DE60011045T2 - Biolgisch abbaubare glaszusammensetzungen und deren verwendung zur herstellung eines medikaments für strahlungstherapie - Google Patents
Biolgisch abbaubare glaszusammensetzungen und deren verwendung zur herstellung eines medikaments für strahlungstherapie Download PDFInfo
- Publication number
- DE60011045T2 DE60011045T2 DE60011045T DE60011045T DE60011045T2 DE 60011045 T2 DE60011045 T2 DE 60011045T2 DE 60011045 T DE60011045 T DE 60011045T DE 60011045 T DE60011045 T DE 60011045T DE 60011045 T2 DE60011045 T2 DE 60011045T2
- Authority
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- Germany
- Prior art keywords
- mol
- glass
- rare earth
- radioisotope
- radioactive
- 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
Links
- 239000011521 glass Substances 0.000 title claims abstract description 377
- 239000000203 mixture Substances 0.000 title claims abstract description 50
- 238000001959 radiotherapy Methods 0.000 title claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 239000003814 drug Substances 0.000 title claims description 4
- 239000000463 material Substances 0.000 claims abstract description 100
- 230000002285 radioactive effect Effects 0.000 claims abstract description 54
- 239000005374 lithium borate glass Substances 0.000 claims abstract description 49
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 210000001124 body fluid Anatomy 0.000 claims abstract description 13
- 239000010839 body fluid Substances 0.000 claims abstract description 13
- 230000000717 retained effect Effects 0.000 claims abstract description 11
- 241000124008 Mammalia Species 0.000 claims abstract description 5
- 239000004005 microsphere Substances 0.000 claims description 126
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 60
- 150000002910 rare earth metals Chemical class 0.000 claims description 45
- 230000005855 radiation Effects 0.000 claims description 39
- 229910018072 Al 2 O 3 Inorganic materials 0.000 claims description 37
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 23
- 229910018068 Li 2 O Inorganic materials 0.000 claims description 22
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 18
- 229910052796 boron Inorganic materials 0.000 claims description 18
- KJZYNXUDTRRSPN-OUBTZVSYSA-N holmium-166 Chemical compound [166Ho] KJZYNXUDTRRSPN-OUBTZVSYSA-N 0.000 claims description 14
- 230000002917 arthritic effect Effects 0.000 claims description 13
- KBQHZAAAGSGFKK-NJFSPNSNSA-N dysprosium-165 Chemical compound [165Dy] KBQHZAAAGSGFKK-NJFSPNSNSA-N 0.000 claims description 13
- -1 rare earth phosphate Chemical class 0.000 claims description 13
- KZUNJOHGWZRPMI-AKLPVKDBSA-N samarium-153 Chemical compound [153Sm] KZUNJOHGWZRPMI-AKLPVKDBSA-N 0.000 claims description 10
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 claims description 8
- WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 claims description 7
- 229910001404 rare earth metal oxide Inorganic materials 0.000 claims description 7
- WUAPFZMCVAUBPE-IGMARMGPSA-N rhenium-186 Chemical compound [186Re] WUAPFZMCVAUBPE-IGMARMGPSA-N 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- WHXSMMKQMYFTQS-BJUDXGSMSA-N (6Li)Lithium Chemical compound [6Li] WHXSMMKQMYFTQS-BJUDXGSMSA-N 0.000 claims description 6
- ZOXJGFHDIHLPTG-BJUDXGSMSA-N Boron-10 Chemical compound [10B] ZOXJGFHDIHLPTG-BJUDXGSMSA-N 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- RIUWBIIVUYSTCN-UHFFFAOYSA-N trilithium borate Chemical group [Li+].[Li+].[Li+].[O-]B([O-])[O-] RIUWBIIVUYSTCN-UHFFFAOYSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 47
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- 238000004090 dissolution Methods 0.000 description 17
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 description 17
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- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
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- 210000000629 knee joint Anatomy 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 8
- 229910052782 aluminium Inorganic materials 0.000 description 8
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
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- 229910001220 stainless steel Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
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- 239000011777 magnesium Substances 0.000 description 4
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- 229910052749 magnesium Inorganic materials 0.000 description 3
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- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 229910052772 Samarium Inorganic materials 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 238000000026 X-ray photoelectron spectrum Methods 0.000 description 2
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
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- 229910052738 indium Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- WHXSMMKQMYFTQS-IGMARMGPSA-N lithium-7 atom Chemical compound [7Li] WHXSMMKQMYFTQS-IGMARMGPSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
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- 238000003801 milling Methods 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
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- 230000036961 partial effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000003439 radiotherapeutic effect Effects 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 239000005361 soda-lime glass Substances 0.000 description 2
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- 229910052722 tritium Inorganic materials 0.000 description 2
- 238000010865 video microscopy Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 101001094044 Mus musculus Solute carrier family 26 member 6 Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004111 Potassium silicate Substances 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
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- PGTAKMRAYVRICI-UHFFFAOYSA-N aluminum lithium borate Chemical compound B([O-])([O-])[O-].[Al+3].[Li+] PGTAKMRAYVRICI-UHFFFAOYSA-N 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- HSBONFIDJMNFJD-UHFFFAOYSA-N aluminum potassium borate Chemical compound B([O-])([O-])[O-].[K+].[Al+3] HSBONFIDJMNFJD-UHFFFAOYSA-N 0.000 description 1
- SXQXMCWCWVCFPC-UHFFFAOYSA-N aluminum;potassium;dioxido(oxo)silane Chemical compound [Al+3].[K+].[O-][Si]([O-])=O.[O-][Si]([O-])=O SXQXMCWCWVCFPC-UHFFFAOYSA-N 0.000 description 1
- 239000005347 annealed glass Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
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- 210000000988 bone and bone Anatomy 0.000 description 1
- ZOXJGFHDIHLPTG-IGMARMGPSA-N boron-11 atom Chemical compound [11B] ZOXJGFHDIHLPTG-IGMARMGPSA-N 0.000 description 1
- 239000002419 bulk glass Substances 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
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- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- UYAHIZSMUZPPFV-NJFSPNSNSA-N erbium-169 Chemical compound [169Er] UYAHIZSMUZPPFV-NJFSPNSNSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001145 finger joint Anatomy 0.000 description 1
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- 239000000156 glass melt Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
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- 210000005067 joint tissue Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- PAZHGORSDKKUPI-UHFFFAOYSA-N lithium metasilicate Chemical compound [Li+].[Li+].[O-][Si]([O-])=O PAZHGORSDKKUPI-UHFFFAOYSA-N 0.000 description 1
- 229910052912 lithium silicate Inorganic materials 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000289 melt material Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
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- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NNHHDJVEYQHLHG-UHFFFAOYSA-N potassium silicate Chemical compound [K+].[K+].[O-][Si]([O-])=O NNHHDJVEYQHLHG-UHFFFAOYSA-N 0.000 description 1
- 229910052913 potassium silicate Inorganic materials 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- KZUNJOHGWZRPMI-NJFSPNSNSA-N samarium-152 Chemical compound [152Sm] KZUNJOHGWZRPMI-NJFSPNSNSA-N 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000005368 silicate glass Substances 0.000 description 1
- 239000003238 silicate melt Substances 0.000 description 1
- 239000012890 simulated body fluid Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000005211 surface analysis Methods 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C3/00—Glass compositions
- C03C3/12—Silica-free oxide glass compositions
- C03C3/14—Silica-free oxide glass compositions containing boron
- C03C3/15—Silica-free oxide glass compositions containing boron containing rare earths
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/009—Neutron capture therapy, e.g. using uranium or non-boron material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C3/00—Glass compositions
- C03C3/04—Glass compositions containing silica
- C03C3/062—Glass compositions containing silica with less than 40% silica by weight
- C03C3/064—Glass compositions containing silica with less than 40% silica by weight containing boron
- C03C3/068—Glass compositions containing silica with less than 40% silica by weight containing boron containing rare earths
-
- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C2213/00—Glass fibres or filaments
- C03C2213/02—Biodegradable glass fibres
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Geochemistry & Mineralogy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Glass Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24189299A | 1999-02-01 | 1999-02-01 | |
| US241892 | 1999-02-01 | ||
| PCT/US2000/002388 WO2000044682A1 (en) | 1999-02-01 | 2000-01-31 | Biodegradable glass compositions and methods for radiation therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60011045D1 DE60011045D1 (de) | 2004-07-01 |
| DE60011045T2 true DE60011045T2 (de) | 2005-05-25 |
Family
ID=22912591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60011045T Expired - Lifetime DE60011045T2 (de) | 1999-02-01 | 2000-01-31 | Biolgisch abbaubare glaszusammensetzungen und deren verwendung zur herstellung eines medikaments für strahlungstherapie |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6379648B1 (https=) |
| EP (1) | EP1149057B1 (https=) |
| JP (1) | JP4397531B2 (https=) |
| AT (1) | ATE267775T1 (https=) |
| AU (1) | AU758560B2 (https=) |
| CA (1) | CA2361573C (https=) |
| DE (1) | DE60011045T2 (https=) |
| ES (1) | ES2222892T3 (https=) |
| WO (1) | WO2000044682A1 (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6616591B1 (en) * | 1999-12-08 | 2003-09-09 | Scimed Life Systems, Inc. | Radioactive compositions and methods of use thereof |
| AUPR098300A0 (en) * | 2000-10-25 | 2000-11-16 | Sirtex Medical Limited | Polymer based radionuclide containing microspheres |
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| US3972721A (en) * | 1974-03-01 | 1976-08-03 | Ppg Industries, Inc. | Thermally stable and crush resistant microporous glass catalyst supports and methods of making |
| US5011797A (en) | 1988-01-29 | 1991-04-30 | The Curators Of The University Of Missouri | Composition and method for radiation synovectomy of arthritic joints |
| US5039326A (en) | 1988-01-29 | 1991-08-13 | The Curators Of The University Of Missouri | Composition and method for radiation synovectomy of arthritic joints |
| US4889707A (en) | 1988-01-29 | 1989-12-26 | The Curators Of The University Of Missouri | Composition and method for radiation synovectomy of arthritic joints |
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1999
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2000
- 2000-01-31 DE DE60011045T patent/DE60011045T2/de not_active Expired - Lifetime
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- 2000-01-31 AU AU28647/00A patent/AU758560B2/en not_active Expired
- 2000-01-31 WO PCT/US2000/002388 patent/WO2000044682A1/en not_active Ceased
- 2000-01-31 JP JP2000595944A patent/JP4397531B2/ja not_active Expired - Lifetime
- 2000-01-31 CA CA2361573A patent/CA2361573C/en not_active Expired - Lifetime
- 2000-01-31 EP EP00907088A patent/EP1149057B1/en not_active Expired - Lifetime
- 2000-01-31 ES ES00907088T patent/ES2222892T3/es not_active Expired - Lifetime
Also Published As
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| DE60011045D1 (de) | 2004-07-01 |
| ES2222892T3 (es) | 2005-02-16 |
| JP2002535237A (ja) | 2002-10-22 |
| US6379648B1 (en) | 2002-04-30 |
| WO2000044682A9 (en) | 2001-08-30 |
| EP1149057B1 (en) | 2004-05-26 |
| ATE267775T1 (de) | 2004-06-15 |
| AU2864700A (en) | 2000-08-18 |
| AU758560B2 (en) | 2003-03-27 |
| EP1149057A1 (en) | 2001-10-31 |
| CA2361573C (en) | 2010-05-25 |
| JP4397531B2 (ja) | 2010-01-13 |
| CA2361573A1 (en) | 2000-08-03 |
| WO2000044682A1 (en) | 2000-08-03 |
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