DE1467850A1 - Diagnostic - Google Patents

Description

CHUGAI SEIYAKU KABUSHIKI KAISHA

No. J5, Nihonbashi Honcho 3-chome, Chuo-ku, Tokyo, Japan

Diagnostic

The invention relates to gastric adjuvants containing novel adjuvants and intestinal fluoroscopic diagnostics and their manufacture.

The diagnostic agents according to the invention are characterized in that, as adjuvants, they contain foaming substance compositions with a Contain defoaming agents that together nut barium sulfate salt can be used and which give a distinct shadow when the esophagus and stomach are due to X-rays be photographed by barium sulfate contrast.

Up until now, it was necessary to introduce air into barium sulfate contrast images in order to ensure effective dispersion and adhesion of the Barium sulphate and create distinct shadows. In this common method, a nasogastric tube had to be inserted and it required that air be swallowed. So that unspecific shadows are avoided, which are smaller as a result Form vesicles that appear inside the organs on small, in the

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Riumsulfatalz adhere to dispersed vesicles, one has, for example Silicone substances are used to switch off such small bubbles.

The diagnostic device according to the invention is characterized by the content an adjuvant that, instead of bringing in air, releases carbon dioxide gas in the stomach and in which the small Eliminate vesicles that impair clear contrasts using defoaming agents contained in the adjuvant.

The adjuvant contained in the diagnostic agent according to the invention consists from a mixture of foaming ingredients and defoaming agents as active components. This is convenient Defoaming agent in liquid form, so that there is always the substance releasing the carbon dioxide, such as carbonates or bicarbonates, or also on the carrier substances, such as lactose or starch, can be adsorbed.

The adjuvant contained in the diagnostic agent according to the invention can foam up in the stomach, and the small ones that arise in the process Blisters become closed due to the action of the defoaming agent with the small blisters adhering to the inner wall of the organs combined in a single gas mass. This facilitates the adhesion of the barium sulfate to the inner walls of the organs, and . one can get clear shadows without any other means, ins- " especially if the defoaming agent is based on carbonates or. Bicarbonate is adsorbed. As a result, the adjuvant needs to be present in the diagnostic agent according to the invention only in comparatively small amounts because there is no separate adsorbent is required and the foaming that occurs through contact with the acidic components can be delayed as a result the adsorption of the defoaming agent on the substances that develop the carbon dioxide.

The subject matter of the invention is described in detail below.

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The foaming components in the diagnostic agent according to the invention contained adjuvant consist of at least one acid component and at least one substance, which is released decomposed by carbon dioxide gas from the acid. As acid components solid acids can be used, for example organic acids such as fumaric acid, succinic acid, citric acid, tartaric acid, Ascorbic acid, adipic acid or their acidic salts, or acidic salts of inorganic acids such as acidic phosphate salts. These connections are also suitable in view of their unimportance. As carbonates or bicarbonates can, for example, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate or magnesium carbonate can be used advantageously.

Silicates can advantageously be used as the carrier material on which the defoaming material is adsorbed, such as, for example Magnesium silicate or aluminum silicate; you can also use aluminum hydroxide, Use magnesium oxide, calcium secondary phosphate, or microcrystalline cellulose other than lactose and starch. If the defoamer is to be adsorbed onto the carbonates or bicarbonates in the composition, then it sets it is best to use magnesium carbonate, since its adsorption activity is advantageous for the defoaming agent; and sodium coder Potassium) bicarbonate has optimal properties in terms of the activity to form a breakable foam. It is therefore for practical purposes are particularly advantageous if a small amount of magnesium carbonate is used to adsorb the defoaming agent and this kit supplements sodium (or potassium) bicarbonate.

As defoaming agents, for example, surface-active agents, like silicone substances, namely dimethylpolysiloxane, higher aliphatic acids such as Nopco Vegefat Y (trademark of Nopco Chemical Co.), Span substances (trademark of Atlas Powder Co.), higher aliphatic alcohols such as 1,12-dihydroxyoctadecane, 1,1,1-o-trihydroxyoctadecane, polyoxyethylene-polyoxypropylene condensation product, among these substances, dimethylpolysiloxane is particularly suitable.

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Preferably the acidic constituent has an equal amount of carbonates or bicarbonates compounded, and the defoaming agent is in an amount of 10-400 mg, preferably 350-100 mg, each 100 ecm of the carbon dioxide gas released from the foaming constituents specified above was added.

If the defoaming agent is present in excess, then this has the consequence that the foaming is only moderate and the contrasting effect gets bad.

The adjuvant contained in the diagnostic agent according to the invention wins by adsorbing the defoaming agent on the carrier substance, such as, for example, lactose or starch, then the mixture Granulated using conventional methods, adding the acidic component and the carbonate or bicarbonate in granulated form and appropriate amounts of a lubricant are admixed, and then the mixture is tabletted. Or you can turn the defoamer on adsorb all or part of the carbonate or bicarbonate, granulate the mixture in the usual way, to do this, add the granulated acidic component, and if necessary, the remaining carbonate or bicarbonate, also in granulated form, add, then suitable amounts of lubricant add and tablet the mixture.

Furthermore, it is also possible that both the support material and the carbonate or bicarbonates can be used as adsorbents at the same time begins. This means that the defoaming agent is adsorbed both on the carrier material and on the carbonates or bicarbonates, the adsorbent is granulated, then the granulated acidic component is added, then, if necessary, the remaining carbonate or bicarbonate is admixed in granulated form, and the granulated mixture is brought into a suitable form .

When the composition is used in a granulated state should, then the tablets are roughly crushed and worked up into uniform granules. If necessary, the tablets can or granules can be coated to facilitate administration.

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Various tests of the adsorption of defoaming agents, such as dimethylpcfysiloxane, Span 85 (trademark of Atlas Powder Co.), 1,12-dihydroxyoetadecane on some carbonates or bicarbonates and some carriers are in the table below illustrated.

Table 1

Amount adsorbed (g)

Adsorbent

Dimethylplysiloxane

Chip

(Trademark )

1 :, 12-dihydroxyootadecane

sodium 7.5 4.0 Potassium bicarbonate 3.2 - Potassium carbonate 6.7 2.0 C alcium carbonate 10.3 4.5 Magnesium carbonate 27.9 25.0 Sodium bicarbonate - 2.4 Magnesium silicate 15.3 17.0 Aluminum silicate 17.4 19.0 Magnesia
secondary calcium
phosphate 13.3
8.0 18.0
5.0 Aluminum hydroxide 24.0 25.0 Cellulose
(microcrystalline) 21.7 11.0 Lactose 5.1 4.4 Starch (grain) 8.7 3.0

3.0

1.0

3.0

5.0

24.0

1.0

12.8

17.0

7.0

5.0 23.0

8.0 4.0 5.0

Note: The amount adsorbed in the table is the amount of mixed solution of lOjfcLger polyvinylpy & lidon paste (solvent: Ethanol) and defoaming agent (weight ratio 27:10 for 1,12-dimethylpolysiloxane and Span 85 (trademarks of Atlas Powder Co.); 1: 4 for 1,12-dihydroxyoctadecane), compared to 20 g adsorbent, in the event that this solvent mixture is added to the adsorbent, the mixture is kneaded through a sieve with sieved through a mesh size of 0.833 mm (20 mesh), is dried and granulated.

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The adjuvant contained in the diagnostic agent according to the invention can be used together with barium sulfate salt, and one then appropriately handles the product as follows:

1. Administration after shadow formation using barium sulfate salt solution is done.

You give a large amount of barium sulfate salt solution to form the shadow, and then you give that Adjuvant with the least amount of water possible.

2. Administration shortly before the start of fluoroscopy.

The adjuvant is administered with a small amount of barium sulfate salt solution very shortly or 2 to 5 minutes before the pluoroscopy.

This type of application achieves particularly good results and gives clear shadows; administration is easy, and double contrasts can be obtained in a simple manner because it is possible to adjust the amount administered to the specific one Adjust and increase or decrease conditions on a case-by-case basis.

example 1

120 g of a 30J & Lgen solution of purified sugar became 1200 g Monosodium fumarate was added and the mixture was kneaded. The mixture was passed through a sieve with a mesh size driven through 1.651 mm (10 mesh), dried and granulated.

30 g of a ^ OJ & gen solution of purified sugar became 500 g Sodium bicarbonate was added and the mixture was kneaded. Then the mixture was passed through a sieve with a mesh size driven through 1.651 mm (10 mesh), dried and granu-

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lates. Separately, there was an emulsified mixture of 110 g lOJ & Lger polyvinylpyrrolidone paste (solvent: ethanol) and 40 g of dimethylpolysiloxane were added to 100 g of magnesium carbonate. The mixture was kneaded, passed through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

The three different types of granules described above were mixed, and 80 g of polyethylene glycol and Added 20 g of magnesium stearate. This mixture was tabletted on a tabletting machine, and tablets were obtained with a weight of 0.12 g per tablet.

Example 2

There were 70 g of a 20 # solution of purified sugar (the 50 # methanol contained) to a mixture of 400 g of tartaric acid and 400 g of sodium dihydrogen phosphate were added. The mixture was kneaded, passed through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

JO g of a 20% solution of purified sugar (containing 50 % methanol) was added to 500 g of sodium bicarbonate. This mixture was kneaded, passed through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

Separately, an emulsified mixture of 73 g of a 10J & Lgen polyvinylpyrrolidone paste (solvent: ethanol) and 27 g of Span "85" were added to a mixture of 60 g of magnesium carbonate and 40 g of calcium carboxymethyl cellulose. The mixture was kneaded, driven through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

The aforementioned three types of granules were mixed together, and 80 g of polyethylene glycol and 20 g of magnesium stearate were added. The mixture was tabletted on a tablet machine. The tablets became uniform granules with a grain diameter corresponding to a mesh sieve with a clear opening

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Mesh size between 2.794 and 1.168 mm worked up so that a granulated product was present.

Example 3

The emulsified mixture was made into 500 g of sodium bicarbonate 44 g 10 # polyvinylpyrrolidone paste (solvent: ethanol) and 16 g of Span "85" (sorbitan trioleate) are added and kneaded. The mixture was sieved through a 1.651 mm (10 mesh) sieve, dried and granulated.

The emulsified mixture of 42 g of a 10 ^ igen polyvinylpyrrolidone paste (solvent: ethanol) and 15 * 4 g of chip "85" were added, and the mixture was kneaded, driven through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

To the mixture of the aforementioned two kinds of granules were added 700 g of citric acid (granules), 80 g of polyethylene glycol 6,000 and 20 g of magnesium stearate added. The mixture was converted into tablets weighing 0.08 g per tablet in tablets.

Example 4

30 g of a 20% solution of purified sugar (containing 50 % methanol) was added to 500 g of potassium bicarbonate. The mixture was kneaded, passed through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

The emulsified mixture became 143 g of microcrystalline cellulose of 110 g of a 10% polyvinylpyrrolidone paste (solvent: Ethanol) and 40 g of dimethylpolysiloxane were added. the Mixture was kneaded, driven through a sieve with a mesh size of 1.168 mm (14 mesh), dried and granulated.

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The two aforementioned types of granules were made into 900 g of acidic ingredients, which were obtained by mixing citric acid and Monosodium fumarate in a ratio of 1: 2 had been obtained, and 80 g of polyethylene glycol 6000, 20 g were added Magnesium stearate was added and this mixture was made on a Tableting machine made into tablets with a weight of 0.08 g per tablet.

Example 5

50 g of a 20 $ 6 solution of purified sugar (the 50 # methanol contained) were added to 550 g of tartaric acid. The mixture was kneaded, passed through a sieve with a mesh size of 1.651 mm (10 mesh), dried and granulated.

50 g of a 20% solution of purified sugar became 500 g Sodium bicarbonate added. The mixture was kneaded through a sieve with a mesh size of 1.651 mm (10 mesh) driven through, dried and granulated.

Separately from this was a mixture of 10 g of a 10 # polyvinylpyrrolidone paste (Solvent: ethanol) and 40 g of dihydroxyoctadecane were added to 200 g of corn starch, the mixture was kneaded, driven through a sieve with a mesh size of 1.168 mm (l4 mesh), dried and granulated.,

There were 80 g of polyethylene glycol "6000" and 17 g of magnesium stearate was added to the aforementioned three kinds of granules, and this mixture was made into tablets on a tabletting machine tabletted with a weight of 0.1 g per tablet.

The diagnostic agent according to the invention is used as follows.

EXPERIMENT :

For the purpose of forming the shadow, 150 ml of a Barium sulfate salt solution was administered, and then 20 tablets of the following composition were given with 10 ml of water:

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In one tablet were included

Sodium bisulfate 25.00 mg Sodium monofumarate 42.00 mg, dimethylpolysiloxane 2.00 mg.

The results are shown in Figures 1 and 2 below, wherein Fig. 1 shows the image when working according to a known method and FIG. 2 is the picture when the diagnostic agent according to the invention is administered: CK. (48) male.

In the case where only barium sulfate was used alone, could only a large constriction on the larger side curvature (Fig. 1) can be observed, but if the invention Diagnostic agent was used, the large ulcer and its course could be clearly recognized (Fig. 2).

Figures 5 and 4 show once by the known method and once by means of the diagnostic agent according to the invention, the image of the patient T.K. (64) male.

If barium sulfate was used on its own, there was a big advantage can be observed on the less curved side. From this knowledge only the vague assumption could be derived, that there is some disease. However, when the diagnostic agent according to the invention was used for testing, a large The ulcer, similar to a crater, can be clearly seen.

5 and 6 show the diagnosis according to a known method or by means of of the diagnostic agent according to the invention on a patient Y.H. (27) female.

If only barium sulfate was used, only a deformed one could do it Duodenal outgrowth can be observed. However, if one examined with the diagnostic agent according to the invention, so could clearly recognize an ulcer and its outgrowths.

Claims

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Claims (6)

A4 Patent claims Diagnostic for gastric and intestinal fluoroscopic Diagnosis, characterized in that it contains an adjuvant which is composed of foam-forming components and defoaming agents, wherein the foam-forming ingredients are composed of at least one acidic component and at least one carbonate or bicarbonate. 2. Diagnostic according to claim 1, characterized in that that the defoamer adsorptively on at least a part the carbonate or bicarbonate and / or a carrier is st off bound. 3>. Diagnostic agent according to claim 1 or 2, characterized in that that the amount of defoaming agent in the adjuvant contained therein 10-400 mg, in particular 50-100 mg, each 100 ecm of carbon dioxide gas released from the foaming components matters. 4. Diagnostic according to claims 1-5, characterized in that that in the adjuvant acidic phosphate salts, fumaric acid, succinic acid, citric acid, tartaric acid, Ascorbic acid, adipic acid or their salts, as carbonates or bicarbonates sodium carbonate, sodium bicarbonate, potassium carbonate, Potassium bicarbonate, calcium carbonate or magnesium carbonate and, as defoaming agents, silicone substances, higher aliphatic Acids, chip substances (trademarks of Atlas Powder Co.) and higher aliphatic alcohols such as dimethylpolysiloxane, Nopco Vegefat Y (trademark of Pa. Nopco Chemical Co.), Span 20, 80, 85 (trademarks of Pa. Atlas Powder Co.), 1,12-dihydroxyoctadecane, 1,1,1-o-trihydroxyoctadecane, polyoxyethylene po lyoxypropylene condensation products are included. 809810/1327 - 11 - 5 .. A method for producing an adjuvant contained in the diagnostic of claims 1-4, characterized in that the defoaming agent on the carbon dioxide-releasing substance and / or on a carrier material such as lactose, starch, magnesium silicate, Aluminum silicate, magnesium oxide, secondary calcium phosphate, aluminum hydroxide or microcrystalline cellulose for Adsorption brings the remaining ingredients and the mixture forms. 6. The method according to claim 5, characterized in that the adsorbate is granulated, in addition the acidic components in granulated Porm and optionally the remaining amounts of carbonates or bicarbonates, also in granulated form, added, and shaping the granulate mixture into a suitable shape, in particular tabletted. 809810/1327 - 12