WO2000045162A1 - Blood coagulation preventing agents and blood collection containers containing the same - Google Patents

Blood coagulation preventing agents and blood collection containers containing the same Download PDF

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Publication number
WO2000045162A1
WO2000045162A1 PCT/JP1999/007159 JP9907159W WO0045162A1 WO 2000045162 A1 WO2000045162 A1 WO 2000045162A1 JP 9907159 W JP9907159 W JP 9907159W WO 0045162 A1 WO0045162 A1 WO 0045162A1
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Prior art keywords
blood
magnesium
blood collection
coagulation
test
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PCT/JP1999/007159
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French (fr)
Japanese (ja)
Inventor
Noriyuki Tatsumi
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Nagase & Co., Ltd.
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Priority to AU16904/00A priority Critical patent/AU1690400A/en
Publication of WO2000045162A1 publication Critical patent/WO2000045162A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5082—Test tubes per se

Definitions

  • the present invention relates to a novel anticoagulant and a blood collection container containing the same. More specifically, the present invention relates to a blood coagulation inhibitor which effectively prevents blood coagulation, and is particularly preferably used to prevent blood coagulation collected for a blood test used for various diagnoses, and The present invention relates to a blood collection container in which is stored. Background art
  • test physiological test
  • Biological components such as blood, urine, and tissues.
  • This blood test includes (1) chemical tests to check electrolytes and pH, (2) measurement of chemical components in blood, measurement of infectious diseases, blood types, cancer-related antigens, etc. Furthermore, they can be broadly divided into biochemical tests for examining bacteria, viruses and pathological cells, and (3) blood tests for examining the morphology and number of blood cells and coagulation function.
  • the blood of the subject is collected in a blood test container, and in this case, measures are taken so that the collected blood does not coagulate before being subjected to the test. It is important.
  • Blood is fluid while circulating in blood vessels, but once removed outside the blood vessels, it loses fluidity, for example, once it is transferred into a test tube. This is because fibrinogen in plasma is converted into fibrin fibrin, forming a fibrin web, This is because the whole liquid becomes a gel and solidifies.
  • Such coagulation is initiated when blood coagulation factor XII in plasma comes into contact with a surface (eg, glass) of a negatively charged solid phase or the like. That is,
  • Factor XII would when adsorbed on the surface activated factor XII (XII a), which is interposed calcium ions, acts on each coagulation factor, ultimately to produce a thrombin, the thrombin Fuiburino one Gen Limited digestion to fipurin, and fibrin is converted to blood coagulation factor XIII (XI
  • Various types of blood have been developed and used to prevent such coagulation of collected blood.
  • metal salts of ethylenediaminetetraacetic acid, sodium citrate, sodium heparin, synthetic hirudin, and a sulfonated gen-based polymer having a weight-average molecular weight of 300 or more or a salt thereof JP-A-8-43337) No. 7 is known as a blood coagulation inhibitor for blood collection.
  • the present invention can be applied to blood tests of all chemical, biochemical and blood items, is versatile, has an excellent effect of preventing blood coagulation, and
  • An object of the present invention is to provide a blood coagulation inhibitor which is stable in effect and is inexpensive, and a blood collection container containing the same. Disclosure of the invention
  • the present inventor has conducted intensive studies to develop a blood coagulation inhibitor having the above preferred properties and a blood collection container containing the same, and as a result, the inorganic acid salt of magnesium has an unexpectedly excellent blood coagulation prevention effect,
  • the present inventors have found that the agent can be used as a universal anticoagulant, and based on this finding, have completed the present invention.
  • the present invention (1) an anticoagulant comprising an inorganic salt of magnesium as an active ingredient,
  • a blood collection container containing a magnesium salt of inorganic acid in the container containing a magnesium salt of inorganic acid in the container
  • the anticoagulant of the present invention contains magnesium as an active ingredient and is particularly effective in preventing coagulation of blood collected for a blood test.
  • Magnesium sulfate and its hydrous salts are particularly preferred in terms of performance and cost.
  • thrombin has a function of converting fibrinogen into fibrin by limited degradation and fibrin network formation by fibrin crosslinking. It is presumed that calcium ions in the blood involved are replaced by magnesium ions.
  • the blood coagulation inhibitor of the present invention together with the inorganic acid salt of magnesium, as far as the object of the invention is not impaired, conventionally known substances having an anticoagulant action, for example, metal salts of ethylenediamine tetrafate, sodium citrate, sodium heparin, synthetic hirudin, sulfonated gen-based polymers, if desired Alternatively, a salt thereof, or another thrombin inhibitor or the like can be appropriately used.
  • thrombin inhibitors include, for example, gabexate methylate, nafamostat mesylate, (2R, 4R) —4-methyl-1- 1— [N 2 — (3-methyl-1,2,3, 4-tetrahydro-18-quinolinesulfonyl) -1-L-arginyl] -12-piperidinecarboxylic acid monohydrate.
  • the amount of the blood coagulation inhibitor of the present invention added to blood is appropriately selected depending on the type of the inorganic acid salt of magnesium and the desired anticoagulation time, but is usually 1 to 50 ragZml, preferably 2 to 4 Omg. / ml range. If the added amount is less than 1 mgZml, the effect of preventing blood coagulation may not be sufficiently exerted, and if it exceeds 5 OmgZinl, the effect is not improved for the amount, but rather adversely affects the blood test. May be given.
  • the form of the anticoagulant of the present invention is not particularly limited, and may be in the form of a powder, an aqueous solution or an aqueous suspension contained in an aqueous medium.
  • an aqueous medium that does not disturb the blood test preferably, physiological saline can be used.
  • the blood collection container of the present invention contains the inorganic salt of magnesium in a container, and the inorganic salt of magnesium is used as a powder, an aqueous solution or an aqueous suspension.
  • the inorganic acid salt of magnesium may be used alone or in combination of two or more.
  • magnesium sulfate and its hydrated salt are particularly preferable. Further, as long as the object of the present invention is not impaired, a conventionally known substance having an anticoagulant effect as described above may be appropriately used in combination.
  • the blood collection container of the present invention means a container such as a blood collection tube, a blood collection bottle, a blood collection bag, or the like for collecting or storing blood for a blood test, for whole blood, for separating serum, for analyzing sugar, and the like.
  • a vacuum blood collection tube is most suitable as the container. is there.
  • This vacuum blood collection tube is usually put into practical use as a vacuum blood collection system combined with accessory devices such as a holder and a blood collection needle.
  • a resin such as a thermoplastic resin, a thermosetting resin or a modified natural resin, or glass can be used.
  • thermoplastic resin examples include polyethylene, polypropylene, poly-4-methylpentene-11, polystyrene, polymethyl methacrylate, polyvinyl chloride, polyethylene terephthalate, polybutylene terephthalate, styrene-acrylonitrile copolymer, and styrene.
  • thermosetting resins such as unsaturated polyester resins, epoxy resins, and epoxy resins. Kishi acrylate resins, and examples of the modified natural resins, cellulose acetate, propyl propionic acid, cellulose acetate butyrate, E chill cellulose, Echirukichin like are used.
  • a silicate glass such as a soda-lime glass, a phosphoric acid glass, a borate glass, or a quartz glass is preferably used.
  • the capacity of the blood collection container is appropriately selected depending on the purpose of use of the container, but is usually in the range of 2 to 2 nil.
  • the amount of inorganic salt of magnesium housed in the blood collection container, per blood l ml for preparative adopted usually 3 to 5 O mg, preferably 3. 1 5 ⁇ 3 1. 5 mg c
  • the blood collection container of the present invention may be of a vacuum type in which a cap made of, for example, butyl rubber is provided and the inside is evacuated, or may be of a non-vacuum type. Types are preferred. Further, before or after storing the inorganic acid salt of magnesium, the magnesium salt can be sterilized if necessary.
  • Magnesium nitrate as well as comparative experiment [Mg (N0 3) 2 ' 6H 2 0, Wako Pure Chemical Industries, Ltd.], zinc sulfate [ZnS0 4 * 7H 2 0, USA Sigma] was measured time of blood coagulation by .
  • the anticoagulant of the present invention can be applied to blood tests of all chemical, biochemical and blood items, is versatile, has an excellent effect of preventing blood coagulation, and its effect is stable. Moreover, it is inexpensive and has high practical value.

Abstract

Blood coagulation preventing agents containing as the active ingredient an inorganic acid salt of magnesium; and blood collection containers containing an inorganic acid salt of magnesium. Because of being capable of effectively preventing blood coagulation, these agents and containers are appropriately usable, in particular, in preventing blood specimens collected for various diagnostic examinations from coagulation.

Description

明細書 血液凝固阻止剤及びそれを収納した採血容器 技術分野  TECHNICAL FIELD A blood coagulation inhibitor and a blood collection container containing the same
本発明は、 新規な血液凝固阻止剤及びそれを収納した採血容器に関する。 さら に詳しくは、 本発明は、 血液の凝固を効果的に防止し、 特に各種診断に使用され る血液検査用に採取した血液の凝固防止に好適に用いられる血液凝固阻止剤、 及 びこのものを収納させてなる採血容器に関するものである。 背景技術  The present invention relates to a novel anticoagulant and a blood collection container containing the same. More specifically, the present invention relates to a blood coagulation inhibitor which effectively prevents blood coagulation, and is particularly preferably used to prevent blood coagulation collected for a blood test used for various diagnoses, and The present invention relates to a blood collection container in which is stored. Background art
近年、 病態の診断、 治療効果の判定を行う上で、 臨床検査は不可欠な要素と なっている。 この臨床検査は、 生体機能の検査が目的で、 （1 ) 生体内を対象と し、 直接的な生体情報を調べる検査 （生理検査） と、 （2 ) 血液、 尿、 組織など の生体構成成分の一部を採取して、 生体内変化を調べる検査 （検体検査） に大別 することができる。 そして、 後者の検体検査においては、 特に血液検査の果たす 役割は大きい。  In recent years, clinical tests have become an indispensable element in diagnosing disease states and determining the effects of treatment. The purpose of this clinical test is to test biological functions. (1) A test (physiological test) that examines direct biological information in the living body, and (2) Biological components such as blood, urine, and tissues. Can be broadly divided into tests for examining biotransformations (specimen tests). In the latter sample test, the blood test plays a particularly important role.
この血液検査は、 （1 ) 電解質、 pHなどを調べる化学項目検査、 （2 ) 血液中 の化学成分の測定や、 免疫反応を用いた感染症、 血液型、 がん関連抗原などの測 定、 さらには細菌、 ウィルス、 病理細胞の検査などを行う生化学項目検査及び ( 3 ) 血液細胞の形態と数及び凝固機能などを調べる血液項目検査に大別するこ とができる。  This blood test includes (1) chemical tests to check electrolytes and pH, (2) measurement of chemical components in blood, measurement of infectious diseases, blood types, cancer-related antigens, etc. Furthermore, they can be broadly divided into biochemical tests for examining bacteria, viruses and pathological cells, and (3) blood tests for examining the morphology and number of blood cells and coagulation function.
このような血液検査を行うためには、 まず被検者の血液を血液検査用容器に採 取するが、 この場合、 採取された血液が、検査に供する前に凝固しないような処 置を講じることが肝要である。  In order to perform such a blood test, first, the blood of the subject is collected in a blood test container, and in this case, measures are taken so that the collected blood does not coagulate before being subjected to the test. It is important.
血液は、 血管内を循環している間は流動性であるが、 いったん血管外に取出さ れると、 例えば試験管の中に移されるとやがて流動性を失う。 これは、 血漿中の フイブリノ一ゲーンが繊維状のフイブリンに転換し、 フイブリン網を形成し、 血 液全体がゲル状になり、 凝固するためである。 Blood is fluid while circulating in blood vessels, but once removed outside the blood vessels, it loses fluidity, for example, once it is transferred into a test tube. This is because fibrinogen in plasma is converted into fibrin fibrin, forming a fibrin web, This is because the whole liquid becomes a gel and solidifies.
このような血液凝固は、血漿中の血液凝固因子 XII因子が陰性荷電を有する固 相などの表面 （例えばガラスなど） に接触することによって始まる。 すなわち、 Such coagulation is initiated when blood coagulation factor XII in plasma comes into contact with a surface (eg, glass) of a negatively charged solid phase or the like. That is,
XII因子は表面に吸着されると活性化 XII因子 （XII a) になり、 これがカルシウム イオンを介在して、 各凝固因子に作用し、 最終的にトロンビンを生成させ、 この トロンビンがフイブリノ一ゲンを限定分解してフィプリンにし、 さらにフィプリ ンは、 トロンビンとカルシウムイオンにより活性化された血液凝固因子 XIII (XIFactor XII would when adsorbed on the surface activated factor XII (XII a), which is interposed calcium ions, acts on each coagulation factor, ultimately to produce a thrombin, the thrombin Fuiburino one Gen Limited digestion to fipurin, and fibrin is converted to blood coagulation factor XIII (XI
Il a) によって架橋され、 フイブリン網を形成して、 血液が凝固する。 It is crosslinked by Il a) to form a fibrin web and the blood clots.
採取した血液のこのような凝固を防止するために、 これまで様々なものが開発 され、 用いられてきた。 例えばエチレンジァミン四酢酸金属塩、 クェン酸ナトリ ゥム、 へパリンナトリウム、 合成ヒルジン、 さらには重量平均分子量 3 0 0 0以 上のスルホン化ジェン系重合体又はその塩 （特開平 8— 4 3 3 7 7号公報） など が、 採血用の血液凝固阻止剤として知られている。  Various types of blood have been developed and used to prevent such coagulation of collected blood. For example, metal salts of ethylenediaminetetraacetic acid, sodium citrate, sodium heparin, synthetic hirudin, and a sulfonated gen-based polymer having a weight-average molecular weight of 300 or more or a salt thereof (JP-A-8-43337) No. 7) is known as a blood coagulation inhibitor for blood collection.
しかしながら、 これらの血液凝固阻止剤は、 前記 3項目 （化学項目、 生化学項 目、 血液項目） の中の一部の項目の検査には適用できるものの、 他の項目の検査 には適用できなかったり、 高価であったり、 あるいは性能が安定でなく、 また、 不充分であるなどの問題を有し、 必ずしも充分に満足しうるものではなかつた。 本発明は、 このような事情のもとで、 化学項目、 生化学項目及び血液項目のす ベての項目の血液検査に適用でき、 万能である上、 血液凝固の防止効果に優れ、 かつその効果が安定であり、 しかも安価な血液凝固阻止剤、 及びそれを収納した 採血容器を提供することを目的としてなされたものである。 発明の開示  However, these anticoagulants can be applied to testing of some of the above three items (chemical items, biochemical items, and blood items), but cannot be applied to tests of other items. However, it was not always satisfactory because of problems such as high price, high price, unstable performance and insufficient performance. Under such circumstances, the present invention can be applied to blood tests of all chemical, biochemical and blood items, is versatile, has an excellent effect of preventing blood coagulation, and An object of the present invention is to provide a blood coagulation inhibitor which is stable in effect and is inexpensive, and a blood collection container containing the same. Disclosure of the invention
本発明者は、 前記の好ましい性質を有する血液凝固阻止剤及びそれを収納した 採血容器を開発すべく鋭意研究を重ねた結果、 マグネシウムの無機酸塩が、 意外 にも血液凝固防止効果に優れ、 万能血液凝固阻止剤としてその目的に適合しうる ことを見い出し、 この知見に基づいて本発明を完成するに至った。  The present inventor has conducted intensive studies to develop a blood coagulation inhibitor having the above preferred properties and a blood collection container containing the same, and as a result, the inorganic acid salt of magnesium has an unexpectedly excellent blood coagulation prevention effect, The present inventors have found that the agent can be used as a universal anticoagulant, and based on this finding, have completed the present invention.
すなわち、 本発明は、 ( 1 ) マグネシウムの無機酸塩を有効成分とする血液凝固阻止剤、 That is, the present invention (1) an anticoagulant comprising an inorganic salt of magnesium as an active ingredient,
( 2 ) マグネシウムの無機酸塩が硫酸マグネシウム又はその含水塩である第 （1 ) 項記載の血液凝固阻止剤、  (2) The anticoagulant according to (1), wherein the inorganic acid salt of magnesium is magnesium sulfate or a hydrate thereof.
( 3 ) 血液検査用に用いられる第 （1 ) 又は （2 ) 項記載の血液凝固阻止剤、 (3) The anticoagulant according to (1) or (2), which is used for a blood test,
( 4 ) 容器内にマグネシウムの無機酸塩を収納させてなる採血容器、 及び (4) A blood collection container containing a magnesium salt of inorganic acid in the container, and
( 5 ) マグネシウムの無機酸塩が硫酸マグネシウム又はその含水塩である第 （4 ) 項記載の採血容器、  (5) The blood collection container according to (4), wherein the inorganic acid salt of magnesium is magnesium sulfate or a hydrate thereof.
を提供するものである。 発明を実施するための最良の形態 Is provided. BEST MODE FOR CARRYING OUT THE INVENTION
本発明の血液凝固阻止剤は、 マグネシウムを有効成分とするものであって、 特 に血液検査用に採取した血液の凝固防止に対して、 有効である。  The anticoagulant of the present invention contains magnesium as an active ingredient and is particularly effective in preventing coagulation of blood collected for a blood test.
マグネシウムの無機酸塩としては、 例えば硫酸マグネシウム、 硫酸マグネシゥ ムアンモニゥム、 硫酸マグネシウムカリウム、 硫酸マグネシウムナトリウム、 硫 酸マグネシウムカルシウム、 硫酸マグネシウムカルシウムカリウム、 塩化マグネ シゥム、 塩化マグネシウムアンモニゥム、 塩化マグネシウムカリウム、 塩化マグ ネシゥムナトリウム、 硝酸マグネシゥム、 リン酸マグネシゥム、 リン酸マグネシ ゥムアンモニゥム、 リン酸水素マグネシウム、 オルトホウ酸マグネシウム、 メタ ホウ酸マグネシウム、 炭酸マグネシウム、 炭酸マグネシウムアンモニゥム、 炭酸 マグネシゥムカルシゥム及びこれらの含水塩などを挙げることができる。 これら は単独で用いてもよいし、 2種以上を組合わせて用いてもよいが、 性能及び価格 などの面から、 特に硫酸マグネシゥム及びその含水塩が好適である。  Examples of the inorganic acid salts of magnesium include magnesium sulfate, magnesium ammonium sulfate, magnesium potassium sulfate, magnesium sodium sulfate, magnesium calcium sulfate, magnesium calcium potassium sulfate, magnesium chloride, magnesium chloride, magnesium potassium chloride, and magnesium chloride. Magnesium sodium, magnesium nitrate, magnesium phosphate, magnesium phosphate ammonium, magnesium hydrogen phosphate, magnesium orthoborate, magnesium metaborate, magnesium carbonate, magnesium carbonate ammonium, magnesium calcium carbonate and their hydrated salts And the like. These may be used alone or in combination of two or more. Magnesium sulfate and its hydrous salts are particularly preferred in terms of performance and cost.
マグネシウムの無機酸塩における血液凝固防止作用の機序については必ずしも 明確ではないが、 フイブリノ一ゲンを限定分解してフイブリンに転換する作用を 有するトロンビンの生成、 及びフイブリンの架橋によるフィプリン網の形成に関 与する血液中のカルシウムイオンが、 マグネシウムイオンに置換されるためと推 察される。  Although the mechanism of the anticoagulant effect of the inorganic salts of magnesium is not always clear, it has been shown that thrombin has a function of converting fibrinogen into fibrin by limited degradation and fibrin network formation by fibrin crosslinking. It is presumed that calcium ions in the blood involved are replaced by magnesium ions.
本発明の血液凝固阻止剤においては、 前記マグネシウムの無機酸塩と共に、 本 発明の目的が損なわれない範囲で、 所望により、 従来公知の血液凝固防止作用を 有する物質、 例えばエチレンジァミン四詐酸金属塩、 クェン酸ナトリウム、 へパ リンナトリウム、 合成ヒルジン、 スルホン化ジェン系重合体又はその塩、 さらに はその他のトロンビンインヒビターなどを、 適宜用いることができる。 ここで、 その他のトロンビンインヒビターとしては、 例えばメチル酸ガべキサート、 ナ ファモスタツ トメシレート、 （2 R， 4 R) — 4—メチル一 1— [N2— ( 3—メ チルー 1， 2， 3， 4ーテトラヒドロ一 8—キノリンスルホニル） 一 L—アルギニ ル] 一 2—ピぺリジンカルボン酸モノヒドレートなどが挙げられる。 In the blood coagulation inhibitor of the present invention, together with the inorganic acid salt of magnesium, As far as the object of the invention is not impaired, conventionally known substances having an anticoagulant action, for example, metal salts of ethylenediamine tetrafate, sodium citrate, sodium heparin, synthetic hirudin, sulfonated gen-based polymers, if desired Alternatively, a salt thereof, or another thrombin inhibitor or the like can be appropriately used. Here, other thrombin inhibitors include, for example, gabexate methylate, nafamostat mesylate, (2R, 4R) —4-methyl-1- 1— [N 2 — (3-methyl-1,2,3, 4-tetrahydro-18-quinolinesulfonyl) -1-L-arginyl] -12-piperidinecarboxylic acid monohydrate.
本発明の血液凝固阻止剤の血液に対する添加量は、 マグネシウムの無機酸塩の 種類及び所望する血液凝固防止時間により、 適宜選定されるが、 通常は 1〜5 0 ragZml、 好ましくは 2〜4 Omg/mlの範囲である。 この添加量が 1 mgZml未満で は血液凝固の防止効果が充分に発揮されないおそれがあるし、 5 OmgZinlを超え るとその量の割には効果の向上が認められず、 むしろ、血液検査に悪影響を与え るおそれがある。  The amount of the blood coagulation inhibitor of the present invention added to blood is appropriately selected depending on the type of the inorganic acid salt of magnesium and the desired anticoagulation time, but is usually 1 to 50 ragZml, preferably 2 to 4 Omg. / ml range. If the added amount is less than 1 mgZml, the effect of preventing blood coagulation may not be sufficiently exerted, and if it exceeds 5 OmgZinl, the effect is not improved for the amount, but rather adversely affects the blood test. May be given.
本発明の血液凝固阻止剤の形態としては特に制限はなく、 粉末状であってもよ 、し、 水性媒体に含有させてなる水性溶液状又は水性懸濁液状であつてもよい。 水性媒体としては、 血液検査を妨害しない水性媒体、 好ましくは生理食塩水を 用いることができる。  The form of the anticoagulant of the present invention is not particularly limited, and may be in the form of a powder, an aqueous solution or an aqueous suspension contained in an aqueous medium. As the aqueous medium, an aqueous medium that does not disturb the blood test, preferably, physiological saline can be used.
次に、 本発明の採血容器について説明する。  Next, the blood collection container of the present invention will be described.
本発明の採血容器は、 前記マグネシウムの無機酸塩を容器内に収納してなるも のであって、 該マグネシウムの無機酸塩は粉末、 水性溶液又は水性懸濁液として 用いられる。 また、 このマグネシウムの無機酸塩は 1種用いてもよいし、 2種以 上を組み合わせて用いてもよいが、 前述のように特に硫酸マグネシゥム及びその 含水塩が好適である。 さらに、 本発明の目的が損なわれない範囲で、 前述のよう に従来公知の血液凝固防止作用を有する物質を適宜併用してもよい。  The blood collection container of the present invention contains the inorganic salt of magnesium in a container, and the inorganic salt of magnesium is used as a powder, an aqueous solution or an aqueous suspension. The inorganic acid salt of magnesium may be used alone or in combination of two or more. As described above, magnesium sulfate and its hydrated salt are particularly preferable. Further, as long as the object of the present invention is not impaired, a conventionally known substance having an anticoagulant effect as described above may be appropriately used in combination.
本発明の採血容器は、 血液検査のために血液を採取し、 または保存するための 全血用、 血清分離用、 糖分析用等の採血管、 採血瓶、採血バッグ等の容器を意味 し、 容器自体の形状は特に限定されないが、 該容器としては真空採血管が最適で ある。 この真空採血管は、 通常、 ホルダー、 採血針等の付属機器と組合せた真空 採血システムとして実用に供される。 これらの採血容器の素材としては、 熱可塑 性樹脂、 熱硬化性樹脂又は変性天然樹脂などの樹脂、 あるいはガラスなどを用い ることができる。 The blood collection container of the present invention means a container such as a blood collection tube, a blood collection bottle, a blood collection bag, or the like for collecting or storing blood for a blood test, for whole blood, for separating serum, for analyzing sugar, and the like. Although the shape of the container itself is not particularly limited, a vacuum blood collection tube is most suitable as the container. is there. This vacuum blood collection tube is usually put into practical use as a vacuum blood collection system combined with accessory devices such as a holder and a blood collection needle. As a material of these blood collection containers, a resin such as a thermoplastic resin, a thermosetting resin or a modified natural resin, or glass can be used.
熱可塑性榭脂としては、 例えば、 ポリエチレン、 ポリプロピレン、 ポリ一 4— メチルペンテン一 1、 ポリスチレン、 ポリメチルメタクリレート、 ポリ塩化ビニ ル、 ポリエチレンテレフタレート、 ポリブチレンテレフタレート、 スチレン一ァ クリロニトリル共重合体、 スチレン一ブタジエン共重合体、 スチレン一イソプレ ン共重合体、 スチレン一無水マレイン酸共重合体、 スチレン一アクリル酸共重合 体、 スチレン一メチルメタクリレート共重合体、 エチレン一プロピレン共重合体、 エチレン一アクリル酸共重合体、 エチレン一アクリル酸エステル共重合体、 ポリ ビニルアルコールァセタール化物、 ポリビニルアルコールブチラール化物等が、 熱硬化性樹脂としては、 例えば、 不飽和ポリエステル樹脂、 エポキシ樹脂、 ェポ キシーアクリレート樹脂等が、 変性天然樹脂としては、 酢酸セルロース、 プロピ オン酸セルロース、 酢酸酪酸セルロース、 ェチルセルロース、 ェチルキチン等が 用いられる。  Examples of the thermoplastic resin include polyethylene, polypropylene, poly-4-methylpentene-11, polystyrene, polymethyl methacrylate, polyvinyl chloride, polyethylene terephthalate, polybutylene terephthalate, styrene-acrylonitrile copolymer, and styrene. Mono-butadiene copolymer, styrene-isoprene copolymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-methyl methacrylate copolymer, ethylene-propylene copolymer, ethylene-acrylic acid Copolymers, ethylene monoacrylate copolymers, polyvinyl alcohol acetalized compounds, polyvinyl alcohol butyralized compounds, etc. are examples of thermosetting resins such as unsaturated polyester resins, epoxy resins, and epoxy resins. Kishi acrylate resins, and examples of the modified natural resins, cellulose acetate, propyl propionic acid, cellulose acetate butyrate, E chill cellulose, Echirukichin like are used.
ガラスとしては、 例えば、 ソーダ石灰ガラス、 リンケィ酸ガラス、 ホウゲイ酸 ガラス等のゲイ酸塩ガラスや石英ガラス等が好ましく用いられる。  As the glass, for example, a silicate glass such as a soda-lime glass, a phosphoric acid glass, a borate glass, or a quartz glass is preferably used.
採血容器の容量は、 該容器の使用目的に応じて適宜選定されるが、 通常 2〜2 O nilの範囲である。  The capacity of the blood collection container is appropriately selected depending on the purpose of use of the container, but is usually in the range of 2 to 2 nil.
本発明においては、 採血容器に収納されるマグネシウムの無機酸塩の量は、 採 取する血液 l ml当たり、 通常 3〜5 O mg、 好ましくは 3. 1 5〜3 1 . 5 mgである c 本発明の採血容器は、 例えばブチルゴム製のキャップが施され、 内部が真空に された真空タイプのものであってもよいし、 非真空タイプのものであってもよい が、 前記したように真空タイプのものが好ましい。 また、 マグネシウムの無機酸 塩を収納する前又は後に、 必要に応じて滅菌処理することができる。 In the present invention, the amount of inorganic salt of magnesium housed in the blood collection container, per blood l ml for preparative adopted, usually 3 to 5 O mg, preferably 3. 1 5~3 1. 5 mg c The blood collection container of the present invention may be of a vacuum type in which a cap made of, for example, butyl rubber is provided and the inside is evacuated, or may be of a non-vacuum type. Types are preferred. Further, before or after storing the inorganic acid salt of magnesium, the magnesium salt can be sterilized if necessary.
実施例 Example
次に、 本発明を実施例によりさらに詳細に説明するが、 本発明は、 これらの例 によってなんら限定されるものではない。 Next, the present invention will be described in more detail with reference to Examples. It is not limited at all.
局方硫酸マグネシウム （MgS04 * 7H20) 結晶粉末にて、 6.3%等張溶 液 （局方硫酸マグネシウム結晶 6.3 mgを lral生理食塩水にて溶解した溶液） を 作成し、 栄研化学（株）製チューブ 3号 （ポリエチレン試験管） にこの溶液を添加 しておき、 50、 100、 200、 300、 500 1 Zml全血 （局方硫酸マグ ネシゥム 3. 15、 6.3、 12.6、 18.9、 25.2、 31.5mg/ml全血に相 当） となる様に、 採取した血液と混和し、 充分に採り混ぜたのち静置し、 血液が 凝固し始めるまでの時間を、 目視観察により測定した。 At Pharmacopoeia magnesium sulfate (MgS0 4 * 7H 2 0) crystalline powder, creating a 6.3% HitoshiCho溶solution (solution prepared by dissolving Pharmacopeia magnesium sulfate crystals 6.3 mg at lral saline), Eiken ( This solution was added to tube No. 3 (polyethylene test tube) manufactured by Co., Ltd., and 50, 100, 200, 300, 500 1 Zml whole blood (magnesium sulfate 3.15, 6.3, 12.6, 18.9, 25.2) , 31.5 mg / ml whole blood), mixed with the collected blood, mixed well, allowed to stand, and the time required for the blood to start coagulating was measured by visual observation.
同様に比較実験として硝酸マグネシウム [Mg(N03)2 ' 6H20、 和光純薬 工業 (株）] 、硫酸亜鉛 [ZnS04 * 7H20、 米国シグマ社] による血液凝固の 時間を測定した。 Magnesium nitrate as well as comparative experiment [Mg (N0 3) 2 ' 6H 2 0, Wako Pure Chemical Industries, Ltd.], zinc sulfate [ZnS0 4 * 7H 2 0, USA Sigma] was measured time of blood coagulation by .
それらの結果を第 1表に示す。  Table 1 shows the results.
第 1表 Table 1
量 (nig/ml) 凝固開始までの時間 溶血 Volume (nig / ml) Time to start coagulation Hemolysis
MgS04 · 7H20 3.15 6時間 なし 施 6.3 48時間 なし 例 12.6〜31.5 48時間以上 なしMgS0 4 · 7H 2 0 3.15 6 hours without facilities 6.3 48 hours None Example 12.6 to 31.5 None 48 hours or more
Mg(N03)2 · 6H20 1 30分後凝固 あり Mg (N0 3) 2 · 6H 2 0 coagulation there after 1 30 minutes
5 24時間後、小さな凝集塊あり あり  5 After 24 hours, small aggregates Yes
48時間後、凝集  48 hours later, aggregation
比 10 採血直後に、小さな黒い塊あり あり  Ratio 10 Immediately after blood collection, small black mass
30 採血直後に、小さな黒い塊あり あり 較 24時間後、 ドロドロしていた  30 Small black mass immediately after blood collection Yes 24 hours later, muddy
48時間後、凝固した  48 hours later, solidified
例 Zn S04 · 7H20 1 直後にゾル状になった 軽度の Example Zn S0 4 · 7H 2 0 1 became sol immediately after mild
5 直後にゾル状になった 溶血あり 5 Immediately after the sol became hemolyzed
10 すぐ凝固を始めた 10 Coagulation started immediately
50 すぐ凝固を始めた また、 全血算測定の為の本血液の安定性について、 例えば局方硫酸マグネシゥ ム 12.6mgZml血液の時、 8時間まで全血算が安定している。 また、 血液凝固 検査 （PT、 ΑΡΤΤ) の利用について、 同様に局方硫酸マグネシウム 12.6 mg/ml血液の時、 PT30〜50秒、 A Ρ ΤΤ約 3分で測定が可能である。 産業上の利用可能性 50 Coagulation started immediately Regarding the stability of the present blood for the measurement of whole blood count, for example, in the case of 12.6 mg Zml blood magnesium sulfate, the whole blood count is stable up to 8 hours. Similarly, the use of a blood coagulation test (PT, ΑΡΤΤ) can be measured in the same manner with 12.6 mg / ml blood of local magnesium sulfate in 30 to 50 seconds of PT and about 3 minutes of A A. Industrial applicability
本発明の血液凝固阻止剤は、 化学項目、 生化学項目及び血液項目のすべての項 目の血液検査に適用でき、 万能である上、 血液凝固の防止効果に優れ、 かつその 効果が安定で、 しかも安価であり、 実用的価値が高い。  The anticoagulant of the present invention can be applied to blood tests of all chemical, biochemical and blood items, is versatile, has an excellent effect of preventing blood coagulation, and its effect is stable. Moreover, it is inexpensive and has high practical value.

Claims

請求の範囲 The scope of the claims
1. マグネシゥムの無機酸塩を有効成分とする血液凝固阻止剤。 1. An anticoagulant containing an inorganic acid salt of magnesium as an active ingredient.
2. マグネシゥムの無機酸塩が硫酸マグネシゥム又はその含水塩である請求項 1 記載の血液凝固阻止剤。  2. The blood coagulation inhibitor according to claim 1, wherein the inorganic salt of magnesium is magnesium sulfate or a hydrate thereof.
3. 血液検査用に用いられる請求項 1又は 2記載の血液凝固阻止剤。  3. The anticoagulant according to claim 1, which is used for a blood test.
4. 容器内にマグネシゥムの無機酸塩を収納させてなる採血容器。  4. A blood collection container containing a magnesium mineral salt in the container.
5. マグネシゥムの無機酸塩が硫酸マグネシゥム又はその含水塩である請求項 4 記載の採血容器。  5. The blood collection container according to claim 4, wherein the inorganic salt of magnesium is magnesium sulfate or a hydrate thereof.
PCT/JP1999/007159 1999-01-26 1999-12-20 Blood coagulation preventing agents and blood collection containers containing the same WO2000045162A1 (en)

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WO2004046723A1 (en) * 2002-11-18 2004-06-03 Denka Seiken Co., Ltd. Immunoassay method preventing deviation between measurement data of serum and plasma

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