JPH0871124A - Container containing antimicrobial material and storing method of the material - Google Patents

Abstract

PURPOSE: To obtain a container and a storing method of material by which the objective material for storage can be stably stored for a long time, effectively prevent growing of microorganisms in the content as the objective material to be stored in the 7 container and store the content for a long time. CONSTITUTION: The objective material for storage is housed in a container containing an antimicrobial material in the walls of the container. Otherwise, the objective material is housed with a solid material containing an antimicrobial material in a container and stored.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a container and a method for preserving an object which can be stably preserved for a long term. According to the present invention, it is possible to effectively prevent microorganisms from propagating in the contents in the container, which is the item to be stored, and to store the contents for a long period of time.
INDUSTRIAL APPLICABILITY The present invention is particularly suitable for long-term storage of difficult-to-preserve substances such as pharmaceuticals, measuring reagents, cosmetics, and foods.

[0002]

2. Description of the Related Art Conventionally, various articles are stored in a container and handled for handling and storage at each stage of production, distribution, sale, use or storage. conventionally,
In order to prevent microorganisms such as bacteria, yeasts and molds from propagating in the articles (contents) contained in the container, the contents have been made to contain an antibacterial substance. The term "antibacterial substance" as used herein means a substance capable of killing or suppressing the growth of microorganisms, and is synonymous with antibacterial agents, bactericides, fungicides and preservatives.

However, the inclusion of an antibacterial substance in the contents of this container has various problems. For example, if the content is food, beverage, drinking water or pharmaceuticals,
The antibacterial substance ingested with this food or the like may have a harmful effect on the body. When the contents are medicines, measuring reagents, cosmetics, etc., the components of these contents may lose their effects due to the antibacterial substance. There are few antibacterial substances that do not have such an adverse effect and have antibacterial activity in the contents to be stored, and it takes a lot of labor, time, and cost to search for them. It was And, even if the content contains an antibacterial substance, the ability to suppress the growth of microorganisms decreases due to decomposition or inactivation over time, and the microorganisms propagate or this antibacterial property is contained. There was a high possibility that a mutant microorganism resistant to the substance would appear.

In a measuring reagent such as a clinical test drug containing a substance involved in an enzyme reaction or a substance involved in an antigen-antibody reaction, sodium azide having an antibacterial activity is included in the measuring reagent for the purpose of preventing the growth of microorganisms. It was often used to be included in. However, depending on the measurement principle, the measurement reaction system, or the measurement item, many measurement reagents cannot use sodium azide. For example, neutral fat (TG), uric acid (UA), whose measured values are negatively affected by ascorbic acid, which is a reducing substance contained in the sample on the principle of measurement,
Creatinine (CRE), total cholesterol (T-CH
O), free cholesterol (F-CHO), phospholipid (PL), inorganic phosphorus (IP), and the like, in a measurement reagent that utilizes a Trinder reaction, ascorbate oxidase is included in the reagent to remove ascorbic acid in the sample. Although this is to be eliminated, since this ascorbate oxidase is inhibited by sodium azide, it was very difficult to use sodium azide as a measuring reagent containing ascorbate oxidase. In addition, neutral fat (T
G) In the measuring reagent, the measured value is positively influenced by the free glycerol contained in the sample due to its measuring principle. Therefore, the free glycerol in the sample may be affected by glycerol kinase and catalase contained in the reagent. Although the elimination of the catalase is inhibited by sodium azide, sodium azide could not be used as the assay reagent containing catalase. Furthermore, in a reagent for measurement by enzyme-linked immunosorbent assay (ELISA, EIA), peroxidase (P
Sodium azide could not be used in a measurement reagent using OD), that is, a POD-labeled antibody or a POD-labeled antigen, since this labeled POD was inhibited by sodium azide.

[0005] With such a measurement reagent that cannot use sodium azide that is commonly used, it is necessary to search for an alternative antibacterial substance suitable for this measurement reagent, but this search requires a large amount. Laborious, time consuming and expensive,
And, it does not adversely affect the components of the substances involved in the enzyme reaction or the substances involved in the antigen-antibody reaction contained in these measurement reagents, the measurement reaction system or the measured value, and prevents the growth of microorganisms in the measurement reagents. It is expected that the number of antibacterial substances that can be used will be few, and it has not been easy to search from conventionally known antibacterial substance candidates.

[0006] By the way, various antibacterial substances are known at present, but in measuring reagents such as clinical test agents, liquids (aqueous solutions) are prepared except for some special ones. Insoluble or sparingly soluble antibacterial substances could not be used. For example, an inorganic antibacterial agent in which a metal such as silver, copper, or zinc is supported on an inorganic compound carrier or an organic antibacterial agent composed of an organic compound has a broad antibacterial spectrum against microorganisms such as bacteria, yeasts and molds. It has been known that it is difficult to produce resistant bacteria and is useful as an antibacterial substance.However, since these antibacterial substances are insoluble or hardly soluble in an aqueous solution, they cannot be conventionally used as measuring reagents. There wasn't. In addition, there are reports of the emergence of resistant bacteria that are resistant to sodium azide in conventional measurement reagents such as clinical test agents that use sodium azide. There has been a demand for a method of stably storing a measurement reagent using a volatile substance.

As described above in detail, the method of containing antibacterial substances in the contents to prevent the proliferation of microorganisms in the contents has various problems. It should be noted that, for the purpose of preventing the growth of microorganisms, it has been carried out to contain an antibacterial substance in the synthetic resin, etc., but this is because the microorganisms propagate in the synthetic resin molded body and the organic substances attached to it To prevent the growth of microorganisms in the contents of the container. [Nomura, Plastics, 143 , 92-96 (1992)]

[0008]

As described above, the conventional method for preventing the growth of microorganisms in the contents by containing the antibacterial substance in the contents in the container is a component in the contents. The effect of the above may be lost or the person who ingested the contents may be adversely affected. And, searching for an antibacterial substance that does not have such an adverse effect and has an antibacterial activity with respect to its specific contents takes a lot of time and effort.
It is time-consuming and expensive, and it has been difficult to search for such antibacterial substances from conventionally known antibacterial substance candidates. Furthermore, over time, the ability to suppress the growth of microorganisms decreases due to the decomposition or inactivation of the antibacterial substances contained in the contents, and the microorganisms propagate or resist this antibacterial substance. There is a high possibility that a sexual mutant microorganism (resistant bacterium) will appear.

The present inventors have conducted diligent research aiming at eliminating the drawbacks of the conventional method for preventing the proliferation of microorganisms in the contents in the container, and as a result, the antibacterial substance is contained in the container wall. By storing and storing the substance to be preserved in the container containing it, or by storing the substance to be preserved and the solid substance containing the antibacterial substance in the same container and storing it.
It has been found that it becomes possible to use antibacterial substances that could adversely affect those who ingested antibacterial substances or antibacterial substances that could not be used previously, such as insoluble or hardly soluble antibacterial substances in aqueous solution. As a result, even for substances (contents) that are difficult to store for a long time with conventional antibacterial substances, it is possible to store them stably for a long time by using antibacterial substances that could not be used conventionally. I found that. Since this increases the range and number of candidate antibacterial substances, it is possible to find an antibacterial substance that does not adversely affect the components or effects of the contents and has antibacterial activity for the specific contents. It has been found that the probability is high and thus the search is efficient and the effort, time and cost for the results of this search can be reduced.

Further, it is possible to store an object to be preserved in a container containing an antibacterial substance in a container wall, or to store an object to be preserved and a solid substance containing an antibacterial substance in the same container. By storing in such a manner, the decomposition or inactivation of the antibacterial substance contained in the container wall or in the solid matter is suppressed, whereby the growth of microorganisms can be suppressed for a long period of time, and the appearance of resistant bacteria is prevented. I also found that it can be suppressed. The present invention has been completed based on the above.

[0011]

The present invention includes the following inventions. (1) A method of preserving an object to be stored by storing the object to be preserved in a container containing an antibacterial substance in the container wall. (2) The method for storing the product according to (1) above, which is a product to be stored or a product containing a substance involved in an enzymatic reaction. (3) The method for storing the product according to (1), wherein the product to be stored contains a substance involved in an antigen-antibody reaction. (4) A method of preserving a substance to be preserved and a solid substance containing an antibacterial substance stored in the same container. (5) The method for storing the product according to (4), wherein the product to be stored contains a substance involved in an enzymatic reaction. (6) The method for storing the product according to (4), wherein the product to be stored contains a substance involved in an antigen-antibody reaction. (7) A container containing an antibacterial substance in the container wall. (8) The container according to (7) above, wherein the container is a container for containing a substance containing a substance involved in an enzymatic reaction. (9) The container according to (7) above, wherein the container is a container for containing a substance containing a substance involved in an antigen-antibody reaction. (10) A container in which a solid material containing an antibacterial substance is contained. (11) The container according to the above (10), wherein the container is a container for containing a substance containing a substance involved in an enzymatic reaction. (12) The container according to the above (10), wherein the container is a container for containing a substance containing a substance involved in an antigen-antibody reaction.

The container in the present invention may be of any shape, and either a sealable one or an open one can be used. The size of the container in the present invention is not particularly limited, and any size can be used.

The material of the container in the present invention is not particularly limited, and synthetic resin, glass, ceramics, metal or the like can be used. And as an example of synthetic resin, polyethylene (PE), polypropylene (P)
P), polystyrene (PS), polycarbonate (P
C), polyvinyl chloride (PVC), polyethylene terephthalate (PET), ethylene vinyl alcohol (EV
OH), acrylonitrile styrene (SAN), polyamide (nylon, PA) and the like. The container in the present invention may be either deformable or non-deformable.

The antibacterial substance in the present invention may be any substance having the ability to kill or suppress the growth of microorganisms such as bacteria, yeasts and molds, and use of known antibacterial agents, bactericides or preservatives. You can For example, use an organic antibacterial agent composed of an organic compound or an inorganic antibacterial agent in which a metal such as silver, copper or zinc is supported on a carrier of an inorganicization product, which is insoluble or hardly soluble in a liquid. You can also

In the present invention, since the antibacterial substance is contained in the container wall of the container or contained in a solid substance and stored in the container for use, the antibacterial substance in the present invention is:
When contained in a container wall of a container or contained in a container after being contained in a solid substance, it is preferable that the container has the following characteristics. By containing a small amount in the container wall or solid matter,
It should be possible to prevent the growth of microorganisms on the contents in the container that you want to store. Do not change the contents of the container that you want to store and its components. It is resistant to the action of chemical substances such as acids and alkalis, is not hydrolyzed, is chemically stable, and maintains its effect for a long time. It has excellent weather resistance and heat resistance, does not easily flow into liquids such as water, and can be used for a long period of time without changing physicochemical properties such as color tone due to light or heat. Examples of such antibacterial substances are shown in Table 1.

[0016]

[Table 1]

In the container containing the antibacterial substance in the container wall according to the present invention, containing the antibacterial substance in the container wall means that the antibacterial substance is contained in the container wall so as to prevent microorganisms from propagating in the contents of the container. It is that it contains.

The concentration of the antibacterial substance to be contained in the container wall is different depending on the antibacterial substance to be used because the concentration at which microorganisms can be prevented from propagating in the contents varies depending on the antibacterial substance. Good. For example, when the antibacterial substance is 10,10′-oxybisphenoxyarsine, the concentration is 0.0001 to 10%, and when the antibacterial substance is a zirconium phosphate carrier carrying silver, the concentration is 0.01 to 10%.
It may be used at a concentration of 50%.

The distribution of the antibacterial substance in the container wall is preferably such that the antibacterial substance is present in an amount sufficient to prevent the growth of microorganisms in the contents on the inner surface of the container in contact with the contents. The distribution is not particularly limited as long as the contents can be prevented from being propagated by microorganisms. In the present invention, the surface of the container wall may be coated with an antibacterial substance. The antibacterial substance contained in the container wall may be of one type or a combination of a plurality of types.

A container containing an antibacterial substance in the container wall is
It can be obtained by mixing an appropriate amount of an antibacterial substance with a raw material of a container such as synthetic resin, glass, ceramics or metal, and thereby manufacturing the container according to a known method such as heat molding. Further, a container containing an antibacterial substance in its container wall can be obtained by manufacturing a container using a raw material containing an antibacterial substance in advance according to a known method such as heat molding. Furthermore, by coating the container wall of the container with an antibacterial substance according to a known method,
It is also possible to obtain a container containing an antibacterial substance in its container wall.

The solid substance containing the antibacterial substance in the present invention is contained in the solid substance contained in the container so that the antibacterial substance can prevent the growth of microorganisms in the contents of the container. Is. By storing the solid substance containing the antibacterial substance in the same container as the substance to be preserved, it is possible to prevent the microorganisms from propagating in the substance to be preserved, which is the content in the container. The form in which the solid containing the antibacterial substance is stored in the same container as the one to be preserved is not particularly limited, and one or more solids containing the antibacterial substance are desired to be preserved. It only needs to be stored in the same container. Moreover, the storage position in the container is not particularly limited.

The shape and size of the solid material containing the antibacterial substance may be any shape and size as long as it can be stored in a container.

The material of the solid material containing the antibacterial substance is not particularly limited, and synthetic resin, glass, ceramics, metal or the like can be used. And
Examples of synthetic resins include polyethylene (PE), polypropylene (PP), polystyrene (PS), polycarbonate (PC), polyvinyl chloride (PVC), polyethylene terephthalate (PET), ethylene vinyl alcohol (EVOH), acrylonitrile styrene ( SA
N) or polyamide (nylon, PA) or the like.

The concentration of the antibacterial substance contained in the solid is
Since each antibacterial substance has a different concentration at which microorganisms can be prevented from propagating in the contents, it may be appropriately set according to the antibacterial substance used. For example, 1 antibacterial substance
In the case of 0,10′-oxybisphenoxyarsine, the concentration is 0.0001 to 10%, and in the case of an antibacterial substance in which silver is supported on a zirconium phosphate carrier, it is 0.01 to 10%.
It may be used at a concentration of 50%.

Further, the distribution of the antibacterial substance in the solid substance is preferably such that the antibacterial substance is present in a sufficient amount on the surface of the solid substance in contact with the contents so as to prevent the proliferation of microorganisms in the contents. However, the distribution is not particularly limited as long as the effect of preventing the reproduction of microorganisms in the contents can be obtained. In the present invention, the surface of the solid material may be coated with an antibacterial substance. The antibacterial substance to be contained in the solid substance may be one kind or a combination of plural kinds.

The solid substance containing the antibacterial substance is obtained by mixing an appropriate amount of the antibacterial substance with a raw material of the solid substance such as synthetic resin, glass, ceramics or metal, and solidifying it according to a known method such as heat molding. It can be obtained by manufacturing a product. Alternatively, a solid material containing an antibacterial substance can be obtained by producing a solid product using a raw material containing an antibacterial substance in advance according to a known method such as heat molding. Then, a solid material containing an antibacterial substance can be obtained by coating the surface of the solid substance with an antibacterial substance according to a known method. Further, the substance containing the antibacterial substance can be used as it is as a solid substance containing the antibacterial substance.

In the present invention, the substance to be preserved is a bacterium,
There is a possibility that microorganisms such as yeasts and molds may propagate, and it is desired to prevent the proliferation of these microorganisms and preserve them. The substances in which microorganisms may propagate are those containing substances serving as nutrient sources for microorganisms, and these substances serving as nutrient sources include organic substances such as sugars, amino acids, proteins or lipids and inorganic substances. There is. Specific examples of the substance to be preserved include medicinal agents, measuring reagents such as clinical test agents, cosmetics, chemical products, foods, agricultural and marine products, beverages or drinking water.

When the substance to be preserved contains a substance having a specific effect such as a medicinal agent, a measuring reagent such as a clinical test drug, a cosmetic or a chemical product, in the present invention, the organic compound, the inorganic compound, the polymer Substances with unique effects, such as substances or substances of biological origin, are less likely to come into direct contact with the antibacterial substance contained in the container wall or in the solid matter, and are therefore subject to the action of decomposition, modification or inactivation by the antibacterial substance. It is preferable because it does not lose its peculiar effect. In particular, in the storage of products containing biologically related substances, whose expression of unique effects depends on their subtle three-dimensional structure, they rarely come into direct contact with antibacterial substances, so they may be directly affected by antibacterial substances. In particular, it is particularly preferable because its unique effect can be maintained. Examples of such biological substances include enzymes, substances that are involved in enzyme reactions such as substrates or coenzymes that are catalyzed by enzymes, antigens, antibodies, or substances such as complements that are involved in antigen-antibody reactions, hormones. Alternatively, various physiologically active substances can be used.

Specific examples of the products utilizing the unique effects of such biological substances are clinical test agents,
Non-medical measuring reagents or measuring reagents such as measuring standards,
Examples include medical drugs, cosmetics, quasi drugs, and the like. When the present invention is applied to these clinical test agents, measurement reagents such as non-medical measurement reagents or measurement standards,
By adding to the candidate an antibacterial substance that could not be used before, it does not adversely affect the components of the measurement reagent, the measurement reaction system or the measurement value, and prevents microorganisms from encroaching on the measurement reagent. This is preferable because it increases the probability of finding an antibacterial substance that can be treated, and thus makes this search more efficient. It is particularly preferable in that

In addition, in a measuring reagent in which microorganisms are prone to breed, it is possible to suppress the growth of microorganisms for a long period of time, to suppress the appearance of resistant bacteria, and to resist sodium azide which is commonly used. It is also preferable in that resistant bacteria can be suppressed. Further, when the substance to be preserved is a substance to be ingested into the body such as food, agricultural and marine products, beverages, drinking water or pharmaceuticals, in the present invention, the antibacterial substance is contained in the container wall or in the solid matter, and therefore antibacterial It is preferable because it is possible to prevent ingestion of the substance into the body, and as a result, it is possible to prevent the body from being adversely affected by the antibacterial substance.

[0031]

In the present invention, the antibacterial substance contained in the container wall of the container or the antibacterial substance contained in the solid substance contained in the container is present in the container wall or the solid substance, respectively. Prevents the growth of microorganisms in the contents of the container for a long period of time by exerting an antibacterial effect on the contents in the container or by being gradually released from the container wall or solid matter and exerting an antibacterial effect on the contents in the container. And save.

[0032]

EXAMPLES The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 Container Containing Antibacterial Substance in Container Wall A container containing an antibacterial substance in the container wall was prepared, and the antibacterial effect on the contents in the container was confirmed. (1) Silver-supported zirconium phosphate (trade name Novalon A
G300, manufactured by Toagosei Kagaku Kogyo Co., Ltd., to be 0.5% polyethylene resin (trade name Sho Rex 6002B,
(Showa Denko KK) is mixed and heat-molded to have an outer diameter of 155 mm (depth, L) x 75 mm (height, H) x 2
A rectangular container [container 1] having a diameter of 1 mm (width, W) and a 12 mm diameter opening on the upper surface was prepared. (2) Silver-supported zirconium phosphate (trade name Novalon A
G300, manufactured by Toagosei Kagaku Kogyo Co., Ltd. so that the content of polyethylene resin is 1.0% (trade name Sho Rex 6002B,
(Showa Denko KK) and heat-molded to form a rectangular container having an outer diameter of 155 mm (L) x 75 mm (H) x 21 mm (W) and a 12 mm diameter opening on the upper surface [Container 2]. Was produced. (3) Silver-supported zirconium phosphate (trade name Novalon A
G300, manufactured by Toagosei Kagaku Kogyo Co., Ltd., is made to have a polyethylene resin content of 2.0% (trade name Sho Rex 6002B,
(Showa Denko Co., Ltd.) and heat-molded to form a rectangular container having an outer diameter of 155 mm (L) x 75 mm (H) x 21 mm (W) and a 12 mm diameter opening on the upper surface [Container 3]. Was produced. (4) Vinyl chloride (90%) and vinyl acetate (10%)
The polyethylene resin (trade name Sho Rex Co., Ltd.) was adjusted to 1.0% of Vinazine SB-1 (manufactured by Morton Thiokol) containing 5% of 10,10′-oxybisphenoxyarsine in the carrier of the above copolymer. 6002B, manufactured by Showa Denko KK) and heat-molded to have an outer diameter of 155 mm.
A rectangular container [container 4] having a size of (L) × 75 mm (H) × 21 mm (W) and having a 12 mm diameter opening on the upper surface was prepared. (5) 1 for carrier of copolymer of ethylene and acrylic acid
A polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) containing 0.8% of binadine SB-1EAA (manufactured by Morton Thiokol) containing 5% of 0,10′-oxybisphenoxyarsine. Mixed with
This is heat molded to have an outer diameter of 155 mm (L) x 75 m
A rectangular container [container 5] having a diameter of m (H) x 21 mm (W) and a 12 mm diameter opening on the upper surface was prepared. (6) Vinazine SB in which 10% of 10,10'-oxybisphenoxyarsine is contained in the carrier of Elpalloy
-1ELV (Morton Thiocole) 0.8% polyethylene resin (trade name Sho Rex 6002
B, manufactured by Showa Denko KK) and heat-molded to have an outer diameter of 155 mm (L) x 75 mm (H) x 21 mm.
(W) A rectangular container [container 6] having a 12 mm diameter opening on the upper surface was prepared. (7) A polyethylene resin (trade name: Sho Rex) containing 1.0% of bainazine SB-1PR (manufactured by Morton Thiokol) containing 5% of 10,10'-oxybisphenoxyarsine in a polypropylene carrier. 600
2B, manufactured by Showa Denko KK), heat-molded this,
Outer diameter is 155 mm (L) x 75 mm (H) x 21 mm
A rectangular container [container 7] (W) having a 12 mm diameter opening on the upper surface was prepared. (8) As a control, a polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) was heat-molded to have an outer diameter of 155 mm (L) x 75 mm (H) x 21 mm.
(W) A rectangular container having a 12 mm diameter opening on the upper surface and containing no antibacterial substance in the container wall [Control container A]
Was produced. (9) Bacteria and fungi collected from the soil in Onodai, Sagamihara City were suspended in 50 mM phosphate buffer (pH 7.0) to prepare a bacterial suspension. (10) The bacterial suspension 100 prepared in (9) was added to each of the eight types of containers 1 to 7 and control container A.
After injecting each ml and sealing the mouth, these were stored in an incubator at 30 ° C., and the viable cell count of the bacterial suspension in these containers was measured with time. The results of this measurement are shown in Table 2.

[0034]

[Table 2]

From this table, in the control container A in which the antibacterial substance is not contained in the container wall, the viable cell count of the bacterial suspension in the container increases with time, whereas the antibacterial substance is contained in the container. In the containers 1 to 7 contained in the wall, it can be seen that the viable cell count of the bacterial suspension in the container decreases with time, and all the bacteria are dead after 96 hours. Therefore, by using a container containing the antibacterial substance of the present invention in the container wall, it is possible to prevent the growth of microorganisms such as bacteria in the contents in the container, and the contents in the container It was shown that can be stably stored.

Example 2 A container containing a solid substance containing an antibacterial substance in a container A solid substance containing an antibacterial substance was prepared, and a container containing the solid substance in a container was prepared. It was prepared and the antibacterial effect on the contents in this container was confirmed. (1) Silver-supported zirconium phosphate (trade name Novalon A
G300, manufactured by Toagosei Kagaku Kogyo Co., Ltd., was mixed with a polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) so as to be 34%, and this was heat-molded to have a diameter of about 3
mm solid particles were prepared. (2) In a rectangular polyethylene container having an outer diameter of 31 mm (depth, L) x 80 mm (height, H) x 23 mm (width, W) and having a 12 mm diameter port on the upper surface, (1) A container formed by putting five prepared solids and storing a solid containing an antibacterial substance in the container [Container 1
1] was produced. (3) Outer diameter is 31 mm (L) x 80 mm (H) x 23
10 solids prepared in (1) were placed in a rectangular polyethylene container having an opening of 12 mm in diameter and having a diameter of mm (W), and the solid containing the antibacterial substance was placed in the container. A container [container 12] to be stored was prepared. (4) Outer diameter is 31 mm (L) x 80 mm (H) x 23
Put 15 solids prepared in (1) in a rectangular polyethylene container having a diameter of 12 mm in diameter and having a diameter of 12 mm, and put the solid containing antibacterial substance in the container. A container [container 13] to be stored was prepared. (5) Vinyl chloride (90%) and vinyl acetate (10%)
Binazine SB-1 (manufactured by Morton Thiokol) containing 5% of 10,10'-oxybisphenoxyarsine (5%) is heat-molded on the carrier of the above copolymer to obtain a diameter of about 3 mm.
A particulate solid material was prepared. The outer diameter of 5 of this solid material is 31 mm (L) x 80 mm (H) x 23 mm (W)
A container [container 14] was prepared by placing the solid material containing the antibacterial substance in a rectangular polyethylene container having a 12 mm diameter opening on the upper surface. (6) 1 for a carrier of a copolymer of ethylene and acrylic acid
Binazine SB-1EAA (manufactured by Morton Thiokol) containing 5% of 0,10′-oxybisphenoxyarsine was heat-molded to prepare a particulate solid having a diameter of about 3 mm. 5 pieces of this solid have an outer diameter of 31 mm
(L) × 80 mm (H) × 23 mm (W), put in a rectangular polyethylene container having a 12 mm diameter opening on the top surface, and store the solid substance containing the antibacterial substance in the container. A container [Container 15] having the following structure was produced. (7) Vinazine SB in which Elballoy carrier contains 5% of 10,10′-oxybisphenoxyarsine
-1ELV (manufactured by Morton Thiokol) was heat-molded to prepare a particulate solid having a diameter of about 3 mm. 5 pieces of this solid have an outer diameter of 31 mm (L) x 80 mm (H)
A container [container 16], which is 23 mm (W) in size, is placed in a rectangular polyethylene container having a 12 mm diameter opening on the upper surface, and a solid substance containing an antibacterial substance is contained in the container. It was made. (8) Pineazine SB-1PR (manufactured by Morton Thiokol) containing 5% of 10,10′-oxybisphenoxyarsine on a polypropylene carrier is heat-molded to obtain a particulate solid having a diameter of about 3 mm. It was made. 5 pieces of this solid have an outer diameter of 31 mm (L) x 80 mm (H)
A container [container 17], which is 23 mm (W) in size, is placed in a rectangular polyethylene container having a 12 mm diameter opening on the upper surface, and a solid substance containing an antibacterial substance is stored in the container. It was made. (9) As a control, polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) was heat-molded,
A particulate solid having a diameter of about 3 mm was produced. 5 pieces of this solid material have an outer diameter of 31 mm (L) x 80 mm (H) x 2
A container [control container B], which is 3 mm (W) and is placed in a rectangular polyethylene container having an opening of 12 mm in diameter on the upper surface to store a solid substance containing no antibacterial substance in the container, is a control container B. It was made. (10) Bacteria and fungi collected from the soil of Onodai, Sagamihara City were suspended in 50 mM phosphate buffer (pH 7.0) to prepare a bacterial suspension. (11) Container 11 to Container 17 and Control Container B 8
After injecting 40 ml of the bacterial suspension prepared in (10) into each kind of container and sealing the mouth,
It was stored in an incubator at 0 ° C., and the viable cell count of the bacterial suspension in these containers was measured over time. The results of this measurement are shown in Table 3.

[0037]

[Table 3]

From this table, in the control container B in which the solid substance containing no antibacterial substance is contained in the container, the viable cell count of the bacterial suspension in the container increases with time. hand,
In the containers 11 to 17 in which a solid substance containing an antibacterial substance is contained in the container, the viable cell count of the bacterial suspension in the container decreases with time, and after 96 hours, all the bacteria die. You can see that Therefore, by using a container containing a solid substance containing the antibacterial substance of the present invention in a container, it is possible to prevent the growth of microorganisms such as bacteria in the contents of the container, It was shown that the contents in the container can be stably stored.

Example 3 Storage of Reagent for Measuring Alkaline Phosphatase in Container Containing Antibacterial Substance in Container Wall Measurement of alkaline phosphatase (ALP) which is a clinical test drug in a container containing antibacterial substance in container wall The reagent was stored and its preservation effect was confirmed. (1) A reagent composed of 1.0 mol / l diethanolamine buffer (pH 9.8) was prepared as a first reagent. Also, a reagent consisting of 1.0 mol / l diethanolamine buffer solution (pH 9.8) containing 1.9 g / dl disodium 4-nitrophenylphosphate was prepared to prepare a second solution.
It was used as a reagent. Then, 100 ml each of the first reagent and the second reagent was poured into the container 3 described in Example 1 containing 2.0% of silver-supported zirconium phosphate as an antibacterial substance in the container wall, and the mouth was closed. After that, it was stored in a refrigerator at 10 ° C. (2) As a control, 100 ml of each of the first reagent and the second reagent of (1), to which the antibacterial substance sodium azide was added so as to be 0.1%, was added. Each was poured into the control container A described in Example 1 containing no antibacterial substance in the container wall, the mouth was sealed, and the container was stored in a refrigerator at 10 ° C. (3) After 61 days of storage, the first reagent and the second reagent of (1)
The linearity of the reagents and the first and second reagents of (2) was tested. (4) The measurement was carried out with a Hitachi 7150 type automatic analyzer, 300 μl of the first reagent was added to 5 μl of the sample, and the mixture was mixed at 37 ° C. for 5
After reacting for 1 minute, 75 μl of the second reagent was added, and the ALP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub wavelength of 505 nm. The sample had an ALP activity value of 3,37.
A 0 unit / l serum sample diluted with pure water in 10 steps was used as a diluted sample. The rate of increase in absorbance when pure water was used as a sample was used as a reagent blind value, and the reagent blind value was subtracted from the measured value to calculate the ALP activity value. The linearity test results of this stored reagent are shown in FIG. In FIG. 1, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated ALP activity value.

[0040]

[Figure 1]

From this figure, the measured value of the ALP measuring reagent contained in the container containing the antibacterial substance in the container wall is:
It can be seen that the measured value is the same as that of the conventional ALP measuring reagent containing an antibacterial substance therein, there is no difference in linearity, and there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container, even an ALP measuring reagent containing no antibacterial substance therein can be stably preserved without deteriorating its performance. It was confirmed that

Example 4 Preservation of Reagent for Measuring γ-Glutamyl Transpeptidase in a Container Containing an Antibacterial Substance in a Container Wall In a container containing an antibacterial substance in a container wall, γ-glutamyl which is a clinical test drug was stored. Transpeptidase (γ-G
The TP) measurement reagent was stored and its storage effect was confirmed.
2.0 g / dl of the first reagent of (1) in Example 3
Changing to a reagent consisting of 100 mmol / l Tris buffer (pH 7.6) containing glycylglycine,
100 mmol containing 0.36 g / dl of γ-L-glutamyl-4-nitroanilide hydrochloride as the second reagent of (1)
/ L of Tris buffer (pH 7.6) was used as the reagent, and the measurement in (4) was performed using 10 μl of the sample as the first reagent 2
After adding 50 μl and reacting at 37 ° C. for 5 minutes, 125 μl of the second reagent was added, and the main wavelength was 405 nm and the sub wavelength was 4
The γ-GTP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at 80 nm, and the sample of (4) was tested for the γ-GTP activity value of 2,740 units / l.
The storage of the reagents and the linearity test of the stored reagents were carried out in the same manner as in Example 3 except that the serum sample of was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 2, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated γ-GTP activity value.

[0043]

FIG. 2

From this figure, the measured values of the γ-GTP measuring reagent contained in the container containing the antibacterial substance in the container wall are the same as those of the conventional γ-GTP measuring reagent containing the antibacterial substance therein. Since it is the same as the measured value and there is no difference in linearity, it can be seen that there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing in the container wall,
It was confirmed that even a γ-GTP measuring reagent containing no antibacterial substance can be stably stored without deteriorating its performance.

Example 5 Preservation of glucose measuring reagent in a container containing an antibacterial substance in the container wall A glucose measuring reagent as a clinical test drug was placed in a container containing an antibacterial substance in the container wall. , Confirmed its preservation effect. The first reagent of (1) in Example 3 was added to 6
100 mmol / l Tris buffer containing 2 units / dl hexokinase, 0.1 g / dl nicotinamide adenine dinucleotide phosphate (oxidized form) and 50 units / dl glucose-6-phosphate dehydrogenase ( pH 8.
0) to the reagent consisting of 100 mmol / l Tris buffer (pH: 0.19 g / dl adenosine-5′-trisodium triphosphate) (pH 2)
8.0), the reagent to be tested for linearity in (3) is a reagent after 40 days of storage, (4)
Measurement was performed by adding 320 μl of the first reagent to 3 μl of the sample, and
After reacting at 7 ° C. for 5 minutes, 80 μl of the second reagent was added, and the glucose concentration was calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 340 nm and the sub-wavelength of 450 nm. ) The preservation of reagents and the linearity test of the preserved reagents were carried out in the same manner as in Example 3 except that the serum sample having a glucose concentration of 1,120 mg / dl was diluted with pure water in 10 steps. I went. The linearity test results of this stored reagent are shown in FIG. In FIG. 3, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated glucose concentration.

[0046]

FIG. 3

From this figure, the measured value of the glucose measuring reagent contained in the container containing the antibacterial substance in the container wall is the same as the measured value of the conventional glucose measuring reagent containing the antibacterial substance therein. Therefore, there is no difference in linearity, which means that there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing in the container wall,
It was confirmed that even a glucose measuring reagent containing no antibacterial substance can be stably stored without deteriorating its performance.

Example 6 Storage of Uric Acid Measuring Reagent in Container Containing Antibacterial Substance in Container Wall A uric acid measuring reagent which is a clinical test drug was stored in a container containing antibacterial substance in the container wall. , Confirmed its preservation effect. 59 mg of the first reagent of (1) in Example 3
100 / dl of N-ethyl-N- (2-hydroxy-3-sulfoprovir) -m-toluidine sodium
mmol / l monopotassium phosphate buffer (pH 7.0)
100 mmol / l monopotassium phosphate buffer containing 48 units / dl of uricase, 24 mg / dl of 4-aminoantibilin and 130 units / dl of peroxidase as the second reagent of (1). Changing to a reagent of (pH 7.0), that the reagent for testing the linearity of (3) is a reagent after 61 days of storage,
For the measurement in (4), after adding 300 μl of the first reagent to 5 μl of the sample and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added.
Add and calculate the uric acid concentration from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 600 nm and the sub-wavelength of 700 nm.
The reagent was stored and the linearity test of the stored reagent was performed in the same manner as in Example 3 except that the serum sample of g / dl was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 4, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated uric acid concentration.

[0049]

FIG. 4

From this figure, the measured value of the uric acid measuring reagent contained in the container containing the antibacterial substance in the container wall is the same as the measured value of the conventional uric acid measuring reagent containing the antibacterial substance therein. Therefore, there is no difference in linearity, which means that there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container wall, the uric acid measuring reagent containing no antibacterial substance can be stably stored without deteriorating its performance. It was confirmed that

Example 7 Storage of Glutamate Oxaloacetate Transaminase Assay Reagent in a Container Containing an Antibacterial Substance in a Container Wall A clinical test drug, glutamic acid oxaloacetate transaminase, was stored in a container containing an antibacterial substance in the container wall. (GOT) A measuring reagent was stored and its storage effect was confirmed. 20 mg / (1) of the first reagent in Example 3
80 mmol / l Tris buffer solution containing dl nicotinamide adenine dinucleotide disodium (reduced form) and 200 units / dl malate dehydrogenase (pH
8.0), the second reagent of (1) is 80 m containing 8.7 g / dl sodium L-aspartate and 0.53 g / dl α-ketoglutarate.
Change to a reagent consisting of mol / l Tris buffer (pH 8.0), save the reagent to test the linearity of (3) 7
It is a reagent after 7 days, and the measurement in (4) is performed using sample 20.
After adding 250 μl of the first reagent to μl and reacting at 37 ° C. for 5 minutes, 125 μl of the second reagent was added, and the main wavelength was 340n.
m and the GOT activity value calculated from the rate of decrease in absorbance 2 minutes to 5 minutes after the addition of the second reagent at the subwavelength of 405 nm, and the sample of (4) was tested for GOT activity values of 2,710
Reagent storage and the linearity test of the stored reagents were carried out in the same manner as in Example 3 except that the unit / l serum sample was changed to a diluted sample diluted with pure water in seven steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 5, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated GOT activity value.

[0052]

[Figure 5]

From this figure, the measured value of the GOT measuring reagent contained in the container containing the antibacterial substance in the container wall is
It can be seen that the measured value is the same as that of the conventional GOT measuring reagent containing an antibacterial substance therein, there is no difference in linearity, and there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container wall, even a GOT measurement reagent containing no antibacterial substance therein can be stably stored without deteriorating its performance. It was confirmed that

Example 8 Storage of Glutamate Pyruvate Transaminase Assay Reagent in a Container Containing an Antibacterial Substance in a Container Wall A clinical test drug, glutamic acid pyruvate transaminase, was stored in a container containing an antibacterial substance in the container wall. The (GPT) measurement reagent was stored and its storage effect was confirmed. 20 mg / (1) of the first reagent in Example 3
100 mmol / l Tris buffer containing 110 units / dl lactate dehydrogenase (pH 8. dl) of nicotinamide adenine dinucleotide disodium (reduced form).
0) and the second reagent of (1) is 9.1 g / dl L-alanine and 0.53 g / dl.
Changing to a reagent consisting of 100 mmol / l Tris buffer (pH 8.0) containing α-ketoglutaric acid,
The reagent for testing the linearity of (3) is a reagent after 77 days of storage, and the measurement of (4) is performed by adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes, and then the second reagent. 125 μl was added, and the GPT activity value was calculated from the rate of decrease in absorbance from 2 minutes to 5 minutes after the addition of the second reagent at the main wavelength of 340 nm and the sub-wavelength of 405 nm. The reagent was stored and the linearity test of the stored reagent was performed in the same manner as in Example 3 except that the 680 unit / l serum sample was changed to a diluted sample diluted with pure water in seven steps. The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG.
The horizontal axis represents the dilution ratio of the serum sample, and the vertical axis represents the calculated GPT activity value.

[0055]

[Figure 6]

From this figure, the measured value of the GPT measuring reagent contained in the container containing the antibacterial substance in the container wall is:
It can be seen that the measured value is the same as that of the conventional GPT measuring reagent containing an antibacterial substance therein, there is no difference in linearity, and there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container wall, the GPT assay reagent containing no antibacterial substance can be stably preserved without deteriorating its performance. It was confirmed that

Example 9 Preservation of cholinesterase measuring reagent in a container containing an antibacterial substance in a container wall A cholinesterase measuring reagent which is a clinical test drug was placed in a container containing an antibacterial substance in the container wall. , Confirmed its preservation effect. First of (1) in Example 3
50 mm containing 20 mg / dl nicotinamide adenine dinucleotide tetrasodium phosphate (reduced form) as a reagent
Change to a reagent composed of μl / l Tris buffer (pH 8.0), and replace the second reagent of (1) with 0.1 g / dl of 4-
Hydroxybenzoylcholine iodine salt, 160 units / d
50 mmol / l Tris buffer (pH 8.0) containing 1-hydroxybenzoic acid hydroxylase and 60 units / dl protocatechuic acid-3,4-dioxygenase
The reagent to be tested for linearity in (3) is a reagent after 77 days of storage, and the measurement in (4) is performed by adding 250 μl of the first reagent to 10 μl of the sample and reacting at 37 ° C. for 5 minutes. After that, 125 μl of the second reagent is added, and the cholinesterase activity value is calculated from the rate of decrease in the absorbance 2 minutes to 5 minutes after the addition of the second reagent at the main wavelength of 340 nm and the sub-wavelength of 450 nm, and (4) Reagent storage and linearity test of the stored reagent in the same manner as in Example 3 except that a serum sample having a cholinesterase activity value of 1,550 units / l was diluted with pure water in eight steps. I went. The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG.
The horizontal axis represents the dilution ratio of the serum sample, and the vertical axis represents the calculated cholinesterase activity value.

[0058]

[Figure 7]

From this figure, the measured value of the cholinesterase measuring reagent contained in the container containing the antibacterial substance in the container wall is the same as the measured value of the conventional cholinesterase measuring reagent containing the antibacterial substance therein. Therefore, there is no difference in linearity, which means that there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container that contains the antibacterial substance in the container, even a cholinesterase assay reagent that does not contain the antibacterial substance can be stored stably without degrading its performance. It was confirmed that

Example 10 Preservation of serum iron measuring reagent in a container containing an antibacterial substance in the container wall A container containing an antibacterial substance in the container wall contains a serum iron measuring reagent as a clinical test drug. Then, the preservation effect was confirmed. 20 m of the first reagent of (1) in Example 3
150 mmol containing mol / l L-ascorbic acid
/ L of Tris buffer (pH 5.5), and the second reagent of (1) 0.45 mmol / l of 2
-Change to a reagent consisting of 150 mmol / l Tris buffer (pH 5.5) containing nitroso 5- (N-propyl-N-sulfopropylamino) -phenol,
The reagent to be tested for linearity in (3) is a reagent after 61 days of storage, and the measurement in (4) was carried out by adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes, and then the second reagent. 100 μl of the enzyme is added, and the serum iron concentration is calculated from the increase in the absorbance at 5 minutes after the addition of the second reagent at the main wavelength of 750 nm and the sub-wavelength of 600 nm. The storage of the reagents and the linearity test of the stored reagents were carried out in the same manner as in Example 3 except that the serum sample of was replaced with a diluted sample diluted with pure water in 10 steps. The results of the linearity test of the stored reagent are shown in FIG. In FIG. 8, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated serum iron concentration.

[0061]

[Figure 8]

From this figure, the measured value of the serum iron measuring reagent contained in the container containing the antibacterial substance in the container wall is
The values are the same as those of the conventional serum iron measuring reagent containing an antibacterial substance therein, and there is no difference in linearity, indicating that there is no practical problem. Therefore, by storing and storing the antibacterial substance in the container containing the antibacterial substance in the container wall, even in the serum iron measurement reagent containing no antibacterial substance, its performance is not deteriorated and stable. It was confirmed that it can be saved.

Example 11 Preservation of a reagent for measuring unsaturated iron binding capacity in a container containing an antibacterial substance in the container wall Unsaturated iron as a clinical test agent was stored in a container containing an antibacterial substance in the container wall. The binding capacity measurement reagent was stored and its storage effect was confirmed. In Example 3, the first reagent of (1) was added to 1 mmol / l of sodium citrate and 0.05
100m containing mmol / l ferric ammonium sulfate
Change to a reagent composed of mol / l Tris-HCl buffer (pH 8.5), and replace the second reagent of (1) with 29 mg / dl.
Of 2-nitroso-5- (N-propyl-N-sulfopropylamino) -phenol of 100 mmol / l Tris-hydrochloric acid buffer solution (pH 8.5) was used, and the linearity of (3) was tested. The reagent to be stored is the reagent after 61 days of storage, and the measurement in (4) was performed after adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes.
125 μl of the second reagent was added, and the unsaturated iron binding capacity was calculated from the increase in absorbance at 5 minutes after the addition of the second reagent at the main wavelength of 750 nm and the sub-wavelength of 600 nm. Reservation of reagents and linearity test of the preserved reagents were carried out in the same manner as in Example 3 except that a serum sample having a binding capacity of 1,090 μg / dl was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 9, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated unsaturated iron binding capacity.

[0064]

[Figure 9]

From this figure, the measured value of the unsaturated iron binding capacity measuring reagent stored in the container containing the antibacterial substance in the container wall is as follows: Since it is the same as the measured value of the performance measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container wall, even in the unsaturated iron binding capacity measurement reagent containing no antibacterial substance therein, its performance is not deteriorated. It was confirmed that it can be stored stably.

Example 12 Storage of Lactate Dehydrogenase Assay Reagent in Container Containing Antibacterial Substance in Container Wall A lactate dehydrogenase, which is a clinical test drug, was placed in a container containing an antibacterial substance in the container wall. The (LDH) measurement reagent was stored and its storage effect was confirmed. In Example 3,
The first reagent of (1) contains 16 mg / dl of nicotinamide adenine dinucleotide disodium (reduced form) 8
Change to a reagent consisting of 0 mmol / l Tris buffer (pH 7.5), 89 mg / dl second reagent of (1)
Changing to a reagent consisting of 80 mmol / l Tris buffer (pH 7.5) containing lithium pyruvate,
The reagent to be tested for linearity in (3) is a reagent after 61 days of storage, and the measurement in (4) was carried out by adding 7 μl of the sample to the first reagent 3
After adding 00 μl and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added, and the main wavelength was 340 nm and the sub wavelength was 40 nm.
The LDH activity value is calculated from the rate of decrease in the absorbance from 5 minutes after the addition of the second reagent at 5 nm, and the serum sample having the LDH activity value of 5,860 units / l is purified with pure water. The reagent was stored and the linearity test of the stored reagent was performed in the same manner as in Example 3 except that the diluted sample was diluted in 10 steps. The results of the linearity test of the stored reagent are shown in FIG. In FIG. 10, the horizontal axis represents the dilution ratio of the serum sample, and the vertical axis represents the calculated L.
The DH activity value is shown.

[0066]

[Figure 10]

From this figure, the measured value of the LDH measuring reagent contained in the container containing the antibacterial substance in the container wall is
It can be seen that the measured value is the same as that of a conventional LDH measuring reagent containing an antibacterial substance therein, there is no difference in linearity, and there is no practical problem. Therefore, by storing and storing the antibacterial substance in a container containing the antibacterial substance in the container wall, the LDH assay reagent containing no antibacterial substance can be stably preserved without deteriorating its performance. It was confirmed that

Example 13 Preservation of alkaline phosphatase assay reagent in a container containing a solid containing an antibacterial substance In a container containing a solid containing an antibacterial substance in a container , A reagent for measuring alkaline phosphatase (ALP), which is a clinical test agent, was housed and its preservative effect was confirmed. (1) Silver-supported zirconium phosphate (trade name Novalon A
G300, manufactured by Toagosei Kagaku Kogyo Co., Ltd., was mixed with a polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) so as to be 34%, and this was heat-molded to have a diameter of about 3
mm solid particles were prepared. Outer diameter is 155 mm
(Depth, L) x 75 mm (height, H) x 21 mm
Put 30 of these solids in a rectangular polyethylene container having a (width, W) and a 12 mm diameter opening on the upper surface, and store the solid containing the antibacterial substance in the container. A container was formed. (2) As a control, a polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) was heat-molded to prepare a particulate solid having a diameter of about 3 mm. 30 pieces of this solid material have an outer diameter of 155 mm (L) x 75 mm (H) x
A container made of a polyethylene of 21 mm (W) and having an opening of 12 mm in diameter on the upper surface was placed to contain a solid substance containing no antibacterial substance. (3) A reagent composed of 1.0 mol / l diethanolamine buffer (pH 9.8) was prepared as a first reagent. Also, a reagent consisting of 1.0 mol / l diethanolamine buffer solution (pH 9.8) containing 1.9 g / dl disodium 4-nitrophenylphosphate was prepared to prepare a second solution.
It was used as a reagent. Then, 100 ml of each of the first reagent and the second reagent is poured into a container in which a solid substance containing the antibacterial substance prepared in (1) is stored, and the mouth is sealed. Stored in the refrigerator. (4) As a control, 10% of each of the first and second reagents of (3) was added with the antibacterial substance sodium azide in an amount of 0.1%.
Each 0 ml of the solid substance containing no antibacterial substance prepared in (2) was poured into a container which was housed in the container and the mouth was sealed, and then stored in a refrigerator at 10 ° C. (5) After 60 days of storage, the first reagent and the second reagent of (3)
The linearity of the reagents and the first and second reagents of (4) was tested. (6) The measurement was carried out with an Hitachi 7150 type automatic analyzer, 300 μl of the first reagent was added to 5 μl of the sample, and the mixture was incubated at 37 ° C. for 5 hours.
After reacting for minutes, 75 μl of the second reagent was added, and the ALP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub wavelength of 505 nm. The sample had an ALP activity value of 3,510.
A unit / l serum sample diluted with pure water in 10 steps was used as a diluted sample. The rate of increase in absorbance when pure water was used as a sample was used as a reagent blind value, and the reagent blind value was subtracted from the measured value to calculate the ALP activity value. The results of the linearity test of this stored reagent are shown in FIG.
In FIG. 11, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated ALP activity value.

[0069]

FIG. 11

From this figure, the measured value of the ALP measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional AL containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an ALP measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 14 Preservation of alkaline phosphatase measuring reagent in a container containing a solid substance containing an antibacterial substance In a container containing a solid substance containing an antibacterial substance in a container , A reagent for measuring alkaline phosphatase (ALP), which is a clinical test agent, was housed and its preservative effect was confirmed. 1.0m of the first reagent of (3) in Example 13
ol / l 2-ethylaminoethanol buffer (pH
9.9), the second reagent of (3) is used as the second reagent of (3), and a 1.0 mol / l 2-ethylaminoethanol buffer solution (pH 9.9) containing 75 mmol / l disodium 4-nitrophenylphosphate. ), The absorbance measurement and the ALP activity value calculation in (6)
Second wavelength at main wavelength 405 nm and sub wavelength 505 nm
AL from the rate of increase in absorbance from 2 to 5 minutes after reagent addition
The same procedure as in Example 13 was performed except that the P activity value was calculated and the sample in (6) was changed to a serum sample having an ALP activity value of 5,480 units / l diluted with pure water in eight steps. The reagents were stored and tested for linearity of the stored reagents. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 12, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated ALP activity value.

[0072]

[Fig. 12]

From this figure, the measured value of the ALP measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional AL containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an ALP measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 15 Preservation of α-amylase measuring reagent in a container in which a solid substance containing an antibacterial substance is contained in a container A container in which a solid substance containing an antibacterial substance is contained in a container The α-amylase measuring reagent, which is a clinical test agent, was stored in the container and its preservative effect was confirmed. In Example 13, the first reagent of (3) was used as a 50 mmol / l Good buffer solution (pH 7.00) containing 2,000 units / dl of glucoamylase and 600 units / dl of α-glucosidase.
0) to a reagent consisting of 0.55 g / dl of blocked-4-nitrophenyl-
changing to a reagent consisting of 50 mmol / l Good's buffer (pH 7.0) containing α-maltoheptaoside,
For the measurement in (6), after adding 300 μl of the first reagent to 6 μl of the sample and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added.
And the α-amylase activity value is calculated from the rate of increase in absorbance 2 minutes to 3 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub wavelength of 505 nm, and (6)
Of the reagent and the linearity of the stored reagent in the same manner as in Example 13 except that the serum sample having an α-amylase activity value of 3,710 units / l was diluted with pure water in 10 steps. A sex test was conducted. The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG.
In, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated α-amylase activity value.

[0075]

[Fig. 13]

From this figure, the measured value of the α-amylase measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional α containing the antibacterial substance. -It is the same as the measurement value of the amylase measurement reagent, and there is no difference in linearity, which shows that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an α-amylase measuring reagent containing no antibacterial substance deteriorates. It was confirmed that it can be stably stored without being allowed to do so.

Example 16 Preservation of γ-glutamyl transpeptidase measuring reagent in a container in which a solid substance containing an antibacterial substance is contained in a container A solid substance containing an antibacterial substance is contained in a container. The reagent for measuring γ-glutamyl transpeptidase (γ-GTP), which is a clinical test drug, was housed in the following container and its preservative effect was confirmed. In Example 13, the first reagent of (3) was added to 100 m containing 2.0 g / dl of glycylglycine.
changing to a reagent consisting of mol / l Tris buffer (pH 7.6), 100 mmol / l containing 0.36 g / dl of γ-L-glutamyl-4-nitroanilide hydrochloride as the second reagent of (3) Change to a reagent consisting of Tris buffer (pH 7.6),
250 μl of the first reagent was added to 1 μl and reacted at 37 ° C. for 5 minutes, then 125 μl of the second reagent was added, and the main wavelength was 405 nm.
Also, the γ-GTP activity value is calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the subwavelength of 480 nm, and the sample of (6) is analyzed for the γ-GTP activity value 2,
The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 13 except that the 755 units / l serum sample was changed to a diluted sample diluted with pure water in 10 steps.
The results of the linearity test of this stored reagent are shown in FIG. In FIG. 14, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated γ-GTP activity value.

[0078]

FIG. 14

From this figure, γ-GTP stored in a container in which a solid substance containing an antibacterial substance is stored
The measurement value of the measurement reagent is the same as the measurement value of the conventional γ-GTP measurement reagent containing an antibacterial substance therein, and there is no difference in linearity, which shows that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a γ-GTP measuring reagent containing no antibacterial substance deteriorates. It was confirmed that it could be stored stably without being allowed to do so.

Example 17 Preservation of creatinine measuring reagent in a container containing a solid substance containing an antibacterial substance In a container containing a solid substance containing an antibacterial substance in a container, A creatinine measurement reagent, which is a clinical test agent, was stored and its preservation effect was confirmed. In Example 13,
The first reagent of (3) was added with 80 kilounits / l creatinase, 18 kilounits / l sarcosine oxidase and 1.4 mmol / l N-ethyl-N- (2-succinylaminoethyl) -m-toluidine. Including 50 mmol
/ L Good's buffer (pH 6.75), the second reagent of (3) 310 kg unit / l creatininase, 2.5 mmol / l 4-aminoantipyrine, 15 kg unit / L creatinase and 3
50 mmol containing 0 kg / l peroxidase
/ L of Good's buffer (pH 6.75), and the measurement in (6)
After adding 00 μl and reacting at 37 ° C. for 5 minutes, 100 μl of the second reagent was added, and the main wavelength was 546 nm and the sub-wavelength was 7
The creatinine concentration is calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at 00 nm, and the serum sample with a creatinine concentration of 125 mg / dl is diluted with pure water in 10 steps to obtain a diluted sample of (6). The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 13 except that the conditions were changed. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 15, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated creatinine concentration.

[0081]

FIG. 15

From this figure, the measured value of the creatinine measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional creatinine measuring reagent containing the antibacterial substance therein. It is the same as the measured value of, and there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of the creatinine measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 18 Preservation of glucose measuring reagent in a container containing a solid containing an antibacterial substance in a container A container containing a solid containing an antibacterial substance in a container, A glucose measuring reagent, which is a clinical test agent, was stored and its preservation effect was confirmed. In Example 13,
62 units / dl of hexokinase, the first reagent of (3),
A reagent composed of 100 mmol / l Tris buffer solution (pH 8.0) containing 0.1 g / dl nicotinamide adenine dinucleotide phosphate (oxidized form) and 50 units / dl glucose-6-phosphate dehydrogenase. Changing,
The second reagent of (3) was added to 0.19 g / dl of adenosine-
100 mmol / l containing 5'-disodium triphosphate
Change to a reagent consisting of Tris buffer solution (pH 8.0), and carry out the measurement in (6) by adding 320 μl of the first reagent to 3 μl of the sample.
1 and then reacted at 37 ° C for 5 minutes, and then the second reagent was added to 80
Add μl, main wavelength 340nm and sub wavelength 450nm
The glucose concentration is calculated from the increase in the absorbance up to 5 minutes after the addition of the second reagent in step (6), and the serum sample having a glucose concentration of 1,120 mg / dl is used as the sample of (6) with pure water.
Example 1 except that the diluted sample was changed in stages.
In the same manner as in 3, the reagent was stored and the stored reagent was tested for linearity. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 16, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated glucose concentration.

[0084]

FIG. 16

From this figure, the measured value of the glucose measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional glucose measuring reagent containing the antibacterial substance therein. It is the same as the measured value of, and there is no difference in linearity, which means that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a glucose measuring reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 19 Storage of Uric Acid Measuring Reagent in a Container Having a Solid Material Containing an Antibacterial Substance Stored in a Container A container having a solid material containing an antibacterial substance stored in a container, A uric acid measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 13, the first reagent of (3) was used as a 100 mmol / l monopotassium phosphate buffer solution containing 59 mg / dl of N-ethyl-N- (2-hydroxy-3-sulfopropyl) -m-toluidine sodium. (3) changing to a reagent consisting of (pH 7.0)
48 units / dl uricase, 24 mg /
dl 4-aminoantipyrine and 130 units / dl
Changing to a reagent consisting of 100 mmol / l monopotassium phosphate buffer (pH 7.0) containing peroxidase, the measurement in (6) was performed using 5 μl of the first reagent 300
After adding μl and reacting at 37 ° C for 5 minutes, the second reagent was added to 7
Add 5 μl, main wavelength 600 nm and sub wavelength 700 n
The uric acid concentration is calculated from the increase in the absorbance up to 5 minutes after the addition of the second reagent in m, and the sample of (6) is used as a diluted sample obtained by diluting a serum sample having a uric acid concentration of 105 mg / dl in 10 steps with pure water. The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 13 except that the conditions were changed. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 17, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated uric acid concentration.

[0086]

FIG. 17

From this figure, the measured value of the uric acid measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional uric acid measuring reagent containing the antibacterial substance therein. It is the same as the measured value of, and there is no difference in linearity, which means that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a uric acid measuring reagent that does not contain the antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 20 Preservation of glutamate oxaloacetate transaminase assay reagent in a container in which a solid substance containing an antibacterial substance is contained in a container A solid substance containing an antibacterial substance is contained in a container In the container, a reagent for measuring glutamic acid oxaloacetate transaminase (GOT), which is a clinical test agent, was stored, and its preservative effect was confirmed. The first reagent of (3) in Example 13 was treated with 20 mg / dl of nicotinamide adenine dinucleotide disodium (reduced form) and 200 units /
changing to a reagent consisting of 80 mmol / l Tris buffer (pH 8.0) containing dl malate dehydrogenase,
The second reagent of (3) was added to 8.7 g / dl sodium L-aspartate and 0.53 g / dl α-ketoglutaric acid in 80 mmol / l Tris buffer (pH 8.
In the measurement in (6), 250 μl of the first reagent was added to 20 μl of the sample, the mixture was reacted at 37 ° C. for 5 minutes, and 125 μl of the second reagent was added, and the main wavelength was 3
The GOT activity value is calculated from the rate of decrease in absorbance from 2 minutes to 5 minutes after the addition of the second reagent at 40 nm and the subwavelength of 405 nm, and the sample of (6) has a GOT activity value of 2.
The reagent was stored and the linearity test of the stored reagent was performed in the same manner as in Example 13 except that the serum sample of 830 units / l was changed to a diluted sample diluted with pure water in 10 steps.
The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG. 18, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated GOT activity value.

[0089]

FIG. 18

From this figure, the measured value of the GOT measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional GO containing the antibacterial substance.
Since it is the same as the measured value of the T measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a GOT measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored.

Example 21 Storage of Glutamate Pyruvate Transaminase Assay Reagent in a Container Having a Solid Material Containing an Antibacterial Substance Stored in a Container A reagent for measuring glutamate-pyruvate transaminase (GPT), which is a clinical test agent, was placed in a container, and its preservative effect was confirmed. The first of (3) in Example 13
The reagents were 20 mg / dl nicotinamide adenine dinucleotide disodium (reduced form) and 110 units / d
changing to a reagent consisting of 100 mmol / l Tris buffer (pH 8.0) containing 1 lactate dehydrogenase,
The second reagent of (3) is 100 containing 9.1 g / dl of L-alanine and 0.53 g / dl of α-ketoglutaric acid.
After changing to a reagent consisting of a mmol / l Tris buffer (pH 8.0) and measuring in (6), after adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes,
125 μl of the second reagent was added, and the GPT activity value was calculated from the rate of decrease in the absorbance at 2 minutes to 5 minutes after the addition of the second reagent at the main wavelength of 340 nm and the sub wavelength of 405 nm. Value 2,720 units / l
The preservation of the reagent and the linearity test of the preserved reagent were performed in the same manner as in Example 13 except that the serum sample of 1 was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG. 19, the horizontal axis represents the dilution ratio of the serum sample, and the vertical axis represents the calculated GPT activity value.

[0092]

FIG. 19

From this figure, the measured value of the GPT measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional GP containing the antibacterial substance.
Since it is the same as the measured value of the T measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a GPT measuring reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 22 Preservation of cholinesterase assay reagent in a container containing a solid substance containing an antibacterial substance In a container containing a solid substance containing an antibacterial substance in a container, A cholinesterase assay reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 13, the first reagent of (3) was used as a 50 mmol / l Tris buffer solution (pH 8.00) containing 20 mg / dl of nicotinamide adenine dinucleotide tetrasodium phosphate (reduced form).
0) of the second reagent of (3), 0.1 g / dl of 4-hydroxybenzoylcholine iodine salt, 160 units / dl of 4-hydroxybenzoic acid hydroxylase and 60 units / dl of Protocatechuic acid-3,
Changing to a reagent consisting of 50 mmol / l Tris buffer (pH 8.0) containing 4-dioxygenase,
For the measurement in (6), 250 μl of the first reagent was added to 10 μl of the sample.
Was added and reacted at 37 ° C. for 5 minutes, then the second reagent was added to 125
Add μl, main wavelength 340nm and sub wavelength 450nm
The cholinesterase activity value is calculated from the rate of decrease in the absorbance from 2 minutes to 5 minutes after the addition of the second reagent in (2), and
The reagent storage and the linearity test of the stored reagent were performed in the same manner as in Example 13 except that the unit / l serum sample was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In addition, in FIG. 20, the horizontal axis represents the dilution ratio of the serum sample,
The vertical axis represents the calculated cholinesterase activity value.

[0095]

FIG. 20

From this figure, the measured value of the cholinesterase measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional cholinesterase measuring reagent containing the antibacterial substance. It is the same as the measured value, and there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a cholinesterase assay reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 23 Preservation of serum iron measuring reagent in a container containing a solid containing an antibacterial substance In a container containing a solid containing an antibacterial substance in a container , Containing the serum iron measuring reagent which is a clinical test agent,
The preservation effect was confirmed. (3) in Example 13
150 mmol / l Tris buffer (pH 5.5) containing 20 mmol / l L-ascorbic acid.
Of the second reagent of (3) to 0.4
5 mmol / l 2-nitroso-5- (N-propyl-
N-Sulfopropylamino) -phenol containing 150
After changing to a reagent consisting of mmol / l Tris buffer (pH 5.5) and measuring in (6), after adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes,
100 μl of the second reagent is added, and the serum iron concentration is calculated from the increase in the absorbance at the main wavelength of 750 nm and the sub-wavelength of 600 nm until 5 minutes after the addition of the second reagent, and (6)
Of the reagent and the linearity test of the preserved reagent in the same manner as in Example 13 except that the serum sample having a serum iron concentration of 1,100 μg / dl was changed to a diluted sample diluted with pure water in 10 steps. I went. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 21, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated serum iron concentration.

[0098]

FIG. 21

From this figure, the measured value of the serum iron measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional serum iron containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance is deteriorated even in a serum iron measurement reagent containing no antibacterial substance therein. It was confirmed that it can be stored stably without any damage.

Example 24 Preservation of a lactate dehydrogenase assay reagent in a container in which a solid substance containing an antibacterial substance is contained. A solid substance containing an antibacterial substance is contained in a container. The container was filled with a reagent for measuring lactate dehydrogenase (LDH), which is a clinical test agent, and its preservative effect was confirmed. Example 1
80 mg / l of Tris buffer (pH 7.3) containing 16 mg / dl of nicotinamide adenine dinucleotide disodium (reduced form) as the first reagent of (3) in 3.
5) changing to a reagent consisting of 8)
80 mmol containing 9 mg / dl lithium pyruvate
/ L of Tris buffer (pH 7.5) was used as the reagent, and the measurement in (6) was carried out by adding the first reagent 30 to the sample 7 μl.
After adding 0 μl and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added, and the main wavelength was 340 nm and the sub wavelength was 405 nm.
calculating the LDH activity value from the rate of decrease in absorbance from 1 minute to 3 minutes after the addition of the second reagent in nm, and (6)
Of the reagent and the linearity of the preserved reagent in the same manner as in Example 13 except that the serum sample having an LDH activity value of 6,890 units / l was diluted with pure water in 10 steps. The test was conducted. The results of the linearity test of the stored reagent are shown in FIG. In FIG. 22, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated LD.
Represents H activity value.

[0101]

FIG. 22

From this figure, the measured value of the LDH measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional LD containing the antibacterial substance.
Since it is the same as the measured value of the H measuring reagent, there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an LDH measuring reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 25 Storage of leucine aminopeptidase measuring reagent in a container containing a solid substance containing an antibacterial substance A container containing a solid substance containing an antibacterial substance in a container A leucine aminopeptidase (LAP) measuring reagent, which is a clinical test agent, was housed in a container and its preservative effect was confirmed. 50 mm of the first reagent of (3) in Example 13
Change to a reagent consisting of ol / l Tris buffer (pH 7.5), the second reagent in (3) is added to 12 mmol / l L
50 mm containing leucine-4-nitroanilide hydrochloride
Change to a reagent composed of ol / l Tris buffer (pH 7.5), and in the measurement in (6), after adding 260 μl of the first reagent to 8 μl of the sample and reacting at 37 ° C. for 5 minutes, the second reagent was added. 130 μl was added, and the LAP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub-wavelength of 480 nm. The reagent storage and the linearity test of the stored reagent were performed in the same manner as in Example 13 except that the unit / l serum sample was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. 23. In FIG. 23, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated LAP activity value.

[0104]

FIG. 23

From this figure, the measured value of the LAP measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional LA containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a LAP measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 26 Preservation of Reagent for Measuring Phospholipids in a Container Having a Solid Material Containing an Antibacterial Substance in a Container A container having a solid material containing an antibacterial substance contained in a container , A phospholipid measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 13,
56 units / dl of phospholipase D of the first reagent of (3)
And 25 mg / dl N- (2-hydroxy-3-sulfopropyl) -3,5-dimethoxyaniline sodium containing 50 mmol / l Good's buffer (pH 8.
0), the second reagent in (3) is 1,200 units / dl choline oxidase, 35 mg
/ Dl 4-aminoantipyrine and 50 mmol / l Good's buffer (pH 8.0) containing 1,800 units / dl peroxidase.
In the measurement in (6), after adding 300 μl of the first reagent to 4 μl of the sample and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added.
Phospholipid concentration is calculated from the amount of increase in absorbance at 5 minutes after the addition of the second reagent at the main wavelength of 600 nm and the sub-wavelength of 700 nm, and the sample of (6) is serum with a phospholipid concentration of 1,050 mg / dl. The reagent was stored and the linearity test of the stored reagent was performed in the same manner as in Example 13 except that the sample was changed to a diluted sample diluted with pure water in eight steps. The results of the linearity test of the stored reagent are shown in FIG. In FIG. 24, the horizontal axis represents the serum sample dilution rate and the vertical axis represents the calculated phospholipid concentration.

[0107]

FIG. 24

From this figure, the measured value of the phospholipid measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional phospholipid containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of the phospholipid measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 27 Preservation of a reagent for measuring unsaturated iron binding capacity in a container in which a solid substance containing an antibacterial substance is stored in a container A solid substance containing an antibacterial substance is stored in a container The reagent for measuring unsaturated iron binding capacity, which is a clinical test agent, was stored in the container, and its preservative effect was confirmed. The reagent comprising the first reagent of (3) in Example 13 consisting of 1 mmol / l sodium citrate and 100 mmol / l Tris-hydrochloric acid buffer solution (pH 8.5) containing 0.05 mmol / l ferric ammonium sulfate. Changing the second reagent of (3) to 29 mmol / dl of 2-nitroso-5- (N-propyl-N-sulfopropylamino) -phenol in 100 mmol / l Tris-HCl buffer (pH 8.
5), the reagent for linearity test of (5) is a reagent after 82 days of storage, and the measurement in (6) is carried out by adding 250 μl of the first reagent to 20 μl of the sample.
After reacting at 5 ° C. for 5 minutes, 125 μl of the second reagent was added, and the unsaturated iron binding capacity was calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 750 nm and the sub-wavelength of 600 nm. Reservation of reagents and linearity of preserved reagents in the same manner as in Example 13 except that the serum sample having an unsaturated iron binding capacity of 855 μg / dl was replaced with a diluted sample diluted with pure water in 10 steps. A sex test was conducted. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 25, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated unsaturated iron binding capacity.

[0110]

FIG. 25

From this figure, the measured value of the unsaturated iron binding capacity measuring reagent stored in the container in which the solid substance containing the antibacterial substance is stored in the container is the conventional value containing the antibacterial substance. It is the same as the value measured by the unsaturated iron binding capacity measurement reagent of No. 1, and there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of the unsaturated iron binding capacity measurement reagent containing no antibacterial substance is also improved. It was confirmed that it can be stored stably without deteriorating.

Example 28 Preservation of Total Cholesterol Measuring Reagent in a Container Containing a Solid Material Containing an Antibacterial Substance In a container containing a solid material containing an antibacterial substance in a container Then, the total cholesterol measuring reagent, which is a clinical test drug, was stored and its preservative effect was confirmed. In Example 13, the first reagent of (3) is a reagent comprising 0.44 mmol / l 4-aminoantipyrine and 1,000 units / l cholesterol esterase in 50 mmol / l Good's buffer (pH 7.0). Change to (3)
330 units / l of cholesterol oxidase, 1.63 mmol / l of N- (2-hydroxy-
3-Sulfoprovir) -3,5-dimethoxyaniline sodium and 1.6 mmol / l peroxidase in 50 mmol / l Good buffer (pH 7.0).
The reagent to be tested for linearity in (5) is a reagent after 82 days of storage, and the measurement in (6) was carried out by adding 300 μl of the first reagent to 4 μl of the sample and heating at 37 ° C.
After reacting for a minute, 100 μl of the second reagent is added, and the total cholesterol concentration is calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 600 nm and the sub wavelength of 700 nm, and the sample of (6) Was stored in the same manner as in Example 13 except that the serum sample having a total cholesterol concentration of 980 mg / dl was changed to a diluted sample diluted with pure water in 10 steps, and the linearity test of the stored reagent was performed. FIG. 26 shows the linearity test results of the stored reagents.
It was shown to. In FIG. 26, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated total cholesterol concentration.

[0113]

FIG. 26

From this figure, the measured value of the total cholesterol measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional total cholesterol containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance is deteriorated even in a reagent for measuring total cholesterol containing no antibacterial substance therein. It was confirmed that it can be stored stably without any damage.

Example 29 Storage of Free Cholesterol Measuring Reagent in a Container Containing Solids Containing Antibacterial Substances in a Container In a container containing solids containing antibacterial substances in a container , A free cholesterol measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 13, the first reagent of (3) was added to 0.35 mmol / l of 4-
Changing to a reagent consisting of 50 mmol / l Good's buffer (pH 7.0) containing aminoantipyrine, (3)
The second reagent of 1.65 kg / l cholesterol oxidase, 2.4 mmol / l sodium N- (2-hydroxy-3-sulfopropyl) -3,5-dimethoxyaniline and 10 kg / l peroxidase. 50 mmol / l Good's buffer (pH 7.
0), the reagent to be tested for linearity in (5) is a reagent after 82 days of storage, and the measurement in (6) was carried out by adding 300 μl of the first reagent to 4 μl of the sample at 37 ° C.
After reacting for 5 minutes with 100 μl of the second reagent,
Second at 600nm main wavelength and 700nm sub wavelength
The free cholesterol concentration is calculated from the increase in the absorbance up to 5 minutes after the addition of the reagent, and the serum sample with the free cholesterol concentration of 685 mg / dl is diluted with pure water to 1) in (6).
The storage of the reagents and the linearity test of the stored reagents were carried out in the same manner as in Example 13 except that the diluted sample was diluted to 0 steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 27, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated free cholesterol concentration.

[0116]

FIG. 27

From this figure, the value measured by the reagent for measuring free cholesterol contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional free cholesterol containing the antibacterial substance. Since it is the same as the measured value of the measurement reagent and there is no difference in linearity, it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a free cholesterol measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 30 Storage of alkaline phosphatase assay reagent in a container containing a solid containing an antibacterial substance In a container containing a solid containing an antibacterial substance in a container , A reagent for measuring alkaline phosphatase (ALP), which is a clinical test agent, was housed and its preservative effect was confirmed. (1) Binazine SB in which 5% of 10,10'-oxybisphenoxyarsine is contained in an Elvalloy carrier
-1ELV (manufactured by Morton Thiokol) was heat-molded to prepare a particulate solid having a diameter of about 3 mm. Outer diameter is 155 mm (depth, L) x 75 mm (height, H) x 2
Place this solid in a rectangular polyethylene container with a 1 mm (width, W) top and a 12 mm diameter opening on top.
A container was prepared in which 0 pieces were placed and the solid substance containing the antibacterial substance was housed in the container. (2) As a control, a polyethylene resin (trade name Sho Rex 6002B, manufactured by Showa Denko KK) was heat-molded to prepare a particulate solid having a diameter of about 3 mm. 30 pieces of this solid material have an outer diameter of 155 mm (L) x 75 mm (H) x
A container made of a polyethylene of 21 mm (W) and having an opening of 12 mm in diameter on the upper surface was placed to contain a solid substance containing no antibacterial substance. (3) A reagent composed of 1.0 mol / l diethanolamine buffer (pH 9.8) was prepared as a first reagent. Also, a reagent consisting of 1.0 mol / l diethanolamine buffer solution (pH 9.8) containing 1.9 g / dl disodium 4-nitrophenylphosphate was prepared to prepare a second solution.
It was used as a reagent. Then, 100 ml of each of the first reagent and the second reagent is poured into a container in which a solid substance containing the antibacterial substance prepared in (1) is stored, and the mouth is sealed. Stored in the refrigerator. (4) As a control, 10% of each of the first and second reagents of (3) was added with the antibacterial substance sodium azide in an amount of 0.1%.
Each 0 ml of the solid substance containing no antibacterial substance prepared in (2) was poured into a container which was housed in the container and the mouth was sealed, and then stored in a refrigerator at 10 ° C. (5) After 60 days of storage, the first reagent and the second reagent of (3)
The linearity of the reagents and the first and second reagents of (4) was tested. (6) The measurement was carried out with an Hitachi 7150 type automatic analyzer, 300 μl of the first reagent was added to 5 μl of the sample, and the mixture was incubated at 37 ° C. for 5 hours.
After reacting for minutes, 75 μl of the second reagent was added, and the ALP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub wavelength of 505 nm. The sample had an ALP activity value of 3,510.
A unit / l serum sample diluted with pure water in 10 steps was used as a diluted sample. The rate of increase in absorbance when pure water was used as a sample was used as a reagent blind value, and the reagent blind value was subtracted from the measured value to calculate the ALP activity value. The results of the linearity test of this stored reagent are shown in FIG.
In FIG. 28, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated ALP activity value.

[0119]

FIG. 28

From this figure, the measured value of the ALP measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional AL containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an ALP measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 31 Preservation of alkaline phosphatase assay reagent in a container containing a solid substance containing an antibacterial substance In a container containing a solid substance containing an antibacterial substance in a container , A reagent for measuring alkaline phosphatase (ALP), which is a clinical test agent, was housed and its preservative effect was confirmed. 1.0m of the first reagent of (3) in Example 30
ol / l 2-ethylaminoethanol buffer (pH
9.9), the second reagent of (3) is used as the second reagent of (3), and a 1.0 mol / l 2-ethylaminoethanol buffer solution (pH 9.9) containing 75 mmol / l disodium 4-nitrophenylphosphate. ), The absorbance measurement and the ALP activity value calculation in (6)
Second wavelength at main wavelength 405 nm and sub wavelength 505 nm
AL from the rate of increase in absorbance from 2 to 5 minutes after reagent addition
The same procedure as in Example 30 was carried out except that the P activity value was calculated and the sample in (6) was changed to a serum sample having an ALP activity value of 5,480 units / l diluted with pure water in eight steps. The reagents were stored and tested for linearity of the stored reagents. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 29, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated ALP activity value.

[0122]

FIG. 29

From this figure, the measured value of the ALP measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional AL containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an ALP measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 32 Preservation of α-amylase measuring reagent in a container containing a solid containing an antibacterial substance A container containing a solid containing an antibacterial substance in a container The α-amylase measuring reagent, which is a clinical test agent, was stored in the container and its preservative effect was confirmed. In Example 30, the first reagent of (3) was used as a Good buffer solution (pH 7.50 mmol / l) containing 2,000 units / dl of glucoamylase and 600 units / dl of α-glucosidase.
0) to a reagent consisting of 0.55 g / dl of blocked-4-nitrophenyl-
changing to a reagent consisting of 50 mmol / l Good's buffer (pH 7.0) containing α-maltoheptaoside,
For the measurement in (6), after adding 300 μl of the first reagent to 6 μl of the sample and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added.
And the α-amylase activity value is calculated from the rate of increase in absorbance 2 minutes to 3 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub wavelength of 505 nm, and (6)
Of the reagent and the linearity of the stored reagent in the same manner as in Example 30 except that the serum sample having an α-amylase activity value of 3,710 units / l was diluted with pure water in 10 steps. A sex test was conducted. The results of the linearity test of this stored reagent are shown in FIG. Note that this FIG.
In, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated α-amylase activity value.

[0125]

FIG. 30

From this figure, the measured value of the α-amylase measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional α containing the antibacterial substance. -It is the same as the measurement value of the amylase measurement reagent, and there is no difference in linearity, which shows that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an α-amylase measuring reagent containing no antibacterial substance deteriorates. It was confirmed that it can be stably stored without being allowed to do so.

Example 33 Storage of γ-glutamyl transpeptidase measuring reagent in a container in which a solid substance containing an antibacterial substance is contained in a container The reagent for measuring γ-glutamyl transpeptidase (γ-GTP), which is a clinical test drug, was housed in the following container and its preservative effect was confirmed. In Example 30, the first reagent of (3) was added to 100 m containing 2.0 g / dl of glycylglycine.
changing to a reagent consisting of mol / l Tris buffer (pH 7.6), 100 mmol / l containing 0.36 g / dl of γ-L-glutamyl-4-nitroanilide hydrochloride as the second reagent of (3) Change to a reagent consisting of Tris buffer (pH 7.6),
250 μl of the first reagent was added to 1 μl and reacted at 37 ° C. for 5 minutes, then 125 μl of the second reagent was added, and the main wavelength was 405 nm.
Also, the γ-GTP activity value is calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the subwavelength of 480 nm, and the sample of (6) is analyzed for the γ-GTP activity value 2,
Reagent storage and the linearity test of the stored reagents were carried out in the same manner as in Example 30 except that the serum sample of 755 units / l was changed to a diluted sample diluted with pure water in 10 steps.
The results of the linearity test of the stored reagent are shown in FIG. In FIG. 31, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated γ-GTP activity value.

[0128]

FIG. 31

From this figure, γ-GTP contained in a container in which a solid substance containing an antibacterial substance is contained.
The measurement value of the measurement reagent is the same as the measurement value of the conventional γ-GTP measurement reagent containing an antibacterial substance therein, and there is no difference in linearity, which shows that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a γ-GTP measuring reagent containing no antibacterial substance deteriorates. It was confirmed that it could be stored stably without being allowed to do so.

Example 34 Preservation of Uric Acid Measuring Reagent in a Container Containing a Solid Material Containing an Antibacterial Substance In a container containing a solid material containing an antibacterial substance in a container, A uric acid measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 30, the first reagent of (3) was used as a 100 mmol / l monopotassium phosphate buffer solution containing 59 mg / dl of N-ethyl-N- (2-hydroxy-3-sulfopropyl) -m-toluidine sodium. (3) changing to a reagent consisting of (pH 7.0)
48 units / dl uricase, 24 mg /
dl 4-aminoantipyrine and 130 units / dl
Changing to a reagent consisting of 100 mmol / l monopotassium phosphate buffer (pH 7.0) containing peroxidase, the measurement in (6) was performed using 5 μl of the first reagent 300
After adding μl and reacting at 37 ° C for 5 minutes, the second reagent was added to 7
Add 5 μl, main wavelength 600 nm and sub wavelength 700 n
The uric acid concentration is calculated from the increase in the absorbance up to 5 minutes after the addition of the second reagent in m, and the sample of (6) is used as a diluted sample obtained by diluting a serum sample having a uric acid concentration of 105 mg / dl in 10 steps with pure water. The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 30, except that the conditions were changed. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 32, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated uric acid concentration.

[0131]

FIG. 32

From this figure, the measured value of the uric acid measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional uric acid measuring reagent containing the antibacterial substance therein. It is the same as the measured value of, and there is no difference in linearity, which means that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a uric acid measuring reagent that does not contain the antibacterial substance is deteriorated. It was confirmed that it could be stably stored without any.

Example 35 Storage of Glutamate Oxaloacetate Transaminase Assay Reagent in a Container Having a Solid Material Containing an Antibacterial Substance Stored in a Container A container was filled with a reagent for measuring glutamate oxaloacetate transaminase (GOT), which is a clinical test agent, and its preservative effect was confirmed. In Example 30, the first reagent of (3) was treated with 20 mg / dl of nicotinamide adenine dinucleotide disodium (reduced form) and 200 units /
changing to a reagent consisting of 80 mmol / l Tris buffer (pH 8.0) containing dl malate dehydrogenase,
The second reagent of (3) was added to 8.7 g / dl sodium L-aspartate and 0.53 g / dl α-ketoglutaric acid in 80 mmol / l Tris buffer (pH 8.
In the measurement in (6), 250 μl of the first reagent was added to 20 μl of the sample, the mixture was reacted at 37 ° C. for 5 minutes, and 125 μl of the second reagent was added, and the main wavelength was 3
The GOT activity value is calculated from the rate of decrease in absorbance from 2 minutes to 5 minutes after the addition of the second reagent at 40 nm and the subwavelength of 405 nm, and the sample of (6) has a GOT activity value of 2.
The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 30 except that the 830 units / l serum sample was changed to a diluted sample diluted with pure water in 10 steps.
The linearity test results of this stored reagent are shown in FIG. In FIG. 33, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated GOT activity value.

[0134]

FIG. 33

From this figure, the measured value of the GOT measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional GO containing the antibacterial substance.
Since it is the same as the measured value of the T measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a GOT measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it could be preserved stably.

Example 36 Preservation of serum iron measuring reagent in a container containing a solid substance containing an antibacterial substance In a container containing a solid substance containing an antibacterial substance in a container , Containing the serum iron measuring reagent which is a clinical test agent,
The preservation effect was confirmed. (3) in Example 30
150 mmol / l Tris buffer (pH 5.5) containing 20 mmol / l L-ascorbic acid.
Of the second reagent of (3) to 0.4
5 mmol / l 2-nitroso-5- (N-propyl-
N-Sulfopropylamino) -phenol containing 150
After changing to a reagent consisting of mmol / l Tris buffer (pH 5.5) and measuring in (6), after adding 250 μl of the first reagent to 20 μl of the sample and reacting at 37 ° C. for 5 minutes,
100 μl of the second reagent is added, and the serum iron concentration is calculated from the increase in the absorbance at the main wavelength of 750 nm and the sub-wavelength of 600 nm until 5 minutes after the addition of the second reagent, and (6)
Of the reagent and the linearity test of the preserved reagent in the same manner as in Example 30 except that the serum sample having a serum iron concentration of 1,100 μg / dl was changed to a diluted sample diluted with pure water in 10 steps. I went. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 34, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated serum iron concentration.

[0137]

FIG. 34

From this figure, the measured value of the serum iron measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional serum iron containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance is deteriorated even in a serum iron measurement reagent containing no antibacterial substance therein. It was confirmed that it can be stored stably without any damage.

Example 37 Storage of Lactate Dehydrogenase Assay Reagent in Container Containing Solid Material Containing Antibacterial Substance Containing Solid Material Containing Antibacterial Substance in Container The container was filled with a reagent for measuring lactate dehydrogenase (LDH), which is a clinical test agent, and its preservative effect was confirmed. Example 3
80 mg / dl Tris buffer (pH 7.) containing 16 mg / dl of nicotinamide adenine dinucleotide disodium (reduced form) as the first reagent of (3).
5) changing to a reagent consisting of 8)
80 mmol containing 9 mg / dl lithium pyruvate
/ L of Tris buffer (pH 7.5) was used as the reagent, and the measurement in (6) was carried out by adding the first reagent 30 to the sample 7 μl.
After adding 0 μl and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added, and the main wavelength was 340 nm and the sub wavelength was 405 nm.
calculating the LDH activity value from the rate of decrease in absorbance from 1 minute to 3 minutes after the addition of the second reagent in nm, and (6)
Of the reagent and the linearity of the stored reagent in the same manner as in Example 30 except that the serum sample having an LDH activity value of 6,890 units / l was diluted with pure water in 10 steps. The test was conducted. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 35, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated LD.
Represents H activity value.

[0140]

FIG. 35

From this figure, the measured value of the LDH measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional LD containing the antibacterial substance.
Since it is the same as the measured value of the H measuring reagent, there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an LDH measuring reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 38 Preservation of Inorganic Phosphorus Measuring Reagent in a Container Containing a Solid Material Containing an Antibacterial Substance In a container containing a solid material containing an antibacterial substance in a container , A clinical laboratory drug containing inorganic phosphorus was stored and its storage effect was confirmed. In Example 30,
The first reagent of (3) was used as 7.0 kg / l xanthine oxidase, 1.0 kg / l purine nucleoside phosphorylase and 5.4 mmol / l N-ethyl-.
-N- (2-succinylaminoethyl) -m-toluidine in 80 mmol / l Good buffer (pH 7.
2) changing the second reagent of (3) to 5.0 mmol / l of 4-aminoantipyrine, 5.0
Xanthine oxidase (kg / l), 13 mmol
80 mmol / l Good's buffer (pH 7.) containing 1 / l inosine and 20 kg / l peroxidase.
In the measurement in (6), the first reagent (300 μl) was added to the sample (3 μl), and the mixture was reacted at 37 ° C. for 5 minutes.
Second reagent addition at 0 nm and subwavelength 700 nm 5
Except that the inorganic phosphorus concentration is calculated from the amount of increase in the absorbance up to the minute and that the sample in (6) is changed to a diluted sample obtained by diluting a serum sample with an inorganic phosphorus concentration of 50 mg / dl in 10 steps with pure water. The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 30. The results of the linearity test of the stored reagent are shown in FIG. In addition, this FIG.
6, the horizontal axis represents the serum sample dilution rate and the vertical axis represents the calculated inorganic phosphorus concentration.

[0143]

FIG. 36

From this figure, the measured value of the inorganic phosphorus measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional inorganic phosphorus containing the antibacterial substance. Since it is the same as the measured value of the measurement reagent and there is no difference in linearity, it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of an inorganic phosphorus measuring reagent not containing the antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 39 Preservation of leucine aminopeptidase assay reagent in a container containing a solid containing an antibacterial substance A container containing a solid containing an antibacterial substance in a container Then, a reagent for measuring leucine aminopeptidase (LAP), which is a clinical test agent, was housed in the container and its storage effect was confirmed. 50 mm of the first reagent of (3) in Example 30
Change to a reagent consisting of ol / l Tris buffer (pH 7.5), the second reagent in (3) is added to 12 mmol / l L
50 mm containing leucine-4-nitroanilide hydrochloride
Change to a reagent composed of ol / l Tris buffer (pH 7.5), and in the measurement in (6), after adding 260 μl of the first reagent to 8 μl of the sample and reacting at 37 ° C. for 5 minutes, the second reagent was added. 130 μl was added, and the LAP activity value was calculated from the rate of increase in absorbance from 1 minute to 5 minutes after the addition of the second reagent at the main wavelength of 405 nm and the sub-wavelength of 480 nm. Reagent storage and the linearity test of the stored reagents were performed in the same manner as in Example 30 except that the serum sample (unit / l) was changed to a diluted sample diluted with pure water in 10 steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 37, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated LAP activity value.

[0146]

FIG. 37

From this figure, the measured value of the LAP measuring reagent contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional LA containing the antibacterial substance.
Since it is the same as the measured value of the P measurement reagent, there is no difference in linearity, and it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a LAP measuring reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 40 Preservation of Reagent for Measuring Phospholipids in a Container Having a Solid Material Containing an Antibacterial Substance in a Container A container having a solid material containing an antibacterial substance contained in a container , A phospholipid measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 30,
56 units / dl of phospholipase D of the first reagent of (3)
And 25 mg / dl N- (2-hydroxy-3-sulfopropyl) -3,5-dimethoxyaniline sodium containing 50 mmol / l Good's buffer (pH 8.
0), the second reagent in (3) is 1,200 units / dl choline oxidase, 35 mg
/ Dl 4-aminoantipyrine and 50 mmol / l Good's buffer (pH 8.0) containing 1,800 units / dl peroxidase.
In the measurement in (6), after adding 300 μl of the first reagent to 4 μl of the sample and reacting at 37 ° C. for 5 minutes, 75 μl of the second reagent was added.
Phospholipid concentration is calculated from the amount of increase in absorbance at 5 minutes after the addition of the second reagent at the main wavelength of 600 nm and the sub-wavelength of 700 nm, and the sample of (6) is serum with a phospholipid concentration of 1,050 mg / dl. The reagents were stored and the stored reagents were tested for linearity in the same manner as in Example 30, except that the sample was changed to a diluted sample diluted with pure water in eight steps. The results of the linearity test of this stored reagent are shown in FIG. In FIG. 38, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated phospholipid concentration.

[0149]

FIG. 38

From this figure, the measured value of the phospholipid measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the value obtained by the conventional phospholipid containing the antibacterial substance. Since it is the same as the measured value of the measurement reagent and there is no difference in linearity, it can be seen that there is no practical problem. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of the phospholipid measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 41 Preservation of a reagent for measuring unsaturated iron binding capacity in a container in which a solid substance containing an antibacterial substance is contained in a container A solid substance containing an antibacterial substance is contained in a container The reagent for measuring unsaturated iron binding capacity, which is a clinical test agent, was stored in the container, and its preservative effect was confirmed. In Example 30, the first reagent of (3) is a reagent consisting of 100 mmol / l Tris-hydrochloric acid buffer solution (pH 8.5) containing 1 mmol / l sodium citrate and 0.05 mmol / l ferric ammonium sulfate. Changing the second reagent of (3) to 29 mmol / dl of 2-nitroso-5- (N-propyl-N-sulfopropylamino) -phenol in 100 mmol / l Tris-HCl buffer (pH 8.
5), the reagent for linearity test of (5) is a reagent after 82 days of storage, and the measurement in (6) is carried out by adding 250 μl of the first reagent to 20 μl of the sample.
After reacting at 5 ° C. for 5 minutes, 125 μl of the second reagent was added, and the unsaturated iron binding capacity was calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 750 nm and the sub-wavelength of 600 nm. Reservation of reagents and the linearity of stored reagents in the same manner as in Example 30 except that the serum sample having an unsaturated iron binding capacity of 855 μg / dl was replaced with a diluted sample diluted with pure water in 10 steps. A sex test was conducted. The linearity test results of this stored reagent are shown in FIG. In FIG. 39, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated unsaturated iron binding capacity.

[0152]

FIG. 39

From this figure, the measured value of the unsaturated iron binding capacity measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional value containing the antibacterial substance. It is the same as the value measured by the unsaturated iron binding capacity measurement reagent of No. 1, and there is no difference in linearity, and it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of the unsaturated iron binding capacity measurement reagent containing no antibacterial substance is also improved. It was confirmed that it can be stored stably without deteriorating.

Example 42 Preservation of Total Cholesterol Measuring Reagent in a Container Containing a Solid Material Containing an Antibacterial Substance In a container containing a solid material containing an antibacterial substance in a container Then, the total cholesterol measuring reagent, which is a clinical test drug, was stored and its preservative effect was confirmed. In Example 30, the first reagent of (3) is a reagent comprising 0.44 mmol / l of 4-aminoantipyrine and 1,000 units / l of cholesterol esterase in 50 mmol / l of Good's buffer solution (pH 7.0). Change to (3)
330 units / l of cholesterol oxidase, 1.63 mmol / l of N- (2-hydroxy-
3-sulfopropyl) -3,5-dimethoxyaniline sodium and 50 mmol / l Good's buffer (pH 7.0) containing 1.6 kg / l peroxidase.
The reagent to be tested for linearity in (5) is a reagent after 82 days of storage, and the measurement in (6) was carried out by adding 300 μl of the first reagent to 4 μl of the sample and heating at 37 ° C.
After reacting for a minute, 100 μl of the second reagent is added, and the total cholesterol concentration is calculated from the increase in absorbance up to 5 minutes after the addition of the second reagent at the main wavelength of 600 nm and the sub wavelength of 700 nm, and the sample of (6) Was stored in the same manner as in Example 30 except that the serum sample having a total cholesterol concentration of 980 mg / dl was changed to a diluted sample diluted with pure water in 10 steps, and the linearity test of the stored reagent was performed. FIG. 40 shows the linearity test result of the stored reagent.
It was shown to. In FIG. 40, the horizontal axis represents the dilution ratio of the serum sample and the vertical axis represents the calculated total cholesterol concentration.

[0155]

FIG. 40

From this figure, the measured value of the total cholesterol measuring reagent stored in the container in which the solid substance containing the antibacterial substance is contained is the conventional total cholesterol containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance is deteriorated even in a reagent for measuring total cholesterol containing no antibacterial substance therein. It was confirmed that it can be stored stably without any damage.

Example 43 Preservation of Free Cholesterol Measurement Reagent in a Container Containing a Solid Material Containing an Antibacterial Substance In a container containing a solid material containing an antibacterial substance , A free cholesterol measuring reagent, which is a clinical test agent, was stored and its preservative effect was confirmed. In Example 30, the first reagent of (3) was added to 0.35 mmol / l of 4-
Changing to a reagent consisting of 50 mmol / l Good's buffer (pH 7.0) containing aminoantipyrine, (3)
The second reagent of 1.65 kg / l cholesterol oxidase, 2.4 mmol / l N- (2-hydroxy-3-sulfopropyl) -3,5-dimethoxyaniline sodium and 10 kg / l peroxidase. 50 mmol / l Good's buffer (pH 7.
0), the reagent to be tested for linearity in (5) is a reagent after 82 days of storage, and the measurement in (6) was carried out by adding 300 μl of the first reagent to 4 μl of the sample at 37 ° C.
After reacting for 5 minutes with 100 μl of the second reagent,
Second at 600nm main wavelength and 700nm sub wavelength
The free cholesterol concentration is calculated from the increase in the absorbance up to 5 minutes after the addition of the reagent, and the serum sample with the free cholesterol concentration of 685 mg / dl is diluted with pure water to 1) in (6).
The reagents were stored and the linearity of the stored reagents was tested in the same manner as in Example 30 except that the diluted sample was diluted to 0 steps. The results of the linearity test of this stored reagent are shown in FIG. 41. In FIG. 41, the horizontal axis represents the serum sample dilution rate and the vertical axis represents the calculated free cholesterol concentration.

[0158]

FIG. 41

From this figure, the measured value of the reagent for measuring free cholesterol contained in the container in which the solid substance containing the antibacterial substance is contained is the conventional free cholesterol containing the antibacterial substance. Since it is the same as the measured value of the measuring reagent and there is no difference in linearity, it can be seen that there is no problem in practical use. Therefore, by storing and storing a solid substance containing an antibacterial substance in a container, the performance of a free cholesterol measurement reagent containing no antibacterial substance is deteriorated. It was confirmed that it can be stored stably without any damage.

Example 44 Effect of Container Containing Antibacterial Substance in Container Wall on Sodium Azide Resistant Bacteria Effect of Container Containing Antibacterial Substance in Container Wall on Sodium Azide Resistant Bacteria I confirmed. (1) Pure culture of a resistant bacterium resistant to sodium azide was carried out. In addition, glucose non-fermenting Gram-negative bacillus identification I
D test NF-18 (manufactured by Nissui Pharmaceutical Co., Ltd.) was used. R. N
edited by Oel et al. "Bergey's Manual ofS"
ystematic Bacteriology Vo
lume 1 ", Williams & Wilkins,
1984. When this bacterium was identified by Pseudomonas sp. (2) The container 2 described in (2) of Example 1, the container 6 described in (6) of Example 1, the control container A described in (8) of Example 1, and the container described in Example 7. Add 10% each of the reagents prepared by adding sodium azide to the second reagent to 0.1%.
0 ml each was injected, and the purely cultured bacteria of (1) were further inoculated into each to seal the mouth. (3) The container 2, container 6 and control container A inoculated with the bacteria in (2) were stored for 1 week in an incubator at 25 ° C, and the viable cell count of sodium azide-resistant bacteria in these containers was measured. I went. The results of this measurement are shown in Table 4.

[0161]

[Table 4]

From this table, in the control container A in which the antibacterial substance is not contained in the container wall, the viable count of sodium azide-resistant bacteria in the container increases with time, whereas the antibacterial substance In the container 2 and the container 6 contained in the container wall, it can be seen that all the sodium azide-resistant bacteria in the container are dead after 1 week of storage. Therefore, by using a container containing the antibacterial substance of the present invention in the container wall, it is possible to prevent sodium azide-resistant bacteria from propagating to the contents in the container, and the contents in the container. It was shown that the product can be stably stored.

[0163]

EFFECTS OF THE INVENTION The present invention has solved the problems of the conventional method for preventing the growth of microorganisms in the contents by containing the antibacterial substance in the contents. According to the present invention, an antibacterial substance is contained in a container wall and a substance to be preserved is stored and stored, or a substance to be preserved and a solid substance containing the antibacterial substance are accommodated in the same container. Used as an antibacterial substance that is useful as an antibacterial substance and may adversely affect the person who ingested the antibacterial substance, or an antibacterial substance that is insoluble or sparingly soluble in an aqueous solution. It has become possible to use antibacterial substances that could not be obtained. As a result, even for substances (contents) that are difficult to store for a long time with conventional antibacterial substances, it is possible to use the antibacterial substances that could not be used conventionally for stable storage for a long period of time. became. And, by enabling the use of an antibacterial substance that could not be used conventionally, it does not adversely affect the components or effects of the substance (content) to be preserved, and the specific substance (content) to be preserved.
When searching for an antibacterial substance having antibacterial activity, the range and number of candidate antibacterial substances increases, so the probability of finding an antibacterial substance that meets the requirements increases, and this search is more effective. It will be more efficient and save time, time and money for the results of this search.
We were able to improve cost performance.

Further, by containing the antibacterial substance in the container wall or by containing the antibacterial substance in the solid matter, the antibacterial substance contained in the container wall or in the solid matter is decomposed or inactivated. It is possible to suppress the proliferation of microorganisms for a long period of time, and to suppress the emergence of resistant bacteria, and to store the desired contents (contents) stably for a long period of time. It has become possible. Then, even if the container is used repeatedly, it is possible to prevent microorganisms from propagating in the contents and to stably store the contents. Furthermore, by making it possible to use antibacterial substances that could not be used in the past, it becomes possible to suppress resistant bacteria resistant to the antibacterial substances that have been used in the past, and it is desired to store the contents (contents). It has become possible to store for a long time stably.

[Brief description of drawings]

FIG. 1 is a graph showing the linearity of an alkaline phosphatase measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 2 is a graph showing the linearity of a γ-glutamyl transpeptidase measurement reagent stored in a container containing an antibacterial substance in the container wall.

FIG. 3 is a graph showing the linearity of a glucose measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 4 is a graph showing the linearity of a uric acid measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 5 is a graph showing the linearity of a glutamate oxaloacetate transaminase assay reagent stored in a container containing an antibacterial substance in the container wall.

FIG. 6 is a graph showing the linearity of a glutamate pyruvate transaminase measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 7 is a graph showing the linearity of a cholinesterase measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 8 is a graph showing the linearity of a serum iron measuring reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 9 is a graph showing the linearity of an unsaturated iron binding capacity measurement reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 10 is a graph showing the linearity of a lactate dehydrogenase assay reagent contained in a container containing an antibacterial substance in the container wall.

FIG. 11 is a graph showing the linearity of an alkaline phosphatase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 12 is a graph showing the linearity of an alkaline phosphatase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 13 is a graph showing the linearity of an α-amylase measuring reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 14 is a graph showing the linearity of a γ-glutamyl transpeptidase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 15 is a graph showing the linearity of a creatinine measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 16 is a graph showing the linearity of a glucose measuring reagent contained in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 17 is a graph showing the linearity of a uric acid measuring reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 18 is a graph showing the linearity of a glutamate oxaloacetate transaminase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 19 is a graph showing the linearity of a glutamate pyruvate transaminase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 20 is a graph showing the linearity of a cholinesterase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 21 is a graph showing the linearity of a serum iron measuring reagent contained in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 22 is a graph showing the linearity of a lactate dehydrogenase assay reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 23 is a graph showing the linearity of a leucine aminopeptidase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 24 is a graph showing the linearity of a phospholipid measurement reagent stored in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 25 is a graph showing the linearity of an unsaturated iron binding capacity measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 26 is a graph showing the linearity of a total cholesterol measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 27 is a graph showing the linearity of a reagent for measuring free cholesterol contained in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 28 is a graph showing the linearity of an alkaline phosphatase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 29 is a graph showing the linearity of an alkaline phosphatase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 30 is a graph showing the linearity of an α-amylase measuring reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 31 is a graph showing the linearity of a γ-glutamyl transpeptidase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 32 is a graph showing the linearity of a reagent for measuring uric acid stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 33 is a graph showing the linearity of a glutamate oxaloacetate transaminase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 34 is a graph showing the linearity of a serum iron measuring reagent contained in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 35 is a graph showing the linearity of a lactate dehydrogenase assay reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 36 is a graph showing the linearity of an inorganic phosphorus measuring reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 37 is a graph showing the linearity of a leucine aminopeptidase measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 38 is a graph showing the linearity of a phospholipid measurement reagent contained in a container in which a solid substance containing an antibacterial substance is contained.

FIG. 39 is a graph showing the linearity of an unsaturated iron binding capacity measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 40 is a graph showing the linearity of a total cholesterol measurement reagent stored in a container in which a solid substance containing an antibacterial substance is stored.

FIG. 41 is a graph showing the linearity of a reagent for measuring free cholesterol contained in a container in which a solid substance containing an antibacterial substance is contained.

Claims (12)

[Claims] 1. A method for preserving an article, which comprises storing an article to be preserved in a container containing an antibacterial substance in a container wall. 2. The method for preserving a substance according to claim 1, wherein the substance to be preserved is a substance containing a substance involved in an enzymatic reaction. 3. The method for preserving a substance according to claim 1, wherein the substance to be preserved is a substance containing a substance involved in an antigen-antibody reaction. 4. A method for preserving an object, wherein an object to be preserved and a solid substance containing an antibacterial substance are contained in the same container for preservation. 5. The method for preserving a substance according to claim 4, wherein the substance to be preserved is a substance containing a substance involved in an enzymatic reaction. 6. The method for preserving an item according to claim 4, wherein the item to be preserved is a substance containing a substance involved in an antigen-antibody reaction. 7. A container containing an antibacterial substance in a container wall. 8. The container according to claim 7, wherein the container is a container for containing a substance containing a substance involved in an enzymatic reaction. 9. The container according to claim 7, wherein the container is a container for containing a substance containing a substance involved in an antigen-antibody reaction. 10. A container comprising a solid material containing an antibacterial substance contained in the container. 11. The container according to claim 10, wherein the container is a container for containing a substance containing a substance involved in an enzymatic reaction. 12. The container according to claim 10, wherein the container is a container for containing a substance containing a substance involved in an antigen-antibody reaction.