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Capsules and method of producing

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US2911338A
US2911338A US41516854A US2911338A US 2911338 A US2911338 A US 2911338A US 41516854 A US41516854 A US 41516854A US 2911338 A US2911338 A US 2911338A
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radioactive
solution
capsule
capsules
solvent
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Donalee L Tabern
Robert H Storey
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Abbott Laboratories
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Abbott Laboratories
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
    • A61J3/071Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12Preparations 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
    • A61K51/1262Capsules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4833Encapsulating processes; Filling of capsules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2121/00Preparations for use in therapy

Description

231L338 Patented Nov. 3, 1959 CAPSULES AND METHOD F PRODUCING Donalee L. Taber-n, Lake Bluff, and Robert H. Storey,

Benton Township, Lake County, 11]., assignors to Abbott Laboratories, North Chicago, Ill, a corporation of Illinois No Drawing. Application March 9, 1954 Serial No. 415,168

13 Claims. (Cl. 167-51) The present invention relates to a new therapeutic form of radioactive compounds and more particularly to an improved encapsuled form of therapeutically useful radioactive compounds.

In the past radioactive compounds, such as sodium radioactive iodide (L131), have been dispensed by measuring out, usually by remote control, of suitable volumes of an aqueous solution of a radioactive compound. For diagnostic uses in particular, most of the radioactive material is given orally and for such use it has been customary to measure or pipette the aqueous solution of the radioactive compound into a cup or glass immediately prior to administering orally to the patient. The foregoing method of administering radioactive materials results in serious contamination of glassware and other equipment, particularly where the radioactive material is used in the small clinic or by the private practitioner.

Recently the foregoing disadvantages have been in part overcome by adding an aqueous solution of a radioactive compound to a gelatin capsule which is filled with sodium phosphate, the latter serving to remove part or all of the Water to form a hydrate with the result that the radioactive material is disposed on a fine, fluffy powder confined within the interior of the said capsule. Experience has shown that the latter capsules are not well suited for this purpose because the action of the water on the gelatin capsules during filling causes the development of irregular areas in the capsules. Moreover, when the capsules are damaged or broken, the remaining capsules and adjacent container becomes seriously radioactively contaminated. The latter contamination is even more serious if the breakage of the capsules occurs during the handling of the capsules while being given to the patient.

It is, therefore, an object of the present invention to provide an improved therapeutic form of radioactive compounds.

It is also an object of the invention to provide an improved therapeutic form of radioactive compounds permitting more conveniently administering accurately measured amounts of the radioactive therapeutic compounds.

It is a further object of the invention to provide an improved encapsuled form of therapeutic radioactive compounds.

It is a still further object of the invention to provide an improved encapsuled form for therapeutic radioactive compounds which reduces the danger of radioactive contamination to a minimum.

Other objects of the invention will be apparent to those skilled in the art from the following detailed description and the claims to follow.

It has been discovered that the foregoing and other objects of the present invention can be achieved by providing a gelatin capsule or capsule of other thermoplastic, water soluble, non-toxic material which has disposed interiorally as an integral part thereof or adsorbed on the interior wall a therapeutic or diagnostic dose of an organic or inorganic radioactive compound, such as sodium radioactive iodide (N-131). More particularly, it has been found possible to provide a capsule composed of a non-toxic therapeutic water soluble material having interiorally disposed as an integral part thereof a therapeutic or diagnostic dose or" a radioactive compound by forming a solution of the said radioactive compound in a relatively volatile essentially non-aqueous organic solvent, depositing a carefully measured volume of the said solution in an empty capsule or half thereof, and completely removing the solvent to leave the radioactive compound adsorbed on the inner walls of the capsule as a firmly attached integral part thereof.

The following specific examples are for the purpose of illustrating the present invention but should not be'construed so as to limit the invention to the precise materials and proportions employed.

Example I A solution of sodium radio-iodide (1-131) is prepared by reducing the mixture of iodide and iodate obtained as a product of nuclear fission. The sodium radio-iodide solution is evaporated to dryness and the iodide salt dissolved in a suitable volume of solvent consisting of approximately ethanol to provide a solution of the said salt in a solvent having a limited amount of water and having an activity of about 0.5 mc./ cc. The solution is then assayed by either beta or gamma counting, and an appropriate volume, as required to provide a capsule having an approximate activity of 30 ,uC. suitable for diagnostic use, is pipetted either by hand or automatically, into each of a set of empty gelatin capsules. The alcohol solvent is then allowed to evaporate, which procedure may be accelerated by a stream of air, or very mild heat. When the solvent is removed, the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Example II A solution of sodium radio-iodide (1-131) is prepared by reducing the mixture of iodide and iodate obtained as a product of nuclear fission. This solution is evaporated to dryness and dissolved in a suitable volume of solvent consisting of a 50:50 mixture of methanol and ether to provide an activity of about 20 mc./cc. The solution is then assayed by either beta or gamma counting, and an appropriate volume, as required to give the desired uptake dose is pipetted either by hand or automatically, into each of a set of empty gelatin capsules. The solvent is allowed to evaporate, which procedure may be accelerated by a stream of air, or very mild heat. Thereafter, the cap of the capsule is applied, preferably after slight wetting with a trace of Water or other suitable hygroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Example III gamma counting, and an appropriate volume, as required to give the desired uptake dose is pipetted either by hand or automatically, into each of a set of empty gelatin capsules. The solvent is allowed to evaporate, which procedure may be accelerated by a stream of air, or very mild heat. After complete removal of the acetone, the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one hour, theseal is complete, and the capsules are assayed again by the usual radio chemical means;

Example IV A solution of sodium radio-iodide (1-131) is prepared by reducing the mixture of iodide and iodate obtained as a product of nuclear fission. This is evaporated to drynessand dissolved ina suitable volume of solvent consisting of dioxane to provide an activity of about 20 mc./ cc. The solution is then assayed by either beta or gamma-counting, and an appropriate volume, as required to give the desired uptake dose is pipetted either by hand orautomatically, into each of a set -of empty gelatin capsules. The dioxane is allowed to evaporate, which procedure may be accelerated by a stream of air, or very mild heat. At the end of-this procedure, the cap of the capsule is applied, preferably after slight wetting with a trace of Water or other suitable hydroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means. 7

Example V A solution is prepared by. adding a small amount of potassium dihydrogen phosphate to a solution of radioactive phosphoric acid, commonly referred to as P-32. The solution is evaporated to dryness and dissolved in a suitable volume of aqueous ethanol consisting of at least about 85% ethanol to produce the desired concentration of radioactive phosphorous for diagnostic use. The solution is then assayed by beta counting, and an appropriate volume as required to give the desired uptake dose is pipetted either by hand or automatically, into each 'of a set of empty gelatin capsules. The solvent is allowed to evaporate, which procedure may be accelerated by a stream of air or very mild heat. At the end of this procedure, the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Example V1 Sodium iodide, the sodium atoms of which are comprised of sodium-22 or sodium-24, is dissolved in a suitable volume of 95% ethanol to provide the desired concentration of radioactive sodium. The solution is then assayed by either beta or gamma counting, and an appropriate volume as required to give the desired uptake dose for therapeutic purposes is pipetted either by hand or automatically, into each of a set of empty gelatin capsules. The alcohol is allowed to evaporate, which procedure may be accelerated by a stream of air or very mild heat. Thereafter, the cap of the capsule is applied, preferably after slight wetting with a trace of Water or other suitable hygroscopic solution or solvent. mately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Example VII Ferric chloride, the ferric iron atoms thereof being comprised of radioactive iron (Fe-55 or Fe59), is dissolved in a suitable volume of methanol to provide the desired concentration of radioactive sodium. The solution is then assayed by beta or gamma counting, and an appropriate volume, as required to give the desired uptake dose for diagnostic purposes is pipetted either by hand or automatically, into each of a set of empty gelatin capsules. The alcohol is allowed to evaporate, which procedure may be accelerated by a stream of air or very mild heat, and thereafter the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After After approxiapproximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Example VIII To provide a therapeutic does of sodium radioactive iodide, carrier free, a 95% ethanol solution of sodium radioactiveiodide, carrier free, equivalent to 10-50 mcs. ofI-l3l activity is formed. The solution is then assayed by either beta or gamma counting and an appropriate volume of the solution is pipetted into an empty gelatin capsule to provide therein a therapeutic dose. The alcohol is allowed to evaporate, which procedure may be accelerated by a stream of air or very mild heat. At the end of this procedure, the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

. Example IX -A solution 'of sodium radio-iodide is prepared by reducing ,the mixture .of iodide and iodate obtained as a product of nuclear fission. Thisis evaporated to dryness and dissolved in a suitable volume of solvent consisting of 95% ethanol. The solution is then assayed by either beta or gamma counting, and an appropriate volume as required ,to give the desired uptake dose is pipetted either by hand or automatically into each of a set of empty methyl cellulose capsules. The alcohol is allowed to evaporate, which procedure may be accelerated by a stream of air vor very mild heat. At the end of this procedure, the .cap of the capsule is applied, preferably afterslig'ht wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one 'hour, the seal is complete, and the capsules are assayed again 'by the usual radio chemical means.

Example X A solution of radioactive sucrose comprised of atoms of carbon is prepared by dissolving the required amount of radioactive sucrose in ethyl alcohol to provide the desired concentration of radioactive sucrose in solution The solution is then assayed by beta counting, and an appropriate volume, as required to give the desired dose is pipetted either by hand or automatically into each of a set of empty methyl cellulose capsules. The alcohol is allowed to evaporate, which procedure may be accelerated by a stream of air or very mild heat. At the end of this procedure, the cap of the capsule is applied, preferably after slight wetting with a trace of water or other suitable hygroscopic solution or solvent. After approximately one hour, the seal is complete, and the capsules are assayed again by the usual radio chemical means.

Another organic compound having high specific activity which is useful therapeutically (250 rnc. activity) or for diagnostic purposes (5-100 ,uC. activity) in the form of radioactive capsules is tritiostreptomycin which contains hydrogen atoms. Gelatin capsules having tritiostreptomycin adsorbed on the inner surface as an integral part thereof can be readily prepared in accordance with the foregoing example by forming the desired concentration of tritiostreptomycin chloride in methyl alcohol as the solvent, and thereafter removing the solvent as in the preceding examples. Penicillin containing radioactive carbon or sulfur can also be utilized in the preparation of radioactive capsules as described herein. The foregoing are merely illustrative of the many pharmaceutically useful radioactive organic compounds having high specific activity which are within the scope of the present invention; 7

Included'among the radioactive elements which are of diagnostic or therapeutic value which can be adsorbed from the gastrointestinal tract or useful in treating said tract and can be conveniently administered in the form of radioactive capsules prepared as disclosed herein are the alkali metals potassium and rubidium and calcium, zinc, and copper. In each instance a form of the desired element is selected which is soluble in a suitable concentration in alcohol or other relatively volatile organic solvent which contains only a limited amount of water and the radioactive salt is deposited within the interior of a thermoplastic, water soluble capsule as described herein wherein it diffuses into the wall surfaces to provide the capsule with an integral interior coating of the radioactive compound. 1

While the present invention has employed, for the purposes of illustrating the invention, primarily gelatin and methyl cellulose capsules, it should be readily understood that other thermoplastic, 'water soluble, non-toxic terials which are therapeutically acceptable can be used without departing from the scope of the present'invention. For example, capsules can also be made of polyvinyl alcohol.

Capsules of radioactive therapeutic compounds prepared in the foregoing manner are found to have an extremely firmly adhering diffused film or adsorbed layer of the radioactive material on the inner surface of the thermoplastic, water soluble capsule which is not detached during preparation, handling, transportation, or use of the capsules, and which can be opened and shaken thoroughly without loss of a significant amount of the radioactive therapeutic compound. The radioactive capsules of the present invention are, nevertheless, very rapidly disintegrated when administering orally and produce a measurable amount of radioactivity in the blood stream very soon after being orally administered to the patient.

The radioactivity of the capsules prepared in the herein described manner is capable of being measured accurately from the outside of the capsule as there is no interference or shielding of the radiation by the solid filler or carrier which has heretofore been used within the gelatin or other thermoplastic capsules. It is thus possible to directly intercompare with a suitable electronic measuring device for gamma rays the amount of activity in the thyroid with that contained in an identical capsule from the same lot as the capsule administered to the patient.

It is also possible, in the absence of a soluble solid filler or carrier for the radioactive material, to seal together the sections of the thermoplastic, water soluble capsule by moistening the contiguous ends of the capsule by traces of water or other suitable adhesive material immediately prior to joining the sections of the capsule.

Others may readily adapt the invention for use under various conditions of service, by employing one or more of the novel features disclosed or equivalents thereof. As at present advised with respect to the apparent scope of our invention, we desire to claim the following subject matter.

We claim:

1. An article of manufacture comprising a pharmaceutical radioactive capsule formed essentially of a nontoxic, water soluble, thermoplastic material adapted to being ingested and rapidly disintegrating on contact with water in the gastro-intestinal tract, and having a firmly adhering pharmaceutically useful radioactive compound absorbable from the gestro-intestinal tract adsorbed onv an inner surface of said capsule as an integral part thereof, whereby accidental contamination during handling and storage is substantially eliminated.

2. An article of manufacture as claimed in claim 1 wherein the said thermoplastic material is gelatin.

3. An article of manufacture as claimed in claim 1 wherein the said thermoplastic material is methyl cellulose.

4. An article of manufacture as claimed in claim 1 wherein the said thermoplastic material is polyvinyl alcohol.

5. An article of manufacture as claimed in claim 1 wherein the radioactive compound is an alkali metal iodide containing radioactive iodine atoms.

6. An article of manufacture as claimed in claim 1 wherein the radioactive compound is potassium dihydrogen phosphate containing radioactive phosphorous atoms.

7. An article of manufacture as claimed in claim 1 wherein the radioactive compound is an alkali metal iodide containing radioactive alkali metal atoms.

8. An article of manufacture as claimed in claim 1 wherein 'the radioactive compound is ferric "chloride wherein the ferric ions are comprised of radioactive iron atoms.

9. An article of manufacture as claimed in claim 1 wherein the radioactive compound is comprised of an organic compound having high specific activity which is absorbable from the gastrointestinal tract.

10. An article of manufacture as claimed in claim 9 wherein the said organic compound is sucrose containing radioactive carbon atoms.

11. A method of making a pharmaceutical radioactive capsule having disposed on the interior surface thereof a firmly adherent integral film of a radioactive compound useful for therapeutic or diagnostic purposes which comprises forming a solution of a radioactive compound which is absorbable from the gastrointestinal tract in a relatively volatile organic solvent having a limited amount of water therein, introducing into a capsule composed of a non-toxic, water soluble, thermoplastic material an accurately measured volume of the said radioactive solution to provide an accurately determined amount of radioactivity Within the capsule, removing the said volatile solvent from the solution within the capsule to provide on the interior surface of the capsule a thin, firmly adherent adsorbed film of radioactive compound Without alternating the normal configuration of the said capsule.

12. A method of making a pharmaceutical capsule as claimed in claim 11 wherein the said solvent contains a maximum of 20% water.

13. A method of making a pharmaceutical capsule as claimed in claim 11 wherein the said solvent contains between about 5 and 15% water.

References Cited in the file of this patent UNITED STATES PATENTS 650,760 Metcalf May 29, 1900 895,478 Lieber Aug. 11, 1908 2,062,897 Michel et a1. Dec. 1, 1936 FOREIGN PATENTS 20,116 Great Britain of 1889 OTHER REFERENCES Lapp et al.: Nuclear Radiation Physics (1948), pages 428430, 436, 437, 439, 440. Prentice-Hall, Inc., N.Y.C.

Peterson et al.: J. of Am. Pharm. Assn, Scientific Edition, vol. 39, No. 11, pages 607-609, November 1950.

Bradford: Radioisotopes in Industry, pages 62-65, 141, 256. Reinhold Publishing Co., N.Y.C. (1953).

UNITED STATES PATENT OFFICE QERTIFICATE 0F CURRECTION Patent No, 2 911 338 November 3, 1959 Donalee L Tabern et a1 It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 2, line 1, for "N lBJJ read M I=-l3l for ''does" read M dose Signed and sealed this 10th day of May 1960..

( SEAL) Attest:

KARL H, AXLINE Commissioner of Patents UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent Now 2,911,338 November 3, 1959 Donalee Lu Tabern et e1o It is hereby certified that error appears in the printed specification of the above numbered patent requiring correct-ion and that the said Letters Patent should read as corrected below.

Column 2, line 1, for "N lBl". reed I=-l3l column 4, line 5,, for "does" read w dose Signed and seeled this 10th day of May 1960.a

(SEAL) Attest:

KARL HWAXLINE ROBERT C. WATSON Attesting Officer Commissioner of Patents

Claims (1)

1. AN ARTICLE OF MANUFACTURE COMPRISING A PHARMACEUTICAL RADIOACTIVE CAPSULE FORMED ESSENTIALLY OF A NONTOXIC, WATER SOLUBLE, THERMOMPLASTIC MATERIAL ADAPTED TO BEING INGESTED AND RAPIDLY DISINTERGRATING ON CONTACT WITH WATER IN THE GASTRO-INTESTINAL TRACT, AND HAVING A FIRMLY ADHERING PHARMACEUTICALLY USEFUL RADIOACTIVE COMPOUND ABSORBABLE FROM THE GESTRO-INTESTINAL TRACT ADSORBED ON AN INNER SURFACE OF SAID CAPSULE AS AN INTEGRAL PART THEREOF, WHEREBY ACCIDENTAL CONTAMINATION DURING HANDLING AND STORAGE IS SUBSTANTIALLY ELIMINATED.
US2911338A 1954-03-09 1954-03-09 Capsules and method of producing Expired - Lifetime US2911338A (en)

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3027391A (en) * 1959-08-28 1962-03-27 Norman A Frigerio Metal phthalocyanines
US3061510A (en) * 1958-08-01 1962-10-30 Olin Mathieson Radioactive iodinated (i131) fatty material admixed with wax-like material in capsule
US3121041A (en) * 1960-07-20 1964-02-11 Olin Mathieson Capsule containing a pharmaceutically useful radioactive material
US3127313A (en) * 1964-03-31 Method of making a radioactive
US3159545A (en) * 1960-10-04 1964-12-01 Abbott Lab Radioactive capsules
US3728351A (en) * 1968-05-31 1973-04-17 Univ Michigan Radioiodinated quinoline derivatives
US3937668A (en) * 1970-07-15 1976-02-10 Ilse Zolle Method for incorporating substances into protein microspheres
USRE29474E (en) * 1966-06-02 1977-11-15 Pharmacia Ab Method for the determination of proteins and polypeptides
US4123382A (en) * 1973-05-25 1978-10-31 Merck & Co., Inc. Method of microencapsulation
FR2480124A1 (en) * 1980-04-14 1981-10-16 Squibb & Sons Inc diagnostic and therapeutic capsules and process for manufacture
US4663149A (en) * 1984-03-21 1987-05-05 Alza Corporation Dispenser comprising inner and outer walls functioning as cooperative unit
US4663148A (en) * 1984-03-21 1987-05-05 Alza Corporation Dispenser comprising telescopically engaging members
US4692326A (en) * 1984-03-21 1987-09-08 Alza Corporation Dispenser comprising inner positioned soft or hard capsule
US4716031A (en) * 1984-03-21 1987-12-29 Alza Corporation Drug dispenser comprising a multiplicity of members acting together for successfully dispensing drug
US5314678A (en) * 1992-01-28 1994-05-24 Mallinckrodt Medical, Inc. Sodium iodide 131 I capsules
WO1995016463A1 (en) * 1992-09-23 1995-06-22 The Dow Chemical Company Radioactive compositions and their use for radiation ablation treatment
US5993374A (en) * 1997-06-17 1999-11-30 Radiance Medical Systems, Inc. Microcapsules for site-specific delivery

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3022137C2 (en) * 1980-06-13 1988-08-11 A. Nattermann & Cie Gmbh, 5000 Koeln, De
DE3022136C2 (en) * 1980-06-13 1986-07-17 A. Nattermann & Cie Gmbh, 5000 Koeln, De
EP0060434B1 (en) * 1981-03-13 1986-11-12 Akademie der Wissenschaften der DDR Process for the preparation of a diagnostic or therapeutic composition containing iodine 131

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US650760A (en) * 1899-12-02 1900-05-29 Frederick H Metcalf Gelatin capsule.
US895478A (en) * 1905-09-21 1908-08-11 Hugo Lieber Radium preparation.
US2062897A (en) * 1931-01-29 1936-12-01 Charles O R Michel Container for a liquid

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US650760A (en) * 1899-12-02 1900-05-29 Frederick H Metcalf Gelatin capsule.
US895478A (en) * 1905-09-21 1908-08-11 Hugo Lieber Radium preparation.
US2062897A (en) * 1931-01-29 1936-12-01 Charles O R Michel Container for a liquid

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3127313A (en) * 1964-03-31 Method of making a radioactive
US3061510A (en) * 1958-08-01 1962-10-30 Olin Mathieson Radioactive iodinated (i131) fatty material admixed with wax-like material in capsule
US3027391A (en) * 1959-08-28 1962-03-27 Norman A Frigerio Metal phthalocyanines
US3121041A (en) * 1960-07-20 1964-02-11 Olin Mathieson Capsule containing a pharmaceutically useful radioactive material
US3159545A (en) * 1960-10-04 1964-12-01 Abbott Lab Radioactive capsules
USRE29474E (en) * 1966-06-02 1977-11-15 Pharmacia Ab Method for the determination of proteins and polypeptides
US3728351A (en) * 1968-05-31 1973-04-17 Univ Michigan Radioiodinated quinoline derivatives
US3937668A (en) * 1970-07-15 1976-02-10 Ilse Zolle Method for incorporating substances into protein microspheres
US4123382A (en) * 1973-05-25 1978-10-31 Merck & Co., Inc. Method of microencapsulation
US4349529A (en) * 1980-04-14 1982-09-14 E. R. Squibb & Sons, Inc. Diagnostic and therapeutic capsules and method of producing
DE3115053A1 (en) * 1980-04-14 1982-02-18 Squibb & Sons Inc radioactive capsules containing compounds and method for filling same
FR2480124A1 (en) * 1980-04-14 1981-10-16 Squibb & Sons Inc diagnostic and therapeutic capsules and process for manufacture
US4663149A (en) * 1984-03-21 1987-05-05 Alza Corporation Dispenser comprising inner and outer walls functioning as cooperative unit
US4663148A (en) * 1984-03-21 1987-05-05 Alza Corporation Dispenser comprising telescopically engaging members
US4692326A (en) * 1984-03-21 1987-09-08 Alza Corporation Dispenser comprising inner positioned soft or hard capsule
US4716031A (en) * 1984-03-21 1987-12-29 Alza Corporation Drug dispenser comprising a multiplicity of members acting together for successfully dispensing drug
US5314678A (en) * 1992-01-28 1994-05-24 Mallinckrodt Medical, Inc. Sodium iodide 131 I capsules
WO1995016463A1 (en) * 1992-09-23 1995-06-22 The Dow Chemical Company Radioactive compositions and their use for radiation ablation treatment
US5993374A (en) * 1997-06-17 1999-11-30 Radiance Medical Systems, Inc. Microcapsules for site-specific delivery

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