CN102256627A - 染料溶液 - Google Patents
染料溶液 Download PDFInfo
- Publication number
- CN102256627A CN102256627A CN2009801515483A CN200980151548A CN102256627A CN 102256627 A CN102256627 A CN 102256627A CN 2009801515483 A CN2009801515483 A CN 2009801515483A CN 200980151548 A CN200980151548 A CN 200980151548A CN 102256627 A CN102256627 A CN 102256627A
- Authority
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- China
- Prior art keywords
- preparation
- syringe
- blue
- dyestuff
- test kit
- 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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- 239000000203 mixture Substances 0.000 claims description 23
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Abstract
本发明涉及用于对人或动物眼睛中的内界膜(ILM)和/或视网膜前膜(ERM)进行选择性染色的生物相容的、非细胞毒性的水基制剂;以及包含根据本发明的所述水基制剂的试剂盒。
Description
技术领域
本发明涉及用于对人或动物眼睛中的内界膜(ILM)和/或视网膜前膜(ERM)进行选择性染色的生物相容性的水基制剂;以及包含根据本发明的生物相容性的水基制剂的试剂盒。
背景技术
由于预期寿命延长等原因,眼睛的疾病,例如白内障、青光眼、年龄相关性黄斑变性和糖尿病性视网膜病变以及视网膜改变或视网膜脱落等不断增加。为治疗这些以及其他眼疾,经常需要实施玻璃体切除术。在实施该手术时必须确保视网膜尽可能不受损伤。为此所需的预防措施则是,在实施玻璃体切除术时移除视网膜的内界膜(必要时也可移除视网膜前膜),以减轻黄斑可能承受的视网膜牵引力。为此,要用解剖钳将所述膜从视网膜上剥下。外科医生必须能够尽可能精确地将视网膜与需要剥离的膜区分开。为此,应通过尽可能特别的染色方式对需剥离的膜进行染色,从而使其清晰可见。适合用于染色的染料必须满足许多标准。它必须具有生物相容性、无毒,而且不能损伤细胞,它应当可溶于水,应当能够进行尽可能特殊的染色,并且又能轻易地被冲洗掉。虽然对于用来对所述膜进行染色的染料及方法已有所阐述,但这些染料及方法却并不令人满意。
例如,US7,014,991号专利中描述了一种对人眼的结构(okularenStruktur)进行染色的方法,在该方法中,染色是通过将染料靛蓝二磺酸盐(Indigotindisulfat)注入相应组织中的方式来实现的。然而,靛蓝二磺酸盐具有细胞毒性。
其他染料,如亮蓝G (Brillantblau G)、艳蓝R(Brilliant Blau R)、专利蓝V(Patentblau V)或亚甲蓝同样也被建议用于眼睛染色。
在玻璃体切除术或外科手术中,眼眶要用冲洗液来冲洗。目前,现已公知的染料溶液的问题在于,染料溶液要用冲洗液来分散、稀释并洗掉。这种做法存在诸多缺点。一方面,冲洗液被着色时,会使外科医生的视线变得模糊。另一方面,所需使用的染料溶液量要比对膜进行染色所需的量多得多。
为克服这一缺点,已有人建议,在染料溶液中添加诸如透明质酸等能够增强染料粘度的增稠剂。粘度增加会由于空间位阻现象而使染料的活动性降低,从而使染料不至于强烈地溶入冲洗液中,因而更容易到达需要染色的膜附近。但是,染料溶液粘度大也会产生这样的结果,即染料因此变得难以渗入膜中,从而使需要使用的染料溶液量多于仅对膜进行染色所需的溶液量。
因此,本发明的一个目的在于提供一种能够对膜进行特殊染色,特别是能够对人眼或动物眼睛中诸如ILM和/或ERM等需要剥离的膜有选择性地加以染色的制剂,该种制剂施用方便,其能够在施用之后立即游走到膜并分散于其上,而不会对冲洗液造成强烈染色。此外,本发明提供的制剂应当既不会使局部视网膜发炎,也不会损伤视网膜,它应不具有细胞毒性,而是能够与细胞相容的。
这一目的是通过如权利要求,特别是权利要求1中所限定的制剂来实现的。
各从属权利要求包含了本发明的其他有利改进方案。
发明内容
令人吃惊的是,我们发现:一种包含至少一种选自三苯甲烷染料和/或偶氮染料和/或花青染料和/或天然染料(如花青素、花色素等)等的染料中的制剂,在其密度调制到1.01g/cm3至1.5g/cm3,优选为1.01g/cm3至1.3g/cm3的范围内时,就能够有选择地对ILM和/或ERM进行有效染色。
我们还发现,在对眼睛实施外科手术的情况下,密度比水大的染色溶液在被注入到眼眶区域中时会下沉(因而避免了它与冲洗液很快混合的现象),并且在下沉之后会分散到膜上并使其染色。这样就避免了染料溶液被冲洗液过快地冲洗掉,同时还防止了染料模糊视野。
根据本发明的制剂是水基的,它以水作溶剂,然而,在必要时也可以包含一定份额的其他溶剂,只要它能够与水均匀混合并且具有生物相容性。这里,可以考虑那些同样应用于医疗领域中的一元或多元醇。如果采用其他的溶剂,那么该溶剂尤其优选为乙二醇或丙三醇。也可以考虑使用上述溶剂的混合物。如果将溶剂掺入到水中,那么该溶剂的重量百分比不应超过20%,优选不超过10%。所述制剂优选为等渗溶液。
除了作为溶剂的水以及染料(下文将对其详细说明)之外,根据本发明的制剂还包含一种重要的组分,即密度调节介质。这种调节介质必须具有生物相容性且不具有细胞毒性,它必须能够与水均匀混合,而且在可能添加微量的诸如乙醇等溶解调和剂的情况下也必须能够与水均匀混合,从而使形成的溶液清澈透明。另外,它必须能够与染料相容,也就是说,它不能对染料的可溶性产生明显的影响。为避免由于渗透作用而导致组织损伤,在调制制剂时还需观察渗透压。渗透压应在280-330mosmol/L的范围内,优选为300mosmol/L。
因此,可以考虑能够与水相容且密度比水的密度更大的液体。用于增大密度的优选介质是重水D2O,利用重水可把密度值调节到期望的范围内。重水的特点是具有出色的相容性。其在水中的浓度达到20%时仍然能为真核细胞所接受,并且不会导致在应用区域内发炎。它能够以任意的浓度与水混合而不会趋于沉淀或析出,而且它与水在可溶性方面并无可证明的区别。在制剂中可对重水的份额适当调节,从而使期望的密度值为1.01g/cm3至1.5g/cm3,优选为1.01g/cm3至1.3g/cm3。重水的量还取决于其他的掺合物;通过简单的实验或计算方式可以确定出合适的重水量。若重水是密度调节介质,则优选采用5-20%的量。由于两种组分均具有良好的可混合性,因而制备带重水的制剂也是非常简单的,通过混合即可方便地实现。因此,用水、重水和染料可以简单、快速地制备出永久稳定且非常适合于有选择性地对膜进行染色这一目的的制剂。
另一种可用于调节密度的介质是二糖或多糖。多糖适用于增大密度,而且很容易得到。另外,它们在毒理学方面令人放心,并具有生物相容性。这里,多糖是指由两个以上,优选五个以上,特别优选十个以上的糖单元(Saccharideinheit)所构成的分子。尽管单糖与二糖通常也能增大密度,但是根据本发明,只有非还原性二糖才被用来增大密度。使用单糖与还原性二糖可能导致非预期的结果,例如,若所使用的单糖或还原性二糖的量达到用于增大密度所需的时则可能会有细胞毒性。与本发明相适宜的非还原性二糖是蔗糖或海藻糖。而诸如羟乙基淀粉和葡聚糖等可溶性淀粉衍生物则可被称为适合的多糖。适合的多糖是那些中性的、没有还原性且不溶于水溶液的化合物。
用于增大密度的其他介质还有中性的聚合物,如聚醚、聚乙烯醇、聚酯、聚丙烯酸共聚物以及聚乙烯吡咯烷酮等。
而且上述介质的混合物,例如由重水与一种或多种多糖组成的混合物也很适合用来调节根据本发明的制剂的密度。
重水和/或其他或另一调节密度的介质的量是这样选定的,即其应使得所形成的制剂的密度须处于1.01g/cm3至1,5g/cm3,优选1.01g/cm3至1,3g/cm3的范围内。在这里,制剂的密度可用本领域技术人员所熟知的通用方法来确定。
事实证明,当密度增大到1.01g/cm3时即已产生预期效果,即,染料溶液在施用后会迅速下沉入眼眶中,然后能在那里分散到膜上。由此就实现了有选择性地对膜进行染色且不降低手术医生视线的目的。若染料制剂相对于水的密度差低于0.01g/cm3,则不足以使染料制剂能够目标明确地下沉。此时,染料制剂会像现有技术中的制剂一样缓慢地下沉,并导致出现上文所述的问题。当制剂的密度大于1.5g/cm3时,则会因为这一密度而使极为敏感的视网膜受损。
根据本发明的制剂的另一重要组分是染料。这样的化合物,即能够对ILM和/或ERM有针对性地进行特殊染色,从而能够在光学上将膜与视网膜区分开的化合物可被用作染料。另外,染料必须能够溶于水或者由水和另一溶剂组成的混合物中。它既不能具有毒性,特别是不能具有细胞毒性或者说不能对细胞有破坏性,而且它还不能导致视网膜受损,或者像吲哚菁绿(ICG)或台盼蓝(Trypanblau)一样通过光化学反应而产生毒理作用。另外,它应当具有良好的染色能力,以便能够保持使用少量的染料。
事实证明有利的是,染料选自由诸如亮蓝G、艳蓝R、艳蓝FCF、专利蓝V、溴酚蓝、里沙明绿SF、里沙明绿G、坚固绿、甲基绿、酸性艳绿、考马斯紫R200、玫苯胺(Rosanillin)等三苯甲烷染料组成的组;由诸如橙色G、丽春红2R、变色酸6R、丽春红6R、柠檬黄、偶氮荧光桃红、丽春红B、伊文思蓝、芝加哥蓝等偶氮或叠氮染料组成的组;由诸如3,3′-二乙基硫菁碘盐((3,3′-Diethylthiacyanine)iodide)、3,3′-二乙基噻碳菁碘化物((3,3-Diethylthiacarbocyanine iodide))、3,3′-二乙基-9-甲基噻碳菁碘化物((3.3′-Diethyl-9-methylthiacarbocyanine iodide))、1,1′-二乙基-4,4′-菁碘化物(1,1′-Diethyl-4,4′-cyanine iodide))等花青染料组成的组,和/或由诸如苔红素、散沫花素、靛蓝、角黄素、苏木素、靛蓝二磺酸钠等天然染料组成的组;和/或花青素,以及上述染料的混合物,也就是说由上述组之一的多种成份所组成的混合物以及由不同组中的成份所组成的混合物。
优选采用亮蓝G、艳蓝R、艳蓝FCF、专利蓝V、甲基绿、考马斯紫R200、溴酚蓝和/或芝加哥蓝。在三苯甲烷染料中,特别优选亮蓝G、考马斯紫R200和芝加哥蓝。在亮蓝染料中,优选亮蓝G,因为它具有特别出色的染色能力。在使用时,其浓度可以低于0.3g/L。即便是这样的低浓度,已足以对ILM/ERM有选择性地进行染色。其他适合的染料为里沙明绿SF、里沙明绿G、坚固绿、酸性艳绿、橙色G、丽春红2R、变色酸6R、丽春红6R、柠檬黄、偶氮荧光桃红、丽春红B、芝加哥蓝、伊文思蓝、3,3′-二乙基硫菁碘盐、3,3′-二乙基噻碳菁碘化物、3,3′-二乙基-9-甲基噻碳菁碘化物、1,1′-二乙基-4,4′-菁碘化物、苔红素、散沫花素、靛蓝、角黄素、苏木素、靛蓝二磺酸钠以及不同的花青素。
为进一步改善根据本发明的制剂的有利特性,还可在制剂中另外添加粘度调节介质。事实表明,添加用于增加根据本发明的制剂粘度的介质可以有改善凝聚性的效果,从而进一步强化根据本发明的制剂所包含的优点。由于粘度增大的缘故,制剂在下沉至膜的过程中将相互粘结在一起,这样那些本就由于密度较大因而下沉较快的制剂在施用后其分散到冲洗液中的量将得以进一步减少。不过,由于通过调整密度已经获得了有利的效果,因此一定不能将粘度增加很多,以免导致现有技术中存在的问题。粘度稍稍提升就会使得从施用仪器中出来的液滴形成更为稳定的单元,因而更加不易被稀释,这样,包含于制剂中的染料就难以被冲刷出来。因此,只有在施用之处,染料才会通过膜上的毛细作用被释放出来,从而将膜染色。通过这种方式可将染料目标明确地施加到膜上。
作为调节粘度的生物相容性介质,亦即用来调节粘度的介质,可以采用一种或多种选自下列组的介质:聚醚、聚乙烯醇、聚酯、聚丙烯酸共聚物、聚乙烯吡咯烷酮以及其他聚合物;诸如丙三醇、丙二醇、丁二醇等多元醇;如甲基纤维素、黄原胶、淀粉、透明质酸以及它们各自的衍生物、硫酸软骨素、硫酸钠等溶于水的纤维素衍生物。作为粘度调节介质也可以使用那些不仅能够增加粘度,而且还能同时增大密度的介质。在这种情况下,重要的是需注意两个参数亦即粘度和密度处于期望范围内。换言之,所投入使用的用来影响密度并调节粘度的介质的量不得使形成的制剂的密度大于1.5g/cm3。当然,本领域技术人员可轻易地(必要时辅以常规实验手段)地确定出合适的用量,并对制剂中的相应值进行调节。
特别适合用作粘度调节剂的是那些与本发明所用的染料之间具有一定的亲和力,并且以铺展能力大为特点的介质。令人惊讶的是,我们发现丁二醇是一种可用来调节粘度,并具有出色铺展能力的介质。因此,添加丁二醇可使得制剂在施用后向下沉降,而且,一旦其抵达膜即会在彼处铺展开来并使膜迅速着色。这一点无需依赖理论而可以这样来解释:一方面,丁二醇与膜具有亲和力,而另一方面则由于亲脂族的缘故,使得丁二醇能够很好地吸收染料。当含有丁二醇与染料的制剂到达膜时,丁二醇将使得染料能够迅速地分散到膜上。
根据本发明的制剂的粘度优选调节成这样,即,使得在温度为25℃且剪切率为10s-1时的剪切粘度处于1至500mPas的范围内。优选将温度为25℃且剪切率为10s-1时的剪切粘度调节到50至275mPas的范围内。粘度的调节可以利用已经提到的粘度调节剂来实现。如果粘度在前面指明的测量条件下处于1至500mPas的范围内,那么根据本发明的制剂所能达到的效果将明显得以增强。包含有能够选择性地进行染色的染料制剂沉降迅速,而且其染料被冲洗液洗去的程度可忽略不计。因此,染料只有在施用之处才会因膜上的毛细管作用而释出,从而对膜进行染色。如果粘度在前文指明的测量条件下小于1mPas,那么就不能进一步增强根据本发明的制剂的快速沉降效果。可能至少有一部分冲洗液在对膜染色之前就被冲洗液除去,因而不能用于膜进行染色。相反,如果在温度为25℃且剪切率为10s-1时的动态粘度高于500mPas,则制剂粘度过高,因而染料将不再理想地从形成的液滴中自由析出。这样会显著降低染料制剂的铺展能力,亦即有助于快速、均匀地对膜进行染色的能力。膜将不能理想地被染料制剂润湿,因而也就无法得以明显着色。如果温度为25℃且剪切率为10s-1时的动态粘度处于50至275mPas的范围内,那么就可取得特别好的染色效果。
我们发现,在将染料溶液注入眼睛中时有可能会出现问题。如果利用通用注射器注入染料溶液,则在注射时达到的压力太高,因而可能使染料陷入视网膜之后。
根据本发明,这一问题是通过采用这样的注射器来解决的,即采用针头直径、针筒直径与针头直径的比例以及长宽比例被调整成能够避免出现损伤的注射器。根据本发明,为了尽可能减小对眼睛造成的损害,优选采用针头直径极小的注射器。此外,将针筒直径调整成与针尖直径相适配,从而尽可能避免出现文丘里效应。换言之,设计用于施药的注射器的针筒直径亦应尽可能地小,从而使针筒直径与针头直径之间的比例处于10至2∶1至0.2,优选20∶1至4∶1,特别优选16∶1至8∶1的范围内。另外,注射器针筒的长宽比,也即是说针筒长度与针筒直径之比应在15-5∶1的范围内。
因此,本发明的另一主题是试剂盒,该包含带有针筒及针头的注射器以及用于对人眼或动物眼睛中的ILM和/或ERM有选择性地进行染色的染料制剂,其中,针筒的直径与针头的直径之间的比例处于10至2∶1至0.2,优选20∶1至4∶1,特别优选16∶1至8∶1的范围内。针筒长度与针筒直径之间的比例关系优选处于15至5∶1的范围内。因此,该试剂盒具有这样一种作为本发明组成部分的注射器,即其针筒直径被调整成与针头的直径相适配。我们发现,在直径的比例更小时,在针头之前的内部空间中不会形成压力,从而可确保均匀地注入溶液,也就是说以相同的压力及稳定不变的速度来注入根据本发明的制剂。所述试剂盒优选包含如前所述的根据本发明的染料制剂。
对于该试剂盒,确切地说,对于该试剂盒的注射器而言,优选采用19至27号针头,特别优选采用23或25号针头。19至27号针头适合用于对眼睛实施注射。这些针头的出口小,因而不会在注射之处留下会被注意到的损伤;但是对于将根据本发明的制剂以足够的速度注入到眼睛之中而言,它们的出口却仍是足够大的。如果将注射器针筒的直径作相应的调整,那么就可避免在注射器或者说针头内部形成压力,而这种压力在注射时会在过大压力下将制剂带入眼睛中,从而使制剂被散布到施用处之外,例如散布到视网膜之后。实践证明,要如所愿地注入制剂的话,采用20、23、25或27号针头,尤其是23或25号针头是特别有利的。在一优选实施方式中采用的是此类的针头以及针筒直径为3至10mm的注射器。如果在温度为25℃且剪切率为10s-1时,制剂的动态粘度处于1至500mPas的范围内,则特别优选23或25号针头。针头与制剂相互之间恰恰就是在这种情况下协调得很好,从而使足量的根据本发明的制剂能够迅速沉降在施用处,而不会使制剂由于压力积聚的缘故从针头中喷溅出来。因此也就避免了制剂被注射到期望之施用处的后面,从而能够有针对性地对膜实施理想的染色。
上述根据本发明的制剂以及为施用该种制剂所提供的注射器能够在眼睛中有针对性地对膜,即ILM和/或ERM进行染色。根据所用染料的不同,可以仅对一种膜,也就是说仅对ILM或者仅对ERM进行染色,当然也可以对两种膜都进行染色。在一种实施方式中,根据本发明的制剂被用于使ERM产生负染效果,以便能够将其去除。在这一实施方式中采用的这样一种染料的溶液,比如亮蓝G,其能够有选择性地对ILM,而不是ERM进行染色。通过这种方式可将未被染色的膜(ERM)与染色的膜(ILM)区分开,从而能够将之去除。
具体实施例
下面通过实施例来对本发明作进一步的解释,这些实施例对密度已经增大的染料溶液及其制备方法进行了描述,但本发明并不限于这样的例子。
实施例1
精确地称量出0.025克亮蓝G、5克蔗糖、0.19克磷酸氢二钠、0.03克磷酸二氢钠和0.82克氯化钠,并冲入100克蒸馏水。在最高为60℃的温度下将原料在玻璃瓶中处理1小时,这样即可获得一种染料浓度为0.25g/L,密度为1.023g/cm3的均匀溶液。
实施例2
精确地称量出0.025克亮蓝G、5克海藻糖、0.19克磷酸氢二钠、0.03克磷酸二氢钠和0.82克氯化钠,并冲入100克蒸馏水。在最高为60℃的温度下将原料在玻璃瓶中处理1小时,这样即可获得一种染料浓度为0.25g/L,密度为1.023g/cm3的均匀溶液。
实施例3
精确地称量出0.025克亮蓝G、0.19克磷酸氢二钠、0.03克磷酸二氢钠和0.82克氯化钠,并冲入100克蒸馏水和重水的混合物。在最高为60℃的温度下将原料在玻璃瓶中处理1小时,这样即可获得一种染料浓度为0.25g/L,密度为1.018g/cm3的均匀溶液。
实施例4
染料+丙三醇
精确地称量出0.025克亮蓝G、0.19克磷酸氢二钠、0.03克磷酸二氢钠和0.82克氯化钠,并冲入10%丙三醇与蒸馏水混合物。在最高为60℃的温度下将原料在玻璃瓶中处理1小时,这样即可获得一种染料浓度为0.25g/L,密度为1.027g/cm3的均匀溶液。
实施例5
利用如实施例1至4所述的方法制备的染料溶液具有如下表所列之成分:
物质 | 标称净重,单位:克 | 实际净重,单位:克 |
聚乙烯吡咯烷酮 | 6 | 6.0067 |
亮蓝G | 0.0125 | 0.0125 |
Na2HPO4·2H2O | 0.095 | 0.0950 |
NaH2PO4·2H2O | 0.015 | 0.0159 |
NaCl | 0.41 | 0.4100 |
水 | 每50克 | 每50克 |
获得之均匀溶液的密度为1.028g/cm3,而粘度则为7.38mPas。
实施例6
利用如实施例1至4所述的方法制备的染料溶液具有如下表所列之成分:
获得之均匀溶液的密度为1.007g/cm3,而粘度则为142.79mPas。
在实施例1至6中所制备的染料溶液被用于对人眼或动物眼睛中的ILM进行染色。我们发现,全部六种溶液均可很好地得以制备(auftragen),均可在施用之后立即沉降并将ILM染色。与为进行比较而制备的如DE10255601所公开的亮蓝溶液相比,在所用染料量相等的情况下,上述六种溶液的染色效果更加强大。
Claims (16)
1.一种具有生物相容性的水基制剂,该制剂用于对人眼或动物眼睛中的内界膜(ILM)和/或视网膜前膜(ERM)有选择性地进行染色,其包含至少一种选自由下列各物质组成的组的染料:三苯甲烷染料、偶氮染料、花青染料和/或天然染料或者它们的混合物,其中所述制剂的密度处于1.01g/cm3至1.5g/cm3的范围内。
2.根据权利要求1所述的制剂,其特征在于,所述染料是亮蓝G。
3.根据权利要求2所述的制剂,其特征在于,在形成的制剂中,亮蓝G的浓度最大为0.3g/L,优选为0.25g/L。
4.根据前述权利要求之一所述的制剂,该制剂被用作使视网膜前膜产生负染效果的染料。
5.根据前述权利要求之一所述的制剂,其特征在于,包含重水和/或选自羟乙基淀粉或葡聚糖的多糖,作为其密度调节介质。
6.根据前述权利要求之一所述的制剂,其特征在于,另外包含至少一种用来调节粘度的介质,该介质选自:聚醚、聚乙烯醇、聚酯、聚丙烯酸共聚物、聚乙烯吡咯烷酮以及其他聚合物;诸如丙三醇、乙二醇、丙二醇、丁二醇的多元醇;甲基纤维素、黄原胶、淀粉、透明质酸以及它们各自的衍生物;硫酸软骨素、硫酸钠。
7.根据权利要求1至6之一所述的制剂,其特征在于,所述制剂在温度为25℃且剪切率为10s-1时所具有的动态粘度在1至500mPas,优选在50至275mPas的范围内。
8.根据权利要求1至7所述的制剂,其特征在于,所形成溶液的渗透压在280-330mosmol/L的范围内,优选为300mosmol/L。
9.一种试剂盒,其包含带有针筒及针头的注射器和用于对人眼或动物眼睛中的内界膜(ILM)和/或视网膜前膜(ERM)有选择性地进行染色的制剂,其中,针筒直径与针头直径的比例为10至2∶1至0.2,优选为20∶1至4∶1。
10.根据权利要求9所述的试剂盒,其特征在于,所述制剂为如权利要求1至8之一所述的制剂。
11.根据权利要求9或10所述的试剂盒,其特征在于,针筒长度与针筒直径之间的比例处于15至5∶1的范围内。
12.根据权利要求9至11之一所述的试剂盒,其特征在于,所述注射器带有19至27号针头,优选带有23或25号针头。
13.根据权利要求12所述的试剂盒,其特征在于,所述注射器的针筒直径为3至10mm。
14.根据权利要求9至13之一所述的试剂盒,其特征在于,所述染料是亮蓝G、艳蓝R、艳蓝FCF、专利蓝V、甲基绿、考马斯紫R200、溴酚蓝和/或芝加哥蓝。
15.根据权利要求9至14之一所述的试剂盒,其特征在于,所述制剂在温度为25℃且剪切率为10s-1时所具有的动态粘度在1至500mPas,优选在50至275mPas的范围内。
16.根据权利要求9至15之一所述的试剂盒,其特征在于,在形成的制剂中,亮蓝G的浓度最大为0.3g/L,优选为0.25g/L。
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CN107660198A (zh) * | 2015-05-26 | 2018-02-02 | 阿基米亚有限责任公司 | 特别地用于眼科手术的手术方法和用于染色蛋白质的染料分子和染料制备物 |
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