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ME00189B - Preparati sa neprekidnim oslobađanjem - Google Patents

Preparati sa neprekidnim oslobađanjem

Info

Publication number
ME00189B
ME00189B MEP-2008-300A MEP2008300A ME00189B ME 00189 B ME00189 B ME 00189B ME P2008300 A MEP2008300 A ME P2008300A ME 00189 B ME00189 B ME 00189B
Authority
ME
Montenegro
Prior art keywords
sustained
tacrolimus
release preparation
preparation according
hydrate
Prior art date
Application number
MEP-2008-300A
Other languages
English (en)
Inventor
Kazunari Yamashita
Eiji Hashimoto
Yukihiro Nomura
Fumio Shimojo
Shigeki Tamura
Takeo Chayamachi 525 HIROSE
Satoshi Ueda
Takashi Saitoh
Rinta Ibuki
Toshio Ideno
Original Assignee
Astellas Pharma Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26420115&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME00189(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Astellas Pharma Inc filed Critical Astellas Pharma Inc
Publication of ME00189B publication Critical patent/ME00189B/me

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/453Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1617Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1617Organic compounds, e.g. phospholipids, fats
    • A61K9/1623Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1635Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1641Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1641Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647Polyesters, e.g. poly(lactide-co-glycolide)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1652Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4858Organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyrane Compounds (AREA)

Abstract

    Predmetni pronalazak se odnosi na preparat sa produženim otpuštanjem koji sadrži takrolimus ili njegov hidrat gde je vreme (T63,2%) koje je potrebno da se rastvori 63,2% od maksimalne količine takrolimusa ili njegovog hidrata od 0,7 do 15 časova, mereno pomoću Japanese Pharmacopeia, 13. izdanje, Test rastvaranja, br. 2 (Puddle metod, 50 rpm), uz korišćenje, kao test rastvora, 0,005% rastvora hidroksipropil celuloze podešenog na pH 4,5, kao i na upotrebu preparata za dobijanje medikamenata. Predmetni pronalazak se odnosi na  preparat sa prod u ž enim otp u š tanjem koji sad r ž i takrolimus ili njegov hidrat  gde  je vreme (T63,2%) koje je potrebno da se rastvori 63,2% od maksimalne kol i č ine takrolimusa ili njegovog hidrata od 0,7 do 15   č asova, mereno pom o ć u Japanese Pharmacopeia, 13. izdanje, Test rastvaranja, br. 2  (Puddle metod , 50 rpm), uz kor i š ć enje, kao test rastvora, 0,005% rastvora hidroksipropil celuloze pod e š enog na pH 4,5, kao i na upotrebu preparata za dobijanje medikamenata.    

Claims (12)

1. Preparat sa produženim otpuštanjem koji sadrži takrolimus ili njegov hidrat, naznačen time što je vreme (T63,2%) koje je potrebno da se rastvori 63,2% od maksimalne količine takrolimusa ili njegovog hidrata od 0,7 do 15 časova, uz korišćenje, kao test rastvora, 0,005% rastvora hidroksipropil celuloze podešenog na pH 4,5.
2. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što sadrži preparat čvrste disperzije, u kome je takrolimus ili njegov hidrat prisutan u amorfnom stanju u čvrstoj osnovi.
3. Preparat sa produženim otpuštanjem prema zahtevu 2, naznačen time što se preparat čvrste disperzije odlikuje time što (1) sadrži laktozu ili kalcijum hidrogen fosfat kao ekscipijent ili lubrikant; (2) ne sadrži dezintegrator; i (3) veličina čestica u navedenom preparatu čvrste disperzije je jednaka ili manja od 350 �m.
4. Preparat sa produženim otpuštanjem prema zahtevu 2, naznačen time što je čvrsta osnova izabrana iz grupe koja se sastoji od polimera rastvorenog u vodi i voska.
5. Preparat sa produženim otpuštanjem prema zahtevu 2, naznačen time što je čvrsta osnova izabrana iz grupe koja se sastoji od 1) hidroskipropilmetilceluloze, u masenom odnosu prema takrolimusu od 0,2 do 0,4 prema 1, i 2) glicerin monostearata, poliglicerinskog estra masne kiseline ili saharoznog estra masne kiseline, u masenom odnosu prema takrolimusu od 0,2 do 20 prema 1.
6. Preparat sa produženim otpuštanjem prema zahtevu 2, naznačen time što se preparat čvrste disperzije odlikuje time što (1) je takrolimus ili njegov hidrat prisutan u amorfnom stanju u hidrokispropilmetilcelulozi u masenom odnosu prema takrolimusu od 0,2 do 0,4 prema 1, (2) sadrži laktozu kao ekscipijent, (3) ne sadrži dezintegratore, i (4) veličina čestica u navedenom preparatu čvrste disperzije je jednaka ili manja od 250 �m.
7. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što je takrolimus ili njegov hidrat prisutan u obliku finog praha koji se odlikuje raspodelom prečnika čestica u opsegu od 0,1 do 50 �m i/ili srednjim prečnikom čestice u opsegu od 0,2 do 20 �m.
8. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što je vreme (T63,2%) od 1,0 do 12 časova.
9. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što je vreme (T63,2%) od 1,3 do 8,2 časova.
10. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što je vreme (T63,2%) od 2 do 5 časova.
11. Preparat sa produženim otpuštanjem prema zahtevu 1, naznačen time što je u obliku praha, finog praha, granula, tableta ili kapsula.
12. Postupak upotrebe preparata sa produženim otpuštanjem koji sadrži takrolimus ili njegov hidrat za proizvodnju medikamenata za postupak lečenja ili prevencije odbacivanja organa ili tkiva usled transplantacije ili autoimunih bolesti bez rizika od neželjenog dejstva izazvanog prolazno previsokom koncentracijom takrolimusa.
MEP-2008-300A 1998-03-26 1999-03-25 Preparati sa neprekidnim oslobađanjem ME00189B (me)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP7903998 1998-03-26
JP18296398 1998-06-29
PCT/JP1999/001499 WO1999049863A1 (en) 1998-03-26 1999-03-25 Sustained release preparations

Publications (1)

Publication Number Publication Date
ME00189B true ME00189B (me) 2011-02-10

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MEP-2008-300A ME00189B (me) 1998-03-26 1999-03-25 Preparati sa neprekidnim oslobađanjem
MEP-300/08A MEP30008A (en) 1998-03-26 1999-03-25 Sustained release preparations

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MEP-300/08A MEP30008A (en) 1998-03-26 1999-03-25 Sustained release preparations

Country Status (31)

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US (5) US6440458B1 (me)
EP (3) EP1421939B9 (me)
JP (4) JP3714970B2 (me)
KR (3) KR100498765B1 (me)
CN (1) CN1229111C (me)
AR (1) AR023299A1 (me)
AT (3) ATE269075T1 (me)
AU (1) AU749623B2 (me)
BR (1) BRPI9909201B8 (me)
CA (1) CA2322516C (me)
CZ (1) CZ300548B6 (me)
DE (2) DE69918074T2 (me)
DK (3) DK1421939T5 (me)
ES (3) ES2343248T3 (me)
HR (1) HRP20000707B1 (me)
HU (1) HU230889B1 (me)
ID (1) ID27825A (me)
IL (1) IL138466A (me)
ME (2) ME00189B (me)
NO (1) NO330578B1 (me)
NZ (1) NZ507211A (me)
PL (1) PL193244B1 (me)
PT (3) PT1421939E (me)
RS (1) RS50164B (me)
RU (1) RU2214244C9 (me)
SI (1) SI1064942T1 (me)
SK (1) SK286887B6 (me)
TR (1) TR200002771T2 (me)
TW (2) TW570814B (me)
WO (1) WO1999049863A1 (me)
ZA (1) ZA200004963B (me)

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