DE1767206B1 - X-ray contrast media - Google Patents

Description

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The invention relates to an oral and enema polyp to be stationary while air bubbles or Applicable X-ray contrast agent based on ferro- faeces move.

magnetic substances. It is also advantageous that only small amounts of the

Contrast media based on barium sulfate are known to require contrast media according to the invention. The application of this orally as well as by 5 z. B. in certain cases only about 100 g of contrast medium that can be administered as a barrel is quite a suspension in 150 cm ^{3 of} water to make the examination easy, but not free from disadvantages. This allows the human stomach to be clearly differentiated from tumors while food remains, faeces and air bubbles do not always require 200 g of barium sulfate for the same purpose, so that are borrowed.

Misinterpretations are possible. Since the contrast medium is good compared to the well-known ferromagnetic conc. B. in the duodenum very quickly again tracing agents, such as iron carbonyl powder, have been given by the Kongos diagnosis is very difficult. The locking means of the present invention has the advantage Radiologist also has practically no control over lower specific gravity and chedie internal diffusion of the barium compound, although being mixed inert; the iron carbonyl is in it is often desirable or necessary to coincide with that contained in the stomach to some extent Concentrate contrast media in body regions, hydrochloric acid around. The contrast media according to the invention which it would normally not penetrate. on the other hand, are inert and non-toxic when taken orally In such cases the radiologist is forced to be applied in or through an enema; you will be Applying pressure to certain areas of the abdomen- rapidly absorbed and quickly restored by mammals the and the examination table to incline to the 20 eliminated.

Bringing the patient into the desired position. Barium The contained in the contrast agent according to the invention

Sulphate contrast media are also often not well tolerated. Tenen magnetic ferrites are ferromagnetic X-ray contrast media and therapeutic agents on the ceramic oxides with two opposite one another Basis of ferromagnetic substances are known from: magnetic crystal lattices, which however do not interfere with each other "Magnetism in Medicine," "Journal of Applied Phy-25. Ferrites umsics suitable as contrast media «, Vol. 31, No. 5 (May 1960), pp. 404s and 405s; hold magnesium ferrite, barium ferrite, manganese »Experimental Approach in the Use and Magnetic Ferrite, Manganese-Zinc Ferrite, Magnesium-Zinc Ferrite, Control of Metallic Iron Particles in the Lymphatic Nickel Ferrite, Magnetite and / or the ferromagnean Vascular System of Dogs as a Contrast and Isotic Grenade. Other ferrites, such as cadmium, zinc topic Agent, "American Journal of Radiology, Vol. 90, 30, and copper ferrite, are less suitable because they are at No. 5 (November 1963), pp. 1068-1077; »Magnet room temperature does not have the required magne-attracts Iron to Thrombosis Aneurysms, "Journal of tables units per gram possess to a Konthe American Medical Association, Vol. 195, No. 11 Allow trolling through magnetic fields. (March 14, 1966), pp. 28 and 29; »Particles Iron Out In some cases, especially when psychological

Cranial Aneurysm, "Medical World News (May 27, 35 somatic difficulties along with the Ver-1966), Pp. 30 and 31. Patient tolerance is of primary importance

These contrast media containing iron particles are, the contrast media preferably contains magnesium ferrite (MgFe ₂ O ₄ ) for diagnostic purposes and / or used in thrombosed intracranial aneurisms. The iron particles are, however, in the human therapeutic examination of the gastrointestinal tract. lent body of the patient is not completely inert, and its 40. This ferrite crystallizes in a spinel structure according to a fairly high density, making it necessary to take its manufacture by sintering at temperatures of large amounts by weight, around a contact between 1000 and 1300 ° C. It is essentially a static effect to achieve. both in water and in hydrochloric acid

The present invention is based on the object of being insoluble at body temperature and capable of forming particles the disadvantages of the known contrast media are over-ground, the one to the commercially available one squirm. This problem is solved by a particle size similar to barium sulfate, i. H. about Orally and enema-applicable X-rays have 1 to 50 microns.

contrast medium based on ferromagnetic substances, the magnetization of magnesium ferrite is of

a magnetic ferrite with a particle size up to depending on the type of manufacture and cooling, to 50 microns and 30 to 80 electromagnetic input 5 ° When cooling with air, the material is removed from the units per gram taken as a ferromagnetic substance furnace and in the containers in which it is contains. has been heated, cool to room temperature

The contrast agent according to the invention has the advantage; in this way a saturation magnetite part, that only small amounts have to be applied, from 30 to 40 electromagnetic units in order to achieve the desired contrast of an organ 55 per gram according to the firing temperature and aim; it has the further advantage of having a percentage excess of MgO in the exterior Magnetic field reaches the contrast agent in certain duct material. When cooling with ice water Body regions, e.g. B. in gastro-intestinal or you quickly take the ferrite out of the oven and throw it Lymphatic tract, can be enriched without removing it from the hot container in an ice bath. To this Position of the patient or the treatment table can have a saturation magnetization of up to 60 while must be changed. In addition, it is made electromagnetic units per gram possible, the contrast agent according to the invention z. B. be.

to distinguish between air bubbles and faeces. If it is also desirable that the invention

and to attract polyps by making proper contrast media a deterred magneman first of all the magnetic contrast medium has this 65 sium ferrite, since this ferrite has a higher Moved towards objects and then the content of electromagnetic units as a not entire mass moved. When fluoroscopic sub-quenched has ferrite, other ferrites do not have to Searches using this method seem necessarily to be treated in this way.

While magnesium-zinc-ferrites, i.e. H. Ferrites that Containing about 10% zinc, having 59 electromagnetic units per gram when after Quenched by heating, these ferrites have a saturation magnetization after their production without quenching of 48 electromagnetic units per gram.

Magnesium ferrite is particularly desirable for oral administration because, depending on the percentage of manufacture, γ-ferric oxide and up to 2 percent by weight Guar gum as a stabilizer.

A contrast 5 is preferably used for the diagnostic examination of the gastrointestinal tract medium, which consists of 90 to 40 percent by weight magnesium ferrite, 10 to 60 percent by weight y-ferric oxide and up to consists of 2 percent by weight guar gum as a stabilizer and a saturation magnetization of 45 to 80 electromagnetic units per gram and

its color ranges from orange-brown to dark-brown with an average particle size of 1 to 50 microns fluctuates. Magnesium ferrite has the further points.

Advantage of remaining without an aftertaste. It is also desirable to use the magnetic

It is assumed that the contrast medium containing sium ferrite as a contrast medium for use in magnesium ferrite coats the mucous membrane of the manure in ulcer therapy with magnesium oxide in the gastrointestinal tract. This coating 15 to mix. The magnesium oxide, a recognized contains a substance of the formula (MgO) · MgFe ₂ O ₁ , the drug for the treatment of ulcers, does not form agglomerates, which can easily be enriched by a magnetic field and a solid solution in the magnesium ferrite the X-ray absorbs these substances well by sintering the mixture with temperature rays. temperatures of about 1000 ⁰ C can be produced. That

When the administration of a black magne- 20 magnesium oxide can be used in amounts of about 10 to table ferrite is not disadvantageous, the contrast contains 100 percent by weight of the magnesium ferrite used medium preferably barium ferrite because of this. It has been found that outstanding when used magnetic properties. lower proportions of magnesium oxide, preferably about In a special case, namely the diagnostic 10%, the magnetization of the ferrite is increased, and / or therapeutic treatment of the lymphatic system 25 By adding higher amounts of magnesium oxide, systems, the preferred contrast medium is the sod. H. for shares in the order of 50% called ferromagnetic grenade. These substances, or more, the magnetization is decreased, however can easily produce extremely fine particles with particles- the structure of the ferrite is noticeably improved and the sizes from 0.1 to 10 microns can be crushed. It lightened the coloring, reflecting the administration to the a ferromagnetic contrast was found to relieve 3 ° patients.

medium with such a particle size is important to It may also be desirable to

a satisfactory X-ray examination of the magnesium ferrites according to the invention as additives To allow lymphatic system. to use for pharmaceutical formulations

The magnetic ferrite contrast according to the invention to facilitate their identification. These substances can medium other than barium contrast medium can serve as marking or labeling additives, contain known additives. However, it is desirable to change the composition of the Worth seeing, especially the preferred magnesium special tablet or other form of medicinal ferrite material to be mixed with y-ferric oxide to identify the agent to which they are admixed. in the To increase the saturation magnetization of this substance in view of the wide range of magnetic and and thereby an improved enrichment of the X-ray absorption properties of the various to achieve trast means by an external magnetic field. Ferrites, the different forms that this A mixture that can be added up to about 60 percent by weight of materials (so can contains y-ferric oxide, a saturation magnetizing spherical ferrites can have a flat ellipsoidal shape or a tion up to 80 electromagnetic units per gram, elongated ellipsoidal shape), and the possible generally from about 45 to 70 electromagnetic 45 ability to manufacture composite ferrite-ele units per gram. y-ferric oxide is essentially inert from two or more individual ferrite elements; it dissolves only weakly in chlorine materials (for example through extrusion processes) Hydrogen acid at a pH of 1 and body it is possible to produce "ferrite markings" that temperature. for a large number of different medicinal products

Preferably the Magnesium Ferrite or one of 50 formulations are specific.

other ferrite-containing contrast media in aqueous The following examples illustrate preferred

Suspension administered by the oral route. It has been wise embodiments of the invention found that stable suspensions of these substances X-ray contrast media and the method for digestion Mixing the ferrite with a stabilizing administration of these agents for diagnostic and / or Agents based on guar gum can be used for therapeutic purposes without the invention being applied to them can; Such a contrast agent consists of 90 to restrict embodiments. 40 percent by weight magnesium ferrite, 10 to 60 Ge. .

weight percent y-ferric oxide and up to 2 weight examples

percent guar gum, the particles of which were used to produce a magnesium ferrite

an average size of 1 to 50 microns and 60 g each of the two containers of a 119 g ball mill a saturation magnetization of 45 to 80 electro-ferric oxide, 62.9 g magnesium carbonate, 560 ml water, have magnetic units per gram. Another 25 porcelain balls with a diameter of 19 mm and known stabilizers, such as pectin, carboxymethyl-20 porcelain balls filled with 12 mm diameter, cellulose, and sodium alginate, are less effective. The mixture was run at 50 rpm for 3 hours

Another preferred means for diagnostic 65 grind. Then the material was made from both and / or therapeutic purposes contains according to the container filled into a Büchner funnel and the Invention at least 40 percent by weight of one or most of the water withdrawn therefrom. The Mamehrerer magnetic ferrites, up to 60 weight material, was in a suitable drying cabinet

Porcelain container dried at 150 "C for 15 hours.

The ferrite was produced by a preheating step which was carried out for 2 hours in a ^{furnace heated to 1000 °} C. under an oxygen atmosphere. Conventional magnesium-ferrite mixtures, on the other hand, are then subjected to a firing stage at temperatures between 1200 and 135O ⁰ C, which leads to the mixture darkening to a black or black-brown color. However, the preheated magnesium ferrite had a less unpleasant reddish brown color. Therefore, the preheated only material was preferred, although the magnetization of the preheated material was only about 27 electromagnetic units per gram, while after firing the mixture a magnetization of 36 electromagnetic units per gram can be achieved. components do not separate themselves under the effect of gravity or magnetic forces.

The contrast agent was administered to a number of guinea pigs as test animals by inserting a flexible tube through the throat of each animal into the stomach and introducing 5 to 10 cm ^{3 of} the contrast agent. Each of the test animals was then viewed about 1 hour after the administration of the contrast agent on the fluorescent screen, while a very effective magnet was passed over the abdomen and sides of the animal under exposure to X-rays, to the effect of the magnetic field generated in this way on the contrast agent in the gastro - Determine the intestinal tract.

Two permanent magnets were applied in this way. One of the magnets was a strong one Horseshoe magnet with a 2 cm wide gap and a maximum field strength in the gap of 1.7 KiIooersted. The field strength at a distance of approximately

Contrast media containing magnesium ferrite
was transferred into an aqueous suspension which contained a γ-ferric oxide as an additional 20 2 cm on the perpendicular to the center of the forehead material for magnetization. The surface area was about 0.4 kiloersted, which corresponds to the γ-ferric oxide produced during 245 g of the magnesium ferrite with 250 g of the experiment inside the test animals, ^{corresponding to about 1000 cm 3 of} the field strength. The second magnet had to produce the desired aqueous suspension. essentially the shape of half a 7 cm disc

This aqueous suspension was in doses of 50-25 diameter, 2 cm thick and was ^{magnetized along the axis or 150 cm 3 to} the patient by the oral route through a cylinder, half of which extends. The patients were about 5 minutes after
the ingestion of the contrast agent is examined radiologically.

A permanent magnet was placed over the abdomen of each patient during irradiation moved to determine the effect on the contrast medium in the gastrointestinal tract. Of the magnetic ferrite generated on the fluorescent screen and on the X-ray film in the same way a darkening characteristic of barium sulphate. In addition, it was found that the

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Movement of the magnet acting from the outside an enrichment of the ferrite material in defined parts of the gastrointestinal area.

Example II

A contrast medium similar to that used in Example I was prepared using twice the stoichiometric amount of the magnesium carbonate given in Example I. After reacting the constituents forming the ferrite in the manner described, a material was obtained which contained MgO dissolved in the ferrite and which, when suspended in an aqueous medium, showed a clearly basic reaction _{due to the formation of Mg (OH) 2.} After administration in the manner described in Example I, this material showed the same darkening effect by absorption of X-rays and could moreover be used in ulcer therapy.

Example III

A mixture of 8 g of a commercially available barium sulfate formulation (available under the name "Barotrast", which contains barium sulfate and an emulsifier) and 6.4 g of powdered manganese-zinc ferrite (MnZZn ₁ ^ Fe ₂ O ₄ , where χ 0.5) were initially mixed by hand and 25 cm ^{3 of} milk were added with stirring. Finally the mixture was ball milled for about 15 minutes. In this way, a stable suspension of the ferrite was produced, the solid Be disk of which had been cut off. This magnet produced a field strength of approximately 0.4 kiloersteds at 1 cm from each of the flat faces.

By using the magnets described, it was made possible to pass the contrast agent through the Move the stomach of each test animal and accumulate the agent on the one approached by the magnet Side of the animal. It was also possible by attaching a horseshoe magnet on the side of the animal, to bring its small intestine between the poles of the magnet. The movement this magnet along the side of the animal prompted the connecting parts of the intestine, the Following magnet movement, and removal of the magnet had an apparent straightening the intestinal sections and their return to their normal position. This procedural step could and was repeated several times during the fluorescopic examination.

A test animal was sacrificed and opened to determine whether particles of the contrast agent were present Walls of the small intestine sections have penetrated which are exposed to the greatest magnetic field strength was. In these histological examinations it was found that no ferrite particles enter the intestine, have penetrated the stomach or liver of the test animals.

Another test animal was sacrificed and opened after the flat permanent magnet was 2 hours had been glued to its side for a long time. The pulp administered to the animal was found to be above everything stayed in the stomach; only a small proportion of the contrast agent had the upper section of the duodenum. This section of the duodenum was attracted to the magnet; this prevented the material from moving further and blocked the exit. Here, too, no ferrite particles were found in deeper regions than on the surface of the intestine.

It was found on both of the experimental animals that had been killed that the contrast medium remaining in the stomach a pH of 3, the one remaining in the intestine

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pH 8. Both samples of the material appeared to be the same consistency as before feeding to own.

The following examples relate to the composition of other contrast media, which guar gum included as a stabilizer (Example IV) and illustrate how the saturation magnetization of the ferrite-containing contrast agent can be modified by varying the manufacturing process can (Examples V to VII).

Example IV

A contrast medium similar to that formulated in Example I was prepared. The contrast agent contained 245 g of the magnesium ferrite described in the example mentioned, 250 g of γ-ferric oxide and 10 g of guar gum as a stabilizer in about 11% aqueous suspension.

Example V

A mixture of 843 g MgCO ₃ was mixed in a large ball mill with 798 g Fe ₂ O ₃ and 71 water. This material contained a hundred percent excess of MgO. The mixture was fired in two parts at 1000 ^{° C. for 4 hours each.} It was then quickly removed from the oven and quenched in an ice-water bath. The magnesium ferrite obtained achieved a saturation magnetization of 48 electromagnetic units per gram.

Example VI

Mixing 676 g of MgCO ₃ with 1038 g of Fe ₂ O ₃ and 51% of water produced a material containing a 30% excess of MgO. It was fired at 1000 ° C. for 6 hours and quenched in an ice-water bath as described. The magnesium ferrite obtained achieved a saturation magnetization of 53 electromagnetic units per gram.

Example VII

Mixing 371 g of MgCO ₃ with 639 g of Fe ₂ O ₃ and 4.5 liters of water produced a material with a 10% excess of MgO. It was fired for 5 hours at HOO ⁰ C and, as already described, quenched with ice water. The magnesium ferrite reached a saturation magnetization of 58 electromagnetic units per gram.

The scope of the invention also includes means relating to the specific composition and its Method of application may differ from the means described in the previous examples.

Claims (5)

Patent claims: 1. Oral and enema-based X-ray contrast medium based on ferromagnetic Substances characterized in that it is a magnetic ferrite with a particle size up to 50 microns and 30 to 80 electromagnetic units per gram as ferromagnetic Contains substance. 2. X-ray contrast medium according to claim 1, characterized in that it is used to diagnose the The gastrointestinal tract contains a magnetic magnesium ferrite. 3. X-ray contrast medium according to claim 2, characterized by an additional content of γ-ferrite oxide. 4. X-ray contrast medium according to claim 1, characterized in that it is used to diagnose the Lymphatic System contains a magnetic garnet. 5. X-ray contrast medium according to claim 1, characterized in that it is a magnetic Contains barium ferrite. 109 540/356