TECHNICAL FIELD

The present invention relates to nanoparticles, a method for preparing the same, a stone removal device comprising nanoparticles, a magnetic target separation instrument and its application.

BACKGROUND ART

Urinary calculi/stone (urolithiasis) have an incidence as high as 5%-10%, and can be found in any part of kidney, bladder, ureter and urethra, in which stones in kidney and ureter are common. It is found in clinical observation that calcium-containing stones are the most common types of urinary stones, that is, about 70% to 80% of all urinary stones. At present, there are only a few cases of calcium-containing stones which pathological causes have been clearly revealed, while the causes for most of calcium-containing stones are not yet clear. According to chemical composition, stones can be divided into four categories: calcium-containing stones, infection induced stones, uric acid stones and cystine stones. Calcium-containing stones can be divided into following types: simple calcium oxalate, calcium oxalate with calcium phosphate, calcium oxalate with a small amount of uric acid; the main components of infection induced stones are ammonium magnesium phosphate and hydroxyapatite; uric acid stones can be divided into following types: uric acid, uric acid amine, or those containing a small amount of calcium oxalate in addition to the above ingredients; cystine stones can be divided into following types: simple cystine, or cystine with a small amount of calcium oxalate.

Soft/hard ureteroscopic lithotripsy is performed through natural channel of the human body, has the advantages of small trauma and definite lithothriptic effect, and is currently the main treatment means for most of ureteral stones and kidney stones. However, the current soft/hard ureteroscopic lithotripsy also has some deficiencies: 1) upper ureteral stones and fragments of stones in ureter may be easily brought back to kidney by the infused water or the recoil force of lithotripsy tools; 2) there is lack of a fast, safe and effective method to take out residual debris of stones in ureteral lumen and kidney calices. It is an important mean to prevent ureteral stones from being recoiled back to kidney that a tool is used to block the ureter above the ureteral stones. At present, there are also some ureteral occluders in clinical practice, and such kind of stones blocking tools are also commonly used to remove stones. However, these ureteral occluders still have some shortcomings in actual use. Stone baskets (such as various stone baskets described in Patent Publication No. JP2009536081A, DE19904569A1, WO2004056275A1, WO2011123274A1 are designed with a net bag) are the most commonly used stone interception and removal tools, which cross over stone and then are opened to form a net so as to prevent the upward drift of stone debris, and at the same time, the stone baskets are also used as stone removal tools to net and take out small stone debris. However, the amount of stone removed by the stone basket every time is limited, so that multiple feeds of ureteroscope are needed, while repeated injection of water and feeds of ureteroscope would increase the risk of residual debris drift; secondly, the use of basket to take stones has great randomness, that is, it is a kind of contingency that the stones enter the basket and fall out of the basket, the basket would not be withdrawn from the ureter if too much stones enter the basket, and the efficiency would be very low if too less stones enter the basket so that more time is required for shaking, thereby extending the operation time, increasing the risk of surgery or anesthesia as well as the cost; thirdly, some stones in special parts such as stones in lower kidney calices can hardly be accessed by endoscopy itself, and the bending performance of endoscopy would decline when a stone basket is introduced, so it occurs frequently that the stones can be seen but cannot be taken out, and it is often needed to press abdomen or adjust posture to assist the removal of stones, which render the operation difficult and inefficient. In addition, the stone basket cannot completely seal the ureteral lumen, and there is still a chance that stones escape from the basket, and smaller stone debris are difficult to remove through the stone basket and generally have to be excreted naturally, which usually result in an extended time for removing stones or incomplete removal of stones, while these residual debris would further play the role of “crystal nucleus” to cause recurrence of stones easily. Moreover, the edges of stones in stone basket may be easily squeezed out from basket holes, and thus may easily scratch the ureter wall when the stones are dragged and removed, thereby causing complications in severe cases. In summary, there is an urgent need for a material and method for removal of stones in urinary system that can collect stones, facilitate the stone taking, do not damage the ureteral wall when the stones are dragged, can be conveniently disposed and are not easy to cause shift of stone.

Contents of the Invention

The present invention is aimed to solve the problem of residual stone debris and difficult removal thereof in the conventional soft/hard ureteroscopic lithotripsy. Therefore, a first object of the present invention is to provide a nano-material that can be used safely and efficiently to remove a stone located at a position such as kidney, ureter and so on in an urinary system; a second object of the present invention is to provide a method for preparing the nano-material with different morphological structures; a third object of the present invention is to provide a use of the nano-material in coordination with a selfmade magnetic target separation instrument in an operation of urinary calculi; a fourth object of the present invention is to provide a use of the nano-material in manufacture of an article for removing a stone in urinary system.

According to the first aspect of the present invention, there is provided a nanoparticle comprising a nanoparticle core composed of a magnetic material; and a nanoparticle shell formed by attaching a surface modifier monomer to the nanoparticle core with an initiator and/or a crosslinking agent.

According to some embodiments of the present invention, the nanoparticle wraps a stone through physical adsorption, chemical bonding, and photosensitive, thermosensitive, and pH-sensitive crosslinking. Specifically, the binding and wrapping forces between the nanoparticles and the stone include: van der Waal's force, hydrophobic interaction, adsorption and surface deposition for binding and wrapping; covalent bonds formed between carboxyl-stone, including hydrogen bonds, ester bonds, amide bonds, and other covalent bonds; physical entanglement and chemical crosslinking between chains.

According to some embodiments of the present invention, the nanoparticle core has a diameter of 2-50 nm, and a weight percentage of 30-95% relative to the whole weight of the nanoparticle, and the magnetic material constituting the core comprises a compound of Fe3+, Fe2+, Mn2+or Ni2+, or a metal element selected from iron, nickel, copper, cobalt, platinum, gold, europium, gadolinium, dysprosium, terbium, or a composite or oxide of the aforementioned metals, or a combination of two or more of the above items, preferably one of or a combination of any two of Fe3+, Fe2+, Mn2+or Ni2+, more preferably Fe3+and Fe2+in a ratio of 15% to 85%, preferably 1:2.5 to 1.5:1. It should be noted that the method for preparing the nanoparticle used in the present invention can well control the size and dimension of the magnetic nanoparticle core; especially, in comparison with the nanoparticles prepared by other methods, among the parameters of the nanoparticle obtained in the present invention that relates to the biomedical application, the dispersibility of the nanoparticle is very good and less than 1.1.

According to certain embodiments of the present invention, the surface modifier includes a surface modifier with hydrophilic, hydrophobic, photosensitive, thermosensitive or pH sensitive function response, wherein the hydrophilic surface modifier includes acrylic acid, methacrylic acid, isobutyl acrylamide or poly N-substituted isopropylacrylamide; the hydrophobic surface modifier comprises oletins, preferably polystyrene, polyethylene or oleic acid; the photosensitive surface modifier is selected from the group consisting of azos and quinolines and benzophenones (PVBP), preferably vinyl benzophenone; the thermosensitive surface modifier is selected from the group consisting of amphiphilic polymers with an amide bond, preferably polyacrylamide or poly N-substituted isopropylacrylamide; the pH-sensitive surface modifier is selected from the group consisting of polymers with a carboxyl group and a quaternary ammonium salt, preferably polyacrylic acid, dimethylaminoethyl ester and dimethylaminopropyl methacrylate.

According to certain embodiments of the present invention, the crosslinking agent comprises 3-(methacryloyloxy)propyltriethoxysilane, divinylbenzene, diisocyanate or N,N-methylenebisacrylamide, and the initiator comprises 3-chloropropionic acid, CuCl, 4,4′-dinonyl-2,2-bipyridine or potassium persulfate.

The second aspect of the invention provides a method of preparing the nanoparticle, comprising the steps of: a) preparing the nanoparticle core using the magnetic material; and b) forming the nanoparticle shell by in situ linking the surface modifier monomer to the nanoparticle core by the initiator and/or crosslinking agent. As used herein, “in situ” means that the surface modifier is directly attached to the surface of the nanoparticle core. The resulting modified nanoparticle has a size between 50 nm and 5000 nm, which varies according to different conditions.

According to some embodiments of the present invention, the nanoparticle core is composed of Fe3O4, MnFe2O4, γ-Fe2O3, or other nanoscale-sized ferrite particles, and these ferrite particles are prepared by the following steps:

dissolving a proportion of the metal salt-containing material in water;

feeding nitrogen to expel oxygen in the solution;

adding a catalyst at a room temperature of 20-30° C. to adjust the pH to 8-12, preferably 10;

keeping agitation and reaction for 20-40 minutes; and

reacting under condition of 50-100° C., preferably 70° C. water bath, for 20-40 minutes, then separating with a magnet and drying to obtain the magnetic nanoparticle core.

In a particular embodiment of the present invention, the oxygen-containing metal salt is FeCl3.6H2O and FeCl2.4H2O, which are dissolved in water in a molar ratio of 15% to 85%, preferably 1:2.5 to 1.5:1, wherein the catalyst is aqueous ammonia. Fe3O4nanoparticles can be obtained by following the above steps.

According to some embodiments of the present invention, the step b) comprises dispersing the prepared nanoparticles in an aqueous solution, adding with an xylene solution of 3-chloropropionic acid, polystyrene, CuCl and 4,4′-dinonyl-2,2-bipyridine, wherein the molar ratio between the solution of iron particles and the reaction solution is 1:1; reacting the mixture for 15-30 hours, preferably 24 hours, at 130° C. under continuous agitation; and collecting the nanoparticles with a magnet, washing repeatedly with toluene to obtain hydrophobic polystyrene-wrapped magnetic iron oxide nanoparticles.

According to some embodiments of the present invention, the step b) comprises dissolving and dispersing the resulting nanoparticle core into xylene, adding with a silane coupling agent, wherein the silane coupling agent, wherein the nanoparticles, xylene and silane coupling agent are added in a ratio of 95:5; reacting under the protection of nitrogen atmosphere at 20-100° C., preferably at 80° C., for 2-5 hours, preferably for 3 hours; washing with an alcoholic solvent (preferably absolute ethanol) and drying for 12 hours, dispersing in an aqueous solution under ultrasonic condition, adding with potassium persulfate; reacting under nitrogen protection, at 40-80° C. for 10 minutes, adding with acrylic acid to continue reaction at 40-80° C. for 1 hour, wherein the reaction temperature is preferably 70° C.; and separating with a magnet, washing and drying to obtain the polyacrylic acid-modified hydrophilic nanoparticles.

According to some embodiments of the present invention, the above step b comprises: dissolving and dispersing Fe3O4nanoparticles into xylene, and adding with a silane coupling agent, wherein the silane coupling agent (the ratio of the Fe3O4nanoparticles and the silane coupling agent as added is 95:5); reacting under protection of nitrogen atmosphere at 80° C. for 2-5 hours, preferably for 3 hours; washing with an alcoholic solvent (preferably absolute ethanol) and drying for 12 hours, dispersing in an aqueous solution under ultrasonic condition, adding with potassium persulfate; reacting under nitrogen protection at 40-80° C. for 10 minutes, adding with a photosensitive monomer such as vinyl benzophenone, a thermosensitive monomer such as N-isopropylacrylamide, or a pH-sensitive monomer such as dimethylaminopropyl methacrylate, etc. (or a blended monomer of acrylic acid and styrene), reacting continuously for 1 hour at 40-80° C., preferably at 70° C.; and separating with a magnet, washing and drying to obtain the photosensitive, thermosensitive or pH sensitive functional monomer-modified magnetic nanoparticles, respectively.

In certain embodiments of the present invention, the photosensitive monomer modification based on the hydrophilic surface modification comprises: dissolving and dispersing the polyacrylic acid-modified magnetic nanoparticles in an alcoholic solvent, dispersing for 5-30 minutes under ultrasonic condition, then adding an initiator and a photosensitive monomer polyvinylbenzophenone, refluxing and reacting at agitation and 130° C. for 24 hours under condition that oxygen is kept out to prepare the photosensitive monomer-modified magnetic nanoparticles.

In the above-mentioned embodiment, when aqueous ammonia is used as catalyst to prepare the nanoparticles, the method for dropping aqueous ammonia is performed in a continuous and dropwise manner with assistance of an electronic pump at a speed of 20-100 drops/minute, preferably 40-60 drops/minute; and when the magnetic material is an element material, the liquid monomer is added in a dropwise and continuous manner with assistance of an electronic pump, and the reaction is carried out under agitation with a speed of 100-1000 rpm, preferably 500-700 rpm.

It should be noted here that the particle size, distribution and morphology (such as a shape of sphere, rod, diamond) of the obtained magnetic nanoparticle core can be relatively easily controlled under the synthetic methods and preparation conditions as we designed above. Furthermore, the surface-modified magnetic nanoparticles prepared by the above method have particle size and distribution superior to those of magnetic nanoparticles obtained by conventional preparation methods. As shown in the following table, the dispersibility index of the obtained nanoparticles (PD.I.) is basically close to 1.0, which clearly shows that the particle size distribution of the obtained particles is narrow. This is very important because, for in vivo biomedical applications, the size and dispersion of nanoparticles determine the breadth of their medical applications. The PD.I described herein for describing the dispersibility of nanoparticles is defined as follows:
PD.I.=<Rh2>/<Rh>2

wherein, Rh represents hydrodynamic radius of particle.

The nanoparticle core and the surface-modified magnetic nanoparticle have distribution PD.I. as shown in the following table:

Magnetic nanoparticle coreAfter surface modificationDiameter/nm40-5080-100PD.I./a.u.0.0050.0055

In addition, as shown inFIG. 2, the structure of the nanoparticles obtained in the present invention is clear.

According to the third aspect of the present invention, there is provided a device for stone removal, which can be used to remove urinary stones in the urinary system more thoroughly, efficiently and safely, and consists of magnetic nanoparticles in combination with a magnetic target separation instrument. The device for stone removal comprises the above-mentioned nanoparticles of the present invention and magnetic target separation instrument for facilitating stone removal. The magnetic target separation instrument can be used for removing stones in urinary system such as kidney stones, ureteral stones and bladder stones, as well as removing stones in human biliary system and stone-like particles in other organs.

Specifically, the magnetic target separation instrument comprises a handle, a flexible rod, a magnetic field source, a magnetically permeable material section, etc. The handle may be provided with an AC or DC power supply, a power switch, a DC battery chamber and an AC plug. The flexible rod is made of a polymer material including, for example, PU, TPU, PE, PVC, NYLON, PEBAX and silicone rubber and the modified materials of the above materials. The magnetic field source made of a permanent magnet or electromagnet can be embedded in the flexible rod, and optionally a high performance magnetically permeable material is connected to the magnetic field source to form a flexible magnetic target separation instrument with different configurations. For example, the permanent magnet is disposed in the middle or back end of the flexible rod, and the magnetically permeable material is disposed in the distal end of the flexible rod. Such a configuration is more useful for the treatment of renal stones under ureteroscope to avoid the situation that the distal end of the flexible rod becomes rigid due to the rigid structure of the permanent magnet or the electromagnet, so that such magnetic target separation instrument can be successfully inserted into the working channel of ureteroscope, and inserted into upper, middle and lower kidney calices to carry out stone removal operation when driven by the ureteroscope.

In one embodiment, the present invention provides a magnetic target separation instrument, which comprises a magnetic end, a connecting rod and a handle; wherein a distal end of the connecting rod is connected to the magnetic end, a proximal end of the connecting rod is connected with the handle; and wherein the connecting rod is made of a material with a certain flexibility. For example, the connecting rod may be composed of a structure of a tube, a wire, a spring tube, a hypotube, a braid tube that is made of a polymer material or a metal material, as well as combinations formed by splicing or nesting the above structures or forms. The connecting rod has a diameter between 0.5 mm and 5 mm. Depending on the method of use, one skilled in the art can choose different diameters for the connecting rod. For example, when the magnetic target separation instrument according to the present invention is introduced into the human body through an endoscope working channel, the diameter of the connecting rod is preferably 0.5 mm to 1.2 mm. Alternatively, when the magnetic target separation instrument according to the present invention is introduced into the human body through the ureteral sheath, the diameter of the connecting rod is preferably 1 mm to 4.5 mm. As an embodiment, when the diameter of the connecting rod is greater than 1 mm, the connecting rod may be a hollow structure, through which a metal wire, a cable, a cord, a catheter, an optical fiber, and any combination of the above can pass, respectively.

In one embodiment, the magnetic end is a magnetic component, and the magnetic component may be a permanent magnet or a soft magnet made of a magnetic material, wherein the magnetic material includes, but not limited to, an alloy magnetic material, a ferrite magnetic material and an intermetallic compound magnetic material, such as: aluminium-nickel-cobalt, iron-chromium-cobalt, iron-cobalt-vanadium, barium ferrite, strontium ferrite, neodymium-iron-boron, samarium-cobalt, manganese-bismuth and other materials. The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel.

Alternatively, the above-mentioned magnetic component may be made of an electromagnet, and the electromagnet is made of a cable-wound coil. Further, as the inner core, a magnetically permeable material for enhancing magnetic field strength may be added to the cable-wound coil, and the magnetically permeable material includes, but is not limited to, pure iron, ferrite soft magnetic material, iron-nickel alloy, ferrosilicon alloy, vanadium-iron-vanadium alloy, nano-crystalline soft magnetic materials, amorphous soft magnetic materials. The handle is connected to the magnetic end through the connecting rod, wherein the handle is characterized in that the handle is provided with an AC plug or a DC battery chamber for supplying power to the electromagnet. Further, the handle is provided with a power switch for controlling whether the electromagnet is electrified or not. Further, the handle is provided with a regulating switch for adjusting the magnitude of the current so as to adjust the magnetic field strength of the electromagnet.

Alternatively, the above-mentioned magnetic component may be composed of a magnetic field source and a high-efficiency magnetically permeable end. The magnetic field source may be made of a permanent magnet, a soft magnet and an electromagnet. The high-efficiency magnetically permeable end is joined the distal end of the magnetic field source and is used to guide, extend, derive, disperse and cross-link the magnetic field produced by the magnetic field source with no loss or low loss, so as to compensate the simplicity in terms of surface area, volume, shape, flexibility and strength of the magnetic end which are caused by the relatively simple type of the magnetic field source, to better adapt to the human blood vessels, urinary system and other anatomical structures, and to ultimately realize the separation of magnetic targets under a complex and volatile environment. The high-efficiency magnetically permeable end material includes, but is not limited to, pure iron, low carbon steel, ferrosilicon alloy, ferroaluminum alloy, sendust, ferronickel alloy, iron-cobalt alloy, soft magnetic ferrite, amorphous soft magnetic alloy, ultra-crystalline soft magnetic alloy and other materials. The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel.

In one embodiment, the shape of the magnetic end may be made into a column shape. Still further, the cross-sectional shape of the magnetic end in column shape includes, but is not limited to, round shape, oval shape, polygon shape, radial shape, cross shape, I-shape, petal shape, annular shape, U-shape, porous shape, spiral shape, torsion shape, coiled shape, twisted shape and other shapes. The shape of the magnetic end may be made into a reticulum shape. Further, the reticulated magnetic end may be woven from a single- or multi-stranded magnetic or magnetically permeable materials, and its shape can be woven reticulum shape, coiled reticulum shape, knotted rope reticulum shape, hollow mesh, radial reticulum shape, convergent reticulum shape, cross-section asymmetric reticulum shape, open reticulum shape, pocket-type reticulum shape, spiral-type reticulum shape, barrel-shaped reticulum shape, spindle-shaped reticulum shape, umbrella-shaped reticulum shape, drop-shaped reticulum shape, funnel-shaped reticulum shape, broom-shaped reticulum shape, disorderly entangled reticulum shape. Furthermore, the wire surface or the woven reticulum surface of the reticulated magnetic end can be coated with a biocompatible material such as Teflon, parylene, polyurethane, thermoplastic polyurethane. Still further, the surface of the reticulated magnetic end may be coated with a magnetic material or a material having a high magnetic permeability (μ>1). The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel.

In one embodiment, the magnetic end is a magnetic component, wherein the magnetic component may be composed of a magnetic field source and a high-efficiency magnetically permeable end. Further, in the magnetic component, the magnetic field source is joined to the high-efficiency magnetically permeable end axially along the axis of the connecting rod, or the magnetic field source is coated by the high-efficiency magnetically permeable end. Still further, there exists a relative movement between the magnetic field source and the high-efficiency magnetically permeable end. In the case that there exists a certain relative movement between the magnetic field source and the high-efficiency magnetically permeable end, an axial rigid rod or rigid tube is connected to the magnetic field source, the rigid rod or the rigid tube passes through the lumen of the connecting rod and the other end is fixed on a control push-rod of the handle, the relative distance between the magnetic field source and the high-efficiency magnetically permeable end can be changed by pushing the control push-rod so as to adjust the magnetic field intensity in the high-efficiency magnetically permeable end. After the magnetic target separation instrument provided by the invention collects, adsorbs and removes magnetic targets, the function can fulfill the quick removal of the magnetic targets from the instrument so as to prepare the instrument for re-entering the human body. The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel. Further, the handle is provided with a control push-rod, which is connected to the magnetic field source in the magnetic end through an axial rigid rod or rigid tube. Further, the rigid rod or the rigid tube passes through the lumen of the connecting rod and is slidingly disposed in the connecting rod; the relative distance between the magnetic field source and the high-efficiency magnetically permeable end can be changed by pushing and pulling the control push-rod so as to change the adsorption strength of the magnetic end to the magnetic target, to make it possible to quickly separate the magnetic targets from the surface of the magnetic end in vitro, thereby facilitating the re-entry of the instrument into the human body to collect, adsorb and remove the magnetic targets.

Alternatively, the magnetic target separation instrument includes a magnetic end, and the magnetic end contains a steel wire or cord for driving the magnetic end to bend. Further, there are optionally one or two or more pieces of the steel wire or cord. The steel wire or cord is within the magnetic end at one end of the steel wire or cord, passes through the lumen of the connecting rod, and is fixed on an angel adjustment shaft of the handle part at the other end of the steel wire or cord, so that by manipulating the angle adjustment shaft, the magnetic end can be controlled to bend at an angle away from the axial direction of the connecting rod. The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel. Further, the handle is provided with an angle adjustment shaft, wherein the angle adjustment shaft pulls the magnetic end via one or two or more pieces of steel wire or cord passing through the connecting rod, so that the magnetic end can bend at an angle away from the axial direction of the connecting rod to adapt to the purpose for separating the magnetic targets from different body cavities under complicated environments.

Alternatively, the magnetic target separation instrument includes a magnetic end, the magnetic end is integrated with an image acquisition module. Further, the image acquisition module comprises a lens and a CCD, or comprises a lens and a CMOS, or comprises a lens and an image transmission fiber, or comprises only an image transmission fiber. Preferably, the image acquisition module is composed of a lens and a CMOS. Further, the magnetic end with the image acquisition module includes a steel wire or cord for driving the magnetic end to bend, wherein the steel wire or cord is fixed within the magnetic end at one end of the steel wire or cord, passes through the lumen of the connecting rod, and is fixed on an angel adjustment shaft of the handle part at the other end of the steel wire or cord; by manipulating the angel adjustment shaft, the magnetic end can be controlled to bend at an angle away from the axial direction of the connecting rod. The handle is connected to the magnetic end through the connecting rod, wherein the handle is used for controlling the magnetic end to enter or leave the endoscope channel. Further, the handle is provided with an angle adjustment shaft, wherein the angle adjustment shaft pulls the magnetic end via one or two or more pieces of steel wire or cord passing through the connecting rod, so that the magnetic end can bend at an angle away from the axial direction of the connecting rod to adapt to the purpose for separating the magnetic targets from different body cavities under complicated environments. Further, the handle is provided with an interface for transmission of video image signal to connect an external video display device so as to facilitate monitoring the surgical field and process recording. The external video display device belongs to the prior art and is not included in the content of the present invention, and thus its details are not described herein.

In the present invention, the connection relationship between the magnetic end and the connecting rod is that the magnetic end is sheathed on the distal end of the connecting rod, or the connecting rod passes through the magnetic end, or the connecting rod and the magnetic end are connected by bonding, or the connecting rod and the magnetic end are connected by covering with a same material, or the connecting rod and the magnetic end are connected by metal crimping, or the connecting rod and the magnetic end are connected by a quick connecting mechanism, wherein the quick connecting mechanism includes, but not limited to, a screw thread, a Luer taper, a snap joint, a screw buckle, a socket component, a plug-in component, a magnetic component, an interference fit component and so on that can achieve quick connection.

The method for using the magnetic target separation instrument according to the present invention is as follows: 1) firstly, the stones in a body are crushed by means of a traditional lithotripsy; 2) functional materials with magnetic properties (for example, but not limited to, the nanoparticles of the present invention) are injected into the region containing the crushed stones through the endoscope working channel; 3) the magnetic functional material has a physical or chemical interaction on the surface of the stones and wraps the surface of the stones so as to finally magnetize the stones; 4) the magnetic target separation instrument is introduced to gather the magnetized stones together in the front end of the instrument by the magnetic field of the magnetic end, and finally the gathered stones together with the instrument are removed from the body to fulfill the purpose of gathering stones in non-contact mode and bulk removal of stones at a high efficiency.

In the forth aspect of the invention, there is provided a use of the nanoparticles of the present invention in manufacture of an article, in which the nanoparticles are prepared in the form of a solution or powder.

The invention provides a novel preparation process for synthesizing hydrophilic, hydrophobic, thermosensitive and pH-sensitive as well as photosensitive magnetic nanoparticles, which has the advantages of simple preparation process, good repeatability and convenient application. By the hydrophobic interaction between the prepared hydrophobic nanoparticles and stones, the chemical bond interaction between hydrophilic nanoparticles and stones, and the polymerization of the photosensitive nanoparticles under illumination, the stones are wrapped; and the thermosensitive and pH-sensitive nanoparticles can wrap stones through physically wrapping action in ureter; thereby, small stones remaining in body can be removed quickly without damage from the body under the action of an externally applied magnetic field, that is, the stones can be drawn and moved without injuring ureteral wall, and meanwhile be disposed conveniently without easy shift.

The present invention is further described with reference to the accompanying drawings.

