MX9303441A - Procedimiento para la preparacion de acido clavulanico. - Google Patents
Procedimiento para la preparacion de acido clavulanico.Info
- Publication number
- MX9303441A MX9303441A MX9303441A MX9303441A MX9303441A MX 9303441 A MX9303441 A MX 9303441A MX 9303441 A MX9303441 A MX 9303441A MX 9303441 A MX9303441 A MX 9303441A MX 9303441 A MX9303441 A MX 9303441A
- Authority
- MX
- Mexico
- Prior art keywords
- clavulanic acid
- preparation
- procedure
- formula
- esters
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60C—VEHICLE TYRES; TYRE INFLATION; TYRE CHANGING; CONNECTING VALVES TO INFLATABLE ELASTIC BODIES IN GENERAL; DEVICES OR ARRANGEMENTS RELATED TO TYRES
- B60C27/00—Non-skid devices temporarily attachable to resilient tyres or resiliently-tyred wheels
- B60C27/006—Non-skid devices temporarily attachable to resilient tyres or resiliently-tyred wheels provided with protective parts, e.g. rubber elements to protect the rim portion
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60C—VEHICLE TYRES; TYRE INFLATION; TYRE CHANGING; CONNECTING VALVES TO INFLATABLE ELASTIC BODIES IN GENERAL; DEVICES OR ARRANGEMENTS RELATED TO TYRES
- B60C27/00—Non-skid devices temporarily attachable to resilient tyres or resiliently-tyred wheels
- B60C27/06—Non-skid devices temporarily attachable to resilient tyres or resiliently-tyred wheels extending over the complete circumference of the tread, e.g. made of chains or cables
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Mechanical Engineering (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Se describe un procedimiento para al preparación de ácido clavulánico o sus sales y ésteres farmacéuticamente aceptables, en el cual se usa una amina de la fórmula (II): (Ver Fórmula II); como un intermediario para formar una sal con ácido clavulánico, R1, R2 y R3 se seleccionan de varios átomos y grupos sustituyentes.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB929212379A GB9212379D0 (en) | 1992-06-11 | 1992-06-11 | Novel process |
GB929222841A GB9222841D0 (en) | 1992-10-31 | 1992-10-31 | Novel process |
GB929226061A GB9226061D0 (en) | 1992-12-14 | 1992-12-14 | Novel process |
GB929226282A GB9226282D0 (en) | 1992-12-17 | 1992-12-17 | Novel process |
Publications (1)
Publication Number | Publication Date |
---|---|
MX9303441A true MX9303441A (es) | 1994-03-31 |
Family
ID=27450891
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX9303441A MX9303441A (es) | 1992-06-11 | 1993-06-09 | Procedimiento para la preparacion de acido clavulanico. |
Country Status (35)
Country | Link |
---|---|
EP (7) | EP0747383A3 (es) |
JP (3) | JPH07507324A (es) |
KR (1) | KR0162264B1 (es) |
CN (3) | CN1037967C (es) |
AP (3) | AP473A (es) |
AT (3) | ATE157981T1 (es) |
AU (3) | AU4342793A (es) |
BG (3) | BG61306B1 (es) |
CA (2) | CA2160768A1 (es) |
CS (1) | CS202194A3 (es) |
CY (1) | CY1895A (es) |
CZ (5) | CZ267694A3 (es) |
DE (6) | DE69313869T2 (es) |
DK (5) | DK0672670T3 (es) |
ES (3) | ES2080710T3 (es) |
FI (7) | FI944031A (es) |
GB (2) | GB2287026B (es) |
GR (4) | GR950300070T1 (es) |
HK (4) | HK6996A (es) |
HU (3) | HUT69374A (es) |
IL (1) | IL105966A (es) |
LU (1) | LU88567A1 (es) |
MA (1) | MA22907A1 (es) |
MX (1) | MX9303441A (es) |
MY (1) | MY131501A (es) |
NL (1) | NL9320037A (es) |
NO (3) | NO943093L (es) |
PT (2) | PT101711A (es) |
RO (3) | RO111193B1 (es) |
RU (1) | RU2081121C1 (es) |
SE (5) | SE9404290L (es) |
SI (1) | SI9300296B (es) |
SK (3) | SK278520B6 (es) |
UY (1) | UY24154A1 (es) |
WO (1) | WO1993025557A1 (es) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT400033B (de) | 1992-03-10 | 1995-09-25 | Biochemie Gmbh | Neues verfahren zur isolierung und reinigung von clavulansäure und zur herstellung von pharmakologisch verträglichen salzen derselben |
AT399155B (de) * | 1992-03-26 | 1995-03-27 | Lek Tovarna Farmacevtskih | Neue alkylendiammonium-diclavulanat-derivate, verfahren zu deren herstellung sowie deren verwendung |
SI9300296B (sl) | 1992-06-11 | 1998-06-30 | Smithkline Beecham P.L.C. | Postopek in intermedianti za pripravo klavulanske kisline |
KR100200239B1 (ko) * | 1992-10-21 | 1999-06-15 | 김충환 | 클라불란산 칼륨염의 제조방법 |
US5821364A (en) * | 1993-03-26 | 1998-10-13 | Gist-Brocades N.V. | Diamine salts of clavulanic acid |
US5741903A (en) * | 1993-03-26 | 1998-04-21 | Gist-Brocades N.V. | Diamine salts for purification of clavulanic acid |
DE647229T1 (de) * | 1993-03-26 | 1996-01-18 | Gist Brocades Nv | Diaminsalze von clavulansäure. |
US5760218A (en) * | 1993-03-26 | 1998-06-02 | Gist-Brocades N.V. | Diamine salts of clavulanic acid |
ES2155839T3 (es) | 1993-11-17 | 2001-06-01 | Biochemie Gmbh | Separacion de isomeros de cefalosporina. |
SI9400107A (en) * | 1994-03-02 | 1995-10-31 | Lek Tovarna Farmacevtskih | New process of the isolation of clavulanic acid and its pharmaceutical salts from fermented broth of streptomyces sp.p 6621 ferm p 2804. |
GB9426261D0 (en) * | 1994-12-24 | 1995-02-22 | Spurcourt Ltd | Clavulanic acid salts |
CA2213563A1 (en) * | 1995-02-25 | 1996-09-06 | Spurcourt Limited | Clavulanic acid salts |
SI9500134B (sl) * | 1995-04-20 | 2004-04-30 | Lek, | Postopek za pripravo čistih alkalijskih soli klavulanske kisline |
GB9515809D0 (en) * | 1995-08-02 | 1995-10-04 | Smithkline Beecham Plc | Process |
SI9500265A1 (en) | 1995-08-28 | 1997-02-28 | Lek Tovarna Farmacevtskih | Process for purification of the aqueous fermented broth filtrate of streptomyces sp. p 6621 ferm p 2804 by ultrafiltration |
AT403375B (de) * | 1995-11-15 | 1998-01-26 | Biochemie Gmbh | Verfahren zur fällung von alkalisalzen der clavulansäure |
ZA975198B (en) | 1996-06-13 | 1997-12-15 | Smithkline Beecham Corp | Improved process for preparing potassium clavulanate. |
PL333247A1 (en) * | 1996-11-11 | 1999-11-22 | Gist Brocades Bv | Method of manufacturing of salts and esters of clavulan acid |
AT404728B (de) * | 1996-11-27 | 1999-02-25 | Biochemie Gmbh | Verfahren zur herstellung von clavulansäure-aminsalzen |
DZ2456A1 (fr) * | 1997-04-04 | 2003-01-18 | Smithkline Beecham Plc | Procédé de préparation de sels de l'acide clavulanique. |
AU5411099A (en) * | 1998-07-16 | 2000-02-07 | Dsm N.V. | Improved process for the preparation of salts and esters of clavulanic acid |
US6440708B1 (en) | 1998-09-29 | 2002-08-27 | Dsm N.V. | Fermentation of clavulanic acid at a controlled level of ammonia |
DE19917428A1 (de) * | 1999-04-19 | 2000-10-26 | Clariant Gmbh | Flammwidrige phosphormodifizierte Epoxidharze |
GB0003305D0 (en) | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
HU228593B1 (en) | 2000-05-13 | 2013-04-29 | Smithkline Beecham Plc | Process for the purification of a salt of clavulanic acid |
ITMI20011764A1 (it) | 2001-08-10 | 2003-02-10 | Dinamite Dipharma Spa | Metodo per l'ottenimento del pemirolast ad elevata purezza |
GB201010439D0 (en) * | 2010-06-21 | 2010-08-04 | Arch Timber Protection Ltd | A method |
CN103304583B (zh) * | 2013-07-09 | 2016-01-20 | 山东新时代药业有限公司 | 一种从克拉维酸胺盐结晶母液中回收克拉维酸的方法 |
CN105384758B (zh) * | 2015-12-01 | 2018-05-01 | 国药集团威奇达药业有限公司 | 克拉维酸胺盐的制备方法 |
JP6835211B2 (ja) | 2017-04-19 | 2021-02-24 | 日本軽金属株式会社 | Al−Si−Fe系アルミニウム合金鋳造材及びその製造方法 |
CN109305978A (zh) * | 2017-07-26 | 2019-02-05 | 山东睿鹰先锋制药有限公司 | 一种制备克拉维酸盐的新方法 |
CN116283498A (zh) * | 2023-03-07 | 2023-06-23 | 国药集团威奇达药业有限公司 | 从克拉维酸钾生产废液中回收有机溶剂的方法 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1508977A (en) * | 1974-04-20 | 1978-04-26 | Beecham Group Ltd | Beta-lactam antibiotic from streptomyces clavuligerus |
GB1507978A (en) | 1974-03-28 | 1978-04-19 | Dunlop Ltd | Pneumatic tyre and wheel rim assemblies |
GB1543563A (en) | 1975-02-07 | 1979-04-04 | Glaxo Lab Ltd | Beta-lactam antibiotic in purified form |
GB1508978A (en) | 1975-04-11 | 1978-04-26 | Beecham Group Ltd | Esters of clavulanic acid |
GB1578739A (en) * | 1976-07-23 | 1980-11-05 | Beecham Group Ltd | Amine salts of clavulanic acid methods for their preparation and compositions containing them |
DE2861607D1 (en) * | 1977-11-26 | 1982-03-11 | Beecham Group Plc | Derivatives of clavulanic acid and pharmaceutical compositions containing them |
BE862211A (fr) | 1977-12-22 | 1978-06-22 | Beecham Group Ltd | Agents antibacteriens |
JPS5562993A (en) | 1978-11-07 | 1980-05-12 | Idemitsu Petrochem Co Ltd | Operation of olefin manufacturing equipment |
JPS55162993A (en) | 1979-06-07 | 1980-12-18 | Sanraku Inc | Preparation of culavulanic acid |
EP0026044B1 (en) | 1979-08-24 | 1983-06-08 | Beecham Group Plc | Amine salt of clavulanic acid, its preparation and use |
MX7417E (es) * | 1984-10-27 | 1988-10-14 | Antibioticos Sa | Metodo para la preparacion de acido clavulanico y sus derivados |
ES2010143A6 (es) * | 1989-03-01 | 1989-10-16 | Pharma Mar S A Pharmar | Un nuevo procedimiento de obtencion del acido z(2r,5r)-3-(2-hiadroxietiliden)-7- oxo-4-oxa-1-azabiciclo(3,2,0) -heptano-2-carboxilico y de sales estares farmaceutiacamente aceptables del mismo,a partir de caldos de fermentacion de streptomyces, sp. |
FR2644543A1 (es) | 1989-03-17 | 1990-09-21 | Renault | |
PT94908B (pt) | 1990-08-03 | 1998-05-29 | Portela & Ca Lda | Processo para a preparacao de derivados carboxilicos beta-lactamicos altamente purificados estaveis e hipoalergenicos |
AT400033B (de) * | 1992-03-10 | 1995-09-25 | Biochemie Gmbh | Neues verfahren zur isolierung und reinigung von clavulansäure und zur herstellung von pharmakologisch verträglichen salzen derselben |
AT399155B (de) * | 1992-03-26 | 1995-03-27 | Lek Tovarna Farmacevtskih | Neue alkylendiammonium-diclavulanat-derivate, verfahren zu deren herstellung sowie deren verwendung |
SI9300296B (sl) * | 1992-06-11 | 1998-06-30 | Smithkline Beecham P.L.C. | Postopek in intermedianti za pripravo klavulanske kisline |
KR100200239B1 (ko) * | 1992-10-21 | 1999-06-15 | 김충환 | 클라불란산 칼륨염의 제조방법 |
GB9305565D0 (en) * | 1993-03-18 | 1993-05-05 | Smithkline Beecham Plc | Novel compounds and processes |
DE647229T1 (de) * | 1993-03-26 | 1996-01-18 | Gist Brocades Nv | Diaminsalze von clavulansäure. |
EP0887178A1 (de) | 1997-06-27 | 1998-12-30 | Pamag Ag | Verfahren zum Bündeln von Seitenfaltbeuteln und Vorrichtung zur Durchführung des Verfahrens |
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1993
- 1993-06-03 SI SI9300296A patent/SI9300296B/sl unknown
- 1993-06-07 CZ CZ942676A patent/CZ267694A3/cs unknown
- 1993-06-07 WO PCT/GB1993/001206 patent/WO1993025557A1/en not_active Application Discontinuation
- 1993-06-07 EP EP96202593A patent/EP0747383A3/en not_active Withdrawn
- 1993-06-07 GB GB9508497A patent/GB2287026B/en not_active Expired - Fee Related
- 1993-06-07 DE DE69313869T patent/DE69313869T2/de not_active Expired - Fee Related
- 1993-06-07 HU HU9402405A patent/HUT69374A/hu unknown
- 1993-06-07 SK SK1532-94A patent/SK278520B6/sk unknown
- 1993-06-07 DK DK95201085.8T patent/DK0672670T3/da active
- 1993-06-07 JP JP6501253A patent/JPH07507324A/ja active Pending
- 1993-06-07 ES ES95201085T patent/ES2080710T3/es not_active Expired - Lifetime
- 1993-06-07 DE DE4345311A patent/DE4345311C1/de not_active Expired - Lifetime
- 1993-06-07 DE DE69306574T patent/DE69306574T2/de not_active Expired - Fee Related
- 1993-06-07 AU AU43427/93A patent/AU4342793A/en not_active Abandoned
- 1993-06-07 SK SK1533-94A patent/SK278367B6/sk unknown
- 1993-06-07 PT PT101711A patent/PT101711A/pt not_active Application Discontinuation
- 1993-06-07 DK DK95201084.1T patent/DK0672669T3/da active
- 1993-06-07 CA CA002160768A patent/CA2160768A1/en not_active Abandoned
- 1993-06-07 DE DE69301571T patent/DE69301571T2/de not_active Expired - Fee Related
- 1993-06-07 ES ES95201084T patent/ES2106615T3/es not_active Expired - Lifetime
- 1993-06-07 KR KR1019940703225A patent/KR0162264B1/ko not_active IP Right Cessation
- 1993-06-07 RO RO95-00880A patent/RO111193B1/ro unknown
- 1993-06-07 DE DE4392664T patent/DE4392664T1/de not_active Withdrawn
- 1993-06-07 EP EP95201085A patent/EP0672670B1/en not_active Revoked
- 1993-06-07 RO RO95-00659A patent/RO111192B1/ro unknown
- 1993-06-07 EP EP97201652A patent/EP0801069A1/en not_active Withdrawn
- 1993-06-07 CS CZ942021A patent/CS202194A3/cs unknown
- 1993-06-07 PT PT101710A patent/PT101710A/pt not_active IP Right Cessation
- 1993-06-07 AT AT95201084T patent/ATE157981T1/de not_active IP Right Cessation
- 1993-06-07 RU RU9595112522A patent/RU2081121C1/ru active
- 1993-06-07 AT AT93913311T patent/ATE146180T1/de not_active IP Right Cessation
- 1993-06-07 ES ES93913311T patent/ES2095059T3/es not_active Expired - Lifetime
- 1993-06-07 EP EP95117448A patent/EP0699682A1/en not_active Withdrawn
- 1993-06-07 DK DK93913311.2T patent/DK0644887T3/da active
- 1993-06-07 EP EP95201084A patent/EP0672669B1/en not_active Expired - Lifetime
- 1993-06-07 AT AT95201085T patent/ATE134192T1/de not_active IP Right Cessation
- 1993-06-07 HU HU9501214A patent/HU9501214D0/hu not_active Application Discontinuation
- 1993-06-07 CZ CZ942675A patent/CZ267594A3/cs unknown
- 1993-06-07 NL NL9320037A patent/NL9320037A/nl not_active Application Discontinuation
- 1993-06-07 CZ CZ96193A patent/CZ19396A3/cs unknown
- 1993-06-07 CZ CZ951254A patent/CZ125495A3/cs not_active IP Right Cessation
- 1993-06-07 EP EP93913311A patent/EP0644887B1/en not_active Expired - Lifetime
- 1993-06-07 DE DE4345286A patent/DE4345286A1/de not_active Ceased
- 1993-06-07 EP EP97201887A patent/EP0806426A1/en not_active Withdrawn
- 1993-06-07 CA CA002117538A patent/CA2117538A1/en not_active Abandoned
- 1993-06-07 RO RO94-01806A patent/RO111191B1/ro unknown
- 1993-06-07 SK SK994-94A patent/SK278561B6/sk unknown
- 1993-06-07 HU HU9500610A patent/HU212583B/hu not_active IP Right Cessation
- 1993-06-07 CZ CZ95544A patent/CZ54495A3/cs unknown
- 1993-06-07 GB GB9508496A patent/GB2287025B/en not_active Expired - Fee Related
- 1993-06-08 MY MYPI93001142A patent/MY131501A/en unknown
- 1993-06-09 MX MX9303441A patent/MX9303441A/es not_active IP Right Cessation
- 1993-06-09 MA MA23206A patent/MA22907A1/fr unknown
- 1993-06-09 IL IL105966A patent/IL105966A/xx not_active IP Right Cessation
- 1993-06-10 AP APAP/P/1995/000737A patent/AP473A/en active
- 1993-06-10 AP APAP/P/1995/000738A patent/AP474A/en active
- 1993-06-10 CN CN93106612A patent/CN1037967C/zh not_active Expired - Fee Related
- 1993-06-10 AP APAP/P/1993/000537A patent/AP471A/en active
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1994
- 1994-08-22 NO NO943093A patent/NO943093L/no unknown
- 1994-09-02 FI FI944031A patent/FI944031A/fi not_active Application Discontinuation
- 1994-10-20 BG BG99639/95A patent/BG61306B1/bg unknown
- 1994-10-20 BG BG99131A patent/BG60999B1/bg unknown
- 1994-12-07 LU LU88567A patent/LU88567A1/fr unknown
- 1994-12-08 DK DK140694A patent/DK140694A/da not_active Application Discontinuation
- 1994-12-09 SE SE9404290A patent/SE9404290L/xx not_active Application Discontinuation
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1995
- 1995-02-27 NO NO950758A patent/NO950758D0/no unknown
- 1995-02-27 SE SE9500718A patent/SE9500718D0/xx not_active Application Discontinuation
- 1995-03-09 AU AU14737/95A patent/AU680099B2/en not_active Ceased
- 1995-03-24 FI FI951414A patent/FI103973B/fi active
- 1995-03-31 JP JP7075492A patent/JPH08134072A/ja active Pending
- 1995-04-26 SE SE9501544A patent/SE503077C2/sv not_active IP Right Cessation
- 1995-04-28 CN CN95104832A patent/CN1041934C/zh not_active Expired - Fee Related
- 1995-05-03 NO NO951725A patent/NO178499C/no not_active IP Right Cessation
- 1995-05-15 CN CN95104675A patent/CN1036592C/zh not_active Expired - Fee Related
- 1995-05-16 BG BG99640A patent/BG61190B1/bg unknown
- 1995-05-19 JP JP7121206A patent/JPH08157480A/ja active Pending
- 1995-06-08 FI FI952820A patent/FI96952C/fi active
- 1995-06-15 DK DK068595A patent/DK170569B1/da not_active IP Right Cessation
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1996
- 1996-01-11 HK HK6996A patent/HK6996A/xx not_active IP Right Cessation
- 1996-01-30 UY UY24154A patent/UY24154A1/es unknown
- 1996-01-31 GR GR950300070T patent/GR950300070T1/el unknown
- 1996-02-15 GR GR960400402T patent/GR3019006T3/el unknown
- 1996-02-29 SE SE9600797A patent/SE504220C2/sv not_active IP Right Cessation
- 1996-04-22 FI FI961739A patent/FI104488B/fi active
- 1996-09-27 CY CY189596A patent/CY1895A/xx unknown
- 1996-12-12 GR GR960403146T patent/GR3022006T3/el unknown
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1997
- 1997-02-14 AU AU14716/97A patent/AU681569B3/en not_active Revoked
- 1997-09-09 GR GR970402308T patent/GR3024666T3/el unknown
- 1997-11-19 SE SE9704244A patent/SE9704244D0/xx unknown
-
1998
- 1998-03-10 HK HK98101974A patent/HK1003245A1/xx not_active IP Right Cessation
- 1998-03-10 HK HK98101976A patent/HK1003222A1/xx not_active IP Right Cessation
- 1998-03-20 FI FI980630A patent/FI980630A/fi not_active Application Discontinuation
- 1998-03-20 FI FI980631A patent/FI980631A0/fi not_active Application Discontinuation
- 1998-06-24 HK HK98106523A patent/HK1007311A1/xx not_active IP Right Cessation
- 1998-12-23 FI FI982790A patent/FI982790A0/fi unknown
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