Methods for synthesizing duct pumps, initiators, and anticoating coatings

Abstract

This invention provides a catheter pump, an initiator synthesis method, and an anticoagulant coating preparation method, relating to the field of medical device technology. The catheter pump provided by this invention includes a blood delivery mechanism, a delivery catheter, and a positioning component. The positioning component includes a positioning catheter, which is connected to the blood delivery mechanism via the delivery catheter. The blood delivery mechanism includes an impeller for pumping blood, and both the impeller and the positioning catheter are coated with an anticoagulant coating. The anticoagulant coating includes an inert layer and an active layer covering the outside of the inert layer. The inert layer isolates the outer surfaces of the impeller and the positioning catheter from the blood, while the active layer is used to acquire clotting factors. The catheter pump provided by this invention not only reduces the interaction between clotting factors in the blood and the device surface but also inhibits the activation pathway of clotting factors, preventing their amplification. The anticoagulant coating can be precisely applied to the wound site, requiring only a small amount of anticoagulant injection from the patient, effectively reducing harm to the patient.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a catheter pump, an initiator synthesis method, and an anticoagulant coating preparation method. Background Technology

[0002] Contact between blood and the surface of implanted devices can trigger the activation of clotting factors, leading to thrombus formation and complications. Common interventions for anticoagulation typically involve either reducing the interaction between clotting factors in the blood and the device surface, or modulating different stages of the coagulation reaction to inhibit the activation pathways of clotting factors and prevent their proliferation. However, using either of these methods alone is insufficient for effective anticoagulation, still requiring the injection of larger amounts of anticoagulants into the patient, which then travel through the systemic circulation to the injury site, causing significant damage and disruption to the patient's blood. Summary of the Invention

[0003] The purpose of this invention is to provide a catheter pump that not only reduces the interaction between coagulation factors in the blood and the instrument surface, but also inhibits the activation pathway of coagulation factors, preventing their amplification. The anticoagulant coating can be precisely applied to the wound site, requiring only a small amount of anticoagulant to be injected, effectively reducing harm to the patient. Additionally, this invention provides a method for synthesizing the initiator used in the aforementioned catheter pump, and a method for preparing the anticoagulant coating for the aforementioned catheter pump.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] In a first aspect, the present invention provides a catheter pump, including a blood delivery mechanism, a delivery catheter and a positioning component. The positioning component includes a positioning catheter, which is connected to the blood delivery mechanism via the delivery catheter. The blood delivery mechanism includes an impeller for pumping blood, and both the impeller and the positioning catheter are coated with an anticoagulant coating.

[0006] The anticoagulant coating includes an inert layer and an active layer covering the outside of the inert layer. The inert layer is used to isolate the outer surfaces of the impeller and the positioning catheter from the blood, respectively, while the active layer is used to obtain clotting factors.

[0007] Furthermore, the material of the inert layer includes amphiphilic acrylic monomers.

[0008] Furthermore, the amphiphilic acrylic monomer includes an ion-substituted amphiphilic (meth)acrylic monomer, wherein the ion-substituted substituent group includes at least one of carboxyl, sulfonyl, and phosphate betaine.

[0009] Furthermore, the materials of the inert layer include N-(2-hydroxypropyl)methacrylamide and carboxybetaine methacrylamide.

[0010] Furthermore, the active layer is grafted with anti-FXⅡa factor.

[0011] Furthermore, an initiator is present between the inert layer and the impeller, and between the inert layer and the positioning guide tube. The inert layer is fixed to the surface of the impeller and the positioning guide tube by grafting the initiator with the polymer.

[0012] Furthermore, the raw materials for the initiator include N-vinylformamide and N-vinylacetamide.

[0013] Furthermore, the blood delivery mechanism includes a pump housing, an impeller concealed within the pump housing, and a liquid outlet disposed around the output end of the impeller.

[0014] Secondly, the present invention also provides an initiator synthesis method for synthesizing the initiator in the above-described conduit pump, using N-vinylformamide and N-vinylacetamide as raw materials, prepared in isopropanol, comprising:

[0015] In hydrochloric acid aqueous solution, the formamide groups partially hydrolyze to produce water-soluble hydrophilic polymers;

[0016] The polymer backbone reacts with N-succinimide-4-azidotetrafluorobenzoate and 2-bromoisobutyric acid N-hydroxysuccinimide ester, using amine groups to introduce surface anchoring groups and initiators.

[0017] Thirdly, the present invention also provides a method for preparing an anti-coating coating for a conduit pump of the above-mentioned scheme, comprising:

[0018] Inert layer coating step: An initiator is coated on the surface of the conduit pump. During this process, nitrile free radicals are generated by ultraviolet irradiation. The nitrile free radicals insert into the C-H of the conduit pump surface. The initiator crosslinks with the material surface. Then, the inert layer polymers N-(2-hydroxypropyl)methacrylamide and carboxybetaine methacrylamide are grafted onto the initiator. Free radical polymerization occurs during the grafting process.

[0019] Active layer coating step: The anti-FXIIa factor is grafted onto the inert layer using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide react with the carboxyl groups of the carboxybetaine comonomer in the inert layer to form an active ester. The active ester portion serves as the catalytic site for the anti-FXIIa factor, thus immobilizing the anti-FXIIa factor there.

[0020] The conduit pump, initiator synthesis method, and anticoating coating preparation method provided by this invention can produce the following beneficial effects:

[0021] In the catheter pump provided by the present invention, both the impeller and the positioning catheter are coated with an anticoagulant coating. The anticoagulant coating includes an inert layer for isolating the outer surfaces of the impeller and the positioning catheter from the blood, and an active layer covering the outside of the inert layer for obtaining coagulation factors.

[0022] Compared to existing technologies, the inert layer in the anticoagulant coating of the catheter pump provided by the first aspect of this invention has an anti-contamination function, making the surface of the medical device invisible to blood and less prone to thrombosis. The active layer in the anticoagulant coating can immediately acquire clotting factors, thereby inhibiting the amplification reaction and diffusion of clotting factors. This not only reduces the interaction between clotting factors in the blood and the device surface, but also inhibits the activation pathway of clotting factors, preventing their amplification. Furthermore, because the catheter pump has anticoagulant coatings on both the impeller surface and the positioning catheter surface, thrombus formation on and near the impeller surface can be avoided. Simultaneously, it can precisely target the wound site, requiring only a small amount of anticoagulant to be injected, effectively reducing harm to the patient.

[0023] Compared with the prior art, the initiator synthesis method provided by the second aspect of the present invention can effectively prepare an initiator, which can be grafted with a polymer to effectively fix the inert layer on the surface of the instrument.

[0024] Compared with the prior art, the grafting of the inert layer in the anticoagulant coating preparation method provided by the third aspect of the present invention can effectively reduce the interfacial tension with water, and the contact angle after grafting is reduced, so that the surface of the instrument after grafting has better hydrophilicity than the surface of the instrument before grafting, minimizing the interfacial energy with water, preventing and inhibiting the adsorption and replication of proteins, and having a better anticoagulant effect. Attached Figure Description

[0025] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0026] Figure 1 This is a three-dimensional structural schematic diagram of a duct pump provided in an embodiment of the present invention;

[0027] Figure 2 A three-dimensional structural schematic diagram of a positioning component provided in an embodiment of the present invention;

[0028] Figure 3 A three-dimensional structural schematic diagram of a motor assembly provided in an embodiment of the present invention;

[0029] Figure 4This is a partially enlarged structural diagram of an impeller and motor in operation, provided by an embodiment of the present invention.

[0030] Figure 5 A schematic diagram of the molecular formula of an initiator synthesis method provided in an embodiment of the present invention.

[0031] Icons: 1 - Blood delivery mechanism; 11 - Motor assembly; 111 - Impeller; 112 - Pump housing; 1121 - Outlet; 113 - Motor; 1131 - Inclined section; 12 - Composite sleeve assembly; 13 - Inlet tube; 2 - Delivery conduit; 3 - Positioning assembly; 31 - Positioning conduit; 32 - Positioning unit. Detailed Implementation

[0032] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0034] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0035] The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0036] A first aspect of the present invention provides a conduit pump, such as Figures 1 to 3As shown, the device includes a blood delivery mechanism 1, a delivery conduit 2, and a positioning component 3. The positioning component 3 includes a positioning conduit 31, which is connected to the blood delivery mechanism 1 via the delivery conduit 2. The blood delivery mechanism 1 includes an impeller 111 for pumping blood. Both the impeller 111 and the positioning conduit 31 are coated with an anticoagulant coating. The anticoagulant coating includes an inert layer and an active layer covering the outside of the inert layer. The inert layer is used to isolate the outer surfaces of the impeller 111 and the positioning conduit 31 from the blood, respectively, and the active layer is used to acquire clotting factors.

[0037] The duct pump provided in the above embodiment has an anti-condensation coating on the exterior of both the impeller 111 and the positioning duct 31, wherein:

[0038] The anticoagulant coating has anti-contamination function, making the surface of medical devices invisible to blood and less prone to thrombosis;

[0039] The active layer can immediately acquire coagulation factors, thereby inhibiting the amplification reaction of coagulation factors and the diffusion of coagulation factors.

[0040] Therefore, the anticoagulant coating provided in the above embodiments can not only reduce the interaction between coagulation factors in the blood and the surface of the catheter pump, but also inhibit the activation pathway of coagulation factors and prevent their amplification.

[0041] Furthermore, the anticoagulant coating on the exterior of impeller 111 prevents thrombus formation on and around its surface during operation. The anticoagulant coating on the exterior of the positioning catheter 31 allows for precise targeting of the wound site, requiring only a small amount of anticoagulant to be injected, effectively reducing harm to the patient.

[0042] Specifically, the thickness of the anti-condensation coating is 5-100 nm, preferably 20-50 nm. For example, the thickness of the anti-condensation coating is 20 nm, 25 nm, 30 nm, 40 nm or 50 nm.

[0043] In some embodiments, the material of the inert layer comprises an ion-substituted amphiphilic (meth)acrylic acid monomer with substituent groups such as carboxyl, sulfonyl, and phosphate betaine. Such polymers, when used as a coating, reduce protein adsorption and inhibit the activation of clotting factors.

[0044] In at least one embodiment, the inert layer is made of N-(2-hydroxypropyl)methacrylamide and carboxybetaine methacrylamide.

[0045] Among them, N-(2-hydroxypropyl)methacrylamide is hereinafter referred to as HPMA, and carboxybetaine methacrylamide is hereinafter referred to as CBMAA.

[0046] In some embodiments, the active layer includes an anti-FXIIa factor, which specifically captures and inactivates FXIIa by grafting the anti-FXIIa factor, thereby inhibiting its continued amplification reaction or coagulation diffusion during the amplification phase of the coagulation mechanism.

[0047] In some embodiments, an initiator is introduced between the inert layer and the impeller 111, and between the inert layer and the positioning conduit 31, and the inert layer is fixed to the surface of the impeller 111 and the positioning conduit 31 by grafting the initiator with the polymer.

[0048] Specifically, an initiator can be prepared in isopropanol using N-vinylformamide and N-vinylacetamide as raw materials.

[0049] N-vinylformamide is hereinafter referred to as NVF, and N-vinylacetamide is hereinafter referred to as VAM.

[0050] In some embodiments, such as Figure 1 As shown, the blood delivery mechanism 1 includes an inlet tube 13, a composite cannula assembly 12, and a motor assembly 11. The motor assembly 11 includes an impeller 111, a pump housing 112, and a motor 113. The pump housing 112 covers the outside of the impeller 111, and the impeller 111 is connected to the motor 113. Part of the inlet tube 13 and a portion of the composite cannula assembly 12 are implanted in the left ventricle, a portion of the composite cannula assembly 12 and the motor assembly 11 are implanted in the aorta, and a portion of the delivery catheter 2 and the positioning assembly 3 are implanted in the arterial blood vessel, with the remaining portion of the positioning assembly 3 outside the body.

[0051] After the motor assembly 11 of the duct pump is activated, the motor 113 rotates, driving the impeller 111 to rotate and draw blood. Blood flows in through the inlet tube 13 and flows out from the tail of the impeller 111, thus achieving the purpose of transferring blood from the left ventricle of the heart to the aorta.

[0052] In some embodiments, such as Figure 3 As shown, in order to reduce the damage of impeller 111 to blood cells, impeller 111 is hidden inside pump housing 112, and pump housing 112 has a liquid outlet 1121 arranged around the output end of impeller 111.

[0053] It should be noted that in the above embodiment, the outlet 1121 is arranged around the output end of the impeller 111, which can prevent most of the structure of the impeller 111 from being exposed in the blood vessel or even the impeller 111 from being completely exposed. The blood flow will not start from the starting part of the impeller 111 and spread to the surrounding area, effectively reducing the impact on the blood vessel and avoiding the loss of axial motion energy.

[0054] The advantages of the above embodiment are as follows: the pump housing 112 rectifies the rotating blood. After the blood enters the pump housing 112, it flows out at the tail (output end) of the impeller 111. The pump housing 112 restricts the radial movement of the blood, converting the blood's kinetic energy mainly into axial movement along the motor 113, reducing the impact of blood flow on blood vessels and energy loss. Thus, the motor 113 can complete the transfer of blood from the left ventricle to the aorta using a lower speed. The lower speed reduces contact with the blood, thus reducing damage to blood cells.

[0055] Among them, the impeller 111 can be injection molded from polymer materials such as PEEK, TPU, PC, POM, etc.

[0056] like Figure 4 As shown, in the motor 113, the end of the housing near the impeller 111 has an inclined portion 1131. The inclined portion 1131 is frustum-shaped, and its diameter gradually decreases as it approaches the impeller 111. The outlet 1121 on the pump housing 112 is positioned opposite to the inclined portion 1131. Guided by the inclined portion 1131, blood is discharged from the output end of the impeller 111 through the outlet 1121, reducing the radial kinetic energy of the blood.

[0057] In some embodiments, such as Figure 2 As shown, the positioning assembly includes a positioning catheter 31 and a positioning unit 32. The positioning catheter 31 passes through the delivery catheter 2, and its outer surface is coated with an anticoagulant coating. During surgery, the positioning catheter 31 is directly inserted into a blood vessel (femoral artery or subclavian artery) and comes into direct contact with the blood.

[0058] A second aspect of the present invention provides an initiator synthesis method, which is used to synthesize the initiator in the aforementioned conduit pump, such as... Figure 5 As shown, it includes:

[0059] In hydrochloric acid aqueous solution, the formamide groups partially hydrolyze to produce water-soluble hydrophilic polymers;

[0060] The polymer backbone reacts with N-succinimide-4-azidotetrafluorobenzoate (PFPA-NHS) and 2-bromoisobutyric acid N-hydroxysuccinimide ester (BIB-NHS) to introduce surface anchoring groups and initiators using amine groups.

[0061] The initiator synthesis method provided in the second aspect of the present invention can effectively prepare an initiator, which can be grafted with a polymer to effectively fix an inert layer on the surface of a device.

[0062] A third aspect of the present invention provides a method for preparing an anticoating coating, which is used in the aforementioned conduit pump and includes:

[0063] Inert layer coating steps: An initiator is coated on the surface of the conduit pump. During this process, nitrile free radicals are generated by ultraviolet irradiation. The nitrile free radicals insert into the C-H of the conduit pump surface. The initiator crosslinks with the material surface. Then, the inert layer polymers HPMA and CBMAA are grafted onto the initiator. Free radical polymerization occurs during the grafting process.

[0064] In the above steps, grafting the inert layer can effectively reduce the interfacial tension with water. As shown in Table 1 below, the contact angle after grafting is smaller, which indicates that the surface of the instrument after grafting has better hydrophilicity than the surface of the instrument before grafting, minimizing the interfacial energy with water and preventing and inhibiting the adsorption and replication of proteins.

[0065] Table 1 Contact Angle Data

[0066]

[0067] In some embodiments, the above-mentioned method for preparing an anti-condensation coating further includes:

[0068] Active layer coating step: The anti-FXIIa factor is grafted onto the inert layer using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide react with the carboxyl groups of the carboxybetaine comonomer in the inert layer to form an active ester. The active ester portion serves as the catalytic site for the anti-FXIIa factor, thus immobilizing the anti-FXIIa factor there.

[0069] Among them, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride is also known as EDC, and N-hydroxysuccinimide is also known as NHS.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A duct pump, characterized in that, The system includes a blood delivery mechanism (1), a delivery conduit (2), and a positioning component (3). The blood delivery mechanism (1) includes an impeller (111) and a pump housing (112) for pumping blood. The pump housing (112) covers the outside of the impeller (111). Both the impeller (111) and the pump housing (112) are located inside the aorta. The impeller (111) rotates to draw blood from the left ventricle. The blood flows through the pump housing (112) and is rectified by the pump housing (112) before moving axially toward the aorta. The positioning component (3) includes a positioning conduit (31), which is connected to the blood delivery mechanism (1) via a delivery conduit (2), and the delivery conduit (2) passes through the interior of the positioning conduit (31). Both the impeller (111) and the positioning guide tube (31) are coated with an anticoagulant coating; The anticoagulant coating includes an inert layer and an active layer covering the outside of the inert layer. The inert layer is used to isolate the outer surfaces of the impeller (111) and the positioning conduit (31) from the blood, respectively, and the active layer is used to acquire clotting factors. The material of the inert layer includes amphiphilic acrylic monomers; The active layer is grafted with anti-FXⅡa factor; An initiator is present between the inert layer and the impeller (111) and between the inert layer and the positioning conduit (31), and the inert layer is fixed to the surface of the impeller (111) and the positioning conduit (31) by grafting the initiator with the polymer.

2. The duct pump according to claim 1, characterized in that, The amphiphilic acrylic monomer includes an ion-substituted amphiphilic (meth)acrylic monomer, wherein the ion-substituted substituent group includes at least one of carboxyl, sulfonyl, and phosphate betaine.

3. The duct pump according to claim 1, characterized in that, The materials of the inert layer include N-(2-hydroxypropyl)methacrylamide and carboxybetaine methacrylamide.

4. The duct pump according to claim 1, characterized in that, The initiator is made from N-vinylformamide and N-vinylacetamide.

5. The duct pump according to any one of claims 1-4, characterized in that, The impeller (111) is hidden inside the pump housing (112), which has an outlet (1121) disposed around the output end of the impeller (111).

6. A method for synthesizing an initiator, characterized in that, The initiator used to synthesize the initiator in the catheter pump as described in claim 1 or 4 is prepared in isopropanol using N-vinylformamide and N-vinylacetamide as raw materials, comprising: In hydrochloric acid aqueous solution, the formamide groups partially hydrolyze to produce water-soluble hydrophilic polymers; The polymer backbone reacts with N-succinimide-4-azidotetrafluorobenzoate and 2-bromoisobutyric acid N-hydroxysuccinimide ester, using amine groups to introduce surface anchoring groups and initiators.

7. A method for preparing an anti-condensation coating, characterized in that, For use with a conduit pump as described in any one of claims 1-5, comprising: Inert layer coating step: An initiator is coated on the surface of the conduit pump. During this process, nitrile free radicals are generated by ultraviolet irradiation. The nitrile free radicals are inserted into CH on the surface of the conduit pump. The initiator crosslinks with the material surface. Then, inert layer polymers N-(2-hydroxypropyl)methacrylamide and carboxybetaine methacrylamide are grafted onto the initiator. Free radical polymerization occurs during the grafting process. Active layer coating step: The anti-FXIIa factor is grafted onto the inert layer using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and the N-hydroxysuccinimide react with the carboxyl groups of the carboxybetaine comonomer in the inert layer to form an active ester. The active ester portion is the catalytic site of the anti-FXIIa factor, thus immobilizing the anti-FXIIa factor thereon.

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