JP4420828B2 - Blood coagulation promoter - Google Patents
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- JP4420828B2 JP4420828B2 JP2005012154A JP2005012154A JP4420828B2 JP 4420828 B2 JP4420828 B2 JP 4420828B2 JP 2005012154 A JP2005012154 A JP 2005012154A JP 2005012154 A JP2005012154 A JP 2005012154A JP 4420828 B2 JP4420828 B2 JP 4420828B2
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Description
本発明は、血液から血清を分離するために用いられる血液凝固促進剤に関する。 The present invention relates to a blood coagulation promoter used for separating serum from blood.
近年、検査技術の進歩に伴って、血清生化学検査、血清免疫学検査、血球検査などの血液検査が広く普及しており、血清生化学検査が大きな割合を占めている。そして、血清生化学検査に供される血清は、採血管内に予め血液凝固促進剤を入れておき、この採血管内に血液を供給して血液を凝固させて遠心分離することにより、比重の重い血餅から分離することによって得ることができる。 In recent years, with the advance of testing technology, blood tests such as serum biochemistry, serum immunology, and blood cell test have become widespread, and serum biochemistry has occupied a large proportion. The serum to be subjected to the serum biochemical test is prepared by placing a blood coagulation promoter in a blood collection tube in advance, supplying the blood into the blood collection tube, coagulating the blood, and centrifuging the blood. It can be obtained by separating it from the bag.
このような血液凝固促進剤としては、特許文献１に、アルミニウム含有量が１５００ｐｐｍ以下のシリカを含有する血液凝固促進剤が提案されている。しかしながら、この血液凝固促進剤は、血液の凝固促進効果が低く、又、製造にあたってアルミニウム含有量の調整のために煩雑な工程を必要とするといった問題点があった。 As such a blood coagulation promoter, Patent Document 1 proposes a blood coagulation promoter containing silica having an aluminum content of 1500 ppm or less. However, this blood coagulation promoter has a problem that the effect of promoting blood coagulation is low, and a complicated process is required for adjusting the aluminum content in the production.
本発明は、血液の凝固促進効果に優れており短時間のうちに血液を凝固させることができる血液凝固促進剤を提供する。 The present invention provides a blood coagulation promoter that is excellent in blood coagulation promoting effect and can coagulate blood within a short time.
本発明の血液凝固促進剤は、吸着性無機物１００重量部と金属酸化物０．００１〜５重量部とからなる無機混合物を３００〜１０００℃に加熱処理してなることを特徴とする。 The blood coagulation promoter of the present invention is obtained by heat-treating an inorganic mixture composed of 100 parts by weight of an adsorptive inorganic substance and 0.001 to 5 parts by weight of a metal oxide at 300 to 1000 ° C.
上記無機混合物を構成する吸着性無機物としては、例えば、シリカ、セライトなどが挙げられ、シリカが好ましい。そして、シリカには、天然シリカと合成シリカとがあるが、合成シリカが好ましい。なお、天然シリカは、例えば、石英砂などの形状で産出する天然シリカを微粉砕して得られ、又、合成シリカとしては、例えば、ケイ酸ナトリウムと酸とを反応させて得られたもの、アルコキシシランの加水分解により得られたもの、カルシウムシリケートと酸との反応により得られたものなどが挙げられる。 As an adsorptive inorganic substance which comprises the said inorganic mixture, a silica, cerite etc. are mentioned, for example, A silica is preferable. Silica includes natural silica and synthetic silica, and synthetic silica is preferred. Natural silica is obtained, for example, by pulverizing natural silica produced in the form of quartz sand or the like, and as synthetic silica, for example, obtained by reacting sodium silicate with an acid, Examples thereof include those obtained by hydrolysis of alkoxysilanes and those obtained by reaction of calcium silicate with acid.
又、上記無機混合物を構成する金属酸化物としては、酸化カルシウム、酸化鉄、酸化マグネシウム、酸化チタン、酸化アルミニウムなどが挙げられ、単独で用いても二種以上が併用されてもよいが、酸化カルシウム、酸化鉄、酸化マグネシウム、酸化チタン及び酸化アルミニウムからなる群から選ばれた二種以上からなることが好ましい。 In addition, examples of the metal oxide constituting the inorganic mixture include calcium oxide, iron oxide, magnesium oxide, titanium oxide, and aluminum oxide. These may be used alone or in combination of two or more. It is preferably composed of two or more selected from the group consisting of calcium, iron oxide, magnesium oxide, titanium oxide and aluminum oxide.
そして、無機混合物中における金属酸化物の総含有量としては、少ないと、血液凝固促進剤の血液の凝固作用が低下し、血液の凝固に時間を要する一方、多いと、血液検査の結果に影響を及ぼす虞れがあるので、吸着性無機物１００重量部に対して０．００１〜５重量部に限定される。 If the total content of metal oxides in the inorganic mixture is small, the blood coagulation action of the blood coagulation promoter is reduced, and it takes time for blood coagulation. Therefore, the amount is limited to 0.001 to 5 parts by weight with respect to 100 parts by weight of the adsorptive inorganic substance.
本発明の血液凝固促進剤は、吸着性無機物と金属酸化物とを所定割合で含有する無機混合物を３００〜１０００℃に加熱処理することによって得ることができる。ここで、無機化合物の加熱処理温度は、低いと、血液凝固促進剤の血液の凝固作用が低下し、血液の凝固に時間を要する一方、高いと、吸着性無機物が溶融してしまい、他の薬剤への分散性が
低下するので、上述のように、３００〜１０００℃に限定される。
The blood coagulation promoter of the present invention can be obtained by heat-treating an inorganic mixture containing an adsorbing inorganic substance and a metal oxide at a predetermined ratio to 300 to 1000 ° C. Here, when the heat treatment temperature of the inorganic compound is low, the blood coagulation action of the blood coagulation accelerator is lowered and it takes time for blood coagulation, while when it is high, the adsorptive inorganic substance is melted and other Since the dispersibility to a chemical | medical agent falls, as above-mentioned, it is limited to 300-1000 degreeC.
次に、上記血液凝固促進剤の製造方法について説明する。この血液凝固促進剤の製造方法としては、先ず、吸着性無機物と金属酸化物とを混合して無機混合物を製造するが、この無機混合物を製造するにあたっては、吸着性無機物と金属酸化物とを均一に混合すると共に吸着性無機物及び金属酸化物を微細なものとすることが好ましく、具体的な無機混合物の製造方法としては、吸着性無機物と金属酸化物とを混合した上で磨り潰して無機混合物を製造する方法が挙げられる。 Next, the manufacturing method of the said blood coagulation promoter is demonstrated. As a method for producing this blood coagulation promoter, first, an inorganic mixture is produced by mixing an adsorbent inorganic substance and a metal oxide. In producing this inorganic mixture, the adsorbent inorganic substance and the metal oxide are mixed. It is preferable to uniformly mix and make the adsorptive inorganic substance and the metal oxide fine. As a specific method for producing the inorganic mixture, the adsorbing inorganic substance and the metal oxide are mixed and then ground and mixed. The method of manufacturing a mixture is mentioned.
次に、上記無機混合物を電気炉などの汎用の加熱処理装置に供給して３００〜１０００℃に加熱処理することによって本発明の血液凝固促進剤を得ることができる。 Next, the blood coagulation promoter of the present invention can be obtained by supplying the inorganic mixture to a general-purpose heat treatment apparatus such as an electric furnace and performing heat treatment at 300 to 1000 ° C.
そして、上記血液凝固促進剤は、採血された血液が収容された採血管などの容器内に添加されてもよいし、予め採血管などの容器内に収容しておいてもよい。又、上記血液凝固促進剤は、固体状のまま使用されてもよいし、水や溶剤に溶解させ或いは懸濁させた状態で使用されてもよい。血液凝固促進剤を水や溶剤に溶解させ或いは懸濁させた状態で採血管などの容器内に収容した場合には、血液凝固促進剤を容器内に収容した後に水や溶剤を除去してもよい。 And the said blood coagulation promoter may be added in containers, such as a blood collection tube in which the collected blood was accommodated, and may be previously accommodated in containers, such as a blood collection tube. The blood coagulation promoter may be used as it is in a solid state, or may be used in a state dissolved or suspended in water or a solvent. When the blood coagulation promoter is dissolved or suspended in water or a solvent and stored in a container such as a blood collection tube, the water or solvent may be removed after the blood coagulation promoter is stored in the container. Good.
更に、上記血液凝固促進剤は、血液が凝固して得られる血餅が、血液を収容した容器の内壁面に付着するのを防止する血液成分付着防止剤と共に用いられてもよい。このような血液成分付着防止剤としては、例えば、ポリビニルピロリドン、シリコーンオイルなどが挙げられる。 Furthermore, the blood coagulation promoter may be used together with a blood component adhesion preventive agent that prevents clots obtained by coagulation of blood from adhering to the inner wall surface of a container containing blood. Examples of such blood component adhesion preventing agents include polyvinyl pyrrolidone and silicone oil.
本発明の血液凝固促進剤は、吸着性無機物１００重量部と金属酸化物０．００１〜５重量部とからなる無機混合物を３００〜１０００℃に加熱処理してなることを特徴とするので、優れた血液凝固作用を有しており、採取された血液を短時間のうちに凝固させて血清と血餅とに分離させることができる。 The blood coagulation promoter of the present invention is characterized by being characterized by heat-treating an inorganic mixture composed of 100 parts by weight of an adsorptive inorganic substance and 0.001 to 5 parts by weight of a metal oxide at 300 to 1000 ° C. The collected blood can be coagulated in a short time and separated into serum and blood clot.
そして、上記血液凝固促進剤において、吸着性無機物がシリカである場合には、より優れた血液凝固作用を発揮し、採取された血液をより短時間のうちに凝固させることができる。 And in the said blood coagulation promoter, when an adsorptive inorganic substance is a silica, the more excellent blood coagulation effect | action is exhibited and the extract | collected blood can be coagulated in a short time.
（実施例１〜５，比較例４）
微粉末状の合成シリカ１０ｇに、表１に示した所定量の酸化カルシルム、酸化鉄、酸化マグネシウム、酸化チタン及び酸化アルミニウムを加えて乳鉢を用いて磨り潰して無機混合物を得た。この無機混合物を表１に示した加熱温度にて５時間に亘って加熱処理を施した後に室温まで冷却して血液凝固促進剤を得た。
(Examples 1-5, Comparative Example 4)
A predetermined amount of calcium oxide, iron oxide, magnesium oxide, titanium oxide and aluminum oxide shown in Table 1 was added to 10 g of finely powdered synthetic silica and ground using a mortar to obtain an inorganic mixture. This inorganic mixture was subjected to heat treatment at the heating temperature shown in Table 1 for 5 hours and then cooled to room temperature to obtain a blood coagulation promoter.
（比較例１）
加熱処理を行わなかったこと以外は実施例１と同様にして血液凝固促進剤を得た。
(Comparative Example 1)
A blood coagulation promoter was obtained in the same manner as in Example 1 except that the heat treatment was not performed.
（比較例２）
ポリビニルピロリドン２ｇ及び変性シリコーンオイル０．４ｇを含有する水溶液４００ｇを用意した。
(Comparative Example 2)
400 g of an aqueous solution containing 2 g of polyvinylpyrrolidone and 0.4 g of modified silicone oil was prepared.
（比較例３）
微粉末状の合成シリカ１０ｇを乳鉢を用いて磨り潰して血液凝固促進剤を得た。
(Comparative Example 3)
10 g of finely powdered synthetic silica was ground using a mortar to obtain a blood coagulation promoter.
得られた血液凝固促進剤及び比較例２の水溶液の血液凝固性を下記の要領で測定し、その結果を表１に示した。 The blood coagulation property of the obtained blood coagulation promoter and the aqueous solution of Comparative Example 2 was measured in the following manner, and the results are shown in Table 1.
（血液凝固性）
ポリビニルピロリドン２ｇ及び変性シリコーン０．４ｇを含有する水溶液４００ｇに、得られた血液凝固促進剤を全量、分散させて分散液を作製した。得られた分散液２０ｍｇを有底円筒状のポリエチレンテレフタレート製の採血管の内壁面にスプレーを用いて塗布し乾燥させた。なお、採血管は、その内径が１５ｍｍ、外径が１７ｍｍ、高さが１１０ｍｍであった。
(Blood coagulation)
The obtained blood coagulation promoter was completely dispersed in 400 g of an aqueous solution containing 2 g of polyvinylpyrrolidone and 0.4 g of modified silicone to prepare a dispersion. 20 mg of the obtained dispersion was applied to the inner wall surface of a bottomed cylindrical polyethylene terephthalate blood collection tube using a spray and dried. The blood collection tube had an inner diameter of 15 mm, an outer diameter of 17 mm, and a height of 110 mm.
次に、二人の正常健康人Ａ、Ｂから血液を採取し、この採取した血液をそれぞれ上記採血管内に４ミリリットル供給した後、採血管の上端開口部を閉止した上で採血管を５回、上下反転させた。しかる後、採血管の上下反転を完了してから血液が流動しなくなるまでの時間（凝固時間）を測定し、血液凝固性の指標とした。 Next, blood is collected from two normal healthy persons A and B, and 4 ml of the collected blood is supplied into the blood collection tube, and then the upper end opening of the blood collection tube is closed and the blood collection tube is collected 5 times. , Upside down. Thereafter, the time from the completion of the upside down of the blood collection tube until the blood stopped flowing (coagulation time) was measured and used as an indicator of blood coagulation properties.
なお、比較例２の水溶液については、この水溶液２０ｍｇを上記採血管の内壁面にスプレーを用いて塗布し乾燥させたこと以外は上述と同様の要領で凝固時間を測定した。
For the aqueous solution of Comparative Example 2, the coagulation time was measured in the same manner as described above except that 20 mg of this aqueous solution was applied to the inner wall surface of the blood collection tube using a spray and dried.
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| JP4420828B2 true JP4420828B2 (en) | 2010-02-24 |
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