JP6933886B2 - Labels, clinical trial bottles, labeling methods and methods that make it difficult to identify the contents - Google Patents

Description

The present invention relates to a label, a clinical trial bottle, a method of attaching a label to a clinical trial bottle, and a method of making it difficult to visually identify the contents of the clinical trial bottle.

For example, when conducting a clinical trial (clinical trial) on a medical protein preparation used as an injection, two types of colorless and transparent clinical trial bottles containing a drug solution or a placebo solution are prepared. Generally, these clinical trial bottles are labeled with the type and product number of the drug solution (see Patent Document 1). Then, at the time of the clinical trial, the contents of the clinical trial bottle are administered to the subject without knowing whether the drug solution or the placebo solution is contained in the clinical trial bottle. This makes it possible to strictly confirm and evaluate the therapeutic effect of the drug solution.

Japanese Unexamined Patent Publication No. 8-231437

However, although the chemical solution is generally colorless and transparent, it may be slightly yellowish or cloudy depending on the type of the chemical solution or individual differences of the chemical solution. In such cases, there is a visual difference between the drug solution and the colorless and transparent placebo solution, allowing the investigator or investigator to distinguish between the drug solution and the placebo solution in the clinical trial bottle. There is sex. If the contents can be discerned by the examinee or the investigator, it may affect the clinical trial results and make it impossible to conduct a clinical trial with sufficient accuracy.

This application was made in view of this point, and labels, clinical trial bottles, labeling methods, and contents of clinical trial bottles that make it difficult to visually distinguish whether the contents of the clinical trial bottle are drug solution or placebo solution. Its purpose is to provide a way to make it difficult to identify.

The present inventors make it difficult to distinguish whether the content of the clinical trial bottle is a drug solution or a placebo solution by coloring the surface to which the label to be attached to the clinical trial bottle is attached and setting the label to a predetermined length and a predetermined width. The present invention was completed by utilizing the above-mentioned knowledge. That is, the present invention provides the following [1] to [10].

[1] A label for a clinical trial bottle containing a drug solution or a placebo solution, the label affixing surface is colored in color, and the length of more than half of the circumference of the body of the bottle and the body of the body. A label that is more than half the height.
[2] The length of the label in the circumferential direction of the body is two points on the surface of the body where one tangent line of the inner peripheral surface of the body and the outer peripheral surface of the body intersect in the cross section of the body. The label according to [1], which is set to be equal to or longer than the length connected in the circumferential direction on the long peripheral side, and the width in the body height direction of the label is set to be equal to the height of the body. ..
[3] The label according to [1] or [2], wherein the drug solution is a protein solution.
[4] The label according to any one of [1] to [3], wherein the sticking surface is colored in the same color as the chemical solution.
[5] The label according to any one of [1] to [4], wherein the sticking surface is colored yellow.
[6] A clinical trial bottle to which the label according to any one of [1] to [5] is affixed.
[7] The clinical trial bottle according to [6], which contains a drug solution or a placebo solution.
[8] A method of affixing a label to a clinical trial bottle containing a drug solution or a placebo solution, which comprises a step of affixing a colored label on the affixed surface to the body of the bottle. , A method of attaching a label, wherein the label is attached to a range of half or more of the circumference of the body portion and is attached to a range of half or more of the height of the body portion.
[9] A label having a colored sticking surface is attached to the clinical trial bottle containing the drug solution or the placebo solution so that the contents of the clinical trial bottle can be seen in the color of the sticking surface in appearance. A method that makes it difficult to visually identify the contents.
[10] For clinical trials, the sticking surface is colored so that the contents of the clinical trial bottle can be seen in the color of the sticking surface so that the contents of the clinical trial bottle are difficult to visually identify. Label for bottles.

By making the label affixed surface colored and setting the label to a predetermined length and width, it becomes difficult to visually distinguish whether the contents of the clinical trial bottle are a drug solution or a placebo solution, and as a result, a clinical trial with sufficient accuracy can be performed. It can be carried out.

It is a front perspective view which shows the outline of the clinical trial bottle. It is a rear perspective view which shows the outline of the clinical trial bottle. It is explanatory drawing which shows the structure of the bottle body. (A) is a diagram showing an example of the front surface of the label, and (b) is a diagram showing an example of the back surface of the label. It is a schematic diagram of the cross section of the body part. It is the schematic of the cross section of the body part for demonstrating the length of another label. It is a rear view of a clinical trial bottle. It is a graph which shows the indistinguishability test result of Test 1. It is a graph which shows the indistinguishability test result of the test 2.

Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings. The same elements are designated by the same reference numerals, and duplicate description will be omitted. In addition, the positional relationship such as up, down, left, and right shall be based on the positional relationship shown in the drawings unless otherwise specified. Furthermore, the dimensional ratios in the drawings are not limited to the ratios shown. Further, the following embodiments are examples for explaining the present invention, and the present invention is not limited to the embodiments thereof.

FIG. 1 is a front perspective view showing an outline of the configuration of the clinical trial bottle 1 in the present embodiment, and FIG. 2 is a rear perspective view.

As shown in FIGS. 1 and 2, the clinical trial bottle 1 is provided on a bottle body 10 that selectively contains a drug solution or a placebo solution (hereinafter, these are also referred to as “liquid A”) and an upper portion of the bottle body 10. It has a lid 11 attached, and a label 12 is affixed to the surface of the bottle body 10.

As used herein, the term "chemical solution" is not limited to a liquid substance itself, but also a solution of a solid drug or a solution of a dry powder such as a protein, which is dissolved at the time of use. included. In addition, the term "protein" used in the present specification includes not only simple proteins composed only of amino acids but also those modified with sugar or phosphoric acid.

As shown in FIG. 3, the bottle body 10 is formed in a substantially cylindrical shape with a bottom, and is molded of a colorless and transparent material such as glass or resin. The bottle body 10 has an upper neck portion 20 to which the lid 11 is attached, and a body portion 21 located below the neck portion 20 and having a diameter larger than that of the neck portion 20.

The body portion 21 is formed in a cylindrical shape having a substantially constant diameter. The body portion 21 is formed from the bottom surface of the bottle body 10 to at least a position higher than the liquid level of the liquid A. In the present embodiment, the body portion 21 is formed from the bottom surface of the bottle body 10 to a position where the diameter starts to gradually decrease.

The neck portion 20 has a shape in which the diameter is reduced from the upper end of the body portion 21 from the bottom to the top, then the diameter of a certain section becomes constant, and finally the diameter increases to form a large diameter portion (flange portion). ing. The bottle body 10 and the lid 11 are examples and are not limited to the above forms.

The label 12 has, for example, a two-layer structure, and has a front surface layer made of paper or resin and a back surface layer made of paper or resin. On the surface 12a of the surface layer of the label 12, as shown in FIG. 4A, information on the chemical solution as the content, a management method of the clinical trial bottle 1, and predetermined necessary information such as a serial number are described on a white background. Has been done. The back surface (attached surface) 12b of the back surface layer of the label 12 is colored in plain yellow as shown in FIG. 4 (b). The term "yellow" here includes Munsell values of 5YR to 5GY in the Munsell color system. The label 12 is manufactured by adhering the printed front layer sheet and the back surface layer sheet solidly printed in yellow.

The label 12 has a predetermined length L in the long side direction and a predetermined width D in the short side direction. As shown in FIG. 5, the predetermined length L of the label 12 has a length of one half or more of the circumference of the body portion 21, preferably two-thirds or more of the length of the circumference of the body portion 21. .. Further, the predetermined width D of the label 12 has a width of half or more of the height of the body portion 21, preferably a width of two-thirds or more of the height of the body portion 21.

Further, as shown in FIG. 6, the predetermined length L of the label 12 is two points where one tangent line K of the inner peripheral surface 21a of the body portion 21 and the outer peripheral surface 21b of the body portion 21 intersect in the cross section of the body portion 21. The length L1 in which X1 and X2 are connected in the circumferential direction on the long peripheral side of the bottle surface may be set to be the same. At this time, the predetermined width D of the label 12 is set to be equivalent to the height H of the body portion 21 as shown in FIG. The term "equivalent" here includes those having a length L1 within a range of ± 5 mm and a height H within a range of ± 2 mm. The predetermined length L of the label 12 is shorter than the entire circumference of the body portion 21, and a gap (a portion without the label 12) is formed between both ends of the label 12.

Next, a method of attaching the label 12 to the clinical trial bottle 1 will be described. Before the label 12 is affixed, the drug solution or the placebo solution is contained in the bottle body 10 of the clinical trial bottle 1, and the bottle body 10 is closed by the lid 11. Next, the label 12 is attached to the body 21 of the bottle body 10. The label 12 has two points X1 and X2 where one tangent K of the inner peripheral surface 21a of the body 21 and the outer peripheral surface 21b of the body 21 intersect in the circumferential direction of the surface of the body 21 in the cross section of the body 21. It is attached in the same range as the length L1 in which the above is connected, and is also attached in the height direction of the body portion 21 in the same range as the height H of the body portion 21.

At the time of the clinical trial, the investigator extracts the drug solution or the placebo solution from the clinical trial bottle 1 with a syringe or the like, and administers the drug solution or the placebo solution to the subject. The subject does not know whether the clinical trial bottle 1 contains either the drug solution or the placebo solution, and the liquid A of either of them is administered by a syringe or the like.

According to the present embodiment, the sticking surface of the label 12 is colored yellow, and the label 12 has a length L that is more than half the circumference of the body portion 21 and a width D that is more than half the height of the body portion 21. Therefore, as shown in FIG. 7, when the chemical solution or the placebo solution in the test bottle 1 is viewed from the gap without the label 12, the sticking surface 12b of the label 12 can be seen in the background of the liquid A, and the liquid. The color of A looks yellow on the sticking surface 12b of the label 12. Even if the attached surface 12b of the label 12 cannot be seen directly on the background of the liquid A, the color of the liquid A looks yellow, which is close to the attached surface 12b of the label 12, due to the reflected light from the attached surface 12b. As a result, even if the drug solution is slightly yellowish or cloudy, the drug solution and the placebo solution in the clinical trial bottle 1 appear to be the same color, making it difficult to visually distinguish between the drug solution and the placebo solution. .. As a result, the clinical trial of the drug solution can be conducted appropriately and accurately.

Further, as shown in FIG. 6 of the present embodiment, the label 12 has two points X1 and X2 at which one tangent line K of the inner peripheral surface 21a of the body portion 21 and the outer peripheral surface 21b of the body portion 21 intersect. When it has a predetermined length L equivalent to the length L1 connected in the circumferential direction on the long peripheral side of the surface of the portion and has a predetermined width D equivalent to the height H of the body portion 21, the label 12 has a predetermined width D. Since the predetermined length L is equivalent to the length L1 as shown in FIG. 6, the surface to which the label 12 is attached can be seen in the background regardless of the direction in which the inside of the clinical trial bottle 1 is viewed through the gap without the label 12. Therefore, it becomes difficult to distinguish whether the content in the clinical trial bottle 1 is a drug solution or a placebo solution.

In the present embodiment, since the resin is used for the sticking surface 12b of the label 12, the label 12 does not peel off or discolor even when dew condensation occurs on the clinical trial bottle 1 during refrigerated storage, for example. Since the sticking surface 12b of the label 12 is in close contact with the bottle surface, it is possible to maintain a state in which it is difficult to distinguish between the chemical solution and the placebo solution.

Further, in the present embodiment, the predetermined length L of the label 12 is equivalent to the length L1 shown in FIG. 6, but the length L1 or more may be used. In this case as well, the affixed surface 12b of the label 12 can be seen in the background regardless of the direction in which the inside of the clinical trial bottle 1 is viewed through the gap without the label 12, and it can be determined whether the content of the clinical trial bottle 1 is a chemical solution or a placebo solution. It is especially difficult to identify. However, if the entire circumference of the body 21 is covered with the label 12, it becomes difficult to check the drug solution in the clinical trial bottle 1.

Further, in the present embodiment, the drug solution is a protein solution, but the present invention can be applied to other drug solutions such as injections to be tested. Further, the color of the sticking surface 12b of the label 12 is not limited to yellow, and may be another color such as red or blue, which makes it difficult to distinguish the chemical solution from the placebo solution depending on the color of the chemical solution or the like. Here, colored means a color other than white. At this time, the color of the sticking surface 12b of the label 12 may be the same as the color of the chemical solution, or may not be the same color as the chemical solution or may be a similar color as long as it is difficult to identify. Further, it may be a color other than the similar color. Further, the color brightness of the sticking surface 12b of the label 12 can be changed according to the color brightness of the chemical solution. Further, the shape and dimensions of the clinical trial bottle 1 are not limited to those of the above embodiment. For example, the clinical trial bottle 1 in the present embodiment has a body portion 21 located below the neck portion 20 and having a diameter larger than that of the neck portion 20, but the body portion has a diameter equivalent to that of the neck portion. Alternatively, the lid may be attached directly to the body without a neck.

Although preferred embodiments of the present invention have been described with reference to the drawings, the present invention is not limited to such examples. It is clear that a person skilled in the art can come up with various modifications or modifications within the scope of the ideas described in the claims, and these also naturally belong to the technical scope of the present invention. It is understood as a thing.

An indistinguishability test of the contents of the clinical trial bottle with the label according to the present invention was conducted.

(Test 1)
<Label>
Manufactured by cutting a double-layered label (hereinafter referred to as "yellow label") in which a PET sheet is solid yellow printed and YUPO (registered trademark) paper for printing is laminated on it, and a polypropylene film is cut. A label (hereinafter referred to as "white label") was prepared. The size of the label was 28.0 mm in length (predetermined width D) x 50.0 mm in width (length L) for a clinical trial bottle having a diameter of 24 mm. When six yellow-labeled samples (1 to 6) were measured with a color reflection densitometer (manufactured by Ihara Denshi Kogyo Co., Ltd .: color reflection densitometer "R710"), the results shown in Table 1 were obtained.

<Formulation>
A protein solution having a concentration of 10 mg / mL was used as the active preparation. The protein solution used in this example was visually yellowish. Using a spectrocolorimeter (SE 6000 (manufactured by Nippon Denshoku Industries Co., Ltd.)), the color difference ΔE of the active preparation and the placebo preparation was measured using water as a standard solution. In this measurement, the reflection measurement diameter is φ30 mm and the measurement wavelength range is 380 nm.
It was carried out at ~ 780 nm and the output interval was 10 nm. The measurement results of the color difference ΔE with water of the active preparation and the placebo preparation were 1.01 and 0.27, respectively.

<Clinical trial bottle>
The clinical trial bottle was made of transparent glass and had a body height H of 31 mm and a body surface length of 24 mm (inner diameter 22 mm). The length of 2/3 of the circumference of the body of the clinical trial bottle was 50.0 mm. The length L1 connecting the two points X1 and X2 where one tangent of the inner peripheral surface of the body of the clinical trial bottle and the outer peripheral surface of the body intersect in the circumferential direction on the long peripheral side of the bottle surface was 65.5 mm. ..

<Sample preparation>
1. 1. 10 or more active preparations and 10 or more placebo preparations were prepared.
2. Randomly take out the active preparation and the placebo preparation so that the total number is 10, and randomly write the numbers 1 to 10 on the lid of the cap. At that time, it was decided to include at least three active or placebo preparations.
3. 3. In the same procedure, a total of 10 formulations were taken out and the numbers 11-20 were written on the cap lid. At that time, it was decided to include at least three active or placebo preparations.
A yellow label was attached to the clinical trial bottle (vial product) No. 4.1-10. The yellow label is cut at a length of 28.0 mm and a width of 50.0 mm. The sticking height was about 1 mm from the bottom of the bottle (hereinafter, these are referred to as "yellow label group").
A white label was affixed to the 5.11.20 clinical trial bottle. The white label was cut at a length of 28.0 mm and a width of 50.0 mm. The sticking height was about 1 mm from the bottom of the bottle (hereinafter, these are referred to as "white label group").
6. The proctor kept a note of whether the formulation with each number was an active formulation or a placebo formulation, but did not disclose it to the testers.

<Exam preparation>
1. 1. A yellow label group and a white label group were prepared in a living room (about 890 lux) under a normal fluorescent lamp.
2.9 testers were selected. In order to prevent the test from being performed with prejudice, the indistinguishability test of the product was performed without giving the characteristic information of the product.

<Start of test>
1. 1. The testers were placed in the living room one by one and the test was conducted.
2. No prior information was given to the testers, and the 10 yellow label groups placed on the table were instructed to identify the difference in the preparations in a time of 2 minutes and divide them into 2 groups.
3. 3. The test supervisor measured for 2 minutes with a stopwatch, and after the measurement, the tester described the results of the grouping. If it cannot be identified, it is described in the "Unidentifiable" column.
4. An indistinguishability test was also performed on the "white label group" in the same procedure, and the tester described the results.
5. The above indistinguishability test was carried out for the number of people.

<Criteria>
The criteria for indistinguishability were set as follows.
In addition, this test is a work of dividing the sample of each group into two groups, and is not a test of directly distinguishing whether one of them is an active preparation or a placebo preparation.
1. 1. Correct answer rate 100%: Completely identifiable.
2. Correct answer rate 80-90%: Almost identifiable.
3. 3. Correct answer rate 50-70%: Not identifiable.
4. Unidentifiable: Unidentifiable.
Correct answer rate 50%: Even if the answer is randomly divided into two groups, there is a 50% chance that the answer will be correct, and the correct answer rate will be "unidentifiable". As a result, active preparations and placebo preparations are mixed. Therefore, it is set as "unidentifiable".

<Results / Discussion>
The results of the indistinguishability test between the yellow label group and the white label group are shown in FIG. As a result, it can be said that the yellow label group is indistinguishable because all the testers were "indistinguishable" or "correct answer rate 50-70%". On the other hand, in the white label group, there is no "indistinguishable", and although there are testers with a "correct answer rate of 50-70%", two-thirds of the testers have a "correct answer rate of 80-90%". Or, the correct answer rate was 100%, and it can be said that the answers were identifiable. Therefore, it can be said that the indistinguishability is not completely ensured.
Table 2 shows the individual results of the testers of the indistinguishability test between the yellow label group and the white label group. Compared with the yellow label group, the correct answer rate was higher in the test of the white label group as a whole, and it was found that almost all the testers tended to easily identify the white label group. In addition, the two testers who were "indistinguishable" in the yellow label group had a "correct answer rate of 100%" in the white label group.
From the above results, it was confirmed that the yellow label included in the present invention is effective in ensuring indistinguishability as compared with the white label usually used for the investigational drug.

(Test 2)
In Test 2, the same test as in Test 1 was performed by changing the horizontal length (length L) of the label.

The dimensions of the yellow label and the white label were 28.0 mm in length (predetermined width D) x 37.5 mm in width (length L) with respect to the clinical trial bottle having a diameter of 24 mm. The horizontal length of this label is half the length of the circumference of the body of the clinical trial bottle. The yellow label and the white label are the same as in Test 1 above except for the horizontal (length L) length.

In Test 2, the same conditions as in Test 1 were carried out except that the yellow label group and the white label group were prepared in the living room under a fluorescent lamp having a brightness of about 934 lux in the <test preparation> of Test 1. That is, Test 2 was performed according to the conditions of <Formulation>, <Clinical Trial Bottle>, <Sample Preparation>, <Test Start>, and <Criteria> of Test 1 above.

<Results / Discussion>
The results of the indistinguishability test between the yellow label group and the white label group are shown in FIG. As a result, it can be said that the yellow label group is indistinguishable because 8 out of 9 testers were "indistinguishable" or "correct answer rate 50-70%". On the other hand, in the white label group, there is no "indistinguishable", and although there are testers with a "correct answer rate of 50-70%", two-thirds of the testers have a "correct answer rate of 80-90%". Or, the correct answer rate was 100%, and it can be said that the answers were identifiable.
Therefore, it can be said that the indistinguishability is not completely ensured.
Table 3 shows the individual results of the testers of the indistinguishability test between the yellow label group and the white label group. Compared with the yellow label group, the correct answer rate was higher in the test of the white label group as a whole, and it was found that 8 out of 9 testers tended to easily identify the white label group. In addition, the two testers who were "indistinguishable" in the yellow label group had a "correct answer rate of 100%" in the white label group.
From the above results, it was confirmed that the yellow label included in the present invention is effective in ensuring indistinguishability as compared with the white label usually used for the investigational drug.

INDUSTRIAL APPLICABILITY The present invention is useful when conducting a clinical trial with sufficient accuracy by making it difficult to visually distinguish whether the content of the clinical trial bottle is a drug solution or a placebo solution.

1 Clinical trial bottle 10 Bottle body 12 Label 12b Sticking surface 21 Body A Liquid L Specified length D Specified width

Claims (7)

A clinical trial bottle containing a drug solution or placebo solution.
It has a colorless and transparent body with a label attached,
The label has a length of more than half the circumference of the body of the bottle and a width of more than half the height of the body.
A clinical trial bottle in which the surface to which the label is attached is colored in the same color as the chemical solution. The length of the label in the circumferential direction of the body is the long peripheral side of the surface of the body at two points where one tangent of the inner peripheral surface of the body and the outer peripheral surface of the body intersect in the cross section of the body. It is set to be equal to or longer than the length connected in the circumferential direction of
The clinical trial bottle according to claim 1, wherein the width of the label in the body height direction is set to be equal to the height of the body. The clinical trial bottle according to claim 1 or 2, wherein the drug solution is a protein solution. The clinical trial bottle according to any one of claims 1 to 3, wherein the sticking surface is colored yellow. The clinical trial bottle according to any one of claims 1 to 4, which contains a drug solution or a placebo solution. A method of attaching a label to a clinical trial bottle containing a drug solution or a placebo solution.
It has a step of attaching a label whose sticking surface is colored in the same color as the chemical solution to the colorless and transparent body of the bottle.
A method of attaching a label, wherein in the step, the label is attached to a range of half or more of the circumference of the body portion and is attached to a range of half or more of the height of the body portion. A colored label with the same color as the drug solution is affixed to the colorless and transparent body of the clinical trial bottle containing the drug solution or placebo solution so that the contents of the clinical trial bottle can be seen in the color of the affixed surface. To make it difficult to visually identify the contents of the clinical trial bottle.

Images