ナトリウムの一部を粉末状態で添加することにより、固形重曹透析用剤の製造時間を短縮することが出来る。 The solid sodium bicarbonate dialysis agent of the present invention can provide a solid sodium bicarbonate dialysis agent excellent in content uniformity by using a tumbling stirring fluidized bed granulator. In addition, a solid baking soda dialysis agent rich in long-term storage stability without the risk of degradation and coloring of glucose can be obtained. Furthermore, the manufacturing time of the solid sodium bicarbonate dialysis agent can be shortened by adding a part of sodium acetate in a powder state.
本発明において固形重曹透析用剤とは、重曹を含まない電解質成分、ｐＨ調整剤および糖成分を含む、重曹含有透析液を調製するために使用する固形製剤である。該固形重曹透析用剤は、少なくとも電解質成分として、塩化ナトリウム、塩化カルシウム、塩化マグネシウム、塩化カリウム、酢酸ナトリウムを含むが、他の電解質成分、例えば、酢酸カリウムやグルコン酸カルシウム等を含んでいてもよい。本発明においてｐＨ調整剤としては、酢酸を用いる。他のｐＨ調整剤、例えば、乳酸、クエン酸、シュウ酸等の固体酸は、必要により添加してもよい。本発明において、糖成分としてはブドウ糖を用いる。他の糖成分、例えば、マルトース、キシリトール、トレハロース等は、必要により添加してもよい。 In the present invention, the solid sodium bicarbonate dialysis agent is a solid preparation used for preparing a sodium bicarbonate-containing dialysate containing an electrolyte component not containing sodium bicarbonate, a pH adjuster and a sugar component. The solid sodium bicarbonate dialysis agent contains at least sodium chloride, calcium chloride, magnesium chloride, potassium chloride, sodium acetate as an electrolyte component, but may contain other electrolyte components such as potassium acetate and calcium gluconate. Good. In the present invention, acetic acid is used as the pH adjuster. Other pH adjusting agents, for example, solid acids such as lactic acid, citric acid and oxalic acid may be added as necessary. In the present invention, glucose is used as the sugar component. Other sugar components such as maltose, xylitol, trehalose and the like may be added as necessary.
本発明の固形重曹透析用剤に含まれる塩化ナトリウムとしては、固体状態であって、核粒子を形成するものであればいかなるものでもよいが、粒径が約７５〜１，７００μｍの結晶状態であるものが好ましい。本発明の固形重曹透析用剤に含まれるブドウ糖としては、粒径が約４５〜１，７００μｍの粉末であるものが好ましい。本発明の固形重曹透析用剤に含まれる塩化カルシウム、塩化マグネシウム、塩化カリウム、酢酸ナトリウムは、水に溶解して水溶液に調製し、前記塩化ナトリウムおよびブドウ糖を含む核粒子に噴霧、乾燥させてコーティング層を形成するものであり、固体状態に限らず、いかなる状態のものであってもよい。上記塩化カルシウムとしては、塩化カルシウム２水和物、塩化カルシウム１水和物、塩化カルシウム無水物などが用いられ、塩化マグネシウムとしては塩化マグネシウム６水和物などが好ましく用いられ、酢酸ナトリウムとしては、無水酢酸ナトリウム、酢酸ナトリウム３水和物などが好ましく用いられる。本発明の固形重曹透析用剤に含まれる酢酸は、氷酢酸、無水酢酸などが好ましく用いられる。 The sodium chloride contained in the solid baking soda dialysis agent of the present invention may be any sodium salt as long as it is in a solid state and forms core particles, but in a crystalline state having a particle size of about 75 to 1,700 μm. Some are preferred. The glucose contained in the solid baking soda dialysis agent of the present invention is preferably a powder having a particle size of about 45 to 1,700 μm. Calcium chloride, magnesium chloride, potassium chloride and sodium acetate contained in the solid baking soda dialysis agent of the present invention are dissolved in water to prepare an aqueous solution, and sprayed and dried on the core particles containing sodium chloride and glucose. It forms a layer and is not limited to a solid state but may be in any state. As the calcium chloride, calcium chloride dihydrate, calcium chloride monohydrate, calcium chloride anhydrous, etc. are used. As magnesium chloride, magnesium chloride hexahydrate is preferably used. As sodium acetate, Anhydrous sodium acetate, sodium acetate trihydrate and the like are preferably used. As the acetic acid contained in the solid sodium bicarbonate dialysis agent of the present invention, glacial acetic acid, acetic anhydride and the like are preferably used.
本発明の固形重曹透析用剤は、重曹又は重曹を主体とする製剤とともに水に溶解させて重曹含有透析液に調製する。該透析液は、例えば下記組成（最終濃度）を有する。
Ｎａ+ １２０〜１５０ ｍＥｑ／Ｌ
Ｋ+ ０．５〜３ ｍＥｑ／Ｌ
Ｃａ2+ １．５〜４．５ ｍＥｑ／Ｌ
Ｍｇ2+ ０．１〜２．０ ｍＥｑ／Ｌ
Ｃｌ- ９０〜１３５ ｍＥｑ／Ｌ
ＣＨ3ＣＯＯ- ５〜１５ ｍＥｑ／Ｌ
ＨＣＯ3 - ２０〜３５ ｍＥｑ／Ｌ
ブドウ糖 ０．５〜２．５ ｇ／Ｌ
The solid baking soda dialysis agent of the present invention is prepared in a baking soda-containing dialysis solution by dissolving it in water together with a preparation mainly containing baking soda or baking soda. The dialysate has, for example, the following composition (final concentration).
Na + 120-150 mEq / L
K + 0.5-3 mEq / L
Ca 2+ 1.5-4.5 mEq / L
Mg 2+ 0.1-2.0 mEq / L
Cl − 90 to 135 mEq / L
CH 3 COO - 5-15 mEq / L
HCO 3 - 20~35 mEq / L
Glucose 0.5-2.5 g / L
本発明における固形重曹透析用剤は、塩化ナトリウムおよびブドウ糖を含む核粒子が、塩化カルシウム、塩化マグネシウム、塩化カリウム、酢酸ナトリウムおよび酢酸からなるコーティング層によって覆われた構造を有する。前記核粒子は、塩化ナトリウムおよびブドウ糖の他に、塩化マグネシウムや塩化カルシウム、塩化カリウム、酢酸ナトリウムを含んでいてもよい。上記核粒子の各々の成分は、本発明の固形重曹透析用剤を製造するにあたり、粉砕せずにそのまま用いてもよいし、あらかじめ粉砕機や整粒機などにより、粒径７５〜１，７００μｍの顆粒状に、ブドウ糖および酢酸ナトリウムに関しては粒径４５〜１，７００μｍの顆粒状に、粉砕するか、あるいは湿式または乾式造粒にて同様のサイズの顆粒状に造粒してもよい。前記コーティング層に含まれる化合物は、上記成分の他に、塩化ナトリウムを含んでいてもよい。該化合物のうち酢酸以外のものは、水に溶解させて水溶液に調製して、前記塩化ナトリウムの核粒子に噴霧、乾燥され、該核粒子にコーティング層を形成する。 The solid sodium bicarbonate dialysis agent in the present invention has a structure in which core particles containing sodium chloride and glucose are covered with a coating layer made of calcium chloride, magnesium chloride, potassium chloride, sodium acetate and acetic acid. The core particles may contain magnesium chloride, calcium chloride, potassium chloride, and sodium acetate in addition to sodium chloride and glucose. In preparing the solid baking soda dialysis agent of the present invention, each component of the above core particles may be used as it is without being pulverized, or may be used in advance by a pulverizer or a granulator to obtain a particle diameter of 75 to 1,700 μm. In the case of glucose and sodium acetate, they may be pulverized into granules having a particle diameter of 45 to 1,700 μm, or may be granulated into granules of the same size by wet or dry granulation. The compound contained in the coating layer may contain sodium chloride in addition to the above components. Of these compounds, those other than acetic acid are dissolved in water to prepare an aqueous solution, and sprayed and dried on the core particles of sodium chloride to form a coating layer on the core particles.
前記コーティング層に含まれる酢酸ナトリウムは、全量が前記水溶液に調製されて使用される必要はなく、その一部が粉末状態で、塩化ナトリウムおよびブドウ糖とともに、核粒子として用いられても良い。この場合、酢酸ナトリウム粉末の粒径は、約４５〜１，７００μｍであるものが好ましい。上記酢酸ナトリウムの一部を粉末状態で使用することにより、コーティングする水溶液の量が減り、コーティングにかかる時間が短縮できる。具体的には、前記酢酸ナトリウム全量の９０％以下を粉末状態で使用するのが好ましく、より好ましくは８０％以下、さらに好ましくは７０％以下である。酢酸ナトリウムを粉末状態で使用する量が９０％を越えると、コーティングする水溶液の量が少なすぎて、均一なコーティング層が形成されず、得られた固形重曹透析用剤の含量が均一にならなくなるおそれがある。 The total amount of sodium acetate contained in the coating layer does not need to be prepared in the aqueous solution, and a part thereof may be used as a core particle together with sodium chloride and glucose in a powder state. In this case, the particle diameter of the sodium acetate powder is preferably about 45 to 1,700 μm. By using a part of the sodium acetate in a powder state, the amount of the aqueous solution to be coated is reduced, and the time required for coating can be shortened. Specifically, it is preferable to use 90% or less of the total amount of sodium acetate in a powder state, more preferably 80% or less, and still more preferably 70% or less. If the amount of sodium acetate used in the powder state exceeds 90%, the amount of aqueous solution to be coated is too small to form a uniform coating layer, and the content of the obtained solid baking soda dialysis agent is not uniform. There is a fear.
本発明における固形重曹透析用剤は、転動攪拌流動層造粒装置を用いた転動攪拌流動層造粒法により、核粒子の周りに該核粒子を覆うコーティング層を形成することによって得られる。該転動攪拌流動層造粒法は、従来の流動層造粒法の特徴である造粒同時乾燥と、攪拌造粒法の特徴である強力な転動攪拌の両方を兼ね備えた造粒法である。さらに、転動攪拌流動層造粒法は従来の流動層造粒法に比べて層内の粒子の攪拌力が強く、コーティング層に含まれる成分の水溶液の噴霧速度が早いため、造粒にかかる時間が短縮される。これにより、ブドウ糖にかかる熱を最小限に抑えることができ、得られた製剤中のブドウ糖が分解および着色しているおそれがなくなる。また、造粒された粒子の含量均一性にも優れている。 The solid baking soda dialysis agent in the present invention is obtained by forming a coating layer covering the core particles around the core particles by a rolling stirring fluidized bed granulation method using a rolling stirring fluidized bed granulator. . The rolling stirring fluidized bed granulation method is a granulation method that combines both simultaneous granulation drying, which is a feature of the conventional fluidized bed granulation method, and strong rolling stirring, which is a feature of the stirring granulation method. is there. Furthermore, the rolling agitation fluidized bed granulation method has a stronger stirring power for particles in the layer than the conventional fluidized bed granulation method, and the spraying speed of the aqueous solution of the components contained in the coating layer is high. Time is shortened. Thereby, the heat concerning glucose can be suppressed to the minimum, and there is no possibility that the glucose in the obtained preparation is decomposed and colored. In addition, the content uniformity of the granulated particles is excellent.
本発明で用いられる転動攪拌流動層造粒装置とは、層壁近傍からの空気流による流動作用と、装置底部のローターの回転による転動作用により、核粒子を転動流動させ、コーティング層に含まれる成分を水に溶解して作成した水溶液を噴霧して、該水溶液中の成分を該核粒子にコーティングするものである。前記空気流の風量は、０．２〜３００ｍ３／ｍｉｎが好ましく、０．５〜２００ｍ３／ｍｉｎが特に好ましい。該風量が０．２ｍ３／ｍｉｎより少ないと核粒子同士が凝集しやすくなる。また、３００ｍ３／ｍｉｎより多いと水溶液中の成分がスプレードライ現象を生じやすくなり、さらに各粒子が受ける衝撃が大きくなるため微粉が生じやすくなる。また、前記ローターの回転数は２０〜１，０００ｒｐｍが好ましく、５０〜５００ｒｐｍが特に好ましい。該回転数が２０ｒｐｍより低いとコーティング層の層厚が不均一になり、１，０００ｒｐｍより高いとコーティングされた粒子同士の衝突や装置内壁との摩擦のためにコーティング層が削れるおそれがある。 The rolling stirring fluidized bed granulator used in the present invention is a coating layer in which core particles are tumbled and flowed by a fluid action by an air flow from the vicinity of a layer wall and a rolling action by rotation of a rotor at the bottom of the apparatus. An aqueous solution prepared by dissolving the components contained in water in water is sprayed to coat the core particles with the components in the aqueous solution. Air volume of the air flow is preferably 0.2~300m 3 / min, 0.5~200m 3 / min is particularly preferred. If the air volume is less than 0.2 m 3 / min, the core particles tend to aggregate. On the other hand, if it exceeds 300 m 3 / min, the components in the aqueous solution are likely to cause a spray-drying phenomenon, and the impact received by each particle is increased, so that fine powder is likely to be generated. Further, the rotational speed of the rotor is preferably 20 to 1,000 rpm, particularly preferably 50 to 500 rpm. When the rotational speed is lower than 20 rpm, the coating layer thickness becomes non-uniform. When the rotational speed is higher than 1,000 rpm, the coating layer may be scraped due to collision between coated particles or friction with the inner wall of the apparatus.
以下、本発明の固形重曹透析用剤の製造方法の一例を説明する。
（１）まず、塩化カルシウム２水和物２７〜８１ｇ、塩化マグネシウム６水和物２．５〜４９．８ｇ、塩化カリウム９〜５４ｇおよび無水酢酸ナトリウム６〜２０２ｇの４種の電解質を水に溶解させて水溶液を調製する。該水溶液中の電解質の濃度は１５〜５０重量％が好ましく、２５〜４０重量％が特に好ましい。該水溶液中の電解質の濃度が１５重量％より低いと水溶液の量が多くなるためコーティング時間が長くなり、５０重量％より高いとコーティング層を形成する化合物が完全に溶解されず懸濁液になるおそれがある。次に、転動攪拌流動層造粒装置に、核粒子となる塩化ナトリウム１，５００ｇおよびブドウ糖粉末１２２．８ｇ〜６１４ｇを投入する。ここで酢酸ナトリウム粉末０〜１９６ｇを添加してもよい。前記核粒子に前記水溶液を噴霧し、乾燥させてコーティング層を形成させる。乾燥は排気温度２５〜７０℃、好ましくは３０〜５０℃で前記噴霧中に継続して行うのが好ましい。乾燥後の造粒物の含水率は、０〜１０％であることが好ましい。
（２）工程（１）で得られた造粒物を前記転動攪拌流動層造粒装置より取り出し、自然冷却した後、Ｖ型混合機などに投入し、氷酢酸２９〜７３ｇを添加し、混合して固形重曹透析用剤を製造する。得られた造粒物の平均粒子径は７５〜１，７００μｍであり、含水率は０〜１０％であることが好ましい。
Hereinafter, an example of the manufacturing method of the solid baking soda dialysis agent of this invention is demonstrated.
(1) First, four kinds of electrolytes of calcium chloride dihydrate 27-81 g, magnesium chloride hexahydrate 2.5-49.8 g, potassium chloride 9-54 g and anhydrous sodium acetate 6-202 g are dissolved in water. To prepare an aqueous solution. The concentration of the electrolyte in the aqueous solution is preferably 15 to 50% by weight, particularly preferably 25 to 40% by weight. When the concentration of the electrolyte in the aqueous solution is lower than 15% by weight, the amount of the aqueous solution increases, so that the coating time becomes longer. When the concentration is higher than 50% by weight, the compound forming the coating layer is not completely dissolved but becomes a suspension. There is a fear. Next, 1,500 g of sodium chloride as a core particle and 122.8 g to 614 g of glucose powder are put into a rolling stirring fluidized bed granulator. Here, 0 to 196 g of sodium acetate powder may be added. The aqueous solution is sprayed on the core particles and dried to form a coating layer. Drying is preferably carried out continuously during the spraying at an exhaust temperature of 25 to 70 ° C, preferably 30 to 50 ° C. The moisture content of the granulated product after drying is preferably 0 to 10%.
(2) The granulated product obtained in the step (1) is taken out from the rolling stirring fluidized bed granulator, naturally cooled, and then charged into a V-type mixer or the like, and 29 to 73 g of glacial acetic acid is added, Mix to produce a solid baking soda dialysis agent. It is preferable that the average particle diameter of the obtained granulated product is 75 to 1,700 μm, and the water content is 0 to 10%.
以下、本発明を実施例を用いてより詳細に説明するが、本発明はこれらの実施例に限定されない。 EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example, this invention is not limited to these Examples.
［実施例１］
塩化カリウム３６．６ｇ、塩化マグネシウム６水和物２５．０ｇ、塩化カルシウム２水和物４５．１ｇおよび無水酢酸ナトリウム１１０．８ｇを精製水５１９．９ｇに溶解して水溶液を調製した。転動攪拌流動層造粒装置（マルチプレックス ＭＰ−０１、パウレック社製）に、平均粒径３００μｍの塩化ナトリウム核粒子１，５００ｇおよび平均粒径１８０μｍのブドウ糖粉末２４５．６ｇを投入し、給気温度８０℃にて、ローター回転数３００ｒｐｍおよび給気風量４０ｍ３／ｈｒの条件下で、前記水溶液を噴霧すると同時に乾燥させて、平均粒径９００μｍの顆粒を得た。該顆粒を装置内より取り出し、室温まで冷却した後、Ｖ型混合機（Ｓ−３型、筒井理化学器械社製）に該顆粒を投入し、該混合機内に氷酢酸３６．９ｇを添加し、均一に混合して平均粒径９００μｍの固形重曹透析用剤を得た。
[Example 1]
An aqueous solution was prepared by dissolving 36.6 g of potassium chloride, 25.0 g of magnesium chloride hexahydrate, 45.1 g of calcium chloride dihydrate and 110.8 g of anhydrous sodium acetate in 519.9 g of purified water. Into a tumbling stirring fluidized bed granulator (Multiplex MP-01, manufactured by POWREC), 1,500 g of sodium chloride core particles having an average particle size of 300 μm and 245.6 g of glucose powder having an average particle size of 180 μm are charged and supplied. The aqueous solution was sprayed and dried at a temperature of 80 ° C. under conditions of a rotor rotation speed of 300 rpm and an air supply rate of 40 m 3 / hr to obtain granules having an average particle size of 900 μm. The granules are taken out from the apparatus and cooled to room temperature, and then the granules are put into a V-type mixer (S-3, manufactured by Tsutsui Riken Kikai Co., Ltd.), and 36.9 g of glacial acetic acid is added to the mixer. The mixture was uniformly mixed to obtain a solid baking soda dialysis agent having an average particle size of 900 μm.
［実施例２］
塩化カリウム３６．６ｇ、塩化マグネシウム６水和物２５．０ｇ、塩化カルシウム２水和物４５．１ｇおよび無水酢酸ナトリウム８０．６ｇを精製水４４７．６ｇに溶解して水溶液を調製した。転動攪拌流動層造粒装置（マルチプレックス ＭＰ−０１、パウレック社製）に、平均粒径３００μｍの塩化ナトリウム核粒子１，５００ｇ、平均粒径１８０μｍのブドウ糖粉末２４５．６ｇおよび平均粒径１５０μｍの無水酢酸ナトリウム３０．２ｇを投入し、給気温度８０℃にて、ローター回転数３００ｒｐｍおよび給気風量４０ｍ３／ｈｒの条件下で、前記水溶液を噴霧すると同時に乾燥させて、平均粒径８８０μｍの顆粒を得た。該顆粒を装置内より取り出し、室温まで冷却した後、Ｖ型混合機（Ｓ−３型、筒井理化学器械社製）に該顆粒を投入し、該混合機内に氷酢酸３６．９ｇを添加し、均一に混合して平均粒径８８０μｍの固形重曹透析用剤を得た。
[Example 2]
An aqueous solution was prepared by dissolving 36.6 g of potassium chloride, 25.0 g of magnesium chloride hexahydrate, 45.1 g of calcium chloride dihydrate and 80.6 g of anhydrous sodium acetate in 447.6 g of purified water. In a tumbling stirring fluidized bed granulator (Multiplex MP-01, manufactured by Paulek), 1,500 g of sodium chloride core particles having an average particle size of 300 μm, 245.6 g of glucose powder having an average particle size of 180 μm, and 150 μm of average particle size. Anhydrous sodium acetate (30.2 g) was added, and the aqueous solution was sprayed and dried at an air supply temperature of 80 ° C. under a rotor rotation speed of 300 rpm and an air supply air volume of 40 m 3 / hr to obtain an average particle size of 880 μm. Granules were obtained. The granules are taken out from the apparatus and cooled to room temperature, and then the granules are put into a V-type mixer (S-3, manufactured by Tsutsui Riken Kikai Co., Ltd.), and 36.9 g of glacial acetic acid is added to the mixer. The resulting mixture was uniformly mixed to obtain a solid baking soda dialysis agent having an average particle size of 880 μm.
［比較例１］
塩化カリウム１２．２ｇ、塩化マグネシウム６水和物８．３ｇ、塩化カルシウム２水和物１５．０ｇおよび無水酢酸ナトリウム３６．９ｇを精製水１７３．３ｇに溶解して水溶液を調製した。流動層造粒装置（フローコーター、ＦＬＯ−１、フロイント産業社製）に、平均粒径３００μｍを有する塩化ナトリウム核粒子５００ｇ及び平均粒子径１８０μｍを有するブドウ糖８１．９ｇを投入し、給気温度８０℃および給気ダンパー開度５０％の条件下で、前記水溶液を噴霧すると同時に乾燥させて、平均粒径９００μｍを有する顆粒を得た。該顆粒を装置内より取り出し、室温まで冷却した後、Ｖ型混合機（Ｓ−３型、筒井理化学器械社製）にを投入し、該混合機内に氷酢酸１２．３ｇを添加し、均一に混合して平均粒径９００μｍを有する固形重曹透析用剤を得た。
[Comparative Example 1]
An aqueous solution was prepared by dissolving 12.2 g of potassium chloride, 8.3 g of magnesium chloride hexahydrate, 15.0 g of calcium chloride dihydrate and 36.9 g of anhydrous sodium acetate in 173.3 g of purified water. A fluidized bed granulator (flow coater, FLO-1, manufactured by Freund Sangyo Co., Ltd.) is charged with 500 g of sodium chloride core particles having an average particle diameter of 300 μm and 81.9 g of glucose having an average particle diameter of 180 μm. The aqueous solution was sprayed at the same time as drying at 50 ° C. and a supply damper opening of 50% to obtain granules having an average particle size of 900 μm. The granules are taken out from the apparatus and cooled to room temperature. Then, a V-type mixer (S-3 type, manufactured by Tsutsui Riken Kikai Co., Ltd.) is introduced, and 12.3 g of glacial acetic acid is added to the mixer, By mixing, a solid baking soda dialysis agent having an average particle size of 900 μm was obtained.
上記実施例１、２および比較例１で得られた固形重曹透析用剤について、各々の電解質およびブドウ糖の含量測定、含量均一性の評価および安定性試験を行った。 With respect to the solid baking soda dialysis agents obtained in Examples 1 and 2 and Comparative Example 1, each electrolyte and glucose content were measured, content uniformity was evaluated, and a stability test was performed.
（含量測定および均一性評価）
上記実施例１、２および比較例１で得られた固形重曹透析用剤から、任意に５０ｇを６回採取し、それぞれを水に溶解させて５００ｍＬの水溶液を調製した。該水溶液中の各成分含量を測定し、理論値に対する測定した含量の平均値の割合（％）およびＣＶ値（％）（変動係数）を表１に示す。Ｎａ及びＫは炎光光度計、Ｃａ及びＭｇはイオンクロマトグラフ、Ｃｌは硝酸銀滴定法、ブドウ糖は旋光度計、酢酸（ＣＨ３ＣＯＯ−）はＨＰＬＣ−ＵＶによりそれぞれ測定した。
(Content measurement and uniformity evaluation)
From the solid sodium bicarbonate dialysis agent obtained in Examples 1 and 2 and Comparative Example 1, 50 g was arbitrarily collected 6 times, and each was dissolved in water to prepare a 500 mL aqueous solution. The content of each component in the aqueous solution was measured, and the ratio (%) of the average value of the measured content to the theoretical value and the CV value (%) (variation coefficient) are shown in Table 1. Na and K were measured by a flame photometer, Ca and Mg were measured by an ion chromatograph, Cl was measured by a silver nitrate titration method, glucose was measured by a polarimeter, and acetic acid (CH 3 COO − ) was measured by HPLC-UV.
下段の括弧内：ＣＶ値（％）
In parentheses at the bottom: CV value (%)
表１から明らかなように、本発明の固形重曹透析用剤はいずれも、各成分含量の平均値が理論値に近く、ＣＶ値も小さく、優れた含量均一性を示したことがわかる。一方、比較例１の流動層造粒装置を用いて得られた固形重曹透析用剤は、ブドウ糖の含量がかなり不均一であった。 As is apparent from Table 1, it can be seen that the solid baking soda dialysis agent of the present invention showed excellent content uniformity because the average value of each component content was close to the theoretical value and the CV value was small. On the other hand, the solid baking soda dialysis agent obtained using the fluidized bed granulator of Comparative Example 1 had a fairly uneven glucose content.
（安定性試験）
上記実施例１、２および比較例１で得られた固形重曹透析用剤５０ｇを１００×１００ｍｍのアルミ包材に封入し、（Ａ）２５℃、６０％ＲＨで６ヶ月間、または（Ｂ）４０℃、７５％ＲＨで３ヶ月間保存した物について、袋内の固形重曹透析用剤の着色、を観察した。着色は、色差計（Ｚ−３００Ａ、日本電色社製）により測定した。その結果を表２に示す。
(Stability test)
50 g of the solid baking soda dialysis agent obtained in Examples 1 and 2 and Comparative Example 1 was enclosed in an aluminum packaging material of 100 × 100 mm, and (A) 6 months at 25 ° C. and 60% RH, or (B) About the thing preserve | saved at 40 degreeC and 75% RH for 3 months, the coloring of the solid baking soda dialysis agent in a bag was observed. Coloring was measured with a color difference meter (Z-300A, manufactured by Nippon Denshoku). The results are shown in Table 2.
表２から明らかなように、本発明の固形重曹透析用剤は、長期間保存後も着色が見られなかった。一方、比較例１の流動層造粒装置を用いて得られた固形重曹透析用剤は、製造直後、既に着色していた。 As apparent from Table 2, the solid baking soda dialysis agent of the present invention was not colored even after long-term storage. On the other hand, the solid baking soda dialysis agent obtained using the fluidized bed granulator of Comparative Example 1 was already colored immediately after production.
本発明の固形重曹透析用剤は、転動攪拌流動層造粒装置を用いることにより、含量均一性に優れた固形重曹透析用剤を提供することが出来る。また、ブドウ糖が分解および着色するおそれがなく、長期保存安定性に富んだ固形重曹透析用剤が得られる。さらに、酢酸ナトリウムの一部を粉末状態で添加することにより、固形重曹透析用剤の製造時間を短縮することが出来る。 The solid sodium bicarbonate dialysis agent of the present invention can provide a solid sodium bicarbonate dialysis agent excellent in content uniformity by using a tumbling stirring fluidized bed granulator. In addition, a solid baking soda dialysis agent rich in long-term storage stability without the risk of degradation and coloring of glucose can be obtained. Furthermore, the manufacturing time of the solid sodium bicarbonate dialysis agent can be shortened by adding a part of sodium acetate in a powder state.
Claims (4)
（１）転動攪拌流動層造粒装置を用いて、塩化ナトリウムおよびブドウ糖粉末を含む核粒子に、塩化カルシウム、塩化マグネシウム、塩化カリウムおよび酢酸ナトリウムを含む水溶液を噴霧し、乾燥させる工程、
（２）工程（１）で得られた生成物に、酢酸を混合して固形重曹透析用剤を得る工程 Solid sodium bicarbonate dialysis agent produced by the following steps (1) and (2).
(1) A step of spraying and drying an aqueous solution containing calcium chloride, magnesium chloride, potassium chloride and sodium acetate onto core particles containing sodium chloride and glucose powder using a tumbling stirring fluidized bed granulator,
(2) Step of obtaining a solid sodium bicarbonate dialysis agent by mixing acetic acid with the product obtained in step (1)
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0338527A (en) * | 1989-07-06 | 1991-02-19 | Terumo Corp | Preparation for blood dialysis and its production |
| JPH0892070A (en) * | 1994-09-27 | 1996-04-09 | Morishita Roussel Kk | Blood dialyzing agent |
| JPH08169836A (en) * | 1994-06-28 | 1996-07-02 | Morishita Roussel Kk | Agent for sodium bicarbonate dialysis and its production |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0338527A (en) * | 1989-07-06 | 1991-02-19 | Terumo Corp | Preparation for blood dialysis and its production |
| JPH08169836A (en) * | 1994-06-28 | 1996-07-02 | Morishita Roussel Kk | Agent for sodium bicarbonate dialysis and its production |
| JPH0892070A (en) * | 1994-09-27 | 1996-04-09 | Morishita Roussel Kk | Blood dialyzing agent |
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