Intravenous implantable heavy metal and radionuclide adsorption device and methods of use thereof

Abstract

This invention belongs to the field of medical adsorption materials technology, and discloses an intravenously implantable heavy metal and radionuclide adsorption device and its usage method. The device consists of a rod-shaped carrier, a functional adsorption material, and a biodegradable protective layer. After implantation via intravenous puncture, it continuously adsorbs harmful substances in the blood. Its innovations lie in: the rod-shaped carrier providing an ultra-high specific surface area; the functional material achieving specific complexation adsorption; the biodegradable protective layer combining initial structural protection and sustained-release function; and surface modification reducing the risk of thrombosis. The device can improve blood purification efficiency and reduce the metabolic burden on the liver and kidneys.

Description

Technical Field

[0001] This invention belongs to the field of medical adsorption materials technology, specifically relating to an intravenously implantable heavy metal and radionuclide adsorption device and its usage method. Background Technology

[0002] In scenarios involving excessive heavy metal levels, nuclear accidents, and radiological medical diagnosis and treatment, the human body may accidentally ingest heavy metals or come into contact with radionuclides. Once inside the body, these heavy metals and radionuclides can damage cells, tissues, and organs, causing various diseases and even endangering life. Currently, clinical methods for clearing heavy metals and radionuclides from the body mainly include conventional methods such as inducing vomiting, gastric lavage, diuresis, and drug intervention. However, these methods have limited effectiveness in clearing heavy metals and radionuclides that have already entered the bloodstream. While some chelating agents can bind to radionuclides and promote their excretion, they have problems such as significant side effects and poor selectivity, making it difficult to efficiently and safely remove heavy metals and radionuclides from the blood.

[0003] Therefore, there is an urgent need to develop a new, efficient and safe device for adsorbing and removing heavy metals and radionuclides from the blood. Summary of the Invention

[0004] To overcome the above-mentioned technical problems, the present invention provides an intravenous implantable heavy metal and radionuclide adsorption device and its usage method. The rod-shaped device is directly implanted into the vein. Through its unique structure and adsorption material, it can efficiently and selectively adsorb heavy metals and radionuclides in the blood, and has good biocompatibility, reducing adverse effects on the human body.

[0005] The present invention adopts the following technical solution: Intravenous implantable heavy metal and radionuclide adsorption devices include: Rod-shaped carrier, 50-500 nm in diameter; Adsorption functional materials loaded on the nanofibers; A biodegradable protective layer covering a rod-shaped carrier, 0.1-1 mm thick, is made of PLGA, PCL, or copolymers thereof.

[0006] Preferably, the rod-shaped carrier is composed of nanofibers.

[0007] The adsorption functional material includes at least one of chitosan, polyacrylic acid, graphene oxide, iron oxide, titanium dioxide nanoparticles, and hydroxyapatite.

[0008] Preferably, the rod-shaped carrier is a porous metal tube or resin tube with a porosity of 30%-50% and a pore size of 100-300μm.

[0009] The adsorbent material comprises zirconium-based compounds or metal-organic framework materials.

[0010] Preferably, the surface of the device is hydrophilic modified, comprising a grafted polyethylene glycol layer or hydrophilic groups formed by plasma treatment.

[0011] Preferably, the device has a length of 1-5cm and a diameter of 0.3-1mm.

[0012] The present invention also discloses a method for implanting the above-mentioned device, comprising: Establish indwelling needle catheter access via intravenous puncture; The catheter is advanced to the target vein location via a catheter delivery device. The catheter was withdrawn to complete the implantation.

[0013] The present invention also discloses a method for replacing the above-mentioned device, comprising: The capture device is introduced through a retention needle catheter; Grab the adsorption saturation device and withdraw it; A new device was implanted.

[0014] Compared with the prior art, the beneficial effects of the present invention are: 1. Highly efficient adsorption: The rod-shaped carrier has a huge specific surface area, which can provide abundant adsorption sites. The loaded functional materials can specifically bind to a variety of radionuclides, thereby achieving highly efficient adsorption of radionuclides in the blood and improving the removal efficiency. 2. Good biocompatibility: The nanofiber materials, functional materials and biodegradable protective layer used all have good biocompatibility, which can reduce the stimulation of human tissues and blood, and reduce the probability of immune response and adverse reactions. 3. Convenient to use: The size of the nanofiber rods is suitable for intravenous implantation. They can be implanted through a simple intravenous puncture procedure without complicated operations. They can also continuously exert an adsorption effect in the body, reducing the patient's treatment pain and time costs. 4. High safety: The protective layer ensures the stability of the nanofiber rod in the early stage of implantation. As it gradually degrades, the device gradually releases its adsorption function, avoiding the risk of premature detachment of nanofibers into the blood circulation and causing embolism. At the same time, the surface modification treatment reduces the risk of thrombosis, further improving the safety of use. 5. Convenient operation and replacement: The implantation and replacement are performed using an indwelling needle, which conforms to routine clinical operating procedures, reduces trauma to patients, and the replacement process is simple, allowing for timely adjustments based on the adsorption status to ensure continuous and effective adsorption. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the adsorption device structure of the present invention. Detailed Implementation

[0016] The embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. Unless otherwise specified, the raw materials and equipment used are commercially available or commonly used in the art. The methods in the embodiments, unless otherwise specified, are conventional methods in the art. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0017] Example 1: Chitosan / Titanium Dioxide Composite Nanofiber Rods 1. Preparation of nanofiber materials: Chitosan was dissolved in acetic acid solution to prepare a 5% (w / w) chitosan solution. An appropriate amount of titanium dioxide nanoparticles was added and stirred until homogeneous, yielding a spinning solution. Electrospinning was performed at a voltage of 15 kV, a receiving distance of 15 cm, and a solution flow rate of 0.5 mL / h to prepare nanofiber materials loaded with chitosan and titanium dioxide nanoparticles. The average diameter of the nanofibers was approximately 200 nm.

[0018] 2. Preparation of nanofiber rods: The above nanofiber material is pressed into rods with a length of 3 cm and a diameter of 0.5 mm by using a mold.

[0019] 3. Preparation of protective layer: Polylactic acid-glycolic acid copolymer (PLGA) is dissolved in dichloromethane to prepare a 10% PLGA solution. The PLGA solution is coated onto the surface of the nanofiber rod by dip coating to form a protective layer with a thickness of about 0.3 mm. After the dichloromethane evaporates, the finished nanofiber rod is obtained.

[0020] 4. Surface modification treatment: The nanofiber rods are immersed in a polyethylene glycol (PEG) solution and reacted at 37°C for 2 hours to graft PEG onto the surface of the nanofiber rods, thereby improving their hydrophilicity and biocompatibility.

[0021] Performance verification Adsorption efficiency (simulated blood: PBS solution containing 100 Bq / mL of 137Cs) Table 1. Experimental results of adsorption efficiency Biocompatibility, according to ISO 10993 standard: Hemolysis rate: 0.38%, <5% is acceptable; Cytotoxicity (L929 fibroblasts): Grade 0 (non-toxic); Thrombosis (72 hours after implantation in rabbit jugular vein): fibrin deposition 0.8 μg / cm² (conventional catheter > 5 μg / cm²).

[0022] Use of the above-mentioned adsorption device: Implantation procedure: Select a 20G indwelling needle to puncture the patient's anterior elbow vein in the forearm. After successful puncture, push the nanofiber rod into the vein to complete the implantation.

[0023] Replacement procedure: Six hours after implantation, the rate of decrease in heavy metals and radionuclides in the blood slowed significantly, indicating adsorption saturation. A retaining needle was inserted through the original puncture site, and the saturated nanofiber rod was removed using a specialized retrieval instrument, followed by the insertion of a new nanofiber rod.

[0024] Withdrawal time ≤ 30s, new rod implantation interval ≤ 5min.

[0025] Example 2: Polyacrylic acid / hydroxyapatite composite nanofiber needles 1. Preparation of nanofiber materials: Polyacrylic acid and hydroxyapatite were mixed and deionized water was added to prepare a homogeneous spinning solution, wherein the mass fraction of polyacrylic acid was 8% and the mass fraction of hydroxyapatite was 10%. Under electrospinning conditions of 18 kV voltage, 18 cm receiving distance, and 0.8 mL / h solution flow rate, nanofiber materials loaded with polyacrylic acid and hydroxyapatite were prepared, with an average nanofiber diameter of approximately 300 nm.

[0026] 2. Preparation of nanofiber rods: The nanofiber material is wound onto a mandrel to form a rod with a length of 2 cm and a diameter of 0.6 mm.

[0027] 3. Preparation of protective layer: Using polycaprolactone (PCL) as raw material, a PCL solution with a mass fraction of 12% was prepared and a protective layer with a thickness of about 0.5 mm was formed on the surface of the nanofiber rod by spraying.

[0028] 4. Surface modification treatment: Using plasma treatment technology, hydrophilic groups are introduced on the surface of nanofiber rods to improve their dispersibility and compatibility in blood.

[0029] Comparative experiment: Table 2 Comparison of experimental results Animal experiments: Model: Beagle dog intravenous injection 90 SrCl2 (50 μCi / kg); Implantation group (n=5): Nanofiber needles were implanted in the femoral vein.

[0030] result: After 6 hours, serum strontium activity decreased to 18.3% of the initial value. Compared to the control group, bone marrow accumulation was reduced by 76%. Pathological examination: The venous endothelium showed no damage.

[0031] Example 3: Zirconium-based adsorbent loaded in a porous stainless steel tube 1. Use 316L stainless steel perforated tube, 4cm in length and 0.8mm in outer diameter.

[0032] 2. Laser drilling diameter 150μm, porosity 40%, and electrolytic polishing of the inner wall of the tube.

[0033] 3. The cavity is filled with zirconium phosphate / graphene oxide composite particles with a particle size of 10-50μm and a filling density of 1.2g / cm³.

[0034] 4. The tube ends are sealed with Loctite 4014 bio-adhesive.

[0035] Performance testing: Table 3 Performance Test Results Example 4: EDTA-MIL-101(Cr) loaded in polyetheretherketone porous tubes 1. Functional modification of MOF materials First, the basic MOF material was synthesized. 2.0 g of chromium nitrate nonahydrate (Cr(NO3)3·9H2O) and 1.66 g of terephthalic acid were dissolved in 30 mL of N,N-dimethylformamide (DMF) and treated with an ultrasonic power of 150 W for 15 minutes to form a homogeneous dark green solution. This solution was transferred to a 50 mL polytetrafluoroethylene high-pressure reactor and subjected to a stepwise temperature-controlled reaction in a temperature-controlled oven: first, the temperature was increased to 110 °C at a rate of 5 °C / min and held for 1 hour, then increased to 220 °C at a rate of 2 °C / min and reacted for 24 hours. After the reaction, the mixture was allowed to cool naturally, and the brown precipitate was collected by centrifugation. The precipitate was washed three times alternately with DMF and anhydrous ethanol (centrifugation conditions: 4000 g, 10 min) to obtain activated MIL-101(Cr) powder.

[0036] Subsequently, carboxylation grafting was performed. 1 gram of activated MOF was dispersed in 100 mL of 0.1 M sodium hydroxide solution, and 50 g of sodium chloroacetate was added. The reaction was carried out at 80 °C with magnetic stirring for 6 hours, during which the pH was maintained at 9.0 ± 0.2 using an automatic titrator. After the reaction was complete, the mixture was filtered through a 0.22 μm polyethersulfone membrane to obtain the carboxylated intermediate.

[0037] Finally, EDTA functionalization was performed. The above intermediate and 30 g of EDTA dianhydride were added to a nitrogen-filled, sealed reactor and stirred continuously for 48 hours at 60°C in the dark (nitrogen flow rate 20 mL / min). The reaction product was dialyzed against ultrapure water with a molecular weight cutoff of 8000 for 72 hours, with the dialysate replaced every 8 hours until the conductivity of the dialysate was ≤5 μS / cm. After freeze-drying, a grayish-white EDTA-MIL-101(Cr) powder was obtained. Thermogravimetric analysis confirmed that the EDTA grafting rate reached 38.2%, and the specific surface area decreased from 3120 m² / g to 2650 m² / g.

[0038] 2. Precision machining of porous tubular carriers Medical-grade polyetheretherketone (PEEK 450G) granules were used to prepare solid tubes with an outer diameter of 1.0 mm via melt extrusion molding. A femtosecond laser drilling system was employed to create a helical array of holes in the tube wall: micropores of 200±10 μm were created with a hole spacing of 300 μm, and the laser head travel speed was controlled at 2 mm / s. After drilling, the tube was immersed in 98% concentrated sulfuric acid for surface etching for 30 seconds, precisely thinning the tube wall to 0.2 mm. After rinsing with ultrapure water, the tube was placed in an oxygen-argon equal-volume mixed gas plasma chamber and treated at 100 watts for 10 minutes to form an activated surface.

[0039] 3. Adsorbent loading and structural encapsulation Functionalized MOF powder and anhydrous ethanol were mixed at a mass ratio of 3:7 to form a slurry, which was then injected into a dedicated vacuum filling device. One end of a PEEK porous tube was connected to a vacuum system and maintained at a negative pressure of -0.1 MPa, while the other end was inserted into the MOF slurry storage tank. The slurry was drawn into the tube cavity at a constant speed of 2 mm / s. After filling, the filling uniformity was checked using an X-ray microscopic imaging system and found to be >95%. Titanium alloy end caps with an outer diameter of 1.0 mm were cut using a precision lathe. The two ends of the tube were then bonded and sealed using Loctite 4305 UV-curing adhesive and cured under 50 mW / cm² UV light for 60 seconds. Finally, a PLGA anti-leakage layer was coated on the outside of the tube by coaxial electrospinning: 8% by mass of PLGA was dissolved in chloroform, and spun at a flow rate of 0.3 ml / h under a voltage of 12 kV and a receiving distance of 10 cm. The tube rotated to form a homogeneous coating layer with a thickness of 50 ± 3 μm.

[0040] Performance testing: Table 4 Performance Test Results Although embodiments of the present invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and variations can be made to the above embodiments without departing from the principles and spirit of the present invention, the scope of which is defined by the claims and their equivalents.

Claims

1. A device for intravenous implantation for adsorbing heavy metals and radionuclides, characterized in that, include: Rod-shaped carrier, 50-500 nm in diameter; Adsorption functional materials loaded on the nanofibers; A biodegradable protective layer covering a rod-shaped carrier, 0.1-1 mm thick, is made of PLGA, PCL, or copolymers thereof.

2. The apparatus of claim 1, wherein: The rod-shaped carrier is composed of nanofibers.

3. The apparatus of claim 2, wherein: The adsorption functional material includes at least one of chitosan, polyacrylic acid, graphene oxide, iron oxide, titanium dioxide nanoparticles, and hydroxyapatite.

4. The apparatus of claim 1, wherein: The rod-shaped carrier is a porous metal tube or resin tube with a porosity of 30%-50% and a pore size of 100-300μm.

5. The apparatus of claim 4, wherein: The adsorbent material comprises zirconium-based compounds or metal-organic framework materials.

6. The apparatus of claim 1, wherein: The surface of the device is hydrophilic modified, including a grafted polyethylene glycol layer or hydrophilic groups formed by plasma treatment.

7. The apparatus of claim 1, wherein: The device is 1-5cm long and 0.3-1mm in diameter.

8. A method of implanting the device of any one of claims 1-7, wherein, include: Establish indwelling needle catheter access via intravenous puncture; The catheter is advanced to the target vein location via a catheter delivery device. The catheter was withdrawn to complete the implantation.

9. The method of replacing the device according to any one of claims 1 to 7, characterized in that, include: The capture device is introduced through a retention needle catheter; Grab the adsorption saturation device and withdraw it; A new device was implanted.

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