Positioning marker made of degradable metal and method for producing same

Abstract

The present application relates to a kind of positioning markers made of degradable metal and its preparation method, the positioning marker is made of pure magnesium or magnesium alloy, wherein, the total content of impurities in pure magnesium and magnesium alloy is less than 0.01% mass fraction, the positioning marker is at least woven by three magnesium wires, and has a winding end and a positioning end connected to the winding end, the positioning end is claw-shaped or anchor-shaped structure, the tensile strength of the positioning marker is greater than 200 MPa, the elongation after break is greater than 10%, the in vivo degradation rate is less than 0.5 mm / year, the positioning marker can be visualized under ultrasound and X-ray, the position of the marker can be detected by ultrasound or molybdenum target X-ray during the operation process and postoperative treatment process, and with the progress of postoperative treatment, the positioning marker gradually degrades, is absorbed or metabolized by surrounding tissue and out of the body, without secondary surgery.

Description

TECHNICAL FIELD

[0001] The present application relates to a positioning marker for preoperative biopsy, intraoperative resection and postoperative treatment of breast tissue in the treatment of breast tumors, in particular a positioning marker made of degradable metal and a preparation method thereof. BACKGROUND

[0002] Breast micro lesions cannot be touched clinically due to small lesions, and precise positioning is required during marking after biopsy sampling, during surgery and postoperative treatment to avoid excessive removal of normal tissue during surgery, while ensuring the accuracy of diagnosis and treatment.

[0003] The current positioning marker material is generally titanium, titanium alloy or stainless steel. For breast tumors that need to be surgically removed, the marker will be removed with the lesion and part of the normal tissue. For patients who do not need surgery after biopsy or postoperative treatment, the marker will remain in the body for a long time. The existing positioning marker is usually made of non-degradable metal material, so it may cause foreign body sensation in patients, and it may also move to other parts, and even need a second surgery to remove the marker, which may cause potential risks and hazards to patients.

[0004] Degradable pure magnesium and magnesium alloy biomaterials have good medical prospects. After being implanted into the human body, they react with water in the surrounding tissue and gradually degrade to form magnesium ions or other alloy ions, and are eventually metabolized and excreted from the body. By selecting appropriate alloy elements and controlling the impurity content in the metal, the degradation rate and biological safety of the magnesium alloy can be controlled to avoid premature disappearance of the marker under imaging or introduction of potential biological safety risks due to too rapid degradation. The marker can also be polished or surface coated to adjust the degradation rate of pure magnesium and magnesium alloy materials, improve biocompatibility, and meet the needs of different treatment purposes.

[0005] The inventors have realized this, and have solved the defects of the existing positioning marker by using degradable pure magnesium or magnesium alloy materials for positioning markers. SUMMARY

[0006] In order to solve the problem that the existing positioning marker is made of non-degradable metal or alloy material, which may cause foreign body sensation in patients, may move to other parts, and even need a second surgery to remove the marker, which may cause potential risks and hazards to patients, the main purpose of the present application is to provide a positioning marker made of degradable metal and a preparation method thereof. The positioning marker is made of pure magnesium or magnesium alloy, wherein the total impurity content in the magnesium alloy is less than 0.01% by mass fraction, and the positioning marker is formed by braiding at least three magnesium wires to form a positioning end. The positioning marker can be fixed in the human body with the positioning end, and gradually degrades over time, is absorbed by the surrounding tissue or metabolized out of the body, and does not need to be removed by a second surgery.

[0007] The technical means used in the present application is to provide a positioning marker made of degradable metal, characterized in that it comprises:

[0008] A marker body in the shape of a long strip made of at least three magnesium wires wound together, one end of the marker body forms a winding end wound together, the other end forms a positioning end separated from each other, the positioning end is used to fix to the human tissue.

[0009] Preferably, the positioning marker has a total impurity content of less than 0.01% mass fraction in the pure magnesium wire or magnesium alloy.

[0010] Preferably, the positioning marker has a tensile strength greater than 200 MPa, an elongation at break greater than 10%, and an in vivo degradation rate less than 0.5 mm / year.

[0011] Preferably, the positioning marker has the positioning end of the marker body uniformly distributed at an angle of 120 degrees, and the positioning end and the winding end are pre-bent into a certain arc.

[0012] Preferably, the positioning marker has the positioning end of the marker body outwardly bent about 135 degrees to 165 degrees in the shape of an inverted V-shaped anchor structure relative to the long axis of the marker body.

[0013] Preferably, the positioning marker has the length of the positioning end accounting for one-third to one-fourth of the total length of the marker body.

[0014] The technical means used in the present application is to provide a method for preparing a positioning marker made of degradable metal, comprising the following steps:

[0015] The magnesium wire forming step, the material can be selected from pure magnesium or magnesium alloy material, the total impurity content is less than 0.01% mass fraction, and the deformation process of extrusion, drawing or swaging is adopted to process the wire material with a diameter of 0.5mm to 0.8mm;

[0016] The positioning marker forming step, the wire material formed in the above step is wound together at one end to form a positioning marker, one end of the positioning marker forms a winding end, and the other end is bent inward or outward to form a positioning end at a certain angle;

[0017] The surface treatment step, the positioning marker can remove the surface oxide layer by electrochemical polishing, or prepare a coating on the surface, so as to adjust the degradation rate of the magnesium alloy and improve the biocompatibility.

[0018] Preferably, in the surface treatment step of the preparation method of the positioning marker, electrochemical polishing is used for treatment, the anode is the positioning marker, and the cathode is a stainless steel electrode. After polishing, a bright mirror polishing layer is formed on the surface of the positioning marker, which is cleaned and dried with anhydrous ethanol.

[0019] Preferably, in the surface treatment step of the preparation method of the positioning marker, when a coating layer is prepared for surface treatment, the coating layer is a degradable polymer material or a magnesium oxide, magnesium hydroxide coating layer, or a bioceramic coating layer that does not contain calcium and phosphorus elements.

[0020] More preferably, in the surface treatment step of the preparation method of the positioning marker, a polylactic acid coating layer is prepared, the positioning marker is electrolytically polished in a polishing solution of anhydrous ethanol and perchloric acid, and after polishing, the positioning marker is cleaned and dried with anhydrous ethanol. A polylactic acid coating layer with a thickness of about 10-30 microns is prepared on the surface of the positioning marker by spraying.

[0021] The positioning marker made of degradable metal and the preparation method thereof provided by the present application can achieve the following effects:

[0022] 1. The positioning marker is made of pure magnesium or magnesium alloy, can be developed under ultrasound and X-ray, and the position of the marker can be detected by ultrasound or molybdenum target X-ray during the operation and postoperative treatment process. The surface oxide layer can be removed by electrochemical polishing, or a coating layer can be prepared on the surface to adjust the degradation rate of the magnesium alloy and improve the biocompatibility.

[0023] 2. The positioning marker can be firmly attached to the human tissue with the positioning end, and is not easy to displace. With the subsequent treatment, the positioning marker gradually degrades over time, is absorbed or metabolized by the surrounding tissue and out of the body, without the need for secondary surgery to remove it. The positioning end of the positioning marker can be compressed and deformed and can rebound, and can form a claw or an anchor, which can effectively grab the human tissue without falling off or displacement. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 is the appearance diagram of the first preferred embodiment of the present application.

[0025] Figure 2 is the appearance diagram of the second preferred embodiment of the present application.

[0026] Figure 3 is the flowchart of the preparation method of the positioning marker of the present application. DETAILED DESCRIPTION

[0027] In order to enable a detailed understanding of the technical features and practical effects of the present application, and to implement according to the content of the specification, and further to the preferred embodiments shown in the drawings, detailed description is as follows, please refer to the first preferred embodiment shown in Figure 1 The positioning marker made of degradable metal includes a marker body 10A.

[0028] The length of the marker body 10A is 10-20mm, and the outermost diameter is 1-3mm. The marker body 10A is a long strip structure made of at least three magnesium wires wound by pure magnesium wires or magnesium alloy, and preferably, the diameter of each magnesium wire is 0.5-0.8mm.

[0029] One end of the marker body 10A forms a winding end 11A which is wound with each other, and the winding end 11A can contact with the push rod part of a puncture needle sleeve. The other end of the marker body 10A forms a positioning end 12A which is separated from each other. The claws of the positioning end 12A are evenly distributed with an angle of about 120 degrees between each other. The contact part between the positioning end 12A and the winding end 11A is pre-bent into a certain arc. The length of the positioning end 12A accounts for one-third to one-fourth of the total length of the marker body 10A, so that the positioning end 12A has sufficient length to form a shape which is beneficial to grasping and fixing. The tensile strength of the positioning marker is greater than 200MPa, the elongation after break is greater than 10%, and the in-vivo degradation rate is less than 0.5mm / year.

[0030] The use method of the first preferred embodiment of the present application is as follows. When used, the marker body 10A is placed in a puncture needle sleeve, and the push rod of the puncture needle sleeve can launch the marker body 10A at the positioning point. The positioning end 12A of the marker body 10A is inserted into the breast tissue and fixed under the action of the pushing force. Since the marker body 10A is made of pure magnesium wire or magnesium alloy, it can be developed under ultrasound and X-ray. The position of the marker body 10A can be detected by ultrasound or molybdenum target X-ray during the operation process and postoperative treatment process. With the progress of postoperative treatment, the marker body 10A can gradually degrade over time, and the average in-vivo degradation rate is less than 0.5mm / year, and preferably, the average in-vivo degradation rate is 0.15-0.38mm / year.

[0031] The second embodiment of the present application is as follows Figure 2As shown, it is substantially the same as the first preferred embodiment, the difference is that the shape of the positioning end 12B of the marker body 10B, one end of the marker body 10B is the winding end 11B, the other end is the positioning end 12B, the length of the positioning end 12B accounts for one-third to one-fourth of the total length of the marker body 10B, the second preferred embodiment forms an inverted V-shaped anchor structure by bending the magnesium wires of the positioning end 12B about 135 degrees to 165 degrees outward relative to the long axis of the marker body 10B, wherein the magnesium wires of the positioning end 12B are uniformly distributed at an angle of 120 degrees in space, and the use method is substantially the same as the first preferred embodiment, which will not be described here.

[0032] The application also provides a positioning marker as shown, which is prepared by the following steps: magnesium wire forming S1, positioning marker forming S2, surface treatment S3, etc. Figure 3 The application also provides a positioning marker as shown, which is prepared by the following steps: magnesium wire forming S1, positioning marker forming S2, surface treatment S3, etc.

[0033] The magnesium wire forming step S1: the material can be selected from pure magnesium material, which can be commercially available pure magnesium ingot with a magnesium content of more than 99.99% by mass, and other impurities such as iron, silicon, nickel, copper, aluminum, manganese, zinc impurities with a total content of less than 0.01% by mass, or can be selected from magnesium alloy materials such as pure magnesium zinc calcium alloy, wherein the magnesium content is greater than 99% by mass, the zinc content is about 0.87% by mass, the calcium content is about 0.046%, and other impurities such as aluminum, copper, iron, manganese, nickel, silicon impurities have a total content of about 0.008% by mass. The pure magnesium material does not need to be solid solution heat treated, and the magnesium alloy material needs to be solid solution heat treated, and then deformed by extrusion, drawing, swaging, etc. to obtain a wire material with a tensile strength greater than 200 megapascals and an elongation after fracture greater than 10%. The melting method includes but is not limited to atmosphere protection melting and vacuum melting. The selection of alloying elements fully considers biological safety, and the magnesium alloy material in the application is preferably magnesium zinc alloy, magnesium calcium alloy, and magnesium zinc calcium alloy to avoid or control the content of aluminum, zirconium, manganese, and rare earth elements.

[0034] When the material can be selected from pure magnesium material, the pure magnesium ingot used is extruded into a wire material with a diameter of 1-2 mm after 250 degrees 3 hours of heat preservation, the extrusion ratio is 16:1, and the extrusion rate is 0.5 mm / s. The extruded wire material is further processed into a wire material with a diameter of 0.5 mm by 16-40 passes of hot drawing process. The tensile strength of this wire material can reach 220 megapascals, and the elongation after fracture is 12%.

[0035] When the material is selected from magnesium alloy material, the magnesium alloy ingot used is subjected to 350-degree 16-hour solid solution heat treatment, extruded into a 12-mm-diameter rod at an extrusion temperature of 330 degrees, an extrusion ratio of 17:1, and an extrusion rate of 0.33 mm / s. The extruded rod is subjected to 22-pass rotary swaging to obtain a 0.8-mm-diameter wire. The tensile strength of the wire is 230 MPa, and the elongation after fracture is 11.5%.

[0036] Positioning marker shaping S2: winding together at least three ends of the wire shaped in step S1 using the magnesium wire to form a positioning marker, forming a winding end at one end of the positioning marker, and bending the other end inward or outward at an angle to form a claw-shaped or anchor-shaped positioning end.

[0037] Surface treatment S3: the positioning marker can remove the surface oxide layer through electrochemical polishing or prepare a coating on the surface to adjust the degradation rate of the magnesium alloy and improve biocompatibility.

[0038] Preferably, when the positioning marker is treated on the surface by electrochemical polishing, the anode is the positioning marker, and the cathode is a stainless steel electrode. The polishing temperature is 0 degrees, the voltage is 7 V, the polishing solution used is 8:1 by volume of anhydrous ethanol and perchloric acid, and the additives are 1.5 g / L of citric acid and 0.3 g / L of glucose solution. After 30 seconds of polishing, a bright mirror polished layer is formed on the surface of the positioning marker. After cleaning and drying with anhydrous ethanol, the positioning marker is used for implanting into breast tissue.

[0039] When the positioning marker is treated on the surface by preparing a coating, the coating type is a degradable polymer material or a magnesium oxide and magnesium hydroxide coating, and a bioceramic coating containing calcium and phosphorus elements is avoided to prevent the deposition of calcium and phosphorus elements in the tissue after degradation. The coating preparation methods include but are not limited to self-assembly, coating, alkali heat treatment, and chemical oxidation.

[0040] Preferably, a polylactic acid coating is prepared on the surface of the positioning marker by the following method. The positioning marker is electrolytically polished in a polishing solution of anhydrous ethanol and perchloric acid for 2 minutes at a temperature of 25 degrees and a voltage of 10 V to remove the surface oxide layer and swaging marks. After polishing, the positioning marker is cleaned and dried with anhydrous ethanol, and then a polylactic acid coating with a thickness of about 10-30 microns is prepared on the surface of the positioning marker by spraying.

[0041] The use examples of the preparation method of the positioning marker of the present application are as follows:

[0042] The positioning marker is prepared as shown in Figure 1The positioning marker 10A shown is made from commercially available pure magnesium ingots with a magnesium content greater than 99.99% by mass and a total impurity content of less than 0.01% by mass for iron, silicon, nickel, copper, aluminum, manganese, and zinc. The ingots are extruded into wires with a diameter of 1-2 mm after being held at 250 degrees Celsius for 3 hours, with an extrusion ratio of 16:1 and an extrusion rate of 0.5 mm / s. The extruded wires are further processed into 0.5 mm diameter wires through 16-40 hot drawing processes. These wires have a tensile strength of 220 MPa and an elongation after fracture of 12%.

[0043] The above-mentioned wire is wound into Figure 1 After the positioning marker 10A is shown, its surface is treated with electrochemical polishing: the anode is the marker, and the cathode is a stainless steel electrode. The polishing temperature is 0 degrees Celsius, the voltage is 7V, and the polishing solution used is an 8:1 volume ratio of anhydrous ethanol and perchloric acid, with additives of 1.5 g / L citric acid and 0.3 g / L glucose solution. After 30 seconds of polishing, a bright mirror-polished layer is formed on the surface of the marker. After cleaning with anhydrous ethanol and drying, it is used as a marker for implantation into breast tissue.

[0044] Using production such as Figure 2 The positioning marker 10B shown is made from pure magnesium ingots, zinc granules, and calcium blocks. It is obtained through vacuum melting, resulting in a zinc content of 0.87% by mass, a calcium content of 0.046% by mass, and a total impurity content of 0.0080% by mass for aluminum, copper, iron, manganese, nickel, and silicon. The ingot is then subjected to solution heat treatment at 350 degrees Celsius for 16 hours, followed by extrusion into 12mm diameter bars at an extrusion temperature of 330 degrees Celsius, an extrusion ratio of 17:1, and an extrusion rate of 0.33mm / s. The extruded bars are then subjected to 22 passes of rotary forging to obtain 0.8mm diameter wire. This wire has a tensile strength of 230 MPa and an elongation after fracture of 11.5%.

[0045] The above-mentioned wire is wound into Figure 2 After the positioning marker 10B is shown, a polylactic acid coating is prepared on its surface. The positioning marker 10B is then electropolished for 2 minutes in a mixed polishing solution of anhydrous ethanol and perchloric acid at a temperature of 25 degrees Celsius and a voltage of 10V to remove the surface oxide layer and forging marks. After polishing, it is cleaned with anhydrous ethanol and dried. Then, a polylactic acid coating with a thickness of approximately 10–30 micrometers is prepared on the surface of the marker by spraying.

[0046] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any equivalent embodiment made by a person skilled in the art without departing from the scope of the technical features disclosed in the present invention, using the technical content disclosed in the present invention, shall still fall within the scope of the technical features of the present invention.

Claims

1. A localization marker made of a degradable metal, characterized in that, The application relates to a positioning marker, which comprises the following steps: a magnesium wire forming step, in which pure magnesium or magnesium alloy material with a total impurity content of less than 0.01% by mass is processed into a wire with a diameter of 0.5mm to 0.8mm through an extrusion, drawing or swaging deformation process; a positioning marker forming step, in which the wire formed in the previous step is wound together at one end to form a positioning marker, and the other end is bent inward or outward to form a positioning end with a certain angle; and a surface treatment step, in which the positioning marker is treated through electrochemical polishing to remove the surface oxide layer, or a coating is prepared on the surface to adjust the degradation rate of the magnesium alloy and improve the biocompatibility. The application relates to a positioning marker, which comprises the following steps: a magnesium wire forming step, in which pure magnesium or magnesium alloy material with a total impurity content of less than 0.01% by mass is processed into a wire with a diameter of 0.5mm to 0.8mm through an extrusion, drawing or swaging deformation process; a positioning marker forming step, in which the wire formed in the previous step is wound together at one end to form a positioning marker, and the other end is bent inward or outward to form a positioning end with a certain angle; and a surface treatment step, in which the positioning marker is treated through electrochemical polishing to remove the surface oxide layer, or a coating is prepared on the surface to adjust the degradation rate of the magnesium alloy and improve the biocompatibility. The magnesium wire has a diameter of 0.5mm to 0.8mm. The pure magnesium wire has a magnesium content of greater than 99.99%. The magnesium alloy comprises magnesium, zinc and calcium, and the content of the magnesium is greater than 99%.

2. The positioning marker of claim 1, wherein, The total impurity content of the pure magnesium wire or the magnesium alloy is less than 0.01% by mass.

3. The positioning marker of claim 2, wherein, The tensile strength of the positioning marker is greater than 200MPa, the elongation after fracture is greater than 10%, and the in-vivo degradation rate is less than 0.5mm / year.

4. The positioning marker of claim 1, wherein, The positioning ends of the marker body are uniformly distributed at a maximum included angle of 120 degrees, and the positioning end and the winding end are pre-bent into a certain arc.

5. The positioning marker of claim 1, wherein, The positioning ends of the marker body are outwardly bent by about 135 degrees to 165 degrees into an anchor-shaped structure with a reverse V shape relative to the long axis of the marker body.

6. A method of making the positioning marker of claim 1, wherein, The application relates to a positioning marker, which comprises the following steps: a magnesium wire forming step, in which pure magnesium or magnesium alloy material with a total impurity content of less than 0.01% by mass is processed into a wire with a diameter of 0.5mm to 0.8mm through an extrusion, drawing or swaging deformation process; a positioning marker forming step, in which the wire formed in the previous step is wound together at one end to form a positioning marker, and the other end is bent inward or outward to form a positioning end with a certain angle; and a surface treatment step, in which the positioning marker is treated through electrochemical polishing to remove the surface oxide layer, or a coating is prepared on the surface to adjust the degradation rate of the magnesium alloy and improve the biocompatibility. In the surface treatment step, the positioning marker is treated through electrochemical polishing, the anode is the positioning marker, and the cathode is a stainless steel electrode; after polishing, a bright mirror polishing layer is formed on the surface of the positioning marker, and the positioning marker is cleaned and dried with anhydrous ethanol. In the surface treatment step, the surface treatment is performed by preparing a coating, and the coating is a degradable polymer material or a magnesium oxide, magnesium hydroxide coating, or a bioceramic coating without calcium and phosphorus elements. In the surface treatment step, a polylactic acid coating is prepared, the positioning marker is electrolytically polished in a polishing liquid mixed with anhydrous ethanol and perchloric acid, and after polishing, the positioning marker is cleaned and dried with anhydrous ethanol; a polylactic acid coating with a thickness of about 10-30 microns is prepared on the surface of the positioning marker by spraying.

7. The method of claim 6, wherein the positioning marker is prepared by, ​ 8. The method of claim 6, wherein the positioning marker is prepared by, ​ 9. The method of claim 6, wherein the positioning marker is prepared by, ​

Images