Classifications

• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G49/00—Compounds of iron
  • C01G49/0018—Mixed oxides or hydroxides
  • C01G49/0036—Mixed oxides or hydroxides containing one alkaline earth metal, magnesium or lead
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
  • A61K49/04—X-ray contrast preparations
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G49/00—Compounds of iron
  • C01G49/0018—Mixed oxides or hydroxides
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G49/00—Compounds of iron
  • C01G49/0018—Mixed oxides or hydroxides
  • C01G49/0072—Mixed oxides or hydroxides containing manganese
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
  • C01G49/00—Compounds of iron
  • C01G49/009—Compounds containing iron, with or without oxygen or hydrogen, and containing two or more other elements
• • G—PHYSICS
  • G11—INFORMATION STORAGE
  • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
  • G11B5/00—Recording by magnetisation or demagnetisation of a record carrier; Reproducing by magnetic means; Record carriers therefor
  • G11B5/62—Record carriers characterised by the selection of the material
  • G11B5/68—Record carriers characterised by the selection of the material comprising one or more layers of magnetisable material homogeneously mixed with a bonding agent
  • G11B5/70—Record carriers characterised by the selection of the material comprising one or more layers of magnetisable material homogeneously mixed with a bonding agent on a base layer
  • G11B5/706—Record carriers characterised by the selection of the material comprising one or more layers of magnetisable material homogeneously mixed with a bonding agent on a base layer characterised by the composition of the magnetic material
  • G11B5/70626—Record carriers characterised by the selection of the material comprising one or more layers of magnetisable material homogeneously mixed with a bonding agent on a base layer characterised by the composition of the magnetic material containing non-metallic substances
  • G11B5/70642—Record carriers characterised by the selection of the material comprising one or more layers of magnetisable material homogeneously mixed with a bonding agent on a base layer characterised by the composition of the magnetic material containing non-metallic substances iron oxides
  • G11B5/70678—Ferrites
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
  • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
  • H01F1/44—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of magnetic liquids, e.g. ferrofluids
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
  • C01P2002/00—Crystal-structural characteristics
  • C01P2002/30—Three-dimensional structures
  • C01P2002/32—Three-dimensional structures spinel-type (AB2O4)
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
  • C01P2004/00—Particle morphology
  • C01P2004/60—Particles characterised by their size
  • C01P2004/61—Micrometer sized, i.e. from 1-100 micrometer
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
  • C01P2006/00—Physical properties of inorganic compounds
  • C01P2006/42—Magnetic properties
• • C—CHEMISTRY; METALLURGY
  • C01—INORGANIC CHEMISTRY
  • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
  • C01P2006/00—Physical properties of inorganic compounds
  • C01P2006/60—Optical properties, e.g. expressed in CIELAB-values

Definitions

• Ferromagnetic contrast media incorporating magnetic ferrites such as magnesium ferrite, barium ferrite, manganese ferrite, manganese-zinc ferrite, nickel ferrite, magnetite, or ferromagnetic garnets; -ferric oxide and a guar gum stabilizer
• Such media are used for diagnostic or therapeutic treatments of the gastrointestinal or lymph tracts, by subjecting the patient to external magnetic fields to concentrate the medium in the body region to be diagnosed or treated.
• This invention relates to improved ferromagnetic contrast media, and more particularly to a method for the diagnostic and/or therapeutic administration of such media.
• barium sulfate as a contrast material in the gastrointestinal tract.
• the ingestion of "barium meals” provides a valuable diagnostic tool, enabling radiological investigation of the stomach and intestines, examination of contractions and movements, and determination of the location and size of ulcers and growths.
• the use of barium enemas facilitates radiological detection of the existence and location of growths along the colon.
• barium contrast media while relatively simple, is not free from complication. Misinterpretation may arise due to the presence in the region opacified of food remnants, feces, and air bubbles, which are sometimes difficult to distinguish from tumors. In some cases as, for example, in the duodenum, the barium compound passes rapidly, making diagnosis quite difficult. Moreover, the radiologist has practically no control over the internal diffusion of the barium compound, despite the frequent desirability or necessity to concentrate the contrast medium in regions to which it might not naturally diffuse. In such instances, the radiologist has been compelled to selectively apply pressure to the abdomen and tilt the examination table to vary the patients orientation as may be desirable.
• barium sulfate contrast media additionally poses problems as to patient acceptability, Thus, frequent variation of the patient's orientation as may be required in connection with barium therapy, may result in disorientation and even nausea of the patient during diagnosis or treatment. Additionally, the chalky taste of barium contrast media further complicates their use in human diagnosis or therapy.
• iron particles as contrast media or as therapeutic agents employed to thrombose intracranial aneurysms. Such iron particles are not, however, fully inert within a patients body and, moreover, possess relatively high densities, necessitating the administration of relatively large quantities by weight to achieve a desired opacifying function.
• a further object of the invention is to provide such a medium which is ferromagnetic in nature and which may thus be administered to a patient and thereafter subjected to a magnetic field applied externally of the patient's body to facilitate its concentration in any portion of the body.
• a ferromagnetic contrast medium incorporating a magnetic ferrite having a particle size of 50 microns or less and exhibiting a remanence magnetization approaching, and nearly approximating, saturization magnetization values of from about 30 to e.m.u.
• the patient may be subjected to an externally applied magnetic field to concentrate the composition in the particular body organ or cavity to be diagnosed or treated.
• the ferromagnetic contrast media hereof may thus be concentrated in given portions of, for example, the gastrointestinal or lymph tracts, without continually shifting the orientation of the patient or the treatment table. Moreover, it is possible to utilize the contrast material hereof to differentiate, for example, between air bubbles or feces and polyps by initially moving the magnetic contrast material relative to such objects, and thereafter moving the entire mass. Upon fluoroscopic examination employing such technique, polyps would appear stationary whereas air bubbles or feces would move.
• ferromagnetic contrast media of the present invention additionally facilitates the development of new therapeutic techniques.
• compositions containing such magnetic media may additionally contain suitable medicaments such as magnesium hydroxide, currently employed in ulcer therapy.
• the novel contrast media of this invention possess several specific advantageous properties, in addition to facilitating the improvements referred to hereinabove,
• the ferrite materials employed in accordance herewith are sufficiently ferromagnetic, exhibiting saturation magnetizations of from about 30 to 80 e.m.u., to facilitate effective concentration of the same by means of an externally applied magnetic field or fields.
• such materials have been found to absorb X-rays for diagnostic purposes, and to adhere to the walls of, for example, the stomach and intestines without clumping of flocculating.
• the ferrite materials may be provided in extremely fine size ranges of 50 microns or lesser magnitudes.
• ferrite contrast media hereof are required to satisfactorily effect any particularly desired contrast function.
• only about grams of ferrite would be suspended in [50 cc. of water to facilitate examination of the human stomach.
• the magnetic ferrites so utilized are ferromagnetic ceramic oxides containing two magnetic lattices which are opposed to one another but which do not cancel each other out.
• Ferrites which may be employed as contrast media include magnesium ferrite, barium ferrite, manganese ferrite, manganese-zinc ferrite, magnesium-zinc ferrite, nickel ferrite, magnetite, and the ferromagnetic garnets.
• Other ferrites, e.g., cadmium, zinc and copper ferrite are not so suitable in that they are not sufficiently magnetic, viz, do not possess a high enough magnetization of 30 e.m.u., per gram, at body temperature to permit control by magnetic fields.
• magnesium ferrite (MgFe O, as a contrast medium for diagnostic and/or therapeutic examination of the gastrointestinal tract.
• MgFe O magnesium ferrite
• Such material crystallizes with a spinel structure after preparation by sintering at temperatures between l,0OO and l,300 C. It is substantially insoluable in either water or hydrochloric acid at body temperatures and can be milled into particles having grain sizes similar to the commercially available barium sulfate materials, i.e., from about 1 to 50 microns.
• the magnetization of magnesium ferrite is dependent upon its mode of preparation and quenching. With air quenching, the materials are taken out of the oven and left to cool at room temperature in the containers they were fired in, and attain a saturation magnetization of 30-40 e.m.u. per gram, depending on firing temperature and percent excess MgO in the material. With ice water quenching, the sample is taken out of the oven very quickly and dumped out of the hot container and into an ice bath. A saturation magnetization of up to 60 e.m.u. per gram may be attained in this manner.
• magnesium-zinc ferrites e.g., one in which about percent zinc is incorporated, possess saturation magnetizations of 59 e.m.u. per gram if quenched after firing, such ferrites possess saturation magnetizations of as much as 48 e.n.u. per gram when prepared without quenching.
• Magnesium ferrite is particularly acceptable for oral consumption, as its color varies from orange-brown to a darkbrown, depending upon its mode of preparation. On the other hand, other magnetic ferrites are black and may thus be less acceptable for patient administration. Moreover, unlike barium sulfate, the oral administration of magnesium ferrite in, for example, an aqueous slurry, leaves no after-taste and is thus particularly suitable for use as an X-ray contrast medium.
• the magnesium ferrite when so administered, coats the mucosa of the gastrointestinal tract, the coating comprising a material of the formula (MgO),MgFe 0,, which does not agglomerate, which may readily be concentrated by magnetic force, and which is readily X-ray absorptive. It will, however, be understood that the present invention is not restricted to the preceding proposed mechanism ofoperation,
• the so-called ferromagnetic garnets may be readily sized into extremely fine particles, i.e., having particle sizes of from (H to 10 microns. It has been found that the use of a ferromagnetic contrast medium possessing such a particle size range is important to effect satisfactory X-ray examination of the lymph tract.
• the magnetic ferrite contrast material of the present invention may be administered together with other known adjuvants employed in connection with barium contrast media. It is, however, desirable, particularly in the case of the preferred magnesium ferrite material, to admix the same with 'yferric oxide.
• the 'y-ferric oxide is admixed with the magnesium ferrite in amounts of up to 60 percent by weight of the mixture to increase the saturation magnetization of the latter material and thereby facilitate improved concentration of the same by an externally applied magnetic field.
• the y-ferric oxide is substantially inert, dissolving only slightly in hydrochloric acid at a pH of l and at body temperatures.
• the mixture of magnesium ferrite and -y-ferric oxide in the amounts specified above, viz, in proportions of up to about 60 percent by weight of the mixture, may possess a saturation magnetization of up to 80 e.m.u. per gram, generally from about 45 to 70 e.m.u. per gram.
• the magnesium ferrite or other ferrite contrast medium is orally administered in aqueous suspension. It has been determined that stable suspensions of such materials may be produced by admixing the ferrite composition with a Guar gum stabilizing agent, other known stabilizers such as pectin, carboxy methyl cellulose and sodium alginate not being so effective.
• a Guar gum stabilizing agent other known stabilizers such as pectin, carboxy methyl cellulose and sodium alginate not being so effective.
• Guar gum which is recognized as a safe food additive, consists of the ground endosperms of the Guar bean (leguminous seed Cyamopsis tetragonolobus), the water-soluble fraction of which (85 percentl primarily comprises mannose and galactose, It is suitably admixed with the magnesium or other ferrite in amounts of from about l percent to Zpercent by weight ofthe mixture.
• the magnesium oxide a recognized medicament in ulcer treatment, forms a solid solution with magnesium ferrite when such materials are prepared in admixture by sintering at temperatures of about l,0O0C.
• the magnesium oxide may be employed in amounts of from about 10 percent to lOO percent by weight of the magnesium ferrite material. Use oflesser proportions of the magnesium oxide, preferably about [0 percent has been found to increase the magnetization of the ferrite. The addition of greater proportions of the magnesium oxide, e.g., amounts of the order of 50 percent or greater, lowers the magnetization but markedly improves the texture of the ferrite composition and lightens its color to facilitate improved patient acceptance.
• EXAMPLE 1 A magnesium ferrite was prepared by filling each of the two jars ofa ball mill with N9 grams of ferric oxide, 62.9 grams of magnesium carbonate, 560 ml. water, 25 porcelain porcelain balls 19 mm. in diameter, and 20 porcelain balls l2 mm. in diameter. The mixture was milled at 50 r.p.m. for 3 hours, after which the material from both jars was emptied into a Buchner funnel and most of the water extracted therefrom. The material was thereafter dried in a suitable porcelain container placed in an oven for 15 hours at l50 C.
• the ferrite was prepared by a prefiring operation conducted for 2 hours in a furnace heated at l,000 C. in an oxygen atmosphere. While conventional magnesium ferrite compositions are thereafter subjected to a firing operation at between ]200 C. and 1350 C., such darkens the color of the composition to a black or brown-black hue.
• the prefired magnesium ferrite on the other hand, had a less objectionable reddishbrown color. Accordingly, although the magnetization of the preflred material was only about 27 e.m.u. per gram as compared with a 36 e.m.u. per gram magnetization attainable after firing of the composition, the former material was preferred.
• the magnesium ferrite contrast material was placed in an aqueous suspension containing a y-ferric oxide magnetization adjuvant. 245 grams of the magnesium ferrite were thus admixed with 250 grams of the y-ferric oxide to produce about 1,000 cc. of the desired aqueous suspension.
• aqueous suspension Fifty or cc. doses of the aqueous suspension were orally administered to human patients. The patients were subjected to radiological examination approximately 5 minutes after ingesting the contrast medium.
• a permanent magnet was simultaneously moved across each patient's abdomen during irradiation to determine the effects of the same upon the contrast material in the gastrointestinal tract.
• the magnetic ferrite produced opacification on the fluoroscope and on X-ray film in the same manner as characteristic of barium sulfate. Moreover, it was found that movement of the externally applied magnet effected concentration of the ferrite material in predetermined portions of the gastrointestinal region.
• EXAMPLE 2 A contrast material similar to that utilized in Example l was prepared, employing twice the stoichiometric amount of magnesium carbonate set forth in the preceding example. Upon reacting the ferrite-forming constituents in the manner set forth above, a material was produced containing MgO dissolved in the ferrite which, when suspended in the aqueous medium, provided a distinctly basic reaction by the formation of Mg(OH),. Such composition, when administered in the manner described in Example I, produced like X-ray opacification and could, moreover, be utilized in connection with ulcer therapy.
• EXAMPLE3 A mixture of 8 grams of a commercially available barium sulfate formulation (available under the trade designation Barotrast" and comprising barium sulfate plus an emulsifier) and 6.4 grams of powdered manganese-zinc ferrite (Mn,Zn, ,Fe,0.. wherein it was about 0.5) were initially mixed by hand and 25 cc. of milk were thereafter added thereto with agitation. Finally. the mixture was ball milled for about minutes. A stable suspension of the ferrite was thus produced from which the solids did not separate by gravity or by magnetic at traction.
• the contrast material was administered to a number of test guinea pigs by inserting a flexible tube through each animal's mouth into its stomach and passing from 5 to It) cc. of the contrast material thereto.
• Each test animal was thereafter fluoroscoped approximately l hour after administration ofthc contrast medium, the test magnet being passed over the abdomen and sides of the animal simultaneous with X-ray irradiation to determine the effect of the magnetic field thus produced upon the contrast material in the gastrointestinal tract.
• the first such magnet was a strong horseshoe type magnet having a 2 cm. wide gap. and a maximum field strength within the gap of L7 kilo-oersted.
• the field strength some 2 cm. away from the gap along the perpendicular to the center of its face was approximately (L4 kilo oersted. which corresponded to the field strength produced within the test animals during the experiments.
• the second magnet was substantially a half disc in shape, 7 cm. in diameter. 2 cm. thick. and magnetized along the axis of a cylinder from which the half disc was cut. Such magnet produced a field strength of about 0.4 kilo-(worsted l cm. from either flat face.
• a further test animal was sacrificed and operated upon after having the flat permanent magnet taped to its side for 2 hours. It was found that the meal which had been fed to the animal remained primarily within its stomach. solely a small portion of the contrast medium having reached the upper section of the duodenum. Such section of the duodenum had been atrscted to the magnet. which prevented the material from moving on. thereby blocking the passage. Here. too. no ferrite particles were found deeper than the intestinal surface.
• Example 4 set forth the composition of further contrast media incorporating a guar gum stabilizer (Example 4 and illustrating the manner in which the saturation magnetization of the ferrite contrast material may be modified by variation in the method of preparation thereof (Examples EXAMPLE 4
• a contrast medium similar to that formulated in Example I was prepared.
• the contrast medium incorporated 245 grams of the magnesium ferrite prepared as described in such example. 250 grams of the y-ferric oxide and 10 grams of a guar gum stabilizer. in about 1 liter of aqueous suspension.
• EXAMPLE 5 A material with 30 percent excess MgO was prepared by mixing 676 grams MgCO, with I038 grams Fe,O,and 5 liters of water. It was fired for 6 hours at 1000C. and quenched in an ice water bath. as described above. The magnesium ferrite composition attained a saturation magnetization of $3 e.m.u. per gram.
• EXAMPLE 7 A material with ID percent excess MgO was prepared by mixing 37l grams MgCO with 639 grams Fqo and 4.5 liters water. It was fired at ll00 C. for 5 hours and ice water quenched as described above. The magnesium ferrite composition attained a saturation magnetization of 58 e.m.u. per gram.
• a method for X-ray visualization gastrointestinal tract of a patient which comprises:
• a contrast medium comprising an aqueous suspension of a magnetic ferrite consisting of a ferromagnetic ceramic oxide containing two magnetic lattices which are opposed to one another but which do not cancel each other out.
• said magnetic ferrite having a particle size of no more than 50 microns and exhibiting a saturation magnetization of from about 30 to e.m.u. per gram. and the contrast medium containing ofthe order of I00 grams of said ferrite per dose;
• said magnetic ferrite is selected from the group consisting of magnesium ferrite. magnesium-zinc ferrite. barium ferrite. manganese ferrite. manganese-zinc ferrite. nickel ferrite. magnetite and ferromagnetic garnets.
• An aqueous suspension of a magnetic ferrite and a guar gum stabilizer consisting of a ferromagnetic ceramic oxide containing two magnetic lattices which are opposed to one another but which do not cancel each other out. having a particle size of no more than 50 microns. and exhibiting a saturation magnetization of from about 30 to 80 e.m.u. per gram; and the suspension incorporating the ferrite in an amount of about I00 grams per cc. of the aqueous medium and the stabilizer in an amount of from 1 percent to 2 percent by welght thereof.
• ferrite is selected from the group consisting of magnesium ferrite. magneslum-zlnc ferrlte. barium ferrite. manganese ferrite. manganese-zinc ferrite. nickel ferrite, magnetite and ferromagnetic garnets.

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• 1967
  • 1967-04-18 US US631597A patent/US3592185A/en not_active Expired - Lifetime
• 1968
  • 1968-04-11 GB GB07500/68A patent/GB1174366A/en not_active Expired
  • 1968-04-11 NL NL6805260A patent/NL6805260A/xx unknown
  • 1968-04-11 DE DE19681767206 patent/DE1767206B1/de not_active Withdrawn
  • 1968-04-16 FR FR148254A patent/FR7403M/fr not_active Expired

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