CN101284146B - 干燥止血组合物及其制备方法 - Google Patents
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Abstract
本发明涉及干燥止血组合物及其制备方法。具体地说,本发明涉及制备干燥交联明胶组合物,这种组合物能迅速再水化以生成宜作止血密封剂用的明胶水凝胶。明胶要在某种再水化助剂如聚乙二醇、聚乙烯吡咯烷酮和葡聚糖存在下进行交联,目的是形成一种干燥的交联明胶粉。已经发现,使用再水化助剂能在再水化水性介质,典型的是含凝血酶的盐水存在下,大幅度提高再水化率。
Description
本申请是申请日为2002年6月21日,申请号为02818207.3,发明名称为“干燥止血组合物及其制备方法”的发明专利申请的分案申请。
发明背景
1.发明领域
本发明一般地涉及胶原与胶原-衍生的组合物以及它们的制备方法。特别是,本发明涉及一种生产能以更高速率吸水的干燥交联明胶或其它胶原或胶原-衍生的组合物的方法。
本申请的受让人Fusion Medical Technologies公司生产一种止血组合物,商品名为FloSeal。FloSeal产品以包括2个注射器的包装出售。第一个注射器装满用一种缓冲溶液预水化的交联牛明胶颗粒。该明胶水凝胶含约85%(重量/重量)水,其形式是一种可流动水凝胶。在即将用于手术室之前,要将盐水中的凝血酶与明胶水凝胶混合。凝血酶要在盐水中制备并吸入第二注射器内,两个注射器互连在一起,以便凝血酶与明胶混合。
业已发现,所得明胶水凝胶颗粒与凝血酶的混合物涂在出血处时是一种非常有效的止血密封剂。一般,该密封剂要用它在其中已混合好的注射器施涂到出血处。血液将渗透过所形成的水凝胶颗粒床,凝血酶与血液中的血纤维蛋白原反应,在明胶周围形成血纤维蛋白凝块,从而封住出血处。
2.背景技术描述
发明概述
本发明提供改进的止血密封组合物、制备这类改进组合物的方法及包含这类改进组合物的试剂盒。这些方法与组合物特别适用于包括手术出血处、外伤出血处等在内的出血处的止血。这类组合物的典型用途可以用于密封在血管导管插入术形成的血管穿透之上的组织系统。
这类组合物包含一种已制成能迅速再水化的干燥交联明胶粉。该明胶粉优选包含较大的颗粒,也称为碎片或次单元,如美国专利6,063,061和6,066,325所述,该专利的全部公开内容已包括在前面供参考。优选的颗粒尺寸范围为150μm-750μm,但在很多情况下也可以用该优选范围之外的颗粒尺寸。这类干燥组合物在暴露于再水化水性介质中时也将表现出大的“平衡溶胀比”。优选溶胀比在400%-1000%范围内,但也可以落在该范围之外,如上述参考专利所述。“平衡溶胀比”可通过将明胶水凝胶粉末完全水化从而完全溶胀时的重量减去其干燥重量确定。然后将差值除以干燥重量并乘以100,以给出溶胀比值。干燥重量应将该物质在高温下处理足够长时间以基本除去所有的残留水份,例如在120℃下处理2小时后测定。实现物质平衡水化的方法可以如下:将干燥物质在适当的再水化介质如盐水中浸泡足够长时间,使水含量达到恒定,一般要在室温下浸泡18-24小时。
本发明的干燥交联明胶粉通常含有一些残留水份,但须足够干燥以达到所要求的稳定性和更长的储存寿命。一般干燥组合物的含湿量低于20重量%或更低,优选含湿量在5重量%-15重量%范围内。为保持其干燥度,组合物一般以适合于防湿气侵入的方式包装,如结合本发明的试剂盒所详述。
在本发明的一个具体方面,组合物将包含含湿量为20%(重量/重量)或更低的交联明胶粉,其中所述粉末要在有再水化助剂存在下交联,以使粉末的再水化率较之不用再水化助剂时所制成的类似粉末的再水化率至少高5%。这里“再水化率”定义为1g粉末(以干燥重量为基准计算)在30秒内吸收的水溶液一般为0.9%(重量/重量)盐水的量,以gm/gm表示。测定该速率的具体技术在下文实验部分描述。本发明优选组合物的再水化率至少为3gm/gm,优选至少3.5gm/gm,通常为3.75gm/gm或更高。不用再水化助剂所制成的类似粉末的再水化率一般低于3,再水化率的增加通常至少为5%,优选至少10%,更优选至少25%或更高。
本发明的再水化率更高的干燥交联明胶粉优选通过在有某种再水化助剂存在下制备粉末而获得。这类再水化助剂将在粉末制备期间存在,但通常要从最终产品中除去。例如,以总固体量约20%存在的再水化助剂在最终产品中一般要降到1重量%以下,通常低于0.5重量%。再水化助剂的实例包括聚乙二醇(PEG),优选分子量约1000;聚乙烯吡咯烷酮(PVP),优选平均分子量约50,000;和葡聚糖,一般平均分子量约40,000。在制备本发明的组合物时,优选使用上述再水化助剂中的至少2种,更优选使用所有这3种。
因此,本发明的方法包含提供一种未交联明胶与再水化助剂组合的水溶液。未交联明胶在水溶液中的存在量一般为5%(重量/重量)-15%(重量/重量),再水化助剂的存在量一般为水溶液中明胶重量的5%-30%(重量/重量)。优选再水化助剂包含明胶重量2.5%-20%(重量/重量)的PEG,1.25%-20%(重量/重量)的PVP和1.25%-20%(重量/重量)的葡聚糖。
然后将未交联明胶与再水化助剂一起以任何适合于形成水凝胶的方法进行交联。例如,聚合物分子可以用双-或多-官能度交联剂进行交联,交联剂以共价键连接在两个或多个聚合物分子链上。典型的双官能度交联剂包括醛、环氧化物、琥珀酰亚胺、碳二亚胺、马来酰亚胺、叠氮化物、碳酸酯、异氰酸酯、二乙烯基砜、醇、胺、亚胺酯、 酸酐、卤化物、硅烷、重氮基乙酸酯、氮丙啶等等。或者也可以用氧化剂和其它试剂如高碘酸盐实现交联,这类试剂能活化聚合物上的侧链或部分,使它们与其它侧链或部分反应,形成交联键。交联的另一种方法包含将聚合物暴露于γ射线之类的射线中以活化聚合物链,以允许发生交联反应。脱氢热交联法也适用。交联明胶分子的优选方法如下所述。
生成交联明胶的典型方法如下。获得明胶并将其悬浮在水溶液中,形成未交联水凝胶,固体含量一般为1重量%-70重量%,通常为3重量%-10重量%。明胶的交联一般是暴露在戊二醛(例如,浓度为0.01%-0.05%重量/重量,在0℃-15℃缓冲水溶液中过夜)、高碘酸钠(例如,浓度为0.05M,在0℃-15℃保持48小时)或1-乙基-3-(3-二甲基氨基丙基)碳二亚胺(“EDC”)中(例如,浓度为0.5%-1.5%重量/重量,在室温下过夜),或暴露在约0.3-3兆拉德γ或电子束辐照中。或者,也可以通过将明胶颗粒悬浮在醇中,优选甲醇或乙醇,固体含量一般为1重量%-70重量%,通常为3重量%-10重量%,然后通过暴露于交联剂中进行交联,交联剂一般是戊二醛(例如,浓度为0.01%-0.1%重量/重量,在室温下过夜)。在戊二醛的情况下,pH值应保持约6-11,优选7-10。用戊二醛交联时,交联是通过Schiff碱形成的,然后可以通过随后的还原如用氢硼化钠处理而稳定化。交联后,所得颗粒可用水清洗,任选地在醇中漂洗,并烘干。然后可将所得干燥粉末装进本发明的涂布器,如下文更详细的描述。
交联后,要从所得水凝胶中除去至少50%(重量/重量)再水化助剂。通常,除去再水化助剂的方法是过滤水凝胶,接着清洗所得的滤饼。为了将产品清洗到所需的水平并除去至少50%,优选至少90%(重量/重量)起始存在的再水化助剂,这样的过滤/清洗步骤可重复一次或多次。
过滤后,明胶要烘干,典型的方法是烘干所得到的最终滤饼。烘干的滤饼随后要经破碎或研磨,以形成颗粒尺寸在上述所需范围内的交联粉末。
按照本发明的试剂盒将包含一个容纳如前所述本发明干燥交联明胶粉末的第一容器。该试剂盒还包含一个容纳再水化水性介质的第二容器,再水化水性介质一般是拟在明胶再水化时与明胶混合的包含凝 血酶的盐水或其它水溶液。两个容器可具有任何形式,但优选允许干明胶与再水化介质混合的注射器形式。
附图简述
图1示意一个按照本发明原理构成的试剂盒。
具体实施方案详述
下列实例仅为说明而给出,无意限制本发明。
实施例1:明胶粉的制备
实施例2:“改性明胶粉”的制备
将再水化助剂(表1)溶解在500mL 50℃去离子水中,然后在该溶液中加入一定量如实施例1那样制备的牛皮衍生明胶粉。明胶在溶液中的最终浓度要选为约8%(重量/重量,以本体明胶粉为基准),再水化助剂在溶液中的总量要如实施例9-44(表1和2)所选。在明胶溶解之后,将溶液倒进带Teflon涂层的金属盘内并干燥之。将干燥的明胶片研磨成“改性明胶粉”。
实施例3:从“改性明胶粉”制备交联明胶粉
将600mL 0.2M磷酸盐缓冲液(pH值9.2±0.2)冷却到低于12℃的温度。在该缓冲液中加入0.32mL戊二醛(25%),然后再加入20g改性明胶粉,使戊二醛的浓度为4000ppm(戊二醛与改性明胶本体重量之比)。用搅拌棒使明胶悬浮在戊二醛溶液中。将各悬浮液的pH值调到9.2±0.2范围内,然后在9-12℃的温度和9.2±0.2的pH值下保持19小时。
过滤该悬浮液并用去离子水清洗滤饼3次,方法是用去离子水完全浸没滤饼,然后使用真空将清洗水吸过滤饼。每次清洗期间,滤饼留在漏斗内。
在烧杯内将0.2g NaBH4溶于600mL浓度为25mM的磷酸盐缓冲液中,pH值为7.4±0.2。在室温(约22℃)下将上述滤饼悬浮在NaBH4溶液中3小时,然后过滤去除液体。
然后在室温(约22℃)下将滤饼悬浮在600mL缓冲液中30min,再过滤。缓冲液由磷酸钠(二元酸酐和一元一水合物)和抗坏血酸钠组成。重复上述步骤2次,以确保盐与明胶以适当比例存在,从而在重构时形成所需的缓冲组合物。干燥该滤饼,然后用Waring Blender研磨成“交联明胶粉”。
本方法也用来从未改性明胶粉制备交联明胶粉;即在制备期间不加再水化助剂的明胶。
实施例4:从交联明胶粉制备辐照产品
在几支5ml注射器的每一支内放进约800mg(本体重量)如实施例2那样制备的交联明胶粉。在室温下用γ射线消毒含粉末注射器。
实施例5:用产品作为止血剂
从改性明胶粉末制备一支注射器内含约0.8g辐照交联明胶粉末的产品。改性明胶粉如实施例2那样制备。改性明胶粉经进一步交联并辐照,如实施例3和4那样。将产品与4mL盐水溶液混合,每ml盐水溶液含约1000单位牛血清凝血酶。混合是通过在由阴-阴直通Luer连接器连接的两个注射器之间往返通过而实现的。当注射器中的粉末与凝血酶溶液混合时粉末就被水化了,形成水凝胶颗粒。
在农庄级猪的肝上产生一片约1cm×1cm×0.2cm深的伤口。该头猪已用肝素抗凝过,因此其活化血凝时间(ACT)是其基础值的3-5倍,该伤口在处理以前不断流血。从混合开始约30秒钟后,将约2mL水化粉 末从注射器中挤到伤口上并压住2分钟。除去压力后,分别在涂抹后3min、10min和50min观察处理伤口的流血情况。3min和10min观察,未见处理伤口流血。10min后用盐水溶液冲洗处理过的伤口。除去过量物质后,仍未见再流血。在涂抹后50min时,再观察伤口,也未见流血。
实施例6:测定粉末的再水化率
粉末的“再水化率”测定如下。装在5mL注射器中的粉末与含一定体积水溶液的第二注射器通过在两个注射器之间由Luer接头连接的通道混合30秒钟。选择的水溶液体积要超过预期在30秒钟内吸收的量。一般是将0.8g(本体重量)粉末与3mL 0.9%氯化钠水溶液混合。然后立即过滤所得混合物,以除去所有未被吸收的液体。称重湿过滤物,然后在120℃烘箱内烘2小时,再称重。这一测量给出从湿物质中除去的总水量以及干粉重量。然后在对原来残留在粉末中的水份作过微小校正后计算出被粉末吸收的水量。“再水化率”以每克干粉末在30秒间隔内吸收的盐水质量给出。
在下面的计算中,本体粉末的固体分数(“S”)是独立地通过将本体粉末在120℃烘2小时并对干燥前后的粉末称重测得的。S值由下式计算:
再水化率计算:
A:盘和滤纸的起始重量
B:盘、滤纸和水化粉末的重量
C:盘、滤纸和样品在烘箱内烘干后的重量
S:注射器内起始本体粉末的固体分数
M:混合期间每克粉末(干重)吸收的盐水克数(“吸收率”)
实施例7:对几批粉末产品测定的再水化率与物理性能
表1和2示意了对几批粉末产品(实施例9-23)中每批测定的再水化率结果。这些批次的粉末分别如实施例1、2、3和4那样的方法制备。除实施例9与17之外,都从改性明胶按不同比例的明胶与下列再 水化助剂制备:平均分子量为1000的聚乙二醇(PEG);牌号为“k-30”对应于平均分子量约50,000的聚乙烯吡咯烷酮(PVP);和平均分子量40,000的葡聚糖。
可以看到,使用不同比例组合的明胶和再水化助剂,能使粉末产品的每克粉末在30秒内吸收的盐水溶液多于用无再水化助剂的明胶制成的粉末产品。还可以看到,用明胶、PEG、PVP和葡聚糖以本体重量比为80∶10∶5∶5的组合(实施例10)的改性明胶所生成的粉末产品,每克在30秒内吸收的盐水溶液比从未改性明胶制成的粉末多约33%。
表1还给出了对这些粉末产品批次测定的其它物理性能值。“固体百分含量”由称取粉末在120℃烘2小时以除去残余水份前后的重量测定。“DSC峰温”是指从1℃-70℃进行的差示扫描量热法测定的温度谱上出现峰的温度。“平衡溶胀比”的测定方法如下:在室温下让粉末悬浮在过量盐水溶液中至少18小时。对该水化粉末称重以确定其“平衡湿重”,然后在120℃烘2小时,再称重,以确定其“干重”。平衡溶胀比计算如下:
“平均颗粒尺寸”值用光散射法在Coulter LS颗粒尺寸分析仪上测定。
从表1给出的数据中显然可看到,适当使用再水化助剂能改变粉末产品的再水化率而不会明显改变其它物理性能。
实施例8:测定聚乙二醇、聚乙烯吡咯烷酮和葡聚糖在改性明胶粉末和交联粉末中的含量
将约50mg改性明胶或250mg交联辐照粉末产品悬浮在10mL去离子水中并在65℃加热3小时。然后将样品以2000rpm离心处理15min。将所得悬浮液滤过一个0.45μm Gelman Acrodisc漏斗,弃去第一mL。所得样品然后用3种不同的高效液相色谱法(HPLC)进行评估,以定量给出样品中聚乙二醇(PEG)、聚乙烯吡咯烷酮(PVP)和葡聚糖的含量。对于PEG,将100μl样品注射到Waters Ultrahydrogel 120柱上,柱子尺寸7.8×300mm,带保护柱和预过滤漏斗,用去离子水作为移动相。用折光指数测定仪监测流出物。对于PVP,将100μl样品注射到Phenomenex Kingsorb C18 5μm柱上,柱子尺寸4.6×150mm,带保护 柱和预过滤漏斗,用梯度甲醇与磷酸钠水溶液作为移动相。用紫外吸收测定仪监测流出物。对于葡聚糖,将100μl样品注射到WatersUltrahydrogel线柱上,柱子尺寸7.8×300mm,带保护柱和预过滤漏斗,用0.1M pH7磷酸钠与乙腈按90∶10作为移动相。用折光指数测定仪监测流出物。为进行分析,所有柱子都加热到40℃。定量极限对PEG和PVP约为0.1%(重量/重量样品),对于葡聚糖,为0.2%(重量/重量样品)。
改性明胶如实施例2那样制备。按上述方法分析改性明胶的PEG、PVP和葡聚糖。结果表明,PEG、PVP和葡聚糖的存在量分别为16%、8%和3%(重量/重量本体)。让改性明胶依次经交联、氢硼化物处理和清洗,如实施例3那样,以形成交联改性明胶粉。当以上述方法用HPLC分析这种粉末的PEG、PVP和葡聚糖时,发现这三种再水化助剂中每一种的含量都低于定量极限。
实施例9:不加再水化助剂制成的粉末产品
按实施例1那样从牛皮条制备未改性明胶—即不加加工助剂的明胶并按实施例3那样进行交联。如实施例4那样将交联未改性明胶装入注射器并进行γ辐照。如实施例6和7那样测定所得产物的物理性能,结果示于表1。
实施例10-23:用再水化助剂制成的粉末产品
如实施例2那样从明胶粉或皮条和1、2或3种再水化助剂制备改性明胶批料。表1给出了所用本体明胶与再水化助剂的比例。然后如实施例3那样交联该改性明胶。除实施例17之外,所用的再水化助剂如下所示:平均分子量约1000的聚乙二醇(PEG);牌号为“k-30”、平均分子量约50,000的聚乙烯吡咯烷酮;和平均分子量约40,000的葡聚糖。在实施例17中,用平均分子量约400的PEG。然后如实施例4那样将该交联改性明胶装进注射器并进行γ辐照。如实施例6和7那样测定从每一种制备方法得到的粉末产品的物理性能,结果示于表1。用实施例10的配方得到的数据是按照该配方制备的9批样品的平均值与标准偏差。
实施例24-44:用各种再水化助剂制成的粉末产品
如实施例2那样从明胶粉或皮条和几种再水化助剂之一制备几批改性明胶。表2给出了每批所用再水化助剂的名称与浓度,浓度以本 体明胶与再水化助剂的重量比和制备改性明胶所用的本体溶质的总百分数表示。然后如实施例3那样交联该改性明胶。然后如实施例4那样将交联改性明胶装进注射器并进行γ辐照。如实施例6和7那样测定从每一种制备方法得到的粉末产品的物理性能,结果示于表2。表2中给出了实施例9的配方的结果作为比较。
虽然以上是本发明优选实施方案的完整描述,但可以用各种变化、改变和等代体。因此不应将以上的描述当作限制由所附权利要求规定的本发明范围。
Claims (21)
1.一种组合物,其含有含湿量为20重量%或更低、平均颗粒尺寸为150μm-750μm以及再水化率为至少3克/克的交联明胶粉末,其中所述粉末的再水化率定义为1g粉末在30秒内吸收的水溶液的量,其中所述粉末在有再水化助剂存在下交联,其中所述再水化助剂以占所述组合物重量少于1%的量存在,并且其中所述再水化助剂为选自以下的一种或多种物质:具有400或1000的平均分子量的聚乙二醇、具有50000平均分子量的聚乙烯吡咯烷酮、和具有40000平均分子量的葡聚糖。
2.如权利要求1的组合物,其中所述交联明胶粉末的再水化率为至少3.5克/克。
3.如权利要求2的组合物,其中所述交联明胶粉末的再水化率为至少3.75克/克。
4.如权利要求1的组合物,其中所述再水化助剂含有至少两种所述物质。
5.如权利要求4的组合物,其中所述再水化助剂含有全部所述物质。
7.如权利要求1的组合物,其中所述交联明胶粉末的含湿量为5重量%至15重量%。
8.如权利要求1的组合物,其中所述再水化助剂以占所述组合物重量少于0.5%的量存在。
9.如权利要求1的组合物,其中所述再水化助剂含有以明胶重量计2.5重量%至20重量%的聚乙二醇。
10.如权利要求1的组合物,其中所述再水化助剂含有以明胶重量计1.25重量%至20重量%的聚乙烯基吡咯烷酮。
11.如权利要求1的组合物,其中所述再水化助剂含有以明胶重量计1.25重量%至20重量%的葡聚糖。
12.用于制备权利要求1的组合物的一种组合物,其含有含湿量为20重量%的未交联明胶粉末和再水化助剂。
13.制造基本干燥的交联明胶粉末的方法,所述方法包括:
提供一种包含未交联明胶与至少一种再水化助剂组合的水溶液;
烘干该明胶与再水化助剂的溶液以形成固体;
研磨该固体以形成粉末;和
交联该粉末以产生含湿量低于20重量%的粉末;
其中所述再水化助剂选自具有40000平均分子量的葡聚糖、具有50000平均分子量的聚乙烯基吡咯烷酮和/或具有400或1000的平均分子量的聚乙二醇,
其中未交联明胶在水溶液中的存在量为5重量%-15重量%,并且
再水化助剂以水溶液中所存在明胶重量的5重量%-30重量%的浓度存在。
14.一种制造基本干燥的交联明胶粉末的方法,所述方法包括:
提供一种包含未交联明胶与至少一种再水化助剂组合的水溶液;
交联明胶以形成水凝胶;
从水凝胶中除去至少50重量%的再水化助剂;以及
烘干该交联明胶以形成一种含湿量低于20重量%的粉末;
其中所述再水化助剂选自具有40000平均分子量的葡聚糖、具有50000平均分子量的聚乙烯基吡咯烷酮和/或具有400或1000的平均分子量的聚乙二醇,
其中未交联明胶在水溶液中的存在量为5重量%-15重量%,并且
再水化助剂以水溶液中所存在明胶重量的5重量%-30重量%的浓度存在。
15.如权利要求14的方法,其中再水化助剂包含1、2或3种选自下列一组的物质:聚乙二醇、聚乙烯基吡咯烷酮和葡聚糖。
16.如权利要求14或15的方法,其中再水化助剂包含的聚乙二醇浓度为2.5重量%-20重量%,聚乙烯基吡咯烷酮浓度为1.25重量%-20重量%,以及葡聚糖浓度为1.25重量%-20重量%。
17.如权利要求14或15的方法,其中交联包括在明胶溶液中加入一种交联剂。
18.如权利要求17的方法,其中交联剂包含戊二醛。
19.如权利要求14或15的方法,其中除去至少50%再水化助剂包括过滤水凝胶以形成滤饼,然后清洗滤饼以除去再水化助剂。
20.如权利要求19的方法,其中清洗滤饼除去至少90重量%起始存在于明胶中的再水化助剂。
21.如权利要求19的方法,其中烘干包括烘干清洗后的滤饼,其中该方法还包括研磨经烘干的滤饼,以形成干燥的研磨明胶粉末。
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Families Citing this family (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7871637B2 (en) | 1996-08-27 | 2011-01-18 | Baxter International Inc. | Dry hemostatic compositions and methods for their preparation |
US7435425B2 (en) * | 2001-07-17 | 2008-10-14 | Baxter International, Inc. | Dry hemostatic compositions and methods for their preparation |
US8603511B2 (en) | 1996-08-27 | 2013-12-10 | Baxter International, Inc. | Fragmented polymeric compositions and methods for their use |
US8303981B2 (en) | 1996-08-27 | 2012-11-06 | Baxter International Inc. | Fragmented polymeric compositions and methods for their use |
US6066325A (en) | 1996-08-27 | 2000-05-23 | Fusion Medical Technologies, Inc. | Fragmented polymeric compositions and methods for their use |
US7923431B2 (en) * | 2001-12-21 | 2011-04-12 | Ferrosan Medical Devices A/S | Haemostatic kit, a method of preparing a haemostatic agent and a method of promoting haemostatis |
MXPA05006193A (es) | 2002-12-11 | 2005-12-05 | Ferrosan As | Materiales basados en gelatina como hisopos. |
US8834864B2 (en) | 2003-06-05 | 2014-09-16 | Baxter International Inc. | Methods for repairing and regenerating human dura mater |
US20060019868A1 (en) * | 2004-01-30 | 2006-01-26 | Pendharkar Sanyog M | Hemostatic compositions and devices |
US7927626B2 (en) | 2003-08-07 | 2011-04-19 | Ethicon, Inc. | Process of making flowable hemostatic compositions and devices containing such compositions |
US8440225B2 (en) * | 2003-08-07 | 2013-05-14 | Ethicon, Inc. | Process of making flowable hemostatic compositions and devices containing such compositions |
US7109163B2 (en) * | 2004-01-30 | 2006-09-19 | Ethicon, Inc. | Hemostatic compositions and devices |
JP2007519450A (ja) * | 2004-01-30 | 2007-07-19 | フェロサン アー/エス | 止血用のスプレーおよび組成物 |
US8119160B2 (en) * | 2004-06-29 | 2012-02-21 | Ethicon, Inc. | Hemostatic compositions and devices |
CA2571981C (en) | 2004-07-09 | 2014-12-30 | Ferrosan A/S | Haemostatic composition comprising hyaluronic acid |
FR2881651A1 (fr) * | 2005-02-09 | 2006-08-11 | Urodelia Sa | Nouveau produit pharmaceutique et procede de fabrication de ce produit pharmaceutique |
WO2007126411A2 (en) * | 2005-07-28 | 2007-11-08 | Carnegie Mellon University | Biocompatible polymers and methods of use |
DE602006020347D1 (de) * | 2005-12-16 | 2011-04-07 | Oxthera Inc | Zusammensetzungen und verfahren zur oxalatreduktion |
US8703122B2 (en) | 2006-05-31 | 2014-04-22 | Baxter International Inc. | Method for directed cell in-growth and controlled tissue regeneration in spinal surgery |
TWI436793B (zh) | 2006-08-02 | 2014-05-11 | Baxter Int | 快速作用之乾密封膠及其使用和製造方法 |
US8133484B2 (en) | 2006-12-15 | 2012-03-13 | Lifebond Ltd | Hemostatic materials and dressing |
CA2672651C (en) | 2006-12-15 | 2014-03-11 | Lifebond Ltd. | Gelatin-transglutaminase hemostatic dressings and sealants |
US20100143447A1 (en) * | 2006-12-19 | 2010-06-10 | Ferrosan A/S | Wound or tissue dressing comprising lactic acid bacteria |
DE102007038125A1 (de) | 2007-08-03 | 2009-02-05 | Aesculap Ag | Kombination zum Verkleben von biologischen Geweben |
AR069109A1 (es) | 2007-10-30 | 2009-12-30 | Baxter Int | Uso de una biomatriz de colageno biofuncional regenerativa para tratar defectos viscerales o parietales |
US20090130756A1 (en) * | 2007-11-20 | 2009-05-21 | Pioneer Surgical Orthobiologics,Inc. | Cryopreservation of cells using cross-linked bioactive hydrogel matrix particles |
CN102014973A (zh) | 2008-02-29 | 2011-04-13 | 弗罗桑医疗设备公司 | 用于促进止血和/或伤口愈合的装置 |
US9629798B2 (en) | 2008-04-03 | 2017-04-25 | Mallinckrodt Pharma Ip Trading D.A.C. | Hemostatic microspheres |
US8367388B2 (en) | 2008-06-18 | 2013-02-05 | Lifebond Ltd. | Cross-linked compositions |
US8110208B1 (en) | 2009-03-30 | 2012-02-07 | Biolife, L.L.C. | Hemostatic compositions for arresting blood flow from an open wound or surgical site |
US9039783B2 (en) | 2009-05-18 | 2015-05-26 | Baxter International, Inc. | Method for the improvement of mesh implant biocompatibility |
CN102802683B (zh) | 2009-06-16 | 2015-11-25 | 巴克斯特国际公司 | 止血海绵 |
US20110081398A1 (en) * | 2009-10-01 | 2011-04-07 | Tyco Healthcare Group Lp | Multi-mechanism surgical compositions |
US20110081701A1 (en) * | 2009-10-02 | 2011-04-07 | Timothy Sargeant | Surgical compositions |
US8968785B2 (en) * | 2009-10-02 | 2015-03-03 | Covidien Lp | Surgical compositions |
KR101811070B1 (ko) | 2009-12-16 | 2017-12-20 | 백스터 인터내셔널 인코포레이티드 | 지혈 스폰지 |
JP5796860B2 (ja) | 2009-12-22 | 2015-10-21 | ライフボンド リミテッドLifebond Ltd | 架橋マトリックスの特性を調節するための酵素的架橋剤の改変 |
SA111320355B1 (ar) | 2010-04-07 | 2015-01-08 | Baxter Heathcare S A | إسفنجة لايقاف النزف |
GB201008404D0 (en) * | 2010-05-20 | 2010-07-07 | Fujifilm Mfg Europe Bv | Hemostatic compositions |
CN103037845B (zh) | 2010-06-01 | 2015-11-25 | 巴克斯特国际公司 | 用于制备干燥、稳定的止血组合物的方法 |
WO2011151400A1 (en) | 2010-06-01 | 2011-12-08 | Baxter International Inc. | Process for making dry and stable hemostatic compositions |
JP5973997B2 (ja) | 2010-06-01 | 2016-08-23 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | 乾燥した安定な止血用組成物を作製するためのプロセス |
CA2807012A1 (en) | 2010-08-05 | 2012-02-09 | Lifebond Ltd. | Dry composition wound dressings and adhesives |
US10086043B2 (en) | 2011-04-03 | 2018-10-02 | The General Hospital Corporation | Efficient protein expression in vivo using modified RNA (MOD-RNA) |
US9149511B2 (en) * | 2011-06-30 | 2015-10-06 | Ethicon, Inc. | Procoagulant peptides and their derivatives and uses therefor |
US20130090291A1 (en) | 2011-10-11 | 2013-04-11 | Baxter Healthcare S.A. | Hemostatic compositions |
AU2012318256B2 (en) * | 2011-10-11 | 2015-10-01 | Baxter Healthcare S.A. | Hemostatic composition |
MX356185B (es) | 2011-10-11 | 2018-05-17 | Baxter Int | Composiciones hemostaticas. |
WO2013053749A2 (en) | 2011-10-11 | 2013-04-18 | Baxter International Inc. | Hemostatic compositions |
SG11201401878SA (en) * | 2011-10-27 | 2014-09-26 | Baxter Int | Hemostatic compositions |
WO2013060769A2 (en) | 2011-10-27 | 2013-05-02 | Baxter International Inc. | Hemostatic compositions |
US8940317B2 (en) | 2011-12-23 | 2015-01-27 | Pioneer Surgical Technology | Continuous matrix with osteoconductive particles dispersed therein, method of forming thereof, and method of regenerating bone therewith |
EP2822474B1 (en) | 2012-03-06 | 2018-05-02 | Ferrosan Medical Devices A/S | Pressurized container containing haemostatic paste |
BR112014030962A2 (pt) | 2012-06-12 | 2017-06-27 | Ferrosan Medical Devices As | métodos para preparação e para reconstituição de uma composição seca adequada para uso em hemostase e cicatrização de feridas, e, kit hemostático |
US9724078B2 (en) | 2013-06-21 | 2017-08-08 | Ferrosan Medical Devices A/S | Vacuum expanded dry composition and syringe for retaining same |
EP3470094B1 (en) | 2013-12-11 | 2020-07-22 | Ferrosan Medical Devices A/S | Dry composition comprising an extrusion enhancer |
EP3177330A4 (en) | 2014-08-08 | 2018-01-17 | The Brigham and Women's Hospital, Inc. | Elastic biopolymer and use as a tissue adhesive |
WO2016058612A1 (en) | 2014-10-13 | 2016-04-21 | Ferrosan Medical Devices A/S | Dry composition for use in haemostasis and wound healing |
WO2016102446A1 (en) | 2014-12-24 | 2016-06-30 | Ferrosan Medical Devices A/S | Syringe for retaining and mixing first and second substances |
EP3270985B1 (en) | 2015-03-19 | 2021-02-24 | The Brigham and Women's Hospital, Inc. | Polypeptide compositions and methods of using the same |
WO2017005590A1 (en) | 2015-07-03 | 2017-01-12 | Ferrosan Medical Devices A/S | Syringe for mixing two components and for retaining a vacuum in a storage condition |
EP3943127A1 (en) | 2015-09-01 | 2022-01-26 | Baxter International Inc | Hemostatic material |
WO2017139318A1 (en) | 2016-02-08 | 2017-08-17 | The Brigham And Women's Hospital, Inc. | Bioadhesive for corneal repair |
CN105879109A (zh) * | 2016-03-31 | 2016-08-24 | 武汉华同信生物科技有限公司 | 一种医用胶粘剂及其制备方法 |
KR20180027126A (ko) * | 2016-09-06 | 2018-03-14 | (주)한국비엠아이 | 가교화 히알루론산 유도체 매트릭스가 포함된 지혈 조성물 |
US11679177B2 (en) | 2017-08-08 | 2023-06-20 | Baxter International Inc. | Polymeric compositions, delivery devices, and methods |
SG11202003797VA (en) | 2017-11-03 | 2020-05-28 | Baxter Int | Polymeric compositions, delivery devices, and methods |
KR20200093600A (ko) * | 2017-11-28 | 2020-08-05 | 백스터 인터내셔널 인코포레이티드 | 상처-치료용 흡수제 |
AU2018396037A1 (en) | 2017-12-29 | 2020-06-18 | Baxter Healthcare Sa | Spray-dried thrombin and methods of using and making spray-dried thrombin |
EP4321182A2 (en) | 2018-05-09 | 2024-02-14 | Ferrosan Medical Devices A/S | Method for preparing a haemostatic composition |
WO2021009014A1 (en) | 2019-07-12 | 2021-01-21 | Gatt Technologies B.V. | Haemostatic powder |
CA3207273A1 (en) | 2021-01-08 | 2022-07-14 | Cilag Gmbh International | Bioresorbable sealing powder |
CN113144277B (zh) * | 2021-04-13 | 2022-06-14 | 武汉理工大学 | 一种可注射流体明胶及其制备方法和应用 |
CN113209357B (zh) * | 2021-05-14 | 2023-02-17 | 南方科技大学 | 复合止血粉 |
CN117940173A (zh) * | 2021-09-16 | 2024-04-26 | 爱惜康股份有限公司 | 用于组织道密封的组合物的试剂盒 |
CN117298327A (zh) * | 2023-11-15 | 2023-12-29 | 北京帝康医药投资管理有限公司 | 一种止血微球颗粒及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1270240A (zh) * | 2000-04-21 | 2000-10-18 | 中国石油化工集团公司 | 止血纤维及其制造方法 |
Family Cites Families (137)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2507244A (en) | 1947-04-14 | 1950-05-09 | Upjohn Co | Surgical gelatin dusting powder and process for preparing same |
CH264752A (de) | 1947-06-03 | 1949-10-31 | Hoffmann La Roche | Verfahren zur Herstellung von Trägern für Arzneimittel. |
US3089315A (en) | 1961-09-25 | 1963-05-14 | Gen Electric | Convertible self-contained cooling unit for air conditioning |
SE420565B (sv) | 1974-06-06 | 1981-10-19 | Pharmacia Ab | Hjelpmedel for intravaskuler administraring for anvendning i samband med intravaskuler administrering av en losning eller en suspension av ett diagnostiseringsmedel |
US4013078A (en) * | 1974-11-25 | 1977-03-22 | Feild James Rodney | Intervertebral protector means |
US4006220A (en) | 1975-06-04 | 1977-02-01 | Gottlieb Sheldon K | Compositions and methods useful for repairing depressed cutaneous scars |
US4164559A (en) * | 1977-09-21 | 1979-08-14 | Cornell Research Foundation, Inc. | Collagen drug delivery device |
DE2843963A1 (de) * | 1978-10-09 | 1980-04-24 | Merck Patent Gmbh | Im koerper resorbierbare geformte masse auf basis von kollagen und ihre verwendung in der medizin |
US4265233A (en) * | 1978-04-12 | 1981-05-05 | Unitika Ltd. | Material for wound healing |
US4179400A (en) | 1978-05-09 | 1979-12-18 | W. R. Grace & Co. | Process for preparing catalytic solutions of sulfonium salts |
AT359652B (de) | 1979-02-15 | 1980-11-25 | Immuno Ag | Verfahren zur herstellung eines gewebekleb- stoffes |
AT359653B (de) * | 1979-02-15 | 1980-11-25 | Immuno Ag | Verfahren zur herstellung eines gewebekleb- stoffes |
DE3036033A1 (de) | 1980-09-24 | 1982-05-06 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Wundbehandlungsmittel in pulverform und verfahren zu seiner herstellung |
US4300494A (en) | 1979-09-26 | 1981-11-17 | Shell Oil Company | Thermal insulated intake ports |
US4292972A (en) | 1980-07-09 | 1981-10-06 | E. R. Squibb & Sons, Inc. | Lyophilized hydrocolloio foam |
US4443332A (en) * | 1980-07-14 | 1984-04-17 | Oros Company | Cross flow solid-to-solid heat transfer apparatus |
DE3105624A1 (de) * | 1981-02-16 | 1982-09-02 | Hormon-Chemie München GmbH, 8000 München | Material zum abdichten und heilen von wunden |
US4424208A (en) * | 1982-01-11 | 1984-01-03 | Collagen Corporation | Collagen implant material and method for augmenting soft tissue |
DE3360633D1 (en) * | 1982-02-12 | 1985-10-03 | Unitika Ltd | Anti-cancer device |
US4482386A (en) | 1982-03-26 | 1984-11-13 | Warner-Lambert Company | Method of conditioning a water swellable hydrocolloid |
US4543332A (en) | 1982-03-29 | 1985-09-24 | Miles Laboratories, Inc. | Method for the preparation of spherical microorganism cell aggregates |
US4540410A (en) | 1982-11-16 | 1985-09-10 | Serono Pharmaceutical Partners | Lyophilized compositions, preparation and use thereof |
EP0132983B2 (en) | 1983-07-14 | 1991-06-12 | Hitachi Chemical Co., Ltd. | Production of gelatin spherical gels and their use |
JPS60100516A (ja) | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | 徐放型マイクロカプセルの製造法 |
US4515637A (en) * | 1983-11-16 | 1985-05-07 | Seton Company | Collagen-thrombin compositions |
AT389815B (de) * | 1984-03-09 | 1990-02-12 | Immuno Ag | Verfahren zur inaktivierung von vermehrungsfaehigen filtrierbaren krankheitserregern in blutprodukten |
US4600574A (en) * | 1984-03-21 | 1986-07-15 | Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte | Method of producing a tissue adhesive |
US4837285A (en) * | 1984-03-27 | 1989-06-06 | Medimatrix | Collagen matrix beads for soft tissue repair |
JPS6144825A (ja) * | 1984-08-09 | 1986-03-04 | Unitika Ltd | 止血剤 |
GB8422950D0 (en) * | 1984-09-11 | 1984-10-17 | Warne K J | Hydrogel |
JPS61122222A (ja) * | 1984-11-19 | 1986-06-10 | Koken:Kk | コラ−ゲン又はゼラチンとプロタミンとよりなる止血剤 |
US5165938A (en) | 1984-11-29 | 1992-11-24 | Regents Of The University Of Minnesota | Wound healing agents derived from platelets |
US5178883A (en) * | 1984-11-29 | 1993-01-12 | Regents Of The University Of Minnesota | Method for promoting hair growth |
US4600533A (en) | 1984-12-24 | 1986-07-15 | Collagen Corporation | Collagen membranes for medical use |
US5007916A (en) * | 1985-08-22 | 1991-04-16 | Johnson & Johnson Medical, Inc. | Method and material for prevention of surgical adhesions |
IE59361B1 (en) * | 1986-01-24 | 1994-02-09 | Akzo Nv | Pharmaceutical preparation for obtaining a highly viscous hydrogel or suspension |
IL78826A (en) * | 1986-05-19 | 1991-05-12 | Yissum Res Dev Co | Precursor composition for the preparation of a biodegradable implant for the sustained release of an active material and such implants prepared therefrom |
US4946870A (en) * | 1986-06-06 | 1990-08-07 | Union Carbide Chemicals And Plastics Company Inc. | Delivery systems for pharmaceutical or therapeutic actives |
US5300494A (en) * | 1986-06-06 | 1994-04-05 | Union Carbide Chemicals & Plastics Technology Corporation | Delivery systems for quaternary and related compounds |
US4832686A (en) * | 1986-06-24 | 1989-05-23 | Anderson Mark E | Method for administering interleukin-2 |
US4803075A (en) * | 1986-06-25 | 1989-02-07 | Collagen Corporation | Injectable implant composition having improved intrudability |
CA1305069C (en) | 1987-03-11 | 1992-07-14 | John Cornell | Wound dressings in sheet or gelled paste form |
US4885161A (en) | 1987-03-11 | 1989-12-05 | Medi-Tech International Corporation | Wound dressings in gelled paste form |
US5080893A (en) * | 1988-05-31 | 1992-01-14 | University Of Florida | Method for preventing surgical adhesions using a dilute solution of polymer |
US5017229A (en) * | 1990-06-25 | 1991-05-21 | Genzyme Corporation | Water insoluble derivatives of hyaluronic acid |
US5350573A (en) * | 1988-05-31 | 1994-09-27 | University Of Florida Research Foundation, Inc. | Method and composition for preventing surgical adhesions |
US5140016A (en) * | 1988-05-31 | 1992-08-18 | University Of Florida | Method and composition for preventing surgical adhesions using a dilute solution of polymer |
US5447966A (en) * | 1988-07-19 | 1995-09-05 | United States Surgical Corporation | Treating bioabsorbable surgical articles by coating with glycerine, polalkyleneoxide block copolymer and gelatin |
US5041292A (en) * | 1988-08-31 | 1991-08-20 | Theratech, Inc. | Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents |
US4925677A (en) * | 1988-08-31 | 1990-05-15 | Theratech, Inc. | Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents |
US5126141A (en) * | 1988-11-16 | 1992-06-30 | Mediventures Incorporated | Composition and method for post-surgical adhesion reduction with thermo-irreversible gels of polyoxyalkylene polymers and ionic polysaccharides |
US5135751A (en) * | 1988-11-16 | 1992-08-04 | Mediventures Incorporated | Composition for reducing postsurgical adhesions |
US5510418A (en) * | 1988-11-21 | 1996-04-23 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
US5162430A (en) * | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
US5614587A (en) * | 1988-11-21 | 1997-03-25 | Collagen Corporation | Collagen-based bioadhesive compositions |
US4891359A (en) * | 1988-12-08 | 1990-01-02 | Johnson & Johnson Patient Care, Inc. | Hemostatic collagen paste composition |
DE3903672C1 (zh) * | 1989-02-08 | 1990-02-01 | Lohmann Gmbh & Co Kg | |
EP0493387B1 (en) | 1989-08-10 | 1993-10-20 | W.L. Gore & Associates, Inc. | A medical dispensing system for tissue adhesive components |
US5196185A (en) | 1989-09-11 | 1993-03-23 | Micro-Collagen Pharmaceutics, Ltd. | Collagen-based wound dressing and method for applying same |
US5061274A (en) | 1989-12-04 | 1991-10-29 | Kensey Nash Corporation | Plug device for sealing openings and method of use |
US5219328A (en) * | 1990-01-03 | 1993-06-15 | Cryolife, Inc. | Fibrin sealant delivery method |
US5134229A (en) * | 1990-01-12 | 1992-07-28 | Johnson & Johnson Medical, Inc. | Process for preparing a neutralized oxidized cellulose product and its method of use |
JPH0813750B2 (ja) * | 1990-03-01 | 1996-02-14 | 持田製薬株式会社 | 経口用トロンビン製剤 |
US5306501A (en) * | 1990-05-01 | 1994-04-26 | Mediventures, Inc. | Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers |
US5595735A (en) * | 1990-05-23 | 1997-01-21 | Johnson & Johnson Medical, Inc. | Hemostatic thrombin paste composition |
US5292362A (en) * | 1990-07-27 | 1994-03-08 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
US5209776A (en) * | 1990-07-27 | 1993-05-11 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
US5108421A (en) * | 1990-10-01 | 1992-04-28 | Quinton Instrument Company | Insertion assembly and method of inserting a vessel plug into the body of a patient |
US5192300A (en) * | 1990-10-01 | 1993-03-09 | Quinton Instrument Company | Insertion assembly and method of inserting a vessel plug into the body of a patient |
NO302481B1 (no) * | 1990-10-16 | 1998-03-09 | Takeda Chemical Industries Ltd | Polymer for et preparat med forlenget frigjöring, samt preparat med forlenget frigjöring |
US5129882A (en) * | 1990-12-27 | 1992-07-14 | Novoste Corporation | Wound clotting device and method of using same |
US5690675A (en) | 1991-02-13 | 1997-11-25 | Fusion Medical Technologies, Inc. | Methods for sealing of staples and other fasteners in tissue |
WO1992022304A1 (en) * | 1991-06-14 | 1992-12-23 | Amgen Inc. | Collagen film drug delivery for proteins |
AT398079B (de) * | 1991-11-04 | 1994-09-26 | Immuno Ag | Präparation mit thrombinaktivität sowie verfahren zu ihrer herstellung |
DE69331096T2 (de) | 1992-02-28 | 2002-08-14 | Cohesion Tech Inc | Injektierbare, keramische verbindungen sowie verfahren zur deren herstellung und anwendung |
ATE193037T1 (de) * | 1992-02-28 | 2000-06-15 | Collagen Corp | Hochkonzentrierte homogenisierte kollagenzusammensetzungen |
US5204382A (en) * | 1992-02-28 | 1993-04-20 | Collagen Corporation | Injectable ceramic compositions and methods for their preparation and use |
US5384333A (en) * | 1992-03-17 | 1995-01-24 | University Of Miami | Biodegradable injectable drug delivery polymer |
WO1993021844A1 (en) * | 1992-04-23 | 1993-11-11 | Scimed Life Systems, Inc. | Apparatus and method for sealing vascular punctures |
IL105529A0 (en) * | 1992-05-01 | 1993-08-18 | Amgen Inc | Collagen-containing sponges as drug delivery for proteins |
AU4406793A (en) * | 1992-06-04 | 1993-12-30 | Clover Consolidated, Limited | Water-soluble polymeric carriers for drug delivery |
US5385606A (en) * | 1992-07-06 | 1995-01-31 | Kowanko; Nicholas | Adhesive composition and method |
US5413571A (en) * | 1992-07-16 | 1995-05-09 | Sherwood Medical Company | Device for sealing hemostatic incisions |
US5428022A (en) * | 1992-07-29 | 1995-06-27 | Collagen Corporation | Composition of low type III content human placental collagen |
US5514379A (en) * | 1992-08-07 | 1996-05-07 | The General Hospital Corporation | Hydrogel compositions and methods of use |
DE4227681C2 (de) | 1992-08-21 | 1995-05-18 | Becker & Co Naturinwerk | Wundabdeckungsmaterial auf der Basis von Kollagenfasern und Verfahren zu seiner Herstellung |
WO1994010913A1 (en) * | 1992-11-12 | 1994-05-26 | Neville Alleyne | Cardiac protection device |
US5667839A (en) * | 1993-01-28 | 1997-09-16 | Collagen Corporation | Human recombinant collagen in the milk of transgenic animals |
ATE203913T1 (de) | 1993-05-31 | 2001-08-15 | Kaken Pharma Co Ltd | Eine gelpräparation aus vernetzter gelatine, die einen basischen wachstumsfaktor für fibroblasten enthält |
FR2715309B1 (fr) * | 1994-01-24 | 1996-08-02 | Imedex | Composition adhésive, à usage chirurgical, à base de collagène modifié par coupure oxydative et non réticulé. |
US5674275A (en) | 1994-04-06 | 1997-10-07 | Graphic Controls Corporation | Polyacrylate and polymethacrylate ester based hydrogel adhesives |
US5531759A (en) * | 1994-04-29 | 1996-07-02 | Kensey Nash Corporation | System for closing a percutaneous puncture formed by a trocar to prevent tissue at the puncture from herniating |
EP0712635B1 (en) * | 1994-05-13 | 2003-05-02 | Kuraray Co., Ltd. | Medical polymer gel |
GB9415739D0 (en) | 1994-07-30 | 1994-09-21 | Scimat Ltd | Gel wound dressing |
US5516532A (en) * | 1994-08-05 | 1996-05-14 | Children's Medical Center Corporation | Injectable non-immunogenic cartilage and bone preparation |
US5931165A (en) * | 1994-09-06 | 1999-08-03 | Fusion Medical Technologies, Inc. | Films having improved characteristics and methods for their preparation and use |
US20030039695A1 (en) | 2001-08-10 | 2003-02-27 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Collagen carrier of therapeutic genetic material, and method |
US5698213A (en) | 1995-03-06 | 1997-12-16 | Ethicon, Inc. | Hydrogels of absorbable polyoxaesters |
US5580923A (en) | 1995-03-14 | 1996-12-03 | Collagen Corporation | Anti-adhesion films and compositions for medical use |
US6129761A (en) | 1995-06-07 | 2000-10-10 | Reprogenesis, Inc. | Injectable hydrogel compositions |
DK1704878T3 (da) * | 1995-12-18 | 2013-07-01 | Angiodevice Internat Gmbh | Tværbundne polymerpræparater og fremgangsmåder til deres anvendelse |
US6458889B1 (en) | 1995-12-18 | 2002-10-01 | Cohesion Technologies, Inc. | Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use |
US5752974A (en) * | 1995-12-18 | 1998-05-19 | Collagen Corporation | Injectable or implantable biomaterials for filling or blocking lumens and voids of the body |
US5748318A (en) * | 1996-01-23 | 1998-05-05 | Brown University Research Foundation | Optical stress generator and detector |
SK284693B6 (sk) | 1996-04-04 | 2005-09-08 | Baxter Aktiengesellschaft | Hemostatická huba, pokrytie rany, kit na prípravu pokrytia rany a spôsob prípravy huby |
US5902832A (en) * | 1996-08-20 | 1999-05-11 | Menlo Care, Inc. | Method of synthesizing swollen hydrogel for sphincter augmentation |
US7435425B2 (en) * | 2001-07-17 | 2008-10-14 | Baxter International, Inc. | Dry hemostatic compositions and methods for their preparation |
US6706690B2 (en) * | 1999-06-10 | 2004-03-16 | Baxter Healthcare Corporation | Hemoactive compositions and methods for their manufacture and use |
US6066325A (en) | 1996-08-27 | 2000-05-23 | Fusion Medical Technologies, Inc. | Fragmented polymeric compositions and methods for their use |
US7871637B2 (en) * | 1996-08-27 | 2011-01-18 | Baxter International Inc. | Dry hemostatic compositions and methods for their preparation |
US6063061A (en) | 1996-08-27 | 2000-05-16 | Fusion Medical Technologies, Inc. | Fragmented polymeric compositions and methods for their use |
US7320962B2 (en) * | 1996-08-27 | 2008-01-22 | Baxter International Inc. | Hemoactive compositions and methods for their manufacture and use |
CN1157355A (zh) * | 1996-10-21 | 1997-08-20 | 山西省化学纤维研究所 | 止血纤维组成及其气体牵伸法纺丝工艺 |
PT986408E (pt) * | 1997-06-03 | 2005-09-30 | Innogenetics Nv | Novos medicamentos baseados em polimeros compostos por gelatina modificada com metacrilamida |
US5908054A (en) | 1997-06-16 | 1999-06-01 | Fusion Medical Technologies, Inc. | Fluid dispersion and delivery assembly and method |
US5997895A (en) | 1997-09-16 | 1999-12-07 | Integra Lifesciences Corporation | Dural/meningeal repair product using collagen matrix |
WO1999013902A1 (en) | 1997-09-16 | 1999-03-25 | Integra Lifesciences Corporation | Product for promoting dural or meningeal tissue growth comprising collagen |
US6179872B1 (en) * | 1998-03-17 | 2001-01-30 | Tissue Engineering | Biopolymer matt for use in tissue repair and reconstruction |
US6227394B1 (en) * | 1998-06-09 | 2001-05-08 | Asahi Glass Company Ltd. | Glass bulb for a cathode ray tube and a method for producing a cathode ray tube |
US6110484A (en) * | 1998-11-24 | 2000-08-29 | Cohesion Technologies, Inc. | Collagen-polymer matrices with differential biodegradability |
US6328229B1 (en) | 1998-12-18 | 2001-12-11 | Cohesion Technologies, Inc. | Low volume mixing spray head for mixing and dispensing of two reactive fluid components |
US6312725B1 (en) | 1999-04-16 | 2001-11-06 | Cohesion Technologies, Inc. | Rapid gelling biocompatible polymer composition |
US6221109B1 (en) | 1999-09-15 | 2001-04-24 | Ed. Geistlich Söhne AG fur Chemische Industrie | Method of protecting spinal area |
US6312474B1 (en) | 1999-09-15 | 2001-11-06 | Bio-Vascular, Inc. | Resorbable implant materials |
WO2002022184A2 (en) | 2000-09-18 | 2002-03-21 | Organogenesis Inc. | Bioengineered flat sheet graft prosthesis and its use |
EE05587B1 (et) | 2001-01-25 | 2012-10-15 | Nycomed Pharma As | Meetod kollageenksna valmistamiseks |
AU2004245086B2 (en) | 2003-06-05 | 2008-06-26 | Baxter Healthcare S.A. | Compositions for repairing and regenerating human dura mater |
US8834864B2 (en) * | 2003-06-05 | 2014-09-16 | Baxter International Inc. | Methods for repairing and regenerating human dura mater |
WO2005049105A2 (en) * | 2003-11-10 | 2005-06-02 | Angiotech International Ag | Medical implants and anti-scarring agents |
US20080091277A1 (en) * | 2004-08-13 | 2008-04-17 | Kai Deusch | Surgical prosthesis having biodegradable and nonbiodegradable regions |
ES2367583T3 (es) | 2005-05-04 | 2011-11-10 | Suprapolix B.V. | Hidrogeles con enlaces de hidrógeno. |
WO2007001926A2 (en) | 2005-06-24 | 2007-01-04 | Hyperbranch Medical Technology, Inc. | Low-swelling hydrogel sealants for wound repair |
US8703122B2 (en) * | 2006-05-31 | 2014-04-22 | Baxter International Inc. | Method for directed cell in-growth and controlled tissue regeneration in spinal surgery |
TWI436793B (zh) | 2006-08-02 | 2014-05-11 | Baxter Int | 快速作用之乾密封膠及其使用和製造方法 |
AR069109A1 (es) * | 2007-10-30 | 2009-12-30 | Baxter Int | Uso de una biomatriz de colageno biofuncional regenerativa para tratar defectos viscerales o parietales |
US9039783B2 (en) | 2009-05-18 | 2015-05-26 | Baxter International, Inc. | Method for the improvement of mesh implant biocompatibility |
CN102802683B (zh) | 2009-06-16 | 2015-11-25 | 巴克斯特国际公司 | 止血海绵 |
-
2001
- 2001-07-17 US US09/908,464 patent/US7435425B2/en not_active Expired - Lifetime
-
2002
- 2002-06-21 ES ES07005206T patent/ES2317600T3/es not_active Expired - Lifetime
- 2002-06-21 DK DK02744588T patent/DK1414370T3/da active
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2004
- 2004-05-10 HK HK04103248A patent/HK1060277A1/xx not_active IP Right Cessation
-
2007
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2008
- 2008-07-21 US US12/176,945 patent/US8383141B2/en not_active Expired - Lifetime
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- 2009-05-19 US US12/468,316 patent/US8092820B2/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1270240A (zh) * | 2000-04-21 | 2000-10-18 | 中国石油化工集团公司 | 止血纤维及其制造方法 |
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