Chemistry: analytical and immunological testing – Optical result – Including reagent preparation
Reexamination Certificate
2000-01-14
2001-11-27
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Optical result
Including reagent preparation
C436S811000, C436S106000, C436S119000, C436S127000, C422S067000, C546S296000, C546S114000, C546S261000, C546S273700, C546S290000, C546S297000, C546S301000, C546S304000, C514S277000, C514S279000, C514S299000, C514S300000, C514S301000, C514S315000, C514S317000, C514S327000
Reexamination Certificate
active
06323038
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a diagnostic reagent for complications associated with diabetes or renal failure, containing a particular pyridinium compound as a main component.
BACKGROUND ART
As well known, in the Mailard reaction between sugars and protein amines, first, sugars and protein amines give rise to non-enzymatic reactions (glycation) to form Schiff bases; the Schiff bases give rise to Amadori rearrangement reactions, whereby early-stage products of Mailard reaction, i.e. ketoamines are formed in a relatively short period; and then, after various steps, late-stage products of Mailard reaction are produced.
Of the early-stage products of Mailard reaction, glycated hemoglobin (HbAlc) and glycated albumin (fructosamine) are clinically utilized as an indication for control of blood sugar.
Meanwhile, the late-stage products of Mailard reaction are known to be produced from proteins of slow metabolic turnover in-vivo, such as collagen, myeline, lens and the like and increase in a prolonged high blood sugar condition (diabetes). In order to explain why the persistent high blood sugar condition, which is the most characteristic change in diabetes, gives rise to specific chronic complications to diabetes, attention is being paid to the late-stage products of Mailard reaction which may be a cause for the above phenomenon; and it has been suggested that the hindrance of production of late-stage products of Mailard reaction may prevent the outbreak and development of the complications.
Also, it is expected that the measurement of the concentration of late-stage products of Mailard reaction in blood, urine or tissue may allow a way to make a diagnosis of the above-mentioned complications.
As the components of late-stage products of Mailard reaction, pyrralin, pentosidine and crossline etc. are reported. Of these, pyrraline was separated from the reaction product between neopentylamine and glucose and its structure was determined. Pyrraline is reported to increase in the blood of diabetes patient. However, pyrraline has no fluorescence and is said to be not an important late-stage product of Mailard reaction.
Pentosidine was separated from a reaction product of lysine, arginine and ribose and its structure was determined. Its concentration is high in the skin collagen of diabetes or renal failure patient and significantly high particularly in the blood of renal failure patient. However, pentosidine contributes to only 1% or less of the total crosslinking between proteins in late-stage products of Mailard reaction and is said to be questionable as an important late-stage product of Mailard reaction.
Crossline was separated from the reaction product between acetyllysine and glucose and its structure was determined. However, its association with diabetes is not clarified yet.
Thus, the findings obtained by the so-far developed test methods for late-stage products of Mailard reaction strongly suggest that there are close relations between the increase of later-stage products of Mailard reaction in-vivo and various tissue disorders. However, the chemical structure of an important late-stage product of Mailard reaction in-vivo is unknown.
In view of the above-mentioned situation of the prior art, the present invention has an object of specifying the structure of a late-stage product of Mailard reaction in-vivo which has a close relation with various tissue disorders and also providing a diagnostic reagent for complications associated with diabetes or renal failure, containing the above compound as a main component.
DISCLOSURE OF THE INVENTION
In order to achieve the above object, the present invention provides a diagnostic reagent for complications associated with diabetes or renal failure, containing a pyridinium compound represented by the following formula as a main component:
The present inventors made an intensive study in order to find a novel important late-stage product of Mailard reaction in-vivo which reflects the change of disease condition. As a result, the present inventors found out a novel fluorescent compound. A further study by the present inventors confirmed that the compound is a pyridinium compound having the above-shown structure. Moreover, it was found out that the pyridinium compound is useful as a diagnostic reagent for complications associated with diabetes or renal failure. These have led to the completion of the present invention.
REFERENCES:
patent: 3530138 (1970-09-01), Undheim et al.
patent: 5374712 (1994-12-01), Monnier et al.
patent: 06-73057 A (1994-03-01), None
patent: WO 97/07803 (1997-03-01), None
Akiba Mitsuo
Kakimoto Norihiro
Kobayashi Hiroyuki
Morimitsu Yasujiro
Osawa Toshihiko
Asai Germanium Research Institute Co., Ltd.
Cole Monique T.
Kubovcik & Kubovcik
Warden Jill
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