CN106267423A - 人Rh阳性红细胞吸附器 - Google Patents
人Rh阳性红细胞吸附器 Download PDFInfo
- Publication number
- CN106267423A CN106267423A CN201610540878.3A CN201610540878A CN106267423A CN 106267423 A CN106267423 A CN 106267423A CN 201610540878 A CN201610540878 A CN 201610540878A CN 106267423 A CN106267423 A CN 106267423A
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- blood
- adsorber
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- cell
- plasma
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Abstract
本发明涉及医学领域的人Rh阳性红细胞吸附器,其特征在于以4℃和37℃的生理盐水清洗新鲜Rh阳性O型红细胞,去除红细胞表面附着的免疫性抗体或天然抗体,经检测抗原性后,将细胞沉淀装配高生物相容性材料制成的圆柱形吸附器,至4/5,再加入3.5%甘露醇红细胞保存液,使红细胞浓度达80%,轻摇混匀,封口,置4℃保存定期使用,其中的净化器在出口处设置筛网,构成防止细胞碎片滤出的防线,当血浆滤过后,Rh抗体被其中的Rh阳性红细胞结合成固定的复合物,被破坏的红细胞碎片及与之结合而成的大分子复合物被净化器的筛网阻留,去除致病物质的血浆从净化器滤出后回输,以通过清除血浆Rh抗体而治疗血型不合溶血病。
Description
技术领域
本发明涉及医学领域的人Rh阳性红细胞吸附器,主要用于母胎血型不合孕妇血浆中抗胎儿红细胞抗体及红细胞溶解产物的清除。
背景技术
胎儿继承父亲和母亲各一半的基因成分,胎儿红细胞可以携带来自父体的抗原,表现为胎儿的血型不同于母体。当胎儿的红细胞进入母体的血液循环后,诱导母体的免疫***产生抗体,抗体经过胎盘进入胎儿血液循环***,结合胎儿红细胞,使胎儿红细胞被破坏,导致胎儿和新生儿的母胎血型不合溶血性疾病。
人类红细胞血型有26种,包括ABO血型、Rh血型以及MN、Lew、Kell和Fya等血型,但能引起母胎血型不合溶血病的血型以Rh血型和ABO血型为最常见。Rh血型抗原是由1号染色体上3对紧密连锁的等位基因决定的,共有6种抗原,即C和c,D和d,E和e。由于D抗原最早被发现,抗原性最强,故临床上凡是D抗原阳性者称为Rh阳性,无D抗原者称为Rh阴性。Rh血型抗原的抗原性决定了溶血病的严重程度,D抗原可引起严重的溶血病,其次为E抗原,再次为C、c和e抗原,d抗原的抗原性最弱,目前尚无抗d抗体发现。在我国汉族人群中Rh阴性的频率约为0.4%,而西北地区少数民族Rh阴性的频率高达10%以上。
虽然ABO血型不合的发生率很高,但胎儿溶血发生率很低,即使发生溶血,症状亦较轻,极少发生核黄疸和水肿,妊娠期无需特殊处理。而Rh血型不合虽然少见,但其引起母胎血型不合溶血病的病情程度要重于ABO血型不合,所以对Rh血型不合的诊断及预防极其重要。Rh血型不合由于母体产生大量抗胎儿红细胞的Rh抗体(IgG抗-D),进入胎儿体内后破坏大量的胎儿红细胞,使胎儿严重贫血、缺氧、心衰、肝脏损伤、低蛋白血症、全身水肿、胸水、腹水甚至胎死宫内。在新生儿时期,Rh血型不合溶血较ABO血型不合出现黄疸时间早,最早出现在出生后12小时内,多数出现在24小时内。由于溶血产生的大量胆红素不能及时从肝脏排除,使新生儿黄疸加重,大量的胆红素渗入脑细胞而引起核黄疸,常死于严重贫血、心力衰竭、核黄疸,死亡率很高。
虽然Rh抗体进入胎儿体内后通过破坏胎儿的红细胞而可引发严重的溶血病,但某些孕妇也能通过预先注射Rh抗体来预防入侵的Rh(D)阳性红细胞致敏机体,进而能预防Rh溶血病的发生。由于目前大多数国家已禁止用志愿者进行D抗原免疫,多克隆Ig抗-D的来源已十分有限,而利用EB病毒转化人B淋巴细胞分泌Ig抗-D或EB病毒转化结合细胞融合制备Ig抗-D,因在体内使用EBV转化的B淋巴细胞株或杂交瘤细胞株分泌的Ig抗-D仍存在很多问题,如所含的EBV有潜在的致病性;可能带有HIV和肝炎病毒等病原体;用杂交瘤技术生产的Ig抗-D含鼠源蛋白、容易引起过敏反应、或带有鼠的癌基因,所以通过直接在体内注射Ig抗-D来预防Rh溶血病就受到了限制。
目前临床上对母胎血型不合溶血病的治疗主要有孕期血浆置换、胎儿输血、终止妊娠和新生儿换血治疗。抗-D效价在32以上需考虑宫内输血,胎儿输血包括胎儿腹腔内输血和胎儿血管内输血,均具有一定风险,且无一被证实有效;新生儿高胆红素血症者可采用蓝光照射、静脉注射免疫球蛋白等药物治疗,必要时换血治疗,换血治疗仍为治疗新生儿溶血病的主要方法;妊娠期间抗-D效价在64以上,需考虑血浆置换治疗,孕妇血浆置换就是在体外循环通路中以滤过法分离孕妇的血细胞和血浆,去除血浆并以等量的置换液(新鲜冰冻血浆或5%白蛋白)补充回输,每次置换量2 000~3 000ml、速度20~30ml/min、治疗时间2~4h、每1~3d治疗1次;或每次取孕妇全血约400ml,低温离心后去其血浆约300ml,补充等量同型新鲜血浆,还输自身红细胞(RBC)。血浆置换能与被去除的血浆量成比例地降低致病抗体的滴度(效价),从而能延长胎儿在母体内的存活和生长发育时间、能延迟终止妊娠的时间,是母胎ABO、Rh或其它血型不合的孕妇在临床早期保胎治疗上的良好选择,具有较好的疗效,也无其他不良反应。但血浆置换只能去除血液中的部分抗体,不能中止抗体的继续产生,也不能逆转已发生的母胎血型不合溶血病,需要不间断地进行血浆置换才有效,仅适用于曾在妊娠20~22周前发生过胎儿水肿的孕妇,或配偶为致病抗原的纯合子者,特别是在去除部份致病抗体的同时,也一同去除了大量的血浆(多种有益成份),虽然以置换液作了补充,但无法完全补足被去除血浆及其各种有益成份,而且替补的置换液量大、费用昂贵,补充异体血浆易致传染病和输液反应等各种副作用,这就限制了血浆置换的普遍开展。
所以,迫切需要一种仅去除致病抗体、不去除血浆及其多种有益成份、无需使用血浆置换液的廉价、安全、无副作用的母胎血型不合溶血病的治疗新方法。
发明内容
为了解决久攻不克的母胎血型不合溶血病的治疗问题,本发明人提出了本发明。
本发明的目的是要提供人Rh阳性红细胞吸附器;另一目的是要提供吸附器的制备及应用方法。
本发明的目的是这样实现的:由采供血机构按成分输血的采集要求,制备新鲜Rh阳性“O”型浓缩红细胞,分别在4℃和37℃的条件下以生理盐水清洗4次,以去除红细胞表面可能存在的免疫性抗体或天然抗体,经检测抗原性后,取细胞沉淀装配高生物相容性材料制成的圆柱形吸附器,至4/5,加入3.5%甘露醇红细胞保存液,使红细胞浓度达80%,轻摇混匀,封口,置4℃保存备用,在吸附器的上下部均设置细胞筛网,顶径为500目,底径为50目,液体出口设置200目的细胞滤网,构成防止细胞碎片进入循环的第二道防线,液体进出口与网筛之间设置缓冲区以使体外循环的稳定,当血浆流经吸附器时,Rh抗体被其中的Rh阳性红细胞结合成固定的免疫复合物,被破坏的红细胞碎片及与之结合而成的大分子免疫复合物被吸附器的筛网阻留,去除致病物质的血浆从吸附器滤出后回输体内,以此清除血浆Rh抗体及红细胞溶解产物。
Rh抗体是母胎Rh血型不合溶血病的致病因子,Rh(D)阳性红细胞是Rh抗体的天然抗原,能与Rh抗体结合而将之吸附清除,本发明选取Rh阳性O型红细胞,在低温和室温下以生理盐水清洗以去除红细胞表面的天然和免疫性血型抗体,但保留吸附Rh抗体的抗原性而不吸附抗-A和抗-B的天然抗体,继之以3.5%甘露醇红细胞保存液为介质装配吸附器,易于定期保存,Rh(D)阳性红细胞易得,制备方法简便,以及因设置了多个极小出入口微孔的特制的吸附器筛网对红细胞碎片和大分子抗原抗体复合物的阻挡特性,形成了Rh阳性红细胞吸附Rh抗体和吸附器网筛机械阻挡红细胞溶解产物的双重净化屏障,使流经吸附器的血浆中的Rh抗体及溶血病患者的红细胞溶解产物被吸附清除,净化后的血浆回输,以此实现将Rh抗体从体内清除的治疗,是一种仅去除致病性抗体和红细胞溶解物,不去除血浆及其多种有益成份的无需血浆置换液的廉价、安全、无副作用的母胎血型不合溶血病的治疗新方法。
具体实施方式
图1是根据本发明提出的人Rh阳性红细胞吸附器的应用示意图。
图2是根据本发明提出的血浆分离器的内部结构示意图。
图3是根据本发明提出的免疫吸附器的内部结构示意图
图1中,动脉血路管(1)的一端与动脉血管相连通,另一端经肝素泵(2)和血液泵(3)与血浆分离器(4)相连,血浆分离器(4)经血浆泵(6)和循环管路(7)与2个并联的吸附器(8)、吸附器(9)相连,然后依次与循环管路(10)、静脉管路(5)相连,静脉管路(5)的另一端与静脉血管相连。
图2中,1是血浆分离器,2是血浆分离器内腔,3是血浆分离器内腔管壁上的微孔,4是不能通过微孔(3)的血细胞,5是能通过微孔(3)的小分子血浆成份,6是血浆分离器外腔,7是血浆流出口,8是可开关的阀门。
图3中,1是吸附器,2是位于吸附器中的Rh阳性红细胞,3是进入吸附器的Rh抗体,4是Rh抗体被Rh阳性红细胞结合而形成的抗原抗体免疫复合物,5为RBC碎片。
下面结合图1、图2和图3,对本发明提出的人Rh阳性红细胞吸附器的实施方案作详细的描述。
一、Rh(D)阳性红细胞的制备
1、Rh(D)阳性红细胞的获取
(1)从浙江省采供血机构购买新鲜浓缩Rh(D)阳性“O”型红细胞;(2)提取新生儿已离体的废弃脐带血中的Rh(D)阳性“O”型血红细胞。
2、主要试剂及作用
3.5%甘露醇红细胞保存液的配方为:取甘露醇17.5g、枸橼酸三钠1.5g、枸橼酸0.2g、葡萄糖7.93g、磷酸二氢钠0.94g、腺嘌呤0.14g、氯化钠4.97g,溶于500ml的蒸馏水中。其中甘露醇稀释浓缩红细胞粘稠度,增加细胞膜稳定性,防止溶血。枸橼酸钠与血液或血浆中的Ca2+结合形成难以离解的可溶性的枸橼酸钙,使血液中Ca2+减少,从而抑制凝血过程,产生抗凝作用,而且对红细胞有保护作用,可防止溶血的发生。枸橼酸防止红细胞添加剂中葡萄糖焦化,与枸橼酸钠形成缓冲对,调节和稳定溶液pH。葡萄糖为红细胞代谢的主要能量来源,正常情况下,葡萄糖的90%通过无氧酵解,10%通过磷酸戊糖途径生成ATP,提供红细胞能量维持其寿命。腺嘌呤可提高血液ATP在4℃贮存期间的活性水平。红细胞对腺嘌呤的需要是特异的,它可以将腺嘌呤转变为磷酸腺苷(AMP),并进一步磷酸化生成ATP,为红细胞新陈代谢活力提供高能化合物来源,大大延长血液在4℃的保存时间。氯化钠调节溶液渗透压为等渗溶液,为红细胞提供适量钠离子。磷酸二氢钠防止红细胞聚集,为红细胞能量代谢提供磷酸盐,减缓2,3-DPG下降速度。
抗-D标准品和Rh(D)标准红细胞购自广州联泰生物技术有限公司。
3、制备方法
(1)由采供血机构按成分输血的采集要求,制备新鲜Rh阳性“O”型浓缩红细胞,取足够量的新鲜Rh阳性O型红细胞,分别在4℃和37℃的条件下,以1500r/min×5min的离心速度,以等体积的生理盐水清洗红细胞4~5次,以去除红细胞表面可能附着的ABO血型和Rh血型以及其他的免疫性抗体或天然抗体。
(2)抗原性检测:①将红细胞与抗-D标准品37℃孵育5min,离心取上清液检测抗-D标准品效价降低数值来确定红细胞的抗原性。具体方法是:取试管10支,分别编号1~10,第1管加入红细胞沉淀1.0ml,其他各管加生理盐水0.5ml,然后从第1管吸红细胞沉淀0.5ml加入到第2管,混匀后吸0.5ml至第3管,以同样操作稀释至第10管,最后管吸出0.5ml弃去,每管加抗-D标准品0.5ml,37℃孵育5min,离心后轻轻混匀,以出现完全凝集、几乎无游离细胞的最大稀释倍数代表红细胞的抗原性,稀释倍数越大,抗原性越强,吸附Rh抗体的能力越强。也可以用Rh(D)标准红细胞测定上清液抗体效价来确定红细胞的抗原性;②用Rh(D)标准红细胞测定上清液抗体效价,抗-D标准品效价(已知)减去上清液抗体效价即为红细胞的抗原性(效价)。上清液抗体效价检测方法为:取10支试管,分别编号1~10,各管加入生理盐水1ml,取上清液1ml加入到第1管混匀后移出1ml转至第2管,以同样操作稀释至第10管,最后管吸出1ml液体弃去,将稀释好的血清40μl与Rh(D)标准红细胞10μl混合,孵育10分钟,离心5分钟判读结果,最大稀释倍数的凝集管即为抗原性(效价),效价应在1∶1500以上。
二、吸附器的制备
1、制备原理
本发明基于母胎Rh血型不合溶血病是因孕妇血浆中的游离Rh抗体进入胎儿血液破坏胎儿红细胞所致,而Rh抗体能被相应的天然抗原即Rh阳性红细胞结合吸附,以及吸附器的外壳可制成仅允许特定小分子通过的筛网以阻挡较大分子通过的机制制备。
2、制备材料
选用与人类血管内皮接近的高生物相容性材料,要求生物相容性好,无补体激活、无炎症反应、无白细胞、血小板、血氧分压、补体C3aC5a的改变。要求通过共价、接枝、聚合等方法改进材料表面的均匀性、亲水性、减少对凝血及氧化应激的影响。在吸附器内表面加亲水凝胶,如固化2甲基丙烯酰氧乙基磷酸胆碱-丁基异丁烯酸在醋酸纤维素膜上,通过控制湿纺过程而生成CA/PMB30、CA/PMB80和CA/PMB30-80,可以提高生物相容性。将某些抗凝物质固化在载体或吸附器内表面,可抑制血液凝固、降低肝素用量甚至实现无肝素化,如将肝素聚合在聚丙烯腈-聚乙烯亚胺膜上,可减少过敏体质的过敏反应;将肝素共价结合到聚醚砜表面,可保持聚醚砜的力学性能和提高吸附器内表面的抗凝血性能。在醋酸纤维膜上共价固化亚油酸膜,或将共价结合到聚丙烯酸的亚油酸嫁接到聚砜膜表面,都可以有更好的组织相容性和抗凝血效果。
3、吸附器外壳的规格
制成50mm×60mm的底径小、顶径大的圆柱形容器,或制成方形、漏斗形,容积约200~300ml,上下部均设有细胞筛网,顶径筛网目数为500目,底径筛网目数为50目,液体出口处设置目数为200目的细胞滤网,构成了防止细胞碎片进入循环的第二道防线,液体进出口与网筛之间设有缓冲区,有利于***循环的稳定性。
4、吸附剂的充填
取本发明制备的Rh(D)阳性红细胞,装入吸附器,至4/5,加入3.5%甘露醇的红细胞保存液,使红细胞浓度达80%,轻摇混匀,封口,置4℃保存备用。
三、血浆分离器的制备
1、制备原理:根据血细胞和血浆成份的分子大小制备。如人体血液中有形成份(血细胞)的大小为:正常红细胞大约为7微米(μm),是双凹圆盘状的细胞;白细胞分为5种,中性粒细胞约12μm,嗜酸性粒细胞略大些,嗜碱性粒细胞与中性粒细胞接近,小淋巴细胞6-8μm,与红细胞近似,单核细胞最大,约15-20μm。血小板为圆盘形,直径1~4微米到7~8微米不等,人的血小板平均直径为2-4微米,厚0.5~1.5微米。
2制备材料:可选用聚醋无纺布、醋酸纤维、脱脂棉等,要求生物相容性好,几乎不激活补体、不引起炎症反应、不引起白细胞、血小板、血氧分压、补体C3a、C5a的改变。可通过共价、接枝、聚合等方法改进材料的结构、调节表面的微观不均匀性、亲水性、减少对凝血及氧化应激的影响、从而提高筛滤充分性和生物相容性、减少并发症的发生。
3规格:就分离器的外形来说,可以醋酸纤维或脱脂棉等材料作滤芯制备成柱形结构、以聚醋无纺布等材料作滤芯制备成扁平结构等形状;按待分离的血细胞和血浆成份的分子大小确定孔径。本发明所涉及的血浆分离器用性质稳定、生物相容性好、通透性高的高分子聚合物制成空心纤维型滤器,空心纤维膜直径为270~370μm,膜厚度为50μm,孔径为0.2~0.6μm,纤维长度为13.5~26μm。该孔仅准许血浆滤过,但能阻挡所有的细胞成分。
四、本发明的应用
需与相关构件共同组成体外循环支路。
1、体外循环支路的构件及用途
(1)吸附器:内部的Rh(D)阳性红细胞用于清除Rh抗体;吸附器外壳进出口的网筛具有滤除RBC碎片、Rh抗体与RBC碎片形成的大分子复合物的作用。
(2)血浆分离器:用于分离血细胞和血浆。
(3)动静脉压监测:动脉压监测主要用以动态监测吸附器微孔的堵塞情况,另外用以监测体外循环血栓、凝固和压力的变化。当血流不足时,动脉压就会降低;当有凝血、血栓形成,特别是吸附器微孔堵塞时,动脉压就会升高;静脉压监测用来监测管路血液回流的压力,当吸附器微孔堵塞、凝血、血栓形成、血流不足以及静脉血回流针头脱落时,静脉压就会下降,如果血路回流管扭曲堵塞或回流针头发生堵塞时,静脉压就会升高。
(4)空气监测(Air Detector):用来监测血液流路的空气气泡,一般用超声波探测的原理,为了避免病人发生空气栓塞而设置。当监测到有空气气泡时,检测***会驱动动、静脉血路夹来阻断血流,防止危险的发生。
(5)血泵(Blood Pump):用来推动血液循环以维持治疗的顺利进行,通常血泵部分往往具有转速检测功能,以监测病人的血流情况,因此血泵转轮与凹槽间距设定要精确,并需要经常调整,根据血路泵管的情况,一般将间距设定为3.2~3.3mm,不可太松,否则会造成血流检测不准;也不可太紧,否则会造成管路破裂。
(6)肝素泵(Heparin Pump):肝素泵相当于临床上应用的微量注射泵,用以持续向筛滤管道(病人血液)中注射肝素,由于病人的血液在体外循环与空气接触,容易发生凝血现象,使用肝素泵可以防止凝血的发生。
此外还包括温度控制***、配液***、除气***、电导率监测***、超滤监测和漏血监测等部分。总之,在本发明关键构成体系的基础上,有望进一步发展为自动化、人性化、个性化、模块化、自动监测及调控、液晶显示、自行判断警报原因及解除信号等微电脑处理***。
2、本发明的使用方法
(1)安装:以无菌操作连接各部件,包括血浆分离器、吸附器及各循环管路等各部。
(2)排气:以无菌生理盐水充液分离器、吸附器及各循环管路,排除分离器、吸附器及其循环管道内的气体、气泡,仔细检查,确认无气体、气泡后使用。
(3)通液:将动脉血路管1接通艾滋病患者的动脉血管,在操作中再次仔细检查排气是否完全,液流是否通畅,并避免管内流液污染。
(4)抗凝:从肝素泵向液流中注射抗凝剂(肝素),初次为2500∪或20~30∪/kg。
(5)启动:将动脉血路管(1)接通治疗者的动脉血管,将静脉管路(5)接通治疗者的静脉血管,然后打开血液泵,血流量为100~150ml/min,如图1,当动脉血液经动脉血路管(1)进入血浆分离器(4),分离出来的血浆在血浆泵(6)的作用下经循环管路(7)到达吸附器(8),待充满血浆、约10分钟,开始放出血浆,经循环管路(10)流出,同步向吸附器(9)灌注血浆,在吸附器(8)内的血浆将近流完时,再次开始灌注血浆,此时吸附器(9)开始放出血浆,两个并联的吸附器(8)、吸附器(9)交替进行。如图2,当待分离的血液进入血浆分离器(1)的内腔(2)时,经阀门(8)的作用,能通过微孔(3)的小分子血浆及其成份(5)进入分离器的外腔(6),然后经血浆出口(7)流出,而不能通过微孔(3)的血细胞(4)经阀门(8)流出。如图3,当Rh抗体(3)随血浆进入吸附器(1)时,被吸附器中的Rh阳性红细胞(2)结合成抗原抗体复合物(4)而不再往下移动,被破坏的红细胞碎片(5)及与之结合而成的大分子抗原抗体复合物不能通过吸附器出口的网筛而被阻留,净化后的血浆与血浆分离器分离出来的血细胞汇合后回输,如此直至事先设定的血浆循环量(通常为9L),治疗才宣告结束,如果配套电脑程序控制,整个治疗过程均由电脑控制,并可随时检测工作状态,使用会更加方便、自动化和安全。
五、本发明应用功效的验证
为了验证吸附器清除Rh抗体的功效,本发明设计了简易的测试方法:取灭菌的2.5×300mm魏氏血沉管9支,吸取Rh(D)阳性红细胞沉淀至250mm刻度,再接着吸取适量的经100℃溶化后保温在42℃备用的1.0%琼脂糖C1-4B,琼脂糖冷却后成为半固体,能将红细胞固定在管内,以此制成简易的园柱形吸附器。另外购买浙江省中心血站的新鲜冰冻血浆200mL及Rh抗体(人抗D型血清干粉标准品,广州联泰生物技术有限公司),以新鲜血浆配成1∶200、1∶300、1∶600抗体滴度,按常规Rh(抗D)滴度检测方法(参考说明书),进一步检测确认上述所配制的抗体滴度是否相符,称为滤前(Rh)抗体(滴度),然后各取10ml滤前抗体分别注入3支血沉管的上端空管,待流经血沉管内的红细胞后,收集流出液,称为滤后(Rh)抗体,按常规Rh(抗D)滴度检测方法确认滴度,再分别将滤后抗体经含有Rh(D)阳性红细胞的血沉管中作第2次滤出,如此重复3次滤过及抗体滴度检测,结果(表1)说明,Rh抗体滤过简易的吸附器后,大部分Rh抗体已被相应的Rh(D)阳性红细胞吸附,经第1次、第2次、第3次滤过后,Rh抗体的平均滴度分别从滤前的1∶367降为滤后的1∶183、1∶58、1∶29,说明随着滤过次数的增加,Rh抗体会不断地被Rh(D)阳性红细胞吸附清除,从而达到降低孕妇(新生儿)血浆Rh抗体滴度而治疗母胎血型不合溶血病的目的。
表1 Rh抗体滤过含有Rh(D)阳性红细胞的吸附器前后滴度检测结果(1/x)
Claims (10)
1.一种用于医学领域的人Rh阳性红细胞吸附器,其特征在于,分别以4℃和37℃的生理盐水清洗Rh阳性“O”型红细胞,去除免疫性和天然抗体,以3.5%甘露醇的红细胞保存液配制80%浓度的细胞悬液,灌注出口处设置筛网的柱状吸附器,用于体外吸附装置中清除血浆Rh抗体和红细胞溶解物。
2.根据权利要求1所述的人Rh阳性红细胞吸附器,其特征在于,所述Rh抗体指Ig抗D、Ig抗E、Ig抗e、Ig抗C、和Ig抗c。
3.根据权利要求1所述的人Rh阳性红细胞吸附器,其特征在于,所述Rh阳性“O”型红细胞指仅能吸附Rh抗体。
4.根据权利要求1所述的人Rh阳性红细胞吸附器,其特征在于,所述吸附器的外壳容积为200~300ml,上下部均设有细胞筛网,顶径筛网目数为500目,底径筛网目数为50目,液体出口处设置目数为200目的细胞滤网,液体进出口与网筛之间设有缓冲区。
5.根据权利要求1所述的人Rh阳性红细胞吸附器,其特征在于,所述体外吸附装置包含血浆分离器。
6.根据权利要求5所述的人Rh阳性红细胞吸附器,其特征在于,所述血浆分离器为空心纤维型滤器,内腔通过管壁上的微孔与外腔相通。
7.根据权利要求6所述的人Rh阳性红细胞吸附器,其特征在于,所述分离器空心纤维滤膜直径为270~370μm,膜厚度为50μm,孔径为0.2~0.6μm,纤维长度为13.5~26μm,能滤过血浆但不能滤过所有的细胞成分。
8.根据权利要求1所述的人Rh阳性红细胞吸附器,其特征在于,所述3.5%甘露醇的红细胞保存液为甘露醇17.5g、枸橼酸三钠1.5g、枸橼酸0.2g、葡萄糖7.93g、磷酸二氢钠0.94g、腺嘌呤0.14g、氯化钠4.97g,溶于500ml的蒸馏水中。
9.根据权利要求1-7任一所述的人Rh阳性红细胞吸附器在制备体外吸附装置中的应用,其特征在于,所述体外吸附装置包括动脉血路管(1)的一端经肝素泵(2)和血液泵(3)与血浆分离器(4)相连,血浆分离器(4)经血浆泵(6)和循环管路(7)与两个并联的吸附器(8)、吸附器(9)相连,然后依次与循环管路(10)、静脉管路(5)相连。
10.根据权利要求9所述的应用,其特征在于,在启用图1所示的体外吸附装置时,动脉血液经动脉血路管(1)进入血浆分离器(4),分离出来的血浆在血浆泵(6)的作用下经循环管路(7)到达吸附器(8),待充满血浆、约10分钟,开始放出血浆,经循环管路(10)流出,同步向吸附器(9)灌注血浆,在吸附器(8)内的血浆将近流完时,再次开始灌注血浆,此时吸附器(9)开始放出血浆,两个并联的吸附器(8)、吸附器(9)交替进行。
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Effective date of registration: 20200908 Address after: 310006 No. 1, bachelor Road, Zhejiang, Hangzhou Co-patentee after: Shu Lan (Hangzhou) Hospital Ltd. Patentee after: WOMEN'S HOSPITAL, SCHOOL OF MEDICINE, ZHEJIANG University Address before: The 317300 Ring Road Zhejiang County of Xianju province to the north, Xianju County Hospital Patentee before: Weng Binghuan |