Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
  • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
  • A61K51/1262—Capsules
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2121/00—Preparations for use in therapy

Definitions

• This invention relates to radioactive capsules and particularly to capsules wherein radioactive compounds are retained without leakage.
• An oil such as glycerol trioleate has been tagged with a radioactive material and has been used as a tool in the study of fat metabolism.
• This radioactive isotope has been commonly deposited within a capsule and has been scaled therein by the simple step of telescoping a top capsule portion over a bottom portion of reduced diameter wherein is contained the radioactive oil.
• This particular embodiment has serious disadvantages in that the oil can possibly leak from the contained capsule, thereby causing serious contamination and reduction of the radioactive energy content. The possibility of such leakage is present and likely in ordinary handling, but the disadvantage is compounded many times by the necessary presence of air freight transport.
• a still further object of this invention is to provide ca sules suitable for oral administration wherein a liquid form of a radioactive compound is incorporated in a waxlike vehicle.
• a radioactive compound is placed in a capsule with a vehicle which is a solid at below body temperatures (37 C.) and melts at higher temperatures. It has now been found that radioactive compounds can be incorporated in those vehicles commonly employed in the suppository art. Such combined vehicle and radioactive compound can then be placed in a capsule suitable for oral ingestion and retained therein as a solid state below body temperatures. This novel article of manufacture significantly decreases any contamination hazard and eliminates the leakage of the radioactive compound from within the capsule.
• the radioactive compound is mixed with a suitable wax and oil of proper proportions so that the resulting mixture is a solid at temperatures lower than 37 C., but melts at temperatures at or above this level.
• the novel pharmaceutical form is prepared by melting a suitable wax and oil, combining therein the desired radioactive compound, transferring the molten mixture into a capsule, allowing the molten mixture to cool into a solid form and, thereafter, encapsulating the capsule so that the solid vehicle and radioactive compound therein is entirely contained within the capsular walls.
• the actual volume of molten mixture which is transferred to the capsule will be determined by the degree of radioactivity desired in the final product which, in turn, is determined by the amount of activity actually in the mixture 'on the day of preparation. Since radioactive decay constantly occurs, the procedure prescribes a preliminary assay of the molten mixture containing the radioactive source and thereafter selecting an appropriate volume of said mixture in order to provide a particular range of activity in the capsule on the day of preparation. Reference to standard decay curves for the particular radioactive source incorporated will enable the practitioner to prepare capsules which will contain a desired activity at some ascertained future date of use.
• Such capsules can be handled with greater assurance of freedom from radioactive contamination and can be quickly transported by air or other means without the extraordinary handling precautions which were necessary prior hereto in order to guard against leakage.
• Air transportation is now an added advantage because the lower temperatures of air flight make the wax-like vehicle harder, therefore, providing greater resistance to the damaged effects of lowered pressure.
• the great advantages obtained in the handling of such capsules are worthwhile because the pharmaceutical form is beneficially absorbed and utilized by the human.
• the attending clinician administers such a capsule to the patient and once the capsule reaches the stomach of the patient, the capsule material is disintegrated, the solid vehicle melts and the radioactive compound is absorbed.
• the capsules comprising an element disclosed herein are composed of a non-toxic, therapeutic, water-soluble material such as gelatin, methyl cellulose, polyvinyl alcohol or other thermoplastic, water-soluble, non-toxic materials which are therapeutically acceptable.
• the vehicle for the radioactive compounds is basically composed of a solid wax generally having melting points materially in excess of 37 C. and a solid oil which is of a lower melting point, but when mixed with the foregoing waxes in proper proportions results in a solid form which melts 1 larger amount of solid oil which melts at a lower level in order to obtain the resultant solid form at temperatures lower than 37 C.
• the choice of the waxes and solid oils is within the ordinary skill of the man in the art, once he is apprised of the teachings of this invention.
• oils and Waxes which are non-toxic and compatible with the human organism. He will next compound the oil and wax in the proper proportion to obtain a solid having the melting characteristics described herein.
• Representative and useful oils are theobroma oil (cocoa butter), hydrogenated or partially hydrogenated vegetable and plant oils such as corn, palm kernel, cottonseed, peanut, saffiower, olive and other operable solid oils.
• Suitable waxes are carbowax, spermaceti, glycerol monostearate, beeswax, cetyl alcohol and other suitable low or highmelting, non-toxic, pharmaceutical waxes.
• Parts 9 theobroma oil 4 spermaceti 13 total parts spermaccti The principles of allegation are also applicable in the event more than two ingredients are intended for combination. An example would be the combination of two solid oils of differing melting points with a solid wax of still another melting point. Recourse may be made to standard pharmaceutical texts in order to ascertain the method for combining such mixtures into a final composition melting at about 37 C.
• the radioactive compounds suitable for incorporation in the combination of the present invention are those compounds which have a known use after oral administration to the human. Such uses may either be diagnostic or therapeutic.
• Radioactive compounds which have been administered orally to the human for numerous purposes are radioactive iodine, glycerol trioleate, oleic acid, triiodothyronine and others.
• the radioisotopes which have a particular utility and which are prescribed orally can be determined by current recourse to the state of this dynamic art, for the new compounds which are tagged with radioactive atoms are constantly increasing in number and in application. If a particular radioisotope has been described in the art as an orally useful agent, then such compound can be incorporated in the novel combination disclosed herein.
• radioactive forms which are particularly useful for the present embodiment are those which occur as oils,
• oils such as glycerol trioleate and oleic acid.
• These comall pounds are liquid oils and, therefore, are particularly adaptable to being incorporated directly in the oil-wax combination which comprises the solid vehicle.
• the foregoing oils have unsaturated bonds in their chains which are suitably tagged with radioactive iodine
• Other oils with double bonds can also be tagged with such radioactive isotopes, e.g., corn oil, sai'llower oil and the like.
• oils tagged with radioactive iodine can be combined in equal volumes with the solid oil-wax combination which has been compounded to melt at 37 C. as set out hereinbefore.
• the combination of an equal volume of oil with the solid vehicle compounded to melt at 37 C. does not significantly alter such melting point.
• another inert oil can be employed as a diluent such as peanut oil or other vegetable oils. It is preferred to use an equal volume of the oil alone or diluted with another oil, which is to be combined with the solid vehicle because such volumes are easy to handle, easy to calculate and do not alter the melting point of the final composition.
• the amount of oil added to the vehicle base is substantially greater than an equal volume, the resulting mixture tends not to form a firm solid melting in the desired range. Therefore, it is a preferred and well-advised practice to incorporate at least an equal volume of the vehicle base to the oil. Of course, lesser volumes of the oil will not significantly affect the desired melting point range even though the mass tends to become more firm.
• radioactive materials which are not oils can also be incorporated in the wax-like vehicle to obtain similar advantages from the invention.
• Such radioactive substances can be either a dry powder form which carries the radioactive compounds or suspensions and emulsions thereof.
• Dry crystalline and powder forms can be incorporated directly into the wax-like vehicle by a mixing step.
• a prepared vehicle base which melts at substantially 37 C., as illustrated hcreinbefore, is melted or softened by heat, and the dry radioactive form is placed therein and mixed. It is apparent that incorporating such dry forms into the present embodiments attains advantages in the subsequent handling and administration of the radioactive materials. Hazards of contamination from capsular leakage or damage are virtually eliminated while, concurrently, an elegant pharmaceutical form for oral administration is provided.
• suspensions and emulsions of radioactive carriers can be incorporated into the embodiments of the present invention.
• a practitioner may desire to employ suspensions rather than placing a waterinsoiuble material directly into the vehicle base as described hereinbefore.
• Such suspensions can be prepared by conforming with the conventional procedures provided by that art and, thereafter, mixing said suspensions with the melted vehicle base.
• Example I Ingredient: Amount Theobroma oil 4.753 gms. 8 1spermaceti 2.334 gms.
• Glycerol triole'ate 1 tagged (1-2 mc./ml.)
• the theobroma oil and spermaceti are melted on a steam bath at temperatures not exceeding 75 C.
• the glycerol trioleate is added to this mixture and thoroughly mixed.
• the combined volume of the theobroma and spermaceti is 8 ml. which results in a vehicle melting at about 37 C.
• the melting point of the final composition is not altered from 37 C.
• a volume of approximately 0.2 ml. of this melted mixture is removed by a pipette and transferred into a bottom half of a gelatin capsule while taking the conventional precautions against radiation hazards.
• the upper half of the gelatin capsule is telescoped over the bottom portion and the melted mixture within the capsule is allowed to solidify.
• the foregoing formulation provides a sufiicient amount of melted material to prepare about 80 gelatin capsules.
• the solidified mixture melts in the range of 3436 C.
• Each capsule contains an activity of about 50-100 ,uc. as calibrated to a future date of use or approximately 120 ,uC. of 1 activity as of day of preparation.
• Example II Ingredient: Amount Glycerol monostearate 4 parts 1 Theobroma oil parts Glycerol trioleate, 1 tagged 4 ml.
• Example II The procedure steps outlined in Example I are followed to prepare 40 gelatin capsules wherein each capsule contains an activity of about 50-100 [10. as calibrated to a future date of use.
• Example III Ingredient: Amount Theobroma oil 4.753 gms. ⁇ 1spermaceti 2.334 gms.
• Oleic acid 1 tagged (l-2 mc./m1.) 8 ml.
• the theobroma and spermaceti are melted and combined with the oleic acid by process steps as described in Example I.
• the combined melted mixture is placed in a syringe which is aflixed to a syringe microburet, Model SE22, manufactured by the Micro-metric Instrument Co. of Cleveland, Ohio.
• a heating tape attached to a rheostat temperature control, is wrapped around the syringe to keep the waxes and oils in a molten state.
• the syringe microburet has a manually motivated plunger arm which terminates at a position flush against the plunger arm of the syringe.
• a dial is connected to the plunger systems whereby the desired volume of expelled molten solids can be determined. Volumes of approximately 0.2 ml. of expelled into each of the bottom portions of the gelatin capsules.
• the opening of the top portion of the gelatin capsule is dipped in an alcoholic solution of polyvinylpyrrolidone and then telescoped over the bottom portion of the capsule containing the melted composition.
• the alcoholic solution of polyvinylpyrrolidone serves to seal the capsule portions.
• the foregoing formulation provides a suflicient amount of melted mate- 6 rial to prepare about gelatin capsules.
• the solidified mixture melts in the range of 3234 C.
• Each capsule contains an activity of about 50-100 ,uC. as calibrated to a future date of use.
• An article of manufacture comprising a pharmaceutical capsule formed of a non-toxic, water-soluble, thermoplastic material and a radioactive composition compounded from pharmaceutical oils and waxes within said capsule, said radioactive composition being a liquid at about 37 C. and remaining a solid at lower temperatures.
• An article of manufacture comprising a pharmaceutical capsule formed of a non-toxic, Water-soluble thermoplastic material containing therein a radioactive composition compounded from pharmaceutical oils and waxes, said composition containing a radioactive material that is liquid, said radioactive composition melting at about normal body temperatures and remaining substantially a solid at lower temperatures.
• composition melting at body temperature is mixed with no more than an equal volume of Oil labeled with radioisotopes.
• An article of manufacture according to claim 2 wherein the capsule is made of gelatin and the radioactive composition is compounded from theobroma oil and spermaceti wax.
• said capsule is essentially composed of gelatin and said composition comprises theobroma oil, spermaceti wax and radioactive oleic acid.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Physics & Mathematics (AREA)
• Medicinal Chemistry (AREA)
• Optics & Photonics (AREA)
• Dispersion Chemistry (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
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• Medicinal Preparation (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

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Cited By (24)

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Citations (6)

• 0
  • NL NL269886D patent/NL269886A/xx unknown
• 1960
  • 1960-10-04 US US60312A patent/US3159545A/en not_active Expired - Lifetime
• 1961
  • 1961-09-21 GB GB33882/61A patent/GB938828A/en not_active Expired
  • 1961-10-02 BE BE608721A patent/BE608721A/fr unknown
  • 1961-12-28 FR FR883228A patent/FR1712M/fr active Active

Patent Citations (6)

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