JPS6069041A - Barium sulfate x-ray contrasting agent - Google Patents

Abstract

PURPOSE:To produce the titled contrasting agent takable extremely easily, stable for a long period, and capable of depositing barium sulfate particles uniformly even to the minute wrinkles of the digestive tracts, by compounding vanillic acid and/or vanillin and tragacanth gum (or its treated product) to a barium sulfate composition. CONSTITUTION:An X-ray contrasting agent containing 50-200W/V%, preferably 100-200W/V% barium sulfate is incorporated with 0.004-4pts.wt., preferably 0.125-1pt.wt. (in terms of solid) of (A) vanillic acid and/or vanillin and (B) tragacanth gum and/or its treated product (e.g. extract with water) based on 100pts.wt. of baruim sulfate. The obtained contrasting agent has low viscosity in spite of high barium sulfate content, has excellent diffusibility, affinity and redispersibility as well as fluidity and adhesivity, and is suitable especially for the accurate recognition of the minute diseased part.

Description

[Detailed description of the invention] The present invention relates to a barium sulfate contrast agent for X-rays.

In general, barium sulfate contrast agents for X-rays have the following conditions: high concentration of barium sulfate, no aggregation in the stomach, excellent fluidity, diffusivity, adhesion, affinity, etc., and ease of administration. is required.

Various types of barium sulfate contrast agents have been known, but none that fully satisfies the above conditions has yet been found. In particular, with recent rapid advances in diagnostic technology, there has been a demand for the development of contrast agents that can accurately depict images of minute lesions.

Generally, it is thought that a high concentration of barium sulfate increases the contrast of the mixed X-ray image, that is, improves the contrast effect, but on the other hand, when the concentration is increased,
The viscosity of the m-swelling agent itself increases, making it difficult to take, and various properties such as adhesion and fluidity tend to decrease, ultimately making it difficult to accurately depict images of minute lesions. That is, in conventional contrast agents with a high concentration of barium sulfate, (1)
Because it is unstable over time, it gradually loses its fluidity over time due to contact and mixing with stomach acid, and aggregation between barium sulfate particles progresses to form a thick layer, which becomes fixed and does not move, a so-called sticky feeling phenomenon. (2
) The contrast medium does not adhere uniformly to the inside of the stomach wall, resulting in so-called uneven adhesion, where there are areas where too much contrast agent adheres and areas where it barely adheres, or if the degree of uneven adhesion is severe, barium sulfate itself may aggregate. There are disadvantages such as forming clumps, turning into clay, and losing fluidity. Therefore, when using a high-concentration barium sulfate swelling agent that has problems such as adhesion and fluidity, the contrast agent may enter the area to be imaged, such as minute lesions on the gastric wall, and the contrast agent may not be applied to the area. Since it is difficult for the agent to adhere uniformly, it is difficult to always obtain stable and accurate images of minute lesions.

In view of the current situation, the present inventors have conducted intensive research to develop a high-concentration barium sulfate contrast agent that does not have the above-mentioned drawbacks, and as a result, a contrast agent with the following composition has achieved the intended purpose of the present invention. I found out what I can do.

The present invention was completed based on this knowledge.

That is, the present invention relates to a barium sulfate contrast agent for X-rays characterized by containing vanillic acid and/or vanillin and gum tragacanth and/or a processed product thereof.

The most important features of the barium sulfate contrast agent of the present invention are:
It has a high barium sulfate concentration and low viscosity, making it easy to take and having excellent adhesion and fluidity. Furthermore, the barium sulfate contrast agent of the present invention has advantages such as excellent diffusibility, affinity, redispersibility, and the like. The barium sulfate contrast agent of the water spray invention satisfies all the conditions required for this type of contrast agent, and is an ideal barium sulfate contrast agent for X-rays. To explain further, the contrast agent of the present invention is extremely easy to take as it is a low viscosity sol like milk, and has particularly excellent fluidity over time, so it can be used to treat minute lesions on the gastric wall. It is easy to penetrate into areas to be imaged, such as irregularities (uneven areas). Once the penetration is completed, the contrast agent has excellent affinity with the gastric wall and gastric subdivisions, and the contrast agent strongly adheres to the site to be imaged, such as a minute lesion on the gastric wall. What's more, when it comes into contact with stomach acid, it is not adversely affected at all by Shikido. The barium sulfate contrast agent of the present invention is
It has excellent adhesion and does not cause uneven adhesion unlike conventional high-concentration barium sulfate contrast agents. Further, the barium sulfate contrast agent of the present invention does not cause a flat feeling phenomenon. Therefore, when the contrast agent is used for diagnosis of indigestion, it is extremely easy to take, and the barium sulfate particles can be attached to even the smallest details of the wall of the gastrointestinal tract, resulting in an extremely accurate contrast imaging of the condition of the wall of the gastrointestinal tract. Furthermore, the barium sulfate contrast agent for X-rays of the present invention is extremely stable over time. In particular, when the contrast agent of the present invention in a suspended form is stored for a long period of time, the suspended particles settle in a part of the lower part, but by applying a light impact, for example, by shaking, it is possible to restore the state to the state at the time of manufacture. , it can be used as a contrast agent without causing any problems.

The barium sulfate contrast agent for X-rays of the present invention essentially contains vanillic acid and/or vanillin (hereinafter referred to as "component A"). The amount of component A to be blended is not particularly limited and may be appropriately selected within a wide range, but it is usually about 0.004 to 0.004 to 100 parts by weight (hereinafter simply referred to as "parts") of solid content per 100 parts by weight of barium sulfate. 4 parts, preferably from about 0.1 to
2 parts, most preferably about 0.125 to 1 part.

Furthermore, the barium sulfate contrast agent for X-rays of the present invention must also contain gum tragacanth or a processed product thereof (hereinafter referred to as "component B"). As the processed product of gum tragacanth, a wide range of conventionally known products can be used, such as those obtained by subjecting gum tragacanth to physical means, chemical means, biological means, or a suitable combination of these, or those isolated from this. and when it is made into an aqueous solution with a concentration of 1 wt%, the viscosity [80
C., 80 rpm, rotor calm 2 or 8, the same hereinafter] is within the range of about 1 to 500 cp can be used. Among these, it is preferable to use those having a viscosity within the range of about 1 to 200 cp. A specific example of the processed product of gum tragacanth is an aqueous extract of gum tragacanth. A water extract of gum tragacanth can be produced by extracting gum tragacanth with water according to a conventional method.

The barium sulfate contrast agent for X-rays of the present invention basically has a powder form consisting of a mixture of barium sulfate, component A, and component B, or a suspension state in which it is suspended in water. The contrast agent may further contain various known additives such as wetting agents, antifoaming agents, sweetening agents, flavoring agents, or preservatives. The contrast agent of the present invention in a suspended form can be prepared by combining, for example, the above-mentioned barium sulfate, component A, and component B, together with additives if necessary, an appropriate amount of water, and a barium sulfate concentration of usually 50 to 200 W/V%.
, preferably 100 to 200 W/V%, is added to water and mixed and stirred. This can be taken directly as a contrast agent.

The contrast agent of the present invention having a powder form can also be produced by simply mixing barium sulfate, component A, and component B in powder form, or, for example, by mixing the suspension prepared above using a spray drying method, a wet granulation method, etc. It can also be produced by drying. This is convenient for storage, transportation, etc., and when used as a contrast agent, it can be easily restored to a liquid form that can be taken by adding water and stirring. The amount of water added is usually 50-2
00W/V% barium sulfate sol, preferably 100-2
The amount may be such that a 0.00 W/V% barium sulfate sol can be formed.

In order to explain the present invention in more detail, a method for producing an aqueous extract of gum tragacanth will be cited as a reference example, and formulation examples and test examples of the contrast agent of the present invention will be listed below.

Reference Example After leaving a 2% aqueous suspension of gum tragacanth prepared in advance overnight, the suspended matter was removed by centrifugation, and the supernatant was taken.
To this is added 1/2 times the weight of ethanol, and the precipitated material is again separated by centrifugation. The separated solids are dried and powdered to obtain gum tragacanth water extract powder with a yield of 80%.

This is [α]25=-+-s5°(C=0.5%, 0
．． 2N-NaOH aqueous solution). On the other hand, suspended solids are [α
]25=+222°CC=0.5%, 0.2N-Na
OH aqueous solution). Viscosity: 15 cp Formulation Example 1 480 kjl of barium sulfate, 25 kN of sugar, 1.920 kf of dried daffodil extract powder obtained in the above reference example, and 800 g of vanillin were added to 1201 purified water and thoroughly stirred with a mixer to give 200 W/V%. Obtain barium sulfate sol. Further, the sol obtained with the above formulation is dried by a blow drying method and then pulverized to obtain a powdered barium sulfate contrast agent.

Formulation Example 2 480kN of barium sulfate, 25kl of sugar, 1.920kg of the water extract dry powder obtained in the above reference example, 5ooy of vanillic acid and 2oo11 of purified water are sufficiently stirred in a mixer to obtain a 150 W/V% barium sulfate sol. .

Prescription example 8 Barium sulfate 480kN, sugar 25% and 11%. ) Lagant gum 5.56kf, vanillin 200y, glycerin 1.
2kf, sorbic acid 0.4kl, silicone resin 4. O
Add f and purified water 8601 and stir thoroughly with a mixer.
o Obtain OW/V% barium sulfate sol.

Formulation example 4 480 kl of barium sulfate, 25 kf of sugar, 5.5 kF of gum lagant, and 25 Of vanillic acid in purified water 2
Add to 621 and stir thoroughly with a mixer to make 120W/V%.
Obtain barium sulfate sol.

Formulation Example 5 480 kl of Barium sulfate A, 25 kN of sugar, 1.920 kF of dried powder of daffodil extract obtained in the above reference example, and vanillic acid 8009 were added to 120 kg of purified water and thoroughly stirred with a mixer to yield 200 W/V%. Obtain barium sulfate sol.

Formulation Example 6 Barium sulfate 480kF, sugar 25kN, water extract dry powder obtained in the above reference example 1.920kF.

Vanillin 800f and purified water 2001 are sufficiently stirred in a mixer to obtain a 150 W/V% barium sulfate sol.

Formulation Example 7 Add barium sulfate 480, sugar 25kl, daffodil extract dry powder 1.920kg, and vanillic acid aooF/1201 to purified water, stir thoroughly with a mixer to make 200 W/
A V% barium sulfate sol is obtained.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Formulation Example 8 480 kg of barium sulfate, 25 kg of sugar, 1.920 kF of water extract dry powder, and 800 g of vanillic acid were added to 1701 purified water and thoroughly stirred with a mixer to produce 170 W
/V% barium sulfate sol is obtained.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Formulation Example 9 Barium sulfate 480 & sugar 25kf, water extract dry powder 1.920kf and vanillin 800y purified water 2
Add to 001 and stir thoroughly with a mixer to make 150 W/V%.
Obtain barium sulfate sol.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Formulation Example 10 480 kl of barium sulfate, 25 kg of sugar, 1.920 kN of water extract dry powder, and 800 g of vanillin were added to 2801 g of purified water and thoroughly stirred with a mixer to produce 140 W/
A V% barium sulfate sol is obtained.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Formulation Example 11 - Add 480 barium sulfate, 25 kg of sugar, 1.920 kf of dried daffodil extract powder, and 800 y of vanillic acid to 2601 wom water and stir thoroughly with a mixer to make 180 W/
A V% barium sulfate sol is obtained.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension agent before use.

Formulation Example 12 480kf of barium sulfate, 25kf of sugar, 5.5ky of dried narcissus extract powder, and 250y of vanillin in 284ml of purified water.
1 and thoroughly stirred with a mixer to obtain a 120 W/V% barium sulfate sol.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Formulation Example 13 Barium sulfate 480 kN, sugar 25 kF, daffodil extract dry powder 5.55 kjl, vanillin 20 Of, glycerin 1.2 &, sorbic acid 0.4 kf, and silicone resin 4. Of is added to purified water 3601 and thoroughly stirred with a mixer to obtain a 100 W/V% barium sulfate sol.

Further, the sol obtained with the above formulation is dried and pulverized by a conventional drying method, such as a spray drying method, to obtain the compound of the present invention as a suspension before use.

Test Example 1 1N-HCl aqueous solution is added to 200 ml of various barium sulfate sols while maintaining the temperature at 80°C. Using Emestara AS-2 (Toyo Kagaku Sangyo Wave), rotation speed 10 Or
After stirring for about 1 minute at pm, the viscosity is measured using a VS-AI model Vismetron single cylinder rotational viscometer manufactured by Shibaura System. The operation of adding more IN'-HCl aqueous solution and measuring the viscosity is repeated, and the relationship between the amount of IN'-HCl aqueous solution added and the viscosity is determined as a pH-dependent viscosity curve.

The results are shown in FIG. In Figure 1, →-← is a graph for the barium sulfate sol of Prescription Example 3, and →
-(G) is a graph for barium sulfate sol of Prescription Example 4, (H) is a graph for Baritogen sol (manufactured by Fushimi Pharmaceutical Co., Ltd.),
20 (manufactured by Fuso Pharmaceutical), →. 1
is a graph for Varitop 120 (manufactured by Sakai Chemical). From FIG. 1, the barium sulfate contrast agent of the present invention is HC
It is clear that the sol viscosity changes stably regardless of the amount of # added or the passage of time.

Test Example 2 An artificial stomach wall was created using a gelatin film in a petri dish, and the first pharmacopoeia liquid and various barium sulfate sols were mixed at a ratio of 5:1, and the walls were heated over time immediately after mixing, 10 minutes later, 20 minutes later, and 80 minutes later. Afterwards, the fluidity, cohesiveness, adhesion, properties, affinity, homogeneity, etc. are observed by gently rolling the mixture back and forth from side to side for 1 hour (same conditions).

a) Appearance b) SOFTEX XEMBW (SOFTEX Co, Lt.
d.) Radiographs obtained using X-rays The results obtained are shown in Table 1. In Table 1, 10+
Juhan-in is particularly excellent, 10++ 10-in is good, 10 + 10-in is somewhat good, + 10-in is usable, and Shiin is unusable. Comparative Control Example 1 uses Baritogen Sol, Comparative Control Example 2 uses Ba'J) Tubu 120, and Comparative Control Example 8
For Comparative Example 4, 480 ky of barium sulfate, 25 kl of sugar, and 1.920 kg of the dried powder of water extract of gum tragacanth obtained in Reference Example were added to 1201 purified water and thoroughly stirred with a mixer. 2 obtained by
00 W/V% barium sulfate sol was used in each case.

Table 1 Table 1 (continued)

[Brief explanation of drawings]

FIG. 1 is a graph showing pH-dependent viscosity curves of various barium sulfate sols. (Above) Agent: Eiji Saegusa, Patent Attorney

Claims (1)

[Claims] (2) A barium sulfate contrast agent for X-rays, characterized by containing vanillic acid and/or vanillin and gum tragacanth and/or a processed product thereof.