JPH07167716A - Sample container lid with heat sensitive indicator - Google Patents

Abstract

(57) [Summary] [Purpose] To provide a sample container lid with a thermosensitive indicator that can be stably stored even at room temperature, has a simple mechanism for setting the temperature monitoring state, and has high accuracy. [Structure] The hollow at the bottom of the cylinder 4 is a lid fitted into the head of the sample container 9. The recess 3 of the cylinder 4 closed by the thin foil 7
The colored heat-fusible substance 6 is stored in. The permeation layer 2 is arranged in contact with the outer surface of the thin foil 7, and the projection 1 connected to the head that can be depressed extends through the hole of the permeation layer 2 to the vicinity of the thin foil 7. Sample container 9 in which sample, blood, etc. are dispensed
By pressing the protrusion 1 when fitting the hollow at the bottom of the cylinder 4 into the, the sharp tip of the protrusion 1 breaks the thin foil 7. When the temperature rises, the solidified colored heat-fusible substance 6 melts and propagates through the protrusions 1 and permeates the permeation layer 2.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample container lid with a heat sensitive indicator which is fitted into a sample container containing a drug during quality control of the drug at a low temperature.

[0002]

2. Description of the Related Art In recent years, with regard to quality control of pharmaceutical products, various measures have been taken, such as revision of the Pharmaceutical Affairs Law and legislation of GMP (standard for manufacturing and quality of pharmaceutical products). In order to ensure the quality of pharmaceuticals, not only quality control at the manufacturing stage but also proper quality control at the distribution stage is important. Depending on the temperature control during the analysis of a special vaccine, human blood, etc., there is a problem that the analysis value changes and the required value cannot be obtained.

One of means for solving such a problem is to use a heat sensitive indicator. For example, Japanese Patent Laid-Open No. Sho 50
-60262, JP-A-51-33432,
Japanese Patent Laid-Open No. 5-72054 discloses a time-temperature integrating type monitor showing a temperature history. JP 61-
No. 13116 and Japanese Patent Laid-Open No. 62-197486 disclose a temperature-time monitor using microcapsules. JP-A-59-164929 and JP-A-59-175172 describe indicators utilizing the capillary phenomenon.

[0004]

Drugs requiring low-temperature control are stored and distributed inside containers. Although the temperature of the drug in the container is controlled by the indicator, it is difficult to actually monitor the storage temperature of the drug in the container because the temperature history is unstable at low temperature. When the temperature is controlled by the indicator, the indicator is sufficiently cooled to the temperature inside the refrigerator to be monitored, and then attached to the container and set in the temperature monitoring state. It takes time for the indicator to detect the temperature after it is set and for the storage temperature to be monitored. The indicator contains a substance that senses temperature changes in the low temperature range. This substance is very volatile at room temperature. The volatility reduces the accuracy of the heat sensitive indicator, making it impossible to accurately control the temperature of the drug.

The present invention has been made to solve the above problems, and provides a specimen container lid with a heat sensitive indicator, which can be stably stored even in a normal temperature range, has a simple mechanism for setting a temperature monitoring state, and has high accuracy. The purpose is to do.

[0006]

A sample container lid with a heat-sensitive indicator of the present invention made to achieve the above object will be described with reference to FIG. 1 corresponding to an embodiment. In the figure, the hollow at the bottom of the cylinder 4 is a lid fitted into the head of the sample container 9. The colored heat-meltable substance 6 is stored in the concave portion 3 of the cylinder 4 which is closed by the thin foil 7. The permeation layer 2 is arranged in contact with the outer surface of the thin foil 7, and the protrusions 1 connected to the retractable head extend through the holes of the permeation layer 2 to the vicinity of the thin foil 7.

The column 4 is made of a material capable of storing the colored heat-fusible substance 6 in the recess 3 for a certain period of time, such as polyvinyl chloride, polystyrene, non-axially oriented polypropylene, high density polyethylene, polyethylene terephthalate, polycarbonate,
Examples include non-stretched nylon, acrylonitrile, and cellulose acetate. Further, a composite material of these may be used.

The thin foil 7 preferably has a thickness that closes the concave portion 3 of the cylinder 4 and is easily broken by the protrusion 1, for example, an aluminum film.

The colored heat-fusible substance 6 contains a heat-fusible substance and a dye. Examples of the heat-fusible substance include substances that melt at a desired temperature, for example, alcohols, esters, hydrocarbon compounds, ketones, ethers, inorganic and organic freezing point depressant substances.

Alcohols include n-octyl alcohol, n-nonyl alcohol, n-decyl alcohol, and n.
-Lauryl alcohol, n-myristyl alcohol, n
-Cetyl alcohol, n-stearyl alcohol, olein alcohol, cyclohexanol, cyclopentanol, benzyl alcohol, cinnamyl alcohol, ethylene glycol, polyethylene glycol, propylene glycol, trimethylolpropane, pentaerythritol, sorbit and the like can be mentioned.

Esters include amyl acetate, octyl acetate, butyl propionate, ethyl caproate, amyl caprylate, ethyl caprate, octyl caprate, lauryl caprate, methyl laurate, octyl laurate, lauryl laurate, Methyl myristate, hexyl myristate, stearyl myristate, butyl palmitate, myristyl palmitate, methyl stearate, ethyl stearate, lauryl stearate, butyl benzoate, amyl benzoate, phenyl benzoate, ethyl acetoacetate, oleic acid Methyl, butyl acrylate, butyl oxalate, diethyl malonate, dibutyl tartrate, dimethyl sebacate, dibutyl phthalate, dioctyl phthalate, dibutyl fumarate, diethyl maleate, triethyl citrate. , 1,2-hydroxystearic acid triglyceride, castor oil, etc. dioxy stearic acid methyl ester.

The hydrocarbon compounds include aliphatic hydrocarbons such as pentadecane, tetradecane, hexadecane, 1-heptadecane and 1-octadecane, and aromatic hydrocarbon compounds such as p-xylene and dodecylbenzene.

Ketones include diethyl ketone, ethyl butyl ketone, methylhexyl ketone, mesityl oxide,
Examples thereof include cyclohexanone, methylcyclohexanone, acetophenone, benzophenone, acetonylacetone and diacetone alcohol.

Examples of ethers include butyl ether, hexyl ether, diphenyl ether, dioxane, ethylene glycol dibutyl ether, diethylene glycol dibutyl ether, ethylene glycol diphenyl ether and ethylene glycol monophenyl ether.

Inorganic and organic aqueous solutions of freezing point depressants include sodium carbonate, ammonium hydrogen carbonate, potassium hydrogen carbonate, ammonium chloride, potassium chloride, sodium chloride, magnesium chloride, calcium chloride, sodium nitrate, ammonium nitrate, urea and hydrogen carbonate. Examples thereof include aqueous solutions of sodium, sodium thiosulfate, glucose, sucrose, fructose and the like. Also, water alone may be used.
These heat-meltable substances may be used alone or in a mixture.

The dye which is the other component of the colored heat-fusible substance 6 may be any dye that can be dissolved in the heat-fusible substance. Examples thereof include oil-soluble dyes, direct dyes, acid dyes, basic dyes, mordant dyes, sulfur dyes, sulfur vat dyes, vat dyes, azoic dyes, disperse dyes, reactive dyes, and oxidation dyes. A pigment may be used depending on the case. Specific examples of the oil-soluble dye include Sudan IV manufactured by Wako Pure Chemical Industries, Ltd., Oil Red 5B, Oil Red RR, Oil Or manufactured by Orient Chemical Industry.
ange 201, Oil Blue 2N, Oplas Violet 732, OilYellow
3G, Oil Brown BB, Oil Brown GR, Oil Green BG, Diaresin Blue J manufactured by Mitsubishi Chemical Co., Ltd., and Kayaset Red 802 manufactured by Nippon Kayaku Co., Ltd. Diacellition Fast manufactured by Mitsubishi Chemical Industries, Ltd.
Violet B, Diacellition Fast Brilliant Blue BM / D,
Nippon Kayaku Co., Ltd. Kayalon Fast Brilliant Green GC
Is mentioned.

The permeation layer 2 is preferably one that allows the colored heat-fusible substance 6 to permeate stably. For example, porous films, qualitative filter papers, quantitative filter papers, glass fiber filter papers, filter papers such as chromatography filter papers, pulp, cotton, non-woven fabrics, silica gel, porous endless sinters and composites thereof are mentioned.

The projection 1 has a sharp tip perpendicular to the thin foil 7 so that the thin foil 7 blocking the recess 3 of the cylinder 4 can be broken. It is preferable that the material of the protrusion 1 has such strength that the head is deformed without being broken by the pressure during use. Examples thereof include polyvinyl chloride, polystyrene, polyethylene terephthalate, polycarbonate, nylon and cellulose acetate.

[0019]

When the sample container lid with a heat sensitive indicator of the present invention is used, the colored heat-meltable substance 6 stored in the recess 3 of the column 4 is solidified by cooling. When the protrusion 1 is pushed when the hollow portion in the lower portion of the sample container lid is fitted into the sample container 9 containing the sample, blood, etc., the sharp tip of the protrusion 1 breaks the thin foil 7. When the temperature rises, the colored heat-fusible substance 6 melts, propagates through the protrusions 1 and permeates the permeation layer 2. Through the stopper 5 which is a transparent material, the coloring of the permeation layer 2 by the colored fusible substance 6 can be visually observed.

[0020]

EXAMPLES Examples of the present invention will be described below. FIG. 1 is a cross-sectional perspective view of essential parts of an embodiment of a sample container lid with a heat sensitive indicator to which the present invention is applied. A recess 3 is formed in the cylinder 4, and the lower part is hollow. The hollow portion is fitted into the head of the sample container 9. A colored heat-melting substance 6 is housed in the concave portion 3, and the concave opening is closed by a thin foil 7. The permeation layer 2 is arranged on the circumscribing surface of the thin foil 7. A hole is formed in the center of the permeation layer 2, and the protrusion 1 is arranged through the hole to the vicinity of the thin foil 7. The column 4, the thin foil 7, the permeation layer 2 and the protrusion 1 are the stoppers 5.
It is fixed at. A transparent material is used for the stopper 5 so that the state in which the permeation layer 2 is colored with the colored fusible substance 6 can be visually observed.

When the protrusion 1 is pushed when the sample container lid with the heat sensitive indicator is fitted into the sample container 9, the sharp tip of the protrusion 1 surely breaks the thin foil 7 at one point. When the temperature rises, the solidified colored heat-fusible substance 6 melts, propagates through the protrusions 1 and permeates the permeation layer 2. Through the stopper 5 which is a transparent material, the coloring of the permeation layer 2 by the colored fusible substance 6 can be visually observed.

FIG. 2 is a cross-sectional perspective view of an essential part of another embodiment of the sample container lid with the heat sensitive indicator to which the present invention is applied.
A transparent material is used for the column 4 so that the state in which the permeation layer 2 is colored with the colored fusible substance 6 can be visually observed. A stopper 8 is inserted between the column 4 and the protrusion 1,
Is fixed. The inner space of the cylinder 4 is filled with the permeation layer 2, and the center of the permeation layer 2 is hollow. The protrusions 1 are arranged through the cavity to the vicinity of the thin foil 7.

When the stopper 8 is pulled out after fitting the sample container lid with the heat sensitive indicator into the sample container 9, the fixed projection 1 drops to the column 4. When dropped, the sharp tip of the protrusion 1 breaks the thin foil 7. When the temperature rises, the solidified colored heat-fusible substance 6 melts, propagates through the protrusions 1 and permeates the permeation layer 2. The coloring of the permeation layer 2 can be visually observed through the cylinder 4 which is a transparent material.

Example 1 0.1 g of the colored heat-meltable substance 6 is filled in the concave portion 3 of the polypropylene cylinder 4. Colored heat-fusible substance 6 is 7.0 g
A mixture of decyl alcohol of 13.0 g and lauryl alcohol of 13.0 g is colored blue with 0.02 g of Spilon Blue 2BNH (Hodogaya Chemical Co., Ltd.) and is liquid at room temperature.
Below 0 degrees, it is a solid. The concave opening of the cylinder 4 is heat-sealed with a thin foil 7 made of an aluminum film coated with a lacquer. The aluminum film may have a thickness that can be easily broken by an external force. The permeation layer 2 is arranged on top of the aluminum film 7. The permeation layer 2 has a filter paper No. 50 (manufactured by Toyo Roshi Kaisha, Ltd.) is used. A hole is formed in the center of the permeation layer 2, and the protrusion 1 is arranged near the thin foil 7 through the hole. The protrusion 1 is made of polyvinyl chloride, which deforms when pressure is applied and is dented in the lower part. The whole was fixed with a stopper 5 made of a transparent material to obtain a sample container lid with a heat sensitive indicator.

This sample container lid with a heat sensitive indicator
It was cooled at 16 ° C. for 3 hours to solidify the encapsulated colored heat-fusible substance 6. Blood or a sample was collected in the sample tube 9, the hollow portion of the lower portion of the indicator-equipped sample container lid was fitted into the sample tube 9, and the head of the protrusion 1 was pressed with a finger. The protrusion 1 pushed in broke the aluminum film 7, and the heat sensitive indicator entered the temperature monitoring state. The tube with the thermosensitive indicator that had entered the temperature monitoring state was stored at 5 ° C., but the permeation layer 2 was not colored. on the other hand,
When exposed to an environment of 10 degrees or more, the heat fusible substance (mixed solution of decyl alcohol and lauryl alcohol) which is a component of the colored heat fusible substance 6 and Spilon Blue 2BNH were melted and diffused into the permeation layer 2. It was confirmed that the permeation layer 2 was colored to raise the temperature.

Example 2 0.1 g of the colored heat-fusible substance 6 is filled in the concave portion 3 of the polypropylene cylinder 4. The coloring heat-meltable substance 6 is water 10
0 g is colored with Acidoviolet 6B (manufactured by Daiwa Kasei Co., Ltd.). An aluminum seal was used for the thin foil 7, and the concave opening of the cylinder 4 was heat-sealed with an aluminum seal as in Example 1. The permeation layer 2 is arranged in the inner space of the cylinder 4. Absorbent cotton is used for the permeation layer 2. The projections 1 made of polyvinyl chloride can easily break this aluminum seal. A stopper 8 was inserted between the protrusion 1 and the column 4 to fix the protrusion 1 to obtain a sample container lid with a thermosensitive indicator.

This sample container lid with an indicator is -16
The colored thermofusible substance 6 contained therein was solidified by cooling at 3 ° C. for 3 hours. After collecting blood and a sample into the sample tube 9, the hollow portion of the sample container lid with an indicator was fitted into the sample tube 9. After that, pull out the stopper 8 and the protrusion 1
By pressing, the thermal indicator entered the temperature monitoring state. When this tube with a heat-sensitive indicator was exposed to an environment of 0 ° C. or higher, water as a component of the colored heat-meltable substance 6 and acid violet 6B were melted and diffused into the permeation layer 2. It was confirmed that the coloring of the permeation layer 2 caused a temperature increase.

[0028]

As described above in detail, according to the sample container lid with the thermosensitive indicator of the present invention, the temperature monitoring during the low temperature control of special vaccines, human blood, etc. can be visually confirmed, so that the temperature control can be performed. The quality control at the distribution stage can be optimized. Fit the hollow part into the sample container,
The temperature can be easily monitored by simply pressing the protrusion.
Since the sharp portion of the protrusion breaks the thin foil at one point, the starting point of permeation of the colored heat-fusible substance becomes constant, and the permeation distance error seen so far is eliminated. The colored heat-fusible substance is sealed in the concave part of the cylinder, so it will not volatilize,
Can be used stably even at room temperature. The melting temperature can be freely adjusted by appropriately changing the type of the heat-melting substance that is the main component of the colored heat-melting substance.

[Brief description of drawings]

FIG. 1 is a perspective cross-sectional view of a main part of an embodiment of a sample container lid with a heat-sensitive indicator to which the present invention is applied.

FIG. 2 is a perspective view of a main part of another embodiment of the sample container lid with the heat-sensitive indicator to which the present invention is applied.

[Explanation of symbols]

Reference numeral 1 is a protrusion, 2 is a permeation layer, 3 is a concave portion, 4 is a cylinder, 5 is a stopper, 6 is a colored heat-fusible substance, 7 is a thin foil, 8 is a stopper, and 9 is a sample container.

Claims (1)

[Claims] 1. A hollow at the bottom of a cylinder is a lid that fits into the head of a sample container, and a colored heat-melting substance is stored in a cylindrical recess closed by a thin foil and is in contact with the outer surface of the thin foil. A sample container lid with a heat-sensitive indicator, wherein a permeation layer is disposed on the sample container, and a projection connected to a retractable head extends through the hole of the permeation layer to the vicinity of the thin foil.