WO2023133928A1 - 一种造影剂、造影剂的制备方法及其应用 - Google Patents
一种造影剂、造影剂的制备方法及其应用 Download PDFInfo
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- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A—HUMAN NECESSITIES
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- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
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- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/14—Peptides, e.g. proteins
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- the invention relates to the field of a medical contrast agent, in particular, the invention relates to a contrast agent, a preparation method of the contrast agent and an application thereof.
- Magnetic Resonance Imaging uses radio frequency pulses to excite atomic nuclei with non-zero spins in a magnetic field. After the radio frequency pulses stop, the nuclei relax. During the relaxation process, an induction coil is used to The signal is collected and reconstructed according to a certain mathematical method to form a mathematical image. Specifically, relaxation refers to the deflection of the macroscopic magnetization vector after the hydrogen nuclei of the water molecules in the subject are excited by radio frequency to absorb energy during the MRI process. When the radio frequency pulse is turned off, the hydrogen nuclei will re-arrange along the direction of the external magnetic field , the process of releasing energy and returning to a state of equilibrium.
- the commonly used clinical MRI is mainly based on T 1 relaxation, T 2 relaxation and T 2 * relaxation imaging.
- exogenous contrast agents In order to enhance the difference in image signal intensity, exogenous contrast agents usually need to be injected during the existing MRI process, and the commonly used exogenous contrast agents are mainly gadolinium-containing contrast agents, which have the risk of causing kidney damage and deposition in the body, and this The contrast agent is only temporarily confined in the blood vessel, and will diffuse to the extravascular space after a few cardiac cycles, which may cause diagnostic bias.
- exogenous contrast agents include iron- and manganese-containing contrast agents, and rapid injection of iron-containing contrast agents is likely to cause complications such as phlebitis and hypotension, and the cost is higher than that of gadolinium-containing contrast agents; Has certain neurotoxicity.
- Oxyhemoglobin oxyhemoglobin
- Oxy-Hb oxyhemoglobin
- the hemoglobin molecule consists of two alpha ( ⁇ ) and two beta ( ⁇ ) subunits, each containing an iron-containing heme group to which oxygen can bind.
- Oxy-Hb has weak diamagnetism because the bonding of the oxygen leads to a configuration around the heme iron that has no unpaired electrons.
- the affinity between carbon monoxide and hemoglobin is 200-300 times higher than the affinity between oxygen and hemoglobin, so carbon monoxide is very easy to combine with hemoglobin, and hemoglobin is not easy to separate after combining with carbon monoxide, forming carbon monoxide hemoglobin (Carboxy-haemoglobin, HbCO for short).
- the present invention provides a contrast agent, a preparation method of the contrast agent and an application thereof.
- a preparation method of a contrast agent comprises the steps of:
- isolated blood containing oxyhemoglobin wherein the isolated blood is the subject's autologous blood or qualified isolated blood that meets the clinical standard allogeneic blood transfusion conditions with the same blood type as the subject;
- Carbon monoxide is passed into the isolated blood until the oxyhemoglobin is saturated with the carbon monoxide to obtain a contrast agent comprising carboxyhemoglobin.
- said obtaining the isolated blood containing oxyhemoglobin comprises the following steps:
- Ex vivo blood that meets preset specifications is collected by presetting a blood collection device and using phlebotomy.
- said passing carbon monoxide into said isolated blood until said oxyhemoglobin is saturated by said carbon monoxide comprises the following steps:
- the isolated blood was protected from light.
- said passing carbon monoxide into said isolated blood until said oxyhemoglobin is saturated by said carbon monoxide comprises the following steps:
- the inert gas is nitrogen or helium.
- the following steps are included:
- a contrast agent comprising carboxyhemoglobin is provided.
- a contrast agent as described in Scheme 2 can be used in MRI examinations.
- a contrast agent provided by the present invention Compared with the prior art, a contrast agent provided by the present invention, a method for preparing the contrast agent and its application have the following beneficial effects:
- a contrast agent, a preparation method of the contrast agent and its application in the present invention generate a contrast agent by using autologous blood or qualified isolated blood that meets the clinical standard allogeneic blood transfusion conditions with the same blood type as the subject, which not only avoids metal ions
- Adverse reactions such as allergies to contrast agents also reduce economic costs to a certain extent and facilitate large-scale and diversified popularization and application.
- Fig. 1 is a schematic flow chart of a preparation method of a contrast agent according to an embodiment of the present invention
- Step S101 Obtain isolated blood containing oxyhemoglobin, wherein the isolated blood is the subject's autologous blood or qualified isolated blood with the same blood type as the subject that meets clinical standard allogeneic blood transfusion conditions.
- the preset blood collection device includes a disposable blood collection needle and a vacuum anticoagulation tube.
- a disposable blood collection needle For specific blood collection, it is only necessary to open the package of the disposable blood collection needle, and quickly insert the needle into the vein cavity in the skin in an oblique direction along the direction of the vein to form an acute angle with the skin.
- the needle When the needle enters the blood vessel, there will be a small amount of blood return. Insert the needle at the other end of the blood collection tube into the vacuum anticoagulation tube. Due to the negative pressure in the vacuum anticoagulation tube, the blood will automatically flow into the test tube, and pull out the vacuum anticoagulation tube after reaching the preset blood collection volume. That's it.
- the range of the preset specification is generally not less than 10 milliliters and less than 50 milliliters.
- the preset specification is usually based on the blood volume of the subject to be examined for magnetic resonance imaging Set, the purpose of doing this is to effectively avoid the occurrence of carbon monoxide hemoglobin poisoning, for example, the concentration of carbon monoxide hemoglobin in mild poisoning is 10%-20%, the instantaneous maximum concentration of carbon monoxide hemoglobin in the blood should be lower than the lowest value of mild poisoning concentration 10% of.
- the preset specification can be selected as 10 milliliters, so that in the follow-up magnetic resonance imaging examination, the instantaneous maximum carbon monoxide hemoglobin concentration in the blood is about 2%, which is far lower than Carbon monoxide hemoglobin is 10%-20% of the concentration of mild carbon monoxide hemoglobin poisoning.
- autologous blood carbon monoxide hemoglobin injection is far lower than the concentration of carbon monoxide hemoglobin poisoning, and after inhaling fresh air, carbon monoxide can be dissociated from carbon monoxide hemoglobin 8 hours later, compared with gadolinium contrast
- the seventy-two hours of the metabolic cycle of the drug is greatly shortened, so that the safety of the patient is fully guaranteed.
- hyperbaric oxygen chamber treatment can be performed; if the subject has a serious adverse reaction related to carbon monoxide hemoglobin, the hyperbaric oxygen chamber can be directly administered treat.
- Step S103 Introducing carbon monoxide into the isolated blood until the oxyhemoglobin is saturated by the carbon monoxide to obtain a contrast agent containing carboxyhemoglobin.
- passing carbon monoxide into the isolated blood until the oxygenated hemoglobin is saturated with carbon monoxide comprises the following steps:
- black tape or opaque adhesive tape can be used to wrap the vacuum anticoagulation tube to protect it from light, especially outdoor ultraviolet radiation.
- a special vacuum anticoagulation tube that is protected from light can also be used.
- passing carbon monoxide into the isolated blood until oxygenated hemoglobin is saturated with carbon monoxide comprises the steps of:
- injecting carbon monoxide into the isolated blood without spilling the isolated blood can be performed by injecting carbon monoxide into the pre-extracted isolated blood stored in an anticoagulant tube until the oxygenated hemoglobin contained in it is completely saturated with carbon monoxide.
- complete saturation of oxyhemoglobin with carbon monoxide is determined by testing methods such as Raman spectroscopy.
- the step of discharging undissolved carbon monoxide is included.
- venting undissolved carbon monoxide includes the steps of:
- the inert gas is nitrogen or helium.
- the following steps are included: isolating the contrast agent from the outside air, and storing it in a preset environment for future use.
- to isolate the contrast agent from the outside air and store it in a preset environment for future use may be to tighten the test tube stopper of the vacuum anticoagulation tube to prevent it from contacting the outside air. °C, save for future use, and can be directly used for MRI-enhanced imaging when needed.
- the contrast agent can be isolated from the outside air, and stored in a preset environment. It can be used to tighten the test tube stopper of the vacuum anticoagulation tube to prevent it from contacting with the outside air. Store it at 4°C within 24 hours. When needed It can be directly used for MRI-enhanced imaging.
- another embodiment of the present invention provides a contrast agent, wherein the contrast agent includes carboxyhemoglobin.
- the same inventive concept as the preparation method of a contrast agent in the embodiment of the present invention and the contrast agent provided in another embodiment of the present invention provide an application of the contrast agent in another embodiment of the present invention.
- Yet another embodiment of the present invention provides a contrast medium application, which can be applied in magnetic resonance imaging examination.
- the prepared carbon monoxide hemoglobin contrast agent can be stored in isolation from the air, and can still be used for enhanced MRI on the same day.
- the carboxyhemoglobin contrast agent can also be prepared directly using the qualified isolated blood of a healthy donor of the same blood type that meets clinical standards.
- a contrast agent Compared with the prior art, a contrast agent, a preparation method of the contrast agent and application thereof of the present invention have the following beneficial effects:
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Abstract
一种造影剂、造影剂的制备方法及其应用，目的为了寻找更为有效的磁共振造影剂的实现方案，其造影剂的制备方法包括如下步骤：获取含有氧合血红蛋白的离体血液，其中，离体血液为受检者的自体血或者与受检者的血型相同的符合临床标准异体输血条件的合格离体血液；将一氧化碳通入离体血液中直至氧合血红蛋白被一氧化碳饱和，得到包含一氧化碳血红蛋白的造影剂。通过使用自体血或者与受检者的血型相同的符合临床标准异体输血条件的合格离体血液生成造影剂的方式，不仅避免了金属离子造影剂的过敏等不良反应，还在一定程度上降低了经济成本，便于大规模多样化的推广应用。
Description
本发明涉及一种医用造影剂领域，具体而言，本发明涉及一种造影剂、造影剂的制备方法及其应用。
磁共振成像(Magnetic Resonance Imaging，简称MRI)是利用射频脉冲对置于磁场中含有自旋不为零的原子核进行激励，射频脉冲停止后，原子核进行弛豫，在其弛豫过程中用感应线圈采集信号，按一定的数学方法重建形成数学图像。具体地，弛豫是指在MRI过程中，被测体中水分子的氢核受到射频激发吸收能量以后，宏观磁化矢量发生偏转，当射频脉冲关闭以后，氢核将重新沿着外磁场方向排列，释放出能量，恢复到平衡状态的过程。临床常用MRI主要基于T
1弛豫、T
2弛豫及T
2*弛豫成像。
为了增强图像信号强度的差异，在现有的MRI过程中通常需要注射外源造影剂，而常用的外源造影剂主要为含钆造影剂，有造成肾损伤及沉积体内的风险，而且这种造影剂只是暂时被限制在血管中，几个心动周期后，就会弥散至血管外间隙，可能造成诊断的偏倚。此外，外源造影剂还有含铁、含锰造影剂，而含铁造影剂快速推注易引起静脉炎、低血压等并发症，且成本较含钆造影剂更高；含锰造影剂则具有一定的神经毒性。
发明内容
为了寻找更为有效的磁共振造影剂的实现方案，考虑到在人体内血液中大部分血红蛋白是氧合血红蛋白(Oxyhemoglobin，简称Oxy-Hb)。血红蛋白分子由两个alpha(α)和两个beta(β)亚基组成，每个亚基都包含一个含铁的血红素基团，氧可以与之结合。Oxy-Hb具有弱抗磁性，因为氧的键合导致血红素铁周围的构型没有未配对的电子。而一氧化碳与血红 蛋白亲和力比氧气与血红蛋白的亲和力高200-300倍，所以一氧化碳极易与血红蛋白结合，血红蛋白与一氧化碳结合后不易分离，生成一氧化碳血红蛋白(Carboxy-haemoglobin，简称HbCO)。而血液中的氧合血红蛋白转变为一氧化碳血红蛋白时，血红蛋白中的氧与铁离子分离，血红蛋白构象发生改变，其阻碍了周围的水分子接近铁离子，因此形成的一氧化碳血红蛋白会有4个不成对电子，因此呈顺磁性，能缩短T1、T2及T2*的驰豫时间，可作为MRI的造影剂。因此，取出部分血液通过一氧化碳完全饱和后制成一氧化碳血红蛋白后，可作为自体或同血型受检者的造影剂应用于磁共振增强成像，避免外源性造影剂的过敏等不良反应。同时因为一氧化碳血红蛋白是大分子物质，不能透过血管内皮间隙渗透到组织中，因此在磁共振上观察到高、低灌注信号后，即可提示病变是富血供或乏血供性质，避免了传统钆剂的外渗到血管外间隙造成对病变血供特性的诊断困难。因此，本发明提供了一种造影剂、造影剂的制备方法及其应用。
方案一：
提供一种造影剂的制备方法，所述造影剂的制备方法包括如下步骤：
获取含有氧合血红蛋白的离体血液，其中，所述离体血液为受检者的自体血或者与所述受检者的血型相同的符合临床标准异体输血条件的合格离体血液；
将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和，得到包含一氧化碳血红蛋白的造影剂。
优选地，所述获取含有氧合血红蛋白的离体血液包括如下步骤：
通过预置采血装置并使用静脉采血法采集满足预设规格的离体血液。
优选地，所述将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和之前，包括如下步骤：
对所述离体血液做避光处理。
优选地，所述将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和包括如下步骤：
使用一氧化碳气体发生装置生成一氧化碳；
将所述一氧化碳通入所述离体血液中且使所述离体血液不外溢，直至 离体血液所含的氧合血红蛋白全部被所述一氧化碳饱和后，停止通入一氧化碳。
优选地，所述停止通入一氧化碳之后，包括如下步骤：
排出未溶解的一氧化碳。
优选地，所述排出未溶解的一氧化碳包括如下步骤：
在停止通入一氧化碳之后，使用惰性气体排出未溶解的一氧化碳。
优选地，所述惰性气体为氮气或氦气。
优选地，所述得到包含一氧化碳血红蛋白的造影剂之后，包括如下步骤：
将所述造影剂与外界空气隔绝，并在预设环境中保存备用。
方案二：
提供一种造影剂，所述造影剂包含一氧化碳血红蛋白。
方案三：
如方案二中所述的一种造影剂，能够应用在磁共振成像检查中。
与现有技术相比，本发明提供的一种造影剂、造影剂的制备方法及其应用具有如下有益效果：
本发明一种造影剂、造影剂的制备方法及其应用通过使用自体血或者与受检者的血型相同的符合临床标准异体输血条件的合格离体血液生成造影剂的方式，不仅避免了金属离子造影剂的过敏等不良反应，还在一定程度上降低了经济成本，便于大规模多样化的推广应用。
本发明附加的方面和优点将在下面的描述中部分给出，这些将从下面的描述中变得明显，或通过本发明的实践了解到。
本发明上述的和/或附加的方面和优点从下面结合附图对实施例的描述中将变得明显和容易理解，其中：
图1为本发明实施例一种造影剂的制备方法的流程示意图；
图2为本发明又一实施例提供一种造影剂应用中含有一氧化碳血红蛋白造影剂的人体血液和未经造影剂处理的人体血液的磁滞回线示意图。
为了使本技术领域的人员更好地理解本发明方案，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述。
在本发明的说明书和权利要求书及上述附图中的描述的一些流程中，包含了按照特定顺序出现的多个操作，但是应该清楚了解，这些操作可以不按照其在本文中出现的顺序来执行或并行执行，操作的序号如101、103等，仅仅是用于区分开各个不同的操作，序号本身不代表任何的执行顺序。另外，这些流程可以包括更多或更少的操作，并且这些操作可以按顺序执行或并行执行。
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
请参阅图1，图1示出了本发明实施例一种造影剂的制备方法的流程示意图，如图1所示，本发明实施例一种造影剂的制备方法包括如下步骤：
步骤S101：获取含有氧合血红蛋白的离体血液，其中，所述离体血液为受检者的自体血或者与所述受检者的血型相同的符合临床标准异体输血条件的合格离体血液。
在一些实施方式中，假设离体血液为受检者提供，则获取含有氧合血红蛋白的离体血液包括如下步骤：
通过预置采血装置并使用静脉采血法采集满足预设规格的离体血液。
在一些实施方式中，预置采血装置包括一次性采血针和真空抗凝管。具体采血时，只需要开一次性采血针包装，沿静脉走向将针头与皮肤成锐角方向斜行快速刺入皮肤内静脉腔。当针头进入血管后会见少量回血，将采血管另一端针插入真空抗凝管中内，因真空抗凝管内负压作用，血液自动流入试管，到达采血量预设规格后拔出真空抗凝管即可。
在一些实施方式中，预设规格的范围一般为不小于10毫升且小于50毫升，但是，需要特别说明的是，预设规格通常是基于待进行磁共振成像 检查的受检者的血容量来设定，这样做的目的是为了有效避免出现一氧化碳血红蛋白中毒情况的发生，譬如，一氧化碳血红蛋白轻度中毒浓度之10％—20％，血液中瞬时最大一氧化碳血红蛋白浓度要低于轻度中毒浓度最低值的10％。
示例地，假设一成年人血容量为5000毫升，则预设规格可以选择10毫升，这样，在做后续的磁共振成像检查中，血液中瞬时最大一氧化碳血红蛋白浓度约为2％，远远低于一氧化碳血红蛋白轻度中毒浓度之10％—20％，因此，自体血一氧化碳血红蛋白注射远低于一氧化碳血红蛋白中毒浓度，且在吸入新鲜空气后，8小时后一氧化碳便能从一氧化碳血红蛋白解离，比钆造影剂的代谢周期之七十二小时而大大缩短，这样就充分保障了患者的安全。特别地，若受检者发生一氧化碳血红蛋白相关的轻度不良反应，呼吸新鲜空气后无缓解，可进行高压氧舱治疗；若受检者发生一氧化碳血红蛋白相关的严重不良反应，可直接进行高压氧舱治疗。
步骤S103：将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和，得到包含一氧化碳血红蛋白的造影剂。
在一些实施方式中，将一氧化碳通入离体血液中直至氧合血红蛋白被一氧化碳饱和之前，包括如下步骤：
对离体血液做避光处理。
具体地，对离体血液做避光处理可以采用黑胶带或不透光胶布包绕真空抗凝管，使其避光，尤其避免室外紫外线照射。优选地，还可使用避光特制的真空抗凝管。
优选地，将一氧化碳通入离体血液中直至氧合血红蛋白被一氧化碳饱和包括如下步骤：
使用一氧化碳气体发生装置生成一氧化碳；
将一氧化碳通入离体血液中且使离体血液不外溢，直至离体血液所含的氧合血红蛋白全部被所述一氧化碳饱和后，停止通入一氧化碳。
示例地，将一氧化碳通入离体血液中且使离体血液不外溢可以采用将一氧化碳通入存放于抗凝管中的预先取出的离体血液，直至其所含氧合血红蛋白完全被一氧化碳饱和。
在一些实施方式中，含氧合血红蛋白完全被一氧化碳饱和由拉曼光谱等测试方法来确定。
在一些实施方式中，停止通入一氧化碳之后，包括如下步骤：排出未溶解的一氧化碳。
在一些实施方式中，排出未溶解的一氧化碳包括如下步骤：
在停止通入一氧化碳之后，使用惰性气体排出未溶解的一氧化碳。
优选地，惰性气体为氮气或氦气。
在一些实施方式中，在得到包含一氧化碳血红蛋白的造影剂之后，包括如下步骤：将造影剂与外界空气隔绝，并在预设环境中保存备用。
示例地，将造影剂与外界空气隔绝，并在预设环境中保存备用可以为拧紧真空抗凝管的试管塞，避免其与外界空气接触，在二十四小时内常温，即20℃—30℃，保存备用，在需要时，即可直接用于进行磁共振增强成像。
优选地，可将造影剂与外界空气隔绝，并在预设环境中保存备用可以为拧紧真空抗凝管的试管塞，避免其与外界空气接触，在二十四小时内4℃保存，在需要时，即可直接用于进行磁共振增强成像。
与本发明实施例一种造影剂的制备方法相同的发明构思，本发明另一实施例提供一种造影剂，其中，造影剂包含一氧化碳血红蛋白。
请参阅图2，同本发明实施例一种造影剂的制备方法以及本发明另一实施例提供一种造影剂相同的发明构思，本发明又一实施例提供一种造影剂应用。本发明又一实施例提供一种造影剂应用，能够应用在磁共振成像检查中。
在具体实施过程中，考虑到常规的增强磁共振检查分为两部分，前半部分是对被检者进行常规结构像序列扫描，约5—10分钟，后半部分是对被检者进行注射造影剂再进行的功能像序列扫描(如灌注加权成像序列)。因此，本发明拟在病人进行磁共振检查前10分钟，先取预设规格，譬如10毫升，血液存放于抗凝管中，而后启动制备高铁血红蛋白的流程，约15分钟内即可完成制备。待病人完成前半部分常规扫描后，可注入10毫升由一氧化碳血红蛋白制备装置处理后的自体血液进行磁共振检查。若常规MRI检查和增强MRI不同时进行，制备的一氧化碳血红蛋白造影剂可隔 绝空气存放，当天仍可用于增强MRI。亦可使用同血型的健康供体的符合临床标准的合格离体血液制备一氧化碳血红蛋白造影剂直接使用。
示例地，如图2所示，图2示出了本发明又一实施例提供一种造影剂应用中含有一氧化碳血红蛋白造影剂的人体血液和未经造影剂处理的人体血液的磁滞回线示意图，其中，HbCO为含有一氧化碳血红蛋白造影剂的人体血液；Oxy-Hb为未经造影剂处理的人体血液；磁滞回线表示磁场强度周期性变化时，强磁性物质磁滞现象的闭合磁化曲线。
从图2中可以看出，含有一氧化碳血红蛋白造影剂的人体血液具有顺磁性，磁矩为8.13，而未经造影剂处理的人体血液不具有顺磁性，磁矩为6.46，因此，本发明又一实施例提供一种造影剂应用可以用于增强MRI成像。
与现有技术相比，本发明一种造影剂、造影剂的制备方法及其应用具有如下有益效果：
本发明一种造影剂、造影剂的制备方法及其应用通过使用自体血或者与自体血相同血型的符合临床异体输血条件的合格离体血液生成造影剂的方式，不仅避免了金属离子造影剂的过敏等不良反应，还在一定程度上降低了经济成本，便于大规模多样化的推广应用。
以上所述仅是本发明的部分实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (10)
- 一种造影剂的制备方法，其特征在于，所述造影剂的制备方法包括如下步骤：获取含有氧合血红蛋白的离体血液，其中，所述离体血液为受检者的自体血或者与所述受检者的血型相同的符合临床标准异体输血条件的合格离体血液；将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和，得到包含一氧化碳血红蛋白的造影剂。
- 如权利要求1所述的造影剂的制备方法，其特征在于，所述获取含有氧合血红蛋白的离体血液包括如下步骤：通过预置采血装置并使用静脉采血法采集满足预设规格的离体血液。
- 如权利要求2所述的造影剂的制备方法，其特征在于，所述将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和之前，包括如下步骤：对所述离体血液做避光处理。
- 如权利要求1所述的造影剂的制备方法，其特征在于，所述将一氧化碳通入所述离体血液中直至所述氧合血红蛋白被所述一氧化碳饱和包括如下步骤：使用一氧化碳气体发生装置生成一氧化碳；将所述一氧化碳通入所述离体血液中且使所述离体血液不外溢，直至离体血液所含的氧合血红蛋白全部被所述一氧化碳饱和后，停止通入一氧化碳。
- 如权利要求4所述的造影剂的制备方法，其特征在于，所述停止通入一氧化碳之后，包括如下步骤：排出未溶解的一氧化碳。
- 如权利要求5所述的造影剂的制备方法，其特征在于，所述排出未溶解的一氧化碳包括如下步骤：在停止通入一氧化碳之后，使用惰性气体排出未溶解的一氧化碳。
- 如权利要求6所述的造影剂的制备方法，其特征在于，所述惰性气体为氮气或氦气。
- 如权利要求1所述的造影剂的制备方法，其特征在于，所述得到包含一氧化碳血红蛋白的造影剂之后，包括如下步骤：将所述造影剂与外界空气隔绝，并在预设环境中保存备用。
- 一种造影剂，其特征在于，所述造影剂包含一氧化碳血红蛋白。
- 如权利要求9所述的一种造影剂，其特征在于，所述造影剂能够应用在磁共振成像检查中。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4984574A (en) * | 1988-11-23 | 1991-01-15 | Seth Goldberg | Noninvasive fetal oxygen monitor using NMR |
| JPH05178900A (ja) * | 1991-12-27 | 1993-07-20 | Nippon Oil & Fats Co Ltd | 粉末状ヘモグロビンの製造方法 |
| WO2013016598A2 (en) * | 2011-07-27 | 2013-01-31 | Sangart, Inc. | Methods for reducing reperfusion injury using a hemoglobin-based carbon monoxide carrier |
| CN107137699A (zh) * | 2017-06-15 | 2017-09-08 | 中国医学科学院输血研究所 | 一种天然血红蛋白类血液代用品的脱氧方法和制备工艺 |
| CN107625954A (zh) * | 2016-07-19 | 2018-01-26 | 上海本素医药科技有限公司 | 含一氧化碳的血红蛋白制剂及其在抗炎症中的应用 |
| WO2021137196A1 (en) * | 2019-12-31 | 2021-07-08 | Crawley Adrian P | Deoxyhemoglobin in magnetic resonance imaging |
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| WO2006096774A2 (en) * | 2005-03-07 | 2006-09-14 | Sangart, Inc. | Composition and methods for delivering carbon monoxide (co) and nitric ozide (no) co to tissue using heme proteins as carriers |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4984574A (en) * | 1988-11-23 | 1991-01-15 | Seth Goldberg | Noninvasive fetal oxygen monitor using NMR |
| JPH05178900A (ja) * | 1991-12-27 | 1993-07-20 | Nippon Oil & Fats Co Ltd | 粉末状ヘモグロビンの製造方法 |
| WO2013016598A2 (en) * | 2011-07-27 | 2013-01-31 | Sangart, Inc. | Methods for reducing reperfusion injury using a hemoglobin-based carbon monoxide carrier |
| CN107625954A (zh) * | 2016-07-19 | 2018-01-26 | 上海本素医药科技有限公司 | 含一氧化碳的血红蛋白制剂及其在抗炎症中的应用 |
| CN107137699A (zh) * | 2017-06-15 | 2017-09-08 | 中国医学科学院输血研究所 | 一种天然血红蛋白类血液代用品的脱氧方法和制备工艺 |
| WO2021137196A1 (en) * | 2019-12-31 | 2021-07-08 | Crawley Adrian P | Deoxyhemoglobin in magnetic resonance imaging |
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