Missouri University of Science and Technology Scholars' Mine Materials Science and Engineering Faculty Research & Creative Works Materials Science and Engineering 06 Dec 1988 Glass Microspheres D. E. Day Missouri University of Science and Technology, [email protected] Gary J. Ehrhardt Follow this and additional works at: https://scholarsmine.mst.edu/matsci_eng_facwork Part of the Ceramic Materials Commons Recommended Citation D. E. Day and G. J. Ehrhardt, "Glass Microspheres," U.S. Patents, Dec 1988. This Patent is brought to you for free and open access by Scholars' Mine. It has been accepted for inclusion in Materials Science and Engineering Faculty Research & Creative Works by an authorized administrator of Scholars' Mine. This work is protected by U. S. Copyright Law. Unauthorized use including reproduction for redistribution requires the permission of the copyright holder. For more information, please contact [email protected]. United States Patent [«] [li] Patent Number: 4,789,501 Day et al. [45] Date of Patent: Dec. 6, 1988 [54] GLASS MICROSPHERES Alkaline Durability of High Elastic Modulus [75] Inventors: Delbert E. Day, Rolla; Gary J. Alumino-Silicate Glasses Containing Y2O3, La203 and Ehrhardt, Columbia, both of Mo. T i0 2, 38 & 39 1980 pp. 661-666. I. V. Grebenschikov Institute of Silicate Chemistry, [73] Assignee: The Curators of the University of Academy of Sciences, USSR-Bonder et al, Phase Equi­ Missouri, Columbia, Mo. libria In The System Y203-AJ.2C>3-SiC>2, Jul. 1964, pp. [21] Appl. No.: 673,123 1325-1326. [22] Filed: Nov. 19,1984 State Scientific-Research and Design Institute of the Rare Metals Industry-Sedykh et al., Refractive Indicies [51] Int. C l.*......................... A61N 5/10; C03C 3/083; in the System Y 203-Si02-Al203 in The Vitrification C03C 3/095; G21G 4/08 Region. Translate from Izvestiya Akademii Nauk [52] U.S. Q ......................................... 252/645; 128/654; SSSR, Neorganicheskie Materialy, vol. 11, No. 6, pp. 252/625; 252/629; 252/644; 424/1.1; 424/9; 1153-1154, Jun. 1975. 428/402; 436/527; 501/64; 501/68; 501/152; Antova et al., Thermal Endurana of Glass Based on 501/153; 501/154 Y203-Al203-Si02, Izv. Akad, Nauk SSSR, Neorg. [58] Field of Search......................... 424/1.1, 16, 9, 22, Mater, 12(4): 783-784, 1976. 424/140, 133, 137; 436/527; 252/629, 478, 625, The American Surgeon-Nolan et al., Intravascular 644, 642; 128/1.1, 654; 501/152, 155, 55, 64, 68; Particulate Radioisotope Therapy, Mar. 1969, vol. 34 428/402, 406, 404; 423/21.1; 604/890-891 No. 3 pp. 181-188. [56] References Cited The American Surgeon-Grady et al., Intra-Arterial U.S. PATENT DOCUMENTS Radioisotopes To Treat Cancer, Oct. 1960, vol. 26, pp. 678-684. 3,334,050 8/1967 Grotenhuis ..................... 252/301.1 4,147,767 4/1979 Yapel, Jr............................... 424/22 Int. J. Appl. Radiat. Isot-Zielinski et al., Synthesis and 4,247,406 1/1981 Widder et al......................... 424/1.1 Quality Control Testing of 32P Labeled Ion Exchange 4.314.909 2/1982 Beall et al............................ 252/629 Resin Microspheres for Radiation Therapy of Hepatic 4,350,675 9/1982 Drake.................................. 424/1.1 Neoplasms, vol. 34, No. 9, pp. 1343-1350, 1983. 4,362,659 12/1982 Macedo et al....................... 252/644 4,406,697 9/1983 Parak et al.......................... 252/644 Primary Examiner— Stephen J. Lechert, Jr. 4,464,294 8/1984 Thiele................................ 252/629 Assistant Examiner—Howard J. Locker 4.530.909 7/1985 Makishima et al.................... 501/73 Attorney, Agent, or Firm—Senniger, Powers, Leavitt and Roedel OTHER PUBLICATIONS [57] ABSTRACT Journal of The American Ceramic Society-Makishima et al., Elastic Moduli and Refractive Indices of Alumi­ A radioactive microsphere for radiation therapy of a nosilicate Glasses Containing Y2O3, La203 and TiO, mammal comprising a biologically compatible glass May-Jun. 1978, pp. 247-249. material containing a beta or gamma emitting radioiso­ Journal of The American Ceramic Society-Loehman, tope distributed substantially uniformly throughout the Preparation and Properties of Yttri­ glass. Advantageously, the radioisotope is produced by um-Silicon-Aluminum Oxynitride Gasses; Sep.-Oct. irradiation of the microsphere. 1979, pp. 491-494. Journal of Non-Crystalline Solids-Makishima et al., 8 Claims, 5 Drawing Sheets ■SiOz U.S. Patent Dec. 6,1988 Sheet 1 of 5 4,789,501 FIG.I U.S. Patent Dec. 6,1988 Sheet 2 of 5 4,789,501 FIG.2 £ £ P ^ £ P l £L£A^£A/r/?L PHasPuayec/s (Vr % U.S. Patent Dec. 6,1988 Sheet 3 of 5 4,789,501 FI G.3 O/K/TOSO/D>££OPUg C /?£o/L° /O ZO SO 40 T /M £(/=>/? ‘S O ) U.S. Patent Dec. 6,1988 Sheet 4 of 5 4,789,501 I $ $ $ V \ § § T/M£, tJOL/ZS § § FIG. 4 FIG. U.S. Patent Dec. 6,1988 Sheet 5 of 5 4,789,501 FIG. 5 T/M£, /Vau/ZS 4,789,501 1 2 theless not without its disadvantages. Processing of GLASS MICROSPHERES these ceramic microspheres is complicated because potentially volatile radioactivity must be added to ce­ BACKGROUND OF THE INVENTION ramic melts and the microspheres must be produced and The present invention relates generally to micro­ 5 sized while radioactive, with concomitant hazards of spheres useful in the treatment of cancerous and tumor exposure to personnel and danger of radioactive con­ bearing tissue and more particularly to novel glass mi­ tamination of facilities. crospheres useful in this treatment. Consequently, a need has remained for a microsphere In the treatment of patients with certain kinds of which is useful in the treatment of cancer or tumor cancer, methods are known in which radioactive parti­ 10 bearing tissue, but which will not release a radioactive cles are introduced intravascularly in order to trap the coating or isotope into remote parts of the body of the radioactive particle at a particular site for its radiation patient after administration, will not require any techni­ effect. According to this technique, a small quantity of cians to handle any radioactive materials during the the radioactive particles are injected into the patient formation and spheroidization of the microsphere and and a diffuse, homogeneous field of radiation within a 15 which have a density which will permit the micro- selected region of the body is achieved by permanent spheres to be suspended in a fluid suitable for injection lodgement of the particles in the capillary bed of the into a human. , proposed area, typically the location of a tumor. In early applications of this technique, yttrium oxide po- SUMMARY OF THE INVENTION 20 weer was suspended in a viscous medium prior to ad­ Among the several objects of the invention, therefore ministration. Yttrium was selected for the technique may be noted the provision of a novel microsphere for because of its suitable characteristics: it emits nearly 100 use in radiation therapy; the provision of such a micro- percent beta radiation. See, e.g., Nolan, et al., Intravas­ sphere wherein the radioactive isotope is uniformly cular Particulate Radioisotope Therapy”, The American distributed throughout the microsphere material; the Surgeon 35: 181-188 (1969) and Grady, et. al., Intra-Ar­ 25 provision of such a microsphere wherein there is no terial Radioisotopes to Treat Cancer”, American Sur­ significant release of the radioactive isotope from the geon 26: 678-684 (1960). This method is not totally microsphere into the body of the patient; the provision satisfactory, however. Two disadvantages of yttrium oxide powder are its high density (5.01 gm /cm 3) and o f such a microsphere in which the microsphere is com­ irregular particle shape. The high density of pure yt­ 30 pletely- nonradioactive until irradiated for use in ther­ trium oxide powder makes it difficult to keep the parti­ apy; the provision of such a microsphere which con­ cles in suspension in the liquids used to inject them into tains a stable element or isotope that can be activated to the body, and accelerates their tendency to settle in the a beta or gamma radiation emitting isotope by neutron blood stream prior to reaching the desired tumor. The irradiation; the provision of such a microsphere which sharp comers and edges of yttrium oxide particles also 35 contains a number of stable elements or isotopes that irritate surrounding tissue in localized areas, and inter­ which forms a number of beta or gamma radiation emit­ fere with the uniform distribution o f the radioactive ting isotopes simultaneously during neutron activation, particles in the tumor to be treated. thereby permitting wide variation in the rate at which In later applications, the particles used have been the radiation is delivered to the body; the provision of microspheres composed of an ion exchange resin, or 40 such a microsphere wherein the density of the sphere is crystalline ceramic core, coated with a radioactive iso­ substantially less than that of yttrium oxide particles; the tope such as P-32 or Y-90. Both ion exchange resin and provision of formulations for treatment of tumors by crystalline ceramic microspheres offer the advantage of parenteral administration; and the provision of pro­ having a density much lower than that of yttrium oxide cesses for radiation therapy as well as the manufacture particles, and the ion exchange resin offers the addi­ 45 of microspheres of the present invention. tional advantage of being particularly easy to label. See, Briefly, therefore, the present invention is directed to e.g., Zielinski and Kasprzyk, “Synthesis and Quality novel radioactive microspheres which may be used for Control Testing of 32 P labelled Ion Exchange Resin radiation therapy of a mammal. These radioactive mi­ Microspheres for Radiation Therapy of Hepatic Neo­ crospheres comprise a biologically compatible glass plasms”, Int.