JP2010279691A5 - - Google Patents
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- JP2010279691A5 JP2010279691A5 JP2010119919A JP2010119919A JP2010279691A5 JP 2010279691 A5 JP2010279691 A5 JP 2010279691A5 JP 2010119919 A JP2010119919 A JP 2010119919A JP 2010119919 A JP2010119919 A JP 2010119919A JP 2010279691 A5 JP2010279691 A5 JP 2010279691A5
- Authority
- JP
- Japan
- Prior art keywords
- lactylate
- coating
- group
- stearoyl
- oleyl
- 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.)
- Pending
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- 239000011248 coating agent Substances 0.000 claims 24
- 238000000576 coating method Methods 0.000 claims 24
- -1 polyethylene Polymers 0.000 claims 19
- 239000000178 monomer Substances 0.000 claims 14
- 235000014113 dietary fatty acids Nutrition 0.000 claims 13
- 229930195729 fatty acid Natural products 0.000 claims 13
- 239000000194 fatty acid Substances 0.000 claims 13
- 239000002250 absorbent Substances 0.000 claims 8
- 230000002745 absorbent Effects 0.000 claims 8
- 229920001577 copolymer Polymers 0.000 claims 8
- 150000004665 fatty acids Chemical class 0.000 claims 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims 6
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 4
- 230000000845 anti-microbial effect Effects 0.000 claims 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 4
- 239000003960 organic solvent Substances 0.000 claims 4
- 239000012071 phase Substances 0.000 claims 4
- 229920000642 polymer Polymers 0.000 claims 4
- 229920001897 terpolymer Polymers 0.000 claims 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims 4
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims 2
- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-UHFFFAOYSA-N 0.000 claims 2
- OZFIGURLAJSLIR-UHFFFAOYSA-N 1-ethenyl-2h-pyridine Chemical compound C=CN1CC=CC=C1 OZFIGURLAJSLIR-UHFFFAOYSA-N 0.000 claims 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 2
- GNSFRPWPOGYVLO-UHFFFAOYSA-N 3-hydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCO GNSFRPWPOGYVLO-UHFFFAOYSA-N 0.000 claims 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims 2
- XBYUGDPGTDLUQF-UHFFFAOYSA-N C(C=C)(=O)O.S(=O)(=O)(O)CCC[K] Chemical compound C(C=C)(=O)O.S(=O)(=O)(O)CCC[K] XBYUGDPGTDLUQF-UHFFFAOYSA-N 0.000 claims 2
- ODQBPQQUECTIBV-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)[AlH2] Chemical compound C(CCCCCCCCCCCCCCC)[AlH2] ODQBPQQUECTIBV-UHFFFAOYSA-N 0.000 claims 2
- CZTLQAUSLIPGSK-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)[Ba] Chemical compound C(CCCCCCCCCCCCCCC)[Ba] CZTLQAUSLIPGSK-UHFFFAOYSA-N 0.000 claims 2
- YFWKQALWEDUUIB-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)[Ca] Chemical compound C(CCCCCCCCCCCCCCC)[Ca] YFWKQALWEDUUIB-UHFFFAOYSA-N 0.000 claims 2
- PMNDCJNNPPHRTI-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)[Mg] Chemical compound C(CCCCCCCCCCCCCCC)[Mg] PMNDCJNNPPHRTI-UHFFFAOYSA-N 0.000 claims 2
- LWXWACSHSJIIBO-UHFFFAOYSA-N C(CCCCCCCCCCCCCCCCC)(=O)[Ba] Chemical compound C(CCCCCCCCCCCCCCCCC)(=O)[Ba] LWXWACSHSJIIBO-UHFFFAOYSA-N 0.000 claims 2
- JWIXJIMMGQOMSN-UHFFFAOYSA-N C(CCCCCCCCCCCCCCCCC)(=O)[Ca] Chemical group C(CCCCCCCCCCCCCCCCC)(=O)[Ca] JWIXJIMMGQOMSN-UHFFFAOYSA-N 0.000 claims 2
- ZAQNTQQVSJVEIN-UHFFFAOYSA-N C(CCCCCCCCCCCCCCCCC)(=O)[Mg] Chemical compound C(CCCCCCCCCCCCCCCCC)(=O)[Mg] ZAQNTQQVSJVEIN-UHFFFAOYSA-N 0.000 claims 2
- OPDBGKQXNHUHTA-UHFFFAOYSA-O CC(=C)C(=O)P(=O)=C(O)C[N+](C)(C)C Chemical compound CC(=C)C(=O)P(=O)=C(O)C[N+](C)(C)C OPDBGKQXNHUHTA-UHFFFAOYSA-O 0.000 claims 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
- 108050004290 Cecropin Proteins 0.000 claims 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 2
- 108010002069 Defensins Proteins 0.000 claims 2
- 102000000541 Defensins Human genes 0.000 claims 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims 2
- 108010019494 Histatins Proteins 0.000 claims 2
- 102000006492 Histatins Human genes 0.000 claims 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims 2
- 101800004361 Lactoferricin-B Proteins 0.000 claims 2
- 108010063045 Lactoferrin Proteins 0.000 claims 2
- 102000010445 Lactoferrin Human genes 0.000 claims 2
- 108060003100 Magainin Proteins 0.000 claims 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims 2
- 239000004677 Nylon Substances 0.000 claims 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 2
- 239000004698 Polyethylene Substances 0.000 claims 2
- 239000004793 Polystyrene Substances 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 229910052782 aluminium Inorganic materials 0.000 claims 2
- 239000008346 aqueous phase Substances 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 2
- 229910052788 barium Inorganic materials 0.000 claims 2
- 229910052791 calcium Inorganic materials 0.000 claims 2
- 239000011575 calcium Substances 0.000 claims 2
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 claims 2
- 108060001132 cathelicidin Proteins 0.000 claims 2
- 102000014509 cathelicidin Human genes 0.000 claims 2
- POIUWJQBRNEFGX-XAMSXPGMSA-N cathelicidin Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C1=CC=CC=C1 POIUWJQBRNEFGX-XAMSXPGMSA-N 0.000 claims 2
- 239000002131 composite material Substances 0.000 claims 2
- 238000012377 drug delivery Methods 0.000 claims 2
- 239000000839 emulsion Substances 0.000 claims 2
- 229920001519 homopolymer Polymers 0.000 claims 2
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 claims 2
- 235000014655 lactic acid Nutrition 0.000 claims 2
- 239000004310 lactic acid Substances 0.000 claims 2
- CFFMZOZGXDAXHP-HOKBLYKWSA-N lactoferricin Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CSSC[C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CO)C(=O)N[C@H](C(N[C@H](C(=O)N1)[C@@H](C)O)=O)[C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CFFMZOZGXDAXHP-HOKBLYKWSA-N 0.000 claims 2
- 229940078795 lactoferrin Drugs 0.000 claims 2
- 235000021242 lactoferrin Nutrition 0.000 claims 2
- 150000002596 lactones Chemical class 0.000 claims 2
- 210000003041 ligament Anatomy 0.000 claims 2
- 229910052749 magnesium Inorganic materials 0.000 claims 2
- 239000011777 magnesium Substances 0.000 claims 2
- 239000011159 matrix material Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 229920001778 nylon Polymers 0.000 claims 2
- 150000002905 orthoesters Chemical class 0.000 claims 2
- 229920000573 polyethylene Polymers 0.000 claims 2
- 229920001451 polypropylene glycol Polymers 0.000 claims 2
- 229920002223 polystyrene Polymers 0.000 claims 2
- PNOXUQIZPBURMT-UHFFFAOYSA-M potassium;3-(2-methylprop-2-enoyloxy)propane-1-sulfonate Chemical compound [K+].CC(=C)C(=O)OCCCS([O-])(=O)=O PNOXUQIZPBURMT-UHFFFAOYSA-M 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 239000004094 surface-active agent Substances 0.000 claims 2
- 210000002435 tendon Anatomy 0.000 claims 2
- 239000002407 tissue scaffold Substances 0.000 claims 2
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims 2
- 239000008096 xylene Substances 0.000 claims 2
- 229910052725 zinc Inorganic materials 0.000 claims 2
- 239000011701 zinc Substances 0.000 claims 2
- 229940012185 zinc palmitate Drugs 0.000 claims 2
- GJAPSKMAVXDBIU-UHFFFAOYSA-L zinc;hexadecanoate Chemical compound [Zn+2].CCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCC([O-])=O GJAPSKMAVXDBIU-UHFFFAOYSA-L 0.000 claims 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 229920003171 Poly (ethylene oxide) Chemical class 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 150000002314 glycerols Chemical class 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/477,629 US8263105B2 (en) | 2004-12-01 | 2009-06-03 | Biomaterial drug delivery and surface modification compositions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010279691A JP2010279691A (ja) | 2010-12-16 |
| JP2010279691A5 true JP2010279691A5 (https=) | 2013-04-25 |
Family
ID=42813114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010119919A Pending JP2010279691A (ja) | 2009-06-03 | 2010-05-25 | 新規な生物材料薬物送達および表面改変組成物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8263105B2 (https=) |
| EP (1) | EP2258410A3 (https=) |
| JP (1) | JP2010279691A (https=) |
| AU (1) | AU2010202065A1 (https=) |
| CA (1) | CA2703303A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8440215B2 (en) | 2004-09-03 | 2013-05-14 | Ethicon, Inc. | Absorbable polymer formulations |
| US9200112B2 (en) | 2009-08-10 | 2015-12-01 | Ethicon, Inc. | Semi-crystalline, fast absorbing polymer formulation |
| CA2772709C (en) * | 2009-09-30 | 2015-07-21 | Colgate-Palmolive Company | Antiperspirant/deodorant composition |
| MX344017B (es) * | 2009-09-30 | 2016-12-02 | Colgate-Palmolive Company * | Composicion antitranspirante/desodorante. |
| US9044524B2 (en) * | 2009-10-30 | 2015-06-02 | Ethicon, Inc. | Absorbable polyethylene diglycolate copolymers to reduce microbial adhesion to medical devices and implants |
| AU2012313984B2 (en) * | 2011-09-30 | 2016-02-11 | Covidien Lp | Reversible stiffening of light weight mesh |
| US9447205B2 (en) | 2012-11-19 | 2016-09-20 | Ut-Battelle, Llc | Atmospheric pressure plasma processing of polymeric materials utilizing close proximity indirect exposure |
| SG11201708815UA (en) * | 2015-05-29 | 2017-12-28 | Hexima Ltd | A method of in vivo treatment |
| CN108348647B (zh) * | 2015-08-26 | 2021-07-06 | 伊西康有限责任公司 | 包括覆盖件的钉 |
| JP2023176279A (ja) * | 2022-05-31 | 2023-12-13 | Ｓｂカワスミ株式会社 | ステントデリバリー装置 |
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| US6203564B1 (en) | 1998-02-26 | 2001-03-20 | United States Surgical | Braided polyester suture and implantable medical device |
| US6177094B1 (en) * | 1998-04-30 | 2001-01-23 | United States Surgical Corporation | Bioabsorbable blends and coating composition containing same |
| JP2003520830A (ja) * | 2000-01-25 | 2003-07-08 | エドワーズ ライフサイエンシーズ コーポレイション | 再狭窄および吻合内膜過形成処置のための送達系 |
| AU2001247346A1 (en) * | 2000-03-10 | 2001-09-24 | Johns Hopkins University | Phosphate based biodegradable polymers |
| US6991809B2 (en) * | 2001-06-23 | 2006-01-31 | Lyotropic Therapeutics, Inc. | Particles with improved solubilization capacity |
| US7378479B2 (en) * | 2002-09-13 | 2008-05-27 | Lubrizol Advanced Materials, Inc. | Multi-purpose polymers, methods and compositions |
| EP2298338B1 (en) * | 2002-09-16 | 2012-08-22 | Agennix Incorporated | Lactoferrin compositions and methods of treatment of skin wounds |
| US7491234B2 (en) * | 2002-12-03 | 2009-02-17 | Boston Scientific Scimed, Inc. | Medical devices for delivery of therapeutic agents |
| US6919100B2 (en) * | 2003-01-22 | 2005-07-19 | Cordis Corporation | Method for coating medical devices |
| CA2526541C (en) * | 2004-12-01 | 2013-09-03 | Tyco Healthcare Group Lp | Novel biomaterial drug delivery and surface modification compositions |
-
2009
- 2009-06-03 US US12/477,629 patent/US8263105B2/en not_active Expired - Fee Related
-
2010
- 2010-05-06 CA CA2703303A patent/CA2703303A1/en not_active Abandoned
- 2010-05-20 AU AU2010202065A patent/AU2010202065A1/en not_active Abandoned
- 2010-05-25 JP JP2010119919A patent/JP2010279691A/ja active Pending
- 2010-06-02 EP EP10251022.9A patent/EP2258410A3/en not_active Withdrawn
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