CN1151196C - 具有抗微生物涂层的生物医疗装置 - Google Patents
具有抗微生物涂层的生物医疗装置 Download PDFInfo
- Publication number
- CN1151196C CN1151196C CNB99121305XA CN99121305A CN1151196C CN 1151196 C CN1151196 C CN 1151196C CN B99121305X A CNB99121305X A CN B99121305XA CN 99121305 A CN99121305 A CN 99121305A CN 1151196 C CN1151196 C CN 1151196C
- Authority
- CN
- China
- Prior art keywords
- lactoferrin
- polymkeric substance
- hydrogel
- medical equipment
- contact lens
- 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.)
- Expired - Lifetime
Links
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- 108010063045 Lactoferrin Proteins 0.000 claims abstract description 63
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- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical class NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- PBQRNTXRLIVYLI-UHFFFAOYSA-N 2-ethyl-3-phenyl-3H-1,2-oxazole Chemical compound C(C)N1OC=CC1C1=CC=CC=C1 PBQRNTXRLIVYLI-UHFFFAOYSA-N 0.000 description 1
- 229940044192 2-hydroxyethyl methacrylate Drugs 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
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Abstract
本发明提供具抗微生物涂层的生物医疗装置，此装置之一或多个表面是经乳铁蛋白涂覆，以将抗微生物性质赋予该表面。
Description
技术领域
本发明涉及经涂覆的装置。特别地，本发明提供表面形成抗微生物蛋白质涂层的生物医疗装置。
背景技术
用于人体中和人体上的装置是业已熟知的。此等装置的表面的化学组成扮演决定此等装置的整体功效的关键性角色。再者，已知提供此等装置以抗微生物表面是有利的。
业已发展出甚多种类的杀细菌及制细菌涂层。例如，阳离子抗生素，如多粘菌素、万古霉素及四环素业已被用作隐形眼镜的涂层。再者，金属螯合剂、经取代及未经取代的多羟基苯酚类、胺基苯酚类、醇类、酸及胺衍生物、以及季铵业经且作隐形眼镜的抗微生物试剂。
然而，此等已知抗微生物涂层的用途具有缺点。使用抗生素涂层时，对抗生素具抵抗性微生物可能发展出来。螯合剂的使用无法对准附着于装置的细菌数量。本领域的一些涂层，例如苯酚衍生物及甲酚，可能产生眼睛毒性或过敏反应。季铵化合物由于其刺激性而有困扰。因此，需要克服至少某些此等缺点的安全且有效的抗微生物涂层。
发明内容
图1描绘在乳铁蛋白中测定细菌生长的试验结果。
本发明提供具抗微生物涂层的生物医疗装置及制造此等生物医疗装置的方法。本发明的不可预期的发现在于某些蛋白质可用以提供生物医疗装置的抗微生物涂层。特别地，本发明的一项发现在于乳铁蛋白(lactoferrin)当作用表面涂层时，可预防附着于生物医疗装置的细菌的生长。
在一个实施方案中，本发明提供一种装置，其实质上包括一生物医疗装置，该装置的至少一表面包含乳铁蛋白。在另一实施方案中，提供一种制造生物医疗装置的方法，其包括将一生物医疗装置的至少一个表面与涂覆有效量的乳铁蛋白接触。
“生物医疗装置”意指经设计为用于人类组织或体液或二者的任何装置。此等装置的实例包括，但不限于，移植片固定模、植入物、导管及眼用镜片。于一较佳实施方案中，此生物医疗装置为一眼用镜片，其包括，但不限于，隐形眼镜或眼内镜。更佳地，该装置为隐形眼镜。
乳铁蛋白为一种人类眼泪中天然存在的蛋白质且为粘膜液体中主要结合铁的蛋白质。乳铁蛋白的功能在于限制可供予细菌的细胞外铁之量。除了其铁螯合效应外，乳铁蛋白亦已知可减低革兰氏阴性细菌的外膜的稳定性。
用于本发明的乳铁蛋白为商业上可取得的，例如人类及牛乳铁蛋白。或者，可使用经已知合成方法所制造的合成乳铁蛋白。较佳地，所使用的乳铁蛋白的纯度为约80％。
乳铁蛋白可经由乳铁蛋白结构中的一个基团与聚合物上的一个基团偶合而结合至生物医疗装置的聚合物表面。此等结合可为一直接反应或一种反应偶合剂以偶合聚合物及乳铁蛋白的反应。直接反应的情况亦可伴随使用一试剂或一种活化聚合物上或乳铁蛋白上的基团使其对乳铁蛋白或聚合物上官能基团具反应性而不需加入偶合剂的反应。
例如，乳铁蛋白上的一或多个胺基团可直接与聚合物上的异硫氰酸酯、异氰酸酯、酰基叠氮化物、N-羟基琥珀酰亚胺酯、磺酰氯、醛、乙二醛、环氧化物、碳酸酯、芳基卤化物、亚胺酸酯或酐基团反应。较佳地，聚合物表面上的羧基团可使用N，N′-羰基二咪唑、碳化二亚胺如1-乙基-3-(3-二甲氨基丙基)碳化二亚胺(“EDC”)、二环己基碳化二亚胺、1-环己基-3-(2-吗啉代乙基)碳化二亚胺、二异丙基碳化二亚胺或其混合物加以活化而与乳铁蛋白的胺基团反应。该碳化二亚胺亦可与N-羟基琥珀酰亚胺或N-羟基硫代琥珀酰亚胺一起使用以形成可与胺反应而形成酰胺的酯。其他可用以促进胺与羧酸反应的试剂包括N-乙基-3-苯基异噁唑鎓-3′-磺酸酯及N，N′-羰基二咪唑。
或者亦可藉由形成可使用如氰基氢硼化钠等的试剂还原形成水解稳定性胺连结的席夫(Schiff)碱，将胺基团偶合至聚合物上。可供使用于此一目的的偶合剂包括(但不仅限于此)：N-羟基琥珀酰亚胺酯类，如二硫代双(丙酸琥珀酰亚胺酯)、3，3′-二硫代双(丙酸硫代琥珀酰亚胺酯)、辛二酸二琥珀酰亚胺酯、辛二酸双(硫代琥珀酰亚胺)酯、酒石酸二琥珀酰亚胺酯等；亚胺酸酯类，包括(但不仅限于此)亚胺己二酸二甲酯(dimethyl adipimate)；二氟苯衍生物，包括(但不仅限于此)1，5-二氟-2，4-二硝基苯；溴官能性醛类，包括(但不仅限于此)谷拉将醛(gluteraldehyde)；以及双环氧化物，包括(但不仅限于此)1，4-丁烷二醇二缩水甘油醚。本领域普通技术人员均可了解亦可使用他种偶合剂，此乃依聚合物表面的官能基而定。
任何具有含适于与根据本发明方法的乳铁蛋白反应的反应性基团的聚合物表面的生物医疗装置均可使用之。本领域普通技术人员均可了解，倘所欲的聚合物表面不含有适当的反应性基团，则可以习知惯用的有机合成方法，将反应性基团并入聚合物中；或者，亦可藉将含有反应性基团的可聚合单体加至用于形成聚合物的单体混合物中，而将反应性基团导入。
有用的聚合物表面的范例为(但不仅限于此)苯乙烯与经取代的苯乙烯、乙烯、丙烯、丙烯酸类与甲基丙烯酸类、N-乙烯基内酰胺、丙烯酰胺类与甲基丙烯酰胺类、丙烯腈、丙烯酸与甲基丙烯酸以及聚胺基甲酸酯类、聚酯类、聚二甲基硅氧烷类及其混合物的聚合物与共聚物所形成的表面。此种聚合物可含有水凝胶和含硅酮的水凝胶。较佳者是使用2-羟乙基甲基丙烯酸酯(“HEMA”)的些微交联的聚合物与共聚物。于此所称的“些微交联”乃是指聚合物有足够低的交联密度，以使得其于室温时是软性且具弹性者。一般而言，一种些微交联的聚合物是每约100个重复单体单元具有约0.1至约1个交联分子。适用的些微交联HEMA聚合物与共聚物的范例包括(但不仅限于此)ETAFILCONTM，以及甲基丙烯酸甘油酯与HEMA的共聚物。还优选使用硅酮水凝胶，特别是由亲水性单体(如N，N-二甲基丙烯酰胺)所得到者。
于制造本发明装置的方法的一个实施方案中，可以任何便利的方法，将欲被涂覆的表面与乳铁蛋白及至少一种偶合剂及/或活化剂接触。举例而言，可将装置置于乳铁蛋白与溶剂的溶液中，并于其中加入偶合剂或活化剂。或者，可先将装置表面以偶合剂或活化剂处理之，然后再将该表面置于乳铁蛋白溶液中，抑或可将乳铁蛋白单独与聚合物表面反应。
本发明适用的溶剂为可溶解乳铁蛋白及/或偶合剂或活化剂者。较佳者，涂覆的程序是于水、醇或其混合物中进行。EDC于水溶液中可展现其效能，故为较佳的活化剂。
偶合剂或活化剂可单独使用，或可结合可稳定化任何所形成的反应性中间体的试剂使用。举例而言，EDC可连同做为稳定剂的N-羟基琥珀酰亚胺一起使用。另外，调整溶液的pH是有必要的，较佳者，将pH调整至约2.0至约9.0，更佳者，将pH调整至约4.0至约7.5。
使用偶合有效量的偶合剂，该量是足以将乳铁蛋白偶合至装置表面上。亦可使用活化有效量的活化剂，该量是足以使乳铁蛋白和聚合物表面彼此反应。偶合剂或活化剂的精确用量是依表面化学以及所选用的试剂而定。一般而言，使用约0.01至约10重量百分比，较佳者约0.01至约5.0，更佳者约0.01至约1重量百分比(以涂覆溶液的重量为基础)的偶合剂。所称的涂覆溶液是指乳铁蛋白与一或多种溶剂、偶合剂、活化剂和缓冲液。涂覆液一般的用量为每一镜片使用约0.1ml至约100ml，较佳者约0.2ml至约80ml，更佳者约0.5ml至约10ml。倘使用活化剂，则每一镜片使用约0.1mg至约100mg，较佳者约1.0至约50mg的活化剂。
于本发明的方法中，所称涂覆有效量的乳铁蛋白意谓当与表面接触时，足可涂覆表面，以使该表面具有所希望的抗微生物特性的量。于隐形眼镜的情形中，一般地，乳铁蛋白用以接触镜片的量是每个镜片约0.1至约100mg，较佳者约2mg至约50mg，而每个隐形眼镜镜片上所形成涂层的量是约0.1至约1000μg。
温度与压力对于本发明方法的影响并不重要，本发明的方法可方便地于室温与常压下进行。所使用的接触时间须足以将表面涂覆至所欲的程度，较佳者，接触时间约为0.5至约24小时。
于接触后，可接着以水或缓冲盐水溶液清洗表面，以移除未反应的乳铁蛋白、偶合剂、活化剂、溶剂与副产物。任选地，可将经涂覆的表面置于水中加热，以萃出残留的涂层、偶合剂、活化剂和副产物，以确保破坏任何可能已经生成的偶合剂-稳定剂络合物。
本领域普通技术人员均了解供制造欲依本发明方法涂覆的表面的聚合物是可含有其他单体与添加剂。例如，可以使用紫外线吸收单体、反应性色调、加工助剂等。
具体实施方式
本发明将更进一步以下列非限制的实例说明之。
实施例1
在35℃下培养所有菌株18小时，之后次培养于10毫升胰胨大豆培养液(TSB；Oxoid)中，或是若为流感嗜血菌时，则次培养于12毫升脑脊髓液(CSF；Oxiod)中。在35℃及无搅拌下于批次培养中将细菌养至静止期18小时，随后在25℃下藉由离心(2060×g)采集，及在10毫升经磷酸盐缓冲的食盐水(PBS；0.137M NaCl，2.6mM KCl，1.5mM KH2PO4，1.66mM Na2HPO4；pH7.4)中清洗三次。最后一次清洗后，细菌经再悬浮于PBS中；在660nm处的光学密度(OD660)为1.0，相当于约1.0×109cfu/ml。
表1
| 菌株 | 菌种 | 来源 |
| Paer1 | 铜绿假单胞菌 | 隐形眼镜引发的急性红眼(CLARE) |
| Paer8 | 铜绿假单胞菌 | 角膜浸润物 |
| 6206 | 铜绿假单胞菌 | 细菌性角膜炎 |
| 6294 | 铜绿假单胞菌 | 细菌性角膜炎 |
| ATCC 15442 | 铜绿假单胞菌 | 环境 |
| ATCC 19660 | 铜绿假单胞菌 | 败血病 |
| Ahyd3 | 嗜水气单胞菌 | CLARE |
| Ecol8 | 大肠杆菌 | CLARE |
| Hinfl | 流感嗜血菌 | CLARE |
| Sliq38 | 液化杀雷氏菌(Serratia liquefaciens) | CLARE |
| Smar5 | 粘质沙雷氏菌 | CLARE |
| Xmal10 | 嗜麦芽狭适应单胞菌(Stenotrophomonasmaltophilia) | CLARE |
为测试蛋白质乳铁蛋白支持细菌生长的能力，在乳铁蛋白存在下进行细菌的存活计数。根据上述方法培养所有十二种菌株的细菌、采集及再悬浮。细菌悬浮液与人体乳乳铁蛋白混合而取得终细菌浓度103cfu/ml及2.5毫克/毫升终乳铁蛋白浓度于终体积200μl。乳铁蛋白浓度经选择以与人类眼泪中的浓度相近。对于各菌株，亦使用负对照组，其于PBS中仅包含细菌(103cfu/μl)。立即分析溶液，或在35℃下培育而无搅拌及在1小时、4小时及24小时的时间间隔中分析。藉由对各悬浮液的对数系列的稀释液涂布至营养性琼脂分析存活数，或若为Hinfl时，涂布至巧克力琼脂以分析存活数。
结果显示于图1中。数据证实乳铁蛋白在25小时培养后并未减少细菌的生长，反而对大多数的菌株诱发生长的增加。值为平均值±标准误差(每一菌株有四个重复组)。以cfu/μl表示的结果为24小时培育者。Hinfl显示4小时后无论在PBS或乳铁蛋白中均无存活数而从图式中省略。
实施例2
以HEMA为基质的水凝胶镜片在35℃下以2.5mg/ml初乳乳铁蛋白处理18小时。处理后，使用经碘-125标记的乳铁蛋白分析吸附至镜片表面的乳铁蛋白的量。镜片以PBS清洗及使用υ-计数器测量乳铁蛋白的量。每平方毫米镜片表面约有17ng乳铁蛋白或每一镜片约有1μg吸附至表面上。
在35℃下于500μl细菌悬乳液中培育三个镜片10分钟，再于1mlPBS中清洗三次。使用二种测量细菌粘附的方法：细菌总数及经粘附的存活细菌数。为计算总数，镜片以结晶紫染色5分钟，于PBS中清洗二次并在显微镜下检视。计算各镜片中5个区域的细菌数及转换为每平方毫米的细菌数。为计算存活数，于2ml PBS中将镜片浸软及随后经一系列的稀释并将等份样品涂布至琼脂盘上。在35℃下培育该盘18小时后，计算每平方毫米的镜片的细菌数。菌株Paer1的结果示于表2。
表2
| 处理 | 细菌生长的减少(％) |
| 吸附乳铁蛋白的镜片 | 50 |
| 无涂覆乳铁蛋白的镜片 | -7 |
经乳铁蛋白涂覆的镜片上的存活数相较于总数显著减少。由于如实施例1所示，溶液中仅含乳铁蛋白无法显著减少回收的细菌，所以此结果是不可预期的。
实施例3
将于16.6ml去离子水中的50mg牛初乳乳铁蛋白(Sigma)及20个水凝胶隐形镜片加至0.30g 1-[3-(二甲氨基)丙基]-3-乙基碳化二亚胺盐酸盐“(EDC)”中。室温下搅拌21小时后，镜片以多变化的溶液漂洗24小时。以4M胍盐酸盐萃取去除每一镜片3μg未经结合的乳铁蛋白。以浓HCl水解及后续的氨基酸分析显示每一镜片有63μg未经结合的乳铁蛋白。
在35℃下于500μl细菌悬浮液中培育三个镜片10分钟，再于1mlPBS中清洗三次。如实施例2所述进行计算经粘附的细菌总数及经粘附的存活细菌数。菌株Paer1的结果示于表3。在粘附至经乳铁蛋白共价涂覆的隐形眼镜之后的生长减少。
表3
| 细菌菌株 | 细菌生长的减少％-不含乳铁蛋白的镜片 | 细菌生长的减少％-含乳铁蛋白的镜片 |
| Paer1 | 0.4 | 98 |
数据显示经共价键结的乳铁蛋白对细菌生长较先前所观察到经吸附/经吸收至隐形眼镜表面的乳铁蛋白者有较大的冲击。
实施例4
将铜绿假单胞菌6294、铜绿假单胞菌ATCC 15442及铜绿假单胞菌6206加至含共价粘附的乳铁蛋白的隐形眼镜并如实施例2所述进行分析。结果显示这些菌株亦显出暴露至经共价连接到隐形眼镜表面的乳铁蛋白后细菌生长的减少。
表4
| 细菌菌株 | 细菌生长的减少％-含乳铁蛋白的镜片 |
| 6294 | 98 |
| ATCC 15442 | 95 |
| 6206 | 90 |
这些结果证实共价结合至水凝胶隐形眼镜的乳铁蛋白能够防止不同细菌菌株的生长。
比较例
在35℃下，小鸡眼睛白色溶菌酶(2.0mg/ml)及牛初乳乳铁蛋白(2.5mg/ml)各吸附至不同的以HEMA为基质的水凝胶镜片18小时。培育及于PBS中清洗三次后，镜片在35℃下于500μl细菌悬浮液中培育10分钟，再于1ml PBS中清洗三次。使用实施例2的二种测量细菌粘附的方法；粘附的细菌总数及经粘附的存活细菌数。菌株Paer1的结果显示于表5。
表5
| 细菌菌株 | 粘附的减少％ | |
| 溶菌酶涂层 | 乳铁蛋白-涂层 | |
| Paer1 | 11％ | 50％ |
由表5可看出，吸附至隐形眼镜的溶菌酶仅减少细菌粘附11％及此存活率的减少相较于总数在统计学上并无显著性。另一方面，经乳铁蛋白吸附的镜片在起始粘附后显示于存活率上有显著的减少(p＜0.05)。因此，并非所有的泪水蛋白质或所有含胺分子均在起始粘附后于细菌生长的能力上表现出显著的减少。
Claims (15)
1.一种生物医疗装置，其中该生物医疗装置的至少一个表面含有与其共价结合的乳铁蛋白。
2.如权利要求1的装置，其中表面另含有一选自下列的聚合物：水凝胶、含硅酮的水凝胶、2-羟基乙基异丁烯酸酯的聚合物与共聚物以及其混合物。
3.如权利要求2的装置，其中的聚合物为水凝胶。
4.如权利要求2的装置，其中的聚合物为含硅酮的水凝胶。
5.如权利要求2的装置，其中的聚合物为2-羟基乙基异丁烯酸酯的聚合物或共聚物。
6.如权利要求5的装置，其中2-羟基乙基异丁烯酸酯的共聚物为每100个重复单体单位中具有0.1到1个交联分子的2-羟基乙基异丁烯酸酯共聚物。
7.一种隐形眼镜，其至少一个表面含有与其共价结合的乳铁蛋白。
8.如权利要求7的隐形眼镜，其中该表面另含有一选自下列的聚合物：水凝胶、含硅酮的水凝胶、2-羟基乙基异丁烯酸酯的聚合物与共聚物以及其混合物。
9.如权利要求8的隐形眼镜，其中的聚合物为水凝胶。
10.如权利要求8的隐形眼镜，其中的聚合物为含硅酮的水凝胶。
11.如权利要求8的隐形眼镜，其中的聚合物为2-羟基乙基异丁烯酸酯的聚合物或共聚物。
12.如权利要求11的隐形眼镜，其中2-羟基乙基异丁烯酸酯的共聚物为每100个重复单体单位中具有0.1到1个交联分子的2-羟基乙基异丁烯酸酯共聚物。
13.一种制造装置的方法，其包括使生物医疗装置的至少一个表面与涂覆有效量的乳铁蛋白接触的步骤，其中所述的生物医疗装置为隐形眼镜。
14.如权利要求13的方法，其中另包括将该生物医疗装置与偶合有效量的偶合剂接触。
15.如权利要求13的方法，其中另包括将该生物医疗装置与活化有效量的活化试剂接触。
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| Application Number | Priority Date | Filing Date | Title |
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| US09/165,562 US6592814B2 (en) | 1998-10-02 | 1998-10-02 | Biomedical devices with antimicrobial coatings |
| US09/165562 | 1998-10-02 |
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| US (1) | US6592814B2 (zh) |
| EP (1) | EP0990924B1 (zh) |
| JP (1) | JP4425384B2 (zh) |
| KR (1) | KR100660756B1 (zh) |
| CN (1) | CN1151196C (zh) |
| AR (1) | AR020694A1 (zh) |
| AU (1) | AU766369B2 (zh) |
| BR (1) | BR9904394A (zh) |
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| DE (1) | DE69902330T2 (zh) |
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Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001056627A1 (en) * | 2000-01-12 | 2001-08-09 | Am-Pharma B.V. | Medical device coated with antimicrobial peptides |
| WO2002064183A1 (en) * | 2001-02-09 | 2002-08-22 | Johnson & Johnson Vision Care, Inc. | Biomedical devices with antimicrobial cationic peptide and protein coatings |
| KR20030023119A (ko) * | 2001-09-12 | 2003-03-19 | 이창 | 기능성 콘택트 렌즈 |
| US7402318B2 (en) | 2001-11-14 | 2008-07-22 | Novartis Ag | Medical devices having antimicrobial coatings thereon |
| WO2003057712A2 (en) * | 2001-12-28 | 2003-07-17 | Campina B.V. | Humanized lactoferrin and uses thereof |
| US6846892B2 (en) * | 2002-03-11 | 2005-01-25 | Johnson & Johnson Vision Care, Inc. | Low polydispersity poly-HEMA compositions |
| AU2003225073A1 (en) | 2002-04-18 | 2003-11-03 | The University Of Iowa Research Foundation | Methods of inhibiting and treating bacterial biofilms by metal chelators |
| US7998699B2 (en) | 2002-08-15 | 2011-08-16 | University Of South Florida | Early detection of pathogens in blood |
| US7513093B2 (en) | 2002-10-04 | 2009-04-07 | Ethicon, Inc. | Method of preparing a packaged antimicrobial medical device |
| US8112973B2 (en) | 2002-10-04 | 2012-02-14 | Ethicon, Inc. | Method of making a packaged antimicrobial suture |
| US9597067B2 (en) | 2002-10-04 | 2017-03-21 | Ethicon, Inc. | Packaged antimicrobial medical device and method of preparing same |
| US8133437B2 (en) | 2002-10-04 | 2012-03-13 | Ethicon, Inc. | Method of preparing an antimicrobial packaged medical device |
| US9474524B2 (en) | 2002-10-04 | 2016-10-25 | Ethicon, Inc. | Packaged antimicrobial medical device having improved shelf life and method of preparing same |
| US20040120982A1 (en) * | 2002-12-19 | 2004-06-24 | Zanini Diana | Biomedical devices with coatings attached via latent reactive components |
| US7368127B2 (en) * | 2002-12-19 | 2008-05-06 | Johnson & Johnson Vision Care, Inc. | Biomedical devices with peptide containing coatings |
| US7282214B2 (en) | 2002-12-19 | 2007-10-16 | Johnson & Johnson Vision Care, Inc. | Biomedical devices with antimicrobial coatings |
| PL1654387T3 (pl) | 2003-08-15 | 2009-10-30 | Univ South Florida | Materiały i sposoby do wychwytywania patogenów i usuwania kwasu aurynotrikarboksylowego z próbki |
| WO2005018701A1 (en) * | 2003-08-25 | 2005-03-03 | Kane Biotech Inc. | Synergistic antimicrobial compositions and methods of inhibiting biofilm formation |
| US7314857B2 (en) | 2003-08-25 | 2008-01-01 | Kane Biotech Inc. | Synergistic antimicrobial compositions and methods of inhibiting biofilm formation |
| US20050163825A1 (en) * | 2004-01-27 | 2005-07-28 | Naidu A. S. | Lactoferrin-treated filament materials |
| WO2005079582A1 (en) * | 2004-02-24 | 2005-09-01 | Campina B.V. | Antimicrobial lactoferrin compositions for surfaces, cavities, and foodstuff |
| US7144992B2 (en) * | 2004-04-01 | 2006-12-05 | Kane Biotech Inc. | Synergistic antimicrobial compositions and methods for reducing biofilm formation |
| US7399742B2 (en) | 2004-07-23 | 2008-07-15 | Depuy Spine, Inc. | Anti-osteolytic therapy involving adiponectin |
| US8715733B2 (en) | 2004-07-23 | 2014-05-06 | DePuy Synthes Products, LLC | Enhanced adipose tissue |
| US7217425B2 (en) * | 2004-07-23 | 2007-05-15 | Depuy Spine, Inc. | Autologous coatings for implants |
| US7857849B2 (en) * | 2004-10-05 | 2010-12-28 | The Board Of Trustees Of The Leland Stanford Junior Iniversity | Artificial corneal implant |
| US7468150B2 (en) * | 2005-09-26 | 2008-12-23 | Board Of Trustees Of Michigan State University | Synthesis of conducto-magnetic polymers as nano-transducers in biosensor design |
| JP5017530B2 (ja) * | 2005-11-17 | 2012-09-05 | 株式会社アップウェル | 眼科用組成物およびコンタクトレンズ用組成物 |
| US20070254006A1 (en) * | 2006-02-15 | 2007-11-01 | Massachusetts Institute Of Technology | Medical Devices and Coatings with Non-Leaching Antimicrobial Peptides |
| GB0616580D0 (en) * | 2006-08-21 | 2006-09-27 | Novathera Ltd | Composite material |
| US8673335B2 (en) * | 2006-09-13 | 2014-03-18 | Southeastern Medical Technologies, Llc | Methods and compositions for sealing and adhering biological tissues and medical uses thereof |
| US8852689B2 (en) * | 2007-05-29 | 2014-10-07 | Innova Dynamics, Inc. | Surfaces having particles and related methods |
| US20090149673A1 (en) * | 2007-12-05 | 2009-06-11 | Semprus Biosciences Corp. | Synthetic non-fouling amino acids |
| WO2009085096A2 (en) * | 2007-12-05 | 2009-07-09 | Semprus Biosciences Corporation | Non-leaching, non-fouling antimicrobial coatings |
| US8178120B2 (en) * | 2008-06-20 | 2012-05-15 | Baxter International Inc. | Methods for processing substrates having an antimicrobial coating |
| US8753561B2 (en) * | 2008-06-20 | 2014-06-17 | Baxter International Inc. | Methods for processing substrates comprising metallic nanoparticles |
| US8277826B2 (en) | 2008-06-25 | 2012-10-02 | Baxter International Inc. | Methods for making antimicrobial resins |
| US20090324738A1 (en) * | 2008-06-30 | 2009-12-31 | Baxter International Inc. | Methods for making antimicrobial coatings |
| US8614189B2 (en) * | 2008-09-24 | 2013-12-24 | University Of Connecticut | Carbon nanotube composite scaffolds for bone tissue engineering |
| US20100227052A1 (en) * | 2009-03-09 | 2010-09-09 | Baxter International Inc. | Methods for processing substrates having an antimicrobial coating |
| FR2945180B1 (fr) | 2009-05-07 | 2013-02-22 | Arjowiggins Security | Support d'information presentant des proprietes antivirales et son procede de fabrication |
| US20110225809A1 (en) * | 2010-03-17 | 2011-09-22 | Alan Francis Daher | Apparatus for removably attaching an item to a surface |
| EP2569004A4 (en) | 2010-05-10 | 2016-01-20 | Univ Connecticut | LACTOFERRIN-BASED BIOMATERIALS FOR TISSUE REGENERATION AND MEDICATION DELIVERY |
| FR2967074B1 (fr) * | 2010-11-08 | 2013-06-28 | Arjowiggins Security | Compositions fluides aptes a former un revetement presentant des proprietes antivirales |
| US10245025B2 (en) | 2012-04-06 | 2019-04-02 | Ethicon, Inc. | Packaged antimicrobial medical device having improved shelf life and method of preparing same |
| US20140088381A1 (en) * | 2012-09-26 | 2014-03-27 | Google Inc. | Facilitation of tear sample collection and testing using a contact lens |
| US20140154297A1 (en) | 2012-10-30 | 2014-06-05 | Baxter Healthcare S.A. | Antimicrobial substrates and methods for processing the same |
| EP2994174A1 (en) | 2013-05-06 | 2016-03-16 | Abbott Cardiovascular Systems Inc. | A hollow stent filled with a therapeutic agent formulation |
| US10816823B2 (en) | 2015-05-04 | 2020-10-27 | École Polytechnique Fédérale de Lausanne | Ophthalmic contact lens with compressible affinity matrix |
| WO2017132573A1 (en) | 2016-01-27 | 2017-08-03 | Sinopsys Surgical, Inc. | Paranasal sinus access implant devices and related products and methods |
| US11376311B2 (en) | 2017-11-02 | 2022-07-05 | Colorado Seminary, Owner and Operator of University of Denver | Methods of treating microbial infection and inflammation |
| CN108295320B (zh) * | 2018-01-25 | 2019-12-24 | 武汉大学 | 一种植入式传感器表面抗污涂层的制备及应用 |
| US12022583B2 (en) | 2020-07-10 | 2024-06-25 | Asiatelco Technologies, Inc. | Portable devices, systems and methods with automated heat control assembly |
| US11512818B2 (en) | 2020-07-10 | 2022-11-29 | Junming Ding | Multi-mode portable lighting device with novel battery charging unit |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4184849A (en) | 1977-12-05 | 1980-01-22 | Technicon Instruments Corporation | Mixed agglutination |
| US4433111A (en) | 1980-10-14 | 1984-02-21 | Kelvin Lenses Limited | Fluorine-containing hydrogel-forming polymeric materials |
| US4895566A (en) | 1986-07-25 | 1990-01-23 | C. R. Bard, Inc. | Coating medical devices with cationic antibiotics |
| US4846844A (en) * | 1987-08-31 | 1989-07-11 | Eli Lilly And Company | Antimicrobial coated implants |
| LU86987A1 (fr) * | 1987-09-07 | 1989-04-06 | Glaverbel | Microbilles de verre a proprietes bacteriostatiques,procede de fabrication de telles microbilles |
| US5571697A (en) * | 1989-05-05 | 1996-11-05 | Baylor College Of Medicine Texas Medical Center | Expression of processed recombinant lactoferrin and lactoferrin polypeptide fragments from a fusion product in Aspergillus |
| GB9002422D0 (en) | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
| US5447914A (en) | 1990-06-21 | 1995-09-05 | Emory University | Antimicrobial peptides |
| JPH06506197A (ja) | 1991-03-01 | 1994-07-14 | ワーナー−ランバート・コンパニー | 活性剤を表面に結合して含有する口腔および身体衛生物品 |
| JPH04334310A (ja) * | 1991-05-01 | 1992-11-20 | Ichimaru Pharcos Co Ltd | 過酸化脂質生成抑制剤 |
| CA2122251C (en) * | 1991-11-05 | 1998-02-03 | Yu-Chin Lai | Wettable silicone hydrogel compositions and methods for their manufacture |
| US5217493A (en) * | 1992-03-11 | 1993-06-08 | Board Of Regents, The University Of Texas System | Antibacterial coated medical implants |
| TW228529B (zh) | 1992-12-23 | 1994-08-21 | Ciba Geigy | |
| US5472703A (en) | 1993-03-02 | 1995-12-05 | Johnson & Johnson Vision Products, Inc. | Ophthalmic lens with anti-toxin agent |
| US5328954A (en) | 1993-04-16 | 1994-07-12 | Icet, Inc. | Encrusting and bacterial resistant coatings for medical applications |
| US5340583A (en) | 1993-05-06 | 1994-08-23 | Allergan, Inc. | Antimicrobial lenses and lens care systems |
| US5514732A (en) | 1993-07-22 | 1996-05-07 | Johnson & Johnson Vision Products, Inc. | Anti-bacterial, insoluble, metal-chelating polymers |
| US5549894A (en) | 1994-01-18 | 1996-08-27 | Allergan, Inc. | Disinfecton formulations and methods using D-enantiomeric anti-microbial peptides |
| JPH07316069A (ja) * | 1994-05-24 | 1995-12-05 | Tokushu Meneki Kenkyusho:Kk | 日和見感染症予防用または治療用組成物 |
| JP3204848B2 (ja) * | 1994-08-09 | 2001-09-04 | 株式会社東芝 | レベル変換回路及びこのレベル変換回路を用いてレベル変換されたデータを出力する方法 |
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| CN1254729A (zh) | 2000-05-31 |
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| US20020068013A1 (en) | 2002-06-06 |
| AU5018599A (en) | 2000-04-06 |
| AU766369B2 (en) | 2003-10-16 |
| BR9904394A (pt) | 2000-11-14 |
| EP0990924A1 (en) | 2000-04-05 |
| SG91832A1 (en) | 2002-10-15 |
| AR020694A1 (es) | 2002-05-22 |
| DE69902330T2 (de) | 2003-01-09 |
| EP0990924B1 (en) | 2002-07-31 |
| JP2000187187A (ja) | 2000-07-04 |
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| US6592814B2 (en) | 2003-07-15 |
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| CA2284364A1 (en) | 2000-04-02 |
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| C56 | Change in the name or address of the patentee |
Owner name: JOHNSON & JOHNSON VISION PROTECTION COMPANY Free format text: FORMER NAME OR ADDRESS: JOHNSON + JOHNSON VISION PRODUCTS, INC. |
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| CP03 | Change of name, title or address |
Address after: American Florida Patentee after: JOHNSON & JOHNSON VISION CARE, Inc. Address before: American Florida Patentee before: INNOTECH, Inc. |
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| TR01 | Transfer of patent right |
Effective date of registration: 20050401 Address after: New South Wales, Australia Patentee after: Eye Institute Address before: American Florida Patentee before: JOHNSON & JOHNSON VISION CARE, Inc. |
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| CX01 | Expiry of patent term |
Granted publication date: 20040526 |
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| CX01 | Expiry of patent term |