JP2022096080A - Contrast agent-containing composition - Google Patents

Abstract

To provide a contrast agent-containing composition that has excellent operability and has imaging properties suitable for X-ray CT markers.SOLUTION: A contrast agent-containing composition contains at least a contrast agent, a styrene-butadiene latex, and an alcohol. The content of the contrast agent is 34-89 mass% in the solid content of the composition. The styrene-butadiene latex has Tg of -50°C to 17°C. The content of the alcohol is 1-5 mass% in the composition.SELECTED DRAWING: None

Description

The present invention relates to a contrast agent-containing composition for an X-ray CT marker, and more particularly to a contrast agent-containing composition having good operability and suitable imaging property for an X-ray CT marker.

X-ray photography is a technique widely known in the medical field as a technique for observing lesions of living hard tissues such as bones and teeth, lungs, and abdomen. Computer tomography using X-rays (hereinafter referred to as X-ray CT) is a technology that can take stereoscopic images of blood vessels, organs, and bones inside the human body in a short time, including cerebral bleeding, submucosal bleeding, and lungs. It is widely used for detecting various diseases such as cancers and fractures of various organs.

In X-ray CT, it is common practice to provide a visual reference point on the captured image to identify the position of the affected area. As a method for providing such a visual reference point, for example, a marking grid including a hydrogel layer containing a contrast medium described in Japanese Patent Application Laid-Open No. 2015-502819 (Patent Document 1) in a frame, or a US patent application. A marking having a pressure-sensitive adhesive on one side of a radiation-permeable substrate and a plurality of parallel bands of a radiation-impermeable material on the other side as described in Japanese Patent Application Laid-Open No. 2003/0081732 (Patent Document 2). The grid can be mentioned.

Further, Japanese Patent Publication No. 2017-518266 (Patent Document 3) discloses a multipurpose medical imaging marker containing a rubber agent, a fluorescent dye, and a contrast agent, and accurately confirms the labeled site by a non-invasive method. It is stated that it can be done.

Japanese Patent Publication No. 2015-502819 U.S. Patent Application Publication No. 2003/0081732 Special Table 2017-518266 Gazette

However, since the grid shape is specified in each of the methods for providing the visual reference point with the marking grid described in Patent Document 1 and Patent Document 2, the grid shape is specified, so that the method is adjusted to the imaging site in advance when it is placed in the imaging site. It was necessary to cut it into a shape and adjust the position of detention, and there was room for improvement in operability during detention. Further, the marker for multipurpose medical imaging described in Patent Document 3 needs to be molded into a circular shape and then dried and crosslinked, and there is also room for improvement in operability.

An object of the present invention is to provide a contrast medium-containing composition having good operability and suitable imaging property for an X-ray CT marker.

As a result of diligent studies to solve the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by a contrast medium-containing composition having the following constitution.

It contains at least a contrast medium, a styrene-butadiene latex, and alcohol, and the content of the contrast medium is 34 to 89% by mass in the solid content of the composition, and the Tg of the styrene-butadiene latex is -50 ° C. to A contrast medium-containing composition having a temperature of 17 ° C. and an alcohol content of 1 to 5% by mass in the composition.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a contrast medium-containing composition having good operability and suitable imaging property for an X-ray CT marker.

An example of a pen-type extrusion container filled with the contrast medium-containing composition of the present invention.

The contrast medium-containing composition of the present invention contains at least a contrast medium, a styrene-butadiene latex, and an alcohol, and the content of the contrast medium is 34 to 89% by mass in the solid content of the composition. The Tg of the butadiene-based latex is −50 ° C. to 17 ° C., and the content of the alcohol is 1 to 5% by mass in the composition.

The contrast medium contained in the contrast medium-containing composition of the present invention is not particularly limited as long as it can be distinguished from the soft tissue of the human body by the difference in CT value (CT image density value). Examples of the contrast agent include barium compounds typified by barium sulfate, iodine compounds typified by iodoform, calcium compounds typified by calcium carbonate, zirconium compounds, bismuth compounds, strontium compounds, gadrinium compounds, and titanium. Examples thereof include compounds, iron compounds, zinc compounds, silver compounds and copper compounds. The shape of the contrast medium is not particularly limited, and examples thereof include a needle shape, a rod shape, a spindle shape, a plate shape, a spherical shape, and an amorphous shape. The average particle size of the contrast medium is preferably 5 μm or less from the viewpoint of dispersibility in the contrast medium-containing composition. Among the above-mentioned contrast media, barium sulfate and calcium carbonate are preferably used from the viewpoints of image quality, chemical stability, material cost, and dispersibility in the contrast medium-containing composition containing the styrene / butadiene latex described later. be able to. Commercially available products include, for example, Tamapearl (registered trademark) TP-121 (spindle-shaped, average particle diameter 3.5 μm) manufactured by Okutama Kogyo Co., Ltd. as calcium carbonate, and Variace (registered trademark) manufactured by Sakai Chemical Industry Co., Ltd. as barium sulfate. B-35 (atypical, average particle diameter 0.3 μm) and the like are exemplified, and these can be preferably used.

The content of the contrast medium in the contrast medium-containing composition of the present invention is 34 to 89% by mass in the solid content of the composition. When the content of the contrast medium is higher than the above range, the dispersibility of the contrast medium is lowered and a line having a uniform line width cannot be placed without a break. Further, when the content of the contrast medium is less than the above range, good image quality cannot be obtained.

The styrene-butadiene latex contained in the contrast agent-containing composition of the present invention is a synthetic rubber latex containing styrene and butadiene as main components, and has a Tg of −50 to 17 ° C. When Tg is in this range, the film-forming property when the contrast medium-containing composition of the present invention is placed at the imaging site is improved, and the operability is improved. Commercially available products can be used as such styrene-butadiene latex, for example, Smarttex (registered trademark) PA9281 (Tg7 ° C.) manufactured by Nippon A & L Inc. and Nipol (registered trademark) LX426 manufactured by Nippon A & L Inc. (Tg-42 ° C.) and the like can be mentioned.

The content of the styrene-butadiene latex in the contrast agent-containing composition of the present invention is preferably 11 to 66% by mass in the solid content of the composition. If the content of the styrene-butadiene latex is less than this range, sufficient film formation may not be obtained, and if it is high, sufficient image quality may not be obtained.

The alcohol contained in the contrast medium-containing composition of the present invention is for improving the film-forming property of the above-mentioned styrene-butadiene latex when the contrast medium-containing composition is placed at an imaging site, and details thereof. Is a lower alcohol having a boiling point of 85 ° C. or lower. Examples of the lower alcohol include ethanol and isopropyl alcohol, and these can also be used in combination.

The content of alcohol in the contrast agent-containing composition of the present invention is 1 to 5% by mass in the composition. When the alcohol content is less than the above range, the film forming property after placement of the contrast medium-containing composition is not sufficient. On the other hand, if the amount is more than the above range, the dispersibility of the contrast medium and the styrene-butadiene latex is lowered, and a uniform contrast medium-containing composition cannot be obtained, and the operability is lowered.

The contrast agent-containing composition of the present invention can contain a thickener for the purpose of adjusting the viscosity. Examples of the thickener include polyvinyl alcohols, poly (meth) acrylic acids, polyethers (eg polyethylene glycol, polypropylene glycol, etc.), polyvinylpyrrolidones, polyvinylformals, proteins (eg, gelatin, casein, glue, etc.). , Polysaccharides (eg, purulan, dextran, dextrin, cyclodextrin, carrageenan, pectin, glucomannan, sodium alginate, xanthan gum, arabia gum, locust bean gum, tragant gum, guar gum, tamarind gum, etc.), starches (eg, starch, oxidation) Glue, carboxyl starch, dialdehyde starch, etc.), cellulose or derivatives thereof (eg, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, etc.), alginate (eg, sodium alginate, potassium alginate, alginate, etc.) (Ammium, etc.) Alginate ester (for example, alginate propylene glycol ester, etc.) and the like can be mentioned. The content of the thickener is preferably 10% by mass or less in the contrast medium-containing composition from the viewpoint of operability when placed in the imaging site.

The contrast agent-containing composition of the present invention is preferably filled in an extrusion container in which the contents can be ejected from the nozzle opening by an extrusion operation. The extruded container is not particularly limited, and for example, a cylindrical container having a nozzle opening on the tip side and a pressing portion on the proximal end side is exemplified, and the pressing portion of the tubular container body is pressed to press the pressure toward the tip. By adding, the contents in the container body can be discharged from the nozzle opening. Examples of such an extruded container include a syringe-shaped container. Alternatively, an elastic container provided with a nozzle opening is exemplified. FIG. 1 shows an example of a pen-type extruded container filled with the contrast medium-containing composition of the present invention. The content (contrast agent-containing composition 2) can be ejected from the nozzle opening by sandwiching the side surface of the pen-type extrusion container 1 with fingers and applying pressure. As the pen-type extruded container 1, an extruded container obtained by molding a polyolefin resin such as polyethylene or polypropylene into a pen shape can be exemplified.

In the contrast medium-containing composition of the present invention, it is desirable that a resin film such as a polyurethane film or a polyolefin film is attached in advance to the imaging location and then placed on the film. The thickness of the film is preferably 50 μm or less, more preferably 20 μm or less.

Further, the contrast medium-containing composition of the present invention can be dried and formed into an arbitrary shape on the above-mentioned film in advance at a place other than the photographing place, and then installed at the photographing place and used for imaging. ..

Hereinafter, the present invention will be described in more detail with reference to Examples, and the present invention will be specifically described, but the present invention is not limited to the following Examples.

(Example 1)
In the container of the stirrer AR250 manufactured by Shinky Co., Ltd., 10.0 g of Smartex PA9281 (styrene-butadiene latex, solid content 48% by mass, Tg7 ° C) manufactured by Nippon A & L Inc. and Variace manufactured by Sakai Chemical Industry Co., Ltd. 1.8 g of B-35 (barium sulfate, as a contrast agent) was added, and the mixture was stirred in a stirring mode (rotation 800 rpm / revolution 2000 rpm) for 10 minutes. Next, 8.0 g of Tamapearl TP-121 (calcium carbonate, as a contrast medium) manufactured by Okutama Kogyo Co., Ltd. was further added to the container, and further stirring was performed for 10 minutes in the above-mentioned stirring mode. Subsequently, 0.6 g of ethanol (purity 99.5%) manufactured by Kishida Chemical Co., Ltd. was added to the container, and the mixture was stirred in the above-mentioned stirring mode for 2 minutes to obtain the contrast medium-containing composition of Example 1. rice field.

(Example 2)
In Example 1, the contrast medium-containing composition of Example 2 was obtained in the same manner except that Smartex PA9281 was 5.0 g, Variace B-35 was 15 g, and Tamapearl TP-121 was not added.

(Example 3)
In Example 1, the amount of Smartex PA9281 was 15.5 g, the amount of Variace B-35 added was 4.5 g, and Tamapearl TP-121 was not added. A contrast medium-containing composition was obtained.

(Example 4)
In Example 1, as a styrene-butadiene latex, Smartex PA9281 was changed to Nipol® LX426 (solid content 50% by mass, Tg-42 ° C.) manufactured by Nippon Zeon Corporation, and the LX426 was changed to 9. The contrast medium-containing composition of Example 4 was obtained in the same manner as in Example 1 except that 6 g was used.

(Example 5)
In Example 1, 0.6 g of ethanol, 0.6 g of ethanol and 1.0 g of polyethylene glycol manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. (average molecular weight 900 to 1,000, as a thickener) were previously added. The contrast agent-containing composition of Example 5 was obtained in the same manner except that the mixture was changed to a mixed one.

(Comparative Example 1)
In Example 1, the contrast medium-containing composition of Comparative Example 1 was obtained in the same manner except that Smartex PA9281 was 3 g, Variace B-35 was 17 g, and Tamapearl TP-121 was not added.

(Comparative Example 2)
In Example 1, the contrast medium-containing composition of Comparative Example 2 was obtained in the same manner except that Smartex PA9281 was 16.5 g, Variace B-35 was 3.5 g, and Tamapearl TP-121 was not added. rice field.

(Comparative Example 3)
In Example 1, as the styrene-butadiene latex, Smartex PA9281 was changed to Nipol LX432M (solid content 41% by mass, Tg-58 ° C.) manufactured by Nippon Zeon Corporation, and 11.7 g of the LX432M was used. In the same manner, the contrast medium-containing composition of Comparative Example 3 was prepared, but the fluidity of the contrast medium-containing composition disappeared immediately after the preparation, and it could not be used for the evaluation of operability and image quality described later.

(Comparative Example 4)
In Example 1, as the styrene-butadiene latex, Smartex PA9281 was changed to Nipol LX407G51 (solid content 48.5% by mass, Tg27 ° C.) manufactured by Nippon Zeon Corporation, and 9.9 g of the LX407G51 was used. In the same manner, a contrast medium-containing composition of Comparative Example 4 was obtained.

(Comparative Example 5)
In Example 1, the contrast agent of Comparative Example 5 was contained in the same manner as in Example 1 except that ethanol having a purity of 99.5% manufactured by Kishida Chemical Co., Ltd. was 1.5 g and Smartex PA9281 was 9.3 g. The composition was obtained.

(Comparative Example 6)
In Example 1, the contrast medium-containing composition of Comparative Example 6 was obtained in the same manner except that ethanol was not added.

<Evaluation of operability>
The obtained contrast medium-containing compositions of Examples 1 to 5, Comparative Examples 1 and 2, and Comparative Examples 4 to 6 were filled in a pen-type extrusion container (capacity: 5 ml) shown in FIG. The opening diameter of the tip (discharge part) of the extruded container is φ1.0 mm. X-ray water phantom (cylindrical plastic container filled with a radioactive aqueous solution that has an effect almost similar to that of human body radiation absorption and X-ray scattering), Mitsubishi Chemical Co., Ltd. polyolefin-based multilayer wrap film, Dialap (registered trademark) Eco-Pita! (Registered trademark) (thickness 6.3 μm) is attached, and each contrast medium-containing composition is discharged linearly and circularly from the tip of the extruded container onto the contrast medium-containing composition on a three-dimensional surface. The operation of detaining was performed. The operability at this time was evaluated according to the following evaluation criteria from the viewpoint of drawability and film formation. The results are shown in Table 1.

<Evaluation criteria for drawability>
◯: The line width is uniform and can be placed neatly without breaks.
X: The line width is uneven or cuts occur, so it cannot be placed neatly.

<Evaluation criteria for film formation>
◯: A film is formed within 10 minutes after indwelling.
X: No film formation within 10 minutes after indwelling.

<Evaluation of image quality>
In the evaluation of the above operability, the X-ray water phantom in which the contrast medium-containing compositions of Examples 1 to 5, Comparative Examples 1 and 2, and Comparative Examples 4 to 6 were placed was subjected to a multi-slice manufactured by GE Healthcare Japan Co., Ltd. The image was taken with a CT scanner Discovery CT750HD-A under soft tissue conditions (conditions in which fat and air can be distinguished). The image quality at this time was evaluated according to the following criteria. The results are shown in Table 1.

<Evaluation criteria for image quality>
◯: The contrast medium-containing composition indwelled on the captured image can be clearly observed, and no virtual image can be seen.
X: The contrast medium-containing composition indwelled on the captured image cannot be clearly observed, or a virtual image is observed.

From the results in Table 1, the effectiveness of the present invention can be seen. The operability and image quality of the contrast medium-containing composition obtained in the same manner except that ethanol was changed to isopropyl alcohol in Example 1 were evaluated and found to be as good as in Example 1. ..

1 Pen type extruded container 2 Contrast medium-containing composition

Claims (1)

A contrast medium-containing composition containing at least a contrast medium, a styrene-butadiene latex, and an alcohol, wherein the content of the contrast medium is 34 to 89% by mass in the solid content of the composition, and the styrene-butadiene A contrast agent-containing composition having a Tg of the system latex of −50 ° C. to 17 ° C. and an alcohol content of 1 to 5% by mass in the composition.

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