JP2833309B2 - Barium sulfate contrast agent for CT - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel CT X-ray contrast agent containing barium sulfate as a main component and having low viscosity and excellent redispersibility even when settled.

[0002]

BACKGROUND OF THE INVENTION X-ray contrast agents for gastrointestinal tract, mainly comprising barium sulfate, are mainly marketed and taken in the form of aqueous suspensions. Since barium sulfate has a specific gravity as high as about 4.5, it is extremely important to select a type and amount of the suspension stabilizer for formulating a stable suspension which is extremely easy to settle. However, even if these choices are appropriate, some sedimentation of barium sulfate over time is unavoidable and requires a few shaking of the vessel during use to promote redispersion. That is, consideration for improving redispersibility is also an important matter in the preparation.

[0003] In the CT diagnosis which has recently become widespread, barium sulfate contrast agents have a barium sulfate concentration in the preparation of 0.5 to 0.5%.
6.0% by weight of barium sulfate contrast agent conventionally used for diagnosis of gastric and intestine (30 to 150% in most cases)
Much lower concentrations. If such a low-concentration preparation has poor redispersibility, the concentration of barium sulfate during use naturally falls below a predetermined concentration. The effect is much greater than the high concentrations of contrast agents commonly used in the stomach and intestines with high barium sulfate concentrations. Therefore, in the case of a CT contrast agent, it is extremely important to prepare a preparation excellent in suspension and redispersibility. That is, if a different concentration is administered to each patient, a different contrast is obtained on the image, which results in a problem in diagnosis.

[0004] In order to minimize the change in concentration, it is only necessary to be able to return to the state immediately after production by shaking during use.

Conventionally, water-soluble polymers (eg, gelatin, gum arabic, sodium alginate, sodium carboxymethylcellulose, etc.) and surfactants have been used to produce such low-concentration suspensions for CT. One to two months after preparation, barium sulfate has the disadvantage of settling out, coagulating firmly, and not being sufficiently redispersed, and a solution to this problem is desired.

[0006]

According to the present invention, barium sulfate contains 0.5% of barium sulfate.
〜6.0% by weight of an aqueous suspension is characterized by containing a physiologically tolerable and insoluble polymer compound which has not been conventionally used. When the barium sulfate suspension for CT diagnosis has an aqueous suspension concentration of barium sulfate of 0.5% by weight or less, contrast in an image in CT diagnosis is insufficient and the image becomes unclear. On the other hand, when the content is 6% by weight or more, there is a problem that an artefact that a high contrast part and a low contrast part run radially on an image occurs, so that it is used in this density range. Particle size of barium sulfate is 0.5 to
2μ is appropriate, preferably 1.0-1.5μ.

[0007] There are biologically acceptable, and carboxymethyl cellulose as a polymer compound insoluble carboxymethyl cellulose calcium, starch, alginic acid, calcium alginate, hydroxypropyl starch and the like. These compounds have the property of being insoluble in water and swelling and exhibiting no viscosity. The amount used is preferably 0.2 to 3% by weight, and particularly preferably 1% by weight.
If it is more than 3% by weight, there is a problem in taking it, and if it is less than 0.2%, redispersibility is poor and it cannot be used. Further, preservatives such as butyl paraoxybenzoate, ethyl paraoxybenzoate, sodium dehydroacetate, and dissolution aids such as propylene glycol, which are generally used as a contrast agent in the present invention,
Antifoaming agents such as dimethylsiloxane, saccharin sodium, sweeteners such as sugar, flavoring agents such as citric acid,
It goes without saying that flavors such as cream soda essence and strawberry essence may be used in combination as appropriate.
The suspension may be produced according to a conventional method, and no special method is required.

[0008]

EXAMPLES Examples of the present invention will be described below, but the present invention is not limited by these examples. A. Preparation of Contrast Agent Example 1 Barium Sulfate (Average Particle Size 1.0 μm) 0.5 g Sodium Carboxymethyl Cellulose (Daicel 1220) 3 g Yogurt Essence 0.05 g manufactured by Daicel Chemical Industries Ltd. Sanei Chemical Sugar 0.5 g Sodium Dehydroacetate 0.06 g The above components were mixed with an appropriate amount of purified water using a homomixer (TK HO).
MO MIXER, manufactured by Tokushu Kikai Kogyo Co., Ltd.) for 3 minutes in a usual manner. Next, 3 g of carboxymethyl cellulose (manufactured by Nichirin, NS-300) was added, and the mixture was dispersed in purified water to make 100 ml for 1 minute.
A barium sulfate contrast agent was prepared. (A-1)

Example 2 A barium sulfate contrast agent for CT was prepared in the same manner as in Example 1 except that 1.5 g of barium sulfate was used. (A-2)

Example 3 In Example 1, 2.5 g of barium sulfate was used (the same applies hereinafter). (A-3)

Example 4 In Example 1, 3.5 g of barium sulfate was used (the same applies hereinafter). (A-4)

Example 5 In Example 1, 4.5 g of barium sulfate was used (the same applies hereinafter). (A-5) The sample is the A series.

Example 6 0.5 g of barium sulfate 2 g of sodium carboxymethylcellulose (Daicel 1220) 0.06 g of sodium dehydroacetate manufactured by Daicel Kagaku Kogyo Co., Ltd. The above components were mixed with an appropriate amount of purified water using a homomixer (TK HO).
MO MIXER, manufactured by Tokushu Kikai Kogyo Co., Ltd.) for 3 minutes in a usual manner. Next, 3 g of carboxymethylcellulose calcium (Nichirin, ECG505) was added to make 100 ml with purified water and dispersed for 1 minute.
A barium sulfate contrast agent was prepared. (B-1)

Example 7 In Example 6, 1.5 g of barium sulfate was used (the same applies hereinafter). (B-2)

Example 8 In Example 6, 2.5 g of barium sulfate was used (the same applies hereinafter). (B-3)

Example 9 In Example 6, 3.5 g of barium sulfate was used (the same applies hereinafter). (B-4)

Example 10 In Example 6, 4.5 g of barium sulfate was used (the same applies hereinafter). (B-5) The sample is a B series.

Comparative Example 1 Barium sulfate (same as in Example 1) 0.5 g Sodium carboxymethylcellulose (Daicel 1220) 3 g Yogurt Essence 0.05 g manufactured by Daicel Chemical Industries, Ltd. 0.5 g Sanei Chemical Sugar 0.5 g Homomixer (T.KHOMO
MIXER, manufactured by Tokushu Kikai Kogyo Co., Ltd.) in a usual manner for 3 minutes. Next, the dispersion was adjusted to 100 ml with purified water for 1 minute to prepare a barium sulfate contrast agent for CT. (C-1)

Comparative Example 2 In Comparative Example 1, 1.5 g of barium sulfate was used (the same applies hereinafter). (C-2)

Comparative Example 3 In Comparative Example 1, 2.5 g of barium sulfate was used (the same applies hereinafter). (C-3)

Comparative Example 4 In Comparative Example 1, 3.5 g of barium sulfate was used (the same applies hereinafter). (C-4)

Comparative Example 5 In Comparative Example 1, 4.5 g of barium sulfate was used (the same applies hereinafter). (C-5) The sample is a C series.

B. Test Method Five prepared samples were prepared, placed in a 300 ml plastic container, and left in a cool and dark place for 30 days. 30 days later,
Each sample was placed on a shaker (THERMONICS, THE
RMO-SHAK-ER-MODEL Z-1 type) 4
After shaking for 0 second, the barium sulfate concentration was analyzed by a gravimetric method (a method of collecting 20 ml of a sample and determining the barium sulfate content by an ashing method by a gravimetric method). About average value and standard deviation of each analysis value, up to Examples 1-10 and Comparative Example 1
The results up to -5 are shown in Table 1 (average value of barium sulfate content and variation in quantitative determination thereof).

[0024]

[Table 1]

Table 1. As shown in the figure, the contrast agent according to the present invention has excellent redispersibility after being left for a long time, and its quantitative standard deviation is smaller than that of the comparative example. In FIG. 1, Table 1
, The horizontal axis shows the barium sulfate concentration, and the vertical axis shows the CT value. The solid line is for A series, barium sulfate concentration and CT
The values showed a linear relationship, and the standard deviation was shown above and below at each concentration. The dotted line shows the CT value range as shown in the figure centered at 1.15% even in the case of 1.5% as in Comparative Example C-2 due to poor dispersion in the C series of Comparative Example. Recognize. That is, it is understood that an expected CT value cannot be obtained. When viewed on actual clinical films, FIG. 2 (Example 2 sample A-2) and FIG. 3 (Comparative example 2 sample C)
-2).

FIG. 2 shows the required contrast in a diagnostic image when the redispersibility at the 1.5% concentration of sample A-2 is good, while FIG. Although the image is a diagnostic image when the density is%, the necessary contrast is not obtained due to poor redispersibility. Needless to say, if such contrast is different on the film, it is inconvenient in diagnosis. . For example, a concentration of 3.5% means that a CT value of 360 to 530 (HU) is shown although it should originally show a CT value of 540 (HU). This appears as a difference in contrast on the film and causes a problem in diagnosis.

[0027]

As described above in detail, the barium sulfate contrast agent for CT according to the present description has good redispersibility by being easily shaken by hand at the time of administration to a patient, and the present invention is excellent. Shows unique effects. That is, a swelling additive such as an insoluble disintegrant is mixed with a barium sulfate suspension (a physiologically acceptable and water-insoluble polymer compound), and the mixture is stirred uniformly at the time of production. Barium and the additive will settle free or coagulate and settle on the lower surface of the vessel, or barium sulfate will layer on the additive to form a settled layer, a soft cake. In other words, since barium sulfate does not directly touch the container, it is easy to separate from the container by reshaking by hand, and because the formed cake is soft, it can be easily broken with a small force and easily redispersed. Conceivable.

[0028]

[Brief description of the drawings]

FIG. 1 is a graph showing the relationship between the barium sulfate concentration and the CT value and the variation in the barium sulfate content shown in Table 1. FIG. 2 is a computed tomographic image showing a diagnostic image of Sample A-2, and FIG. 3 is a computed tomographic image showing a diagnostic image of Sample C-2.

Claims (1)

(57) [Claims] (1) a C-containing barium sulfate containing a physiologically tolerable and insoluble polymer compound;
X-ray contrast agent for T.