Disclosure of Invention
In order to solve the problems that the damage to animals is large, the blood taking amount is not easy to control, the timing and quantitative sampling cannot be performed for many times and the like in the prior art, the invention provides a catheter for intubation in animal experiments, which can fix the catheter on animals by a three-point fixing method, thereby not only preventing the catheter from falling off, but also achieving the purpose of continuous research.
In order to achieve the above purpose, the present invention provides the following technical solutions:
a catheter for intubation in animal experiments comprises a hose and three fixing points arranged on the surface of the hose.
According to the invention, the hose comprises a wedge-shaped end and a flat-shaped end, and a first fixed point, a second fixed point and a third fixed point are sequentially arranged along the wedge-shaped end to the flat-shaped end of the hose.
According to the invention, the flat end is also provided with the conduit plug, the diameter of the conduit plug is slightly larger than the inner diameter of the flat end, and the conduit plug can be plugged into the flat end and seal the hose.
According to the invention, the wedge angle of the wedge end is about 25 to 45 °, preferably 25 to 35 °, more preferably 30 °.
According to the invention, the fixing point is in the shape of a water drop or a sphere.
Preferably, the outer diameter of the fixed point is 1.1-1.5 times of the outer diameter of the hose.
Preferably, the hose and the fixing point are made of the same material.
Preferably, the hose is a medical silicone tube, and the fixing point is a silicone ball. The catheter made of the silica gel material is rich in elasticity, so that experimental operation is convenient, and the adaptability of animals is good.
According to the invention, the catheter may be used in cannula sampling or administration experiments of different animals, such as mice, rats, dogs, monkeys, etc., in particular in mouse or rat experiments.
Preferably, the weight of the rat is 180g-220g.
Preferably, the weight of the mice is 15g-25g.
According to the invention, the catheter is used for catheterizing parts such as veins, intestinal tracts, bile ducts and the like of animals, and the outer diameter and the length of the hose can be selected according to specific sizes of different animals and different parts. The pipe diameter is too large, the dead volume is too large, the residual liquid medicine in the pipe is too much, and animals are difficult to receive; too small tube diameter, slow blood sampling and much hemolysis will directly affect the detection of blood indexes and the accuracy of experimental data.
According to the invention, when the catheter is used for carrying out intubation experiments on animals, the wedge mouth end is inserted into the incision of the target part and reaches the target part, the first fixing point is plugged into the incision of the target part, and the outer side of the first fixing point is fixed with the organ wall of the target part. Can prevent the fixed part from falling off at the cannula caused by rhythmic movement or animal movement. The target site organ wall may be a vein (e.g., jugular), bile duct, or duodenal wall.
According to the invention, the second fixation point is fixed inside the muscle layer of the animal.
According to the invention, the third fastening point is placed outside the epidermis at the incision in the skin of the animal, the flat end being left outside the body for sampling or administration. The catheter can prevent falling off and can also prevent the catheter from completely entering the body, so that the incapability of experiments is avoided.
According to the invention, the catheter size is reasonably designed, and the length from the wedge mouth end to the first fixed point mainly depends on the animal type and specific part of the catheter to be subjected to intubation experiments, and the judgment is carried out according to actual needs. If the length between the wedge mouth end and the first fixed point is too long, for example, when the catheter is inserted into the duodenum, the cannula can be too deep, a large amount of liquid medicine directly enters the ileum during administration, the absorption of the liquid medicine is affected, and the pharmacokinetic parameters are greatly disturbed; if the length between the wedge end and the first fixation point is too short, for example, when the catheter is inserted into the bile duct, the cannula is too shallow, and the tube is removed due to intestinal peristalsis.
According to the invention, the length from the first fixation point to the second fixation point is mainly dependent on the distance of the target site to the muscle layer. Too short a length between the first fixed point and the second fixed point can easily cause tube detachment, and too long a length can easily cause catheter distortion, and drug administration or sampling is not smooth.
According to the invention, the length from the second fixing point to the third fixing point is mainly dependent on the distance of the muscle layer to the back of the animal's neck. Too short a length between the second fixation point and the third fixation point, the catheter is easily retracted into the skin by the movement of the animal, resulting in no catheter being found; too long leads the catheter to easily extend out of the skin, and too long extension leads the catheter to be easily scratched by animals.
According to the invention, the length from the third fixing point to the flat end is mainly dependent on the length of the catheter exposed to the skin. The length from the third fixed point to the flat mouth end is too long to be easily scratched by animals, and too short is not beneficial to taking blood after administration.
According to the invention, the hose length is 7 to 19cm, preferably 9 to 15cm, and the hose outer diameter is 0.4 to 5mm, preferably 0.6 to 3mm, taking rat experiments as an example.
Preferably, the first fixing point is 1-5 cm, preferably 1.5-4 cm, away from the wedge opening end;
Preferably, the second fixing point is 0.5-4 cm, preferably 1-3 cm, from the first fixing point;
preferably, the third fixed point is 3-11 cm, preferably 3.5-9 cm, from the second fixed point;
Preferably, the third fixing point is 1-2 cm, preferably 1.2-1.8 cm, from the flat end.
According to the present invention, taking a rat experiment as an example, the length of the hose is 7 to 12cm, preferably 8 to 10cm, more preferably 9cm, when performing jugular vein catheterization; the outer diameter of the hose is 0.8-1 mm, preferably 1mm;
Preferably, the first fixed point is 2-4 cm, preferably 3cm, away from the wedge mouth end;
preferably, the second fixing point is 1-1.5 cm, preferably 1cm, from the first fixing point;
preferably, the third fixed point is 3-5 cm, preferably 3.5cm, from the second fixed point;
preferably, the third fixing point is 1-2 cm, preferably 1.5cm, from the flat end.
According to the present invention, taking a rat test as an example, the length of the hose is 13 to 19cm, preferably 13 to 15cm, more preferably 13.5cm, when performing a biliary catheterization test; the outer diameter of the hose is 0.4-0.6 mm, preferably 0.6mm;
Preferably, the first fixed point is 1-2 cm, preferably 1cm, away from the wedge mouth end;
preferably, the second fixing point is 2-4 cm, preferably 2cm, from the first fixing point;
Preferably, the third fixed point is 8-11 cm, preferably 9cm, from the second fixed point;
preferably, the third fixing point is 1-2 cm, preferably 1.5cm, from the flat end.
According to the present invention, taking a rat test as an example, the length of the hose is 11 to 15cm, preferably 12 to 14cm, more preferably 13.5cm, when performing a duodenal intubation test; the outer diameter of the hose is 1-5 mm, preferably 1-2 mm, more preferably 1mm;
the distance between the first fixed point and the wedge opening end is 1-1.5 cm, preferably 1cm;
the second fixed point is 1.5-2 cm, preferably 2cm, away from the first fixed point;
the third fixed point is 8.5-9.5 cm, preferably 9cm, away from the second fixed point;
The third fixing point is 1-2 cm, preferably 1.5cm, from the flat mouth end.
The invention also provides a preparation method of the catheter, which comprises the following steps:
(1) Cutting one end of the hose into a wedge opening and the other end is aligned;
(2) Three fixing points are formed on the hose in the step (1) by using a silica gel adhesive.
According to the invention, in step (1), the outer diameter and length of the hose are selected according to the specific dimensions of the different animals and the different sites.
According to the invention, in step (2), the position of the three fixing points on the catheter is selected according to the kind and specific location of the animal to be intubated by the catheter.
According to the invention, in step (2), after three fixing points are formed on the hose, the hose is dried and solidified.
The invention also provides application of the catheter in animal intubation administration or sampling experiments, such as intravenous intubation administration, intravenous intubation blood sampling, intestinal tract administration, bile duct bile sampling and other experiments.
Preferably, the catheter is used for jugular vein catheterization.
In order to solve the problems that the drug is easy to cause death and unstable in administration and continuous administration cannot be realized when the dosage of the drug is large or the toxicity is large in the prior art; meanwhile, the drug delivery device is not firm and is easy to fall off along with the action of animals, so that the problem of inaccurate drug delivery results and the like is solved.
In order to achieve the above purpose, the present invention provides the following technical solutions:
The invention also provides an infusion administration device which comprises a catheter for an intravenous needle or cannula, an intravenous needle, a syringe and a syringe pump; one end of the catheter for the venous indwelling needle or the cannula is inserted into a vein, and the other end of the catheter is connected with the venous transfusion needle; the other end of the intravenous infusion needle is connected with an injector which is arranged in the injection pump.
According to the invention, the vein is preferably a tail vein.
According to the present invention, the catheter for intubation is selected from the catheters for intubation in the animal experiments described above.
According to the present invention, it will be understood by those skilled in the art that the choice of the intravenous needle is not limited, and an intravenous needle of an appropriate size is selected according to the experimental model to be administered.
According to the present invention, it will be understood by those skilled in the art that the choice of the iv needle is not limited, and an iv needle of a suitable size is selected according to the experimental model to be administered.
It will be appreciated by those skilled in the art that the choice of the syringe is not limited, and that a syringe of an appropriate capacity may be selected depending on the amount of drug to be administered. As an example, when the dose of the drug to be administered is less than 1mL, a 1mL syringe may be selected, and when the dose of the drug to be administered is greater than 1mL and less than 2.5mL, a 2.5mL syringe may be selected.
The invention also provides application of the infusion administration device, which is applied to experiments of animal administration, such as intravenous administration, intestinal administration and the like, and is particularly applicable to experiments of intravenous infusion administration, intestinal infusion administration and the like.
Preferably for tail vein infusion administration.
The invention also provides an animal test model for pharmacological experiments, which comprises an animal model, the catheter and the infusion administration device.
According to the invention, the animal model is preferably a rat or a mouse.
Preferably, the weight of the rat is 180g-220g.
Preferably, the weight of the mice is 15g-25g.
The invention also provides a using method of the animal test model for pharmacological experiments, which comprises the following steps:
a) Performing intubation operation on the animal model, and inserting the catheter of the invention into the animal model;
b) Infusing a drug into an animal model by the infusion drug delivery device;
c) Sampling was performed by a catheter inserted into the animal model.
According to the invention, in the step b), the infusion method can be that an intravenous needle or a catheter for a cannula in an infusion administration device is used for penetrating into tail veins of an animal model, the other end of the intravenous needle or the catheter for the cannula is connected with an intravenous needle, the other end of the intravenous needle is connected with a syringe, and the syringe controls the administration volume and the administration rate through a syringe pump.
According to the invention, in step c), the sampling may be performed during the administration process, or may be performed before or after the administration process; the sampling may be blood or bile sampling, etc.
The invention also provides application of the animal test model in continuous pharmacological research such as in-vivo drug metabolism research of animals.
The invention also provides a method for administration and sampling, which is characterized in that the method comprises the use of the animal test model for pharmacological experiments.
The method according to the invention is characterized in that the method further comprises the steps of:
a) Performing intubation operation on the animal model, and inserting the catheter of the invention into the animal model;
b) The drug is infused into the animal model body through the infusion administration device, the infusion method uses the venous indwelling needle or the catheter for the cannula in the infusion administration device to penetrate into the tail vein of the animal model, the other end of the catheter for the venous indwelling needle or the cannula is connected with the venous transfusion needle, the other end of the venous transfusion needle is connected with the injector, and the injector controls the administration volume and the administration rate through the injection pump;
c) Sampling through a catheter inserted into the animal model; the sampling is performed during the administration process or before and after the administration; the sampling may be blood or bile sampling, etc.
Preferably, the administration and sampling according to the invention are performed simultaneously.
The beneficial effects are that:
1. The invention provides a catheter for intubation in animal experiments; compared with the prior art, the catheter for the intubation has the following advantages:
(1) The injury is small, and the method accords with animal ethics; the medicine can be sampled for multiple times or continuously administered, and the sampling amount or the administration amount can be controlled, so that the continuous research is facilitated;
(2) In the sampling process, the animal is in a waking state, and the accuracy of a test result is high;
(3) The structure and the size are fully designed, so that the animal cannot bite the animal and the falling off is avoided;
(4) The catheter has the advantages of simple structure, convenient production and manufacture, easy obtainment of materials, lower manufacturing cost, no back piece, convenient popularization and application, and high success rate of intubation by adopting the catheter disclosed by the invention, and shortened operation time, and accords with the international following 3R principle.
2. Compared with the conventional research model, the infusion administration device and the animal test model provided by the invention have the obvious advantages that the animal test model is adopted for experiments:
(1) Compared with femoral vein catheterization, the tail vein infusion administration has no operation wound, reduces infection risk, has small harm to animals, accords with the 3R principle of international ethics requirement, is convenient to administer, can ensure that the set medicine volume is almost completely administered into the animal body, and can remain part of medicine liquid in a catheterization catheter when femoral vein catheterization is administered;
(2) Compared with the femoral vein cannula for taking blood, the external jugular vein cannula for taking blood has a cannula catheter which is short, so that the risk of thrombus blocking the catheter caused by residual blood in the catheter after taking blood is reduced, and the external jugular vein cannula catheter directly passes from external jugular vein to the neck and back of a rat, has no influence on the movement of limbs, and is simple to operate;
(3) Compared with femoral vein cannula infusion and external jugular vein cannula blood taking, the method has the advantages that the operation difficulty is low, only the external jugular vein cannula needs to be developed, the operation is few, the risk of postoperative infection of rats is reduced, administration and blood taking are not interfered with each other, and experimental operation errors caused by indistinct administration and blood taking of the administration tube are reduced.
3. The method for administration and sampling can effectively relieve pain of an animal model in the administration and sampling processes, has no influence on limb activities, is simple to operate, can realize simultaneous administration and sampling, and greatly reduces experimental errors.
Detailed Description
The invention will be further illustrated with reference to specific examples. It is understood that these examples are provided only for illustrating the present invention and are not intended to limit the scope of the present invention. Further, it is understood that various changes and modifications of the present invention may be made by those skilled in the art after reading the disclosure of the present invention, and such equivalents are intended to fall within the scope of the present invention as defined by the appended claims.
In the invention, the injection pump is Lei Fubeng with the model TYD 02-01.
Example 1
As shown in figure 1, the catheter for intubation in animal experiments comprises a hose and three fixing points arranged on the surface of the hose. The hose comprises a wedge-shaped opening end 1 and a flat-shaped opening end 2, and a first fixed point 11, a second fixed point 12 and a third fixed point 13 are sequentially arranged along the wedge-shaped opening end 1 to the flat-shaped opening end 2 of the hose.
The catheter may be used in cannula sampling or administration experiments for different animals, such as rats, dogs, monkeys, mice, etc., in particular in mouse or rat experiments. The general cannula parts are parts such as veins, intestinal tracts, bile ducts and the like, and the outer diameter and the length of the hose can be selected according to the sizes of different parts.
In the above catheter experiment, the wedge-shaped end 1 is inserted into the target organ, wherein the first fixing point 11 is fixed in the organ wall, the second fixing point 12 is fixed on muscle tissue, the third fixing point 13 is fixed outside the skin suture, and the flat-mouth end 2 is positioned outside the body.
Example 2
Specifically, according to different experimental animals and parts, a silica gel hose with proper outer diameter and length is selected, one end of the silica gel hose is provided with a wedge opening (about 25-45 degrees), and the other end of the silica gel hose is provided with a regular opening. According to the requirement, three fixed point positions with proper sizes are respectively selected, and a silica gel adhesive (K-780 s, jing Gu) is used for dripping water drops or spherical bulges, and the mixture is dried and solidified for standby.
Taking a rat experiment as an example, wherein the length of the hose is 7-19 cm, and the outer diameter of the hose is 0.4-5 mm; the first fixed point is 1-5 cm away from the wedge opening end; the second fixed point is 0.5-4 cm away from the first fixed point; the distance between the third fixed point and the second fixed point is 3-11cm, and the distance between the third fixed point and the flat mouth end is 1-2 cm.
Specifically, when the catheter is used for a rat jugular vein catheterization catheter, the dimensions are selected as follows:
The length of the hose is 7-12 cm, the outer diameter of the hose is 0.8-1 mm, a wedge opening (about 30 degrees) is cut at one end, a first fixed point silica gel ball is manufactured at a position which is 2-4 cm away from the wedge opening end, a second fixed point silica gel ball is manufactured at a position which is 1-1.5 cm away from the first fixed point silica gel ball, a third fixed point silica gel ball is manufactured at a position which is 3-5 cm away from the second fixed point, and the third fixed point silica gel ball is 1-2 cm away from the flat opening end.
In a preferred embodiment of the invention, the hose is 9cm long, the first fixing point is 3cm from the wedge end, the second fixing point is 1cm from the first fixing point, and the third fixing point is 1.5cm from the flat end.
Specifically, when the catheter is used for rat bile duct insertion catheter, the dimensions thereof are selected as follows:
The length of the hose is 13-19 cm, and the outer diameter of the hose is 0.4-0.6 mm; the first fixed point is 1-2 cm away from the wedge mouth end, the second fixed point is 2-4 cm away from the first fixed point, the third fixed point is 8-11 cm away from the second fixed point, and the third fixed point is 1-2 cm away from the flat mouth end.
In a preferred embodiment of the invention, the hose is 13.5cm long, the outer diameter of the hose is 0.6mm, the first fixing point is 2cm from the wedge end, the second fixing point is 2cm from the first fixing point, the third fixing point is 8cm from the second fixing point, and the third fixing point is 1.5cm from the flat end.
Specifically, when the catheter is used for rat insertion of a duodenal catheter, the dimensions thereof are selected as follows:
The length of the hose is 11-15 cm, the outer diameter of the hose is 1-5 mm, the distance between the first fixed point and the wedge opening end is 1-1.5 cm, the distance between the second fixed point and the first fixed point is 1.5-2 cm, the distance between the third fixed point and the second fixed point is 8.5-9.5 cm, and the distance between the third fixed point and the flat opening end is 1-2 cm.
In a preferred embodiment of the invention, the hose length is 13.5cm and the hose outer diameter is 1mm, the first fixing point is 1cm from the wedge end, the second fixing point is 2cm from the first fixing point, the third fixing point is 9cm from the second fixing point, and the third fixing point is 1.5cm from the flat end.
Example 3
As shown in fig. 2, an infusion administration device including an iv needle 31 or a catheter for cannula (not shown) described in embodiment 1, an iv needle 32, a syringe 33, and a syringe pump 34; one end of the venous indwelling needle 31 or the catheter for intubation described in embodiment 1 is inserted into a vein, and the other end is connected to the venous transfusion needle 32; the other end of the intravenous needle 32 is connected with a syringe 33, and the syringe 33 is arranged in a syringe pump 34.
Example 4 rat intubation experiment
The silica gel catheter is irrigated and washed by 0.02% heparin sodium physiological saline solution for anticoagulation treatment, so that each part of the catheter is ensured to be fully contacted with heparin sodium; before the silicone tube is used, the silicone tube is soaked in physiological saline.
Experiment one: rat external jugular vein catheterization experiment
The cannula catheter is selected, the length of the catheter is 9cm, the outer diameter of the catheter is 1mm, the distance from the wedge opening end to the silica gel ball of the first fixed point is 3cm, the distance from the silica gel ball of the second fixed point to the silica gel ball of the first fixed point is 1cm, the distance from the silica gel ball of the third fixed point to the silica gel ball of the second fixed point is 3.5cm, and the distance from the silica gel ball of the third fixed point to the flat opening end is 1.5cm.
The wedge mouth end stretches into a rat blood vessel, the silica gel ball of the first fixed point is plugged into the blood vessel, the outer side of the silica gel ball is fixed on an external jugular vein blood vessel, the outer side of the silica gel ball of the second fixed point is fixed on neck muscle tissue, the silica gel ball at the third fixed point is placed outside the body, the inner side of the silica gel ball is fixed at the suture position of the external skin of the neck back, and the flat mouth end is left outside the body. The catheter plug is pulled out during administration or sampling. When blood is collected, a syringe is adopted to collect blood through the flat port end; when in administration, the flat end of the cannula catheter is connected with a disposable intravenous infusion needle (flat end needle head), then is connected with a 2.5mL syringe, and is administrated by adopting a syringe pump with the administration rate parameters set.
After the external jugular vein catheterization catheter is fixed by a three-point method, the external jugular vein catheterization catheter can be firmly fixed and is not easy to take off the catheter; for the rats of 180g-220g, the distance between the silica gel balls provided by the technology is optimal, and heparin sodium physiological saline and heparin sodium glycerol solution are adopted for sealing the tube, so that the smooth blood collection can be ensured, the cannula catheter can be shortest, heparin sodium glycerol is reserved in the tube, and the risk of thrombus blockage is reduced; the catheter plug is of a section of columnar structure with the diameter slightly larger than the inner diameter of the catheter, so that the sealing effect can be achieved, and the rat can be well prevented from falling off due to mutual biting.
Experiment II: rat duodenal intubation experiment
The cannula catheter is selected, the length of the catheter is 13.5cm, the outer diameter is 1mm, the distance between the wedge opening end and the first fixed point silica gel ball is 1cm, the distance between the second fixed point silica gel ball and the first fixed point silica gel ball is 2cm, the distance between the third fixed point silica gel ball and the second fixed point silica gel ball is 9cm, and the distance between the third fixed point silica gel ball and the flat opening end is 1.5cm.
During intubation, the wedge mouth end stretches into the duodenum of the rat, the first fixed point silica gel ball is fixed at the pylorus, the second fixed point silica gel ball is fixed on the abdominal muscle of the rat, the third fixed point silica gel ball is fixed on the outer side of the skin of the neck and the back of the rat, and the flat mouth end is arranged outside the body.
Experiment III: rat bile duct intubation experiment
The cannula catheter is selected, the length of the catheter is 13.5cm, the outer diameter is 0.6mm, the distance between the wedge opening end and the first fixed point silica gel ball is 1cm, the distance between the second fixed point silica gel ball and the first fixed point silica gel ball is 2cm, the distance between the third fixed point silica gel ball and the second fixed point silica gel ball is 9cm, and the distance between the third fixed point silica gel ball and the flat opening end is 1.5cm.
During intubation, the wedge mouth end stretches into the rat bile duct, the first fixed point silica gel ball is fixed in the bile duct wall, the second fixed point silica gel ball is fixed in the rat belly muscle, the third fixed point silica gel ball is fixed in the rat neck and back skin outside, the flat mouth end is arranged in vitro.
Example 5 Tail vein infusion administration + external jugular vein cannula blood sampling
1) Animal model selection
6 SD rats (purchased from Beijing Veitz laboratory animal technologies Co., ltd.) were obtained, SPF-grade, and the weight was 180-220g, and the male and female were half.
2) Tail vein infusion administration
The rat is placed in a fixed cage, the tail part of the rat is punctured into the tail vein by adopting a disposable venous indwelling needle with the specification of 24G x19 mm/Y-G type, the other end of the venous indwelling needle is connected with a disposable venous transfusion needle with the specification of 0.6G (23G), the other end of the disposable venous transfusion needle is connected with a syringe with the specification of 2.5mL, and the syringe is placed in a syringe pump, so that the administration volume and the administration rate are set.
3) External jugular vein catheterization
After the beginning of tail vein infusion administration, the rats were timed, and at the designated time point (the time point was set to be executed according to the pharmacokinetic experiment scheme of the specific drug), the tail vein infusion tube was sucked out of the rat external jugular vein catheterization tube by using a 2.5mL flat-mouth syringe, discarded, 200-300. Mu.L of blood was sucked again for the experiment, after which 0.3mL of 2% heparin sodium physiological saline solution was administered to pull the blood in the catheter back into the rat body, and then 0.03mL of 2% heparin sodium glycerol solution was capped.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.