Contrast catheter with photo-controllable deformation and its use

Abstract

The application provides a contrast medium catheter with photo-controllable deformation and application thereof. The contrast medium catheter with photo-controllable deformation comprises a catheter seat, a tube body, a transition section and a photo-controllable deformation head; one end of the tube body is connected to the catheter seat, the inner cavity of the tube body is communicated with the spherical inner cavity of the catheter seat, the other end of the tube body is connected to the transition section, the other end of the transition section is connected to the photo-controllable deformation head, and the photo-controllable deformation head is prepared from raw materials including photo-responsive polymer materials and near-infrared light conversion materials. The contrast medium catheter can realize the change of the shape of the head of the contrast medium catheter, deflect a certain angle, and then more accurately and quickly enter the correct blood vessel branch through the irradiation of the near-infrared light outside the body.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, further relates to a contrast catheter with photo-induced controllable deformation and application thereof. BACKGROUND

[0002] Angiography is a safe and effective method for diagnosing various cardiovascular and cerebrovascular diseases. As a key device for angiography, the contrast catheter plays a crucial role in the process of angiography. Clinical practice shows that the distribution of cardiovascular and cerebrovascular is relatively complex, and the contrast catheter itself does not have the selectivity of power and direction. Therefore, in the blood vessel intersection, the doctor needs to manually adjust the position of the contrast catheter or the contrast guide wire in the external environment with the aid of medical imaging equipment, so as to reach the affected area. Angiography requires a high level of operation from the doctor, and generally requires the doctor to have excellent professional knowledge and rich practical experience. However, at present, the number of doctors who can master angiography is far less than the number of patients required, and this phenomenon is particularly serious in remote areas. In the blood vessel intersection, the doctor needs to continuously adjust the position of the contrast catheter in the external environment to make it enter the correct branch. On the one hand, this process lasts for a long time, which is not conducive to the treatment of the patient. On the other hand, the catheter will rub against the blood vessel wall, which can easily damage the surrounding tissue and cause secondary damage. Angiography needs to be performed with the aid of medical imaging equipment, and the radiation accumulated for a long time can have a certain impact on the health of the doctor.

[0003] Therefore, it is necessary to study a contrast catheter which can effectively control the shape change of the head end of the contrast catheter in the external environment, so as to deflect the angle, change the direction, and more accurately and quickly enter the correct blood vessel branch. SUMMARY

[0004] In order to solve the technical problems existing in the prior art, the present application provides a contrast catheter with photo-induced controllable deformation and application thereof.

[0005] The contrast catheter of the present application has a head end with photo-induced controllable deformation. In the blood vessel intersection, the shape of the head end of the contrast catheter can be changed by irradiating the external near-infrared light, deflecting a certain angle, and then more accurately and quickly entering the correct blood vessel branch.

[0006] The present application overcomes the problem that the doctor takes a long time to adjust the position of the contrast catheter to make it enter the correct branch, or the catheter rubs against the blood vessel wall, which can easily damage the surrounding tissue. At the same time, the present application shortens the time for the doctor to perform angiography with the aid of medical imaging equipment, which is beneficial to the protection of the health of the doctor.

[0007] One of the purposes of the present application is to provide a contrast catheter with photo-controllable deformation.

[0008] The contrast catheter with photo-controllable deformation comprises a catheter seat, a tube body, a transition section and a photo-controllable deformation head; one end of the tube body is connected to the catheter seat, the inner cavity of the tube body is in communication with the inner cavity of the catheter seat, the other end of the tube body is connected to the transition section, and the other end of the transition section is connected to the photo-controllable deformation head.

[0009] The photo-controllable deformation head is prepared from raw materials including photo-responsive high molecular materials and near-infrared light conversion materials.

[0010] In a preferred embodiment of the present application,

[0011] The photo-responsive high molecular material is polymerized by free radical polymerization or other polymerization methods, preferably the main chain is at least one of polyacrylate, polyimide, polyurethane and polysiloxane, and the side chain is at least one of azobenzene and its derivatives, stilbene and its derivatives, spiro-pyrans and its derivatives, and captax and its derivatives; more preferably, the main chain is polyacrylate, and the side chain is azobenzene and its derivatives and stilbene and its derivatives.

[0012] The near-infrared light conversion material is at least one of up-conversion luminescent material, inorganic light-heat conversion material and organic light-heat conversion material.

[0013] In a preferred embodiment of the present application,

[0014] The photo-responsive high molecular material is at least one of poly(2-(ethyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)ethyl acrylate), poly(6-(4-((4-propyloxyphenyl)diazenyl)phenoxy)hexyl methacrylate) and poly(6-(4-(1-cyano-2-phenylvinyl)phenoxy)hexyl acrylate).

[0015] Poly(2-(ethyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)ethyl acrylate) is obtained by free radical polymerization.

[0016] Preparation method:

[0017] In a 250 mL beaker, 2-(ethyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)ethyl acrylate (10 g) and initiator benzoyl peroxide (BPO) (20 mg) are vacuum dried for 1 h, 100 mL of anhydrous tetrahydrofuran (THF) is added under argon protection, then the reaction system is purged with high-purity nitrogen for 20 min to remove oxygen, and sealed. Finally, the reaction system is heated to 60℃ under vacuum and sealed conditions for 24 hours. After the reaction is completed, the reaction liquid is precipitated with anhydrous ethanol to obtain a solid, which is dried to obtain the target product;

[0018] The structural formula is:

[0019]

[0020] Poly 6-(4-((4-propoxyphenyl) diazenyl) phenoxy) methyl hexyl methacrylate is obtained by free radical polymerization;

[0021] Preparation method:

[0022] In a 250 mL round-bottom flask, monomer 6-(4-((4-propoxyphenyl) diazenyl) phenoxy) methyl hexyl methacrylate (10 g) and initiator azobisisobutyronitrile (AIBN) (20 mg) were vacuum-dried for 1 h, 100 mL of anhydrous tetrahydrofuran (THF) was added under argon protection, and then the reaction system was purged with high-purity nitrogen for 20 min to remove oxygen and sealed. Finally, the reaction system was heated to 60 DEG C under vacuum and sealed conditions for 24 hours. After the reaction was completed, the reaction liquid was precipitated with anhydrous ethanol to obtain a solid, which was dried to obtain the target product;

[0023] The structural formula is:

[0024]

[0025] Poly 6-(4-(1-cyano-2-phenylvinyl) phenoxy) hexyl acrylate is obtained by free radical polymerization;

[0026] Preparation method:

[0027] In a 250 mL round-bottom flask, monomer 6-(4-(1-cyano-2-phenylvinyl) phenoxy) hexyl acrylate (10 g) and thermal initiator benzoyl peroxide (BPO) (20 mg) were vacuum-dried for 1 h, 100 mL of anhydrous tetrahydrofuran (THF) was added under argon protection, and then the reaction system was purged with high-purity nitrogen for 20 min to remove oxygen and sealed. Finally, the reaction system was heated to 80 DEG C under vacuum and sealed conditions for 24 hours. After the reaction was completed, the reaction liquid was precipitated with anhydrous methanol to obtain a solid, which was dried to obtain the target product;

[0028] The structural formula is:

[0029]

[0030] The up-conversion luminescent material is at least one of a rare earth luminescent crystalline material and a rare earth luminescent amorphous material; and / or,

[0031] The inorganic light-heat conversion material is at least one of a carbon nanotube, graphene, and a metal nanomaterial; and / or,

[0032] The organic light-heat conversion material is at least one of a conjugated polymer, a near-infrared dye.

[0033] In a preferred embodiment of the present application,

[0034] The rare earth luminescent crystalline material is at least one of a single crystal and a nanocrystal powder; the single crystal is at least one of YVO4, YAG and BaY2F8; the nanocrystal powder is at least one of a rare earth doped fluoride, oxide and phosphate; the rare earth doped fluoride is at least one of NaYF4:Yb / Tm and NaYF4:Yb / Er; and / or,

[0035] The rare earth luminescent amorphous material is at least one of a ceramic and a glass; and / or,

[0036] The metal nanomaterial is preferably at least one of CuS and Fe3O4 nanomaterial; and / or,

[0037] The conjugated polymer is preferably at least one of a polythiophene and a polydopamine; and / or,

[0038] The near-infrared dye is preferably indocyanine green.

[0039] In a preferred embodiment of the present application,

[0040] The mass ratio of the light-responsive polymer material to the near-infrared light conversion material is 1:(0.01-100); preferably 1:(0.05-1).

[0041] The amount of the near-infrared light conversion material is related to the size and speed of the deformation of the head end of the light-induced controllable deformation; for the same kind of near-infrared light conversion material, as the proportion increases, the hardness of the material increases, the deformation amount decreases, and the deformation speed increases; the above mass ratio should be determined according to different situations.

[0042] In a preferred embodiment of the present application,

[0043] The catheter seat is a hollow structure, having a catheter seat inlet and a catheter seat outlet; the catheter seat inlet is in communication with the outside world; the pipe body and the catheter seat are in communication through the catheter seat outlet; the catheter seat has two flaps on opposite positions of the side surface, which are perpendicular to the outer surface of the catheter seat; the flaps on the side surface facilitate the rotation of the catheter seat;

[0044] The pipe body comprises a pipe body inner layer, a pipe body intermediate woven layer and a pipe body outer layer;

[0045] The transition section comprises a transition section inner layer and a transition section outer layer; preferably, it further comprises a transition section intermediate woven layer;

[0046] The layered structure of the tube body and the transition section endows the angiography catheter with good support, twist control, elasticity and bending resistance;

[0047] The hardness of the tube body, the transition section and the light-induced controllable deformation head end decreases in turn;

[0048] The Shore hardness of the outer layer of the tube body is 40-70D;

[0049] The Shore hardness of the outer layer of the transition section is 25-40D;

[0050] The Shore hardness of the light-induced controllable deformation head end is 5-25D.

[0051] In a preferred embodiment of the present application,

[0052] The catheter seat is made by injection molding;

[0053] The tube body is made by extrusion and braiding process; preferably, the inner tube of the tube body is extruded by an extruder first, then stainless steel wires are cross-braided on the outer surface of the inner tube of the tube body by a braiding machine, and then the outer tube of the tube body is extruded by an extruder;

[0054] The inner and outer layers of the transition section are made by extrusion process;

[0055] The middle braided layer of the transition section is made by braiding process, and the braiding machine can cross-braid stainless steel wires on the outer surface of the inner tube of the transition section;

[0056] The light-induced controllable deformation head end is made by injection molding, extrusion molding or 3D printing process; the light-induced controllable deformation head end is first doped by a physical doping method, using a light-responsive polymer as a substrate, doping near-infrared light conversion material, and then the light-induced controllable deformation head end is obtained by injection molding, extrusion molding or 3D printing by loading into a 3D printer;

[0057] The tube body and the catheter seat are connected by adhesion, injection molding or welding;

[0058] The tube body, the transition section and the light-induced controllable deformation head end are welded, and the tube body, the transition section and the light-induced controllable deformation head end are three sections connected by welding process.

[0059] In a preferred embodiment of the present application,

[0060] The catheter seat is made of acrylonitrile-butadiene-styrene terpolymer (ABS) or nylon 12; and / or,

[0061] The inner layer of the tube body is made of polytetrafluoroethylene (PTFE), nylon 12 or block polyether amide elastomer (PEBAX) material; the block polyether amide elastomer is preferably at least one of PEBAX 6333 SA 01, PEBAX 5533 SA 01, PEBAX 4533 SA 01, PEBAX MV 1074 SA 01; wherein PTFE meets the requirements of high temperature resistance, corrosion resistance, low friction coefficient, non-stick, non-toxic, which is beneficial to the smooth passage of the contrast guide wire;

[0062] The middle braided layer of the tube body is made of stainless steel material; preferably made of 10-30 stainless steel round wires or flat wires, with a braiding density of 50-70 PPI; the stainless steel is a medical grade stainless steel, preferably SUS304 or SUS316 (medical grade); more preferably a flat wire, which can further reduce the thickness of the tube wall, increase the inner cavity, improve the flow of the input contrast agent, and at the same time provide a large surface area for support, giving the tube excellent rigidity and support;

[0063] The outer layer of the tube body is made of at least one of block polyether amide elastomer (PEBAX), nylon, thermoplastic polyurethane, polyimide, styrene-based thermoplastic elastomer, acrylonitrile-butadiene-styrene terpolymer, thermoplastic silicone elastomer; the block polyether amide elastomer is preferably at least one of PEBAX 7433 SA 01, PEBAX 7233 SA 01, PEBAX 7033 SA 01, PEBAX 6333 SA 01, PEBAX 5533 SA 01, PEBAX 4533 SA 01, PEBAX MV 1074 SA 01; the nylon is preferably nylon 12;

[0064] The medical grade PEBAX material has a low friction coefficient, which can reduce the damage to the human body during use, and the PEBAX material has passed the USP class VI and FDA certification of the US Food and Drug Administration, which can be used for medical care products. Compared with other thermoplastic elastomers, especially TPU, the rheological performance of PEBAX material allows a wider processing temperature, which can be injected into very thin parts, with a wall thickness as thin as 0.005 inches, and has accurate size controllability; the stable melt flow of PEBAX material makes it have excellent processing performance, which can realize smooth transition from the soft section to the hard section of the catheter, meeting the requirements of different segment hardness and elasticity of the contrast catheter.

[0065] The inner layer of the transition section is made of polytetrafluoroethylene (PTFE), nylon 12 or block polyether amide elastomer (PEBAX) material; the block polyether amide elastomer is preferably at least one of PEBAX MV 1074 SA 01, PEBAX 4033 SA 01, PEBAX 3533 SA 01;

[0066] The outer layer of the transition section is made of at least one of block polyether amide elastomer (PEBAX), nylon, thermoplastic polyurethane, polyimide, styrene-based thermoplastic elastomer, acrylonitrile-butadiene-styrene terpolymer, thermoplastic silicone elastomer; the block polyether amide elastomer is preferably at least one of PEBAX 4533 SA 01, PEBAX MV 1074 SA 01, PEBAX 4033 SA 01, PEBAX 3533 SA 01; the nylon is preferably nylon 12;

[0067] The intermediate braided layer of the transition section is made of stainless steel material; preferably made of 10-30 stainless steel round wires or flat wires, with a braiding density (PPI) of 70-100 PPI; the stainless steel is medical-grade stainless steel, preferably SUS304 or SUS316 (medical grade); preferably stainless steel round wires, which provide a small surface area for support, giving the transition section excellent flexibility and elasticity.

[0068] In a preferred embodiment of the present application,

[0069] The outer layer of the tube body and the outer layer of the transition section are also doped with X-ray developing additives;

[0070] The X-ray developing additive is at least one of tungsten, Bi2O3, (BiO)2CO3, BaSO4;

[0071] The mass fraction of the X-ray developing additive in the total mass of the outer layer material of the tube body is 10%-30%;

[0072] The mass fraction of the X-ray developing additive in the total mass of the outer layer material of the transition section is 10%-30%;

[0073] The doping method is physical doping, first mixing the block polyether amide elastomer and other raw materials and X-ray developing additives and other doping materials according to the above proportions by a high-speed disperser, then melting and extruding granulation in a certain temperature range by an extruder, and then extruding or injection molding the granulated composite material to obtain the outer layer of the tube body or the outer layer of the transition section; the tungsten, Bi2O3, (BiO)2CO3, BaSO4 and other developing materials doped in the outer layer material during the processing process can absorb X-rays and play a developing role.

[0074] The second object of the present application is to provide an application of the contrast medium catheter with photo-controllable deformation in cardiovascular and cerebrovascular angiography.

[0075] Compared with the prior art, the present application has the following beneficial effects:

[0076] The present application prepares a contrast medium catheter with photo-controllable deformation, which comprises a catheter seat, a tube body, a transition section and a photo-controllable deformation head end. The photo-controllable deformation head end can produce macroscopic deformation under the irradiation of near-infrared light in vitro, so as to realize the change of the shape of the head end of the contrast medium catheter, deflect a certain angle, and then more accurately and quickly enter the correct blood vessel branch. Compared with thermal deformation and magnetic deformation, in thermal deformation, the heat accumulation in high-flow liquid is not reliable, and the excess heat can cause cell death and tissue damage. In magnetic deformation, the magnetic field can affect the normal operation of other implanted devices, and the working area is "field", which is difficult to realize accurate positioning. The present application is beneficial to photo-controllable deformation. Light is inherent in biological environment, and the stimulation produced is non-destructive. The working area is "point", which is convenient for accurate and dynamic control.

[0077] The segmented structure of the present application ensures that the tube body has a certain hardness, provides excellent propulsion performance, the transition section has a certain flexibility and elastic recovery ability, and does not appear to be bent when entering the corresponding blood vessel branch. The photo-controllable deformation head end has a certain flexibility, which avoids damaging the surrounding tissue during the propulsion process. The medical grade PEBAX material used in the present application has a low friction coefficient, which can reduce the damage to the human body during use. The stable melt flow of the PEBAX material has excellent processing performance, which can realize smooth transition from the soft section to the hard section of the catheter, meet the requirements of different segment hardness and elasticity of the contrast medium catheter, and provide good support and torque control performance. The inner layer preferably uses PTFE material, which meets the requirements of high temperature resistance, corrosion resistance, low friction coefficient, non-adhesion, non-toxicity and the like.

[0078] The present application overcomes the problem that the doctor manually adjusts the position of the contrast medium catheter outside the body to make it enter the correct branch during the angiography operation, which takes a long time, or the catheter rubs against the blood vessel wall, which easily damages the surrounding tissue. At the same time, the present application shortens the time of the doctor performing angiography with the aid of medical imaging equipment, which is beneficial to the protection of the health of the doctor. BRIEF DESCRIPTION OF DRAWINGS

[0079] Figure 1 It is a structural schematic diagram of the contrast medium catheter with photo-controllable deformation.

[0080] 1 catheter seat, 2 tube body, 3 transition section, 4 photo-controllable deformation head end.

[0081] Figure 2 It is an A-A' tube body cross-sectional schematic diagram.

[0082] 5 outer layer of the tube body, 6 intermediate braided layer of the tube body, 7 inner layer of the tube body;

[0083] Figure 3 schematic cross section of the transition layer B-B' Figure 1 ;

[0084] 8 outer layer of the transition section, 9 inner layer of the transition section;

[0085] Figure 4 schematic cross section of the transition layer B-B' Figure 2 ;

[0086] 10 outer layer of the transition section, 11 intermediate braided layer of the transition section, 12 inner layer of the transition section. DETAILED DESCRIPTION

[0087] The following specific description of the application is made in conjunction with the specific drawings and examples. It is necessary to point out that the following examples are only used to further illustrate the application and cannot be understood as limiting the scope of protection of the application. Some non-essential improvements and adjustments of the application made by those skilled in the art based on the content of the application still fall within the scope of protection of the application.

[0088] The raw materials used in the examples are all conventional commercially available raw materials;

[0089] 6-(4-((4-propoxyphenyl)diazenyl)phenoxy)hexyl methacrylate is purchased from SYNTHON Chemicals GmbH & Co. KG;

[0090] 6-(4-(1-cyano-2-phenylvinyl)phenoxy)hexyl acrylate is purchased from Shanghai Naifu Biological Technology Co., Ltd.;

[0091] 2-(ethyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)ethyl acrylate, azobis isobutyronitrile, dibenzoyl peroxide, anhydrous tetrahydrofuran, anhydrous ethanol, anhydrous methanol are purchased from Sigma-Aldrich;

[0092] The manufacturers of the rare earth doped fluoride materials NaYF4:Yb / Tm and NaYF4:Yb / Er are Xi'an Ruiyi Biological Technology Co., Ltd.;

[0093] Nanometer Fe3O4 particles are purchased from Shanghai Chaowei Nanometer Technology Co., Ltd.;

[0094] Indocyanine green is purchased from Kangdis Chemical Co., Ltd.;

[0095] The manufacturers of PEBAX4533, PEBAX5533, PEBAX4033, PEBAX3533 and nylon 12 are Arkema, France;

[0096] The manufacturer of the TPU is BASF, Germany.

[0097] Test method:

[0098] The light irradiation deformation ability of the head end of the contrast medium catheter with photo-controllable deformation: the test was carried out in a dry air environment at 25℃, and the time required for the photo-controllable deformation head end to deflect 20° under the irradiation of an 808nm near-infrared light source was tested; the deflection angle of the photo-controllable deformation head end under continuous irradiation for 1h was tested.

[0099] As shown in Figure 1 , the contrast medium catheter with photo-controllable deformation of the application comprises a catheter seat 1, a tube body 2, a transition section 3 and a photo-controllable deformation head end 4, one end of the tube body 2 is connected to the catheter seat 1, the tube body lumen is sealingly connected to the spherical lumen of the catheter seat, the other end is connected to the transition section 3, and the other end of the transition section 3 is connected to the photo-controllable deformation head end 4;

[0100] As shown in Figure 2 , the tube body 2 comprises a tube body outer layer 5, a tube body intermediate braided layer 6 and a tube body inner layer 7;

[0101] As shown in Figure 3 , it is a structure of the transition section 3, comprising a transition section outer layer 8 and a transition section inner layer 9;

[0102] As shown in Figure 4 , it is another structure of the transition section 3, comprising a transition section outer layer 10, a transition section intermediate braided layer 11 and a transition section inner layer 12.

[0103] Example 1

[0104] Poly(2-(ethyl(4-((4-nitrophenyl)diazene)phenyl)amino)acrylate) was obtained by free radical polymerization;

[0105] Preparation method:

[0106] In a 250mL beaker, 2-(ethyl(4-((4-nitrophenyl)diazene)phenyl)amino)acrylate (10g) and initiator benzoyl peroxide (BPO) (20mg) were vacuum dried for 1h, 100mL of anhydrous tetrahydrofuran (THF) was added under argon protection, then the reaction system was purged with high-purity nitrogen for 20min to remove oxygen, and sealed. Finally, the reaction system was heated to 60℃ under vacuum and sealed conditions for 24 hours. After the reaction was completed, the reaction liquid was precipitated with anhydrous ethanol to obtain a solid, which was dried to obtain the target product.

[0107]

[0108] The contrast catheter with photo-controllable deformation comprises a catheter seat, a tube body, a transition section and a photo-controllable deformation head; one end of the tube body is connected to the catheter seat, the inner cavity of the tube body is in sealed communication with the inner cavity of the catheter seat, the other end of the tube body is connected to the transition section, and the other end of the transition section is connected to the photo-controllable deformation head; the photo-controllable deformation head is prepared by injection molding after mixing poly(2-(ethyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)ethyl acrylate) and NaYF4:Yb / Tm in a mass ratio of 1:0.05.

[0109] The catheter seat is a hollow structure with front and rear openings, and has two pages perpendicular to the outer surface of the catheter seat on the side surface; the catheter seat is prepared by injection molding using acrylonitrile-butadiene-styrene terpolymer material; the tube body comprises a tube body inner layer, a tube body intermediate braided layer and a tube body outer layer; the tube body inner layer is made of polytetrafluoroethylene material; the tube body intermediate braided layer is made of 16 316 stainless steel flat wires with a braiding density of 60PPI; the tube body outer layer is made of PEBAX 5533 SA 01 and Bi2O3, and the mass fraction of Bi2O3 in PEBAX 5533 SA 01 and Bi2O3 is 20%; the tube body is prepared by extrusion and braiding process, that is, an inner tube is first extruded by an extruder, then the stainless steel wires are cross-braided on the outer surface of the inner tube by a braiding machine, and then an outer tube is extruded by another extruder;

[0110] The transition section comprises a transition section inner layer and a transition section outer layer; the transition section inner layer is made of polytetrafluoroethylene; the transition section outer layer is made of PEBAX MV 1074 SA 01 and Bi2O3, and the mass fraction of Bi2O3 in PEBAX MV 1074 SA 01 and Bi2O3 is 20%; the transition section inner and outer layers are prepared by extrusion process;

[0111] The hardness of the tube body, the transition section and the photo-controllable deformation head decreases in turn; the hardness of the tube body outer layer is 50D, the hardness of the transition section outer layer is 40D, and the hardness of the photo-controllable deformation head is 5D.

[0112] The tube body is welded to the catheter seat; the tube body, the transition section and the photo-controllable deformation head are welded.

[0113] The test environment is a dry air environment at 25℃, under the irradiation of a near-infrared light source with a wavelength of 808nm, the photo-controllable deformation head bends towards the light source side, a deflection of 20° occurs in 17 minutes, and the maximum deflection angle is 55° under continuous irradiation for 1h.

[0114] Example 2

[0115] Poly(6-(4-((4-propoxyphenyl)diazenyl)phenoxy)methyl hexyl methacrylate) is obtained by free radical polymerization;

[0116] Preparation method:

[0117] In a 250 mL round bottom flask, monomer 6-(4-((4-propoxyphenyl)diazene) phenoxy) methyl hexyl acrylate (10 g) and initiator azobisisobutyronitrile (AIBN) (20 mg) were vacuum dried for 1 h, 100 mL of anhydrous tetrahydrofuran (THF) was added under argon protection, and then the reaction system was purged with high-purity nitrogen for 20 min to remove oxygen and sealed. Finally, the reaction system was heated to 60°C under vacuum and sealed conditions for 24 hours. After the reaction was completed, the reaction liquid was precipitated with anhydrous ethanol to obtain a solid, which was dried to obtain the target product

[0118]

[0119] The difference between Example 2 and Example 1 is that the light-induced controllable deformation head is made by mixing poly-6-(4-((4-propoxyphenyl)diazene) phenoxy) methyl hexyl acrylate and NaYF4:Yb / Er in a mass ratio of 1:1 and then extruding and molding; the inner layer of the tube body is made of nylon 12 material; the middle braided layer of the tube body is made of 30 304 stainless steel flat wires, and the braided density is 50 PPI; the outer layer of the tube body is made of nylon 12 and (BiO)2CO3; the mass fraction of (BiO)2CO3 in nylon 12 and (BiO)2CO3 is 30%; the inner layer of the transition section is made of nylon 12, and the outer layer of the transition section is made of PEBAX4033 and BaSO4, and the mass fraction of BaSO4 in PEBAX4033 and BaSO4 is 30%; the hardness of the outer layer of the tube body is 70D, the hardness of the outer layer of the transition section is 35D, and the hardness of the light-induced controllable deformation head is 25D; the tube body is bonded to the catheter seat;

[0120] In addition to the above differences, the other structures of Example 2 are the same as those of Example 1.

[0121] In an in-vitro dry air environment at 25°C, under the irradiation of a near-infrared light source with a wavelength of 808 nm, it was found that the light-induced controllable deformation head bends towards the light source side, deflects by 20° in 5 minutes, and the maximum deflection angle is 36° when continuously irradiated for 1 h.

[0122] Example 3

[0123] Poly-6-(4-(1-cyano-2-phenylvinyl)phenoxy) hexyl acrylate is obtained by free radical polymerization;

[0124] Preparation method:

[0125] In a 250 mL round-bottom flask, monomer 6-(4-(1-cyano-2-phenylvinyl)phenoxy)hexyl acrylate (10 g) and thermal initiator dibenzoyl peroxide (BPO) (20 mg) were vacuum-dried for 1 h, 100 mL of anhydrous tetrahydrofuran (THF) was added under argon protection, and then the reaction system was purged with high-purity nitrogen for 20 min to remove oxygen and sealed. Finally, the reaction system was heated to 80°C under vacuum and sealed conditions for 24 h. After the reaction was completed, the reaction solution was precipitated with anhydrous methanol to obtain a solid, which was dried to obtain the target product.

[0126]

[0127] Example 3 differs from Example 1 in that the light-induced controllable deformation head is made by mixing poly-6-(4-(1-cyano-2-phenylvinyl)phenoxy)hexyl acrylate and NaYF4:Yb / Tm at a mass ratio of 1:0.5, and then using a 3D printing process, the tube body braiding layer is made of 10 304 stainless steel flat wires, and the braiding density is 70 PPI; the tube body outer layer is made of PEBAX MV 1074 SA 01 and Bi2O3, the mass fraction of Bi2O3 in PEBAX MV 1074 SA 01 and Bi2O3 is 10%, the transition section outer layer is made of PEBAX 4033 SA 01 and Bi2O3, the mass fraction of Bi2O3 in PEBAX 4033 SA 01 and Bi2O3 is 10%; the catheter seat and the tube body are connected by injection molding; the hardness of the tube body outer layer is 40D, the hardness of the transition section outer layer is 35D, and the hardness of the light-induced controllable deformation head is 15D;

[0128] In addition to the above differences, the other structures of Example 3 are the same as those of Example 1.

[0129] In a dry air environment at 25°C in vitro, under the irradiation of a near-infrared light source with a wavelength of 808 nm, it was found that the light-induced controllable deformation head bent towards the light source side, and a 20° deflection occurred in 8 minutes. Continuous irradiation for 1 h resulted in a maximum deflection angle of 48°.

[0130] Example 4

[0131] Example 4 differs from Example 1 in that the near-infrared light conversion material uses nano-Fe3O4 particles, and the transition section adopts a three-layer structure, i.e., an inner layer, an intermediate braiding layer, and an outer layer; the intermediate braiding layer of the transition section uses 16 304 stainless steel flat wires, and the braiding density is 100 PPI; the outer layer uses PEBAX 3533 SA 01, and the hardness of the transition section outer layer is 25D.

[0132] In addition to the above differences, the other structures of Example 4 are the same as those of Example 1.

[0133] The test environment is a dry air environment at 25°C, under the irradiation of a near-infrared light source with a wavelength of 808 nm, the head end of the light-induced controllable deformation bends towards the light source side, and a 20° deflection occurs in 21 minutes. The continuous irradiation lasts for 1 h, and the maximum deflection angle is 51°.

[0134] Example 5

[0135] The difference between Example 5 and Example 1 is that the near-infrared light conversion material uses indocyanine green, and the transition section adopts a three-layer structure, i.e., an inner layer, a middle woven layer, and an outer layer. The inner layer uses nylon 12. The middle woven layer of the transition section uses 16 316 stainless steel flat wires with a weaving density of 70 PPI. The outer layer uses TPU, and the hardness of the outer layer of the transition section is 40D.

[0136] In addition to the above differences, the other structures of Example 5 are the same as those of Example 1.

[0137] In a dry air environment at 25°C in vitro, under the irradiation of a near-infrared light source with a wavelength of 808 nm, it is found that the head end of the light-induced controllable deformation bends towards the light source side, and a 20° deflection occurs in 25 minutes. The continuous irradiation lasts for 1 h, and the maximum deflection angle is 49°.

[0138] Comparative Example 1

[0139] Chinese invention patent CN108295357A, the invention name is "contrast catheter".

[0140] Comparative Example 1 sets a traction line on the inner cavity of the contrast catheter on both sides, one end is connected with the middle part, and the other end extends from the tail part. When the first traction line is pulled, the middle part drives the head to bend to one side. When the second traction line is pulled, the middle part drives the head to bend to the other side. By tightening and loosening the traction line, the movement of the head end of the catheter is controlled to reach the lesion site.

[0141] Comparative Example 2

[0142] Chinese utility model patent CN202554709U, the utility model name is "a new vascular catheter".

[0143] Comparative Example 2 sets a hole cavity on the side wall of the contrast catheter, which extends along the side wall. The traction line is placed therebetween. The head end of the contrast catheter is inclined to one side of the hole cavity. The top end of the traction line is connected with the head end of the contrast catheter which is inclined to one side of the hole cavity. A knob is connected to the side wall of the tail part of the contrast catheter. The end of the traction line is connected with the knob through the hole cavity.

[0144] In the prior art, in order to solve the problem that the contrast catheter enters the blood vessel more quickly and accurately, the end of the contrast catheter is controlled by setting a traction line, such as Comparative Examples 1-2, and this method of using a traction line has many defects. First, the traction line is difficult to have a large effect in a small-caliber blood vessel cavity. Second, there are too many components, such as traction lines and knobs, which are difficult to use in a small-caliber blood vessel cavity; moreover, the more components there are, the more complex the operation is, and it is difficult to apply to angiography surgery.

[0145] The mechanical principle of setting a traction line to pull in Comparative Examples 1-2 is completely different from that of Examples 1-5, which use a light-induced controllable deformation head based on a chemical mechanism, and the operation is simpler and more sensitive.

[0146] The deformation ability of the light-induced controllable deformation head of Examples 1-5 under irradiation of far-infrared light and the maximum deflection angle under continuous irradiation for 1 h were tested. The light-induced controllable deformation head of Examples 1-5 can produce macroscopic deformation under irradiation of near-infrared light with a wavelength of 808 nm. The time required for a deflection of 20° is 5-25 minutes, and the maximum deflection angle is 36-55° under continuous irradiation for 1 h. At present, in the actual operation process of angiography surgery, a contrast guide wire is needed to pull a contrast catheter to a blood vessel branch, and then the position of the guide wire and the catheter is manually adjusted to enter the correct branch. In fact, as long as the catheter head is deflected by a small angle at the blood vessel branch, it is very beneficial to the realization of the whole process, but the control difficulty of the guide wire pulling is very large, and Examples 1-5 can be deflected by a large angle under irradiation of near-infrared light for a short time, which can enter the corresponding blood vessel branch by controlling the irradiation time to deflect different angles, greatly reducing the difficulty of the doctor in adjusting the angle of the end in vitro, and shortening the time of the surgery.

[0147] The segmented structure of Examples 1-5 ensures that the catheter body has a certain hardness, provides excellent propulsion performance, the transition section has a certain flexibility and elastic recovery ability, and does not appear to be bent when entering the corresponding blood vessel branch, and the soft head section has a certain flexibility to avoid damage to the surrounding tissue during the propulsion process; the medical-grade PEBAX material used in the application has a low friction coefficient, which can reduce the damage to the human body during use; the stable melt flow of the PEBAX material makes it have excellent processing performance, which can realize smooth transition from the soft section to the hard section of the catheter, meet the requirements of different segment hardness and elasticity of the contrast catheter, and the stainless steel woven net used in the braided layer can provide good support and torque control performance; the inner layer is preferably made of PTFE material, which meets the requirements of high temperature resistance, corrosion resistance, low friction coefficient, non-stick, and non-toxicity.

[0148] Embodiments 1-5 overcome the problem that when performing an angiography operation, a doctor needs to spend a long time to adjust the position of a contrast catheter to make it enter a correct branch, or the catheter is rubbed against a blood vessel wall, which is easy to damage surrounding tissues, and meanwhile, the doctor does not need to perform angiography with the aid of a medical imaging device, which is beneficial to the health protection of the doctor, and is a contrast catheter which can simply, quickly and accurately control the direction of a head end and has excellent performance.

Claims

1.A contrast catheter with light-induced controllable deformation, characterized in that: the contrast catheter with light-induced controllable deformation comprises a catheter seat, a tube body, a transition section and a light-induced controllable deformation head; one end of the tube body is connected to the catheter seat, the inner cavity of the tube body is in communication with the inner cavity of the catheter seat, the other end of the tube body is connected to the transition section, and the other end of the transition section is connected to the light-induced controllable deformation head; the light-induced controllable deformation head is prepared from raw materials comprising a light-responsive polymer material and a near-infrared light conversion material; the main chain of the light-responsive polymer material is at least one of polyacrylate, polyimide, polyurethane and polysiloxane, and the side chain is at least one of azobenzene and its derivatives, stilbene and its derivatives, spiropyran and its derivatives, and fulgide and its derivatives; the near-infrared light conversion material is at least one of an up-conversion luminescent material, an inorganic light-heat conversion material and an organic light-heat conversion material; the mass ratio of the light-responsive polymer material to the near-infrared light conversion material is 1: (0.01-100) ; the catheter seat is a hollow structure, has a catheter seat inlet and a catheter seat outlet, the catheter seat inlet is in communication with the outside, and the tube body and the catheter seat are in communication through the catheter seat outlet; the tube body comprises a tube body inner layer, a tube body intermediate braided layer and a tube body outer layer; the transition section comprises a transition section inner layer and a transition section outer layer; the hardness of the tube body, the transition section and the light-induced controllable deformation head decreases in turn. 2.The contrast catheter with light-induced controllable deformation according to claim 1, characterized in that: the light-responsive polymer material is at least one of poly (2- (ethyl (4- ( (4-nitrophenyl) diazenyl) phenyl) amino) acrylate), poly (6- (4- ( (4-propoxyphenyl) diazenyl) phenoxy) methyl hexyl acrylate) and poly (6- (4- (1-cyano-2-phenylvinyl) phenoxy) hexyl acrylate) ; and / or, the up-conversion luminescent material is at least one of a rare earth luminescent crystalline material and a rare earth luminescent amorphous material; and / or, the inorganic light-heat conversion material is at least one of carbon nanotubes, graphene and metal nanomaterials; and / or, the organic light-heat conversion material is at least one of a conjugated polymer and a near-infrared dye. 3.The contrast catheter with light-induced controllable deformation according to claim 2, characterized in that: the rare earth luminescent crystalline material is one of a single crystal and a nanocrystalline powder; the single crystal is one of YVO4, YAG and BaY2F8; the nanocrystalline powder is one of a rare earth doped fluoride, oxide and phosphate; the rare earth doped fluoride is at least one of NaYF4: Yb / Tm and NaYF4: Yb / Er; and / or, the rare earth luminescent amorphous material is at least one of a ceramic and a glass; and / or, the metal nanomaterial is at least one of CuS and Fe3O4 nanomaterials; and / or, the conjugated polymer is at least one of polythiophene and polydopamine; and / or, the near-infrared dye is indocyanine green. 4.The contrast catheter with light-induced controllable deformation according to claim 1, characterized in that: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The mass ratio of the photoresponsive polymer material and the near-infrared light conversion material is 1:(0.05-1). 5.The contrast agent catheter with photo-controllable deformation according to claim 1, wherein: the opposite sides of the catheter hub are provided with two flaps perpendicular to the outer surface of the catheter hub; and / or, the transition section further comprises a middle braided layer of the transition section; and / or, the Shore hardness of the outer layer of the tube body is 40-70D; and / or, the Shore hardness of the outer layer of the transition section is 25-40D; and / or, the Shore hardness of the head end of the photo-controllable deformation is 5-25D. 6.The contrast agent catheter with photo-controllable deformation according to claim 5, wherein: the catheter hub is made by injection molding; and / or, the tube body is made by extrusion and braiding process; and / or, the inner and outer layers of the transition section are made by extrusion process; and / or, the middle braided layer of the transition section is made by braiding process; and / or, the head end of the photo-controllable deformation is made by injection molding, extrusion molding or 3D printing process; and / or, the tube body and the catheter hub are connected by adhesion, injection molding or welding; and / or, the tube body, the transition section and the head end of the photo-controllable deformation are welded. 7.The contrast agent catheter with photo-controllable deformation according to claim 5, wherein: the catheter hub is made of acrylonitrile-butadiene-styrene or nylon 12; and / or, the inner layer of the tube body is made of polytetrafluoroethylene, nylon 12 or block polyether amide elastomer material; and / or, the middle braided layer of the tube body is made of stainless steel material; and / or, the outer layer of the tube body is made of at least one of block polyether amide elastomer, nylon, thermoplastic polyurethane, polyimide, styrene-based thermoplastic elastomer, acrylonitrile-butadiene-styrene and thermoplastic silicone elastomer; and / or, the inner layer of the transition section is made of polytetrafluoroethylene, nylon 12 or block polyether amide elastomer material; and / or, the middle braided layer of the transition section is made of stainless steel material; and / or, the outer layer of the transition section is made of at least one of block polyether amide elastomer, nylon, thermoplastic polyurethane, polyimide, styrene-based thermoplastic elastomer, acrylonitrile-butadiene-styrene and thermoplastic silicone elastomer. 8.The contrast agent catheter with photo-controllable deformation according to claim 7, wherein: the middle braided layer of the tube body is made of 10-30 stainless steel round wires or flat wires with a braiding density of 50-70PPI; the stainless steel is SUS304 or SUS316; and / or, the middle braided layer of the transition section is made of 10-30 stainless steel round wires or flat wires with a braiding density of 70-100PPI; the stainless steel is SUS304 or SUS316. 9.The contrast agent catheter with photo-controllable deformation according to claim 7 or 8, wherein: the outer layer of the tube body and the outer layer of the transition section are further doped with X-ray developing additives; the X-ray developing additives are at least one of tungsten, Bi2O3, (BiO)2CO3 and BaSO4. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The mass fraction of the X-ray developing additive in the total mass of the outer layer material of the tube body is 10% to 30%; The mass fraction of the X-ray developing additive in the total mass of the outer layer material of the transition section is 10% to 30%.

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