Cannula for jugular vein of rat and using method thereof

Abstract

The invention provides an intubation tube for jugular veins of rats and a use method of the intubation tube. The cannula comprises a cannula head, a cannula body and a coating, and the cannula head is connected with the cannula body; the coating comprises a nitroglycerin coating on the outer wall of the tube head and a low-molecular heparin sodium coating on the inner wall of the tube body. The improved intubation tube improves the success rate of intubation and reduces postoperative complications, and has important clinical and experimental values.

Description

Technical Field

[0001] The present invention relates to the technical field of experimental animal medicine, and particularly relates to an intubation tube for a rat jugular vein and a method for using the same. Background Art

[0002] The rat jugular vein intubation and blood collection system is an excellent solution for pharmacokinetics, drug metabolism research, and related animal experiments, and particularly shows significant advantages in the field of traditional Chinese medicine research. This system realizes precise intubation of the jugular vein through minimally invasive technology, can collect blood samples in real time and dynamically, significantly reduces the stress response of experimental animals caused by traditional blood collection methods, and improves the blood collection efficiency and sample quality at the same time. Its characteristics of simple operation and strong stability ensure the accuracy and repeatability of pharmacokinetic parameters, providing reliable data support for studying the absorption, distribution, metabolism, and excretion processes of drugs in vivo.

[0003] Traditional rat jugular vein intubation often uses PU intubation tubes and silicone intubation tubes separately. The PU intubation tube has good rigidity, is not easily folded, and is convenient to insert, but may cause obvious tissue reactions or inflammation; the silicone intubation tube has good biocompatibility, little irritation to tissues, and is suitable for long-term use, but is too soft, easily folded, and requires more skills when inserting. Due to the same thickness at both ends of the traditional intubation tube and the reasons of the aforementioned materials, it is difficult to operate when inserting into the jugular vein, with a low success rate and low efficiency, seriously restricting the experimental efficiency and scientific research progress. Therefore, developing an improved intubation tube that can improve the intubation success rate and reduce postoperative complications has important clinical and experimental value. Summary of the Invention

[0004] The purpose of the present invention is to provide an intubation tube for a rat jugular vein and a method for using the same. The intubation tube includes a tube head, a tube body, and an anti-detachment structure. The tube head is connected to the tube body; the anti-detachment structure is divided into a subcutaneous anti-detachment structure and an in vitro anti-detachment structure; the parts forming the subcutaneous anti-detachment structure and the in vitro anti-detachment structure are all spherical joints arranged around the tube body and having a diameter larger than the outer diameter of the tube body; the subcutaneous anti-detachment structure is arranged on the part of the tube body close to the tube head and includes at least two spherical joints arranged at intervals; the in vitro anti-detachment structure is arranged between the subcutaneous anti-detachment structure and the tube tail and includes at least one spherical joint.

[0005] Further, the end of the tube head gradually tapers towards the head, and the hardness gradually increases.

[0006] Further, the tube head is made of PU material and / or the tube body is made of silicone material.

[0007] Further, the outer wall of the tube head is coated with a nitroglycerin coating.

[0008] Further, the thickness of the nitroglycerin coating is 5 - 10 μm.

[0009] Furthermore, the inner wall of the tube body is coated with a low molecular weight heparin sodium coating.

[0010] Furthermore, the thickness of the heparin sodium coating is 5 - 10 μm.

[0011] Furthermore, the outer diameter of the tube body is 0.9 - 1.2 mm, and the outer diameter of the spherical joint is 1.27 - 1.57 mm.

[0012] Furthermore, the outer diameter of the tube body is 1 mm, and the outer diameter of the spherical joint is 1.37 mm.

[0013] The usage method of the cannula for the rat jugular vein includes the following steps: Step 1: Fix the anesthetized rat in a supine position on the operating table, and expose the jugular vein incision. Step 2: Insert the tube head into the jugular vein incision. The subcutaneous anti - detachment structure follows the tube head into the subcutaneous tissue, and at least one spherical joint closest to the tube head enters the blood vessel, and the remaining spherical joints can extend into the vein or be outside the vein; the external anti - detachment structure is exposed outside the rat skin. Step 3: Connect the tail of the cannula to the syringe and draw blood.

[0014] The beneficial effects of the present invention: 1. The head end of the cannula gradually tapers and its hardness gradually increases, which is convenient for quickly inserting into the jugular vein, improving the insertion success rate and efficiency.

[0015] 2. The outer wall is coated with a nitroglycerin coating, which can prevent the jugular vein from spasm and collapse during cannulation, further improving the cannulation success rate.

[0016] 3. The inner wall of the cannula is coated with a low molecular weight heparin sodium coating to prevent blood coagulation inside the cannula, reduce the risk of consecutive blood drawing failure after surgery, and save experimental costs.

[0017] 4. The subcutaneous anti - detachment structure and the external anti - detachment structure are provided, which can fix the cannula, prevent displacement, and greatly improve the cannulation success rate.

[0018] 5. The tube head is made of PU material and the tube body is made of silica gel material, which enables the cannula to be conveniently inserted into the venous duct, has good biocompatibility, little tissue irritation, and is suitable for long - term use. Description of the Drawings

[0019] Figure 1 It is a schematic diagram of the external structure of the present invention.

[0020] Figure 2 It is a schematic cross - section diagram of the present invention. Detailed Embodiments

[0021] Such as Figure 1As shown in the figure, the mouse jugular vein cannula involved in the present invention includes a tube head, a tube body, and an anti-detachment structure, which will be introduced separately below.

[0022] (I) Tube head The end of the tube head gradually tapers towards the head, and the hardness gradually increases. It is preferably made of PU (polyurethane) material, which has the advantages of good rigidity, not easy to fold, and convenient for insertion. The tapered design improves the smoothness and success rate of intubation.

[0023] (II) Tube body The tube body is cylindrical. It is preferably made of silica gel material. Silica gel cannula has good biocompatibility, little irritation to tissues, and is suitable for long-term use.

[0024] To solve the interface bonding problem between silica gel and polyurethane, the most commonly used and simplest synergistic strategy of plasma surface activation + chemical coupling is adopted. This process has the advantages of wide industrial application, low difficulty, and low cost: ① Interface modification: The silica gel surface is treated with low-temperature oxygen plasma (50W / 120s) to generate active hydroxyl groups (-OH); the PU is treated with nitrogen plasma (40W / 90s) to introduce amino groups (-NH2), and molecular-level bonding is achieved through Si-O-C-NH2 covalent bonds, with a shear strength of 3.5MPa. ② Co-extrusion process optimization: A two-stage extruder is used. The temperature of the silica gel section is controlled at 60 - 85°C (to prevent pre-vulcanization), and the temperature of the PU section is controlled at 150 - 180°C (to maintain fluidity). Pre-stretching and fitting are achieved through differential traction (the silica gel is 5% faster), and the bonding strength is increased by 200%. ③ Biocompatibility guarantee: The silica gel / PU composite passes the ISO 10993 cytotoxicity (≤ grade 1) and sensitization (negative) tests, meeting the requirements for long-term in vivo indwelling.

[0025] (III) Anti-detachment structure The anti-detachment structure is divided into a subcutaneous anti-detachment structure and an in vitro anti-detachment structure. The parts constituting the subcutaneous anti-detachment structure and the in vitro anti-detachment structure are all spherical joints (such as Figure 1 shown, the spherical joints of the tube body) arranged around the tube body. There is a gap between the subcutaneous anti-detachment structure and the in vitro anti-detachment structure.

[0026] The subcutaneous anti-detachment structure is arranged on the part of the tube body close to the tube head and includes at least two spherical joints. During use, at least one spherical joint closest to the tube head is used for intravascular fixation, that is, it extends into the blood vessel. The remaining spherical joints can be selected to extend into the blood vessel or be located between the mouse skin and the blood vessel according to needs. There is a spacing between each spherical joint for winding medical silk thread.

[0027] The external anti-displacement structure is arranged between the subcutaneous anti-displacement structure and the tube tail, and includes at least one spherical joint. When only one spherical joint is included, the interval between the spherical joint and the subcutaneous anti-displacement structure can also be used to wind the medical silk thread. By fixing the medical silk thread, the displacement of the intubation can be effectively prevented. When multiple spherical joints are included, there is an appropriate distance between each spherical joint for winding the medical silk thread. Especially when a longer tube body is required in special occasions, multiple spaced spherical joints can fully ensure the winding space of the medical silk thread.

[0028] During use, the subcutaneous anti-displacement structure enters the subcutaneous tissue along with the intubation, and at least one spherical joint is inserted into the blood vessel. Since the outer diameter of the spherical joint is larger than the diameter of the blood vessel of the rat, it can prevent partial displacement of the intubation in the blood vessel. Other spherical joints of the subcutaneous anti-displacement structure can extend into the blood vessel or be outside the blood vessel to further prevent the displacement of the intubation driven by blood flow. The external anti-displacement structure is located outside the skin of the rat, further enhancing the stability of the intubation position.

[0029] Furthermore, the present application also includes a plug.

[0030] (IV) Plug As Figure 1 shown, the part inserted into the end of the tube tail is the plug. The plug is used to seal the end of the intubation. The plug needs to be removed when using the intubation, and the syringe is connected to the intubation. Preferably, the plug is made of a material that is not easy to rust, such as stainless steel.

[0031] Furthermore, the present application also includes a coating.

[0032] (V) Coating There is no coating on the inner and outer walls of the traditional intubation, which causes obvious tissue reactions or inflammations, resulting in thrombosis or catheter blockage and affecting patency.

[0033] To solve the problems that the PU material may cause obvious tissue reactions or inflammations and lead to blood coagulation in the intubation, and the traditional intubation causes vasospasm and blood coagulation due to the lack of coating, a nitroglycerin coating is applied to the outer wall of the tube head. Preferably, the thickness of the nitroglycerin coating is 5-10 μm. In this embodiment, a precision spraying technique is used to form a 5-10 μm anti-spasmodic layer. Using a precision pneumatic spraying device (nozzle diameter 0.3 mm, spraying pressure 0.2 MPa), a nitroglycerin solution (concentration 1%) is prepared with polyethylene glycol (PEG-400) as the carrier, and sprayed repeatedly three times, evenly sprayed on the outer wall of the intubation, and vacuum dried and cured at 50 °C to form an anti-spasmodic layer with a thickness of 5-10 μm.

[0034] The inner wall of the tube body is coated with a low molecular weight heparin sodium coating. Preferably, the thickness of the heparin sodium coating is 5-10 μm. Using the electrostatic spraying technique, low molecular weight heparin sodium (molecular weight 4.5 kDa) and polyvinylpyrrolidone (PVP K30) are mixed in a ratio of 1:3 and sprayed on the inner wall of the cannula. Spraying is repeated three times, and the coating thickness is 5-10 μm. Cross-linking by γ-ray irradiation enhances the adhesion. In this embodiment, by applying the coating on the inner wall of the tube body and the outer wall of the tube head simultaneously, the problems of vasospasm and blood coagulation caused by the traditional cannula without a coating can be effectively solved.

[0035] The following describes the relevant dimension settings of the present application. The total length of the cannula is 110-150 mm, preferably 120 mm. If it is set too short, the purpose of effective blood collection cannot be achieved, and if it is set too long, it may not be effectively fixed during use. The length of the tube body shall not be shorter than 100 mm. The length of the tube head is 9-12 mm, the outer diameter of the tube body is 0.9-1.2 mm, the inner diameter of the tube body is 0.53-0.73 mm, and the outer diameter of the spherical joint is 1.27-1.57 mm. In this embodiment, the total length of the cannula is 120 mm, the length of the tube body is 110 mm, the tube head is 10 mm, the outer diameter of the tube body is 1.00 mm, the inner diameter is 0.63 mm, and the outer diameter of the spherical joint is 1.37 mm. The subcutaneous anti-detachment structure has two spherical joints. The distance between the spherical joint closest to the tube head and the tube head is 26 mm, and the interval between this spherical joint and the adjacent spherical joint is 4 mm. The in vitro anti-detachment structure has one spherical joint, and its distance from the tube tail is 40 mm.

[0036] The following combines Figure 2 to detail the usage process of the cannula.

[0037] Step 1: Fix the anesthetized rat in the supine position on the operating table. Make a longitudinal incision along the right side of the midline of the neck to expose the right external jugular vein, and make a small incision on the vein wall.

[0038] The rat can be anesthetized intraperitoneally with 10% chloral hydrate at 0.35 ml / 100 g body weight or isoflurane gas.

[0039] Step 2: Gently insert the tube head into the vein. The subcutaneous anti-detachment structure follows the tube head into the subcutaneous tissue, and at least one spherical joint closest to the tube head enters the blood vessel, and the remaining spherical joints can extend into the blood vessel or be outside the vein. The in vitro anti-detachment structure is exposed outside the rat's skin.

[0040] Generally, for a rat weighing about 250 grams, the insertion depth of the cannula is about 2.5 cm; for a rat weighing about 150 grams, the insertion depth is about 2.2 cm. In actual operation, the cannula should be inserted to a position close to the right atrium. Usually, the total insertion depth is about 7.5 cm, but it needs to be adjusted according to the actual situation. If resistance is encountered during insertion, the position or direction of the cannula may need to be adjusted.

[0041] Step 3: After confirming that the intubation position is correct, remove the plug, connect the tail of the intubation to the syringe, and draw blood.

[0042] It should be noted that it is preferably to tie a knot on the tube body at the subcutaneous anti-detachment structure and the external anti-detachment structure in advance with medical silk thread (generally 4-0 non-absorbable surgical suture) to fix the intubation.

[0043] The above embodiments are only used to illustrate the present invention. The structures, connection methods, manufacturing processes, etc. of each component can be changed. Any equivalent transformation and improvement based on the technical solution of the present invention should not be excluded from the protection scope of the present invention.

Claims

1. An intubation tube for a rat jugular vein, characterized in that: It includes a tube head, a tube body, and an anti - detachment structure. The tube head is connected to the tube body. The anti - detachment structure is divided into a subcutaneous anti - detachment structure and an extracorporeal anti - detachment structure. The parts forming the subcutaneous anti - detachment structure and the extracorporeal anti - detachment structure are spherical joints arranged around the tube body and having a diameter larger than the outer diameter of the tube body. The subcutaneous anti - detachment structure is arranged at the part of the tube body close to the tube head and includes at least two spherical joints. The extracorporeal anti - detachment structure is arranged between the subcutaneous anti - detachment structure and the tube tail and includes at least one spherical joint.

2. The cannula for the jugular vein of a rat according to claim 1, wherein: The tube head gradually tapers from the end to the head, and the hardness gradually increases.

3. The cannula for the jugular vein of a rat according to claim 1, characterized in that: The tube head is made of PU material and / or the tube body is made of silicone material.

4. The cannula for the jugular vein of a rat according to any one of claims 1 to 3, characterized in that: The outer wall of the tube head is coated with a nitroglycerin coating.

5. The cannula for the jugular vein of a rat according to claim 4, characterized in that: The thickness of the nitroglycerin coating is 5 - 10 μm.

6. The cannula for rat jugular vein according to any one of claims 1 to 3, characterized in that: The inner wall of the tube body is coated with a low - molecular - weight heparin sodium coating.

7. The intubation tube for the jugular vein of a rat according to claim 6, wherein: The thickness of the heparin sodium coating is 5 - 10 μm.

8. The cannula for the jugular vein of a rat according to claim 1, characterized in that: The outer diameter of the tube body is 0.9 - 1.2 mm, and the outer diameter of the spherical joint is 1.27 - 1.57 mm.

9. The cannula for the jugular vein of a rat according to claim 8, characterized in that: The outer diameter of the tube body is 1 mm, and the outer diameter of the spherical joint is 1.37 mm.

10. A method for using an intubation tube for a rat jugular vein according to any one of claims 1-9, characterized in that, It includes the following steps: Step 1: Fix the anesthetized rat in a supine position on the operating table and expose the jugular vein incision. Step 2: Insert the tube head into the jugular vein incision. The subcutaneous anti - detachment structure follows the tube head into the subcutaneous tissue, and at least one spherical joint closest to the tube head enters the blood vessel, and the remaining spherical joints can extend into the vein or be outside the vein. The extracorporeal anti - detachment structure is exposed outside the rat skin. Step 3: Connect the tail of the cannula to a syringe and draw blood.

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