CN116459342A - Thrombolytic composition for acute myocardial infarction occlusion of distal end of blood vessel - Google Patents
Thrombolytic composition for acute myocardial infarction occlusion of distal end of blood vessel Download PDFInfo
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- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
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Abstract
The invention provides a thrombolytic composition for occluding a distal end of a blood vessel in acute myocardial infarction, which comprises a thrombolytic agent, a contrast agent and a solvent matched with the osmotic pressure of blood plasma for a human body, wherein the solvent is histidine-tryptophan-ketoglutarate liquid. The microcatheter is guided by the guide wire to pass through the blood vessel at the occlusion section to the distal end, the thrombolytic composition is injected to the distal end of the blood vessel at the occlusion, the imaging of the blood vessel at the distal end of the occlusion can be seen in the injection process, the contrast agent is remained, at the moment, the thrombolytic composition fills the blood vessel at the occlusion, and the thrombolysis effect starts to be exerted. The contrast agent contained in the thrombolytic composition for acute myocardial infarction occlusion of the distal end of a blood vessel can realize real-time observation of the whole thrombolytic process, can adjust the dosage and the administration speed of the thrombolytic agent in real time, and can be matched with the thrombolytic agent to act on a lesion together by adopting a solvent of histidine-tryptophan-ketoglutarate liquid, thereby improving acidosis of cells, effectively thrombolysis and simultaneously obtaining better rescuing opportunity for patients.
Description
Technical Field
The invention relates to the technical field of thrombolysis, in particular to a thrombolytic composition for occluding a distal end of a blood vessel in acute myocardial infarction.
Background
Acute Myocardial Infarction (AMI) is a serious life threatening acute critical disorder, and clinical studies have confirmed that in ST elevation AMI, more than 90% of coronary artery is completely occluded due to acute thrombosis. Opening the infarct-related artery sufficiently in time is the most effective therapeutic measure. The emergency PCI operation establishes a green channel in the shortest time for saving the life of the critical acute myocardial infarction, and improves the rescue success rate of critical patients.
At present, there are two approaches for thrombolysis treatment of acute myocardial infarction, namely intravenous thrombolysis and intracoronary thrombolysis through a guide catheter, and the two approaches are forward thrombolysis, namely thrombolysis agent reaches the infarct position along with the direction of blood flow, and plays roles of thrombolysis and vessel opening. Intravenous thrombolysis: in the time window of acute ST elevation type myocardial infarction, a large amount of thrombolytic agent is applied to dissolve coronary thrombosis and open the therapy of blocking coronary artery by intravenous administration. Coronary thrombolysis through the guide catheter: in emergency intervention, after the catheter is guided to reach the coronary artery opening, thrombolytic agents are injected into the coronary artery through the catheter to dissolve thrombus and open the coronary artery.
However, the thrombolysis processes of the two thrombolysis modes are invisible, the process and effect of thrombolysis cannot be directly and continuously observed, and in addition, the thrombolysis agents are required to be used in large doses, so that related complications such as bleeding and the like are easily caused. Along with the development of technology, in the operation of treating acute myocardial infarction, a novel method for treating thrombus is also provided, and urokinase is injected into the distal end of an occlusion vessel to perform thrombolysis of the distal end of the occlusion vessel of the acute myocardial infarction, and the method has the following problems in application: the adopted solvent is usually sodium chloride injection or glucose injection, when the solvent is used in an acute myocardial infarction operation, the solvent has a certain difference with the osmotic pressure matching of human plasma, the myocardial infarction part is in an acidic environment, and the solvent is unfavorable for the correction of the acidic environment and has a great room for improvement.
Disclosure of Invention
The invention aims to solve the problems and provide a thrombolytic composition for occluding the distal end of a blood vessel in acute myocardial infarction, so as to relieve acidosis of the heart during operation caused by ischemia, thereby being beneficial to competing for rescue time.
The technical aim of the invention is realized by the following technical scheme: a thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction comprising: thrombolytic agents and contrast agents, and a solvent for matching the osmotic pressure of human plasma, wherein the solvent is histidine-tryptophan-ketoglutarate liquid.
The invention is further provided with: the weight ratio of the thrombolytic agent to the solvent is as follows: 1:3000-5000.
The invention is further provided with: the volume ratio of the contrast agent to the solvent is 1:3-5.
The invention is further provided with: the thrombolytic agent is one or more of urokinase, prourokinase, alteplase and reteplase.
The invention is further provided with: the contrast agent is iopromide or iodixanol.
The invention is further provided with: the thrombolytic agent is first mixed with the solvent and then with the contrast agent.
The invention also provides a using method of the thrombolytic composition for occluding the distal end of a blood vessel in acute myocardial infarction, which comprises the following steps: the distal thrombolytic agent for coronary occlusion vessel is injected into the diseased vessel, wherein 1-2ml is injected once every 30 s.
In summary, the invention has the following beneficial effects:
the thrombolytic composition for the distal end of an occluded blood vessel of acute myocardial infarction mixes thrombolytic agent, contrast agent and solvent of histidine-tryptophan-ketoglutarate liquid together, in the process of thrombolysis of the distal end of an occluded blood vessel of acute myocardial infarction, firstly, a lesion blood vessel is judged through conventional radiography, then a guide wire is selected to pass through an occluded section of the lesion blood vessel to the distal end of the lesion blood vessel, a microcatheter passes through the occluded section blood vessel to the distal end of the occluded section by the guide wire to be 2-3cm, and the guide wire is withdrawn; the thrombolytic agent is shot through the microcatheter, 1-2ml of the thrombolytic agent is shot for 1 minute each time, and the microcatheter is gradually retracted and gradually reaches the occlusion. The development of the blood vessel distal to the occlusion can be seen during the injection, with the contrast agent remaining, indicating that the thrombolytic agent has filled the occluded blood vessel and begun to exert thrombolytic effects. The action is carried out in two directions simultaneously, namely, in the microcirculation direction, the micro thrombus in the microcirculation vascular bed can be fully contacted with thrombolytic agent to be dissolved; secondly, thrombolysis at the distal end of the occlusion vessel of acute myocardial infarction dissolves coronary artery trunk thrombus until the trunk thrombus is completely dissolved, the occlusion vessel is opened, and forward blood flow is restored, so that a doctor can conveniently perform balloon dilation combined stent implantation treatment on a patient according to pathological conditions.
In addition, the solvent of histidine-tryptophan-ketoglutarate liquid can have better effect of preventing and neutralizing acidosis generated during hot ischemia in a larger temperature range, and simultaneously, the thrombolytic agent and the solvent of histidine-tryptophan-ketoglutarate liquid can jointly act on an affected part, so that acidosis of cells can be greatly improved, thrombolysis can be effectively realized, and better rescuing time is provided for patients.
Detailed Description
In order to make the solution of the present invention better understood by a person skilled in the art, the following description of the solution of the present invention is given in further detail by way of examples of the present invention, it being obvious that the examples described are only some, not all, examples of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.
It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other. The present invention will be described in detail with reference to examples.
Examples:
the invention provides a thrombolytic composition for occluding a distal end of a blood vessel in acute myocardial infarction, which comprises a thrombolytic agent, a contrast agent and a solvent matched with the osmotic pressure of human plasma, wherein the solvent is histidine-tryptophan-ketoglutarate liquid.
Wherein the thrombolytic agent may be one or more thrombolytic agents such as: one or more of urokinase, prourokinase, alteplase and reteplase. The contrast agent may be iopromide or iodixanol.
In addition, the weight ratio of thrombolytic agent to solvent is: 1:3000-5000, more preferably 1:4000 by weight. The volume ratio of contrast agent (referenced to Uygur display 370) to solvent is 1:3-5, with a more preferred volume ratio of contrast agent to solvent being 1:4.
The histidine-tryptophan-ketoglutarate solution can be modified by using HTK solution in the prior art.
The thrombolytic composition for acute myocardial infarction occlusion blood vessel distal end and the use method thereof provided in the embodiment are characterized in that the thrombolytic composition for acute myocardial infarction occlusion blood vessel distal end is prepared by mixing a thrombolytic agent, a contrast agent and a solvent of histidine-tryptophan-ketoglutarate liquid together during use. In the thrombolysis process of the distal end of the occlusion vessel of the acute myocardial infarction, the application of the double-cavity microcatheter plays an important role, and avoids the risk of entering the false coronary cavity caused by frequent entering and exiting of the guide wire in the past. The double-cavity microcatheter is guided by the guide wire to pass through the lesion site in the blood vessel to reach the distal end of the blood vessel, and then the thrombolytic composition for the distal end of the acute myocardial infarction occlusion blood vessel of the embodiment is injected into the non-guide wire passing hole of the double-cavity microcatheter by using the injector, so that the thrombolytic composition for the distal end of the acute myocardial infarction occlusion blood vessel is injected to the distal end of the lesion site, the blood flow speed at the distal end of the lesion site is very slow or even stagnates, and the thrombolytic composition for the distal end of the acute myocardial infarction occlusion blood vessel stays at the distal end of the lesion site and contacts thrombus to perform thrombolysis.
The thrombolytic composition at the distal end of the occlusion vessel of the acute myocardial infarction contains a contrast agent, so that a doctor can observe the whole thrombolytic process under X-ray perspective, the thrombolytic process can be judged, the dosage and the administration speed of the thrombolytic can be adjusted in real time, the use efficiency of the thrombolytic composition at the distal end of the occlusion vessel of the acute myocardial infarction can be greatly improved, and the doctor can rescue and treat a patient conveniently.
In addition, the thrombolytic agent, the contrast agent and the solvent have mixability, namely, the physical property and the chemical property are stable, no sediment, no turbidity, no gas generation and no color change are generated, and the thrombolytic effect of the thrombolytic agent is not reduced. The preferred thrombolytic agent is first mixed with the solvent and then with the contrast agent. It should be noted that, the thrombolytic composition for acute myocardial infarction occlusion of the distal end of the blood vessel in this embodiment may be prepared by mixing the thrombolytic agent with a histidine-tryptophan-ketoglutarate solution solvent according to a predetermined formulation ratio, so as to ensure that the thrombolytic agent can be completely dissolved in the solvent, thereby improving the therapeutic effect of the thrombolytic composition for acute myocardial infarction occlusion of the distal end of the blood vessel. Then adding contrast agent into the mixed solution of thrombolytic agent and solvent for immediate use. Thus, the effect of reducing thrombolysis can be avoided when thrombolytic agent and other drugs are mixed for a long time.
It should be noted that, because thrombolytic agents and other drugs can reduce thrombolytic effect after a long period of time, three substances, namely thrombolytic agents, contrast agents and solvents, are separated before being used, and are respectively packaged in three containers to form three independent packages, and the three substances are mixed together when being applied.
The embodiment of the invention also provides a using method of the thrombolytic composition for occluding the distal end of a blood vessel in acute myocardial infarction, which comprises the following steps: the thrombolytic composition at the distal end of the occluded vessel of acute myocardial infarction is injected into the diseased vessel, wherein the bolus injection is performed once every 30s-1min, and 1ml is injected once. But with simultaneous attention to X-ray fluoroscopy, the injection time can be prolonged if the contrast agent is stagnant.
In the embodiment, firstly, a guide wire is selected to pass through a lesion vascular occlusion section to the far end of the lesion vascular occlusion section, a double-cavity microcatheter passes through the vascular occlusion section to the far end of the lesion vascular occlusion section by the guide wire to be 2-3cm, the guide wire is reserved, the thrombolytic composition at the far end of the acute myocardial infarction occlusion vascular is shot-injected by the microcatheter, 1ml of the thrombolytic composition is shot for 1 time every 30s-1min, and the microcatheter is gradually retracted to approach the occlusion position according to the X-ray perspective result. The development of the blood vessel distal to the occlusion can be seen during the injection, and the contrast agent remains, indicating that the thrombolytic composition distal to the occluded vessel of acute myocardial infarction has filled the occluded vessel and begun to exert thrombolytic effects. The method of imaging the distal end of the occlusion vessel of acute myocardial infarction and simultaneous forward imaging can be adopted, so that the length and the stenosis degree of a stenosis can be seen. The action is carried out in two directions simultaneously, namely, in the microcirculation direction, the micro thrombus in the microcirculation vascular bed can be fully contacted with thrombolytic agent to be dissolved; secondly, thrombolysis at the distal end of an occlusion vessel of acute myocardial infarction dissolves coronary artery trunk thrombus until the trunk thrombus is completely dissolved, and the occlusion vessel is opened to restore forward blood flow, and then saccule dilation combined stent implantation treatment is carried out according to pathological conditions.
It is worth to say that when histidine-tryptophan-ketoglutarate solution solvent and thrombolytic agent are adopted to act on diseased blood vessels together, interaction is mutually influenced, so that cytopenia at the diseased site occurs due to acidosis caused by ischemia, the activity of the cells can be improved, after the occluded blood vessels are dredged under the action of the thrombolytic agent, rapid recovery of the diseased site is facilitated, the coronary artery is opened flexibly and slowly, reperfusion pre-adaptation is generated, and reperfusion injury reaction is slight. Compared with the sodium chloride solution in the prior art for implementing thrombolysis of the distal end of the occluded blood vessel of the acute myocardial infarction, the histidine-tryptophan-ketoglutarate solution is used for implementing thrombolysis of the distal end of the occluded blood vessel of the acute myocardial infarction. The occurrence rate of malignant arrhythmia is lower, the occurrence ratio of slow blood flow/no-reflow is reduced, and the thrombus residue is less.
Wherein, histidine-tryptophan-ketoglutarate solution of modified version, it includes the following component: each 1000ml of modified histidine-tryptophan-ketoglutarate solution contains 0.8766g NaCl, 0.2609g KCl-0.4100 g MgCl 2 ·6H 2 O0.8132 g, histidine, HCl, H 2 O3.7733g, histidine 27.9289g, tryptophan 0.4085g, mannitol 5.4651g and CaCl 2 ·2H 2 O0.0022 g, 2-ketoglutarate-hydrogen-potassium 0.1842g. The concentration of potassium in the modified histidine-tryptophan-ketoglutarate solution is adjusted to 3.5-5.5mmol/l, so that the potassium concentration is reduced, and damage to cardiac muscle and coronary artery endothelium can be better avoided.
The following examples are given for prourokinase, iopromide injection (Uyghur 370), histidine-tryptophan-ketoglutarate:
example 1
Thrombolytic urokinase 5mg was dissolved in 15000mg (15 ml) histidine-tryptophan-ketoglutarate solution (weight ratio 1:3000). And then taking 5ml of a contrast agent iopromide injection (Uygur display 370), and adding the iopromide into a mixed solution of prourokinase and histidine-tryptophan-ketoglutarate (volume ratio is 1:3) to obtain 20ml of thrombolytic composition for occluding distal vascular ends of acute myocardial infarction. The physician passes the guidewire through the occluded segment of the diseased vessel and the microcatheter passes through the occluded segment to its distal end with the guidewire support. The thrombolytic composition at the distal end of the occluded vessel of the acute myocardial infarction was withdrawn using a 2ml syringe, and the thrombolytic composition was injected at the distal end of the occluded segment. At this time, thrombolysis in the diseased vessel can be seen by X-ray. The doctor injects 1ml of thrombolytic composition into the diseased vessel every 30 seconds, and observes the thrombolytic condition by X-ray fluoroscopy. At the beginning, the thrombolytic composition is remained at the distal end of thrombus, and gradually dissolves the thrombus, the average time is about 4-10 minutes, the retention phenomenon of contrast agent is disappeared, the blood vessel is opened, the forward blood flow is restored, and the opening rate is 95%.
Example 2
Thrombolytic urokinase 5mg was dissolved in 25000mg (25 ml) histidine-tryptophan-ketoglutarate solution (weight ratio 1:5000). And then taking 5ml of a contrast agent iopromide injection (Uygur display 370), and adding the iopromide into a mixed solution of prourokinase and histidine-tryptophan-ketoglutarate (volume ratio is 1:5) to obtain 30ml of thrombolytic composition for occluding distal vascular ends of acute myocardial infarction. The physician passes the guidewire through the occluded segment of the diseased vessel and the microcatheter passes through the occluded segment to its distal end with the guidewire support. The thrombolytic composition is withdrawn using a syringe and injected into the distal end of the occluded segment. At this time, thrombolysis in the diseased vessel can be seen by X-ray. The doctor injects 1ml of thrombolytic composition into the diseased vessel every 30 seconds, and observes the thrombolytic condition by X-ray fluoroscopy. At the beginning, the thrombolytic composition is remained at the distal end of thrombus, gradually dissolves the thrombus, and has average about 5-12 minutes, the contrast agent retention phenomenon disappears, the blood vessel is opened, the forward blood flow is restored, and the opening rate is 90%.
Example 3
Thrombolytic agent urokinase 5mg was dissolved in 20000mg (20 ml) histidine-tryptophan-ketoglutarate solution (weight ratio 1:4000). And then taking 5ml of a contrast agent iopromide injection (Uygur display 370), and adding the iopromide into a mixed solution of prourokinase and histidine-tryptophan-ketoglutarate solution (volume ratio is 1:4), thus obtaining 25ml of thrombolytic composition for occluding distal vascular ends of acute myocardial infarction. The physician passes the guidewire through the occluded segment of the diseased vessel and the microcatheter passes through the occluded segment to its distal end with the guidewire support. The thrombolytic composition is withdrawn using a syringe and injected into the distal end of the occluded segment. At this time, thrombolysis in the diseased vessel can be seen by X-ray. The doctor injects 1ml of the solution into the diseased vessel every 30s and observes the thrombolysis condition using X-ray fluoroscopy. At the beginning, the thrombolytic composition is remained at the distal end of thrombus, gradually dissolves the thrombus, and has average about 6-14 minutes, the contrast agent retention phenomenon disappears, the blood vessel is opened, the forward blood flow is restored, and the opening rate is 85%.
The following is a comparative table of test data for each of the above examples:
when the weight ratio of the thrombolytic agent to the solvent is 1:3000; the contrast agent (referenced by the Uygur display 370) has a better effect when the volume ratio of the contrast agent to the solvent is 1:3.
The thrombolytic agent dosage of the technology is one tenth to one tenth of that of the conventional intravenous thrombolytic agent, the bleeding risk is greatly reduced, the safety is greatly improved, the thrombolytic process can be directly seen under X-ray perspective by the application of the formula, the thrombolytic process can be judged, and the thrombolytic agent dosage and the administration speed can be timely adjusted, so that the thrombolytic agent is more efficiently used and saved. The method is flexible and gentle to the opening of coronary artery, and the reperfusion injury response is slight.
The present embodiment is only for explanation of the present invention and is not to be construed as limiting the present invention, and modifications to the present embodiment, which may not creatively contribute to the present invention as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present invention.
Claims (7)
1. A thrombolytic composition for occluding a distal end of a blood vessel in acute myocardial infarction, comprising: thrombolytic agents and contrast agents, and a solvent for matching the osmotic pressure of human plasma, wherein the solvent is histidine-tryptophan-ketoglutarate liquid.
2. The thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in claim 1, wherein: the weight ratio of the thrombolytic agent to the solvent is as follows: 1:3000-5000.
3. The thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in claim 1, wherein: the volume ratio of the contrast agent to the solvent is: 1:3-5.
4. The thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in claim 1, wherein: the thrombolytic agent is one or more of urokinase, prourokinase, alteplase and reteplase.
5. The thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in claim 1, wherein: the contrast agent is iopromide or iodixanol.
6. Thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in any one of claims 1 to 5, wherein: the thrombolytic agent is first mixed with the solvent and then with the contrast agent.
7. Thrombolytic composition for occluding a distal end of a blood vessel for acute myocardial infarction as recited in any one of claims 1 to 5, wherein: the thrombolytic composition for acute myocardial infarction occlusion distal to the vessel is injected into the diseased vessel, wherein 1-2ml is injected once every 30 s.
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