CN110675717B - Bionic equipment for simulating vascular stenosis and thrombus - Google Patents

Bionic equipment for simulating vascular stenosis and thrombus Download PDF

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Publication number
CN110675717B
CN110675717B CN201910960737.0A CN201910960737A CN110675717B CN 110675717 B CN110675717 B CN 110675717B CN 201910960737 A CN201910960737 A CN 201910960737A CN 110675717 B CN110675717 B CN 110675717B
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thrombus
bottle
silicone tube
liquid
bottle body
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CN110675717A (en
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李亚鹏
姚顺雨
于艳辉
刘晔
沈美丽
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Jilin University
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Jilin University
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Abstract

The invention discloses bionic equipment for simulating angiostenosis and thrombus, and belongs to the technical field of design of experimental instruments. Consists of a peristaltic pump (1), a pressure maintaining bottle (2), a vascular stenosis and thrombus simulator (3), an anti-suck-back switch (4) and a reflux bottle (5); the parts are sequentially connected by a silicone tube to form a closed loop. The device has a simple structure, is convenient to use, can effectively simulate the drug release of the nano-drugs with mechanical stress response in vitro by using the device, and can also perform thrombolysis quantitative analysis and thrombus targeting test aiming at various stimulation response targeting drugs.

Description

Bionic equipment for simulating vascular stenosis and thrombus
Technical Field
The invention belongs to the technical field of design of experimental instruments, and particularly relates to bionic equipment for simulating vascular stenosis and thrombus.
Background
The incidence of thrombotic diseases is also increasing year by year due to the continuous improvement of the living standard of modern people and irregular life and rest. The greatest threat is vascular rupture due to thrombosis and unstable plaque, leading to cardiovascular and cerebrovascular complications such as Acute Coronary Syndrome (ACS) and stroke. In the past decade, anti-thrombolytic drug therapies including aspirin, statins and other potent anti-platelet drugs, as well as various drugs that lower the level of Low Density Lipoprotein (LDL), targeted nano-drug carriers of mechanical stress and other stimuli have also been introduced.
However, the targeted nano-drugs responding to stimuli such as mechanical stress have high in-vivo experimental cost, long cycle, large individual difference and the like, and most importantly, cannot be quantified in vivo, so that the targeted nano-drugs cannot be popularized comprehensively. In the existing instruments and equipment, the drug release rate and the thrombolytic effect of the antithrombotic and thrombolytic targeting drugs can not be comprehensively measured in vitro by simulating the in vivo environment. Therefore, a bionic device which can simulate in-vivo blocking of blood vessels in vitro and is used for in-vitro drug release and thrombolysis and antithrombotic effect detection of targeted nano-drugs responding to stimuli such as mechanical stress and the like is urgently needed to be developed.
Disclosure of Invention
The invention aims to overcome the defects in the background technology and provide a brand new bionic device which can simulate the in vivo vessel occlusion environment under the in vitro condition.
The technical scheme adopted by the invention is as follows:
a bionic device for simulating angiostenosis and thrombus consists of a peristaltic pump 1, a pressure maintaining bottle 2, a angiostenosis and thrombus simulator 3, an anti-suck-back switch 4 and a reflux bottle 5; the parts are sequentially connected by a silicone tube to form a closed loop;
the vascular stenosis and thrombus simulation device 3 consists of an organic glass main body 31, a screw 32 and a gasket 33; a through inner passage 34 with a fixed diameter is arranged in the organic glass main body 31, a screw hole is arranged on one side of the organic glass main body 31 in the direction vertical to the inner passage 34, and a screw 32 is screwed into the organic colored glaze through the screw hole to extrude a silicone tube covered by the inner passage 34; a gasket 33 is arranged between the screw 32 and the organic colored glaze main body 31;
the pressure maintaining bottle 2 is specifically composed of a pressure maintaining bottle body 21, a deflation valve 22, a first opening 23 and a second opening 24, the rest parts of the pressure maintaining bottle body 21 except the two openings are sealed, wherein the first opening 23 is connected with the peristaltic pump 1 through a silicone tube, the second opening 24 is connected with the vascular stenosis and thrombosis simulator 3 through a silicone tube, the port of the silicone tube connected with the second opening 24 in the bottle body 21 is lower than the liquid level in the bottle body 21, and the port of the silicone tube connected with the first opening 23 in the bottle body 21 is higher than the liquid level in the bottle body 21; after connection, sealing the two openings;
the reflux bottle 5 is specifically composed of a reflux bottle body 51, a liquid outlet 52, a liquid inlet 53 and a medicine adding hole 54, wherein the rest parts of the reflux bottle body 51 except the liquid outlet 52, the liquid inlet 53 and the medicine adding hole 54 are sealed; the liquid outlet 52 is connected with the peristaltic pump 1 by a silicone tube, the liquid inlet 53 is connected with the anti-suck-back switch 4 by the silicone tube, and the liquid outlet 52 and the liquid inlet 53 are sealed after connection; when the medicine adding hole 54 is sealed by a rubber plug during working, liquid is stored in the bottle body 51, the end of the silicone tube inserted into the liquid inlet 53 is lower than the end of the silicone tube inserted into the liquid outlet 52, and the ends of the silicone tubes are lower than the liquid level of the liquid in the bottle body 51.
Preferably, in the vascular stenosis and thrombus simulation device 3, the screw 32 is hollow, the thrombus fixing needle 35 longitudinally penetrates through the screw 32 is arranged in the hollow, and the thrombus fixing needle 35 penetrates through the silica gel tube wall in the inner passage 34 and is inserted into the liquid in the silica gel tube.
The diameter of the inner path 34 of the blood vessel stenosis and thrombus simulation device 3 can be 12mm, 8mm or 6 mm.
The number of the gaskets 33 is preferably 1-5, and the thickness of each gasket is preferably 3mm or 1 mm.
Has the advantages that:
the device has a simple structure, is convenient to use, can effectively simulate the drug release of the nano-drug with mechanical stress response in vitro by using the device, and further analyzes the drug release efficiency. Different narrow blood vessels and thrombus simulation devices are replaced, and thrombolysis quantitative analysis and thrombus targeting test can be performed aiming at various stimulation response targeting drugs.
Drawings
FIG. 1 is a schematic view of the cycle of a biomimetic apparatus for simulating stenosis and thrombosis of a blood vessel in example 1.
FIG. 2 is a schematic view of a vascular stenosis and thrombus simulation device of another structure according to example 3.
FIG. 3 is a schematic view of a vascular stenosis and thrombus simulation device according to example 2.
FIG. 4 is a schematic view of the pressure-maintaining bottle of example 4.
FIG. 5 is a schematic view of the reflux flask of example 5.
Detailed Description
The present invention is described in detail by the following examples, but does not limit the scope of the invention as claimed.
Example 1: integral structure of the invention
The overall structure of the invention is schematically shown in figure 1, and comprises a peristaltic pump 1, a pressure maintaining bottle 2, a vascular stenosis and thrombus simulator 3, an anti-suck-back switch 4 and a reflux bottle 5, wherein all parts are connected by a silicone tube in sequence to form a closed loop. Injecting a target nano-drug mixed solution to be analyzed into the pressure maintaining bottle 2, enabling the solution in the pressure maintaining bottle 2 to sequentially flow through the vascular stenosis and thrombus simulator 3, the suck-back prevention switch 4, the reflux bottle 5 and the peristaltic pump 1 through a silicone tube under the pressure of the peristaltic pump 1, and finally refluxing to the pressure maintaining bottle 2.
Example 2: structure and function of blood vessel stenosis and thrombus simulator 3
Fig. 3 is a schematic view of the blood vessel narrowing and thrombus simulation device 3. The vascular stenosis and thrombus simulation device 3 is composed of an organic glass main body 31, a screw 32 and a gasket 33; a through inner passage 34 with a fixed diameter (12mm, 8mm or 6mm) is arranged in the organic glass main body 31, a screw hole is arranged on one side of the organic glass main body 31 in a direction vertical to the inner passage 34, and a screw 32 is screwed into the organic glass through the screw hole to extrude a silicone tube covered by the inner passage 34; there is fixed thickness (1mm or 3mm) gasket 33 between screw 32 and the organic colored glaze main part 31, and the quantity of gasket 33 is 1 ~ 5 adjustable, can quantify through the quantity of adjusting the gasket and regulate and control the narrow degree of silicone tube to the early stage, middle stage and the later stage of simulation thrombus formation. The dimensions of the various parts indicated in the figures are preferred dimensions.
Example 3: another structure and function of the blood vessel stenosis and thrombus simulation device 3
In order to detect the thrombolytic effect of different drugs, in the structure of the vascular stenosis and thrombus simulation device 3, the screw 32 may also be designed to be hollow, as shown in fig. 2, a thrombus fixing needle 35 longitudinally passing through the screw 32 is arranged inside the hollow, and the thrombus fixing needle 35 pierces through the silica gel tube wall in the inner passage 34 and protrudes into the liquid in the silica gel tube. The solution mixed with the nano targeting drug with mechanical stress response is added into a circulation system, and flows through the thrombus fixing needle 35 with thrombus along with the solution, so that the thrombolytic effect quantification experiment for detecting different types of drugs in vitro is realized. After the experiment is finished, the thrombus is taken out for quantitative analysis. By adjusting the number of the spacers 33, a plurality of drug release rates of the nano-drug in different disease periods can be obtained. The dimensions of the various parts indicated in the figures are preferred dimensions.
Example 4: structure and function of pressure maintaining bottle 2
As shown in fig. 4, the pressure maintaining bottle 2 is specifically composed of a pressure maintaining bottle body 21, a deflation valve 22, a first opening 23 and a second opening 24, the remaining parts of the pressure maintaining bottle body 21 except for the two openings are sealed, wherein the first opening 23 is connected with the peristaltic pump 1 by a silicone tube, the second opening 24 is connected with the blood vessel stenosis and thrombus simulation device 3 by the silicone tube, the port of the silicone tube connected with the second opening 24 in the bottle body 21 is lower than the liquid level in the bottle body 21, and the port of the silicone tube connected with the first opening 23 in the bottle body 21 is higher than the liquid level in the bottle body 21; after the connection, the two openings are also sealed. The peristaltic pump 1 (in the example, a BT100-1F type peristaltic pump is selected) is used as a power source to pump the liquid in the reflux bottle 5 into the pressure-maintaining bottle 2, and the liquid in the bottle flows into the vascular stenosis simulation device 3 along the silicone tube under the pressure condition because the bottle is sealed. When the pressure of the whole system is higher than the threshold value, the air release valve 22 can automatically release partial pressure, and the function of protecting the whole circulation system is further achieved.
Example 5: structure and function of reflux bottle 5
The structure of the reflux bottle 5 is shown in fig. 5, and specifically comprises a reflux bottle body 51, a liquid outlet 52, a liquid inlet 53 and a medicine adding hole 54, wherein the rest parts of the reflux bottle body 51 except the liquid outlet 52, the liquid inlet 53 and the medicine adding hole 54 are sealed; the liquid outlet 52 is connected with the peristaltic pump 1 by a silicone tube, the liquid inlet 53 is connected with the anti-suck-back switch 4 by the silicone tube, and the liquid outlet 52 and the liquid inlet 53 are sealed after connection; when the medicine adding hole 54 is sealed by a rubber plug during working, liquid is stored in the bottle body 51, the end of the silicone tube inserted into the liquid inlet 53 is lower than the end of the silicone tube inserted into the liquid outlet 52, and the ends of the silicone tubes are lower than the liquid level of the liquid in the bottle body 51. A small amount of liquid is accumulated in the reflux bottle 5 to stabilize the system pressure. The dosing holes 54 are used to replenish the liquid or drug as needed during the experiment. There is anti-suck-back switch 4 before backward flow bottle 5, and when circulation system internal pressure was too big, closed peristaltic pump 1 earlier and then closed anti-suck-back switch 4, can effectually stop the transmission of liquid and leave the decompression time for the automatic bleed valve, the integrity of protection backward flow bottle 5 and pressurize bottle 2, the internal pressure of stable system. The suck-back prevention switch 4 can be simply realized by using a clamp, when the pressure in the circulating system is overlarge, the peristaltic pump 1 is firstly closed, and then a silica gel tube in front of the liquid outlet of the reflux bottle 5 is clamped by using the clamp so as to prevent the liquid from suck back.
As can be seen from the above embodiments, the invention has simple structure and convenient use. By using the device disclosed by the invention, the drug release of the nano-drug with mechanical stress response can be effectively simulated in vitro, and the drug release efficiency can be further analyzed. Different narrow blood vessels and thrombus simulation devices are replaced, and thrombolysis quantitative analysis and thrombus targeting test can be performed aiming at various stimulation response targeting drugs.

Claims (4)

1. A bionic device for simulating angiostenosis and thrombus consists of a peristaltic pump (1), a pressure maintaining bottle (2), a angiostenosis and thrombus simulating device (3), an anti-suck-back switch (4) and a reflux bottle (5); the parts are sequentially connected by a silicone tube to form a closed loop; it is characterized in that the preparation method is characterized in that,
the vascular stenosis and thrombus simulation device (3) consists of an organic glass main body (31), a screw (32) and a gasket (33); a through inner passage (34) with a fixed diameter is arranged in the organic glass main body (31), a screw hole is arranged on one side of the organic glass main body (31) in the direction vertical to the inner passage (34), and a screw (32) is screwed into the organic glass through the screw hole to extrude the silicone tube coated by the inner passage (34); a gasket (33) is arranged between the screw (32) and the organic colored glaze main body (31);
the pressure maintaining bottle (2) is composed of a pressure maintaining bottle body (21), an air release valve (22), a first opening (23) and a second opening (24), the rest parts of the pressure maintaining bottle body (21) except the two openings are sealed, wherein the first opening (23) is connected with the peristaltic pump (1) through a silicone tube, the second opening (24) is connected with the vascular stenosis and thrombus simulation device (3) through the silicone tube, the port of the silicone tube connected with the second opening (24) in the bottle body (21) is lower than the liquid level in the bottle body (21), and the port of the silicone tube connected with the first opening (23) in the bottle body (21) is higher than the liquid level in the bottle body (21); after connection, sealing the two openings;
the reflux bottle (5) is specifically composed of a reflux bottle body (51), a liquid outlet (52), a liquid inlet (53) and a medicine adding hole (54), wherein the rest parts of the reflux bottle body (51) except the liquid outlet (52), the liquid inlet (53) and the medicine adding hole (54) are sealed; the liquid outlet (52) is connected with the peristaltic pump (1) through a silicone tube, the liquid inlet (53) is connected with the anti-suck-back switch (4) through the silicone tube, and the liquid outlet (52) and the liquid inlet (53) are sealed after connection; when the medicine adding bottle works, the medicine adding hole (54) is sealed by a rubber plug, liquid is stored in the bottle body (51), the end of the silicone tube inserted into the liquid inlet (53) is lower than the end of the silicone tube inserted into the liquid outlet (52), and the ends of the silicone tubes are lower than the liquid level of the liquid in the bottle body (51).
2. The bionic equipment for simulating the stenosis and the thrombus of the blood vessel as claimed in claim 1, wherein in the stenosis and the thrombus simulating device (3), the screw (32) is hollow, the thrombus fixing needle (35) longitudinally penetrates through the screw (32) is arranged in the hollow, and the thrombus fixing needle (35) penetrates through the wall of the silica gel tube in the inner passage (34) and is inserted into the liquid in the silica gel tube.
3. A biomimetic apparatus for simulating vascular stenosis and thrombus as claimed in claim 1, wherein the diameter of the inner channel (34) of the vascular stenosis and thrombus simulation device (3) is 12mm, 8mm or 6 mm.
4. The bionic equipment for simulating the stenosis and the thrombus of the blood vessel as claimed in claim 1, wherein the number of the gaskets (33) is 1-5, and the thickness of each gasket is 3mm or 1 mm.
CN201910960737.0A 2019-10-10 2019-10-10 Bionic equipment for simulating vascular stenosis and thrombus Expired - Fee Related CN110675717B (en)

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