CN102657894B - 光稳定的抗菌材料 - Google Patents

光稳定的抗菌材料 Download PDF

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CN102657894B
CN102657894B CN201210156137.7A CN201210156137A CN102657894B CN 102657894 B CN102657894 B CN 102657894B CN 201210156137 A CN201210156137 A CN 201210156137A CN 102657894 B CN102657894 B CN 102657894B
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P·鲍勒
E·亚克奎斯
D·帕森斯
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Abstract

描述了在医用材料中增强银的光稳定性的方法，更具体地说，该方法增加了某些包含亲水、两性或阴离子聚合物的材料中银的光稳定性，包括将聚合物用含有有机溶剂和银的溶液处理，在此期间或之后，加入一种或多种促进材料光稳定化的试剂。

Description

光稳定的抗菌材料
本申请是申请日为2001年11月29日、中国申请号01819802.3、题为“光稳定的抗菌材料”的中国专利申请的分案申请。
本申请要求2000年12月29日提交的美国临时申请No.60/250,182的优先权，其全部内容在此引作参考。
技术领域
本发明涉及光稳定的抗菌材料和制备用于创伤敷料及医疗器件的抗菌聚合物的方法。
背景技术
感染是与创伤相关的一个问题。感染对于受外伤的患者会阻碍创伤恢复，并且会大大增加治疗的费用和时间。因此需要既预防又治疗由创伤引起的感染或与创伤敷料或者使用其他医疗器件相关的伤口。这些有潜在危险的器件的例子包括假体器件、移植物或用于急性或慢性分泌创伤的创伤敷料。这个问题可以通过采用局部抗菌剂来解决。
已知可以在用来制造医疗器件如创伤敷料、造瘘术器具以及其他器件的材料中包括抗菌剂。其中一种抗菌剂是以多种形式使用的银，如盐或其他银化合物，并且它可以用于纤维、聚合物、织物和粘合剂组分以制造这些器件。含银材料的一个问题是它们通常对光敏感，这会导致含银材料不可控制的褪色。已经作了许多努力以使这些材料对光稳定，但是仍然需要在某些包含亲水、两性和阴离子聚合物的材料中增强银的光稳定性。特别是当这些聚合物用于医疗器件中时尤其如此。因此，探讨了光稳定性改善的含银聚合物和它们的生产方法。
美国专利No.5,770,255描述了在医疗器件的表面上形成抗菌涂层的方法。所述涂层包括金属离子如银。
但是该方法需要高于常压的压力和低温，不太方便并且成本较高。此外，该方法导致的一个明显缺点是涂层使医疗器件的尺寸发生了变化。医疗器件如移植物尺寸的变化会影响产品的使用性。而且在医疗器件如敷料的表面上金属离子作为涂层存在也会使产品有毒性。
美国专利No.5,326,567描述了制造用于医疗领域的含银组合物的方法。该组合物含有丙烯酸聚醚聚合物如聚乙二醇，并且与硝酸银偶联。但是该体系仅适用于溶液，并且对溶剂和盐条件相当敏感。此外，该体系不足以杀灭创伤敷料中通常存在的残存细菌。而且该体系在用于纤维或水状胶体的创伤敷料时并不很有效。
美国专利No.3,422,183公开了在如绷带的物品中使用紫外照射氟化银组合物。据报道紫外线处理会使银的活性增强，但没有解决光稳定性的问题。此外，该方法的问题在于氟化合物与伤口接触时的安全性，特别是使用能够达到效果的氟化合物的浓缩液时。
美国专利No.4,646,730公开了对光稳定的聚乙烯基吡咯烷酮/磺胺嘧啶银(PVP/SSD)水凝胶敷料，其中凝胶通过采用电子束照射交联PVP而形成。据报道通过向凝胶中添加三硅酸镁来提供光稳定性，并且优选还添加过氧化氢和/或聚丙烯酸。该方法需要特定的装置来进行电子束照射。此外，该方法使用水凝胶，因此与其他创伤敷料种类及加工不相容。
WO 00/01973描述了用于创伤敷料的稳定的含银抗菌组合物。其中银是与伯、仲或叔氨基的络合物形式，并且该络合物与一种或多种亲水聚合物结合。但是该处理方法限制了可以生产的产品种类并且还改变了银的释放速率。该方法更适用于水状胶体产品，由于粘性基质，该产品中银的利用率较低。该体系配制完毕后不适用于可水溶胀的/可溶于水的材料。
美国专利No.4,906,466和5,413,788公开了适用于局部使用或创伤保护的抗菌组合物，并且表现出光不稳定性的降低。该组合物包含一种沉积在特定形状的生理惰性氧化合成载体材料，如氧化钛上的抗菌银化合物。但是已经发现由于银化合物还原为金属银而使所得产品易于发暗。此外，使用不溶颗粒如氧化钛作为载体在创伤修复产品中是不受欢迎的，因为颗粒会被认为是异体并且必需除去。
美国专利No.4,446,124涉及使用氨合SSD结合到动物组织中以制备烧伤敷料。通过将组织浸泡在氨合SSD溶液或悬浮液中而将SSD结合到组织中。同时据报道铵溶液会增加可以结合到敷料中的银的浓度，没有提到光稳定性并且也不可能改善光稳定性。此外，该方法采用动物组织作为基质，这不希望用于创伤。
根据本发明，公开了一种新的用于制备光稳定的含银亲水、两性和阴离子聚合物的方法。本发明描述了用于制备这些聚合物的简单而且低廉的方法，这些聚合物可以在定期消毒的可水溶胀的材料中提供有效而且无毒的抗菌活性。
发明内容
本发明涉及制备含有一种或多种亲水、两性或阴离子聚合物的材料的方法，其中该材料具有抗菌活性。优选该材料含有可用于医疗器件、创伤敷料或造瘘术器件的聚合物。本发明还包括由本文所述方法制备的聚合物和材料。本发明与现有技术相比的优点是它可以容易地用于可溶于水和/或可水溶胀的材料。
在本发明的方法中，制备一种包含有机溶剂和银源的溶液。通常银源先溶于水中，然后通过将水和有机溶剂混合来形成溶液。银的量应当足以在材料中提供所需的银浓度。适当的银源包括银盐，如硝酸银、氯化银、硫酸银、乳酸银、溴化银、乙酸银、碳酸银、碘化银、柠檬酸银、月桂酸银、草酸银、水杨酸银、对氨基苯甲酸银、对氨基水杨酸银和/或它们的混合物。其他合适的银源包括但不限于任何简单的可溶于水和/或醇的银盐。
接下来，聚合物用溶液处理一段时间，足以结合所需的银浓度。在聚合物用溶液处理期间或之后，将聚合物用一种或多种使银和聚合物结合在一起的试剂进行处理，合适的试剂包括氨、铵盐、硫代硫酸盐、氯化物、和/或过氧化物。在一个优选的实施方案中，该试剂是氯化铵水溶液。
在材料干燥后，所得材料完全是光稳定的。但是该材料如果再次水合时，将会离解释放出银。
具体实施方式
我们已经发现可以使银在用于医疗有关的材料的聚合物中稳定化。其优点是材料表现出抗菌活性，同时不容易光降解或光敏感。这种光稳定的医用材料特别适用于创伤敷料，这会产生一个湿润的创伤修复环境，特别是用于中度或重度渗出伤口如慢性或急性创伤。其他可以从本文所述方法受益的医用材料包括造瘘术产品、造瘘术用具、或其他暴露于可能的感染源的医用材料。
因此本发明提供了制备含有一种或多种亲水、两性或阴离子聚合物的材料的方法，其中聚合物具有抗菌活性。优选该材料含有可用于医疗器件、创伤敷料或造瘘术器件的聚合物。特别适用于本发明方法的材料包括成凝胶纤维如Aquacel(WO 93/12275，WO 94/16746，WO99/64079和美国专利No.5,731,083)，或WO 00/01425、PCT/GB01/03147中所述的那些；在不连续或多孔皮肤接触层之下或之上含有类似成凝胶纤维的创伤敷料，如Versiva(美国专利No.5,681,579，WO 97/07758和WO 00/41661)；DuoDerm(美国专利No.4,538,603)，DuoDerm CGFTM(美国专利No.4,551,490和EP 92 999)，或者两种或多种纤维的混合物如Carbofleirm(WO 95/19795)。本发明非常适用于其他含有羧甲基纤维素的材料。此外，本发明与现有技术相比的优点是它可以容易地用于可溶于水和/或可水溶胀的材料。
适用于本发明的聚合物包括，但不限于多糖或改性多糖、聚乙烯基吡咯烷酮、聚乙烯醇、聚乙烯基醚、聚氨酯、聚丙烯酸酯、聚丙烯酰胺、胶原、明胶、或它们的混合物。在优选的实施方案中，聚合物含有羧甲基纤维素(CMC)如CMC钠。在一个实施方案中，聚合物可以是包含羧甲基纤维素或海藻酸盐或羧甲基纤维素和海藻酸盐混合物的多糖。在其他实施方案中，聚合物含有成凝胶纤维，其中包含CMC钠，并且可以结合到创伤敷料如Aquacel TM(ConvaTec，Skillman，NJ)中。
在本发明的方法中，制备了一种包含有机溶剂和银源的溶液。该溶液的制备量应当足以在所得产品中提供所需的银浓度。聚合物随后用溶剂/银溶液处理以将银结合到聚合物中。处理后的聚合物用一种或多种试剂进行处理，以使含银材料光稳定化，并且进一步当材料再次水合时，银将会随后离解释放。
有机溶剂可以是任何已知的溶剂。合适溶剂的例子包括但不限于工业甲基化酒精(IMS，主要是乙醇)、乙醇、甲醇、丙酮和异丙醇。
银源可以是任何合适的原材料。银源的适当例子包括银盐，如硝酸银、氯化银、硫酸银、乳酸银、溴化银、乙酸银、碳酸银、碘化银、柠檬酸银、月桂酸银、草酸银、水杨酸银、对氨基苯甲酸银、对氨基水杨酸银和/或它们的混合物。其他合适的银源包括但不限于任何简单的可溶于水和/或醇的银盐。
银的用量应当足以在材料中提供所需的银浓度。材料中银的终浓度为，例如占所得医用敷料重量的约0.1重量％-20重量％。在一些实施方案中，银的浓度为0.1-10％，1-10％，10-20％，5-20％，5-10％或0.1-1％。在一个优选的实施方案中，银的终浓度为敷料重量的约1-5％。在处理溶液中优选浓度为0.001g/g聚合物-0.2g/g聚合物，更优选0.01g/g聚合物-0.05g/g聚合物。优选银源更容易先溶于水而不是纯有机溶剂中，随后以适当用量加入以在最终的聚合物中得到所需银浓度。
水可以用于本发明，特别是用于在银加入到有机溶剂之前将银先溶解。水的用量应当足以使银完全溶于溶液中，但是不能太多，以免导致聚合物的水合。尽管过量的银可以存在于悬浮液中，例如形成储存液，但是结合到聚合物中的有效量应该是在溶液中。对于本领域的技术人员而言，这些用量可以很容易地确定，而不需要额外的实验。但是，水的用量不超过50/50w/w水/醇。
用溶液处理材料的时间应该足以将所需银浓度结合到聚合物中。优选该材料用溶液处理1-120分钟。在一些实施方案中，保持时间介于1-60分钟。在一些实施方案中，保持时间介于15-45分钟。在其他实施方案中，保持时间介于10-60、10-45、15-30、5-15或10-20分钟。通常材料用溶液处理的时间长度将取决于所使用的材料并且可以很容易地由本领域技术人员确定。
本发明所采用的合适温度范围是0-100℃，但优选是室温。在不同阶段可以在所述范围内采用不同温度。
在聚合物用溶液处理期间或之后，用一种或多种有利于光稳定化的试剂进行处理。合适的试剂包括氨、铵盐、硫代硫酸盐、氯化物、和/或过氧化物。优选的试剂是铵盐，如氯化铵、乙酸铵、碳酸铵、硫酸铵和金属卤化物如氯化钠、氯化钾、氯化钙、氯化镁和氯化锌。该试剂可以任选地包括上述盐的混合物。在一个优选的实施方案中，该试剂作为铵盐水溶液如氯化铵加入到处理混合物中，或者分别加入。
该试剂的用量将取决于要制备的含聚合物的材料的量以及溶液的总体积。优选该试剂的存在浓度为处理溶液总体积的0.01-50％。在一些实施方案中，该试剂的浓度介于处理溶液总体积的0.01-25％、0.01-10％、0.01-5％、0.1-5％、0.1-25％、0.1-10％、1-25％、1-10％、1-5％、5-25％、10-25％或25-50％。
使用这种试剂时，处理时间要延长一段，例如增加5-30分钟，或者足以产生光稳定化的时间。
本发明还有一个重要的方面是银溶解于有机溶剂中以使银盐增溶并且防止聚合物的水合。银盐可以直接加入到溶剂中并且轻轻搅拌直至溶解。该方法的光稳定化步骤可以在加载银步骤之后进行，或者可以在加载银步骤期间进行。
除上述制品之外，本发明还适用于医用制品如创伤敷料和护肤产品。
术语“加载”在本文中是指聚合物的阳离子与银离子的离子交换。
本发明中所使用的术语“光稳定”是指随时间推移，颜色变化受控制并且变化很小。
本发明的术语“结合”是指形成光稳定化合物。
所得聚合材料在干燥后基本上是光稳定的。但是该材料如果再次水合时会离解释放出银。
在一个举例说明的方法中，Aquacel创伤敷料(例如20g，购于ConvaTec)可以置于例如127.5ml IMS/水中(77.5∶50 v/v)。例如，用水和硝酸银制备硝酸银溶液，浓度足以提供在Aquacel敷料中银的所需终浓度(例如0.0316g/mL水，10mL加入到IMS/水溶液中)。敷料中银的终浓度范围可以是敷料重量的0.1％-20％。优选浓度为1-5％。敷料用IMS/硝酸银处理一段所需时间，例如15-45分钟。优选在银处理后，将浓度为0.01-50％的氯化钠(优选1-10％)加入到IMS/硝酸银浴中，继续处理一段时间，例如5-30分钟。
已经发现含有占敷料重量1-5％的银的Aquacelm创伤敷料是光稳定的，并且具有优异的抗菌活性。此外，辐射不会对这种含银敷料产生不利影响。
本说明书中引述的所有出版物和文献，包括但不限于专利和专利申请，均在此以其全部内容引作参考，如同具体而单独地指出每篇单独的出版物和文献在本文中引作参考。

Claims (11)

1.一种制备光稳定的抗菌材料的方法，所述方法包括以下步骤：
a) 制备包含有机溶剂和银盐源的溶液，其中银盐源的量足以在光稳定的抗菌材料中提供所需的银浓度；
b) 将含有包含阴离子聚合物的成凝胶聚合物的材料用所述溶液处理，处理时间足以将所需浓度的银结合到成凝胶聚合物中，其中所述成凝胶聚合物选自羧甲基纤维素、羧甲基纤维素钠、海藻酸盐、透明质酸纤维、改性纤维素纤维、或其它多糖纤维或源于树胶的纤维、或它们的混合物；和
c) 在步骤(b)之后，用一种或多种试剂处理所述成凝胶聚合物，所述试剂有利于将所述银结合到所述成凝胶聚合物上，其中所述一种或多种试剂选自铵盐、硫代硫酸盐、氯化物和过氧化物，
其中当干燥时，银在所述光稳定的抗菌材料中基本上是光稳定的，但在光稳定的抗菌材料水合时，银会从光稳定的抗菌材料中离解出来。
2.权利要求1的方法，其中所述银盐选自硝酸银、氯化银、硫酸银、乳酸银、溴化银、乙酸银和它们的混合物。
3.权利要求1的方法，其中所述一种或多种试剂选自氯化铵和氯化钠。
4.权利要求1的方法，其中所述一种或多种试剂是氯化物。
5.权利要求1的方法，其中所述一种或多种试剂包括选自氯化铵、乙酸铵、碳酸铵、硫酸铵和它们的混合物的铵盐。
6.权利要求1的方法，其中所述有机溶剂选自工业甲基化酒精、变性乙醇、甲醇、丙酮、异丙醇和乙醇。
7.权利要求1的方法，其中所需的银浓度为0.1－20 wt%。
8.权利要求1的方法，其中所需的银浓度为1－20 wt%。
9.权利要求1的方法，其中所述足以将所需浓度的银结合到成凝胶聚合物中的时间为1－120分钟。
10.权利要求1的方法，其中所述足以将所需浓度的银结合到成凝胶聚合物中的时间为1－60分钟。
11.权利要求1的方法，其中在步骤(c)中，将成凝胶聚合物用一种或多种试剂处理5－30分钟。
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Families Citing this family (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6605751B1 (en) * 1997-11-14 2003-08-12 Acrymed Silver-containing compositions, devices and methods for making
US7179849B2 (en) * 1999-12-15 2007-02-20 C. R. Bard, Inc. Antimicrobial compositions containing colloids of oligodynamic metals
US8679523B2 (en) * 1999-12-30 2014-03-25 Kimberly-Clark Worldwide, Inc. Oxygen-delivery closed cell foam matrix for wound treatment
US20070009586A1 (en) * 2000-02-29 2007-01-11 Cohen Kelman I Wound dressings containing complexes of transition metals and alginate for elastase sequestering
DE60142180D1 (de) * 2000-11-29 2010-07-01 Convatec Technologies Inc Lichtstabilisierte antimikrobielle mittel
CA2458708C (en) 2001-09-12 2011-08-02 Acordis Speciality Fibres Limited Antibacterial wound dressing
CN1612804A (zh) 2001-12-03 2005-05-04 C·R·巴德公司 抗微生物医用器材、抗微生物聚合物涂层及其制备方法
GB0215023D0 (en) * 2002-06-28 2002-08-07 Bristol Myers Squibb Co Wound dressing
US8486426B2 (en) 2002-07-29 2013-07-16 Kimberly-Clark Worldwide, Inc. Methods and compositions for treatment of dermal conditions
DK1536845T3 (da) 2002-09-11 2007-06-11 Johnson & Johnson Medical Ltd Sårforbindingsmaterialer indeholdende komplekser af anioniske polysaccharider med sölv
US7025982B2 (en) * 2002-09-19 2006-04-11 Medtronic, Inc. Medical assembly suitable for long-term implantation and method for fabricating the same
GB0222259D0 (en) * 2002-09-25 2002-10-30 First Water Ltd Antimicrobial compositions
US6921546B2 (en) 2003-02-20 2005-07-26 Gemtron Corporation Antimicrobial glass and glass-like products and method of preparing same
US20040180093A1 (en) * 2003-03-12 2004-09-16 3M Innovative Properties Company Polymer compositions with bioactive agent, medical articles, and methods
GB2408206B (en) * 2003-11-18 2007-11-28 Johnson & Johnson Medical Ltd Antioxidant and antimicrobial wound dressing materials
US7745509B2 (en) 2003-12-05 2010-06-29 3M Innovative Properties Company Polymer compositions with bioactive agent, medical articles, and methods
US20050123621A1 (en) * 2003-12-05 2005-06-09 3M Innovative Properties Company Silver coatings and methods of manufacture
CN102783499A (zh) * 2004-07-30 2012-11-21 金伯利-克拉克环球有限公司 抗微生物的装置和组合物
US8361553B2 (en) 2004-07-30 2013-01-29 Kimberly-Clark Worldwide, Inc. Methods and compositions for metal nanoparticle treated surfaces
BRPI0513967A (pt) 2004-07-30 2008-05-20 Acrymed Inc composições de prata antimicrobianas
US20060035039A1 (en) * 2004-08-12 2006-02-16 3M Innovative Properties Company Silver-releasing articles and methods of manufacture
US20060034899A1 (en) * 2004-08-12 2006-02-16 Ylitalo Caroline M Biologically-active adhesive articles and methods of manufacture
US8900610B2 (en) * 2004-08-30 2014-12-02 Southwest Research Institute Biocidal fibrous and film materials comprising silver and chlorite ions
US9364579B2 (en) * 2004-08-30 2016-06-14 Southwest Research Institute Biocidal fibrous and film materials utilizing silver ion
WO2006034249A2 (en) * 2004-09-20 2006-03-30 Acrymed, Inc. Antimicrobial amorphous compositions
KR100652941B1 (ko) * 2004-10-12 2006-12-07 (주)석경에이.티 무색 투명한 은계 항균제 및 그의 제조방법
CA2529236A1 (en) * 2004-12-07 2006-06-07 Centre Des Technologies Textiles New antimicrobial material
US8399027B2 (en) * 2005-04-14 2013-03-19 3M Innovative Properties Company Silver coatings and methods of manufacture
US20060233888A1 (en) * 2005-04-14 2006-10-19 3M Innovative Properties Company Silver coatings and methods of manufacture
GB2425474A (en) * 2005-04-26 2006-11-01 Ethicon Inc Photostable wound dressing materials and methods of production thereof
EP1890740A4 (en) * 2005-06-17 2013-01-09 Rimon Therapeutics Ltd POUCH IN THERAPEUTIC POLYMER
GB0513552D0 (en) 2005-07-01 2005-08-10 Bristol Myers Squibb Co Bandage
GB0513555D0 (en) 2005-07-01 2005-08-10 Bristol Myers Squibb Co Carboxymethylated cellulosic wound dressing garment
GB0525504D0 (en) 2005-12-14 2006-01-25 Bristol Myers Squibb Co Antimicrobial composition
US20070154506A1 (en) * 2005-12-30 2007-07-05 Patton David L Antimicrobial agent to inhibit the growth of microorganisms on disposable products
US20070154505A1 (en) * 2005-12-30 2007-07-05 Manico Joseph A Antimicrobial agent to inhibit the growth of microorganisms on building materials
US20070166399A1 (en) * 2006-01-13 2007-07-19 3M Innovative Properties Company Silver-containing antimicrobial articles and methods of manufacture
KR100788997B1 (ko) 2006-03-10 2007-12-28 김주영 은이 화학 결합된 항균성 습윤 드레싱재 제조방법 및 그습윤 드레싱재
GB0608437D0 (en) 2006-04-28 2006-06-07 Adv Med Solutions Ltd Wound dressings
EP2015722B1 (en) * 2006-04-28 2016-11-16 Avent, Inc. Antimicrobial site dressings
WO2007149386A2 (en) * 2006-06-22 2007-12-27 Biomet 3I, Llc. Deposition of silver particles on an implant surface
US20100098949A1 (en) * 2006-10-18 2010-04-22 Burton Scott A Antimicrobial articles and method of manufacture
KR100797098B1 (ko) * 2006-11-23 2008-01-22 요업기술원 항균 섬유 가공제 조성물, 및 상기 조성물로 처리된 기능성섬유
DE102007003538A1 (de) * 2007-01-24 2008-07-31 Raumedic Ag Verfahren zur Herstellung eines medizinischen Arbeitsmittels, nach einem derartigen Verfahren hergestelltes medizinisches Arbeitsmittel sowie Verwendung eines derartigen medizinischen Arbeitsmittels
US7939578B2 (en) * 2007-02-23 2011-05-10 3M Innovative Properties Company Polymeric fibers and methods of making
US8513322B2 (en) * 2007-05-31 2013-08-20 3M Innovative Properties Company Polymeric beads and methods of making polymeric beads
CN101790568B (zh) * 2007-08-02 2015-09-30 科发龙技术公司 抗微生物的耐光涂料组合物
GB2452720A (en) * 2007-09-11 2009-03-18 Ethicon Inc Wound dressing with an antimicrobial absorbent layer and an apertured cover sheet
DE102007044648B4 (de) † 2007-09-18 2020-11-26 Carl Freudenberg Kg Bioresorbierbarer Gelatinevliesstoff
JP5330404B2 (ja) * 2007-12-12 2013-10-30 スリーエム イノベイティブ プロパティズ カンパニー 微小構造化された抗微生物フィルム
KR100861399B1 (ko) 2007-12-17 2008-10-02 주식회사 잉크테크 은 나노입자 분산 수지의 제조 방법
GB2455962A (en) 2007-12-24 2009-07-01 Ethicon Inc Reinforced adhesive backing sheet, for plaster
EP3409304B1 (en) 2008-03-05 2022-07-27 3M Innovative Properties Company Dressing for applying reduced pressure to and collecting and storing fluid from a tissue site
ITVI20080061A1 (it) * 2008-03-12 2009-09-13 Giovanni Costantini Apparato per la filtrazione dei liquidi e relativo elemento filtrante.
GB0805162D0 (en) * 2008-03-19 2008-04-23 Bristol Myers Squibb Co Antibacterial wound dressing
US8062615B2 (en) 2008-04-11 2011-11-22 Eastman Kodak Company Production of silver sulfate grains using carboxylic acid additives
JP2011518222A (ja) * 2008-04-21 2011-06-23 スリーエム イノベイティブ プロパティズ カンパニー 酸化窒素放出組成物、デバイス、及び方法
GB0808376D0 (en) 2008-05-08 2008-06-18 Bristol Myers Squibb Co Wound dressing
US20100190004A1 (en) * 2008-11-24 2010-07-29 Gibbins Bruce L Antimicrobial laminate constructs
US9221963B2 (en) * 2008-11-27 2015-12-29 Speciality Fibres And Materials Ltd. Absorbent material
US8293267B2 (en) 2009-06-12 2012-10-23 AG Biotech, LLC Method for preparing an antimicrobial cotton of cellulose matrix having chemically and/or physically bonded silver and antimicrobial cotton prepared therefrom
US8845801B2 (en) 2009-12-30 2014-09-30 Regents Of The University Of Minnesota Bone cement and method
US8882730B2 (en) 2010-03-12 2014-11-11 Kci Licensing, Inc. Radio opaque, reduced-pressure manifolds, systems, and methods
US8814842B2 (en) 2010-03-16 2014-08-26 Kci Licensing, Inc. Delivery-and-fluid-storage bridges for use with reduced-pressure systems
CN103816808B (zh) 2010-06-07 2017-01-11 3M创新有限公司 过滤方法和装置
GB201020236D0 (en) 2010-11-30 2011-01-12 Convatec Technologies Inc A composition for detecting biofilms on viable tissues
GB2488749A (en) 2011-01-31 2012-09-12 Systagenix Wound Man Ip Co Bv Laminated silicone coated wound dressing
GB201106491D0 (en) 2011-04-15 2011-06-01 Systagenix Wound Man Ip Co Bv Patterened silicone coating
AU2012352000B2 (en) 2011-12-16 2017-06-29 Solventum Intellectual Properties Company Releasable medical drapes
US10940047B2 (en) 2011-12-16 2021-03-09 Kci Licensing, Inc. Sealing systems and methods employing a hybrid switchable drape
GB201209745D0 (en) * 2012-05-31 2012-07-18 Convatec Technologies Inc Wound dressing
CN111991092A (zh) 2012-11-16 2020-11-27 凯希特许有限公司 具有图案粘合剂层的医用盖布及其制造方法
GB201222770D0 (en) 2012-12-18 2013-01-30 Systagenix Wound Man Ip Co Bv Wound dressing with adhesive margin
AU2013366038A1 (en) 2012-12-20 2015-07-16 Convatec Technologies Inc. Processing of chemically modified cellulosic fibres
EP3434236B1 (en) 2013-03-14 2021-12-29 3M Innovative Properties Company Absorbent dressing with hybrid drape
EP3578209B1 (en) 2013-08-26 2023-12-20 3M Innovative Properties Company Dressing interface with moisture controlling feature and sealing function
EP3062753B1 (en) 2013-10-28 2018-11-21 KCI Licensing, Inc. Hybrid sealing tape
EP3656362A1 (en) 2013-10-30 2020-05-27 KCI Licensing, Inc. Condensate absorbing and dissipating system related application
TR201807060T4 (tr) 2013-10-30 2018-06-21 Kci Licensing Inc Farklı boyutlarda perforasyonlara sahip sargı.
WO2015065615A1 (en) 2013-10-30 2015-05-07 Kci Licensing, Inc. Absorbent conduit and system
WO2015065616A1 (en) 2013-10-30 2015-05-07 Kci Licensing, Inc. Dressing with sealing and retention intereface
EP3848009A1 (en) 2014-02-28 2021-07-14 3M Innovative Properties Company Hybrid drape having a gel-coated perforated mesh
US11026844B2 (en) 2014-03-03 2021-06-08 Kci Licensing, Inc. Low profile flexible pressure transmission conduit
EP3137029B1 (en) 2014-05-02 2020-09-09 KCI Licensing, Inc. Fluid storage devices, systems, and methods
EP3854361B8 (en) 2014-06-05 2024-03-27 Solventum Intellectual Properties Company Dressing with fluid acquisition and distribution characteristics
US10398604B2 (en) 2014-12-17 2019-09-03 Kci Licensing, Inc. Dressing with offloading capability
EP3294245B1 (en) 2015-05-08 2019-09-04 KCI Licensing, Inc. Low acuity dressing with integral pump
CA3121872C (en) * 2015-07-24 2023-09-05 Molnlycke Health Care Ab Absorbent antimicrobial wound dressings
WO2017040045A1 (en) 2015-09-01 2017-03-09 Kci Licensing, Inc. Dressing with increased apposition force
EP3892310A1 (en) 2015-09-17 2021-10-13 3M Innovative Properties Co. Hybrid silicone and acrylic adhesive cover for use with wound treatment
CN105709262A (zh) * 2016-03-16 2016-06-29 张家港耐尔纳米科技有限公司 一种载银抗菌敷料及其制备方法
US10512705B2 (en) * 2017-01-17 2019-12-24 Oxiscience, Llc Halogenated heterocyclic N-halamine composition for the prevention and elimination of odors
CN108084476A (zh) * 2017-12-26 2018-05-29 宁波远欣石化有限公司 一种光稳定抗菌聚氨酯改性材料制品
CN112457420B (zh) * 2020-10-22 2022-09-02 青岛大学 一种超低烟海藻多糖材料的制备方法
CN113499473B (zh) * 2021-06-21 2022-05-10 四川大学 一种多功能抗菌敷料、制备方法及应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0328421A2 (en) * 1988-02-11 1989-08-16 The Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
CN1069884A (zh) * 1992-07-28 1993-03-17 江西医学院第一附属医院 生物敷料辐照药物猪皮的制备方法
CN1140977A (zh) * 1993-11-18 1997-01-22 韦斯泰姆技术有限公司 抗菌材料

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2785106A (en) * 1952-08-16 1957-03-12 Ions Exchange And Chemical Cor Process for making antiseptic article
EP0124536A4 (en) 1982-11-05 1985-06-06 Baxter Travenol Lab ANTIMICROBIAL COMPOSITIONS.
US4612337A (en) * 1985-05-30 1986-09-16 The Trustees Of Columbia University In The City Of New York Method for preparing infection-resistant materials
US4728323A (en) * 1986-07-24 1988-03-01 Minnesota Mining And Manufacturing Company Antimicrobial wound dressings
AU656384B2 (en) * 1991-04-10 1995-02-02 Christopher C. Capelli Antimicrobial compositions useful for medical applications
US5662913A (en) * 1991-04-10 1997-09-02 Capelli; Christopher C. Antimicrobial compositions useful for medical applications
ATE239431T1 (de) * 1992-10-21 2003-05-15 Gynetech Lab Inc Abgabesystem bestehend aus einem vaginaschwamm
US5567495A (en) * 1993-08-06 1996-10-22 The Trustees Of Columbia University In The City Of New York Infection resistant medical devices
JP3121503B2 (ja) 1994-10-18 2001-01-09 レンゴー株式会社 抗菌剤
EP0896541A1 (en) * 1995-06-30 1999-02-17 CAPELLI, Christopher C. Silver-based pharmaceutical compositions
AU735373B2 (en) * 1996-08-16 2001-07-05 Christopher C. Capelli Silver-based antimicrobial compositions
AU7989100A (en) * 1999-10-01 2001-05-10 Acrymed Silver-containing compositions, devices and methods for making
DE60142180D1 (de) * 2000-11-29 2010-07-01 Convatec Technologies Inc Lichtstabilisierte antimikrobielle mittel
US20020172709A1 (en) 2001-03-30 2002-11-21 Brian Nielsen Medical dressing comprising an antimicrobial silver compound and a method for enhancing wound healing
GB0215023D0 (en) 2002-06-28 2002-08-07 Bristol Myers Squibb Co Wound dressing

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0328421A2 (en) * 1988-02-11 1989-08-16 The Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
CN1069884A (zh) * 1992-07-28 1993-03-17 江西医学院第一附属医院 生物敷料辐照药物猪皮的制备方法
CN1140977A (zh) * 1993-11-18 1997-01-22 韦斯泰姆技术有限公司 抗菌材料

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