JPH0623756B2 - Urobilinogen composition - Google Patents
Urobilinogen compositionInfo
- Publication number
- JPH0623756B2 JPH0623756B2 JP1994986A JP1994986A JPH0623756B2 JP H0623756 B2 JPH0623756 B2 JP H0623756B2 JP 1994986 A JP1994986 A JP 1994986A JP 1994986 A JP1994986 A JP 1994986A JP H0623756 B2 JPH0623756 B2 JP H0623756B2
- Authority
- JP
- Japan
- Prior art keywords
- urobilinogen
- catalyst
- raney
- composition
- present
- 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
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- Investigating Or Analysing Biological Materials (AREA)
- Pyrrole Compounds (AREA)
Description
【発明の詳細な説明】 ＜産業上の利用分野＞ 本発明はウロビリノーゲン組成物に関し、詳しくは、ラ
ニー触媒とりわけラニーニッケル触媒、ラニー銅触媒、
ラニー鉄触媒を用いてビリルビンを還元し、これを凍結
乾燥してなる安定なウロビリノーゲン組成物に関する。DETAILED DESCRIPTION OF THE INVENTION <Field of Industrial Application> The present invention relates to a urobilinogen composition, and more particularly to a Raney catalyst, especially a Raney nickel catalyst, a Raney copper catalyst,
The present invention relates to a stable urobilinogen composition obtained by reducing bilirubin using a Raney iron catalyst and freeze-drying this.
＜従来の技術＞ ウロビリノーゲンは、生体内においては腸内細菌によっ
てビリルビンが還元されて生成される。通常、健常者で
も尿中に微量のウロビリノーゲンが排泄され、臨床検査
では肝疾患や溶血性疾患あるいは胆管閉塞などの検査方
法として尿ウロビリノーゲンの検査が古くから知られて
いる。このようなウロビリノーゲンを人工的に生成する
方法として、従来、ナトリウムアマルガムやバナジウ
ム、或いは白金を触媒に用いてビリルビンを還元する方
法が知られている。<Prior Art> Urobilinogen is produced in vivo by reduction of bilirubin by enterobacteria. Normally, even a healthy person excretes a small amount of urobilinogen in the urine, and the urinary urobilinogen test has long been known as a test method for liver disease, hemolytic disease, bile duct obstruction and the like in clinical tests. As a method of artificially producing such urobilinogen, a method of reducing bilirubin using sodium amalgam, vanadium, or platinum as a catalyst has been conventionally known.
＜発明が解決しようとする問題点＞ しかし、これら従来の方法でウロビリノーゲンを生成す
る場合、次のような問題があった。すなわち、ナトリウ
ムアマルガムを触媒に用いる方法では廃棄物の水銀によ
る環境汚染の問題があった。またバナジウムや白金を触
媒に用いる方法では高価で特殊な設備を必要とした。特
に、これら従来の方法によって生成されたウロビリノー
ゲンは非常に不安定で酸化されやすく、尿ウロビリノー
ゲン測定用のコントロール等の臨床検査用として用いる
ことができなかった。<Problems to be Solved by the Invention> However, when urobilinogen is produced by these conventional methods, there are the following problems. That is, the method using sodium amalgam as a catalyst has a problem of environmental pollution due to waste mercury. Further, the method of using vanadium or platinum as a catalyst requires expensive and special equipment. In particular, urobilinogen produced by these conventional methods is very unstable and easily oxidized, and cannot be used for clinical tests such as control for measuring urinary urobilinogen.
そこで本発明は上記従来技術の欠点を解消し、環境汚染
の問題なく安全に且つ安価に製造できると共に特に臨床
検査の分野等においても十分好適に使用できる安定なウ
ロビリノーゲン組成物の提供を目的とする。Then, the present invention solves the above-mentioned drawbacks of the prior art, and aims to provide a stable urobilinogen composition which can be produced safely and inexpensively without the problem of environmental pollution and can be suitably used particularly in the field of clinical examination. .
＜問題点を解決するための手段＞ 本発明者らは上記目的に鑑み、従来からの問題を解決す
べく鋭意研究した結果、ラニー触媒を用いてビリルビン
を還元し、これを凍結乾燥することにより、廃棄物によ
る環境汚染の心配がなく安全に且つ高価な設備も不要で
安価に製造でき、特に性状が非常に安定であるウロビリ
ノーゲン組成物を得ることができることを見出し、本発
明に到達した。<Means for Solving Problems> In view of the above-mentioned objects, the present inventors have earnestly studied to solve the conventional problems, and as a result, reduced bilirubin using a Raney catalyst and freeze-dried the bilirubin. The present inventors have found that it is possible to obtain a urobilinogen composition which is safe and inexpensive, does not require expensive equipment, and is particularly stable in properties without worrying about environmental pollution due to waste, and has reached the present invention.
すなわち、本発明は、ラニー（Ｒａｎｅｙ）触媒とりわ
けラニーニッケル触媒、ラニー銅触媒、ラニー鉄触媒を
用いてビリルビンを還元し、これを凍結乾燥してなるウ
ロビリノーゲン組成物をその構成とする。That is, the present invention comprises a urobilinogen composition obtained by reducing bilirubin using a Raney catalyst, especially a Raney nickel catalyst, a Raney copper catalyst, and a Raney iron catalyst, and freeze-drying the bilirubin.
本発明に用いられるラニー触媒は、ラニー（Ｒａｎｅ
ｙ）によって発明され、一般にラニー触媒として文献に
掲載されている触媒で、合金をカセイアルカリ等で処理
して得られる金属触媒である。また本発明におけるラニ
ー触媒においては、合金される金属の種類はとくに限定
されるものではないが、ニッケルとアルミニウムの合金
から作られるラニーニッケル触媒、銅とアルミニウムの
合金から作られるラニー銅触媒、鉄とアルミニウムの合
金から作られるラニー鉄触媒等が還元効率上好ましい。
そしてこれらラニーニッケル触媒、ラニー銅触媒、ラニ
ー鉄触媒において、ニッケル、銅、鉄のそれぞれの含有
率はとくに限定されないが、３０％〜６０％程度の含有
率が好ましい。それ以上では触媒能が弱くなり、それ以
下では粉砕されにくいからである。The Raney catalyst used in the present invention is a Raney catalyst.
The catalyst invented by y) and generally described in the literature as a Raney catalyst, is a metal catalyst obtained by treating an alloy with caustic alkali or the like. Further, in the Raney catalyst in the present invention, the kind of metal to be alloyed is not particularly limited, but Raney nickel catalyst made from an alloy of nickel and aluminum, Raney copper catalyst made from an alloy of copper and aluminum, iron A Raney iron catalyst made of an alloy of aluminum and aluminum is preferable in terms of reduction efficiency.
In the Raney nickel catalyst, Raney copper catalyst, and Raney iron catalyst, the contents of nickel, copper, and iron are not particularly limited, but the contents are preferably about 30% to 60%. This is because if it is more than that, the catalytic ability becomes weak, and if it is less than that, it is difficult to be pulverized.
本発明において、凍結乾燥とは、水溶液を凍結させ、凍
結状態のまま真空下水分を直接昇華させて乾燥すること
をいう。凍結温度、真空度、乾燥温度はとくに限定され
ないが、たとえば凍結時の品温を−10℃〜−40℃、真空
度を0.2〜0.1Torr（トール）、乾燥温度を40℃〜25℃と
して凍結乾燥することができる。In the present invention, freeze-drying refers to freezing an aqueous solution and directly sublimating water under vacuum in a frozen state to dry. Freezing temperature, degree of vacuum, and drying temperature are not particularly limited. For example, freeze at -10 ° C to -40 ° C, freezing temperature of 0.2 to 0.1 Torr, and drying temperature of 40 ° C to 25 ° C. Can be dried.
本発明におけるウロビリノーゲン組成物とは、ビリルビ
ンを還元することによって得られる数種類の異性体、例
えばｄ−ウロビリノーゲン、ｉ−ウロビリノーゲン、１
−ウロビリノーゲン等を含む混合物としてのウロビリノ
ーゲンの意味である。The urobilinogen composition in the present invention means several isomers obtained by reducing bilirubin, for example, d-urobilinogen, i-urobilinogen,
-Means urobilinogen as a mixture containing urobilinogen and the like.
本発明のウロビリノーゲン組成物は凍結乾燥によって得
られるものであり、その物理的集合状態は固体粉末状で
ある。この点従来方法よって得られているウロビリノー
ゲンはいずれも液体状態のものであり、その物理的集合
状態が両者において全く異なる。The urobilinogen composition of the present invention is obtained by freeze-drying, and its physical assembly state is solid powder. In this respect, all of the urobilinogens obtained by the conventional method are in the liquid state, and the physical aggregation state is completely different between the two.
本発明のウロビリノーゲン組成物は、例えば、ビリルビ
ンをアルカリ性溶液等で溶解し、これを冷却しながらラ
ニー触媒を加えて反応させ、その濾過液を凍結乾燥する
ことにより製造できる。ここで、冷却しながらというの
は、ラニー触媒を加えて反応させることによって得られ
るウロビリノーゲン組成物が直ちに別のものになってし
まうことのないような温度で反応させるという意味であ
る。勿論ラニー触媒についての条件や凍結乾燥について
の条件は特に限定されるものではない。また反応に関与
しないものであれば、賦形剤を凍結乾燥前に添加しても
よい。賦形剤を含むウロビリノーゲン組成物は凍結乾燥
後の仕上がりが良好である。賦形剤としては、糖類、多
糖類及びそれらの分解物、蛋白質、合成高分子化合物等
から適当に選択して用いることができる。本発明はこの
ような賦形剤を含むウロビリノーゲン組成物もその範囲
に包含する。The urobilinogen composition of the present invention can be produced, for example, by dissolving bilirubin in an alkaline solution or the like, adding a Raney catalyst while reacting with cooling, and lyophilizing the filtrate. Here, “while cooling” means that the reaction is carried out at a temperature at which the urobilinogen composition obtained by adding the Raney catalyst and reacting with each other does not immediately become another. Of course, the conditions for the Raney catalyst and the conditions for freeze-drying are not particularly limited. Further, an excipient may be added before lyophilization as long as it does not participate in the reaction. The urobilinogen composition containing the excipient has a good finish after freeze-drying. The excipient can be appropriately selected and used from sugars, polysaccharides and their decomposition products, proteins, synthetic polymer compounds and the like. The present invention also includes within its scope urobilinogen compositions containing such excipients.
なお、製造時においては、空気との接触及び温度の上昇
をさけ、また遮光の状態で行うのが品質上好ましいが、
実際には短時間で製造が完了するので必ずしもそのよう
な条件を完全に確保しておく必要はない。At the time of manufacturing, it is preferable in terms of quality to avoid contact with air and temperature rise, and to carry out light shielding,
In reality, since the production is completed in a short time, it is not always necessary to completely secure such conditions.
本発明の組成物がウロビリノーゲンを含有していること
は臨床検査で用いられる尿ウロビリノーゲン検出試薬で
あるエールリッヒ試薬で確認できる。The fact that the composition of the present invention contains urobilinogen can be confirmed by the Ehrlich reagent which is a urine urobilinogen detection reagent used in clinical tests.
従来、ウロビリノーゲンは液状で得られるためか、非常
に不安定で、冷蔵庫で保存しても１日たつと10％以上が
別物質に変化してしまうことから、臨床検査用等として
の実用性がなかった。本発明のウロビリノーゲン組成物
は、凍結乾燥により固体粉末として生成され、その性状
が長期間安定であることが後述の実施例から確認されて
いる。Probably because urobilinogen is conventionally obtained in liquid form, it is very unstable, and even if it is stored in the refrigerator, 10% or more of it will change to another substance after 1 day, making it practical for clinical tests. There wasn't. The urobilinogen composition of the present invention is produced as a solid powder by freeze-drying, and its properties have been confirmed to be stable for a long period of time from the examples described below.
＜発明の効果＞ 以上の構成よりなる本発明のウロビリノーゲン組成物
は、非常に安定である。さらに水銀等を使用しないので
従来の方法により得られるウロビリノーゲンに比べて公
害等の問題がなく安全に製造できる。またバナジウムや
白金を用いる場合のように高価な設備を必要とせず、安
価に製造することができる。よって、本発明のウロビリ
ノーゲン組成物は尿ウロビリノーゲン測定用のコントロ
ールとして或いはその他の臨床検査用に実用することが
でき、その際、保存が非常に容易で、データを正確に得
ることができ、またそれら検査を安価に行うことが可能
となる。<Effects of the Invention> The urobilinogen composition of the present invention having the above constitution is very stable. Further, since mercury or the like is not used, it can be produced safely without problems such as pollution as compared with urobilinogen obtained by the conventional method. Further, unlike the case of using vanadium or platinum, it does not require expensive equipment and can be manufactured at low cost. Therefore, the urobilinogen composition of the present invention can be practically used as a control for urinary urobilinogen measurement or for other clinical tests, in which case it is very easy to store, and data can be accurately obtained. The inspection can be performed at low cost.
＜実施例＞ 以下に本発明の実施例を示すが、本発明はこれら実施例
に限定されるのではない。<Examples> Examples of the present invention are shown below, but the present invention is not limited to these examples.
実施例１ ビリルビン100mgを0.4規定の水酸化ナトリウム溶液100m
l溶解し、10℃以下に冷却しながらニッケル含量50％の
ラニーニッケル触媒６ｇを加えて１時間撹拌する。これ
を濾過して得た瀘液を褐色のバイアル瓶に小分けして凍
結乾燥した。凍結乾燥の条件は、真空度を0.15Torr、品
温を凍結時−20℃、凍乾時25℃に設定した。得られたウ
ロビリノーゲン組成物を精製水で溶解して10倍に希釈
し、これをヘンリーらの改良法で定量したところ、ウロ
ビリノーゲン濃度として9.5エールリッヒ単位／dlであ
った。すなわち、ビリルビンから95％の生成率でウロビ
リノーゲン組成物を得ることができた。また上記10倍に
希釈した液を更に100倍まで段階に希釈し、同様に定量
して検量線を作成したところ直線性が得られた。Example 1 100 mg of bilirubin was added to 100 m of 0.4N sodium hydroxide solution.
1 g of a Raney nickel catalyst having a nickel content of 50% is added while being dissolved and cooled to 10 ° C. or lower, and stirred for 1 hour. The filtrate obtained by filtering this was divided into brown vials and freeze-dried. Freeze-drying conditions were set such that the degree of vacuum was 0.15 Torr, the product temperature was -20 ° C when frozen, and 25 ° C when freeze-dried. The obtained urobilinogen composition was dissolved in purified water, diluted 10-fold and quantified by the modified method of Henry et al. As a result, the urobilinogen concentration was 9.5 Ehrlich unit / dl. That is, the urobilinogen composition could be obtained from bilirubin at a production rate of 95%. The 10-fold diluted solution was further diluted up to 100-fold in stages, and similarly quantified to prepare a calibration curve, whereby linearity was obtained.
実施例２ ニッケル含量40％のラニーニッケル触媒を用いて、実施
例１と同様の条件でウロビリノーゲン組成物を得た。そ
の結果、同様に95％の生成率でウロビリノーゲン組成物
を得ることができた。Example 2 A urobilinogen composition was obtained under the same conditions as in Example 1 using a Raney nickel catalyst having a nickel content of 40%. As a result, it was possible to obtain the urobilinogen composition with a production rate of 95%.
実施例３ 銅含量50％のラニー銅触媒を用いて実施例１と同様の方
法でウロビリノーゲン組成物を得た。生成率は95％であ
った。Example 3 A urobilinogen composition was obtained in the same manner as in Example 1 using a Raney copper catalyst having a copper content of 50%. The production rate was 95%.
実施例４ 鉄含量50％のラニー鉄触媒を用いて、実施例１と同様に
してウロビリノーゲン組成物を得た。生成率は40％であ
った。Example 4 A urobilinogen composition was obtained in the same manner as in Example 1 using a Raney iron catalyst having an iron content of 50%. The production rate was 40%.
実施例５ 実施例１で得た得たウロビリノーゲン組成物を引き続
き、バイアル瓶に入れたまま（遮光状態）、真空下（実
施例１における真空度のまま）、37℃に保持し、これを
ヘンリーらの改良法で定量して、その含有量の減少割合
を計った。その結果ウロビリノーゲン組成物の含有量低
下は２週間経過しても測定上認められなかった。Example 5 The urobilinogen composition obtained in Example 1 was continuously kept in a vial (light-shielded state) under vacuum (vacuum degree in Example 1) at 37 ° C., which was used as Henry. They were quantified by the improved method, and the reduction rate of the content was measured. As a result, the decrease in the content of the urobilinogen composition was not observed in the measurement even after 2 weeks.
実施例２、３、４で得たウロビリノーゲン組成物の場合
も同様であった。The same was true for the urobilinogen compositions obtained in Examples 2, 3, and 4.
次に従来得られる液状のウロビリノーゲンを用いて、同
様の条件でその含有量の減少割合を測定した。その結
果、従来のウロビリノーゲンは１時間の保持で含有量が
90％以上減少、すなわち90％以上が別物質に変化してし
まった。Next, using liquid urobilinogen obtained conventionally, the reduction rate of the content was measured under the same conditions. As a result, conventional urobilinogen has a content of 1 hour after being stored.
90% or more decrease, that is, 90% or more has changed to another substance.
Claims (4)
これを凍結乾燥してなるウロビリノーゲン組成物1. Reduction of bilirubin using a Raney catalyst,
Urobilinogen composition obtained by freeze-drying this
許請求の範囲第１項記載のウロビリノーゲン組成物2. The urobilinogen composition according to claim 1, wherein the Raney catalyst is a Raney nickel catalyst.
の範囲第１項記載のウロビリノーゲン組成物3. The urobilinogen composition according to claim 1, wherein the Raney catalyst is a Raney copper catalyst.
の範囲第１項記載のウロビリノーゲン組成物4. The urobilinogen composition according to claim 1, wherein the Raney catalyst is a Raney iron catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1994986A JPH0623756B2 (en) | 1986-01-30 | 1986-01-30 | Urobilinogen composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1994986A JPH0623756B2 (en) | 1986-01-30 | 1986-01-30 | Urobilinogen composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62175666A JPS62175666A (en) | 1987-08-01 |
| JPH0623756B2 true JPH0623756B2 (en) | 1994-03-30 |
Family
ID=12013455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1994986A Expired - Lifetime JPH0623756B2 (en) | 1986-01-30 | 1986-01-30 | Urobilinogen composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0623756B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5866424A (en) * | 1995-07-10 | 1999-02-02 | Bayer Corporation | Stable liquid urobilinogen control composition |
| JP5880849B2 (en) * | 2012-05-15 | 2016-03-09 | 住友電装株式会社 | Crimp terminal |
-
1986
- 1986-01-30 JP JP1994986A patent/JPH0623756B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62175666A (en) | 1987-08-01 |
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