ES2371601T3 - Composición para inhalación. - Google Patents

Composición para inhalación. Download PDF

Info

Publication number: ES2371601T3
Authority: ES; Spain
Prior art keywords: micrometers; dry powder; lactose; diameter; formoterol
Prior art date: 2002-08-21
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

Application number

ES03751884T

Other languages

English (en)

Spanish (es)

Inventor

Xian-Ming Zeng

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Norton Healthcare Ltd

Original Assignee

Norton Healthcare Ltd

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.)

2002-08-21

Filing date

2003-08-21

Publication date

2012-01-05

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=9942746&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2371601(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-08-21 Application filed by Norton Healthcare Ltd filed Critical Norton Healthcare Ltd

2012-01-05 Application granted granted Critical

2012-01-05 Publication of ES2371601T3 publication Critical patent/ES2371601T3/es

2023-08-21 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 90
239000002245 particle Substances 0.000 claims abstract description 70
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 claims abstract description 56
239000008101 lactose Substances 0.000 claims abstract description 56
239000003814 drug Substances 0.000 claims abstract description 54
239000000843 powder Substances 0.000 claims abstract description 36
BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims abstract description 34
229960002848 formoterol Drugs 0.000 claims abstract description 33
150000003839 salts Chemical class 0.000 claims abstract description 13
229940079593 drug Drugs 0.000 claims description 34
229940112141 dry powder inhaler Drugs 0.000 claims description 11
RATSWNOMCHFQGJ-TUYNVFRMSA-N (e)-but-2-enedioic acid;n-[2-hydroxy-5-[(1s)-1-hydroxy-2-[[(2s)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide;dihydrate Chemical compound O.O.OC(=O)\C=C\C(O)=O.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1 RATSWNOMCHFQGJ-TUYNVFRMSA-N 0.000 claims description 6
229960003610 formoterol fumarate dihydrate Drugs 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 2
229960001375 lactose Drugs 0.000 description 44
238000000034 method Methods 0.000 description 22
238000009826 distribution Methods 0.000 description 14
239000010419 fine particle Substances 0.000 description 13
239000000546 pharmaceutical excipient Substances 0.000 description 13
239000002775 capsule Substances 0.000 description 8
239000004480 active ingredient Substances 0.000 description 7
-1 and the like) Substances 0.000 description 7
239000013065 commercial product Substances 0.000 description 7
238000009472 formulation Methods 0.000 description 7
238000003860 storage Methods 0.000 description 7
230000008021 deposition Effects 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
150000001875 compounds Chemical class 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
230000014509 gene expression Effects 0.000 description 4
239000000463 material Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
238000011282 treatment Methods 0.000 description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
229960003556 aminophylline Drugs 0.000 description 3
FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000002483 medication Methods 0.000 description 3
238000002156 mixing Methods 0.000 description 3
238000005070 sampling Methods 0.000 description 3
XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 2
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
229930182837 (R)-adrenaline Natural products 0.000 description 2
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000000048 adrenergic agonist Substances 0.000 description 2
229940126157 adrenergic receptor agonist Drugs 0.000 description 2
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 2
229940092705 beclomethasone Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
229940124630 bronchodilator Drugs 0.000 description 2
239000000168 bronchodilator agent Substances 0.000 description 2
229960004436 budesonide Drugs 0.000 description 2
239000000812 cholinergic antagonist Substances 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
239000003246 corticosteroid Substances 0.000 description 2
229960001334 corticosteroids Drugs 0.000 description 2
229960005139 epinephrine Drugs 0.000 description 2
229960000676 flunisolide Drugs 0.000 description 2
229960000193 formoterol fumarate Drugs 0.000 description 2
229960001361 ipratropium bromide Drugs 0.000 description 2
KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 2
229960002657 orciprenaline Drugs 0.000 description 2
MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 2
229960002052 salbutamol Drugs 0.000 description 2
229960004017 salmeterol Drugs 0.000 description 2
238000007873 sieving Methods 0.000 description 2
229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 2
229960000195 terbutaline Drugs 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
NWLPAIVRIWBEIT-SEPHDYHBSA-N (e)-but-2-enedioic acid;dihydrate Chemical compound O.O.OC(=O)\C=C\C(O)=O NWLPAIVRIWBEIT-SEPHDYHBSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
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 description 1
WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical group 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 description 1
239000005711 Benzoic acid Substances 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
239000002253 acid Substances 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000006698 induction Effects 0.000 description 1
238000002664 inhalation therapy Methods 0.000 description 1
230000003434 inspiratory effect Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
238000002356 laser light scattering Methods 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000003801 milling Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000005563 spheronization Methods 0.000 description 1
238000005507 spraying Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
229940110309 tiotropium Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles

Landscapes

Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Pulmonology (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Otolaryngology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ES03751884T 2002-08-21 2003-08-21 Composición para inhalación. Expired - Lifetime ES2371601T3 (es)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB0219513A GB0219513D0 (en)	2002-08-21	2002-08-21	Inhalation compositions including coarse carrier
GB0219514		2002-08-21
GB0219513		2002-08-21

Publications (1)

Publication Number	Publication Date
ES2371601T3 true ES2371601T3 (es)	2012-01-05

Family

ID=9942746

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES03751884T Expired - Lifetime ES2371601T3 (es)	2002-08-21	2003-08-21	Composición para inhalación.

Country Status (8)

Country	Link
BR (1)	BRPI0313647A2 (pt)
CA (1)	CA2499273C (pt)
ES (1)	ES2371601T3 (pt)
GB (1)	GB0219513D0 (pt)
NO (1)	NO20051461L (pt)
TN (1)	TNSN05047A1 (pt)
WO (1)	WO2004017914A2 (pt)
ZA (1)	ZA200502177B (pt)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005102429A1 (en)	2004-04-21	2005-11-03	Innovata Biomed Limited	Inhaler
PL2708225T3 (pl)	2004-04-23	2019-07-31	Cydex Pharmaceuticals, Inc.	Formulacja DPI zawierająca eter sulfoalkilowy cyklodekstryny
GB0409197D0 (en)	2004-04-24	2004-05-26	Innovata Biomed Ltd	Device
RU2007133547A (ru) *	2005-02-10	2009-03-20	Глаксо Груп Лимитед (GB)	Способы получения лактозы с использованием методов предварительной сортировки и приготовляемые из нее фармацевтические композиции
US7629331B2 (en)	2005-10-26	2009-12-08	Cydex Pharmaceuticals, Inc.	Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof
GB0605723D0 (en)	2006-03-23	2006-05-03	3M Innovative Properties Co	Powder filling processes
WO2008134817A1 (en) *	2007-05-03	2008-11-13	The University Of Sydney	Composite carriers for dry powder inhalation therapy
TR201105367A2 (tr) *	2011-06-02	2012-12-21	Bi̇lgi̇ç Mahmut	Akış özellikleri geliştirilmiş bir kuru toz formülasyonu.
TR201205852A2 (tr) *	2011-06-02	2012-12-21	Bi̇lgi̇ç Mahmut	Geliştirilmiş yeni kuru toz formülasyonu.
UA115989C2 (uk)	2012-07-05	2018-01-25	Арвен Айлак Санайі Ве Тіджарет А.С.	Фармацевтична композиція для інгалятора сухого порошку, що містить антагоністи мускаринових рецепторів тривалої дії
NZ703866A (en)	2012-07-19	2016-05-27	Adamis Pharmaceuticals Corp	Powder feeding apparatus
JP6251667B2 (ja)	2014-06-03	2017-12-20	アサヒカルピスウェルネス株式会社	錠剤型即放性製剤及びその製造方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK1283036T3 (da) *	1998-11-13	2008-03-25	Jagotec Ag	Törpulver til inhalation
DE69818872T2 (de) *	1998-12-11	2004-05-19	Pharmachemie B.V.	Pharmazeutische zubereitungen zur inhalation eines opioids
PL200063B1 (pl)	2000-10-12	2008-12-31	Boehringer Ingelheim Pharma	Nowe proszki do inhalacji zawierające tiotropium
UA75375C2 (en)	2000-10-12	2006-04-17	Boehringer Ingelheim Pharma	Method for producing powdery preparations for inhaling

2002
- 2002-08-21 GB GB0219513A patent/GB0219513D0/en not_active Ceased
2003
- 2003-08-21 ES ES03751884T patent/ES2371601T3/es not_active Expired - Lifetime
- 2003-08-21 BR BRPI0313647A patent/BRPI0313647A2/pt active Search and Examination
- 2003-08-21 CA CA2499273A patent/CA2499273C/en not_active Expired - Fee Related
- 2003-08-21 WO PCT/US2003/026385 patent/WO2004017914A2/en not_active Ceased
2005
- 2005-02-18 TN TNP2005000047A patent/TNSN05047A1/en unknown
- 2005-03-15 ZA ZA200502177A patent/ZA200502177B/en unknown
- 2005-03-18 NO NO20051461A patent/NO20051461L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
WO2004017914A3 (en)	2004-04-29
NO20051461L (no)	2005-05-20
GB0219513D0 (en)	2002-10-02
WO2004017914A2 (en)	2004-03-04
TNSN05047A1 (en)	2007-05-14
CA2499273C (en)	2011-06-21
ZA200502177B (en)	2006-05-31
WO2004017914A8 (en)	2005-07-07
BRPI0313647A2 (pt)	2019-02-19
CA2499273A1 (en)	2004-03-04

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