Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Stablizing an enzyme by forming a mixture – an adduct or a...
Reexamination Certificate
1997-05-08
2002-02-26
Prouty, Rebecca E. (Department: 1652)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Stablizing an enzyme by forming a mixture, an adduct or a...
C435S015000, C435S017000, C435S018000, C435S021000, C435S025000, C435S026000, C435S183000, C435S196000, C435S194000, C435S193000, C435S190000, C435S212000, C436S008000, C436S015000, C436S016000, C436S018000, C530S350000, C530S362000, C530S363000, C424S094500, C424S094600, C424S094640, C424S094630
Reexamination Certificate
active
06350601
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a novel enzyme composition for use in clinical examination. More particularly, the present invention is concerned with a stabilized enzyme composition for use in clinical examination, comprising (a) an enzyme component comprising at least two enzymes selected from the group consisting of alkaline phosphatase, creatine kinase and alanine aminotransferase; (b) a stabilizer component comprising effective stabilizing amounts of an albumin, and at least one saccharide selected from the group consisting of trehalose and sorbitol; and (c) an aqueous medium having dissolved therein the components (a) and (b).
The enzyme composition of the present invention is stable for a prolonged period of time not only under non-freeze refrigeration conditions, but also under freezing conditions or under conditions for non-freeze refrigeration after thawing of the frozen composition, as compared to conventional enzyme compositions. Specifically, with respect to each of at least two enzymes contained in the enzyme composition of the present invention, the activity can be maintained, for a prolonged period of time, in the liquid state or in the frozen state (i.e., in a non-lyophilized state). Therefore, the enzyme composition of the present invention is advantageous from the economical viewpoint and from the viewpoint of ease in handling.
In a clinical examination for measuring the enzymatic activity in a sample, such as serum or the like, the enzyme composition of the present invention can be advantageously used for the purpose of checking the precision in measurement, correcting measured values and calibrating the activity of an enzyme in the sample.
PRIOR ART
In clinical examinations, for measuring the enzymatic activity in a sample, such as serum or the like, enzyme compositions are used for the purpose of checking the precision in measurement, correcting. measured values and calibrating the amount and activity of an enzyme in the sample. At present, as such enzyme compositions, various compositions containing a single type of enzyme or containing an enzyme system comprising a plurality of types of enzymes which participate in consecutive reactions are commercially available. These enzyme compositions are used as control serum for checking the precision in measurement and as reference materials (standard materials) for rectifying differences between measured values obtained in different testing facilities, and also as calibrators for calibrating the amount and activity of enzymes. [With respect to the terms “control serum”, “reference material” and “calibrator”, which will be further explained below, reference can be made, for example, to “Kensa-to-Gijutsu (MODERN MEDICAL LABORATORY)”, vol. 22, No. 8, p. 594, 1994]. Such an enzyme composition is prepared by adding the same enzyme as the enzyme to be determined to a serum product, such as pooled human serum, pooled animal serum, human albumin, bovine serum albumin or the like.
As the enzyme to be added to a serum product in order to prepare an enzyme composition, various enzymes derived from human sources and animal sources have been reported. For example, as control sera, “Monitrol” and “Monitrol L” (registered trade marks; both manufactured and sold by International Reagents Corporation, Japan), each of which is produced by adding an enzyme from animal sources to pooled human serum, are commercially available as a lyophilized product and as a frozen product, respectively. As examples of commercially available reference materials, there can be mentioned “SERACLEAR-HE” (trade name; manufactured and sold by NIPPON SHOJI KAISHA, Ltd., Japan) which is produced by adding an enzyme from established human cell lines or human source (erythrocyte) to pooled human serum, and “Enzyme reference” which is produced by adding the above-mentioned human-derived enzyme to bovine serum albumin. Among these commercially available enzyme compositions, with respect to those containing pooled human serum as a serum product, there is a danger that they have been contaminated with a known virus (such as HIV) or an unknown virus. Therefore, in use of such enzyme compositions containing pooled human serum, minute care is required for preventing biohazard.
The enzymatic activity of each of these enzyme compositions is determined by using an enzymatic assay reagent specific for the enzyme in the enzyme composition. Generally, in the measurement of a catalytic activity, such as an enzymatic activity, the measured value greatly varies depending on not only the type and concentration of the substrate, but also the reaction conditions, such as pH and reaction temperature.
In judging the condition of a patient by utilizing the enzymatic activity in a sample from the patient, such as serum or the like, wherein the enzymatic activity is measured by a diagnostic reagent, the above-mentioned fact that the measured value of enzymatic activity varies depending on the measuring conditions poses a serious problem. Further, various kits of reagents for measurement of an enzymatic activity are sold by many manufacturers. When a plurality of samples from the same lot are individually measured by using a plurality of reagent kits wherein the measuring conditions are greatly different among the measurements, largely different measured values are obtained with respect to the samples from the same lot, thus causing a confusion in the diagnosis.
In order to solve the above-mentioned problem, socalled “recommended methods”, each of which prescribes detailed measuring conditions agreed to by many scientists, have been proposed by scientific societies. For example, there can be mentioned a recommended method proposed by the International Federation of Clinical Chemistry (IFCC) and a recommended method proposed by the Japan Society of Clinical Chemistry (JSCC). However, such recommended methods have a problem in that they do not use an automatic analyzer and, therefore, cannot be used in a testing facility which has to deal with a large number of samples in a day. Accordingly, for enabling the accuracy of such a recommended method to be directly reflected in the test results obtained by using an automatic analyzer, it becomes necessary to use a reference material which has been measured with respect to the enzymatic activity thereof by using the recommended method. Specifically, a measured value obtained routinely by means of an automatic analyzer using commercially available reagents can be corrected based on a standard value obtained by the measurement of a reference material using a recommended method, so that the enzymatic activity of a sample can be accurately measured to obtain a reliable value which does not depend on the measuring conditions. Thus, by using a reference material, differences among measured values obtained by different testing facilities can be suppressed to a minimum.
As explained above, a reference material is used for reflecting the accuracy of a recommended method in a routine measuring method. Therefore, it is required that a reference material have the same properties as those of a human-derived sample. Recently, from the viewpoint of achieving the interchangeability of test data, the importance of reference materials have been greatly recognized, and a reference material produced using a human-derived enzyme has also been commercially available. There exist a wide variety of human-derived enzymes. Some human-derived enzymes assume the form of isozymes, for example, derived from different organs, which isozymes are identical to one another in the enzymatic function but are different from one another in characteristics, such as specificity to organs. Further, the content of an enzyme in human-derived serum varies depending on the individual as a source of the serum and on the disease condition of the individual as a source of serum. For example, it is well known that there are various types of alkaline phosphatases which are derived from placenta, small intestine and a tumor cell, and these various types o
Aoki Ryoji
Ueda Shigeru
Asahi Kasei Kogyo Kabushiki Kaisha
Hutson Richard
Pennie & Edmonds LLP
Prouty Rebecca E.
LandOfFree
Enzyme composition for use as a clinical diagnostic reagent does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Enzyme composition for use as a clinical diagnostic reagent, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Enzyme composition for use as a clinical diagnostic reagent will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2934037