CN1270689C - 固体口腔用抗牙垢和抗牙菌斑组合物 - Google Patents
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Abstract
口香糖形式的口腔用制剂,其包含:a.多磷酸盐;b.水合二氧化硅;c.氟离子源;d.由壳多糖衍生得到的聚合物,或其它天然的水胶体或其混合物;e.任选地,植物来源的提取物或活性成分和/或抗菌剂/消毒剂。本发明的组合物可在牙齿卫生中用作辅助药,特别是用于减少牙垢沉积。
Description
本发明涉及可在牙齿口腔医学卫生(odontostomatological hygiene)中用作辅助药的口腔用抗牙垢和抗牙菌斑组合物。
发明背景
人们已经对牙菌斑和牙垢形成问题进行了长期研究,且正在积极研究可用于抵抗和延缓上述牙菌斑和牙垢形成的活性剂。
导致牙垢沉积的机制众所周知;这些沉积物由沉淀在牙菌斑细胞外基质中的磷酸钙晶体构成。牙垢在牙周病如脓溢、牙周炎、龈炎以及相关疾病中的致病作用同样是众所周知的。
已证实有多种物质可有效减少或预防牙齿上的牙垢形成和沉积,包括可溶性焦磷酸盐和多磷酸盐、锌盐、氟化物、二膦酸盐、抗菌剂如三氯生以及磨擦剂如二氧化硅或氧化铝。目前市售的大部分抗牙垢牙膏的组成中均包括以各种方式相互组合的这些物质。这些牙膏的临床功效已在多项研究中进行了检验,综述于J.Clin.Dent.IV卷(3),71-81,1993中。
大部分普通牙膏均含有可溶性多磷酸盐以及氟化物和二氧化硅,还可能含有具有生物粘附性的聚合物,如例如US 4327977、US 4889713、US5017362、US 5139769、US 4921693和EP 492997中所述。
例如在GB 2200551中描述了添加了抗菌剂如三氯生的类似组合物。除牙膏以外,已经开发了含有类似组成的口香糖和糖果。
这些牙膏的功效已成为多项研究的目的(J.Clin.Dent.X卷(3),99-102,1999;Oral Surg.Oral Med.Oral Pathol.,70卷(4),529-536,1990;J.Clin.Dent.IX卷(4),101-104,1998),该功效的原因是与唾液中的钙离子络合的多磷酸盐对磷酸钙沉淀的抑制作用、二氧化硅的磨擦作用、氟化物对牙釉质的加固作用以及生物粘附性聚合物的作用,使用时,该聚合物保护粘膜并引起其它成分的缓慢释放。
旨在控制牙垢的组合物中最常使用的聚合物是由丙烯酸或甲基丙烯酸衍生得到的聚羧酸酯,特别是马来酸酐和甲基乙烯基醚的共聚物(GANTREX)。但是,这些聚合物未被批准用于食品,这就意味着它们只能用于制备牙膏和漱口剂。
另一方面,旨在通常在牙齿卫生和口腔卫生中用作辅助药的糖果和口香糖正变得越来越流行,这些糖果和口香糖具有可描述为抗牙垢、抗腐蚀、洁白和/或清凉的性质。除了活性成分(功能成分)的释放比普通牙膏更缓慢和更规律这一事实以外,这些施用形式的主要优势是它们在全天中、任何地点以及任何场合均可自由地和方便地使用。
发明内容
本发明涉及固体形式、优选口香糖形式的口腔用制剂,其功效优于类似的已知制剂。
本发明的组合物含有有效量的:
a.多磷酸盐,优选碱金属焦磷酸盐和三聚磷酸盐的混合物;
b.磨擦剂(优选水合二氧化硅);
c.氟离子源;
d.由壳多糖衍生得到的聚合物,或其它天然的水胶体或其混合物;
e.任选地,植物来源的提取物或活性成分;
f.任选地,抗菌剂或消毒剂。
除了以上提及的活性成分外,本发明的组合物还含有适合用于确定最终施用形式的赋形剂。
因此,例如,口香糖制剂将需要由胶基、甜味剂、多元醇如木糖醇、山梨醇和甘露醇、芳香剂、染料、软化剂、增塑剂、稳定剂、增稠剂等组成的适合的基质。
本发明的组合物包含能在口腔粘膜上成膜的系统这一事实增强了抗牙垢沉积的保护作用,因为活性成分能与使用者的牙齿和胶接触更长时间,且多磷酸盐被保护免受口腔的水解作用。
在本发明中,该系统包括壳多糖的脱乙酰基衍生物,其可能被化学修饰,并任选地与其它聚合物联合,以便增强其生物粘附性和其保护多磷酸盐抗水解剂的能力。
在过去的十年中,对针对口腔粘膜的控释系统给予了很多科学关注(J.Clin.Phar.Ther.(2000)25,21-42)。所研究的聚合物包括部分脱乙酰基壳多糖、高度脱乙酰基壳多糖或壳聚糖以及水解壳聚糖或寡糖,已经证明由于铵基团的正电荷,它们能粘附在组织上。部分归结于它们的生物粘附性,这些聚合物可加速伤口愈合和止血(Biom.1999,20(22):2139-45;J.Oral.Max.Surg.57:49-52)。具体研究证明了壳聚糖对口腔粘膜的生物粘附性(Biom.16(1995)617-624;J.Control Rel.61:175-183;Int.J.Pharm.73:43-48)。
在所述形式中,优选的形式是壳聚糖寡糖(chitosan oligosaccharide),其为市售化合物,包含以β-1,4键相互结合的二至七个单体D-葡糖胺单元,主要通过具有较高分子量的壳聚糖的酶水解获得。
尽管所述方法是已知的,但其似乎并未应用于与本发明的目的类似的组合物中。
任选地,天然存在的多糖水胶体可作为具有类似生物粘附性的替代物使用。这类多糖水胶体有:黄原胶、刺槐豆胶、藻酸盐、角叉菜胶、吉兰糖胶等。
一般而言,上述以聚合物为基础的系统占整个组合物的重量比总计为0.5至5%,优选1至3%。
组合物中所用的多磷酸盐可以是碱金属焦磷酸盐(二磷酸盐)、六偏磷酸盐、三聚磷酸盐或其混合物。特别优选二磷酸二氢二钠(disodium diaciddiphosphate)和三聚磷酸钠或三聚磷酸钾的混合物。已经证明含有该混合物的牙膏比含有焦磷酸盐但不含三聚磷酸盐的牙膏能更显著地减少牙垢(J.Clin.Dent.IX卷(4),101-104,1998)。
一般而言,多磷酸盐占本发明所涉及的整个组合物的重量比总计为0.5至5%。
磨擦剂的作用是增强普通口香糖已具有的除牙菌斑作用。其可以由单独的或相互组合的(适合形式的)水合二氧化硅、(适合形式的)碳酸钙或滑石粉形成。这些磨擦剂也可以全部或部分地、单独地或以其混合物、以囊化形式、特别是囊化于藻酸钙中的形式存在。已证明含有囊化于藻酸钙中的水合二氧化硅微粒的口香糖比不含微粒的相同配方的口香糖能更有效地去除牙菌斑(Doc.Os 06.2001 779-781)。根据本发明,囊化微粒可以含有染料、芳香剂、功能成分和草药提取物。所述磨擦剂通常以0.5至7%的重量百分比存在。
适合的氟离子源包括氟化钠、氟化钾、氟化铵、单氟磷酸钠和其它已知的无毒含氟盐,其浓度应能提供重量百分比0.005至0.2%的氟化物。
可存在于本发明组合物中的植物提取物将优选选自以下物质的提取物:积雪草(Centella asiatica)、锦葵(Malva sylvestris)、互叶白千层(Melaleucaalternifolia)、没药(Commiphora abyssinica)、秘鲁拉坦尼(Krameriatriandra)、儿茶(Acacia catechu)、紫苜蓿(Medicago sativa)、安息香(Styrax)属如安息香(Styrax benzoin)的树脂、母菊(Matricaria recutita)、紫锥菊(Echinacea purpurea)和血竭(Croton lechleri)。这些植物提取物是市售可得的,其活性一段时间以来已经为人们所熟知。
这些提取物的组合产生了具有抗炎/减轻充血、润滑、愈合伤口、抗菌防腐和收敛性质的制剂。在本发明范围内这些性质在至少两方面是有利的:
第一,帮助和加强由牙垢减少导致的口腔粘膜疾病的减少,和
第二,在特别易患病的人中,控制和预防与使用牙膏所出现的称为“牙膏口炎”类似的接触性毒性口炎。
在本发明的制剂中,这些提取物可以与磨擦剂一起囊化于藻酸盐中。
所述提取物可以以0.01至2%的重量百分比加入制剂中。
本发明的制剂可用常规技术制备,对于口香糖而言是将各种成分加入胶基中并混合,然后可根据同样常规的技术对其进行包衣操作。
本发明的制剂可以以重量比0.1至5%的浓度包含单独的或相互组合的消毒剂或抗菌剂如三氯生、锌盐或氧化锌。这些活性剂旨在对抗导致牙垢沉积的牙菌斑的形成。
本发明的制剂还可以包含美饰性晶体,该晶体优选由沉积于产品表面的具有纯粹美学作用的阿拉伯胶和染料组成。
每天使用本发明的口香糖可以减少牙垢沉积,并对口腔和齿龈粘膜状况具有其它的有益作用。
以下实施例更详细地阐述了本发明。
实施例1
重1.4g的包衣口香糖。
| 百分比组成(以重量计) | |
| 成分胶基木糖醇山梨醇甘露醇芳香剂二氧化硅阿拉伯胶甘油二磷酸二氢二钠三聚磷酸钠壳聚糖寡糖麦芽糖醇糖浆二氧化钛(E 171)Quick Coat阿司帕坦美饰性晶体丁磺氨巴西棕榈蜡氟化钾 | %24.523.523.2161.83111110.930.70.60.60.050.050.050.02100 |
实施例2
含有植物提取物的重1.4g的包衣口香糖。
| 百分比组成(以重量计) | |
| 成分胶基木糖醇山梨醇甘露醇芳香剂(*)二氧化硅阿拉伯胶甘油二磷酸二氢二钠三聚磷酸钠壳聚糖寡糖麦芽糖醇糖浆二氧化钛(E 171)Quick Coat阿司帕坦丁磺氨巴西棕榈蜡氟化钾锦葵、没药、积雪草、白千层、秘鲁拉坦尼和儿茶提取物总计 | %24.523.523.2161.83111110.930.70.60.60.050.050.020.05100 |
实施例3
功效试验:牙垢沉积的减少。
进行了双盲交叉临床试验以比较实施例1的口香糖和安慰剂胶的功效。
28名成年人入选试验并用两种口香糖每天治疗4次,每次5分钟,持续6周。在上述周期结束时,根据改进的Volpe和Manhold指标(J.Periodont.Res.(增刊)14:31-60,1974)进行牙垢沉积的定量评价。在整个治疗期内,患者全部使用相同的牙膏(不含抗牙垢剂)并食用类似的食物。然后按照与以前相同的治疗方法在第一次牙垢沉积评价后立即用另一种口香糖(实施例1或安慰剂)对相同患者进行6周治疗。治疗期结束时根据上述的相同方法进行第二次牙垢沉积定量评价。
用Student’s双尾配对样本“t”检验对结果进行统计学分析。
患者咀嚼实施例1中所述的胶后所进行的评价表明:与咀嚼安慰剂胶后所观察到的结果相比,牙垢沉积减少了13.9%。所述减少具有统计学显著性。研究结果总结在表1中。
表1
“T”检验:用于计算均值的成对样本
| 安慰剂 | 实施例1 | |
| 均值方差观察人数皮尔逊相关假设均值偏差P(T<=t)双尾 | 4.241071410.53926928 | 3.65178577.9599041280.985801106.884-05 |
Claims (12)
1.固体形式的口腔用制剂,其包含:
a.多磷酸盐;
b.磨擦剂;
c.氟离子源;
d.由壳多糖衍生得到的聚合物,或其它天然水胶体或其混合物;
e.植物来源的提取物或活性成分;
f.任选地,抗菌剂/消毒剂,
其中的提取物具有抗炎、愈合伤口、抗出血、缓解、润滑、减轻充血和抗菌防腐性质并且选自以下物质的提取物:积雪草、锦葵、互叶白千层、没药、秘鲁拉坦尼、儿茶、紫苜蓿、安息香属的树脂、母菊、紫锥菊和血竭。
2.权利要求1的制剂,其中的多磷酸盐选自三聚磷酸盐、焦磷酸盐或其混合物。
3.权利要求2的制剂,其包含碱金属焦磷酸盐和三聚磷酸盐的混合物。
4.权利要求1的制剂,其还含有选自胶基、甜味剂、多元醇、芳香剂、染料、软化剂、增塑剂、稳定剂和增稠剂的赋形剂。
5.权利要求1的制剂,其中的磨擦剂是单独的水合二氧化硅、碳酸钙和滑石粉,或其混合物。
6.权利要求1的制剂,其中由壳多糖衍生得到的聚合物是壳多糖的部分或全部脱乙酰基衍生物,其任选地被化学修饰,任选地与其它多糖水胶体联合。
7.权利要求6的制剂,其中的聚合物是壳聚糖。
8.权利要求7的制剂,其中的壳聚糖是壳聚糖寡糖。
9.权利要求1的制剂,其中天然水胶体是黄原胶、刺槐豆胶、藻酸盐、角叉菜胶、吉兰糖胶或其它具有生物粘附性的多糖。
10.权利要求1的制剂,其含有重量比0.5至5%的多磷酸盐、重量比0.5至7%的磨擦剂、重量比0.5至5%的由壳多糖衍生得到的聚合物、能保证0.005至0.2%的氟化物摄入量的氟离子源以及重量比0.01至2%的植物提取物,其中所述摩擦剂可为全部或部分囊化的。
11.权利要求10的制剂,其以0.1%至5%的浓度包含单独的或相互组合的选自三氯生、氧化锌和锌盐的消毒剂和/或抗菌剂。
12.权利要求1-11任一项所述的制剂,其中所述的制剂是口香糖或糖果。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001MI002320A ITMI20012320A1 (it) | 2001-11-06 | 2001-11-06 | Composizioni orali solide anti-tartaro e anti-placca batterica, utilicome coadiuvanti nell'igiene odonto-stomatologica |
| ITMI2001A002320 | 2001-11-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1599593A CN1599593A (zh) | 2005-03-23 |
| CN1270689C true CN1270689C (zh) | 2006-08-23 |
Family
ID=11448571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB028242696A Expired - Fee Related CN1270689C (zh) | 2001-11-06 | 2002-11-05 | 固体口腔用抗牙垢和抗牙菌斑组合物 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20050042184A1 (zh) |
| EP (1) | EP1441688B1 (zh) |
| JP (1) | JP2005512992A (zh) |
| CN (1) | CN1270689C (zh) |
| AT (1) | ATE396772T1 (zh) |
| BR (1) | BR0213930A (zh) |
| CA (1) | CA2465687A1 (zh) |
| DE (1) | DE60226887D1 (zh) |
| DK (1) | DK1441688T3 (zh) |
| ES (1) | ES2306801T3 (zh) |
| IT (1) | ITMI20012320A1 (zh) |
| PT (1) | PT1441688E (zh) |
| RU (1) | RU2316312C2 (zh) |
| WO (1) | WO2003039503A1 (zh) |
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|---|---|---|---|---|
| US7445769B2 (en) | 2002-10-31 | 2008-11-04 | Cadbury Adams Usa Llc | Compositions for removing stains from dental surfaces and methods of making and using the same |
| US7390518B2 (en) | 2003-07-11 | 2008-06-24 | Cadbury Adams Usa, Llc | Stain removing chewing gum composition |
| US20060024245A1 (en) | 2004-07-29 | 2006-02-02 | Cadbury Adams, Llc. | Tooth whitening compositions and delivery systems therefor |
| US7641892B2 (en) | 2004-07-29 | 2010-01-05 | Cadburry Adams USA, LLC | Tooth whitening compositions and delivery systems therefor |
| WO2006029893A2 (en) * | 2004-09-17 | 2006-03-23 | Oystershell Nv | Composition for inhibiting or preventing the formation of a biofilm |
| ITME20040015A1 (it) * | 2004-12-07 | 2005-03-07 | Vincenzo Savica | Chewing gum, caramelle gommose, pastiglie, compresse a lento rilascio di chelanti fosfato e/o fosforo salivare e capsule a lento rilascio di chelanti fosfato e/o fosforo a livello gastroenterico. |
| EP1688162A1 (en) * | 2005-01-28 | 2006-08-09 | Gumlink A/S | Multi functional oral care chewing gum possessing tooth cleaning effects |
| US8551455B2 (en) | 2005-01-28 | 2013-10-08 | Gumlink A/S | Tooth cleaning kit comprising at least one set of chewing gum pieces |
| EP1685875A1 (en) * | 2005-01-28 | 2006-08-02 | Gumlink A/S | Multi functional oral care chewing gum |
| US20060182693A1 (en) | 2005-01-28 | 2006-08-17 | Gumlink A/S | Chewing gum possessing tooth cleaning effect and a teeth cleaning method |
| EP1693086A1 (en) * | 2005-01-28 | 2006-08-23 | Gumlink A/S | Multi functional oral care chewing gum |
| WO2006079343A1 (en) * | 2005-01-28 | 2006-08-03 | Gumlink A/S | A compressed chewing gum table |
| EP1693085A1 (en) * | 2005-01-28 | 2006-08-23 | Gumlink A/S | A kit for cleaning teeth by chewing of a set of chewing gum pieces |
| US9198448B2 (en) | 2005-02-07 | 2015-12-01 | Intercontinental Great Brands Llc | Stable tooth whitening gum with reactive ingredients |
| US20090076132A1 (en) * | 2005-03-11 | 2009-03-19 | Gary Pekoe | Antiviral compositions and methods of treatment |
| US20080166307A1 (en) * | 2007-01-10 | 2008-07-10 | Jose Eder Fontana | Oral Care Compositions Comprising a Hippophae Extract |
| EP1946751A1 (en) * | 2007-01-22 | 2008-07-23 | Documedica S.A. | Carrageenan-based chewing gum |
| WO2009099405A2 (en) * | 2008-01-30 | 2009-08-13 | Dalos, Llc | Antibacterial compositions and methods of treatment |
| US8568697B2 (en) | 2008-03-21 | 2013-10-29 | Colgate-Palmolive Company | High fluoride ion recovery compositions |
| TWI392514B (zh) | 2010-01-29 | 2013-04-11 | Colgate Palmolive Co | 具有高微生物效力之不含氟化物及陰離子表面活性劑的潔牙劑 |
| IT1400386B1 (it) * | 2010-05-27 | 2013-05-31 | Roberto Logi | Kit di parti per il trattamento e/o prevenzione delle ulcere cutanee |
| CN103340797A (zh) * | 2013-07-15 | 2013-10-09 | 柳州两面针股份有限公司 | 积雪草提取物在中药牙膏中的应用 |
| JP7368858B2 (ja) * | 2018-09-21 | 2023-10-25 | 株式会社山田養蜂場本社 | バイオフィルム形成抑制剤 |
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| US4374824A (en) * | 1981-01-27 | 1983-02-22 | Krishan Dyal Mathur | Dentifrice |
| US4512968A (en) * | 1982-11-30 | 1985-04-23 | Lion Corporation | Oral compositions |
| GB8421226D0 (en) * | 1984-08-21 | 1984-09-26 | Int Conferences Ab | Tooth cleaning tablet |
| JPS61151113A (ja) * | 1984-12-24 | 1986-07-09 | Lion Corp | 口腔用組成物 |
| US4931273A (en) * | 1985-09-13 | 1990-06-05 | Colgate-Palmolive Company | Anticalculus oral composition |
| US4627977A (en) * | 1985-09-13 | 1986-12-09 | Colgate-Palmolive Company | Anticalculus oral composition |
| JPS6345214A (ja) * | 1986-06-09 | 1988-02-26 | ザ、プロクタ−、エンド、ギャンブル、カンパニ− | 経口組成物 |
| IN168400B (zh) * | 1987-01-30 | 1991-03-23 | Colgate Palmolive Co | |
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| GB8804817D0 (en) * | 1988-03-01 | 1988-03-30 | Unilever Plc | Anticalculas oral compositions |
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| JP2555001B2 (ja) * | 1990-03-01 | 1996-11-20 | 株式会社サンギ | 固型歯磨き剤 |
| US5015466A (en) * | 1990-06-26 | 1991-05-14 | The Procter & Gamble Company | Anticalculus compositions using tartrate-succinates |
| JPH04198131A (ja) * | 1990-11-28 | 1992-07-17 | Takeda Chem Ind Ltd | 創傷治癒促進剤およびそれを含有する外用組成物 |
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| NZ243667A (en) * | 1991-08-02 | 1995-02-24 | Kurihara Yoshie | Chewing gum containing coated curculin derivative or fruit containing curculin |
| US5281410A (en) * | 1991-10-23 | 1994-01-25 | The Proctor & Gamble Company | Methods of reducing plaque and gingivitis with reduced staining |
| JPH0840859A (ja) * | 1994-07-28 | 1996-02-13 | Lion Corp | 口腔用組成物 |
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| JPH08301742A (ja) * | 1995-04-28 | 1996-11-19 | Ezaki Glico Co Ltd | だ液のpH低下を防止する口腔用組成物 |
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| US5958380A (en) * | 1997-07-07 | 1999-09-28 | Enamelon, Inc. | Chewing gum products and the use thereof for remineralizing subsurface dental lesions and for mineralizing exposed dentinal tubules |
| FR2767057B1 (fr) * | 1997-08-08 | 1999-10-29 | Lvmh Rech | Utilisation du ginsenoside rb1 comme agent destine a stimuler la synthese de l'elastine |
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| DE10015662A1 (de) * | 2000-03-29 | 2001-10-04 | Henkel Kgaa | Zahnpflegemittel in Portionskapseln |
-
2001
- 2001-11-06 IT IT2001MI002320A patent/ITMI20012320A1/it unknown
-
2002
- 2002-11-05 RU RU2004113653/15A patent/RU2316312C2/ru not_active IP Right Cessation
- 2002-11-05 EP EP02787566A patent/EP1441688B1/en not_active Expired - Lifetime
- 2002-11-05 PT PT02787566T patent/PT1441688E/pt unknown
- 2002-11-05 WO PCT/EP2002/012329 patent/WO2003039503A1/en not_active Ceased
- 2002-11-05 BR BR0213930-8A patent/BR0213930A/pt not_active IP Right Cessation
- 2002-11-05 DK DK02787566T patent/DK1441688T3/da active
- 2002-11-05 JP JP2003541794A patent/JP2005512992A/ja active Pending
- 2002-11-05 CN CNB028242696A patent/CN1270689C/zh not_active Expired - Fee Related
- 2002-11-05 ES ES02787566T patent/ES2306801T3/es not_active Expired - Lifetime
- 2002-11-05 US US10/494,570 patent/US20050042184A1/en not_active Abandoned
- 2002-11-05 AT AT02787566T patent/ATE396772T1/de not_active IP Right Cessation
- 2002-11-05 CA CA002465687A patent/CA2465687A1/en not_active Abandoned
- 2002-11-05 DE DE60226887T patent/DE60226887D1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE396772T1 (de) | 2008-06-15 |
| EP1441688A1 (en) | 2004-08-04 |
| US20050042184A1 (en) | 2005-02-24 |
| DK1441688T3 (da) | 2008-09-29 |
| RU2004113653A (ru) | 2005-03-20 |
| ES2306801T3 (es) | 2008-11-16 |
| CN1599593A (zh) | 2005-03-23 |
| PT1441688E (pt) | 2008-08-14 |
| DE60226887D1 (de) | 2008-07-10 |
| BR0213930A (pt) | 2004-08-31 |
| HK1070836A1 (zh) | 2005-06-30 |
| WO2003039503A1 (en) | 2003-05-15 |
| CA2465687A1 (en) | 2003-05-15 |
| ITMI20012320A1 (it) | 2003-05-06 |
| RU2316312C2 (ru) | 2008-02-10 |
| JP2005512992A (ja) | 2005-05-12 |
| EP1441688B1 (en) | 2008-05-28 |
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