US3592185A - Ferromagnetic contrast media and method of use - Google Patents
Ferromagnetic contrast media and method of use Download PDFInfo
- Publication number
- US3592185A US3592185A US631597A US3592185DA US3592185A US 3592185 A US3592185 A US 3592185A US 631597 A US631597 A US 631597A US 3592185D A US3592185D A US 3592185DA US 3592185 A US3592185 A US 3592185A
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- United States
- Prior art keywords
- ferrite
- magnesium
- ferromagnetic
- manganese
- magnetic
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- Expired - Lifetime
Links
- 230000005294 ferromagnetic effect Effects 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims description 11
- 239000002872 contrast media Substances 0.000 title abstract description 52
- 229940039231 contrast media Drugs 0.000 title abstract description 19
- 229910000859 α-Fe Inorganic materials 0.000 claims abstract description 78
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000011777 magnesium Substances 0.000 claims abstract description 29
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 29
- 230000005291 magnetic effect Effects 0.000 claims abstract description 20
- 239000003381 stabilizer Substances 0.000 claims abstract description 11
- 229920002907 Guar gum Polymers 0.000 claims abstract description 8
- 229910001289 Manganese-zinc ferrite Inorganic materials 0.000 claims abstract description 8
- JIYIUPFAJUGHNL-UHFFFAOYSA-N [O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[Mn++].[Mn++].[Mn++].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Zn++].[Zn++] Chemical compound [O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[Mn++].[Mn++].[Mn++].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Zn++].[Zn++] JIYIUPFAJUGHNL-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000665 guar gum Substances 0.000 claims abstract description 8
- 235000010417 guar gum Nutrition 0.000 claims abstract description 8
- 229960002154 guar gum Drugs 0.000 claims abstract description 8
- 239000011572 manganese Substances 0.000 claims abstract description 8
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims abstract description 7
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052748 manganese Inorganic materials 0.000 claims abstract description 7
- NQNBVCBUOCNRFZ-UHFFFAOYSA-N nickel ferrite Chemical compound [Ni]=O.O=[Fe]O[Fe]=O NQNBVCBUOCNRFZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- AJCDFVKYMIUXCR-UHFFFAOYSA-N oxobarium;oxo(oxoferriooxy)iron Chemical compound [Ba]=O.O=[Fe]O[Fe]=O.O=[Fe]O[Fe]=O.O=[Fe]O[Fe]=O.O=[Fe]O[Fe]=O.O=[Fe]O[Fe]=O.O=[Fe]O[Fe]=O AJCDFVKYMIUXCR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 230000005415 magnetization Effects 0.000 claims description 23
- 239000002245 particle Substances 0.000 claims description 14
- 239000007900 aqueous suspension Substances 0.000 claims description 10
- PGTXKIZLOWULDJ-UHFFFAOYSA-N [Mg].[Zn] Chemical compound [Mg].[Zn] PGTXKIZLOWULDJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000001747 exhibiting effect Effects 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 229910001308 Zinc ferrite Inorganic materials 0.000 claims description 4
- 239000000919 ceramic Substances 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 3
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 abstract description 9
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- 238000011282 treatment Methods 0.000 abstract description 6
- 210000002751 lymph Anatomy 0.000 abstract description 5
- 239000012141 concentrate Substances 0.000 abstract description 4
- 230000002496 gastric effect Effects 0.000 abstract description 4
- 210000000746 body region Anatomy 0.000 abstract description 3
- 239000000463 material Substances 0.000 description 26
- 239000000203 mixture Substances 0.000 description 21
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 13
- 239000000395 magnesium oxide Substances 0.000 description 10
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 10
- 210000002784 stomach Anatomy 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000001035 gastrointestinal tract Anatomy 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000025865 Ulcer Diseases 0.000 description 6
- 229910052788 barium Inorganic materials 0.000 description 6
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 231100000397 ulcer Toxicity 0.000 description 6
- 210000000936 intestine Anatomy 0.000 description 5
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010304 firing Methods 0.000 description 4
- 229910052573 porcelain Inorganic materials 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 230000000171 quenching effect Effects 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 210000001198 duodenum Anatomy 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 206010002329 Aneurysm Diseases 0.000 description 2
- 244000303965 Cyamopsis psoralioides Species 0.000 description 2
- 206010013911 Dysgeusia Diseases 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001553 barium compounds Chemical class 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000005245 sintering Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000008222 Cyamopsis psoralioides Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 201000008450 Intracranial aneurysm Diseases 0.000 description 1
- 229910019440 Mg(OH) Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000005307 ferromagnetism Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 230000003311 flocculating effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 238000011849 radiological investigation Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 229910052596 spinel Inorganic materials 0.000 description 1
- 239000011029 spinel Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
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, besides iron, two or more other elements, with the exception of oxygen or hydrogen
-
- 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.
Abstract
Ferromagnetic contrast media incorporating magnetic ferrites such as magnesium ferrite, barium ferrite, manganese ferrite, manganese-zinc ferrite, nickel ferrite, magnetite, or ferromagnetic garnets; gamma -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.
Description
United States Patent l 13,592,l85
[72] [mentors Ephnlmltl'rd: 3,235,46l 2/1966 Habichtetal [67/95 Eh'orn cunmbolh flhho hd rl l 3,356,575 l2/[967 Arbaeusetal [67/95 Apr. [8, 1967 July [3, I97 I Yeda Research and Development (20., Ltd. ltehovoth, [Ind [21 I Appl. No. [22] Filed [45) Patented [73) Assignee [54] IERROMAGNETIC CONTRAST MEDIA AND METHOD OF USE 4 Claims. No Drawings [52] US. Cl it [28/2, [28/260, 424/4, 424/[58 [5!] lnt.C[ ..A6lk27/08 [50] Field 0! Search [67/55, 95, 84.5; 424/4; [28/260, 2 R
[56] References Cited UNITED STATES PATENTS 2,67l,45l 3/1954 Bolger [67/95 X OTHER REFERENCES Bozorth, Ferromagnetism," D, Van Mostrand Co., New York,( [95 pp, 244- 249.
JAMA, Vol. [95, No. ll, p. 28- 29 [966) Husa' s Pharmaceutical Dispensing, Eric Martin et a[ Mack Publishing Co., Easton, Pa. [959) Primary ExaminerA[bert T. Meyers Assistant Examiner-Vera C. Clarke Atrorney-0strolenk, Faber, Gerb and Soffen ABSTRACT: 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.
FERROMAGNETIC CONTRAST MEDIA AND METHOD OF USE This invention relates to improved ferromagnetic contrast media, and more particularly to a method for the diagnostic and/or therapeutic administration of such media.
It is well known to employ barium sulfate as a contrast material in the gastrointestinal tract. The ingestion of "barium meals" (slurries of barium sulfate in water, with or without a stabilizing agent) 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. Similarly. the use of barium enemas facilitates radiological detection of the existence and location of growths along the colon.
The use of 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.
The use of 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.
The use of magnetic particles as contrast or therapeutic media has previously been proposed in, for example, the fol lowing publications: Magnetism in Medicine," "Journal of Applied Physics," Vol. 3|, No. 5 (May, I960), pages 404s- 405s; Experimental Approach in the Use and Magnetic Control of Metallic lron Particles in the Lymphatic and Vascular System of Dogs as a Contrast and Isotopic Agent," American Journal of Radiology, Vol. 90, No. 5 (Nov. 1963), pages 1068- I077;Magnet Attracts iron to Thrombose Aneurysms, Journal of the American Medical Association, Vol. 195, No. ll (Mar. I4, 1966), pages 28-29; Particles Iron Out Cranial Aneurysm, Medical World News (May 27, I966), pages 30--3 l.
The preceding literature refers to the use ofiron 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.
It is accordingly among the objects of the present invention to provide novel contrast media, and a method for the diagnostic and/or therapeutic administration of same, which may be readily administered and accurately employed to opacify and predetermined body region.
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.
It is yet a further object of the invention to provide such a contrast medium which is chemically inert to body fluids and tissue and which possesses a density such that relatively small quantities by weight of the material are required to produce adequate contrast ofdesired body organs.
These and other objects and advantages of the present in vention will be more fully apparent from a consideration of the following detailed description of preferred embodiments of the ferromagnetic contrast medium and diagnostic and/or therapeutic method hereof.
We have found that improved diagnostic and/or therapeutic results may be achieved by administering to the patient to be treated 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. Upon the administration of such a composition, 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.
Use of ferromagnetic contrast media of the present invention additionally facilitates the development of new therapeutic techniques. Thus, it is possible to treat ulcers by covering the same for prolonged periods with compositions containing such magnetic media; such compositions may additionally contain suitable medicaments such as magnesium hydroxide, currently employed in ulcer therapy.
It has been found that the novel contrast media of this invention possess several specific advantageous properties, in addition to facilitating the improvements referred to hereinabove, Thus, 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. Secondly, 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. Moreover, the ferrite materials may be provided in extremely fine size ranges of 50 microns or lesser magnitudes.
Additionally, only small amounts of the ferrite contrast media hereof are required to satisfactorily effect any particularly desired contrast function. Thus, in some cases, only about grams of ferrite would be suspended in [50 cc. of water to facilitate examination of the human stomach. On the other hand, and as indicated above, it is presently necessary to utilize, for example, about 200 grams of barium sulfate for a suspension to fill the human stomach to effect X-ray examination thereof.
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.
It is preferred to employ magnesium ferrite (MgFe O, as a contrast medium for diagnostic and/or therapeutic examination of the gastrointestinal tract. 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.
While it is thus desirable to utilize a quenched magnesium ferrite in the practice of the present invention (since the magnetization of such material is substantially greater than that of the corresponding unquenched ferrite), other ferrites need not be necessarily so treated. Thus, while 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.
it is believed that 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,
In one particular instance, i.e., for diagnostic and/or therapeutic treatment of the lymph tract, it is preferred to em ploy as the contrast medium the so-called ferromagnetic garnets. Such materials 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.
Preferably, 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. 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.
it is additionally desirable to admix the magnesium ferrite contrast agent with magnesium oxide for ulcer therapy applications. 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.
The following examples illustrate preferred, nonlimiting embodiments of the X-ray contrast media, and the diagnostic and/or therapeutic method of administering such media, of the present invention:
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.
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.
Two permanent magnets were thus employed. 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.
Employing the preceding magnet elements, it was found possible to move the contrast material through the stomach of each test animal to effect concentration of the medium adjacent to one side of the animal in proximity to the magnet. It was additionally possible, by placing a horseshoe magnet against the animal's side. to pull its small intestine between the pole pieces of the magnet. Movement of such magnet along the animal: side caused the adjacent sections of the intestine to follow the magnet, removal of the same resulting in an apparent unfolding of the intestinal sections and return of the same to their normal relation. Such operation could, and was. repeated several times during fluoroscopic examination.
One test animal was sacrificed and operated upon to determine whether sny particles of the contrast medium had penetrated the wall of the small intestine sections which had been subjected to the greatest magnetic force. In these histological examinations. no ferrite particles were found to have penetrated the intestines. stomach or liver of the test animal.
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.
It was found. in both test animals sacrificed. that the contrast material remaining within the stomach had a pH of 3 whereas that remaining within the intestine had a pH of 8. Both such material samples appeared to have the same consistency as prior to feeding.
The following examples 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 EXAMPLEb 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.
What we claim is:
I. A method for X-ray visualization gastrointestinal tract of a patient, which comprises:
a. orally administering or administering by enema to the patient 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;
b. applying an external magnetic field in the region of the patient: gastrointestinal tract to affect the disposition of the contrast medium therein; and
e. detecting the presence of said contrast medium in the gastrointestinal tract by X-ray examination.
2. The method as defined in claim I. in which 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.
3. An aqueous suspension of a magnetic ferrite and a guar gum stabilizer. the 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. 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.
4. The aqueous suspension of claim 3, wherein said 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.
Claims (3)
- 2. The method as defined in claim 1, in which 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.
- 3. An aqueous suspension of a magnetic ferrite and a guar gum stabilizer, the 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, 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 100 grams per 150 cc. of the aqueous medium and the stabilizer in an amount of from 1 percent to 2 percent by weight thereof.
- 4. The aqueous suspension of claim 3, wherein said 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.
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Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3832457A (en) * | 1969-06-20 | 1974-08-27 | Rikagaku Kenkyusho | Ferrite contrast media with metallic oxides |
US3862301A (en) * | 1973-06-18 | 1975-01-21 | Stanley M Chernish | Glucagon as a diagnostic aid in gastrointestinal radiology |
US4020152A (en) * | 1973-12-18 | 1977-04-26 | Thann & Mulhouse | Barium titanate and barium zirconate in radiological contrast products |
US4079124A (en) * | 1976-04-21 | 1978-03-14 | Medi-Physics, Inc. | Method of preparing X-ray contrast media containing ores of hafnium, tantalum and tungsten |
US4101646A (en) * | 1970-05-13 | 1978-07-18 | Rikagaku Kenkyusho | Ferrite vascular contrast media |
US4193985A (en) * | 1977-03-30 | 1980-03-18 | A/S Alfred Benzon | Multiple-units drug dose |
US4197846A (en) * | 1974-10-09 | 1980-04-15 | Louis Bucalo | Method for structure for situating in a living body agents for treating the body |
US4731239A (en) * | 1983-01-10 | 1988-03-15 | Gordon Robert T | Method for enhancing NMR imaging; and diagnostic use |
US6203487B1 (en) * | 1997-12-31 | 2001-03-20 | Thomas Jefferson University | Use of magnetic particles in the focal delivery of cells |
US20010034528A1 (en) * | 1994-09-16 | 2001-10-25 | Foerster Seth A. | Methods and devices for defining and marking tissue |
US6420436B1 (en) * | 1991-04-12 | 2002-07-16 | Alliance Pharmaceutical Corp. | Imaging contrast media and methods of use |
US20030121788A1 (en) * | 2001-12-20 | 2003-07-03 | Peter Gascoyne | Dielectric gate and methods for fluid injection and control |
EP1386886A1 (en) * | 2002-07-31 | 2004-02-04 | General Electric Company | Nanoparticle having an inorganic core |
US20050080338A1 (en) * | 1998-12-24 | 2005-04-14 | Sirimanne D. Laksen | Biopsy cavity marking device and method |
US20060248944A1 (en) * | 2003-04-15 | 2006-11-09 | Koninklijke Philips Electronics N.V. | Method to determine the spatial distribution of magnetic particles and magnetic particle administering compositions |
CN105142680A (en) * | 2013-03-15 | 2015-12-09 | 加利福尼亚大学董事会 | Enteric ct contrast material based on low-Z atoms |
US9492570B2 (en) | 1998-12-24 | 2016-11-15 | Devicor Medical Products, Inc. | Device and method for safe location and marking of a biopsy cavity |
US9669113B1 (en) | 1998-12-24 | 2017-06-06 | Devicor Medical Products, Inc. | Device and method for safe location and marking of a biopsy cavity |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE431214B (en) * | 1977-06-02 | 1984-01-23 | Klaus H Mosbach | SET TO MAKE MAGNETIC POLYMER PARTICLES BASED ON A PREFERRED BIOLOGY ACTIVE SUBSTANCE |
FR2508802A1 (en) * | 1981-07-03 | 1983-01-07 | Thomson Csf | Magnetic powders for use in hyperthermic treatments - e.g. of tumours, heated by hysteresis in alternating magnetic field |
US5618514A (en) * | 1983-12-21 | 1997-04-08 | Nycomed Imaging As | Diagnostic and contrast agent |
US5720939A (en) * | 1985-08-15 | 1998-02-24 | Nycomed Imaging As | Method of contrast enhanced magnetic resonance imaging using magnetically responsive-particles |
GB8408127D0 (en) * | 1984-03-29 | 1984-05-10 | Nyegaard & Co As | Contrast agents |
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US3235461A (en) * | 1966-02-15 | Esters of j,s-diiodo-x-pyridone-n- acetic acid | ||
US3356575A (en) * | 1965-04-13 | 1967-12-05 | Leo Ab | Autosterile injectable iodinated oil X-ray contrast medium |
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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/en not_active Withdrawn
- 1968-04-16 FR FR148254A patent/FR7403M/fr not_active Expired
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US2671451A (en) * | 1952-06-16 | 1954-03-09 | Stephen J Bolger | Remedial pill |
US3356575A (en) * | 1965-04-13 | 1967-12-05 | Leo Ab | Autosterile injectable iodinated oil X-ray contrast medium |
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Title |
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Cited By (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3832457A (en) * | 1969-06-20 | 1974-08-27 | Rikagaku Kenkyusho | Ferrite contrast media with metallic oxides |
US4101646A (en) * | 1970-05-13 | 1978-07-18 | Rikagaku Kenkyusho | Ferrite vascular contrast media |
US3862301A (en) * | 1973-06-18 | 1975-01-21 | Stanley M Chernish | Glucagon as a diagnostic aid in gastrointestinal radiology |
US4020152A (en) * | 1973-12-18 | 1977-04-26 | Thann & Mulhouse | Barium titanate and barium zirconate in radiological contrast products |
US4197846A (en) * | 1974-10-09 | 1980-04-15 | Louis Bucalo | Method for structure for situating in a living body agents for treating the body |
US4079124A (en) * | 1976-04-21 | 1978-03-14 | Medi-Physics, Inc. | Method of preparing X-ray contrast media containing ores of hafnium, tantalum and tungsten |
US4193985A (en) * | 1977-03-30 | 1980-03-18 | A/S Alfred Benzon | Multiple-units drug dose |
US4731239A (en) * | 1983-01-10 | 1988-03-15 | Gordon Robert T | Method for enhancing NMR imaging; and diagnostic use |
US6420436B1 (en) * | 1991-04-12 | 2002-07-16 | Alliance Pharmaceutical Corp. | Imaging contrast media and methods of use |
US20010034528A1 (en) * | 1994-09-16 | 2001-10-25 | Foerster Seth A. | Methods and devices for defining and marking tissue |
US20020193815A1 (en) * | 1994-09-16 | 2002-12-19 | Foerster Seth A. | Methods and devices for defining and marking tissue |
US7044957B2 (en) | 1994-09-16 | 2006-05-16 | Ethicon Endo-Surgery, Inc. | Devices for defining and marking tissue |
US8277391B2 (en) | 1994-09-16 | 2012-10-02 | Devicor Medical Products, Inc. | Methods and devices for defining and marking tissue |
US7625397B2 (en) | 1994-09-16 | 2009-12-01 | Ethicon Endo-Surgery, Inc. | Methods for defining and marking tissue |
US7229417B2 (en) | 1994-09-16 | 2007-06-12 | Ethicon Endo-Surgery, Inc. | Methods for marking a biopsy site |
US6203487B1 (en) * | 1997-12-31 | 2001-03-20 | Thomas Jefferson University | Use of magnetic particles in the focal delivery of cells |
US8600481B2 (en) | 1998-12-24 | 2013-12-03 | Devicor Medical Products, Inc. | Subcutaneous cavity marking device |
US8320993B2 (en) | 1998-12-24 | 2012-11-27 | Devicor Medical Products, Inc. | Subcutaneous cavity marking device |
US9986974B2 (en) | 1998-12-24 | 2018-06-05 | Devicor Medical Products, Inc. | Biopsy cavity marking device |
US9669113B1 (en) | 1998-12-24 | 2017-06-06 | Devicor Medical Products, Inc. | Device and method for safe location and marking of a biopsy cavity |
US9492570B2 (en) | 1998-12-24 | 2016-11-15 | Devicor Medical Products, Inc. | Device and method for safe location and marking of a biopsy cavity |
US7668582B2 (en) | 1998-12-24 | 2010-02-23 | Ethicon Endo-Surgery, Inc. | Biopsy site marker |
US9380998B2 (en) | 1998-12-24 | 2016-07-05 | Devicor Medical Products, Inc. | Subcutaneous cavity marking device and method |
US20050080338A1 (en) * | 1998-12-24 | 2005-04-14 | Sirimanne D. Laksen | Biopsy cavity marking device and method |
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US8320994B2 (en) | 1998-12-24 | 2012-11-27 | Devicor Medical Products, Inc. | Biopsy cavity marking device and method |
US20030121788A1 (en) * | 2001-12-20 | 2003-07-03 | Peter Gascoyne | Dielectric gate and methods for fluid injection and control |
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JP4713067B2 (en) * | 2002-07-31 | 2011-06-29 | ゼネラル・エレクトリック・カンパニイ | Method for forming nanoparticles |
JP2004075530A (en) * | 2002-07-31 | 2004-03-11 | General Electric Co <Ge> | Nanoparticle having inorganic core |
US6797380B2 (en) | 2002-07-31 | 2004-09-28 | General Electric Company | Nanoparticle having an inorganic core |
US20060248944A1 (en) * | 2003-04-15 | 2006-11-09 | Koninklijke Philips Electronics N.V. | Method to determine the spatial distribution of magnetic particles and magnetic particle administering compositions |
CN105142680A (en) * | 2013-03-15 | 2015-12-09 | 加利福尼亚大学董事会 | Enteric ct contrast material based on low-Z atoms |
JP2016516072A (en) * | 2013-03-15 | 2016-06-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Intestinal CT contrast material with low Z atoms |
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JP2020193223A (en) * | 2013-03-15 | 2020-12-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Enteric ct contrast material based on low-z atoms |
US11033640B2 (en) | 2013-03-15 | 2021-06-15 | The Regents Of The University Of California | Enteric CT contrast material based on low-z atoms |
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Also Published As
Publication number | Publication date |
---|---|
FR7403M (en) | 1969-11-03 |
NL6805260A (en) | 1968-10-21 |
GB1174366A (en) | 1969-12-17 |
DE1767206B1 (en) | 1971-09-30 |
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