US3368944A - X-ray-contrast medium with a density of 0.8-1.1 - Google Patents

X-ray-contrast medium with a density of 0.8-1.1 Download PDF

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US3368944A
US3368944A US431428A US43142865A US3368944A US 3368944 A US3368944 A US 3368944A US 431428 A US431428 A US 431428A US 43142865 A US43142865 A US 43142865A US 3368944 A US3368944 A US 3368944A
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contrast medium
ray
ray contrast
density
water
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Sandmark Stig Johs Gustav
Hagstam Ernst Helmer
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STIG JOHS GUSTAV SANDMARK
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Sandmark Stig Johs Gustav
Hagstam Ernst Helmer
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    • 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
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • 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
    • A61K49/0404—X-ray contrast preparations containing barium sulfate
    • 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
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0442—Polymeric X-ray contrast-enhancing agent comprising a halogenated group
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/90—In vivo diagnostic or in vivo test agent which contains an additional ingredient to reduce the toxicity or side effects of the active ingredient

Definitions

  • the abdominal cavity is filled mainly with mobile organs of about the same density as water and usually the density of these mobile organs is about 1.03 to 1.06
  • the contents of the gastro-intestinal tract are also of about the same density. Pressure measurements have shown that the abdominal cavity behaves like a closed cavity filled with water. Thus, with normal gastrointestinal contents the hydrostatic pressure acting on the inside and the outside of a given segment of the intestinal wall is about the same.
  • the contrast media hitherto used for the X-ray examinations of the gastro-intestinal tract are of high density (about 1.4 to 2.0 g./cm. and therefore the hydrostatic pressure within the gastro-intestinal tract when being filied with such a contrast medium is higher than the hydrostatic pressure within the abdominal cavity but outside the gastro-intestinal tract.
  • This difference in pressure distorts the gastrointestinal tract with the result that the contrast medium cannot readily pass through the gastrointestinal tract and possibly does not reach the parts of the stomach or intestine to be examined because the X-ray contrast medium sinks to those parts of the gastrointestinal tract which happen to be lowermost at the time of the examination.
  • This disadvantageous eifect may cause difliculties in examinations for e.g. hiatus hernia.
  • an X-ray contrast medium of about the same density as that of the abdominal organs so that the X-ray contrast medium can pass through the gastro-intestinal tract like ordinary food in a physiologically correct way and independently of the patients posture. Hitherto it has, however, not been possible to produce such contrast media and as far as we know priorart contrast media all are of a density of at least 1.4 g./cm. which density cannot be reduced by known methods.
  • An object of the invention is to provide an X-ray contrast medium having such a density that it can pass through the gastro-intestinal tract like ordinary food in a physiologically correct way and independently of the patients posture.
  • Another object of the invention is to provide an X-r'ay contrast medium having a density of 0.8 to 1.1 g./cm.
  • Still another object of the invention is to provide an X-ray contrast medium consisting of an X-ray absorber, a particulate resin foam, water and a thickening agent,
  • the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • a further object of the invention is to provide an X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam, iodine chemically bonded to said resin foam, water 'and a non-toxic thickening agent, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • the X-ray contrast medium comprises an X-ray absorber comprising a memberof the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, water and a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • the X-ray absorber is preferably homogeneously incorporated in the resin foam and in this case it is possible to prevent the X-ray absorber from coming in direct contact with the contents of the gastro-intestinal tract.
  • an X-ray absorber one may use an element or a compound that is toxic per se.
  • the X-ray contrast medium according to the invention may be prepared by preparing a thixotropic suspension of the X-ray absorber, e.g. barium sulphate, water, a suitable amount of a carrier material comprising particulate therapeutically acceptable resin foam and a nontoxic thickening agent, the relative amounts of the said components being such that the final X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • the X-ray absorber e.g. barium sulphate
  • a suitable amount of a carrier material comprising particulate therapeutically acceptable resin foam and a nontoxic thickening agent
  • Another possibility of preparing the X-ray contrast medium according to the invention is to melt the resin and incorporate the X-ray absorber by mixing it with the molten resin.
  • the mixture may then be treated with air or gas, whereupon the mixture is allowed to set.
  • the set material is ground and sieved to the desired particle size.
  • the particles are then expanded in a well known way by heating them for a short period to about C. so that the resin softens and the enclosed air or gas expands.
  • a suitable solvent e.g. ethyl acetate
  • the suspension is spread in a thin layer and dried and then the dried material obtained is ground and sieved to the desired particle size.
  • the particles are placed in a suitable fluid such as petroleum ether or pentane, for a period of e.g. 12 hours. During this time the particles swell. Excess fluid is then sucked off and the swollen particles are stirred in water at 90 C., thereby expanding.
  • the expanded particles prepared in either of the two above mentioned methods from a molten mass or a solution of the thermoplastic resin material contain the bulk of the X-ray absorber within the particles. Any X-ray absorber on the surface of the particles can be washed off by artificial gastro-intestinal juice so that all X- ray absorber substance is contained within the resin particles and withdrawn from the gastro-intestinal juices in the patients stomach and intestines.
  • X-ray absorbers which because of their toxicity could not hitherto with safety be considered as components of X-ray contrast media.
  • the invention has made it possible to use bismuth subcarbonate and thorium oxide as X-ray absorbers in X-ray contrast media for X-ray examination of the gastrointestinal tract.
  • Still another possibility of preparing the X-ray contrast medium according to the invention is to prepare a solution of a volatile liquid and a film forming substance insoluble in the stomach comprising a member of the group consisting of shellac and cellulose acetate phthalate and to suspend the X-ray absorber in the solution.
  • the foamed resin particles are then coated with the resultant mixture and the volatile liquid driven off. Any X-ray absorber not contained in and covered by the coating is removed eg. by washing with artificial gastric juice.
  • This X-ray contrast medium is especially suitable in the X-ray examination of the ventricle and esophagus.
  • iodine When iodine is used as the X-ray absorber it is possible to incorporate the absorber with the particulate res in foam by modifying the starting monomer from which the resin is prepared. In this case the iodine is chemically bonded to the monomer in a first stage and then the monomer is polymerized in well known manner.
  • This modified iodine containing resin in a third stage is expanded in a manner well known in the art to produce particulate modified resin foam which is mixed with water and the non-toxic thickening agent, the proportions of the particulate modified resin foam, the water and the thickening agent being such that the final X-ray contrast iedium has a density of 0.8 to 1.1 g./cm.
  • the particulate resin foam in the X-ray contrast medium of the invention it is possible to use a polystyrene, polyethylene and urea resin.
  • the preferred resins are the polystyrenes. All these resins can be prepared by methods well known in the art.
  • non-toxic thickening agent for use in the X-ray contrast medium of the invention it is possible to use vegetable gums.
  • water, soluble cellulose esters and thickeners of seaweed origin e.g. alginates, agars and carrageens.
  • thickening agents that have been used in X-ray contrast media of the invention are sodium alginate, potassium alginate, propylene glycol alginate, ammonium alginate, agar-agar, sodium carrageenate, potassium carrageenate, gum acacia, gum guar, gum locust, gum tragacanth, sodium carboxyl methyl cellulose, ethyl hydroxy ethyl cellulose and methyl cellulose.
  • Example 1 Foamed polystyrene particles prepared in a known manner and having a diameter of about 0.5 mm. and a bulk density of about 0.1 to 0.2 g./cm. were stirred into a 1% sodium alginate solution in water to provide them with a coating of sodium alginate. The particles were then removed from the sodium alginate solution and washed with water. Thereafter, the coated particles were suspended in a 0.1 N calcium chloride solution in water. Excess calcium chloride solution was allowed to drain off. In the meantime, barium sulphate (grade U.S.P.) had been suspended in the remainder of the original sodium alginate solution, and into this suspension the coated particles treated with calcium chloride were suspended.
  • barium sulphate grade U.S.P.
  • the calcium ions act as a stabilizer for the sodium alginate coating of the polystyrene particles and thus prevent the suspended barium sulphate and polystyrene particles from separating too rapidly when the X-ray contrast medium passes through the gastro-intestinal tract.
  • the relative amounts of the ingredients were chosen in such a way that the final X-ray contrast medium had a bulk density of about 0.95 to 1.05 g./cm.
  • the density of the X-ray contrast medium was about the same as that of the organs in the abdominal cavity the X-ray contrast medium could pass rapidly through the stomach, the small intestine and large intestine in a physiologically correct way without it being necessary for the patient to be in a recumbent position and without any extraneous influence by pressure or turning of the patient.
  • the X-ray contrast medium spread successively and in a thin even layer over the inner surfaces of the organs.
  • Example 2 The preparation of the X-ray contrast medium was carried out as described in Example 1 except that foamed polyethylene particles with a diameter of about 0.5 mm. and ammonium alginate were used instead of the poly styrene particles and the sodium alginate, respectively.
  • the resulting X-ray contrast medium was found to act in a physiologically correct way when passing through the stomach, the small intestine and the large intestine, whereby the barium sulphate suspension spread successively and was distributed in a thin even layer over the inner surfaces of the organs.
  • Example 3 A 10 to 15% alcoholic solution of schellac or cellulose acetate phthalate was prepared. In this solution barium sulphate was suspended. Spherical foamed polystyrene particles having a diameter of about 0.1 mm. and prepared in a manner well known in the art were added to the suspension under stirring in such a quantity that the ratio of polystyrene particles to barium sulphate was about 1:2.5 by Weight. The formation of large conglomerates of particles was prevented by means of talc or colloidal silica. Thereafter the material was dried and sieved and any unabsorbed barium sulphate was removed.
  • the polystyrene particles thus coated with barium sulphate incorporated in a shellac or cellulose acetate phthalate layer were suspended in a 1% solution of ethyl hydroxy ethyl cellulose in water in such a quantity, that the final X-ray contrast medium had a density of about 0.8 to 1.1 g./cm.
  • the X-ray contrast medium prepared in this way was found to be an excellent X-ray contrast medium for the X-ray examination of the gastro-intestinal tract.
  • Example 4 Example 3 was repeated except that thorium oxide was substituted for the barium sulfate and that gum tragacanth was substituted for the ethyl hydroxy ethyl cellulose.
  • the final X-ray contrast medium having a density of about 0.8 to 1.1 g./cm. was found to be an excellent X-ray contrast medium in the X-ray examination of the gastrointestinal tract.
  • Example 5 100 g. polystyrene were dissolved in 300 ml. ethyl acetate. The solution was filtered and 200 g. bismuth subcarbonate were stirred into the filtrate. The solution was homogenized and spread in a thin layer on a polyethylene foil, where it was allowed to dry. After drying the material was ground in a mill with rotating knives until the material passed through a 50 mesh sieve (U.S. standard sieve). The powder was covered with petroleum ether and was allowed to stand for about 12 hours during which it was occasionally stirred. Afterwards excess petroleum ether was sucked off and the powder was sieved through a coarse sieve into water having a temperature of about C. and in which the powder was vigorously stirred.
  • U.S. standard sieve 50 mesh sieve
  • the powder particles were thereby expanded and then they were immediately removed from the hot water, rinsed in cold water, dried and aired for some days. 50 g. of this material were stirred in about ml. of a 1% solution of sodium carrageenate in water. The material thus prepared was an excellent X-ray contrast medium in X-ray examination of the gastro-intestinal tract.
  • Example 6 Example 5 was repeated except that thorium oxide was substituted for the bismuth subcarbonate. The final suspension was found to be an excellent X-ray contrast medium in X-ray examination of the gastrointestinal tract.
  • Example 7 100 g. of a mixture of ortho and para iodine styrene monomer were polymerized in some well known manner e.g. through storing the monomer at 60 C. for a few hours with a small quantity of benzoylperoxide added. The obtained product containing 55% iodine was crushed into small particles and expanded as described in Example 5. The expanded iodine-containing resin particles were stirred into a 1% solution of methyl cellulose in water in such a quantity that the final product had a density of 0.95 to 1.05 g./cm. This product could be used as an X-ray contrast medium in X-ray examination of the gastro-intestinal tract.
  • Example 8 100 g. barium sulphate were thoroughly mixed into 50 g. of a urea resin premix. A curing agent solution was added and the mixture was whipped to obtain a foam with small homogeneous cells. After curing the product was ground and sieved and the fraction with a particle size between 0.1 and 0.5 mm. was used. This fraction was mixed with a 1% solution of potassium carrageenate in water in such a quantity that the final X-ray contrast medium had a density of 0.8 to 1.1 g./cm. This X-ray contrast medium was suitable for use in X-ray examination of the gastro-intestinal tract.
  • Example 9 100 g. polyethylene granules prepared in a known manner and containing an incorporated organic blowing agent were mixed with 100 g. barium sulphate. This material was extruded in thin sheets which during the extrusion expanded to a cellular product. This product was comminuted into particles about 0.5 mm. in diameter and was used in preparing an X-ray contrast medium by stirring the particles into an agar-agar gel in such a quantity that the final X-ray contrast medium had a density of about 0.95 to 1.05 g./cm. This X-ray contrast medium was suitable for use in X-ray examination of the gastrointestinal tract.
  • An X-ray contrast medium comprising an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, water, and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm
  • An X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, said X-ray absorber being homogeneously incorporated in said particulate resin foam, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • An X-ray contrast medium comprising a particulate, therapeutically acceptable polystyrene resin foam, iodine chemically bonded to said resin, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • An X-ray contrast medium comprising an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, and thorium oxide, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, said particulate resin foam being coated with said X-ray absorber, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and Water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
  • An X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, and thorium oxide, a film forming substance insoluble in the stomach comprising a member of the group consisting of shellac and cellulose acetate phthalate, said film forming substance substantially covering each particle of said particulate resin foam and said X-ray absorber being distributed in and covered by said film forming substance, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.

Description

United States Patent Ofi ice 3,368,944- Patented Feb. 13, 1968 3,368,944 X lRAY-CQNTRAST MEDIUM WITH A DENSITY F 0.84.1 Stig .ltihs Gustav Sandman-k, Knut Wicksells Veg 19,
Lund, Sweden, and Ernst Helmcr Hagstam, 'luhorgsgatan 1B, Mahno, Sweden No Drawing. iIontinuation-in-part of appiication Ser. No. 251,760, Jan. 16, 1963. This application Feb. 9, 1965, Ser- No. 431,428 Claims priority, application Sweden, Jan. 23, 1962, 723/62 7 Claims. (Cl. 167-95) as they are of high density because of the addition of the heavy X-ray absorber.
The abdominal cavity is filled mainly with mobile organs of about the same density as water and usually the density of these mobile organs is about 1.03 to 1.06
g./cm. The contents of the gastro-intestinal tract are also of about the same density. Pressure measurements have shown that the abdominal cavity behaves like a closed cavity filled with water. Thus, with normal gastrointestinal contents the hydrostatic pressure acting on the inside and the outside of a given segment of the intestinal wall is about the same.
The contrast media hitherto used for the X-ray examinations of the gastro-intestinal tract are of high density (about 1.4 to 2.0 g./cm. and therefore the hydrostatic pressure within the gastro-intestinal tract when being filied with such a contrast medium is higher than the hydrostatic pressure within the abdominal cavity but outside the gastro-intestinal tract. This difference in pressure distorts the gastrointestinal tract with the result that the contrast medium cannot readily pass through the gastrointestinal tract and possibly does not reach the parts of the stomach or intestine to be examined because the X-ray contrast medium sinks to those parts of the gastrointestinal tract which happen to be lowermost at the time of the examination. This disadvantageous eifect may cause difliculties in examinations for e.g. hiatus hernia.
Thus there is a need for an X-ray contrast medium of about the same density as that of the abdominal organs so that the X-ray contrast medium can pass through the gastro-intestinal tract like ordinary food in a physiologically correct way and independently of the patients posture. Hitherto it has, however, not been possible to produce such contrast media and as far as we know priorart contrast media all are of a density of at least 1.4 g./cm. which density cannot be reduced by known methods.
An object of the invention is to provide an X-ray contrast medium having such a density that it can pass through the gastro-intestinal tract like ordinary food in a physiologically correct way and independently of the patients posture.
Another object of the invention is to provide an X-r'ay contrast medium having a density of 0.8 to 1.1 g./cm.
Still another object of the invention is to provide an X-ray contrast medium consisting of an X-ray absorber, a particulate resin foam, water and a thickening agent,
the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
A further object of the invention is to provide an X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam, iodine chemically bonded to said resin foam, water 'and a non-toxic thickening agent, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
According to the invention, the X-ray contrast medium comprises an X-ray absorber comprising a memberof the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, water and a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
The X-ray absorber is preferably homogeneously incorporated in the resin foam and in this case it is possible to prevent the X-ray absorber from coming in direct contact with the contents of the gastro-intestinal tract. Thus, as an X-ray absorber one may use an element or a compound that is toxic per se.
The X-ray contrast medium according to the invention may be prepared by preparing a thixotropic suspension of the X-ray absorber, e.g. barium sulphate, water, a suitable amount of a carrier material comprising particulate therapeutically acceptable resin foam and a nontoxic thickening agent, the relative amounts of the said components being such that the final X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
Another possibility of preparing the X-ray contrast medium according to the invention is to melt the resin and incorporate the X-ray absorber by mixing it with the molten resin. The mixture may then be treated with air or gas, whereupon the mixture is allowed to set. The set material is ground and sieved to the desired particle size. The particles are then expanded in a well known way by heating them for a short period to about C. so that the resin softens and the enclosed air or gas expands. Instead of melting the resin it is 'also possible to prepare a solution of the resin in a suitable solvent e.g. ethyl acetate and to suspend the X-ray absorber in the solution. Next, the suspension is spread in a thin layer and dried and then the dried material obtained is ground and sieved to the desired particle size. The particles are placed in a suitable fluid such as petroleum ether or pentane, for a period of e.g. 12 hours. During this time the particles swell. Excess fluid is then sucked off and the swollen particles are stirred in water at 90 C., thereby expanding.
The expanded particles prepared in either of the two above mentioned methods from a molten mass or a solution of the thermoplastic resin material, contain the bulk of the X-ray absorber within the particles. Any X-ray absorber on the surface of the particles can be washed off by artificial gastro-intestinal juice so that all X- ray absorber substance is contained within the resin particles and withdrawn from the gastro-intestinal juices in the patients stomach and intestines. Thus, when using these methods of preparing the X-ray contrast medium it is possible to use X-ray absorbers which because of their toxicity could not hitherto with safety be considered as components of X-ray contrast media. Thus the invention has made it possible to use bismuth subcarbonate and thorium oxide as X-ray absorbers in X-ray contrast media for X-ray examination of the gastrointestinal tract.
Still another possibility of preparing the X-ray contrast medium according to the invention is to prepare a solution of a volatile liquid and a film forming substance insoluble in the stomach comprising a member of the group consisting of shellac and cellulose acetate phthalate and to suspend the X-ray absorber in the solution. The foamed resin particles are then coated with the resultant mixture and the volatile liquid driven off. Any X-ray absorber not contained in and covered by the coating is removed eg. by washing with artificial gastric juice. The coated particles are then suspended in a gel of water and a thickening agent in such a quantity that the final X-ray contrast medium has a density of 0.8 to l.=l g./cm. This X-ray contrast medium is especially suitable in the X-ray examination of the ventricle and esophagus.
When iodine is used as the X-ray absorber it is possible to incorporate the absorber with the particulate res in foam by modifying the starting monomer from which the resin is prepared. In this case the iodine is chemically bonded to the monomer in a first stage and then the monomer is polymerized in well known manner. This modified iodine containing resin in a third stage is expanded in a manner well known in the art to produce particulate modified resin foam which is mixed with water and the non-toxic thickening agent, the proportions of the particulate modified resin foam, the water and the thickening agent being such that the final X-ray contrast iedium has a density of 0.8 to 1.1 g./cm.
As the particulate resin foam in the X-ray contrast medium of the invention it is possible to use a polystyrene, polyethylene and urea resin. However, the preferred resins are the polystyrenes. All these resins can be prepared by methods well known in the art.
As a non-toxic thickening agent for use in the X-ray contrast medium of the invention it is possible to use vegetable gums. water, soluble cellulose esters and thickeners of seaweed origin e.g. alginates, agars and carrageens.
Specific examples of thickening agents that have been used in X-ray contrast media of the invention are sodium alginate, potassium alginate, propylene glycol alginate, ammonium alginate, agar-agar, sodium carrageenate, potassium carrageenate, gum acacia, gum guar, gum locust, gum tragacanth, sodium carboxyl methyl cellulose, ethyl hydroxy ethyl cellulose and methyl cellulose.
The following examples will serve to illustrate the invention without limiting the same. In these examples all percentages and ratios refer to percentages and ratios by weight.
Example 1 Foamed polystyrene particles prepared in a known manner and having a diameter of about 0.5 mm. and a bulk density of about 0.1 to 0.2 g./cm. were stirred into a 1% sodium alginate solution in water to provide them with a coating of sodium alginate. The particles were then removed from the sodium alginate solution and washed with water. Thereafter, the coated particles were suspended in a 0.1 N calcium chloride solution in water. Excess calcium chloride solution was allowed to drain off. In the meantime, barium sulphate (grade U.S.P.) had been suspended in the remainder of the original sodium alginate solution, and into this suspension the coated particles treated with calcium chloride were suspended. The calcium ions act as a stabilizer for the sodium alginate coating of the polystyrene particles and thus prevent the suspended barium sulphate and polystyrene particles from separating too rapidly when the X-ray contrast medium passes through the gastro-intestinal tract. The relative amounts of the ingredients were chosen in such a way that the final X-ray contrast medium had a bulk density of about 0.95 to 1.05 g./cm. Since the density of the X-ray contrast medium was about the same as that of the organs in the abdominal cavity the X-ray contrast medium could pass rapidly through the stomach, the small intestine and large intestine in a physiologically correct way without it being necessary for the patient to be in a recumbent position and without any extraneous influence by pressure or turning of the patient. The X-ray contrast medium spread successively and in a thin even layer over the inner surfaces of the organs.
Example 2 The preparation of the X-ray contrast medium was carried out as described in Example 1 except that foamed polyethylene particles with a diameter of about 0.5 mm. and ammonium alginate were used instead of the poly styrene particles and the sodium alginate, respectively. The resulting X-ray contrast medium was found to act in a physiologically correct way when passing through the stomach, the small intestine and the large intestine, whereby the barium sulphate suspension spread successively and was distributed in a thin even layer over the inner surfaces of the organs.
Example 3 A 10 to 15% alcoholic solution of schellac or cellulose acetate phthalate was prepared. In this solution barium sulphate was suspended. Spherical foamed polystyrene particles having a diameter of about 0.1 mm. and prepared in a manner well known in the art were added to the suspension under stirring in such a quantity that the ratio of polystyrene particles to barium sulphate was about 1:2.5 by Weight. The formation of large conglomerates of particles was prevented by means of talc or colloidal silica. Thereafter the material was dried and sieved and any unabsorbed barium sulphate was removed. The polystyrene particles thus coated with barium sulphate incorporated in a shellac or cellulose acetate phthalate layer were suspended in a 1% solution of ethyl hydroxy ethyl cellulose in water in such a quantity, that the final X-ray contrast medium had a density of about 0.8 to 1.1 g./cm. The X-ray contrast medium prepared in this way was found to be an excellent X-ray contrast medium for the X-ray examination of the gastro-intestinal tract.
Example 4 Example 3 was repeated except that thorium oxide was substituted for the barium sulfate and that gum tragacanth was substituted for the ethyl hydroxy ethyl cellulose. The final X-ray contrast medium having a density of about 0.8 to 1.1 g./cm. was found to be an excellent X-ray contrast medium in the X-ray examination of the gastrointestinal tract.
Example 5 100 g. polystyrene were dissolved in 300 ml. ethyl acetate. The solution was filtered and 200 g. bismuth subcarbonate were stirred into the filtrate. The solution was homogenized and spread in a thin layer on a polyethylene foil, where it was allowed to dry. After drying the material was ground in a mill with rotating knives until the material passed through a 50 mesh sieve (U.S. standard sieve). The powder was covered with petroleum ether and was allowed to stand for about 12 hours during which it was occasionally stirred. Afterwards excess petroleum ether was sucked off and the powder was sieved through a coarse sieve into water having a temperature of about C. and in which the powder was vigorously stirred. The powder particles were thereby expanded and then they were immediately removed from the hot water, rinsed in cold water, dried and aired for some days. 50 g. of this material were stirred in about ml. of a 1% solution of sodium carrageenate in water. The material thus prepared was an excellent X-ray contrast medium in X-ray examination of the gastro-intestinal tract.
Example 6 Example 5 was repeated except that thorium oxide was substituted for the bismuth subcarbonate. The final suspension was found to be an excellent X-ray contrast medium in X-ray examination of the gastrointestinal tract.
Example 7 100 g. of a mixture of ortho and para iodine styrene monomer were polymerized in some well known manner e.g. through storing the monomer at 60 C. for a few hours with a small quantity of benzoylperoxide added. The obtained product containing 55% iodine was crushed into small particles and expanded as described in Example 5. The expanded iodine-containing resin particles were stirred into a 1% solution of methyl cellulose in water in such a quantity that the final product had a density of 0.95 to 1.05 g./cm. This product could be used as an X-ray contrast medium in X-ray examination of the gastro-intestinal tract.
Example 8 100 g. barium sulphate were thoroughly mixed into 50 g. of a urea resin premix. A curing agent solution was added and the mixture was whipped to obtain a foam with small homogeneous cells. After curing the product was ground and sieved and the fraction with a particle size between 0.1 and 0.5 mm. was used. This fraction was mixed with a 1% solution of potassium carrageenate in water in such a quantity that the final X-ray contrast medium had a density of 0.8 to 1.1 g./cm. This X-ray contrast medium was suitable for use in X-ray examination of the gastro-intestinal tract.
Example 9 100 g. polyethylene granules prepared in a known manner and containing an incorporated organic blowing agent were mixed with 100 g. barium sulphate. This material was extruded in thin sheets which during the extrusion expanded to a cellular product. This product was comminuted into particles about 0.5 mm. in diameter and was used in preparing an X-ray contrast medium by stirring the particles into an agar-agar gel in such a quantity that the final X-ray contrast medium had a density of about 0.95 to 1.05 g./cm. This X-ray contrast medium was suitable for use in X-ray examination of the gastrointestinal tract.
The foregoing detailed description has been given for the purposes of illustration only and is not intended to limit the scope of the present invention which is to be determined from the appendant claims.
What we claim and desire to secure by Letters Patent 1s:
1. An X-ray contrast medium comprising an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, water, and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm
2. The X-ray contrast medium according to claim 1, in which the proportions of said components are such that the X-ray contrast medium has a density of 0.95 to 1.05 g./cm
3. An X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, thorium oxide and iodine, said X-ray absorber being homogeneously incorporated in said particulate resin foam, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
4. The X-ray contrast medium according to claim 3, wherein said X-ray absorber is barium sulphate and said resin foam is a polystyrene.
5. An X-ray contrast medium comprising a particulate, therapeutically acceptable polystyrene resin foam, iodine chemically bonded to said resin, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
6. An X-ray contrast medium comprising an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, and thorium oxide, a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, said particulate resin foam being coated with said X-ray absorber, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and Water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
7. An X-ray contrast medium comprising a particulate, therapeutically acceptable resin foam comprising a member of the group consisting of polystyrenes, polyethylenes and urea resins, an X-ray absorber comprising a member of the group consisting of barium sulphate, bismuth subcarbonate, and thorium oxide, a film forming substance insoluble in the stomach comprising a member of the group consisting of shellac and cellulose acetate phthalate, said film forming substance substantially covering each particle of said particulate resin foam and said X-ray absorber being distributed in and covered by said film forming substance, water and at most 1% based on the X-ray contrast medium of a non-toxic thickening agent of the group consisting of thickeners of seaweed origin, vegetable gums and water soluble cellulose esters, the proportions of said components being such that the X-ray contrast medium has a density of 0.8 to 1.1 g./cm.
References Cited FOREIGN PATENTS 657,979 10/1951 Great Britain 16795 ELBERT L. ROBERTS, Primary Examiner.
LEWIS GOTTS, Examiner.
R. L. H-UFF, Assistant Examiner.

Claims (1)

1. AN X-RAY CONTRAST MEDIUM COMPRISING AN X-RAY ABSORBER COMPRISING A MEMBER OF THE GROUP CONSISTING OF BARIUM SULPHATE, BISMUTH SUBCABONTE, THORIUM OXIDE AND IODINE, A PARTICULATE, THERAPEUTICALLY ACCEPTABLE RESIN FOAM COMPRISING A MEMBER OF THE GROUP CONSISTING OF POLYSTYRENES, POLYETHYLENES AND UREA RESINS, WATER, AND AT MOST 1% BASED ON THE X-RAY CONTRAST MEDIUM OF A NON-TOXIC THICKENING AGENT OF THE GROUP CONSISTING OF THICKENERS OF SEAWEED ORIGIN, BEGETABLE GUMS AND WATER SOLUBLE CELLULOSE ESTERS, THE PROPORTION OF SAID COMPONENTS BEING SUCH THAT THE X-RAY CONTRAST MEDIUM HAS A DENSITY OF 0.8 TO 1.1 G./CM3.
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US4193985A (en) * 1977-03-30 1980-03-18 A/S Alfred Benzon Multiple-units drug dose
EP0092993A2 (en) * 1982-04-23 1983-11-02 A/S Alfred Benzon Composition for investigating alimentary functions
EP0568155A1 (en) * 1992-05-01 1993-11-03 Nycomed Imaging As X-ray contrast formulations containing film-forming materials
EP0609587A2 (en) * 1993-02-02 1994-08-10 Nycomed Imaging As Compositions of iodophenoxy alkanes and iodophenyl ethers in film-forming materials for visualization of the gastrointestinal tract
EP0609589A2 (en) * 1993-02-04 1994-08-10 Nycomed Imaging As Compositions of alkylbenzenes in film-forming materials for visualization of the gastrointestinal tract
EP0617970A2 (en) * 1993-03-31 1994-10-05 Nycomed Imaging As Compositions of iodophenyl esters and iodophenyl sulfonates in film-forming materials for visualization of the gastrointestinal tract
WO1994025075A1 (en) * 1993-04-26 1994-11-10 Sterling Winthrop Inc. Polymeric x-ray contrast compositions containing iodinated polymeric beads
US20040122509A1 (en) * 2002-12-20 2004-06-24 Scimed Life Systems, Inc. Radiopaque ePTFE medical devices
US10350311B2 (en) 2014-03-04 2019-07-16 Otsuka Pharmaceutical Co., Ltd. Iohexol powder and method of using the same

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GB1566609A (en) 1977-03-10 1980-05-08 Reckitt & Colmann Prod Ltd Pharmaceutical compositions containing cholestyramine and alginic acid

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4193985A (en) * 1977-03-30 1980-03-18 A/S Alfred Benzon Multiple-units drug dose
EP0092993A2 (en) * 1982-04-23 1983-11-02 A/S Alfred Benzon Composition for investigating alimentary functions
WO1983003762A1 (en) * 1982-04-23 1983-11-10 A/S Alfred Benzon Composition and method for investigating alimentary functions
EP0092993A3 (en) * 1982-04-23 1984-07-18 A/S Alfred Benzon Composition and method for investigating alimentary functions
US4657755A (en) * 1982-04-23 1987-04-14 A/S Alfred Benzon Composition and method for investigating alimentary functions
EP0568155A1 (en) * 1992-05-01 1993-11-03 Nycomed Imaging As X-ray contrast formulations containing film-forming materials
EP0609587A3 (en) * 1993-02-02 1995-09-06 Sterling Winthrop Inc Compositions of iodophenoxy alkanes and iodophenyl ethers in film-forming materials for visualization of the gastrointestinal tract.
EP0609587A2 (en) * 1993-02-02 1994-08-10 Nycomed Imaging As Compositions of iodophenoxy alkanes and iodophenyl ethers in film-forming materials for visualization of the gastrointestinal tract
EP0609589A2 (en) * 1993-02-04 1994-08-10 Nycomed Imaging As Compositions of alkylbenzenes in film-forming materials for visualization of the gastrointestinal tract
EP0609589A3 (en) * 1993-02-04 1995-09-06 Sterling Winthrop Inc Compositions of alkylbenzenes in film-forming materials for visualization of the gastrointestinal tract.
EP0617970A2 (en) * 1993-03-31 1994-10-05 Nycomed Imaging As Compositions of iodophenyl esters and iodophenyl sulfonates in film-forming materials for visualization of the gastrointestinal tract
EP0617970A3 (en) * 1993-03-31 1995-09-06 Sterling Winthrop Inc Compositions of iodophenyl esters and iodophenyl sulfonates in film-forming materials for visualization of the gastrointestinal tract.
WO1994025075A1 (en) * 1993-04-26 1994-11-10 Sterling Winthrop Inc. Polymeric x-ray contrast compositions containing iodinated polymeric beads
US20040122509A1 (en) * 2002-12-20 2004-06-24 Scimed Life Systems, Inc. Radiopaque ePTFE medical devices
US8088158B2 (en) * 2002-12-20 2012-01-03 Boston Scientific Scimed, Inc. Radiopaque ePTFE medical devices
US10350311B2 (en) 2014-03-04 2019-07-16 Otsuka Pharmaceutical Co., Ltd. Iohexol powder and method of using the same
RU2711501C2 (en) * 2014-03-04 2020-01-17 Оцука Фармасьютикал Ко., Лтд. Iohexol powder and method for use thereof

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