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
  • A61K51/02—Preparations 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
  • A61K51/04—Organic compounds
  • A61K51/06—Macromolecular compounds, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
  • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
  • A61N5/1027—Interstitial radiation therapy
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2121/00—Preparations for use in therapy
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
  • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
  • A61N2005/1019—Sources therefor

Definitions

• the present invention relates to the art of medicine and has particular reference to a radioactive preparation absorbable in organism and to a method of obtaining said preparation.
• the herein-disclosed radioactive preparation absorbable in organisms is applicable in treating carcinoma of salivary glands, mammary gland, thyroid gland, as well as malignant tumors arising from muscular tissue, fasciae, intramuscular connective tissue, tendon sheaths, synovial bursae, cartilages, and the like (sarcoma, myosarcoma, angiosarcoma, chondrosarcoma, synovioma, and others), and also in treating cerebral tumors and in oncological practice in ophthalmology.
• radioactive preparations absorbable in organisms such as a preparation in the form of films based on gelatin in conjunction with radioactive chromium phosphate (P or a filiform preparation of germanium dioxide in combination with radioactive isotopes of Au.
• P radioactive chromium phosphate
• the method of obtaining said filiform preparation containing the isotopes of Au consists in that powderlike germanium dioxide of a highest purity is wetted with an inactive solution of aurous chloride. The resulted mixture is melted at 1200' C. After a molten mass has been obtained, one proceeds to touch its surface with a silver or golden stick to draw threads therefrom which are then activated in a flux of thermal neutrons. Threads containing radioactive isotope of P are obtainable in a similar way using germanium dioxide and radioactive titanium phosphate as initial components. Threads 1.7 mm. in diameter are thus obtained which dissolve in the organisms fluids within 7 to 14 days.
• a filament is formed from the dough-like mass obtained and is then dried at C. within 10-12 hours.
• the obtained thread is 1.1 mm. in diameter, possessing a linear activity of 1.0 to 1.8 mc./crn. and the preparation is absorbed in the organism within 7 days.
• Another method of obtaining a filitorm radioactive preparation absorbable in organism comprises mixing a methyl cellulose solution, starch, glycerol and radioactive isotope of Y in the form of yttrium oxide, with subsequent filament shaping and drying at -140 C. within 12 hours.
• a method of radioactive preparations in the form of films comprise mixing high-viscosity polyvinyl alcohol with gelatin, glycerol, a radioactive isotope and antibiotics to a uniform mass with the subsequent polymerization at 20-25 C. within 12 hours (cf. Am. J. Roentgenol. Rad. Therapy and Nuclear Med, 1956, '75, pp. 1084-1092; Collection of Abstracts on Nuclear Medicine, Moscow, 1962, v. 5, pp. 189-190; Proceedings of International Conference on Peaceful Use of Atomic Energy (held at Geneva, 1955), Moscow, 1958, v. 10, pp. 143-145).
• the afore-discussed radioactive preparations absorbable in organisms sufifer from a number of disadvantages.
• the preparations made as films based upon gelatin are liable to quickly dissolve in the organism (in 3-4 days), resulting in that the liberated isotope is resorbed from the site of injection, thereby inflicting a radiation load upon the sound organs and tissues, such films possess inadequate mechanical strength making manipulation difficult when placing and fixing the films in the operative field.
• the application of gelatin as a base constituent demands special storage precautions for the preparations, since gelatin is a good nutrient medium for the growth of micro organisms. Preparations based upon gelatin cannot be subjected to heat treatment.
• a. radioactive preparation absorbable in organism contains methyl oxypropyl cellulose in combination with radioactive isotopes.
• Methyl oxypropyl cellulose is also known as methyl hydroxypropyl cellulose.
• radioactive preparations absorbable in organisms and containing methyl oxypropy cellulose in combination with radioactive isotope of An or such preparations containing methyl oxypropyl cellulose in combination with radioactive isotope of Y in the form of yttrium silicate.
• the herein-disclosed radioactive preparations absorbable in organisms can be made as films, filaments or threads, granules, and the like.
• films and threads are in effect thin (0.08 to 0.1 mm), transparent or light-red coloured preparations featuring high mechanical strength and good elasticity, and their specific activity being 0.1-1.0 mc./cm.
• the present preparation when filiform is in fact fine, elastic threads 20-50 cm. long and 0.3-0.5 mm. in diameter, and their linear activity being 0.025-03 mc./cm.
• the film-shaped preparation is applicable in treating carcinoma of salivary glands, mammary gland and malignant tumors arising from muscular tissue, fasciae, intramuscular connective tissue, tendon sheaths, synovial bursae, cartilages, and the like.
• radioactive films absorbable in the organism are laid throughout the length of the operative field and fixed by suturing.
• the filiform radioactive preparation of this invention is used for stitching small-sized tumors such as those of the eye, tumors occurring in the central nervous system, especially in those cases where intratissue beam therapy is the only means to affect the growth of a neoplasm. They are also useful for stitching up the pathways of possible metastatic spreading of the tumor (i.e., along lymphatic vessels and at lymphatic nodes).
• Intratissue beam therapy combined with the use of radio-active films and threads absorbable in the organism may be particularly effective when applied in conjunction with external irradiation.
• the implantation therapy proves to yield especially good results in the form of an additional efiect on the residual tumor after external irradiation.
• Curing of the same tumor with the use of films containing the isotope of Y has taken place When the specific activity of the films has been equal to 0.18 mc./cm. (the average diameter of the tumors before beginning of the treatment having been equal to 1.0: 0.1 mm.) which when referred to an averaged absorbed dose in the tissues surrounding the preparation over a distance of the mean path of beta-particles, amounts to 9300 rad. Curing of the tumor NMP-l has occurred after treatment with radioactive films containing the isotope of Y and having a specific activity of 0.373 mc./crn. (an averaged absorbed dose being 20,000 rad).
• the proposed method consists in that methyl oxypropyl cellulose is mixed with distilled water, then centrifuged and the resultant centrifugate is mixed with a solution of radioactive isotope, whereupon the mixture is shaped and dried.
• colloidal solution of Au or of Y in the form of yttrium silicate
• colloidal solution of radioactive isotope it is most preferable that colloidal solution of Au or of Y (in the form of yttrium silicate) be made use of as the solution of radioactive isotope.
• methyl oxypropyl cellulose at a dynamic viscosity of 10 to 50 cp. is mixed with distilled water in the amounts necessary for obtaining a paste which is then centrifuged and the centrifugate is mixed with a colloidal solution of Au or a colloidal solution of yttrium silicate in amounts that the content of methyl oxypropyl cellulose in the mixture is 10-25 weight percent and its specific activity is equal to 4-10 mc./:g., whereupon threads or filaments, are shaped from the mixture obtained and dried at IOU- C. until a dry filament is formed.
• Methyl oxypropyl cellulose taken in an amount of 3-4 weight percent in the case of films and 12-25 weight percent in the case of paste, is mixed with distilled water.
• concentration of the mixture should be selected so that when mixing it with a solution of radioactive isotope the Weight percentage of methyl oxypropyl cellulose be equal to 2.7-4 for films and 10-25 for threads. When said percentage is below 2.7 the film will be too thin and inadequately strong, whereas if that percentage is in excess of 4, the film gets overthickened and less elastic.
• methyl oxypropyl cellulose be mixed with distilled water at 20-50 C. under continuous stirring to accelerate the process.
• a viscous solution is obtained in the case of films, or a paste in the case of threads or filaments.
• the obtained mixture is centrifuged to eliminate air bubbles arising in the viscous solution during stirring and which impeding adequate spreading of isotopes over the emitting surface of the film, as well as to eliminate solid impurities present in the paste-like mass.
• Use may be made either of betaor gamma-emitting short-lived isotopes such as Y An P, Pd and others.
• radioactive isotopes are utilized as solutions. It isfavourable'to employ as the solutions of radioactive isotopes, colloidal solutions of Au or of yttrium silicate (Y since when using colloidal solutions, isotopes are less liable to resorb from the site of implantation during the preparation absorption, at the same time maintaining a uniform distribution of isotopes over the emitting surface of films and threads.
• the absorption period of the preparations in the organism rises with an increase in the viscosity of methyl oxypropyl celloluse; it should therefore be borne in mind that if the most short-lived isotopes (Y Au are used as radiation sources, lowerviscosity methyl oxypropyl cellulose is to be employed.
• the finished films are sterilized and stored in an absolute ethyl alcohol contained in sterile ampoules. It takes 2-5 hours for the films to sterilize in an absolute ethyl alcohol, the extraction of isotopes by the absolute ethyl alcohol being not in excess of 2.10- to 3.10 weight percent.
• the mixture of methyl oxypropyl cellulose with the colloidal solution of isotope is shaped into filaments which are then dried at IOU-150 C. till a dry filament is formed.
• the finished filaments possess a linear activity of 0.025- 0.3 mc./cm., the coefficient of variation for those containing the isotope of Au being 0.86%, for those containing the isotope of Y 2.64%. Threads or granules are sealed up into ampoules and sterilized at 130 C. for 2-3 hours.
• the use of methyl oxypropyl cellulose of dilferent viscosity makes it possible to obtain preparations with different periods of absorption in organisms, said periods being alterable to suit the particular anatomic region 6 where the preparation is to be injected and the half-life of the radioactive isotope selected.
• methyl oxypropyl cellulose is not a nutrient medium for the growth of microorganisms and does not possess cancerogenic properties.
• EXAMPLE 1 A batch of 1.2 g. of methyl oxypropyl cellulose at a dynamic viscosity of 20 cp. is mixed with 29 g. of distilled water at 40 C. while continuously stirring till a transparent, slightly opalescent uniform solution is obtained. Then the solution obtained is subjected to centrifugation at 3000 r.p.m. for 10 min. The resulting centrifugate is transferred into a clean glass chemical vessel, and 6 ml. of colloidal solution of yttrium silicate (Y) with a specific activity of 8.3 mc./ml. are added thereto.
• Y yttrium silicate
• the resultant radioactive mixture is carefully and cautiously agitated with a glass stick, the specific activity of the mixture becoming 1.66 mc./ml.; this done, the mixture is poured into a Petri dish preliminarily coated with glycerol and possessing a plain horizontal surface. Then the 'Petri dish coated with the radioactive mixture is placed in a drying cabinet at 40 C. and kept there till a thin readily separated film is obtained. The area of the film is '60 cm. its specific activity being 0.83 mc./cm.
• the finished film is placed in glass sterile ampoules containing an absolute ethyl alcohol and the ampoules are sealed.
• EXAMPLE 2 A batch of 1.2 g. of methyl oxypropyl cellulose at a dynamic viscosity of 50 cp. is mixed with distilled water at 40 C. while continuously stirring till obtaining a uniform paste. Then the resultant paste is centrifuged at 5000 r.p.m. for 15 min., whereupon 0.2 ml. of glycerol and 2.5 ml. of colloidal solution of Au with a specific activity of 20 mc./ml. are added and the mixture is thoroughly agitated. The paste obtained possesses a specific activity of 5 mc./g.
• the obtained radioactive paste is shaped into threads or filaments by using a special device, the threads or filaments are placed onto a glass heated up to C. which is then quickly transferred into a drying cabinet and kept there for 15 min.
• the threads or filaments obtained possess a linear activity of 0.125 mc./cm.; they are scaled up in sterile ampoules and sterilized at C. for 2 hrs.
• a method for preparing shaped absorbable radioactive articles for tissue implantation which comprises mixing methyl oxypropyl cellulose having a viscosity range of from 10 to 50 cp. (1%) with water in sufiicient amounts to form viscous solutions to pastes of the mixture; centrifuging the resultant mixture; mixing the centrifugate with a colloid or solution of a radioisotope from the group of radiogold (Au and radio-yttrium (Y forming said shaped articles from said radioactive mixture; and then removing the water from said shaped article by heating at temperatures below about C.
• a radioactive absorbable shaped article for tissue implantation comprising a mixture of methyl oxypropyl cellulose of dynamic viscosity 10-50 cp. (1%) and a radioactive isotope of Au or Y said isotope being uniformly distributed through the methyl oxypropyl cellulose matrix from colloid or solution, and said shaped article having specific activities of 0.05 to 1.0 mc./cm. for films and 0.02 to 0.3 mc./cm. for filaments.

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• 1970
  • 1970-03-11 DE DE2011612A patent/DE2011612C3/de not_active Expired
  • 1970-03-12 FR FR7008834A patent/FR2081570A1/fr active Granted
  • 1970-03-16 US US00020047A patent/US3719750A/en not_active Expired - Lifetime

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