FR2569564A1 - Method for the stabilisation of a contrast product comprising barium sulphate, and product resulting therefrom - Google Patents

Abstract

Radiological contrast product comprising barium sulphate. It contains a sodium carboxymethylcellulose having a degree of etherification of at least 1.50 as a suspension/dispersion stabilising agent.

Description

 The present invention relates to a novel radiological contrast product comprising barium sulfate.

 Barium sulphate is a compound that is very chemically stable and non-toxic physiologically and has a strong X-ray masking effect. It is therefore widely used as a radiological contrast medium.

 For its internal application as a contrast agent, barium sulphate must be converted to a fluid soil, in which a suspending agent is added to prevent barium sulfate from precipitating and to stabilize its dispersion. Hitherto, sodium carboxymethylcellulose (hereinafter referred to as CMC) has been widely used as a suspending agent for this purpose.

 In recent years, there has been a demand for a contrast product comprising highly concentrated barium sulfate. However, it is very difficult for conventional CMC to completely and simultaneously satisfy all the requirements imposed on such a contrast medium, such as good fluidity, suppression of precipitation and high resistance to acids.

Under these conditions, the Applicant has studied the development of a CMC which is optimal for use in the preparation of a contrast medium comprising barium sulfate, and ultimately resulted in the present invention, based on on the discovery that all the properties such as low viscosity, good fluidity and suppression of precipitation, which are required of a contrast medium, can be imparted simultaneously with the high-concentration barium sulphate, by incorporating therein a
CMC with a degree of etherification of at least 1.50.

 It is an object of the present invention to provide a radiological contrast product comprising barium sulfate, wherein sodium carboxymethylcellulose having a degree of etherification of at least 1.50 is used as a suspension-dispersion stabilizer for the contrast product. In addition, it is desirable that the CMC has a viscosity of 2.10 2 Pas in a 2 X aqueous solution.

 In general, the concentration of barium sulfate in the contrast medium of the invention should be in the range of 55 to 70%. As the CMC which is used as the suspension-dispersion stabilizer in the present invention has a degree of etherification reaching at least 1.50> the contrast product which is incorporated therein retains its acid resistance, fluidity and screw cosity, so that it is easy to drink and still has an improved adhesion to the inner wall of the stomach, thanks to which one can obtain an effect of increased contrast.

 The following nonlimiting examples are given by way of illustration of the invention.

EXAMPLE 1
Barium sulfate sols with the following ingredients, containing a CMC having a given viscosity (5-10-2 Pa.s in 2% aqueous solution) and varying degrees of etherification, are prepared using a biaxial mixer. Table 1 gives the results of evaluation tests for barium sulphate soils.

Ingredients:
Barium sulphate compliant
at the Japanese pharmacopoeia 7.0 kg
CMC 0.12 kg
purified water 5.0 kg
The evaluation tests were carried out by the following methods
Conditions for determining viscosity
Brookfield Viscometer, 25 "C, 60 rpm
Sedimentation test
A prepared soil is placed with sufficient stirring and dispersion in a 100 ml graduated test tube and allowed to stand for 10 days, and the volume of the supernatant liquid is determined.

Acid resistance test
30 ml of artificial gastric juice is placed in a glass test tube, and one drop of soil is added.

The soil is examined with the naked eye immediately after it has been added dropwise, and after 30 minutes it is allowed to stand, and its coagulation state, represented as 0 or X, is evaluated.

0: the soil is deposited and dispersed in fines by
ticules and the liquid becomes strongly cloudy.

: the soil coagulates into small particles and
deposited, and the liquid becomes cloudy
X -: the soil coagulates into coarse particles and
settles, and the liquid becomes slightly
cloudy or limpid.

Determination at tg e
This is one of the methods for determining fluidity. The closer the fluid is to a Newtonian flow, the higher the value of tg 9 is to 0. The higher the thixotropic properties, the higher the tg O value.

viscosity at 6 rpm
1 og
viscosity at 60 rpm
tan e =
log 60
6
TABLE 1 - Evaluation Test Results
of Example 1.

<Tb>

Expe- <SEP> Degree <SEP> of Ether- <SEP> Viscosity <SEP><SEP> Test of <SEP> Resistance <SEP> tg <SEP> e <SEP>
<SE> SEP <SEP><SEP> Reaction <SEP><SEP><SEP> Reaction
<tb> N <SEP> the <SEP> CMC <SEP><SEP> CMC <SEP> mentation <SEP> acids <SEP>
<tb><SEP> 10-3 <SEP> Pa <SEP> ml
<tb><SEP> 1 <SEP> 0.65 <SEP> 351 <SEP> 13.0 <SEP> X <SEP> 0.33
<tb><SEP> 2 <SEP> 0.95 <SEP> 280 <SEP> 5.6 <SEP> a <SEP><SEP> 0.25
<tb><SEP> 3 <SEP> 1.25 <SEP> 93 <SEP> 0.5 <SEP> 0 <SEP> 0.21
<tb><SEP> 4 <SEP> 1.55 <SEP> 1 <SEP> 88 <SEP> 0.4 <SEP> O <SEP> 0.050
<tb><SEP> 5 <SEP> 1.85 <SEP> 75 <SEP> 0.3 <SE> O <SEP> 0.051
<tb><SEP> 6 <SEP> 2.15 <SEP> 71 <SEP> 0.3 <SEP> O <SEP> 0.048
<tb><SEP> 7 <SEP> 2.41 <SEP> 70 <SEP> 0.3 <SEP> O <SEP> 0.043
<tb><SEP> 8 <SEP> 2.85 <SEP> 65 <SEP> 0.3 <SEP> O <SEP> 0.040
<Tb>
As can be seen from Table 1, the incorporation of a
CMC with a degree of etherification of 1.50 or more is found to have remarkable effects on lowering the viscosity of the soil, improving its fluidity and preventing sedimentation
EXAMPLE 2
Barium sulphate sols with the following CMC-containing ingredients having a given viscosity <1.5 × 10-1 Pa.s in 2% aqueous solution) and various degrees of etherification are prepared using a biaxial mixer. Table 2 gives the results of evaluation tests for barium sulphate soils
Ingredients:
Barium sulphate following the
japanese pharmacopoeia 7.0 kg
CMC 0.08 kg
Purified water 5.0 kg
The evaluation tests were carried out by the same methods as in Example 1.

TABLE 2 - Evaluation Test Results
of Example 2.

<Tb>

Expe- <SEP> Degree <SEP> of Ethe <SEP> Viscosity <SEP><SEP> Test of <SEP> Resistan- <SEP> tg <SEP> tt <SEP>
<SE> SEP <SEP> Reaction <SEP><SEP><SEP><SEP><SEP>
<tb> N <SEP> the <SEP> CMC <SEP> CM <SEP> tation <SEP> acids
<tb><SEP> 10 <SEP> Pa.s <SEP> ml
<tb><SEP> 9 <SEP> 0.65 <SEP> 400 <SEP> 15.4 <SEP> X <SEP> 0.39
<tb><SEP> 10 <SEP> 0.95 <SEP> 294 <SEP> 7.9 <SEP>#<SEP><SEP> 0.31
<tb><SEP> 11 <SEP> 1.25 <SEP> 106 <SEP> 0.7 <SEP> 0 <SEP> 0.20
<tb><SEP> 12 <SEP> 1.50 <SEP> 89 <SEP> 0.5 <SEP> o <SEP> - <SEP> 0.057
<tb><SEP> 13 <SEP> 1.60 <SEP> 90 <SEP> 0.6 <SEP> O <SEP> 0.051
<tb><SEP> 14 <SEP> 2.00 <SEP> 91 <SEP> 0.6 <SEP> o <SEP> 0.045
<tb><SEP> 15 <SEP> 2.50 <SEP> 87 <SEP> 0.5 <SEP> o <SEP> 0.046
<tb><SEP> 16 <SEP> 2.85 <SEP> 84 <SEP> 0.3 <SE> O <SEP> 0.044
<Tb>

Claims (2)

 A method of stabilizing a radiological contrast material comprising barium sulphate in suspension and dispersion, which comprises adding sodium carboxymethylcellulose having a degree of etherification of at least 1.50 as a suspension stabilizer dispersion for the contrast product.  2 - Contrast medium comprising barium sulphate in suspension and dispersion and as a stabilizer for carbonyl methylcellulose sodium having an etherification degree of at least 1.50.