US3340151A - Method to produce roentgenographic pictures and composition for realization of the method - Google Patents

Method to produce roentgenographic pictures and composition for realization of the method Download PDF

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Publication number
US3340151A
US3340151A US369580A US36958064A US3340151A US 3340151 A US3340151 A US 3340151A US 369580 A US369580 A US 369580A US 36958064 A US36958064 A US 36958064A US 3340151 A US3340151 A US 3340151A
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US
United States
Prior art keywords
polyethylene glycol
parts
composition
gall bladder
water
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US369580A
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English (en)
Inventor
Eriksson Sven Axel
Fischler Max
Gidlund Ake Samuel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AstraZeneca AB
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Astra AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of US3340151A publication Critical patent/US3340151A/en
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Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/25—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl

Definitions

  • This invention relates to compositions having utility in X-ray examination of the gall bladder and its ducts.
  • An alternative is to liberate the bile duct during the operation and to introduce a solution of an X-ray contrast medium by a catheter into the bile duct and make a radiograph.
  • This method prolongs the operation considerably and involves greater risks for the patient.
  • a normal gall-stone operation lasts between 25 and 45 minutes, while such an extra X-ray examination of the bile ducts requires about 30 minutes more.
  • the toxic action of the narcotic becomes greater than necessary, with accompanying stronger after-effects and greater risks for the patient. If, on the other hand, it were possible pre-operatively, a short time after the first X-ray examination of the gall, to cause a gall-evacuation, the following advantages should be attained.
  • the present invention provides a composition whose use makes possible pre-operative X-ray photography of the bile ducts and the contracted gall bladder a very short time after the first picture has been taken, by which the advantages described above as resulting from a rapid and complete evacuation of the gall bladder are attained. More particularly the invention provides an orally administrable composition which causes some contraction of the gall bladder as little as 5 minutes after ingestion and complete evacuation of the gall bladder in about 15 minutes.
  • compositions of the invention comprise as active components a hexitol, a non-toxic ester or ether of a polyalkylene glycol or a polyoxyalkylene adduct, and a solid or liquid animal or vegetable edible fat.
  • Bo polyoxyalkylene adduct we mean a compound obtained by the reaction of a number of molecules of an alkylene oxide with a compound capable of forming an ester or ether linkage with the polyoxyalkylene chain so produced.
  • a composition is administered orally after a conventional composition to render the gall bladder visible, and a series of X-ray photographs are taken.
  • the contraction of the gall bladder is followed r0- entgenographically from the non-contracted to the maximally contracted state by a small number of exposures.
  • the first may be made immediately before the intake of the gall bladder contracting composition followed by two others 5 and 15 minutes after the intake respectively.
  • Suitable hexitols for use in the gall bladder contracting compositions are for instance sorbital, mannitol, dulcitol and iditol. Of these sorbitol and mannitol are the most easily available and of these sorbitol is especially suitable owing to its solubility properties.
  • Suitable polyethylene glycol adducts are: among the esters for instance polyethylene glycol stearate (Myrj), among the ethers, for instance polyethylene glycol lauryl ethers (Brij) and among other polyethylene glycol adducts for instance polyethylene glycol sorbitan esters, such as monooleate, monostearate, monopalrnitate and trioleate thereof (Tween).
  • polyethylene glycol 'sorbitan monooleate Teween and polyethylene glycol stearate (Myrj 51).
  • suitable fats to be included in the gall bladder contracting compositions may be mentioned peanut oil, soya bean oil, cotton-seed oil, castor oil, linseed oil, rape-seed oil, olive oil, sesame oil, coconut oil, palm oil, anise oil, fish oils, cocoa-butter and coconut butter. Of these peanut oil has been found especially suitable.
  • compositions of the invention are preferably administered in liquid form, with the active components dissolved or dispersed in water together with conventional additives such as fiavouring agents, preserving agents, stabilizing agents etc., but it is also possible to administer them in the solid form, ie without water, although contraction then is somewhat delayed owing to the time needed for the breaking up of the solid composition and the dispersion or solution of the solid components.
  • This disadvantage may be diminished by the addition of disintegrating agents such for instance as sodium bicarbonate in combination with tartaric acid, calcium citrate etc.
  • the active ingredients are preferably in an extremely finely dispersed form, preferably in colloidal solution, that is with a particle size less than 0.1 since compositions of greater particle size are resorbed too slowly for the quickest action.
  • preserving agents which may be included in the composition to prevent the growth of micro-organ- 3 isms are propyl-p-hydroxybenzoic acid (Nipasol), salicylic acid and sorbic acid.
  • stabilizing agents are complexforming substances or stabilizers such for example as ascorbic acid (a typical anti-oxidant), and citric acid, ethylenediaminotetra-acetic acid, or citraconic acid (complex-forming substances).
  • Suitable flavouring agents are sweeteners such as saccharin sodium, sodium cyclamate, sodium glutamate and flavouring essences such as orange essence, etc.
  • the pH of the liquid composition is preferably about 2-5.
  • the amounts of the active components in the gall bladder-contracting composition may be varied within wide limits; for instance the amount of the hexitol will depend partly on its solubility properties. From the point of view of effectiveness and taste the hexitol content of the liquid composition is preferably 10-70 parts, the amount of polyalkylene glycol ester or ether or polyoxyalkylene adduct 2-1 5 parts, and the amount of fat 0.1-l.5 parts, all per 100 parts of water. (All parts are by weight.) Specially suitable are compositions containing 25-35 parts hexitol, 6-10 parts polyalkylene glycol ester or ether or polyoxyalkylene adduct, and 0.2-0.7 part of fat per 100 parts of water.
  • the amount of hexitol is preferably 25-70%, the amount of polyalkylene glycolester or ether or polyoxyalkylene adduct 25-70%, and the amount of fat 1-7% of the weight of the composition.
  • Specially suitable are compositions containing 35-60% of hexitol, 35-60% of polyalkylene glycol ester or ether or polyoxyalkylene adduct, and 2-6% of fat.
  • the polyethylene glycol sorbitan monooleate was heated to 50 C., after which the peanut oil and the water-soluble flavoun'ng agents were added with continuous stirring at 50 C.
  • the resulting solution was allowed to cool to 30 C., when an aqueous solution containing the watersoluble flavouring agents and V of the amount of sorbitol was incorporated with stirring.
  • the remaining sorbitol was added with stirring at a temperature of -30 C., after which the resulting solution was diluted to a volume of 100 ml. and the pH was adjusted to 4.5.
  • Example II In the same manner as in Example I a solution was prepared from the following ingredients:
  • the polyethylene glycol stearate was melted at 4050 C.
  • the peanut oil and the flavouring agents and the colourants were dissolved in the melt, after which the sorbitol was mixed in and the resulting mixture was moulded into tablets.
  • Example IV In the same manner as in Example III solid tablets of the following composition were prepared:
  • liquid compositions are suitably administered in such an amount that as much as possible of the intestine mucosa is covered with the gall-emptying composition.
  • Suflicient effect is obtained at a dose of about 50 ml., but it may in certain cases be preferable to use a double dose, and this can be swallowed by the patient without difficulty.
  • the toxicity of the gall bladder contracting compositions is so small that it cannot be determined. Tests performed in mice show an oral LD 50 greater than 50 g./ kg. mouse.
  • a method for contracting the gall bladder for X-ray diagnosis which comprises administering orally an effective dose of a composition consisting essentially of, as its active constituents, (a) a material of the [group consisting of sorbitol and mannitol, (b) a material of the group consisting of nontoxic water-dispersible polyethylene glycol esters and ethers containing at least about 5 oxyethylene groups per molecule, of the class consisting of (1) polyethylene glycol esters of higher fatty'acids, (2) polyethylene glycol ethers of higher fatty alcohols, and (3) polyoxyethylene derivatives of cyclized 'hexitols esterified with higher fatty acids, and (c) a material of the :group consisting of solid and liquid animal and vegetable edible fats, said constituents being dispersed in water, said constituents being within the limits of 10 to parts by weight of sorbitol and mannitol, 2 to 115 parts by weight of said polyethylene glycol esters or ethers, or
  • component (b) is a material of the group consisting of polyethylene glycol sorbitan monooleate and polyethylene glycol stearate
  • the fat (c) is a material of the group consisting of peanut oil, soya bean oil, grape seed oil, castor oil, olive oil, coconut oil, fish oil, cocoa-butter, and coconut butter.
  • composition contains also a preserving agent and a stabilizer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Emergency Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Measurement Of Radiation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
US369580A 1963-03-21 1964-05-22 Method to produce roentgenographic pictures and composition for realization of the method Expired - Lifetime US3340151A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SE311663 1963-03-21

Publications (1)

Publication Number Publication Date
US3340151A true US3340151A (en) 1967-09-05

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Family Applications (1)

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US369580A Expired - Lifetime US3340151A (en) 1963-03-21 1964-05-22 Method to produce roentgenographic pictures and composition for realization of the method

Country Status (9)

Country Link
US (1) US3340151A (bg)
BE (1) BE644901A (bg)
CH (1) CH464445A (bg)
DE (1) DE1206118B (bg)
DK (1) DK107250C (bg)
FI (1) FI44669C (bg)
FR (2) FR3196M (bg)
GB (1) GB1061440A (bg)
NL (1) NL6402989A (bg)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4192859A (en) * 1978-09-29 1980-03-11 E. R. Squibb & Sons, Inc. Contrast media containing liposomes as carriers

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB803078A (en) * 1956-10-16 1958-10-15 Schenley Lab Inc Oral fat emulsions
GB806723A (en) * 1955-09-02 1958-12-31 Ici Ltd New pharmaceutical compositions
US2977283A (en) * 1956-04-30 1961-03-28 Upjohn Co Therapeutic intravenous fat compositions
US3169094A (en) * 1960-08-26 1965-02-09 Wretlind Arvid Johannes Method of preparing intravenously injectable fat emulsions free from side reactions or complications

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB806723A (en) * 1955-09-02 1958-12-31 Ici Ltd New pharmaceutical compositions
US2977283A (en) * 1956-04-30 1961-03-28 Upjohn Co Therapeutic intravenous fat compositions
GB803078A (en) * 1956-10-16 1958-10-15 Schenley Lab Inc Oral fat emulsions
US3169094A (en) * 1960-08-26 1965-02-09 Wretlind Arvid Johannes Method of preparing intravenously injectable fat emulsions free from side reactions or complications

Also Published As

Publication number Publication date
FI44669B (bg) 1971-08-31
FI44669C (fi) 1971-12-10
GB1061440A (en) 1967-03-15
BE644901A (bg) 1964-07-01
DE1206118B (de) 1965-12-02
FR3196M (fr) 1965-03-15
FR3197M (fr) 1965-03-15
CH464445A (de) 1968-10-31
NL6402989A (bg) 1964-09-22
DK107250C (da) 1967-05-08

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