CN110075365B

CN110075365B - Hydrogel thrombus removal stent entrapping hydrophilic drugs and preparation method thereof

Info

Publication number: CN110075365B
Application number: CN201910361799.XA
Authority: CN
Inventors: 朱悦琦; 程英升; 张一然; 相宜; 肖钧元; 崔文国
Original assignee: SHANGHAI INSTITUTE OF TRAUMATOLOGY AND ORTHOPEDICS; Shanghai Sixth Peoples Hospital
Current assignee: SHANGHAI INSTITUTE OF TRAUMATOLOGY AND ORTHOPEDICS; Shanghai Sixth Peoples Hospital
Priority date: 2019-04-30
Filing date: 2019-04-30
Publication date: 2022-02-01
Anticipated expiration: 2039-04-30
Also published as: CN110075365A

Abstract

The invention provides a hydrogel thrombus taking bracket for entrapping hydrophilic drugs and a preparation method thereof, and the hydrogel thrombus taking bracket comprises a thrombus taking bracket and a hydrogel layer coated on the surface of the thrombus taking bracket; the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion; the inner water phase of the W/O/W type nano-emulsion is a hydrophilic drug solution, the oil phase is an emulsifier, and the outer water phase comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate. On the premise of not influencing the flexibility and the expansion function of the metal stent, the hydrogel layer membrane can be quickly swelled after meeting blood, so that the quick release of internal medicines is accelerated, the released hydrophilic medicines can be efficiently absorbed through tissues, the utilization degree of local tissues is improved, and the clinical treatment purposes of inhibiting thrombosis and promoting thrombolysis are further realized.

Description

Hydrogel thrombus removal stent entrapping hydrophilic drugs and preparation method thereof

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a hydrogel thrombus removal stent entrapping a hydrophilic drug and a preparation method thereof.

Background

With the continuous publication of five randomized clinical findings related to mechanical embolectomy for the treatment of acute ischemic stroke since 2015, stent embolectomy technology has been recommended by guidelines as the first line of clinical treatment for the opening of intracranial large vessel occlusion. Compared with the pure venous thrombolysis, the stent thrombolysis can realize the quick recanalization of the occluded great vessel, so that the stroke patient can obtain better prognosis without increasing the bleeding risk.

As an invasive surgical operation, a metal stent needs to have a certain radial supporting force in order to improve the thrombus removal efficiency, and the thrombus is cut, attached and clamped to be recovered. Therefore, the above-mentioned stent needs to be in an open state in the whole process of withdrawing the stent, and the stent wire can generate obvious scraping effect on the vascular wall. Earlier researches show that for stent embolectomy operation in a normal lumen, damage is mainly limited to an endothelial layer and an inner elastic plate, and a scanning electron microscope shows that endothelial cell focal spots are lost as a main characteristic; for stent embolectomy procedures within a narrow lumen, lesions can involve damage to the intima, media and even the entire wall (J Neurointerv Surg.2018; 10: 1085-. Once the intimal endothelial cells of blood vessels are widely damaged or the vessel wall is seriously damaged, so that the collagen fibers are excessively exposed, the extrinsic coagulation pathway is triggered to induce the formation of new thrombus.

Different from European and American people, the incidence rate of intracranial atherosclerosis lesion of Asian people can reach 33% -50%, and the stent has higher radial supporting force when passing through a narrow lumen in a compressed state in the thrombus taking process under the condition of existing lesion and even severe stenosis of a blood vessel, so that the blood vessel wall is easier to damage; likewise, the wire inevitably cuts the existing thrombus after stent release, causing the thrombus to tear. After being exposed to blood components, the collagen fibers of the vessel wall or the fiber components in the thrombus can be used as new coagulation promoting substances, and the new coagulation promoting substances can further spread to form a fresh thrombus on the basis of the existing thrombus; finally, metal stents, despite their good biocompatibility in the blood system, repeat the procedures of implantation and recovery in vivo, combined with the lengthy surgical time and the hemodynamic characteristics of local stasis of the lesion, are used as foreign bodies and inevitably present the potential risk of new thrombosis on the surface.

Therefore, the current intracranial large vessel occlusion lesion based on the treatment of stenosis by the embolectomy stent has the technical defects of high reocclusion rate and heavy vessel wall damage, and the reocclusion is mainly formed by secondary fresh thrombus.

Disclosure of Invention

The invention aims to provide a hydrogel thrombus removal stent entrapping a hydrophilic drug and a preparation method thereof.

The invention provides a hydrogel thrombus taking bracket for entrapping hydrophilic drugs, which comprises a thrombus taking bracket and a hydrogel layer coated on the surface of the thrombus taking bracket;

the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion;

the inner water phase of the W/O/W type nano-emulsion is a hydrophilic drug solution, the oil phase is soybean oil and an emulsifier, and the outer water phase comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate.

Preferably, the emulsifier is tween-80 and span-80;

the mass ratio of the tween-80 to the span-80 is (1-3): 1;

the mass ratio of the soybean oil to the emulsifier is 1: (1-5).

Preferably, the mass fraction of the methacrylated gelatin in the external water phase is 5-20%; the mass fraction of the photoinitiator is 0.5-2%; the mass fraction of the polyvinylpyrrolidone is 0.1-2%; the mass fraction of the sodium dodecyl sulfate is 0.1-1%.

Preferably, the mass concentration of the hydrophilic drug solution is (0.01-1) mug/muL.

Preferably, the mass ratio of the internal water phase to the oil phase is (0.05-0.2): (0.8-0.95);

the mass ratio of the total mass of the inner water phase and the oil phase to the outer water phase is (2-3): 1.

the invention provides a preparation method of a hydrogel thrombus removal bracket entrapping a hydrophilic drug, which comprises the following steps:

A) under the condition of stirring, dropwise adding the internal water phase into the oil phase solution to obtain W/O type nano colostrum; the inner water phase is hydrophilic medicine solution;

B) under the condition of stirring, dropwise adding the W/O type nano primary emulsion into the external water phase solution to obtain W/O/W type nano emulsion; the oil phase is an emulsifier, and the external water phase comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate;

C) soaking the thrombus taking support in the W/O/W type nano-emulsion, taking out the thrombus taking support, and performing crosslinking reaction under ultraviolet irradiation to obtain the hydrogel thrombus taking support entrapping the hydrophilic drugs.

Preferably, the thrombus removal support is subjected to abrasive flow polishing and/or carboxylation surface treatment before being soaked in the W/O/W type nanoemulsion.

Preferably, the soaking time in the step C) is 30-120 s.

Preferably, the wavelength of the ultraviolet light in the step C) is 365 nm;

the irradiation intensity of the ultraviolet light is 500-700 mW/cm²；

The irradiation time of the ultraviolet light is 100-200 s;

the spot diameter of the ultraviolet light is 1.2 cm.

Preferably, the ultraviolet light irradiation step further comprises drying;

the drying temperature is 35-40 ℃;

the drying time is 0.5-4 hours.

The invention provides a hydrogel thrombus taking bracket for entrapping hydrophilic drugs, which comprises a thrombus taking bracket and a hydrogel layer coated on the surface of the thrombus taking bracket; the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion; the inner water phase of the W/O/W type nano-emulsion is a hydrophilic drug solution, the oil phase is an emulsifier, and the outer water phase comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate. According to the invention, a hydrophilic drug-loaded methacrylated gelatin hydrogel (GelMA) solution is constructed, the viscosity is increased by adding PVP, the drugs are fixed in the hydrogel by utilizing the physical wrapping and combining of the GelMA hydrogel, the hydrogel is further uniformly stabilized on the surface of the metal stent, and a polymer film is formed after drying, so that the thrombus taking stent wrapping the drug-loaded hydrogel is formed. On the premise of not influencing the flexibility and the expansion function of the metal stent, the hydrogel layer membrane can be quickly swelled after meeting blood, so that the quick release of internal medicines is accelerated, the released hydrophilic medicines can be efficiently absorbed through tissues, the utilization degree of local tissues is improved, and the clinical treatment purposes of inhibiting thrombosis and promoting thrombolysis are further realized. Experimental results show that the swelling rate of the hydrogel layer can reach 212.50%, and after the hydrogel layer is conveyed and released for multiple times, the hydrogel layer is still uniformly attached to the surface of the thrombus removal support, so that the hydrogel layer has good adhesiveness.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is a graph showing the particle size distribution of W/O type nano-colostrum in example 1 of the present invention;

FIG. 2 is an SEM photograph of the hydrogel coating on the surface of the product in example 1 of the present invention;

FIG. 3 is a photograph of W/O/W type nano-emulsions in example 1 and comparative examples 1 to 2;

FIG. 4 is a graph showing the in vitro release rate of hydrogel coated stent in example 1 of the present invention;

FIG. 5 is a graph showing the behavior of hydrogel-coated stents of example 1 and comparative example 3 after release by multiple deliveries.

Detailed Description

the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion;

the inner water phase of the W/O/W type nano-emulsion is a hydrophilic drug solution, the oil phase is an emulsifier, and the outer water phase comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate.

In the present invention, the thrombectomy stent is a commonly used thrombectomy stent in the art, and the invention is not particularly limited thereto.

In the invention, the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion, the thickness of the hydrogel layer is preferably 20-100 μm, and a proper thickness can be selected within the range according to actual requirements.

In the present invention, the inner aqueous phase is a hydrophilic drug solution, and the hydrophilic drug is preferably a thrombolytic drug, and the type of the thrombolytic drug is not particularly limited, and a thrombolytic drug commonly used by those skilled in the art may be used, and specifically, Bovine Serum Albumin (BSA) or ADAMTS13 protein powder may be used in the present invention. The mass concentration of the hydrophilic drug in the internal water phase is preferably (0.01-0.1) mg/muL, more preferably (0.02-0.08) mg/muL, and most preferably (0.04-0.06) mg/muL.

In the present invention, the oil phase preferably comprises soybean oil and an emulsifier, the emulsifier is preferably span-80 and tween-80, and the mass ratio of the soybean oil to the emulsifier is preferably 1: (1-5), more preferably 1: (2-4), most preferably 1: 3; the mass ratio of the tween-80 to the span-80 is preferably (1-3): 1, more preferably 2: 1.

in the invention, the external water phase is a hydrogel solution, preferably comprises methacrylated gelatin (GelMA), a photoinitiator, polyvinylpyrrolidone and Sodium Dodecyl Sulfate (SDS), and the mass fraction of the methacrylated gelatin in the external water phase is preferably 5-20%, more preferably 10-15%; the mass fraction of the photoinitiator is 0.5-2%, and more preferably 1-1.5%; the mass fraction of the polyvinylpyrrolidone is 0.1-2%, and more preferably 1-1.5%; the mass fraction of the sodium dodecyl sulfate is 0.1-1%, and more preferably 0.5-0.6%.

The type of the photoinitiator is not particularly limited, and the photoinitiator commonly used in the art can be adopted, specifically, the photoinitiator of an Igracure 2959 type can be used in the invention, and the MA rate of the GelMA molecular chain is preferably 40-80%, and more preferably 50-60%.

In the present invention, the mass ratio of the internal aqueous phase to the oil phase is preferably (0.05 to 0.2): (0.8 to 0.95), more preferably 0.11: 0.89; the mass ratio of the sum of the masses of the internal aqueous phase and the oil phase to the external aqueous phase is preferably 1: (2-3), more preferably 1: 2.5.

The invention also provides a preparation method of the hydrogel thrombus removal bracket for entrapping the hydrophilic drug, which comprises the following steps:

The invention preferably prepares the inner water phase solution, the oil phase solution and the outer water phase solution respectively,

inner water phase solution: the hydrophilic drug is added into deionized water to prepare an inner water phase solution, and the hydrophilic drug is preferably hydrophilic thrombolytic drug, in particular Bovine Serum Albumin (BSA) or ADAMTS13 protein powder in the embodiment of the invention. The mass concentration of the hydrophilic drug in the internal water phase is preferably (0.01-0.1) mg/muL, more preferably (0.02-0.08) mg/muL, and most preferably (0.04-0.06) mg/muL;

oil phase solution: mixing an emulsifier with soybean oil to prepare an oil phase solution, wherein the emulsifier is preferably tween-80 and span-80, and the mass ratio of the soybean oil to the emulsifier is preferably 1: (1-5), more preferably 1: (2-4), most preferably 1: 3; the mass ratio of the tween-80 to the span-80 is preferably (1-3): 1, more preferably 2: 1.

external water phase solution: preparing methacrylated gelatin (GelMA), a photoinitiator, polyvinylpyrrolidone and Sodium Dodecyl Sulfate (SDS) into a solution by using deionized water, wherein the photoinitiator is preferably Igracure 2959; in the external water phase, the mass fraction of the methacrylated gelatin is preferably 5-20%, and more preferably 10-15%; the mass fraction of the photoinitiator is 0.5-2%, and more preferably 1-1.5%; the mass fraction of the polyvinylpyrrolidone is 0.1-2%, and more preferably 1-1.5%; the mass fraction of the sodium dodecyl sulfate is 0.1-1%, and more preferably 0.5-0.6%. The external aqueous phase solution needs to be protected from light during preparation, use and storage.

After the three solutions are prepared, the invention firstly takes the internal water phase solution, dropwise adds the oil phase solution into the internal water phase solution under the conditions of room temperature and magnetic stirring, forms transparent liquid crystal with a layered structure between two phases, continuously adds the oil phase solution dropwise, and balances for 2 hours under the conditions of room temperature and magnetic stirring after dropwise adding, thus obtaining the W/O type nano colostrum.

In the present invention, the mass ratio of the internal aqueous phase to the oil phase is preferably (0.05 to 0.2): (0.8 to 0.95), more preferably 0.11: 0.89; the magnetic stirring speed is preferably 50-200 rpm, more preferably 100-150 rpm, and the dripping speed of the oil phase solution is preferably 20-200 muL/min, more preferably 50-150 muL/min, and most preferably 100-120 muL/min.

After the W/O type nano colostrum is obtained, the W/O type nano colostrum is preferably dropwise added into the external water phase solution under the conditions of light shielding, room temperature and magnetic stirring, and the balance is carried out for 15-30 min, so that the W/O/W type nano emulsion is obtained.

In the invention, the ratio of the mass of the W/O type nano colostrum to the volume of the external water phase solution is preferably 1: (2-3), more preferably 1: 2.5; the speed of the magnetic stirring is preferably 600-800 rpm, and more preferably 700-750 rpm; the dripping speed of the external water phase solution is preferably 20-200 mu L/min, more preferably 50-150 mu L/min, and most preferably 100-120 mu L/min.

The W/O/W type nano-emulsion prepared by the invention is a nano-emulsion-hydrogel system coated with hydrophilic drugs.

After the W/O/W type nanoemulsion is obtained, the thrombus taking support is soaked in the W/O/W type nanoemulsion, and after the thrombus taking support is taken out, the hydrogel thrombus taking support carrying the hydrophilic drug is obtained through a crosslinking reaction under the condition of ultraviolet irradiation.

According to the invention, the surface treatment is preferably carried out on the embolectomy support to enhance the adhesiveness of the hydrogel on the surface of the metal support, the surface treatment of the embolectomy support can be abrasive flow polishing or surface carboxylation treatment, or the combination of the abrasive flow polishing and the surface carboxylation treatment, the abrasive flow polishing and the surface carboxylation treatment used in the invention are surface treatment technologies well known to those skilled in the art, and the detailed description of the invention is omitted.

In the invention, the thrombus removal stent is preferably soaked in the W/O/W type nanoemulsion and then slowly rotated for 360 degrees, so that the thrombus removal stent stays in the W/O/W type nanoemulsion for at least 30 seconds or more, the metal surface of the thrombus removal stent is fully contacted with the nanoemulsion, and the soaking time is preferably 30-120 seconds, and more preferably 60-80 seconds.

And after soaking, slowly taking out the soaked thrombus taking support, carrying out photocrosslinking reaction under the irradiation of ultraviolet light, and turning the thrombus taking support for 90 degrees every 30-50 seconds until the thrombus taking support is turned for 360 degrees, namely, finishing crosslinking.

In the present invention, the wavelength of the ultraviolet light is preferably 365 nm; the irradiation intensity of the ultraviolet light is preferably 500-700 mW/cm²More preferably 600W/cm²(ii) a The irradiation time of the ultraviolet light is preferably 100-200 s, and more preferably 120-160 s; during photocrosslinking, the spot diameter was kept at 1.2 cm.

In order to ensure that the hydrogel wrapping layer on the surface of the metal bracket reaches a certain thickness, the steps of soaking and photo-crosslinking can be repeated until the hydrogel layer reaches the required thickness.

After the hydrogel layer reaches the required thickness, the thrombus removal support is preferably dried in the invention, and the hydrogel film is tightly attached to the surface of the metal support.

In the invention, the drying is preferably drying, and the drying temperature is preferably 35-40 ℃, more preferably 36-37 ℃; the drying time is preferably 0.5 to 4 hours, and more preferably 1 to 2 hours.

In order to further illustrate the present invention, the following examples are provided to describe the hydrogel thrombectomy stent loaded with hydrophilic drugs and the preparation method thereof in detail, but the scope of the present invention should not be construed as being limited thereto.

Example 1

Stock solution for preparing each phase of W/O/W type nano-emulsion

Internal water phase: 20mg of ADAMTS13 protein powder was precisely weighed and made up into a solution with 890uL of deionized water (blank using deionized water as the internal aqueous phase).

Oil phase: 2.28g of span-80 and 4.55g of Tween-80 are precisely weighed and prepared into solution by using 2.28g of soybean oil.

External water phase: 100mg of GelMA, 10mg of Igracure 2959 and 6mg of SDS (deionized water solution of SDS was used as an external aqueous phase in the control group) were precisely weighed and prepared into a solution with 1000uL of deionized water. The external water phase needs to be protected from light during preparation, use and storage.

Preparing W/O type nano colostrum: taking 890 mu L of the drug-loaded internal water phase solution, dropwise adding the oil phase solution into the drug-loaded internal water phase solution under magnetic stirring (50rpm) at room temperature to form transparent liquid crystal with a laminated structure between two phases, continuously dropwise adding 0.11g of the oil phase solution under the condition, namely the total amount of W/O type colostrum is 10.0g, and balancing for 2h under the condition.

Preparing W/O/W type nano-emulsion: and (3) dropwise adding 0.40g W/O single emulsion into 1000 mu L of external water phase solution under the conditions of light protection, room temperature and magnetic stirring (600rpm), balancing for 15 minutes, and adding 10mg of polyvinylpyrrolidone (PVP) to obtain the ADAMTS 13-entrapped nanoemulsion-hydrogel system.

And (3) taking the pretreated metal bracket, soaking the metal bracket in W/O/W type nano-emulsion stock solution which is prepared in advance and stored in a dark place at room temperature in a dark place, slowly rotating the metal bracket for 360 degrees, and staying the metal bracket in the stock solution for 60 seconds to ensure that the stock solution can be fully contacted with the metal surface. Slowly taking out, standing for a period of time, draining off excessive stock solution on the stent, and then performing filtration at a wavelength of 365nm and 600mW/cm²(keeping the spot diameter at 1.2cm) ultraviolet light to induce a light crosslinking reaction, turning 90 degrees every 30 seconds of exposure until the rotation is 360 degrees, and completing crosslinking. Then the metal stent is placed in an oven at 37 ℃ to be dried for 1h, and the hydrogel-coated embolectomy stent is obtained.

The weight of the obtained embolectomy stent with the hydrogel coating is increased by only 1.6mg after drying (the weight of the metal stent is 12.5mg), the thickness of the coating is only 40 mu m (the thickness of the metal wire of the stent is 80 mu m), the mechanical properties of delivery, compression and release of the stent are not influenced, and the swelling rate of 212.5 percent can be realized.

The structural test of the obtained W/O type nano colostrum showed that fig. 1 shows that fig. 1 is a distribution diagram of the particle size of the W/O type nano colostrum in example 1 of the present invention, and it can be seen from fig. 1 that the particle size of the W/O type structure of the nano colostrum is 581.9nm, the particle size distribution is relatively uniform (PDI <0.3), and the drug loading of the protein is measured to be 2.14 mg/mL.

SEM electron microscope examination was performed on the hydrogel coating on the surface of the product, and the result is shown in fig. 2, and fig. 2 is an SEM image of the hydrogel coating on the surface of the product in example 1 of the present invention. In FIG. 2, A and B are GelMA + PVP (external aqueous solution) crosslinked lyophilized samples; c and D are GelMA + PVP + nano-emulsion (W/O/W type nano-emulsion) crosslinked freeze-dried samples, D shows a large number of particles (arrows) in the amplified freeze-dried GelMA + PVP + nano-emulsion samples, namely BSA particles in the nano-emulsion, and B shows that the surface of the amplified common GelMA is smoother. The hydrogel coating in this example was shown to be successfully coated with a hydrophilic drug.

The in vitro release test of the product of this example is shown in FIG. 4, and FIG. 4 is the in vitro release curve of the hydrogel-coated stent in example 1 of the present invention. In vitro release studies show that the release rates of BSA can reach 30.54%, 43.51%, 53.60% and 72.71% in 1, 3, 5 and 10 minutes after the nano-emulsion microspheres are swelled by GelMA. The actual drug loading of BSA was 0.823 mg/mL.

Comparative example 1

Hydrogel coated thrombogenic stents were prepared as in example 1 except that tween-80 was used in this comparative example instead of SDS in the outer aqueous phase.

Comparative example 2

Hydrogel coated embolic stents were prepared as in example 1, except that lecithin was used in this comparative example instead of SDS in the external aqueous phase.

FIG. 3 is a graph showing W/O/W type nanoemulsions of example 1 and comparative examples 1 to 2, which are comparative example 1 (Tween-80) and comparative example 2 (lecithin) in this order from the left, and the right graph shows the data before addition of PVP (SDS) and after addition of PVP (SDS + PVP) in example 1, respectively. As can be seen from FIG. 2, when Tween 80 is used as the emulsifier, an oil film floats on the surface; when lecithin was used as the emulsifier, the solution was cloudy; the two have poor emulsification effects, surface tension cannot be reduced, the effect of a surfactant cannot be achieved, and a stable nanoemulsion system cannot be formed. And when SDS is used as an emulsifier, the solution can maintain a W/O/W nanoemulsion system. In the last column, based on SDS as an emulsifier, PVP is added as a viscosity enhancer, and the characteristics of the emulsion are not changed, so that a good nano-emulsion system can be still maintained.

Comparative example 3

Hydrogel coated embolic stents were prepared as in example 1, except that no polyvinylpyrrolidone PVP was added in this comparative example.

The invention releases the thrombus removal stent in the embodiment 1 and the thrombus removal stent in the comparative example 3 for multiple times, and as a result, as shown in fig. 5, PVP is added into the hydrogel coating in the embodiment 1, when the stent is contracted into a conveyor and folded and released again, part of hydrogel on the surface of the metal stent is scraped off by the conveyor, the total amount of hydrogel is reduced, the surface is not smooth, and the hydrogel is easy to fall off in the blood vessel cavity in vivo, so that blockage can be caused. This condition is most pronounced when repeated multiple times. The GelMA hydrogel coating added with PVP has better adhesiveness, so that the surface of the metal support rod is relatively smooth, and the thickness of the coating can be larger, thereby obtaining higher drug-loading capacity; after the conveyor is retracted and released again, the surface of the stent rod can retain more hydrogel, has small change of shape and can maintain enough thickness after swelling.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. A hydrogel thrombus taking bracket for entrapping hydrophilic drugs comprises a thrombus taking bracket and a hydrogel layer coated on the surface of the thrombus taking bracket;

the hydrogel layer is prepared by photo-crosslinking W/O/W type nano-emulsion;

the inner water phase of the W/O/W type nano-emulsion is a hydrophilic drug solution, the oil phase of the W/O/W type nano-emulsion is soybean oil and an emulsifier, and the outer water phase of the W/O/W type nano-emulsion comprises methacrylated gelatin, a photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate;

the emulsifier is tween-80 and span-80; the mass ratio of the tween-80 to the span-80 is (1-3): 1; the mass ratio of the soybean oil to the emulsifier is 1: (1-5);

in the external water phase, the mass fraction of the methacrylated gelatin is 5-20%; the mass fraction of the photoinitiator is 0.5-2%; the mass fraction of the polyvinylpyrrolidone is 0.1-2%; the mass fraction of the sodium dodecyl sulfate is 0.1-1%.

2. The hydrogel embolectomy stent of claim 1, wherein the mass concentration of the hydrophilic drug solution is (0.01-1) μ g/μ L.

3. The hydrogel embolectomy stent of any one of claims 1 to 2, wherein the mass ratio of the internal water phase to the oil phase is (0.05-0.2): (0.8-0.95);

4. a method for preparing the hydrogel thrombus removal stent entrapping the hydrophilic drug according to claim 1, comprising the steps of:

B) under the condition of stirring, dropwise adding the W/O type nano primary emulsion into the external water phase solution to obtain W/O/W type nano emulsion; the oil phase is soybean oil and emulsifier, and the external water phase comprises methacrylated gelatin, photoinitiator, polyvinylpyrrolidone and sodium dodecyl sulfate;

5. The method for preparing the nano-emulsion according to claim 4, wherein the thrombus removal scaffold is subjected to abrasive flow polishing and/or carboxylation surface treatment before being soaked in the W/O/W type nano-emulsion.

6. The preparation method according to claim 4, wherein the soaking time in the step C) is 30-120 s.

7. The method according to claim 4, wherein the wavelength of the ultraviolet light in the step C) is 365 nm;

the irradiation intensity of the ultraviolet light is 500-700 mW/cm²；

The irradiation time of the ultraviolet light is 100-200 s;

the spot diameter of the ultraviolet light is 1.2 cm.

8. The method according to claim 4, wherein the ultraviolet irradiation step is further followed by drying;

the drying temperature is 35-40 ℃;

the drying time is 0.5-4 hours.