Surgery – Diagnostic testing – Liquid collection
Reexamination Certificate
2001-05-11
2002-04-30
Hindenburg, Max (Department: 3736)
Surgery
Diagnostic testing
Liquid collection
Reexamination Certificate
active
06379318
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a method for preventing the denaturation of blood, particularly hemoglobin, and a blood test tool to be used therein.
BACKGROUND ART
Hemoglobin Alc (HbAlc) in which hemoglobin (Hb) is bonded to glucose reflects the average glucose level of the body one or two months earlier. Therefore, it is widely used in physical examinations for geriatric diseases or treatment and consultation therefor. However, since it takes a long time to measure HbAlc, for example, even if the blood is collected from outpatients when they visits to hospital, the result of the examination of HbAlc is generally evaluated when the patient visits to the hospital the next time. Therefore, although the measurement value of HbAlc is an important factor for diagnosis of diabetes, actually, it has not been used effectively for treatment.
To solve this problem, a blood collection card made of filter paper has been proposed (“Diabetes” Vol. 38, No. 10 (1995), JP10-104226A, etc.). The patients collect blood onto the collection card by themselves and allow the collection card to be impregnated with the collected blood, dried, and then mail the card to the hospital. In the hospital where this card is received, the part impregnated with the blood of the card is cut out or punched out (punch-out), and then blood is eluted therefrom. The eluted blood is examined for the predetermined items including HbAlc, etc. When the patient visits to the hospital, the treatment or diagnosis is performed based on the examination results.
However, one to several days are required for collecting blood onto the collection card, mailing the collection card, and examining the blood. Furthermore, since the blood is held in a dried state in this case, Hb may be denatured. For example, if Hb and glucose react with each other in the blood collection card, and HbAlc is newly produced, the value of HbAlc produced in the body cannot be determined exactly. Furthermore, if the protein-denaturation of Hb occurs, a denatured Hb peak appears in the measurement using the high performance liquid chromatography (HPLC), and a denatured Hb peak appears and affects the peak of HbAlc, which may lead to the inability to measure or measurement errors.
DISCLOSURE OF INVENTION
It is therefore an object of the preset invention to provide a method for preventing the denaturation of blood in a dried state and the blood test tool for using the method.
In order to attain the above-mentioned object, the present invention provides a method for preventing the denaturation of blood in a dried state, wherein the blood in a dried state and a carboxylic acid are allowed to be present together
When carboxylic acid and blood are allowed to be present together, even in a dried state, the production of new HbAlc is prevented and also the protein-denaturation of Hb is prevented. In the production of HbAlc, first Hb and glucose are reacted nonenzymatically with each other (a reversible reaction) to produce an unstable aldoimine, which is formed into a stable ketoamine (HbAlc) through an Amadori rearrangement. Carboxylic acid is believed to prevent the production of the unstable aldimine so as to prevent the production of new HbAlc. On the other hand, a mechanism of preventing the protein-denaturation of Hb is not clear. However, as known from the below mentioned Examples, the effect is significant.
Furthermore, in the present invention, “Hb is denatured” means not only that the structure of the protein is changed like protein-denaturation, but also modification of Hb by other materials, and the like.
It is preferable in the method for preventing the denaturation of blood of the present invention that carboxylic acid is added to blood in a non-dry state and then the blood is dried. In this way, if carboxylic acid is added to a liquid blood before being dried, since the blood and carboxylic acid can be brought into contact with each other sufficiently, it is possible further to prevent the denaturation of the blood in the following dried state.
It is preferable in the present invention that the carboxylic acid is citric acid because it exhibits a high effect in preventing the denaturation of Hb. However, in the present invention, as the carboxylic acid, for example, oxalic acid, pyruvic acid, acetic acid, etc. may be used. The amount of carboxylic acid to be added is generally 1.5 to 10 parts by weight, and preferably 2.5 to 6 parts by weight, with respect to 100 parts by weight of the blood in a non-dry state.
It is preferable in the method for preventing the blood denaturation of the present invention that in addition to carboxylic acid, a non-reducing sugar and the blood are allowed to be present together because the non-reducing sugar is not likely to be reacted with Hb and can prevent the denaturation of Hb further. It is preferable that the non-reducing sugar is sucrose. Besides, a non-reducing sugar such as trehalose can be used. The amount of the non-reducing sugar is generally 10 to 50 parts by weight, and preferably 20 to 30 parts by weight, with respect to 100 parts by weight of the blood in a non-dry state.
It is preferable in the method for preventing the blood denaturation of the present invention that, in addition to the carboxylic acid and the non-reducing sugar, at least one of an anticoagulant and an antioxidant is allowed to be present together with blood. An example of the anticoagulant includes ethylenediaminetetraacetic acid (EDTA), heparin, oxalic acid salt, and the like. Among them, EDTA is preferable. The amount of the anticoagulant is generally 1 to 5 parts by weight, and preferably 1.5 to 3 parts by weight, with respect to 100 parts by weight of the blood in a non-dry state. An example of the antioxidant includes glutathione (GSH), &agr;-tocopherol, and the like. Among them, GSH is preferable. The amount of the antioxidant is generally 0.1 to 8 parts by weight, and preferably 0.1 to 3 parts by weight, with respect to 100 parts by weight of the blood in a non-dry state.
It is preferable in the method for preventing the blood denaturation of the present invention that the blood is in a dried state, with a porous material being impregnated with the blood and the blood dried.
Next, according to the blood test tool of the present invention, the blood test tool holds blood in a dried state with a porous material impregnated with the blood, and a part for holding the blood of the porous material (hereinafter, “blood holding part” will be referred to) contains carboxylic acid.
In the blood test tool of the present invention, like in the method for storing the blood of the present invention, it is preferable that the carboxylic acid is citric acid. The above-mentioned carboxylic acids may be used. Furthermore, the amount of carboxylic acid is the same as in the above.
It is preferable in the blood test tool of the present invention that the blood holding part contains a non-reducing sugar, in addition to carboxylic acid. The non-reducing sugar is preferably sucrose, and the above-mentioned non-reducing sugar can also be used. Furthermore, the amount of the non-reducing sugar is the same as in the above.
It is preferable in the blood test tool of the present invention that the blood holding part contains at least one of an anticoagulant and an antioxidant in addition to carboxylic acid and non-reducing sugar. The anticoagulant is preferably EDTA, and the above-mentioned anticoagulants also can be used. Furthermore, the amount of the anticoagulant is the same as in the above. The above-mentioned antioxidant is preferably GSH, and the above-mentioned antioxidants also can be used. The amount of the antioxidant is the same as in the above.
It is preferable in the blood test tool of the present invention that the blood holding part is surrounded by a blood anti-diffusion layer provided in or around the porous material.
When the blood test tool of the present invention has such a liquid anti-diffusion layer, it is possible to prevent the blood smeared on the porous material from diffusing, so that the diffusion of the b
Higashino Kouji
Nishimura Satoshi
Arkray Inc.
Hindenburg Max
Merchant & Gould P.C.
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