AP858A - Process for preparing solid dosage forms of very low-dose drugs. - Google Patents
Process for preparing solid dosage forms of very low-dose drugs. Download PDFInfo
- Publication number
- AP858A AP858A APAP/P/1998/001170A AP9801170A AP858A AP 858 A AP858 A AP 858A AP 9801170 A AP9801170 A AP 9801170A AP 858 A AP858 A AP 858A
- Authority
- AP
- ARIPO
- Prior art keywords
- composition according
- drug
- carrier
- daily dose
- excipient
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 229940127021 low-dose drug Drugs 0.000 title description 7
- 239000007909 solid dosage form Substances 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 56
- 239000003814 drug Substances 0.000 claims abstract description 47
- 239000000203 mixture Substances 0.000 claims abstract description 46
- 229940079593 drug Drugs 0.000 claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 206010012289 Dementia Diseases 0.000 claims abstract description 12
- 238000011321 prophylaxis Methods 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000013583 drug formulation Substances 0.000 claims abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 13
- 239000002245 particle Substances 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 229960001021 lactose monohydrate Drugs 0.000 claims description 7
- 239000007884 disintegrant Substances 0.000 claims description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000314 lubricant Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 230000001419 dependent effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- -1 methoxyimino Chemical group 0.000 claims description 4
- HWPKGOGLCKPRLZ-UHFFFAOYSA-M monosodium citrate Chemical compound [Na+].OC(=O)CC(O)(C([O-])=O)CC(O)=O HWPKGOGLCKPRLZ-UHFFFAOYSA-M 0.000 claims description 4
- 239000002524 monosodium citrate Substances 0.000 claims description 4
- 235000018342 monosodium citrate Nutrition 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 229960004977 anhydrous lactose Drugs 0.000 claims description 3
- 239000008119 colloidal silica Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 229960001855 mannitol Drugs 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 16
- 238000001035 drying Methods 0.000 description 11
- 239000000843 powder Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 5
- 238000005507 spraying Methods 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000007907 direct compression Methods 0.000 description 3
- 229940088679 drug related substance Drugs 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical group CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009477 fluid bed granulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9515624.6A GB9515624D0 (en) | 1995-07-29 | 1995-07-29 | Novel process |
| GBGB9606684.0A GB9606684D0 (en) | 1996-03-29 | 1996-03-29 | Novel process |
| PCT/EP1996/003326 WO1997004750A2 (en) | 1995-07-29 | 1996-07-29 | Process for preparing solid dosage forms of very low-dose drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9801170A0 AP9801170A0 (en) | 1998-01-31 |
| AP858A true AP858A (en) | 2000-07-12 |
Family
ID=26307485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1998/001170A AP858A (en) | 1995-07-29 | 1996-07-29 | Process for preparing solid dosage forms of very low-dose drugs. |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP0841902A2 (cs) |
| JP (1) | JPH11510493A (cs) |
| KR (1) | KR19990035972A (cs) |
| CN (1) | CN1196677A (cs) |
| AP (1) | AP858A (cs) |
| AR (1) | AR004178A1 (cs) |
| AU (1) | AU716961B2 (cs) |
| BG (1) | BG102266A (cs) |
| BR (1) | BR9609804A (cs) |
| CA (1) | CA2228048A1 (cs) |
| CZ (1) | CZ24798A3 (cs) |
| DZ (1) | DZ2077A1 (cs) |
| EA (2) | EA199901055A1 (cs) |
| HU (1) | HUP9900521A3 (cs) |
| IL (1) | IL122897A0 (cs) |
| MA (1) | MA23953A1 (cs) |
| MX (1) | MX9800809A (cs) |
| NO (1) | NO980384L (cs) |
| NZ (1) | NZ315632A (cs) |
| OA (1) | OA10659A (cs) |
| PL (1) | PL325242A1 (cs) |
| SK (1) | SK11098A3 (cs) |
| TR (1) | TR199800156T1 (cs) |
| UY (1) | UY24297A1 (cs) |
| WO (1) | WO1997004750A2 (cs) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9619074D0 (en) * | 1996-09-12 | 1996-10-23 | Smithkline Beecham Plc | Composition |
| JP2002506031A (ja) | 1998-03-11 | 2002-02-26 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 組成物 |
| FR2796840B1 (fr) * | 1999-07-26 | 2003-06-20 | Ethypharm Lab Prod Ethiques | Comprimes faiblement doses et procede de preparation |
| DE60139087D1 (de) | 2000-12-14 | 2009-08-06 | Ortho Mcneil Janssen Pharm | Verfahren zu Herstellung von Zubereitungen enthaltend einen Steroidhormon und ein Stabilisierungsmittel in nicht-kristallinen Form |
| WO2005097076A2 (en) * | 2004-04-09 | 2005-10-20 | Smithkline Beecham Corporation | Low dose pharmaceutical products |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898736A (en) * | 1988-03-09 | 1990-02-06 | Merck & Co., Inc. | Method for tablet preparation |
| EP0392803A1 (en) * | 1989-04-13 | 1990-10-17 | Beecham Group p.l.c. | Novel compounds |
| WO1995017168A1 (en) * | 1993-12-21 | 1995-06-29 | Applied Analytical Industries, Inc. | Method for preparing low dose pharmaceutical products |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4489026A (en) * | 1982-09-07 | 1984-12-18 | The Upjohn Company | Process for preparing solid unit dosage forms of ultra-low dose drugs |
| JPS5970614A (ja) * | 1982-10-14 | 1984-04-21 | Asahi Chem Ind Co Ltd | 微量主薬系湿式固形製剤方法 |
-
1996
- 1996-07-25 AR ARP960103748A patent/AR004178A1/es not_active Application Discontinuation
- 1996-07-26 MA MA24329A patent/MA23953A1/fr unknown
- 1996-07-26 UY UY24297A patent/UY24297A1/es not_active IP Right Cessation
- 1996-07-27 DZ DZ960121A patent/DZ2077A1/fr active
- 1996-07-29 SK SK110-98A patent/SK11098A3/sk unknown
- 1996-07-29 PL PL96325242A patent/PL325242A1/xx unknown
- 1996-07-29 NZ NZ315632A patent/NZ315632A/xx unknown
- 1996-07-29 JP JP9507243A patent/JPH11510493A/ja active Pending
- 1996-07-29 MX MX9800809A patent/MX9800809A/es unknown
- 1996-07-29 CN CN96197054A patent/CN1196677A/zh active Pending
- 1996-07-29 EA EA199901055A patent/EA199901055A1/ru unknown
- 1996-07-29 WO PCT/EP1996/003326 patent/WO1997004750A2/en not_active Ceased
- 1996-07-29 AP APAP/P/1998/001170A patent/AP858A/en active
- 1996-07-29 AU AU67384/96A patent/AU716961B2/en not_active Ceased
- 1996-07-29 BR BR9609804A patent/BR9609804A/pt not_active Application Discontinuation
- 1996-07-29 CA CA002228048A patent/CA2228048A1/en not_active Abandoned
- 1996-07-29 KR KR1019980700633A patent/KR19990035972A/ko not_active Ceased
- 1996-07-29 EA EA199800179A patent/EA000740B1/ru not_active IP Right Cessation
- 1996-07-29 HU HU9900521A patent/HUP9900521A3/hu unknown
- 1996-07-29 TR TR1998/00156T patent/TR199800156T1/xx unknown
- 1996-07-29 IL IL12289796A patent/IL122897A0/xx unknown
- 1996-07-29 CZ CZ98247A patent/CZ24798A3/cs unknown
- 1996-07-29 EP EP96927621A patent/EP0841902A2/en not_active Withdrawn
-
1998
- 1998-01-28 OA OA9800013A patent/OA10659A/en unknown
- 1998-01-28 NO NO980384A patent/NO980384L/no unknown
- 1998-02-20 BG BG102266A patent/BG102266A/xx unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4898736A (en) * | 1988-03-09 | 1990-02-06 | Merck & Co., Inc. | Method for tablet preparation |
| EP0392803A1 (en) * | 1989-04-13 | 1990-10-17 | Beecham Group p.l.c. | Novel compounds |
| WO1995017168A1 (en) * | 1993-12-21 | 1995-06-29 | Applied Analytical Industries, Inc. | Method for preparing low dose pharmaceutical products |
Also Published As
| Publication number | Publication date |
|---|---|
| UY24297A1 (es) | 1997-01-23 |
| PL325242A1 (en) | 1998-07-06 |
| EA000740B1 (ru) | 2000-02-28 |
| CA2228048A1 (en) | 1997-02-13 |
| NO980384L (no) | 1998-03-26 |
| EA199800179A1 (ru) | 1998-10-29 |
| SK11098A3 (en) | 1998-07-08 |
| CZ24798A3 (cs) | 1998-06-17 |
| MA23953A1 (fr) | 1997-04-01 |
| OA10659A (en) | 2002-09-18 |
| WO1997004750A2 (en) | 1997-02-13 |
| MX9800809A (es) | 1998-04-30 |
| AP9801170A0 (en) | 1998-01-31 |
| KR19990035972A (ko) | 1999-05-25 |
| NZ315632A (en) | 1999-11-29 |
| HUP9900521A2 (hu) | 1999-06-28 |
| NO980384D0 (no) | 1998-01-28 |
| EA199901055A1 (ru) | 2000-06-26 |
| EP0841902A2 (en) | 1998-05-20 |
| AU6738496A (en) | 1997-02-26 |
| TR199800156T1 (xx) | 1998-04-21 |
| DZ2077A1 (fr) | 2002-07-22 |
| JPH11510493A (ja) | 1999-09-14 |
| AU716961B2 (en) | 2000-03-09 |
| HUP9900521A3 (en) | 2001-04-28 |
| BR9609804A (pt) | 1999-07-06 |
| IL122897A0 (en) | 1998-08-16 |
| AR004178A1 (es) | 1998-11-04 |
| BG102266A (en) | 1998-10-30 |
| CN1196677A (zh) | 1998-10-21 |
| WO1997004750A3 (en) | 1997-03-27 |
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