Rat and mouse carotid artery catheterization administration device and model establishment method

Abstract

The invention belongs to the technical field of carotid artery catheterization, and particularly relates to a rat and mouse carotid artery catheterization drug delivery device and a model establishment method. The carotid artery indwelling catheter administration device comprises a 34G medical thin needle head, a 1ml injector, a PP tube with the outer diameter of 0.2 mm and the inner diameter of 0.1 mm, and an in-vitro injection pump; one end of the PP tube is nested in the 34G medical thin needle head, the PP tube and the 34G medical thin needle head are sealed through animal tissue glue, and the 1ml injector is connected with the in-vitro injection pump. According to the carotid artery catheterization drug delivery device for the rats and the mice, the pipelines are thinner, the device can be matched with an in-vitro injection pump, operation in an operation is easy, convenient and rapid, the complication rate and the death rate of carotid artery catheterization are low, the drug delivery effect is stable, repeatability is high, and a carotid artery catheterization drug delivery model for the rats and the mice is established on the basis of the device.

Description

Technical Field

[0001] The present invention belongs to the technical field of carotid artery catheterization, and particularly relates to a carotid artery catheterization drug delivery device for rats and mice and a method for establishing a model. Background Technique

[0002] Intravascular drug delivery is a commonly used drug delivery method in rodent experiments, usually by injection through the tail vein or femoral vein, etc. However, in the study of the physiology or pathology of the central nervous system, after intravenous drug administration, it takes a long time for the drug to circulate to the brain tissue through the blood circulation, and the drug may be partially metabolized or absorbed by blood cells before reaching the brain tissue. In addition, after intravenous drug administration, the drug passes through the pulmonary circulation and is pumped out by the heart, diffusing into various organs throughout the body, and the drug concentration in the brain tissue is the same as that in the whole body organs, and the proportion of the drug acting on the brain is not high. Carotid artery catheterization drug delivery can enable the drug to directly reach the brain tissue without redundant blood circulation paths, avoid blood metabolism and blood cell absorption to the greatest extent, reduce drug loss, and ensure that there is the maximum drug concentration in the brain tissue immediately after drug administration, improving the actual effect of the drug acting on the brain tissue. Therefore, a safe, stable and easy-to-operate carotid artery catheterization device can assist in the research related to the central nervous system.

[0003] Currently, the tubing used in the carotid artery catheterization drug delivery device for rats and mice is relatively thick, resulting in difficult intraoperative operation, increasing the operation time and the occurrence of death events caused by carotid artery catheterization, especially in mice with smaller blood vessels; at the same time, the preparation of some carotid artery catheterization drug delivery devices has poor repeatability, a long preparation process time, unstable drug delivery effects, and cannot be adapted to an external injection pump. Summary of the Invention

[0004] The purpose of the present invention is to provide a carotid artery catheterization drug delivery device for rats and mice and a method for establishing a model. By establishing a carotid artery catheterization drug delivery device for rats and mice with simple preparation, thinner tubing, simple and rapid intraoperative operation, low complication rate and mortality rate of carotid artery catheterization, stable drug delivery effect, strong repeatability and being able to be adapted to an external injection pump, and establishing a carotid artery catheterization drug delivery model for rats and mice based on this device, to solve the problems existing in the above background technique.

[0005] To achieve the above purpose, the present application is realized through the following technical solutions:

[0006] A carotid artery catheterization drug delivery device for rats and mice, comprising a 34G medical fine needle, a 1 ml syringe, a PP tube with an outer diameter of 0.2 mm and an inner diameter of 0.1 mm, and an external injection pump;

[0007] One end of the PP tube is sleeved on the 34G medical fine needle, and animal tissue glue is provided between the PP tube and the 34G medical fine needle, and the 1 ml syringe is connected to the external injection pump.

[0008] Further, the axial cross-section of the other end of the PP tube is semi-circular.

[0009] Further, the animal tissue glue is 3M Vetbond animal tissue glue.

[0010] A method for establishing a carotid artery catheterization drug administration model for rats and mice, using the carotid artery catheterization drug administration device for rats and mice according to any one of the above, comprising the following steps:

[0011] S1. Isolate the common carotid artery, external carotid artery, and internal carotid artery of the pre-treated rat or mouse, and expose the pterygopalatine artery;

[0012] S2. Clamp the common carotid artery with an artery clip;

[0013] S3. Ligate the external carotid artery with a thin thread at the distal end of the external carotid artery;

[0014] S4. Ligate the internal carotid artery with a slipknot at the proximal end of the internal carotid artery;

[0015] S5. Make a slipknot at the proximal end of the external carotid artery for later use;

[0016] S6. Insert the PP tube of the carotid artery catheterization drug administration device from the external carotid artery into the common carotid artery;

[0017] S7. Untie the slipknot at the proximal end of the internal carotid artery to open the internal carotid artery;

[0018] S8. Infuse drugs to the distal brain tissue through the carotid artery catheterization drug administration device;

[0019] S9. After drug infusion, open the artery clip, release the common carotid artery, wash all the drugs to the distal blood vessels, and then clamp the common carotid artery with the artery clip;

[0020] S10. Withdraw the PP tube of the carotid artery catheterization drug administration device, tighten the loose ligature at the proximal end of the external carotid artery to ligate the external carotid artery, and remove the artery clip on the common carotid artery.

[0021] Further, the pre-treatment in step S1 includes anesthetizing the rat or mouse and placing it supine on the operating table, with the head and limbs fixed.

[0022] Further, between step S2 and step S3, it further includes:

[0023] S21. Ligate the superior thyroid artery, a branch of the external carotid artery, at the proximal end of the external carotid artery;

[0024] S22. Ligate the anterior auricular artery, a branch, at the bifurcation of the internal carotid artery and the external carotid artery;

[0025] S23. Ligate the pterygopalatine artery at the distal end of the internal carotid artery.

[0026] Further, in step S6, use a micro-scissors to cut an opening at the distal end of the slipknot of the external carotid artery. After inserting the PP tube of the carotid artery catheterization drug delivery device, tighten the slipknot at the proximal end of the external carotid artery.

[0027] The beneficial effects of the present invention are as follows:

[0028] The pipeline of the carotid artery catheterization drug delivery device for rats and mice of the present invention is thinner, and the device can be adapted to an external injection pump, making the intraoperative operation simple and rapid, with a low complication rate and mortality rate of arterial catheterization, stable drug delivery effect, strong repeatability, and establishing a carotid artery catheterization drug delivery model for rats and mice based on this device. Description of the Drawings

[0029] Figure 1 It is a schematic structural diagram of the carotid artery catheterization drug delivery device for rats and mice of the present invention.

[0030] Figure 2 It is a diagram of carotid artery intubation for rats and mice.

[0031] Description of the reference numerals:

[0032] 1. 34G medical fine needle; 2. 1ml syringe; 3. External injection pump; 4. PP tube. Detailed Embodiments

[0033] The technical solutions of the present invention will be described in detail below with reference to the drawings. The following embodiments are merely exemplary and can only be used to explain and illustrate the technical solutions of the present invention, rather than being construed as a limitation to the technical solutions of the present invention.

[0034] As Figure 1 shown, the present application provides a carotid artery catheterization drug delivery device for rats and mice, including a 34G medical fine needle 1, a 1ml syringe 2, a PP tube 4 with an outer diameter of 0.2 mm and an inner diameter of 0.1 mm, and an external injection pump 3.

[0035] The 34G medical fine needle involved in the present application has an outer diameter of about 0.18 mm, which is a prior art. One end of the PP tube is sleeved on the 34G medical fine needle. The length of the PP tube in the present application is about 10 cm, the inner diameter of the PP tube is 0.1 mm, and 3M Vetbond animal tissue glue is provided between the PP tube and the 34G medical fine needle for sealing. The length of the PP tube sleeved on the 34G medical fine needle is about 5 mm. The 1ml syringe is connected to the external injection pump. The specific connection method is a prior art, and those skilled in the art and corresponding medical staff are clear about how to install and use it.

[0036] In this application, in order to avoid the resistance during the insertion of the end edge of the PP and the damage to the arterial inner wall, the axial cross-section of the other end of the PP tube is semi-circular.

[0037] In this application, during the process of low-speed and stable drug delivery using an in vitro injection pump, it also includes detecting the pressure of the blood in the artery. The in vitro injection pump adjusts the drug flow rate according to the detected pressure of the blood in the artery. Specifically, the initial arterial blood pressure data is detected. During the drug infusion process, for every 0.1% increase in pressure, the corresponding drug flow rate is decreased, that is, the drug flow rate is decreased by 0.1%. For every 0.1% decrease in pressure, the corresponding drug flow rate is increased, that is, the drug flow rate is increased by 0.1%.

[0038] The advantage of this device is that compared with other carotid artery catheterization devices, the pipeline of this device is thinner, the operation of inserting into the carotid artery of rats or mice is simple, the success rate is high, the repeatability is strong, and the occurrence of complication events is reduced. This device can be inserted into the external carotid artery, common carotid artery or internal carotid artery. When there is no previous experiment specifying the operation on the common carotid artery or internal carotid artery, it is recommended to insert it into the external carotid artery to retain the blood flow of the common carotid artery and internal carotid artery and restore the physiological blood perfusion of the brain tissue after the operation.

[0039] As Figure 2 shown, this application also provides a method for establishing a carotid artery catheterization drug delivery model for rats and mice. Using the carotid artery catheterization drug delivery device for rats and mice according to any one of the above, it includes the following steps:

[0040] 1) Anesthetize the rat or mouse and place it supine on the operating table, fixing the head and limbs.

[0041] 2) Shave the hair on the neck and upper chest, and disinfect the neck and upper chest with iodophor.

[0042] 3) Use scissors to cut open the skin from the mandible to the suprasternal notch along the midline of the neck, and use dissecting forceps to bluntly separate the anterior cervical tissues layer by layer until the carotid sheath is exposed.

[0043] 4) Use ophthalmic forceps to tear open the carotid sheath, separate the common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA) and expose the pterygopalatine artery. During the separation process, pay attention to protecting the vagus nerve, gently pull the carotid artery to avoid bleeding.

[0044] 5) Clamp the common carotid artery with an arterial clip.

[0045] 6) Tie the external carotid artery with a thin thread at the distal end of the external carotid artery.

[0046] 7) Tie the superior thyroid artery, a branch of the external carotid artery, with a thin thread at the proximal end of the external carotid artery.

[0047] 8) Tie the anterior auricular artery, a branch, with a thin thread at the bifurcation of the internal carotid artery and the external carotid artery.

[0048] 9) Ligate the branch pterygopalatine artery with a fine thread at the distal end of the internal carotid artery.

[0049] 10) Ligate the internal carotid artery with a slip knot of fine thread at the proximal end of the internal carotid artery.

[0050] 11) Tie a slip knot at the proximal end of the external carotid artery for standby.

[0051] 12) Use a micro-scissors to make a small incision at the distal end of the slip knot of the external carotid artery, insert the PP pipeline of the prepared carotid artery catheterization drug delivery device into the common carotid artery (keep the longer insertion length to ensure the pipeline is stable and not easy to fall out), and tighten the loose knot at the proximal end of the external carotid artery for fixation.

[0052] 13) Untie the slip knot at the proximal end of the internal carotid artery to open the internal carotid artery.

[0053] 14) Manually push the injection or connect an external injection pump to infuse the drug into the distal brain tissue.

[0054] 15) After the drug infusion, open the artery clamp of the common carotid artery, flush all the drugs into the distal blood vessels, and then clamp the common carotid artery with the artery clamp.

[0055] 16) Withdraw the pipeline of the carotid artery catheterization device, ligate the external carotid artery with the loose knot at the proximal end of the external carotid artery, remove the artery clamp of the common carotid artery, observe for 1 minute for any active bleeding. If there is no active bleeding, suture the neck tissue and skin layer by layer and disinfect.

[0056] The purpose of steps 7) to 9) of the present application is to ensure that the drug enters the brain tissue through the carotid artery to the greatest extent without being shunted. If there are no strict requirements in the experiment, these steps can also be skipped to simplify the operation.

[0057] The above shows and describes the basic principle of the present invention and the advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification only illustrates the principle of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of the present invention claimed is defined by the appended claims and their equivalents.

Claims

1. A carotid artery catheterization drug administration device for rats and mice, characterized in that It includes a 34G medical fine needle, a 1ml syringe, a PP tube with an outer diameter of 0.2mm and an inner diameter of 0.1mm, and an external injection pump; One end of the PP tube is sleeved on the 34G medical fine needle, and is sealed between the PP tube and the 34G medical fine needle with animal tissue glue. The 1ml syringe is connected to the external injection pump.

2. The carotid artery catheterization drug delivery device for rats and mice according to claim 1, wherein, The axial cross-section of the other end of the PP tube is semi-circular.

3. The carotid artery catheterization drug administration device for rats and mice according to claim 1, wherein The animal tissue glue is 3M Vetbond animal tissue glue.

4. A method for establishing a carotid artery catheterization drug administration model for rats and mice, characterized in that, Using the carotid artery catheterization drug delivery device for rats and mice according to any one of claims 1 to 3 above, it includes the following steps: S1. Isolate the common carotid artery, external carotid artery, and internal carotid artery of the pre-treated rat or mouse, and expose the pterygopalatine artery; S2. Clamp the common carotid artery with an artery clamp; S3. Ligate the external carotid artery with a thin thread at the distal end of the external carotid artery; S4. Ligate the internal carotid artery with a thin thread slipknot at the proximal end of the internal carotid artery; S5. Make a slipknot at the proximal end of the external carotid artery for standby; S6. Insert the PP tube of the carotid artery catheterization drug delivery device from the external carotid artery into the common carotid artery; S7. Untie the slipknot at the proximal end of the internal carotid artery to open the internal carotid artery; S8. Infuse drugs to the distal brain tissue through the carotid artery catheterization drug delivery device; S9. After drug infusion, open the artery clamp, release the common carotid artery, flush all the drugs to the distal blood vessels, and then clamp the common carotid artery with the artery clamp; S10. Withdraw the PP tube of the carotid artery catheterization drug delivery device, tighten the loose ligation at the proximal end of the external carotid artery to ligate the external carotid artery, and remove the artery clamp on the common carotid artery.

5. The method for establishing a carotid artery catheterization drug administration model for rats and mice according to claim 4, wherein The pre-treatment in step S1 includes anesthetizing the rat or mouse and placing it supine on the operating table, fixing the head and limbs.

6. The method for establishing a carotid catheterization drug administration model for rats and mice according to claim 4, characterized in that, Between step S3 and step S4, it also includes: S21. Ligate the superior thyroid artery, a branch of the external carotid artery, at the proximal end of the external carotid artery; S22. Ligate the anterior auricular artery, a branch, at the bifurcation of the internal carotid artery and the external carotid artery; S23. Ligate the pterygopalatine artery at the distal end of the internal carotid artery.

7. The method for establishing a carotid artery catheterization drug administration model for rats and mice according to claim 4, characterized in that, In step S6, use a micro-scissors to cut an opening at the distal end of the slipknot of the external carotid artery. After inserting the PP tube of the carotid artery catheterization drug delivery device, tighten the slipknot at the proximal end of the external carotid artery.

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