JP2809971B2 - Hemodialysis preparation - Google Patents
Hemodialysis preparationInfo
- Publication number
- JP2809971B2 JP2809971B2 JP5166769A JP16676993A JP2809971B2 JP 2809971 B2 JP2809971 B2 JP 2809971B2 JP 5166769 A JP5166769 A JP 5166769A JP 16676993 A JP16676993 A JP 16676993A JP 2809971 B2 JP2809971 B2 JP 2809971B2
- Authority
- JP
- Japan
- Prior art keywords
- hemodialysis
- preparation
- acetic acid
- electrolyte
- granular composition
- 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.)
- Expired - Lifetime
Links
- 238000001631 haemodialysis Methods 0.000 title claims description 38
- 230000000322 hemodialysis Effects 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 110
- 239000000203 mixture Substances 0.000 claims description 81
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 56
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 34
- 239000008103 glucose Substances 0.000 claims description 34
- 239000003792 electrolyte Substances 0.000 claims description 33
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 28
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 28
- 235000017281 sodium acetate Nutrition 0.000 claims description 28
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 28
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 28
- 239000001632 sodium acetate Substances 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000000843 powder Substances 0.000 claims description 20
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 14
- 239000001110 calcium chloride Substances 0.000 claims description 14
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 14
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 14
- 238000000502 dialysis Methods 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 239000003002 pH adjusting agent Substances 0.000 claims description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 229960000583 acetic acid Drugs 0.000 description 38
- 238000004519 manufacturing process Methods 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000008187 granular material Substances 0.000 description 18
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 14
- 239000008213 purified water Substances 0.000 description 13
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000003860 storage Methods 0.000 description 8
- 239000001103 potassium chloride Substances 0.000 description 7
- 235000011164 potassium chloride Nutrition 0.000 description 7
- 229910052782 aluminium Inorganic materials 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 235000010724 Wisteria floribunda Nutrition 0.000 description 5
- 238000002834 transmittance Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000011812 mixed powder Substances 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- -1 polyethylene Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000003113 alkalizing effect Effects 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000000004 hemodialysis solution Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 239000007784 solid electrolyte Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1654—Dialysates therefor
- A61M1/1656—Apparatus for preparing dialysates
- A61M1/1666—Apparatus for preparing dialysates by dissolving solids
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Vascular Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- External Artificial Organs (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、血液透析用製剤のため
のｐＨ調整剤および血液透析用顆粒状組成物に関する。The present invention relates to a pH adjusting agent for a preparation for hemodialysis and a granular composition for hemodialysis.
【０００２】[0002]
【従来の技術】腎不全患者に対する血液透析療法では、
体外循環させた患者の血液を人工腎臓装置を用いて浄化
するが、この人工腎臓の内部には透析液が灌流されてお
り、その透析液が透析膜を介して血液と接触し、血液中
の老廃物を透析液側に移行させることにより、血液を浄
化している。従来、血液透析液に含まれる緩衝剤（アル
カリ化剤）としては酢酸塩が用いられてきたが、透析膜
の改良が進んで透過性が高められ、いわゆる高効率透析
が行われるようになると、透析液から血液中へ移行する
酢酸量が増加し、心血管系に悪影響を与える原因となる
ことが指摘されるようになった。このため、近年では生
体にとって負担の少ない炭酸水素ナトリウム（重炭酸ソ
ーダ）を緩衝剤に用いた重炭酸型透析液が主流になって
きている。2. Description of the Related Art In hemodialysis therapy for renal failure patients,
The blood of the patient who has been circulated extracorporeally is purified using an artificial kidney device.A dialysate is perfused inside the artificial kidney, and the dialysate comes into contact with the blood through the dialysis membrane, and Blood is purified by transferring waste products to the dialysate side. Conventionally, acetate has been used as a buffer (alkalizing agent) contained in a hemodialysis solution. However, when dialysis membranes are improved and permeability is increased, so-called high-efficiency dialysis is performed. It has been pointed out that the amount of acetic acid transferred from the dialysate into the blood increases, which may cause a bad influence on the cardiovascular system. For this reason, in recent years, a bicarbonate dialysate using sodium bicarbonate (sodium bicarbonate) as a buffer, which has a small burden on a living body, has become mainstream.
【０００３】透析用製剤中には、透析用電解質成分（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、など）、緩衝剤（従来は酢酸塩、現在は炭
酸水素ナトリウムが主）、ｐＨ調整用酸（通常は、酢
酸）、ブドウ糖などが含まれている。そして、炭酸水素
ナトリウムについては、カルシウム、マグネシウム塩
と反応して炭酸塩を生じ、水分存在下でのブドウ糖に
対する着色、酸との配合禁忌などの問題点が存在す
る。そこで、これらを考慮して、(1)透析用電解質成分
とｐＨ調整用酸を含む濃厚原液および(2)炭酸水素ナト
リウム水溶液または粉末を組み合わせた２液タイプまた
は１液１粉末タイプの形態で市販されている。この市販
の形態では、濃厚原液は１０〜２０ｋｇのポリエチレン
製容器入り製品として市販されているが、重量および容
量が大きく、運搬および保管に欠点があった。そこで、
透析用製剤を粉末化し、小型・軽量化する試みがなされ
ている。In dialysis preparations, dialysis electrolyte components (sodium chloride, potassium chloride, calcium chloride, magnesium chloride, etc.), buffers (conventionally acetate, currently sodium bicarbonate), pH adjustment It contains acids (usually acetic acid), glucose and the like. Sodium bicarbonate reacts with calcium and magnesium salts to form carbonates, and has problems such as coloring glucose in the presence of water and contraindications with acids. Therefore, in consideration of these, commercially available in the form of a two-liquid type or a one-liquid one-powder type combining (1) a concentrated stock solution containing an electrolyte component for dialysis and an acid for adjusting pH and (2) an aqueous solution or powder of sodium hydrogen carbonate. Have been. In this commercially available form, the concentrated stock solution is marketed as a product in a polyethylene container weighing 10 to 20 kg, but has a large weight and volume, and has disadvantages in transportation and storage. Therefore,
Attempts have been made to reduce the size and weight of dialysis preparations by powdering.
【０００４】しかし、粉末状組成物においても炭酸水素
ナトリウムによる欠点は相変わらず存在する。すなわ
ち、水分存在下での酸または炭酸水素ナトリウムにより
ブドウ糖が着色するという欠点がある。これを避けるた
め、製造を無水環境下で行う炭酸水素ナトリウムおよび
ブドウ糖よりなる粉末状組成物からなる血液透析用製剤
（特開平２−３１１４１８号）や、透析用固体電解質、
ブドウ糖および液体酸よりなる粉末状組成物と、炭酸水
素ナトリウムよりなる粉末状組成物からなる血液透析用
製剤（特開平２−３１１４１９号）が提案された。ま
た、特開平３−３８５２７号は、血液透析用製剤を透析
用固体無機塩、ブドウ糖、酢酸ナトリウムおよび酢酸よ
りなる粉末状組成物と、炭酸水素ナトリウムおよび酢酸
ナトリウムよりなる粉末状組成物からなる２つの組成物
としているが、ブドウ糖の変色を完全には抑制し得ない
ことがわかった。[0004] However, the disadvantages of sodium bicarbonate still exist in powdery compositions. That is, there is a disadvantage that glucose is colored by an acid or sodium bicarbonate in the presence of water. In order to avoid this, a preparation for hemodialysis comprising a powdery composition comprising sodium bicarbonate and glucose which is produced in an anhydrous environment (Japanese Patent Laid-Open No. 2-311418), a solid electrolyte for dialysis,
A hemodialysis preparation comprising a powdery composition comprising glucose and a liquid acid and a powdery composition comprising sodium hydrogen carbonate (JP-A-2-311419) has been proposed. JP-A-3-38527 discloses a hemodialysis preparation comprising a powdery composition comprising a solid inorganic salt for dialysis, glucose, sodium acetate and acetic acid, and a powdery composition comprising sodium bicarbonate and sodium acetate. However, it was found that discoloration of glucose could not be completely suppressed.
【０００５】また、粉末状組成物固有の欠点がある。す
なわち、特公昭５７−３４２４８号には、スプレードラ
イ法による透析用電解質粉末の製造方法が開示されてい
るが、スプレードライ法では、製品の水分、粒度にばら
つきが認められ、特に酸成分が乾燥時に揮散し、重炭酸
透析液に一定のｐＨを与えるのが難しい。また、特公昭
５８−２７２４６号には、電解質粉末の成分である塩化
ナトリウムに氷酢酸を噴霧添加してｐＨ調節した重炭酸
型透析用電解質粉末を得る方法が開示されている。塩化
ナトリウムに氷酢酸を噴霧添加する方法では、塩化ナト
リウムの使用量が多いため、酸の揮散も多くなり、これ
を予定して過剰の酸を用いるため、多量の氷酢酸を必要
とする。さらに、特開昭６２−３０５４０号には、酢酸
ナトリウムを主剤とする透析用製剤において、塩化カル
シウムおよび塩化マグネシウムを酢酸ナトリウムおよび
水と共に混和微粉末化することにより、電解質混合物の
組成の部分的不均一を少なくする技術が開示されてい
る。これは確かに均一性は改善するが、製造・運搬並び
に保存中に潮解したりあるいは固結したりするという欠
点があらわれる。There are also disadvantages inherent in powdery compositions. That is, Japanese Patent Publication No. 57-34248 discloses a method for producing an electrolyte powder for dialysis by a spray-drying method. In the spray-drying method, the moisture and the particle size of the product vary, and especially the acid component is dried. Sometimes it volatilizes and it is difficult to give a constant pH to the bicarbonate dialysate. Japanese Patent Publication No. 58-27246 discloses a method for obtaining a bicarbonate-type electrolyte powder for dialysis in which pH is adjusted by spraying glacial acetic acid to sodium chloride which is a component of the electrolyte powder. In the method of spray-adding glacial acetic acid to sodium chloride, the amount of sodium chloride used is large, so that the volatilization of the acid also increases, and a large amount of glacial acetic acid is required because an excess acid is used for this purpose. Further, Japanese Patent Application Laid-Open No. Sho 62-30540 discloses that in a dialysis preparation containing sodium acetate as a main component, calcium chloride and magnesium chloride are mixed and finely powdered with sodium acetate and water, whereby the composition of the electrolyte mixture is partially impaired. Techniques for reducing uniformity have been disclosed. This certainly improves the uniformity, but has the disadvantage of deliquescent or consolidation during manufacture, transport and storage.
【０００６】先に、発明者らは（イ）血液透析用電解
質、（ロ）ブドウ糖および（ハ）炭酸水素ナトリウムを
含む血液透析用顆粒剤において、（i）（イ）、（ロ）
および（ハ）を別々の顆粒状組成物とすること、（ii）
（イ）を、（イ）の成分中少なくとも１種を水溶液と
し、残りの成分を微粉状で使用して顆粒状組成物に調製
すること、を特徴とする血液透析用顆粒剤を開発した
（特開平５−７０３５７号）。しかしながら、この方法
でも、ｐＨ調整用の酢酸を（イ）の水溶液中に添加した
後、乾燥して、顆粒剤とすることから、乾燥中に揮散す
る量に相当する酢酸の過量をあらかじめ加えておく必要
があった。従って、この血液透析用顆粒剤を製造するに
は、大過剰量の酢酸を使用しなければならなかった。ま
た、酢酸を使用する製造工程では、酸による金属の腐食
のために工程を自動化が難しく、作業環境も悪化する。First, the inventors of the present invention have proposed (i) a hemodialysis electrolyte, (b) glucose and (c) sodium bicarbonate granules for hemodialysis containing (i) (a), (b)
And (c) as separate granular compositions, (ii)
A granule for hemodialysis, characterized in that (a) is prepared into a granular composition by using at least one of the components of (a) as an aqueous solution and using the remaining components in the form of a fine powder, JP-A-5-70357). However, also in this method, acetic acid for pH adjustment is added to the aqueous solution of (a) and then dried to obtain granules. Therefore, an excess amount of acetic acid corresponding to the amount volatilized during drying is added in advance. Had to be kept. Therefore, a large excess of acetic acid had to be used to produce the granules for hemodialysis. Further, in a manufacturing process using acetic acid, it is difficult to automate the process due to corrosion of the metal by the acid, and the working environment is deteriorated.
【０００７】[0007]
【課題を解決するための手段】これらの欠点は、本発明
に従って、酢酸を吸着させた粒状の酢酸ナトリウムの形
態である血液透析用製剤用ｐＨ調整剤を使用し、これを
含む顆粒状組成物である血液透析用製剤によって解決で
きる。本発明の血液透析用製剤の好ましい一態様は、
（イ）血液透析用電解質およびブドウ糖からなる顆粒状
組成物、特に塩化カルシウムおよび塩化マグネシウム以
外の血液透析用電解質およびブドウ糖微粉末に、塩化カ
ルシウムおよび塩化マグネシウムを水に溶解した水溶液
を加え、練合、造粒、乾燥、整粒して調製した顆粒状組
成物、（ロ）粒状の酢酸ナトリウムに酢酸を加えて、酢
酸ナトリウムに酢酸を吸着させたものを整粒して調製し
た顆粒状組成物であるｐＨ調整剤、および（ハ）炭酸水
素ナトリウムよりなる顆粒状組成物の３つの組成物から
なる血液透析用製剤を用いる。上記のように、酢酸は血
液透析用製剤の製造工程で作業の自動化の障害となる。
しかし、本発明では、血液透析用製剤の（イ）、（ロ）
および（ハ）の成分において、通常、量的割合は（イ）
＞（ハ）＞（ロ）の順であり、酢酸を使用する（ロ）は
最も使用量が少なく、従って、作業の自動化率が高ま
り、生産コストが低減されている。According to the present invention, there is provided a granular composition comprising a pH adjusting agent for a hemodialysis preparation in the form of granular sodium acetate to which acetic acid has been adsorbed. It can be solved by the preparation for hemodialysis. One preferred embodiment of the preparation for hemodialysis of the present invention,
(A) To a granulated composition comprising an electrolyte for hemodialysis and glucose, in particular, an electrolyte for hemodialysis other than calcium chloride and magnesium chloride and fine glucose powder, an aqueous solution in which calcium chloride and magnesium chloride are dissolved in water is added and kneaded. Granular composition prepared by granulating, drying and sizing, (b) Granular composition prepared by adding acetic acid to granular sodium acetate and sizing acetic acid to sodium acetate And a hemodialysis preparation comprising three compositions, a granular composition comprising (c) a sodium bicarbonate. As described above, acetic acid hinders automation of operations in the production process of hemodialysis preparations.
However, in the present invention, the hemodialysis preparations (a) and (b)
In the components of (c) and (c), the quantitative ratio is usually (a)
The order of>(c)> (b) is that the use of acetic acid (b) is the least used, so that the automation rate of work is increased and the production cost is reduced.
【０００８】本発明の血液透析用製剤は、上記したとお
り、（イ）〜（ハ）の３種の顆粒状組成物からなるもの
である。血液透析用電解質およびブドウ糖よりなる顆粒
状組成物（イ）は、（イ）の電解質成分のうち、少なく
とも１種、好ましくは塩化カルシウムまたは塩化マグネ
シウムを水に溶解させて水溶液とし、該水溶液を残りの
成分を含む血液透析用電解質およびブドウ糖微粉末に加
えて、練合、造粒、乾燥、整粒して調製する。[0008] As described above, the hemodialysis preparation of the present invention comprises the three types of granular compositions (a) to (c). The granular composition (a) comprising an electrolyte for hemodialysis and glucose is obtained by dissolving at least one of the electrolyte components (a), preferably calcium chloride or magnesium chloride, in water to form an aqueous solution. In addition to the hemodialysis electrolyte and glucose fine powder containing the above components, the mixture is kneaded, granulated, dried and sized.
【０００９】血液透析用電解質には、Ｎａ+、Ｋ+、Ｃａ
2+、Ｍｇ2+、Ｃｌ-、ＣＨ3ＣＯＯ−などが含まれ、一般
に、ｍＥｑ／ｌの単位で、Ｎａ＋は１３２〜１４０、Ｋ
+は２.０〜２.５、Ｃａ2+は２.５〜３.５、Ｍｇ2+は１.
０〜１.５、Ｃｌ-は１０５〜１１０、ＣＨ3ＣＯＯ-は６
〜８を含むことができる。（イ）の電解質成分中、水に
溶解させる成分は、潮解性を有するものが好ましく、通
常は塩化カルシウムおよび塩化マグネシウムなどであ
る。塩化カルシウム、塩化マグネシウム以外の電解質粉
末としては、塩化ナトリウムおよび塩化カリウムなどが
挙げられる。（イ）に含まれる電解質成分およびブドウ
糖の使用量は、通常、次のような範囲にある：塩化ナト
リウム；７５〜８５重量％、塩化カリウム；１〜３重量
％、塩化カルシウム；２〜４重量％、塩化マグネシウ
ム；１〜２重量％、ブドウ糖１０〜２０重量％である。The electrolytes for hemodialysis include Na + , K + , Ca
2+ , Mg 2+ , Cl − , CH 3 COO − and the like. In general, in units of mEq / l, Na + is 132 to 140, K
+ Is 2.0 to 2.5, Ca 2+ is 2.5 to 3.5, and Mg 2+ is 1.0.
0 to 1.5, Cl - is 105~110, CH 3 COO - 6
~ 8. The component dissolved in water in the electrolyte component (a) is preferably deliquescent, and is usually calcium chloride or magnesium chloride. Examples of the electrolyte powder other than calcium chloride and magnesium chloride include sodium chloride and potassium chloride. The amounts of the electrolyte component and glucose contained in (a) are usually in the following ranges: sodium chloride; 75 to 85% by weight, potassium chloride; 1 to 3% by weight, calcium chloride; %, Magnesium chloride; 1-2% by weight, and glucose 10-20% by weight.
【００１０】この場合、（イ）の残りの成分を含む血液
透析用電解質と、ブドウ糖および炭酸水素ナトリウム
は、造粒性および均一性を良くするために、微粉状であ
ることが好ましい。従って、粒子径の下限は特に限定さ
れないが、微粉状とは、大部分の粒子径が１５０μｍ以
下、好ましくは粒子径５０μｍ以下であり、さらに好ま
しくは、５０μｍ〜１０μｍである。大部分とは、好ま
しくは９０％以上、通常は７０％以上、さらに５０％以
上であってもよい。In this case, the hemodialysis electrolyte containing the remaining components (a), glucose and sodium bicarbonate are preferably in the form of fine powder in order to improve granulation and uniformity. Therefore, the lower limit of the particle diameter is not particularly limited, but the fine powder means that most of the particle diameter is 150 μm or less, preferably 50 μm or less, and more preferably 50 μm to 10 μm. The majority is preferably at least 90%, usually at least 70%, even more preferably at least 50%.
【００１１】（ロ）の酢酸ナトリウムは、通常は無水の
酢酸ナトリウムを用い、粒径が５０μｍ〜１４００μ
ｍ、好ましくは１５０μｍ〜１４００μｍのものを使用
する。そのほか、酢酸ナトリウム・三水和物および他の
含水物を用いることもできる。酢酸ナトリウムに対する
酢酸の吸着は、例えば、撹拌型混合機を用いて酢酸ナト
リウムに氷酢酸をスプレーするなどの方法により行う。
酢酸ナトリウムに対する酢酸の量は、１８〜１７：８〜
４、好ましくは、１８〜１７：５〜４、より好ましく
は、１７.２：４.２である。ここで用いられる酢酸ナト
リウムは、緩衝剤中に含まれる生体のアルカリ化作用を
目的とする酢酸ナトリウムであってもよく、本発明の血
液透析用製剤全体の組成に大きな変化を与えない。ま
た、酢酸として氷酢酸なども使用することができる。
（ロ）および（ハ）の顆粒状組成物は、通常、他に固形
成分を配合しない。The sodium acetate of (b) is usually anhydrous sodium acetate and has a particle size of 50 μm to 1400 μm.
m, preferably 150 μm to 1400 μm. In addition, sodium acetate trihydrate and other hydrates can be used. Adsorption of acetic acid to sodium acetate is performed by, for example, spraying glacial acetic acid on sodium acetate using a stirring mixer.
The amount of acetic acid based on sodium acetate is 18-17: 8-
4, preferably 18 to 17: 5 to 4, more preferably 17.2 to 4.2. The sodium acetate used here may be sodium acetate for the purpose of alkalizing the living body contained in the buffer, and does not significantly change the composition of the entire hemodialysis preparation of the present invention. Also, glacial acetic acid or the like can be used as acetic acid.
The granular compositions (b) and (c) generally do not contain any other solid components.
【００１２】本発明の顆粒状組成物は、最終的に各々、
１４００μｍ（１２メッシュ）に整粒し、製剤として貯
蔵、運搬する。使用に際して、混合した顆粒状組成物を
水に溶解するか、または各々を水に溶解してこれを混合
することもできる。本発明の顆粒剤における顆粒状組成
物（イ）、（ロ）および（ハ）の使用割合（重量比）
は、３５〜２０：４〜２：９〜５、好ましくは３０〜２
５：３〜２：８〜６、より好ましくは２６：２.１：８.
８または２９：２.１：７.４である。The granular compositions of the present invention are each finally
It is sized to 1400 μm (12 mesh), stored and transported as a preparation. In use, the mixed granular composition may be dissolved in water, or each may be dissolved in water and mixed. Use ratio (weight ratio) of the granular compositions (a), (b) and (c) in the granules of the present invention
Is 35 to 20: 4 to 2: 9 to 5, preferably 30 to 2
5: 3 to 2: 8 to 6, more preferably 26: 2.1: 8.
8 or 29: 2.1: 7.4.
【００１３】[0013]
【実施例】次に実施例を挙げて本発明をさらに詳しく説
明するが、これらに限定されるものではない。 実施例１ （１）血液透析用電解質およびブドウ糖よりなる顆粒状
組成物（イ）の製造 塩化ナトリウム８０.５０ｋｇ、塩化カリウム１.９８ｋ
ｇおよびブドウ糖１３.２５ｋｇをとり、それぞれ、粉
砕機（不二パウダル株式会社製アトマイザー）を使用し
て粉砕およびスクリーンを通過させて５０μｍ以下の微
粉状にした後、各成分を混合した。この混合粉末に塩化
カルシウム２.９２ｋｇおよび塩化マグネシウム１.３５
ｋｇを精製水７.０ ｌに溶解した水溶液を添加して練合
した後、０.７ｍｍ径のバスケット型造粒機を用いて造
粒した。得られた造粒物を通気式箱型乾燥機（不二パウ
ダル株式会社製通気式乾燥機４００Ｂ台車型）を用いて
水分含量が０.５％以下になるように乾燥した。乾燥物
を１４００μｍ（１２メッシュ）のシフターを用いて整
粒して、顆粒状組成物（イ）を得た。Next, the present invention will be described in more detail with reference to Examples, but it should not be construed that the invention is limited thereto. Example 1 (1) Production of granular composition (a) comprising electrolyte for hemodialysis and glucose 80.50 kg of sodium chloride, 1.98 k of potassium chloride
g and 13.25 kg of glucose were crushed using a crusher (Atomizer manufactured by Fuji Paudal Co., Ltd.) and passed through a screen to make a fine powder of 50 μm or less, and then each component was mixed. 2.92 kg of calcium chloride and 1.35 of magnesium chloride are added to this mixed powder.
An aqueous solution obtained by dissolving kg in 7.0 L of purified water was added and kneaded, followed by granulation using a basket-type granulator having a diameter of 0.7 mm. The obtained granules were dried using a ventilated box type drier (Fuji Paudal Co., Ltd., type 400B bogie type drier) so that the water content was 0.5% or less. The dried product was sized using a 1400 μm (12 mesh) shifter to obtain a granular composition (a).
【００１４】（２）酢酸ナトリウムおよび酢酸よりなる
顆粒状組成物（ロ）の製造 粒状（１５０μｍ〜１４００μｍ）の酢酸ナトリウム８
０.３７ｋｇをとり、撹拌型混合機（パウレック製）を
用いて２１.９８ｋｇの氷酢酸を均等に噴霧しつつ分散
して吸着させた後、１４００μｍ（１２メッシュ）のシ
フターを用いて整粒して、顆粒状組成物（ロ）を得た。(2) Production of Granular Composition (B) Consisting of Sodium Acetate and Acetic Acid Granular (150 μm to 1400 μm) sodium acetate 8
0.37 kg was taken, 21.98 kg of glacial acetic acid was uniformly dispersed and adsorbed using a stirring mixer (made by Powrex), and then sized using a 1400 μm (12 mesh) shifter. Thus, a granular composition (b) was obtained.
【００１５】（３）炭酸水素ナトリウムよりなる顆粒状
組成物（ハ）の製造 炭酸水素ナトリウム１００ｋｇをとり、粉砕機（不二パ
ウダル株式会社製アトマイザー）を使用して粉砕および
スクリーンを通過させて５０μｍ以下の微粉状にしたも
のに精製水１０.０ ｌを加えて練合した後、０.７ｍｍ
径のバスケット型造粒機を用いて造粒した。得られた造
粒物を通気式箱型乾燥機（不二パウダル株式会社製通気
式乾燥機４００Ｂ台車型）を用いて水分含量が０.５％
以下となるように乾燥した。乾燥物を１４００μｍ（１
２メッシュ）のシフターを用いて整粒して、顆粒状組成
物（ハ）を得た。(3) Production of Granular Composition (C) Consisting of Sodium Bicarbonate 100 kg of sodium bicarbonate was taken, pulverized using a pulverizer (Atomizer manufactured by Fuji Paudal Co., Ltd.) and passed through a screen to 50 μm. After adding 10.0 l of purified water to the following fine powder and kneading the mixture, 0.7 mm
Granulation was performed using a basket-type granulator having a diameter. The water content of the obtained granules was 0.5% by using a ventilated box-type drier (ventilation type 400B bogie type manufactured by Fuji Paudal Co., Ltd.).
It was dried as follows. The dried product is 1400 μm (1
The mixture was sized using a 2 mesh) shifter to obtain a granular composition (c).
【００１６】実施例２ （１）血液透析用電解質およびブドウ糖よりなる顆粒状
組成物（イ）の製造 塩化ナトリウム７６.６９ｋｇ、塩化カリウム１.８０ｋ
ｇおよびブドウ糖１８.０７ｋｇをとり、それぞれ、実
施例１に記載と同様に粉砕して５０μｍ以下の微粉状に
した後、各成分を混合した。この混合粉末に塩化カルシ
ウム２.２１ｋｇおよび塩化マグネシウム１.２３ｋｇを
精製水７.０ ｌに溶解した水溶液を添加して練合した
後、０.７ｍｍ径のバスケット型造粒機を用いて造粒し
た。得られた造粒物を通気式箱型乾燥機（不二パウダル
株式会社製通気式乾燥機４００Ｂ台車型）を用いて水分
含量が０.５％以下となるように乾燥した。乾燥物を１
４００μｍ（１２メッシュ）のシフターを用いて整粒し
て、顆粒状組成物（イ）を得た。Example 2 (1) Production of granular composition (a) comprising electrolyte for hemodialysis and glucose (a) 76.69 kg of sodium chloride, 1.80 k of potassium chloride
g and 18.07 kg of glucose were crushed in the same manner as described in Example 1 to obtain a fine powder of 50 μm or less, and then each component was mixed. An aqueous solution obtained by dissolving 2.21 kg of calcium chloride and 1.23 kg of magnesium chloride in 7.0 liter of purified water was added to the mixed powder, kneaded, and then granulated using a basket type granulator having a diameter of 0.7 mm. did. The obtained granules were dried using a ventilated box-type dryer (Ventilation dryer 400B manufactured by Fuji Paudal Co., Ltd.) so that the water content was 0.5% or less. 1 dry matter
The granules were sized using a 400 μm (12 mesh) shifter to obtain a granular composition (a).
【００１７】（２）酢酸ナトリウムおよび酢酸よりなる
顆粒状組成物（ロ）の製造 実施例１の（２）酢酸ナトリウムおよび酢酸よりなる顆
粒状組成物（ロ）の製造と同様に操作し、酢酸ナトリウ
ムおよび酢酸よりなる顆粒状組成物（ロ）を得た。(2) Production of a granular composition (b) composed of sodium acetate and acetic acid The same operation as in the production of a granular composition (b) composed of sodium acetate and acetic acid (b) of Example 1 was carried out. A granular composition (b) consisting of sodium and acetic acid was obtained.
【００１８】（３）炭酸水素ナトリウムよりなる顆粒状
組成物（ハ）の製造 実施例１の（３）炭酸水素ナトリウムよりなる顆粒状組
成物（ハ）の製造と同様に操作し、炭酸水素ナトリウム
よりなる顆粒状組成物（ハ）を得た。(3) Production of granular composition (c) comprising sodium hydrogencarbonate The same operation as in the production of granular composition (c) comprising (3) sodium hydrogencarbonate of Example 1 was carried out. To obtain a granular composition (c).
【００１９】比較例１ (１)血液透析用電解質及びブドウ糖よりなる顆粒状組成
物の製造 塩化ナトリウム７４.４８ｋｇ、塩化カリウム１.８３ｋ
ｇ、酢酸ナトリウム６.０３ｋｇおよびブドウ糖１２.２
５ｋｇをとり、それぞれ、実施例に記載と同様に粉砕し
て５０μｍのシフターにかけて、５０μｍ以下の微粉状
にした後、各成分を混合した。この混合粉末に塩化カル
シウム２.７０ｋｇおよび塩化マグネシウム１.２５ｋｇ
を精製水３.５ｌに溶解し、適量の氷酢酸を加えて酢酸
酸性とした溶液を添加して練合した後、０.７ｍｍ径の
バスケット型造粒機を用いて造粒した。得られた造粒物
を通気式箱型乾燥機を用いて氷酢酸含量が１.４〜１.６
重量％となるように乾燥した。乾燥物を１４００μｍ
（１２メッシュ）のシフターを用いて整粒して、顆粒状
組成物を得た。Comparative Example 1 (1) Production of granular composition comprising hemodialysis electrolyte and glucose 74.48 kg of sodium chloride, 1.83 k of potassium chloride
g, sodium acetate 6.03 kg and glucose 12.2
5 kg was taken, each was pulverized in the same manner as described in Examples, and passed through a 50 μm shifter to form a fine powder of 50 μm or less, and then each component was mixed. 2.70 kg of calcium chloride and 1.25 kg of magnesium chloride are added to this mixed powder.
Was dissolved in 3.5 l of purified water, and a solution made acidic by adding an appropriate amount of glacial acetic acid was added and kneaded, followed by granulation using a basket type granulator having a diameter of 0.7 mm. The obtained granulated product was subjected to a glacial acetic acid content of 1.4 to 1.6 using a ventilated box drier.
It was dried to a weight percent. 1400 μm dry matter
The granules were sized using a (12 mesh) shifter to obtain a granular composition.
【００２０】(２)炭酸水素ナトリウムよりなる顆粒状組
成物の製造 実施例１の(３)炭酸水素ナトリウムよりなる顆粒状組成
物(ハ)の製造と同様に操作し、炭酸水素ナトリウムより
なる顆粒状組成物を得た。(2) Preparation of Granular Composition Consisting of Sodium Bicarbonate The same operation as in the preparation of the granular composition (c) consisting of (3) Sodium Bicarbonate in Example 1 was carried out to obtain a granule consisting of sodium bicarbonate. A composition was obtained.
【００２１】比較例２ (１)血液透析用電解質及びブドウ糖よりなる顆粒状組成
物の製造 塩化ナトリウム７１.４４ｋｇ、塩化カリウム１.６７ｋ
ｇ、酢酸ナトリウム５.５１ｋｇおよびブドウ糖１６.８
３ｋｇをとり、それぞれ、実施例に記載と同様に粉砕し
て５０μｍ以下の微粉状にした後、各成分を混合した。
この混合粉末に塩化カルシウム２.０６ｋｇおよび塩化
マグネシウム１.１４ｋｇを精製水３.５ｌに溶解し、適
量の氷酢酸を加えて酢酸酸性とした溶液を添加して練合
した後、０.７ｍｍ径のバスケット型造粒機を用いて造
粒した。得られた造粒物を通気式箱型乾燥機を用いて氷
酢酸含量が１.３〜１.５重量％となるように乾燥した。
乾燥物を１４００μｍ（１２メッシュ）のシフターを用
いて整粒して、顆粒状組成物を得た。Comparative Example 2 (1) Production of Granular Composition Comprising Hemodialysis Electrolyte and Glucose 71.44 kg of sodium chloride, 1.67 k of potassium chloride
g, 5.51 kg of sodium acetate and glucose 16.8
After taking 3 kg, each was pulverized in the same manner as described in the Examples to obtain a fine powder of 50 μm or less, and then each component was mixed.
To this mixed powder, 2.06 kg of calcium chloride and 1.14 kg of magnesium chloride were dissolved in 3.5 l of purified water, and a solution made acidic by adding an appropriate amount of glacial acetic acid was kneaded, and then kneaded. Was granulated using a basket type granulator. The obtained granules were dried using a ventilated box drier so that the glacial acetic acid content was 1.3 to 1.5% by weight.
The dried product was sized using a 1400 μm (12 mesh) shifter to obtain a granular composition.
【００２２】(２)炭酸水素ナトリウムよりなる顆粒状組
成物の製造 実施例２の(３)炭酸水素ナトリウムよりなる顆粒状組成
物(ハ)の製造と同様に操作し、炭酸水素ナトリウムより
なる顆粒状組成物を得た。(2) Preparation of Granular Composition Consisting of Sodium Bicarbonate The same operation as in the preparation of the granular composition (c) consisting of (3) Sodium Bicarbonate in Example 2 was carried out, and the granules consisting of sodium bicarbonate were obtained. A composition was obtained.
【００２３】試験例１ 実施例１で得られた顆粒状組成物において、電解質およ
びブドウ糖よりなる顆粒状組成物（イ）７.５５ｇ、酢
酸ナトリウムおよび酢酸よりなる顆粒状組成物（ロ）
０.６１ｇをとり、精製水に溶かし１.０ ｌとした液に
つき、各電解質およびブドウ糖の含量ならびにｐＨを測
定し、各成分ならびにｐＨの均一性について検討した。
その結果を表１に示す。Test Example 1 In the granular composition obtained in Example 1, 7.55 g of a granular composition comprising an electrolyte and glucose (a), and a granular composition comprising sodium acetate and acetic acid (b)
0.61 g was dissolved in purified water to make 1.0 liter, and the contents of each electrolyte and glucose and the pH were measured, and the uniformity of each component and pH was examined.
Table 1 shows the results.
【表１】 [Table 1]
【００２４】試験例２ 実施例２で得られた顆粒状組成物において、電解質およ
びブドウ糖よりなる顆粒状組成物（イ）８.３０ｇ、酢
酸ナトリウムおよび酢酸よりなる顆粒状組成物（ロ）
０.６１ｇをとり、精製水に溶かし１.０ ｌとした液に
つき、各電解質およびブドウ糖の含量ならびにｐＨを測
定し、各成分ならびにｐＨの均一性について検討した。
その結果を表２に示す。Test Example 2 In the granular composition obtained in Example 2, 8.30 g of a granular composition comprising an electrolyte and glucose, and a granular composition comprising sodium acetate and acetic acid (b)
0.61 g was dissolved in purified water to make 1.0 liter, and the contents of each electrolyte and glucose and the pH were measured, and the uniformity of each component and pH was examined.
Table 2 shows the results.
【表２】 [Table 2]
【００２５】試験例３ 実施例１で得られた顆粒状組成物において、電解質およ
びブドウ糖よりなる顆粒状組成物（イ）２６４２ｇをと
り、アルミニウム袋に封入した。また、酢酸ナトリウム
および酢酸よりなる顆粒状組成物（ロ）２１４ｇをと
り、アルミニウム袋に封入した。更に、炭酸水素ナトリ
ウム顆粒状組成物（ハ）８８２ｇをとり、ポリエチレン
袋に封入した。各袋を室温あるいは加温加湿条件（４０
℃、７５％ＲＨ）で一定期間保存した後、（イ）７.５
５ｇおよび（ロ）０.６１ｇをとり、精製水に溶かし１.
０ ｌとした液につき、各成分含量およびｐＨを測定
し、長期保存時における安定性について検討した。ただ
し、含量については、経時的な変化率を比較する意味
で、製造直後の値を１００とし、以後の各測定時点の値
を製造直後の値に対する比率に換算して比較尺度を統一
した。その結果を表３に示す。Test Example 3 From the granular composition obtained in Example 1, 2642 g of a granular composition (a) comprising an electrolyte and glucose was taken and sealed in an aluminum bag. In addition, 214 g of a granular composition (b) composed of sodium acetate and acetic acid was taken and sealed in an aluminum bag. Further, 882 g of the sodium hydrogencarbonate granular composition (c) was taken and sealed in a polyethylene bag. Place each bag at room temperature or under humidified conditions (40
At 75 ° C., 75% RH) for a certain period of time.
Take 5 g and 0.61 g of (b) and dissolve in purified water to obtain 1.
The content and pH of each component were measured for the 0 L solution, and the stability during long-term storage was examined. However, as for the content, in order to compare the rate of change over time, the value immediately after production was set to 100, and the value at each subsequent measurement was converted into a ratio to the value immediately after production to standardize the comparison scale. Table 3 shows the results.
【表３】 [Table 3]
【００２６】また、（ハ）についても、同様に、一定期
間保存後の含量およびｐＨを測定し、含量については製
造直後の値を１００とし、それに対する比率で表し、ｐ
Ｈについては、５％水溶液とした時の値を示した。その
結果を表４に示す。Similarly, for (c), the content and pH after storage for a certain period of time were measured, and the content was expressed as a ratio to the value immediately after production, which was taken as 100.
As for H, the value when a 5% aqueous solution was used was shown. Table 4 shows the results.
【表４】 [Table 4]
【００２７】試験例４ 実施例２で得られた顆粒状組成物において、電解質およ
びブドウ糖よりなる顆粒状組成物（イ）２９０６ｇをと
り、アルミニウム袋に封入した。また、酢酸ナトリウム
および酢酸よりなる顆粒状組成物（ロ）２１４ｇをと
り、アルミニウム袋に封入した。更に、炭酸水素ナトリ
ウム顆粒状組成物（ハ）７３５ｇをとり、ポリエチレン
袋に封入した。各袋を室温あるいは加温加湿条件（４０
℃、７５％ＲＨ）で一定期間保存した後、（イ）８.３
０ｇおよび（ロ）０.６１ｇをとり、精製水に溶かし１.
０ ｌとした液につき、各成分含量およびｐＨを測定
し、長期保存時における安定性について検討した。ただ
し、含量については、経時的な変化率を比較する意味
で、製造直後の値を１００とし、以後の各測定時点の値
を製造直後の値に対する比率に換算して比較尺度を統一
した。その結果を表５に示す。Test Example 4 From the granular composition obtained in Example 2, 2906 g of a granular composition (a) comprising an electrolyte and glucose was taken and sealed in an aluminum bag. In addition, 214 g of a granular composition (b) composed of sodium acetate and acetic acid was taken and sealed in an aluminum bag. Further, 735 g of the sodium hydrogencarbonate granular composition (c) was taken and sealed in a polyethylene bag. Place each bag at room temperature or under humidified conditions (40
(75 ° C., 75% RH) for a certain period, and then (a) 8.3.
Take 0 g and 0.61 g of (b) and dissolve in purified water to obtain 1.
The content and pH of each component were measured for the 0 L solution, and the stability during long-term storage was examined. However, as for the content, in order to compare the rate of change over time, the value immediately after production was set to 100, and the value at each subsequent measurement was converted into a ratio to the value immediately after production to standardize the comparison scale. Table 5 shows the results.
【表５】 [Table 5]
【００２８】また、（ハ）についても、同様に、一定期
間保存後の含量およびｐＨを測定し、含量については製
造直後の値を１００とし、それに対する比率で表し、ｐ
Ｈについては、５％水溶液とした時の値を示した。その
結果を表６に示す。Similarly, for (c), the content and pH after storage for a certain period of time were measured, and the content was expressed as a ratio to the value immediately after production, which was taken as 100.
As for H, the value when a 5% aqueous solution was used was shown. Table 6 shows the results.
【表６】 [Table 6]
【００２９】試験例５ 実施例１で得られた顆粒状組成物を試験例３と同様に包
装し、室温あるいは加温加湿条件（４０℃、７５％Ｒ
Ｈ）で一定期間保存した後、電解質およびブドウ糖より
なる顆粒状組成物（イ）２６.４２ｇおよび酢酸ナトリ
ウムおよび酢酸よりなる顆粒状組成物（ロ）２.１４ｇ
をとり、精製水に溶かし１００ｍｌとした液につき、透
過率を測定した。同様に実施例２で得られた顆粒状組成
物についても試験例４と同様に包装し、各条件下で、一
定期間保存した後、（イ）２９.０６ｇおよび（ロ）２.
１４ｇをとり、精製水に溶かし１００ｍｌとした液につ
き、透過率を測定した。また、比較例１で得られた顆粒
状組成物についても、電解質およびブドウ糖よりなる顆
粒状組成物を１包２８５６ｇのアルミニウム製包装と
し、各条件下で、一定期間保存した後、２８.５６ｇを
とり、精製水に溶かし１００ｍｌとした液につき、透過
率を測定した。Test Example 5 The granular composition obtained in Example 1 was packaged in the same manner as in Test Example 3, and was packaged at room temperature or under a humidified condition (40 ° C., 75% R).
After storing for a certain period of time under H), a granular composition comprising electrolyte and glucose (a) 26.42 g and a granular composition comprising sodium acetate and acetic acid (b) 2.14 g
Was dissolved in purified water to make 100 ml, and the transmittance was measured. Similarly, the granular composition obtained in Example 2 was packed in the same manner as in Test Example 4 and stored under a certain period of time under each condition, after which (A) 29.06 g and (B) 2.
14 g was taken and dissolved in purified water to make 100 ml, and the transmittance was measured. In addition, as for the granular composition obtained in Comparative Example 1, the granular composition comprising the electrolyte and glucose was packaged in aluminum of 2856 g per package, and after storing for a certain period of time under each condition, 28.56 g was obtained. The sample was dissolved in purified water to make 100 ml, and the transmittance was measured.
【００３０】同様に比較例２で得られた顆粒状組成物に
ついても、電解質およびブドウ糖よりなる顆粒状組成物
を１包３１２０ｇのアルミニウム製包装とし、各条件下
で、一定期間保存した後、３１.２０ｇをとり、精製水
に溶かし１００ｍｌとした液につき、透過率を測定し
た。以上の測定結果を表７に示す。ただし、経時的な変
化率を比較する意味で、製造直後の値を１００とし、以
後の各測定時点の値を製造直後の値に対する比率に換算
して比較尺度を統一した。透過率９７％以下では目視に
て着色が認められる。Similarly, with regard to the granular composition obtained in Comparative Example 2, the granular composition comprising the electrolyte and glucose was packed in an aluminum package of 3120 g per package, and after preserving under each condition for a certain period of time, 31% A .20 g sample was dissolved in purified water to make 100 ml, and the transmittance was measured. Table 7 shows the above measurement results. However, in order to compare the rate of change with time, the value immediately after production was set to 100, and the value at each subsequent measurement point was converted into a ratio to the value immediately after production to standardize the comparison scale. At a transmittance of 97% or less, coloring is visually observed.
【表７】 以上の結果から明らかなように、本発明により得られる
血液透析用顆粒剤は、試験例１および２において、変動
係数がいずれも１以下と極めて小さく、各成分の組成に
変化がないことが判った。加えてｐＨのばらつきも殆ど
無い。さらに、試験例３〜５に示されたように、長期保
存における安定性にも優れていた。[Table 7] As is clear from the above results, the granules for hemodialysis obtained according to the present invention have very small coefficients of variation of 1 or less in Test Examples 1 and 2, and show that there is no change in the composition of each component. Was. In addition, there is almost no variation in pH. Further, as shown in Test Examples 3 to 5, the stability in long-term storage was excellent.
【００３１】[0031]
【発明の効果】本発明による血液透析用製剤は、顆粒状
組成物であるから、従来の濃厚原液を用いた透析液に比
べて極めて軽量であるばかりでなく、粉体と違って付
着、凝集性が無視できるため、流動性、充填性に優れて
いる。また、粉体に比べて表面積が小さいため、吸湿な
どによる変化も受けにくい。更に、従来潮解性が高いた
め、均一な配合が困難であった塩化カルシウムと塩化マ
グネシウムを水溶液とした後、顆粒剤としているので、
各成分の組成にばらつきがない。更にまた、ｐＨ調整剤
としての酢酸を酢酸ナトリウムに吸着させたため、製造
工程中に酢酸が揮散せず、ｐＨのばらつきを非常に小さ
くすることができ、また、揮散による酢酸臭気の発生が
ないことから、作業環境が快適なものとなる。加えて、
従来方法に比べて酢酸を使用する製造工程率を１０分の
１以下と大幅に減らすことができるため、作業の自動化
が容易になり、製造コストが低減される。なおまた、本
顆粒剤は微粉末を造粒した顆粒剤であるから、溶解性に
も優れている。この顆粒剤を密封包装することにより長
期の貯蔵に耐え、運搬等の簡便な製剤とすることができ
る。Since the preparation for hemodialysis according to the present invention is a granular composition, it is not only lighter than conventional dialysate using a concentrated stock solution, but also adheres and aggregates unlike a powder. Since the properties are negligible, it has excellent fluidity and filling properties. Further, since the surface area is smaller than that of powder, it is hardly affected by a change due to moisture absorption. Furthermore, because calcium chloride and magnesium chloride, which had previously been difficult to uniformly mix because of their high deliquescent, were made into aqueous solutions, they were made into granules,
There is no variation in the composition of each component. Furthermore, since acetic acid as a pH adjuster is adsorbed to sodium acetate, acetic acid does not volatilize during the manufacturing process, the variation in pH can be extremely reduced, and no odor of acetic acid is generated due to volatilization. Therefore, the working environment becomes comfortable. in addition,
Compared with the conventional method, the production process rate using acetic acid can be greatly reduced to 1/10 or less, so that the work can be easily automated and the production cost can be reduced. In addition, since the present granules are granules obtained by granulating fine powder, they are excellent in solubility. By sealing and packaging this granule, it can withstand long-term storage and can be made into a simple preparation such as transport.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 清水 敏文 大阪府大東市平野屋新町４番１号 扶桑 薬品工業株式会社大東工場内 (56)参考文献 特開 平５−70357（ＪＰ，Ａ) 特開 平６−178802（ＪＰ，Ａ) 特開 平４−257522（ＪＰ，Ａ) 特開 平３−38527（ＪＰ，Ａ) 特開 平２−311419（ＪＰ，Ａ) 特開 平７−59864（ＪＰ，Ａ) (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 33/00 A61M 1/14──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Toshifumi Shimizu 4-1 Hiranoya Shinmachi, Daito-shi, Osaka Fuso Pharmaceutical Co., Ltd. Daito Plant (56) References JP-A-5-70357 (JP, A) JP JP-A-6-178802 (JP, A) JP-A-4-257522 (JP, A) JP-A-3-38527 (JP, A) JP-A-2-311419 (JP, A) JP-A-7-59864 (JP) , A) (58) Field surveyed (Int. Cl. 6 , DB name) A61K 33/00 A61M 1/14
Claims (7)
剤の形態である血液透析用製剤のためのｐＨ調整剤。1. A pH adjusting agent for a hemodialysis preparation in the form of a solid preparation containing acetic acid and sodium acetate.
の形態である、請求項１記載のｐＨ調整剤。2. The pH adjusting agent according to claim 1, which is in the form of granular sodium acetate to which acetic acid has been adsorbed.
と、血液透析用電解質、ブドウ糖および炭酸水素ナトリ
ウムを含む血液透析用製剤。3. A preparation for hemodialysis comprising one agent containing the pH adjuster according to claim 1, an electrolyte for hemodialysis, glucose and sodium hydrogencarbonate.
糖、（ロ）請求項１に記載のｐＨ調整剤、（ハ）炭酸水
素ナトリウムを別々の顆粒状組成物とする、請求項３記
載の血液透析用製剤。4. The blood according to claim 3, wherein (a) an electrolyte for hemodialysis and glucose, (b) the pH adjuster according to claim 1, and (c) sodium hydrogencarbonate as separate granular compositions. Preparation for dialysis.
とも１種を水溶液とし、残りの成分を微粉状で使用して
顆粒状組成物に調製する、請求項４記載の血液透析用製
剤。5. The method for hemodialysis according to claim 4, wherein (a) is prepared into a granular composition by using at least one of the electrolyte components in (a) as an aqueous solution and using the remaining components in the form of fine powder. Formulation.
は塩化マグネシウムである、請求項５記載の血液透析用
製剤。6. The hemodialysis preparation according to claim 5, wherein the component to be converted into an aqueous solution is calcium chloride or magnesium chloride.
に水を加えて、顆粒状に調製するものである、請求項４
〜６のいずれか１項に記載の血液透析用製剤。7. The method according to claim 4, wherein (c) is prepared by adding water to finely powdered sodium hydrogen carbonate to obtain a granular form.
The preparation for hemodialysis according to any one of claims 6 to 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5166769A JP2809971B2 (en) | 1993-07-06 | 1993-07-06 | Hemodialysis preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5166769A JP2809971B2 (en) | 1993-07-06 | 1993-07-06 | Hemodialysis preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0724061A JPH0724061A (en) | 1995-01-27 |
| JP2809971B2 true JP2809971B2 (en) | 1998-10-15 |
Family
ID=15837359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5166769A Expired - Lifetime JP2809971B2 (en) | 1993-07-06 | 1993-07-06 | Hemodialysis preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2809971B2 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3415291B2 (en) * | 1994-09-27 | 2003-06-09 | 味の素ファルマ株式会社 | Bicarbonate dialysis agent |
| JP3714050B2 (en) | 1999-09-07 | 2005-11-09 | ニプロ株式会社 | Solid baking soda dialysis agent and method for producing the same |
| JP5376480B1 (en) * | 2012-10-10 | 2013-12-25 | 富田製薬株式会社 | A dialysis agent containing acetic acid and acetate, and two-agent dialysis agent using the same |
| JP5517322B1 (en) | 2013-10-02 | 2014-06-11 | 富田製薬株式会社 | Three-part dialysis agent containing acetic acid and acetate |
| JP5517321B1 (en) | 2013-10-02 | 2014-06-11 | 富田製薬株式会社 | Solid dialysis agent A containing alkali metal diacetate, and two-agent type low-acetate dialysis agent using the same |
| JP2016153391A (en) * | 2015-02-16 | 2016-08-25 | 日本合成化学工業株式会社 | Anhydrous sodium acetate crystal |
| JP6312957B1 (en) * | 2016-10-28 | 2018-04-18 | 富田製薬株式会社 | Agent A for hemodialysis |
| CN109890370B (en) * | 2016-10-28 | 2021-06-29 | 富田制药株式会社 | Agent A for hemodialysis |
| JP7532763B2 (en) * | 2019-11-18 | 2024-08-14 | ニプロ株式会社 | Dialysis fluid solid preparations |
-
1993
- 1993-07-06 JP JP5166769A patent/JP2809971B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0724061A (en) | 1995-01-27 |
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