POLYMER-BASED ARTERIAL HEMANGIOMA EMBOLIZATION DEVICE, MANUFACTURING METHOD AND APPLICATION OF SAME

Abstract

A polymer-based embolization device comprises a helix constructed by a linear structure. The linear structure is either a fibrous structure or composed of an A structure (1) and a B structure (2), wherein the A structure (1) is a protrusion on the linear structure and the B structure (2) is a pillar-shaped structure positioned between two A structures (1) for connecting the two A structures (1). The embolization device adopts a linear structural design and is integrally manufactured using a polymer material via a four-axis rapid forming system or via a compression method, thereby addressing issues of generation of image artifacts during CT and magnetic resonance imaging. The combination of design, material, and technique of the invention provides the device with improved flexibility and embolus formation, and can satisfy different clinical requirements. When a biodegradable macromolecular material is selected for manufacturing, blood vessel obstruction caused by implant degrading can be avoided, allowing the blood vessel to return to a normal structural state.

Claims

1. A polymer-based embolization device, the embolization device being a helix constructed by a linear structure, wherein the linear structure is either a fibrous structure or composed of a structure A and a structure B, the structure A is a protrusion on the linear structure and the structure B is a pillar-shaped structure positioned between two A structures for connecting the two A structures.

2. The embolization device according to claim 1, wherein the diameter (D) of the helix is 1-40 mm, preferably 3-30 mm.

3. The embolization device according to claim 1, wherein the A structure is spherical, cylindrical, square, cuboid and/or conical, preferably spherical; preferably, the cross section of the structure A is circular, elliptical, rectangular and/or triangular; and the cross section of the structure B is circular, elliptical and/or oval.

4. The embolization device according to claim 1, wherein an average diameter or length of the cross-section of the A structure is 0.05-6 mm, an average diameter of the cross-section of the B structure is 0.05-6 mm, and a length of the connecting axis is 0.05-6 mm.

5. The embolization device according to claim 1, wherein the embolization device is made of a raw material comprising a biodegradable thermoplastic polymer and/or a non-degradable thermoplastic polymer.

6. The embolization device according to claim 5, wherein the biodegradable thermoplastic polymer is selected from the group consisting of polylactic acid, polyethylene glycol-polyglycolic acid, polycaprolactone, polyethylene glycol, polyanhydrides, polyhydroxyalkanoates, polydioxanone, polyiminocarbonates, polyfumaric acid, and copolymers or mixtures thereof; the non-degradable thermoplastic polymers comprise polyethylene terephthalate, nylon, polypropylene, polyethylene, polyurethane, and copolymers or mixtures thereof.

7. The embolization device according to claim 5, wherein the raw material further comprises a radiopaque additive; preferably, the radiopaque additive is one or more selected from the group consisting of calcium phosphate as well as iodine compound, barium sulfate, zirconium dioxide and strontium halide used as contrast agents.

8. The embolization device according to claim 1, wherein the surface or a part of the surface of the embolization device is wrapped with polymer cilia.

9. The embolization device according to claim 1, wherein the surface of the embolization device is modified with gelatin, collagen, chitosan, alginate or a material containing an embolizing agent.

10. A method for manufacturing a polymer-based embolization device of claim 1, the method being carried out using a four-axis rapid forming system as a manufacturing equipment, wherein the four-axis rapid forming system comprises: (i) a base; (ii) a three-axis X-Y-Z positioning system connected to the base, the X-Y-Z positioning system defining X, Y, and Z directions, respectively; (iii) a dispensing system mounted on the X-Y-Z positioning system and movable by the X-Y-Z positioning system, the dispensing system comprising an extrusion head; (iv) a fourth-axis system connected to the base, located below the extrusion head and including a rotating rod connected to the base, wherein the rotating rod is rotatable in a clockwise or an anti-clockwise direction around its central axis and the central axis of the rotating rod is parallel to the Y axis; and (v) a computer controlled system which can precisely control the X-Y-Z positioning system according to a set program so as to precisely control the movement of the extrusion head of the dispensing system in the X, Y, Z directions and precisely control the rotation of the rotating rod of the fourth-axis system around the central axis thereof; and the method comprises the steps of: 1) preparing a mold or a rotation rod which has a specific surface contour in accordance with the structure of the embolization device to be manufactured; 2) designing a computer program for a pattern of depositing raw materials for preparing the embolization device; 3) g attach the mold to the rotating fourth-axis of the four-axis rapid forming system so that the mold can rotate clockwise or anti-clockwise along with the rotation of the fourth-axis of the four-axis system under the control of a computer control system; and adding raw materials for preparing the embolization device into the dispensing system; and 4) controlling the X-Y-Z positioning system and the fourth-axis system by a computer controlled system according to the computer program designed in step 2), enabling the dispensing system to accurately extrude raw materials according to a pre-designed deposition pattern so that the extruded raw materials deposit onto a specific position of a rotatable mold on the fourth axis or deposit directly on the rotating rod, thereby obtaining the embolization device.

11. The method according to claim 10, the method for making the polymer-based embolization device can be a extrusion or an compress molding.

12. The method according to claim 11, wherein when the linear structure is fibrous, the extrusion molding process includes: melt extruding a polymer through an extrusion device into a polymer filament with a diameter of 0.05-6 mm, spirally winding the polymer filament onto a rod-shaped support, and carrying out heat treatment to fix the shape to obtain the embolization device; when the linear structure is composed of both a structure A and a structure B, the extrusion molding method includes: firstly melt extruding a polymer through an extrusion device into a polymer filament with a diameter of 0.05-6 mm, putting the polymer filament into a mold having an inner cavity with a required arrangement of structure A and B structure at a molding temperature, then carrying out closed mold pressurization to shape and solidify the polymer filament, spirally winding the polymer filament on a rod-shaped support, and carrying out heat treatment to fix the shape to obtain a polymer helix having the desired arrangement of structures A and B, i.e., the embolization device.

13. (canceled)

14. A polymer-based embolization device, the embolization device being a helix constructed by a linear structure, wherein the linear structure is either a fibrous structure or composed of both a structure A and a structure B, the structure A is a protrusion on the linear structure and the structure B is a pillar-shaped structure positioned between two structures A for connecting the two structures A, made by the method comprising: 1) preparing a mold in accordance with the structure of the embolization device to be manufactured; 2) designing a program for a pattern of depositing raw materials for preparing the embolization device by using a computer; 3) attaching the mold to the rotating rod of the fourth-axis system of the four-axis rapid forming system so that the mold can rotate clockwise and anti-clockwise along with the rotating rod of the fourth-axis system under the control of a computer control system; and adding raw materials for preparing the embolization device into the dispensing system; and 4) controlling the X-Y-Z positioning system and the fourth-axis with a computer control system according to the program designed in step 2), enabling the dispensing system to accurately extrude raw materials according to a pre-designed deposition pattern so that the extruded raw materials deposit at a specific position of a rotatable mold on the fourth axis or deposit directly onto the rotating rod, thereby obtaining the embolization device.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0056] For a more complete understanding of the features and advantages of the present invention, reference is now made to the detailed description of the invention along with the accompanying figures and in which:

[0057] FIG. 1 is a schematic view showing a primary structure of the embolization device of the present invention;

[0058] FIG. 2 is a schematic view showing a secondary structure of the embolization device of the present invention;

[0059] FIG. 3 is a schematic view showing the polymer-based embolization device of the present invention in use;

[0060] FIG. 4 is a photograph of the final configuration of the embolization device made in Example 1.

DETAILED DESCRIPTION OF THE INVENTION

[0061] The invention is further illustrated by the following examples, which are intended to be illustrative only and are in no way intended to limit the scope of the invention.

Example 1

[0062] The example provides a polymer-based embolization device used in peripheral embolization surgery and a manufacturing method thereof, the method comprising:

[0063] 1) preparing a mold according to a structure of the embolization device to be manufactured;

[0064] 2) designing a program for preparing a raw material deposition pattern of the embolization device by using a computer;

[0065] 3) fixing the mold at the rotating rod of the fourth-axis system of the four-axis rapid forming system, so that the mold can rotate forwards or backwards along with the rotating rod of the fourth-axis system under the control of a computer control system; adding raw materials for manufacturing the embolization device into the dispensing system; and

[0066] 4) controlling the X-Y-Z positioning system and the fourth-axis system by means of a computer control system according to the program designed in the step 2), enabling the dispensing system to accurately extrude raw materials according to a pre-designed deposition pattern so that the extruded raw materials deposit at a specific position of a rotatable mold on the fourth axis or deposit directly on the rotating rod, thereby finishing the manufacturing of the main body of the embolization device of the invention; and placing in 5 mg/ml collagen type I solution for 1 minute, taking out and washing the surface for 2 to 3 times with PBS solution and then drying in a vacuum oven.

[0067] A photograph of the embolization device manufactured in this example is shown in FIG. 4. The embolization device released itself in a free space as spherical, and released in a limited space according to the spatial pattern to form randomly; the raw material used was a mixture of polyethylene terephthalate and contrast agent powder; and the effect of the type I collagen was mainly to modify the surface of the material so as to promote thrombosis in tumors and endothelialization at tumor mouths. The embolization device manufactured in this example has a spherical A structure with a cross-sectional diameter of 0.9 mm, and a B structure with a cross-sectional diameter of 0.5 mm and a length of 0.5 mm.

[0068] The device may be used to block blood flow in the peripheral vasculature during embolization procedures and may be delivered through a 5 F catheter.

Example 2

[0069] The example provides a degradable polymer-based embolization device used in vascular embolization surgery and a preparation method thereof, the method comprising:

[0070] 1) preparing a mold according to a structure of the embolization device to be manufactured;

[0071] 2) designing a program for preparing a raw material deposition pattern of the embolization device by using a computer;

[0072] 3) fixing the mold at the rotating rod of the fourth-axis system of the four-axis rapid forming system, so that the mold can rotate forwards or backwards along with the rotating rod of the fourth-axis system under the control of a computer control system; adding raw materials for manufacturing the embolization device into the dispensing system; and

[0073] 4) controlling the X-Y-Z positioning system and the fourth-axis system by means of a computer control system according to the program designed in the step 2), enabling the dispensing system to accurately extrude raw materials according to a pre-designed deposition pattern so that the extruded raw materials deposit at a specific position of a rotatable mold on the fourth axis or deposit directly on the rotating rod, thereby finishing the manufacturing of the main body of the embolization device of the invention; and then manually weaving micro-cilia (diameter 10 m or so) on the device surface, where the micro-cilia were made by stretching monofilament fibers.

[0074] The embolization device released itself in a free space as spherical, and released in a limited space according to the spatial pattern to form randomly; the raw material used was a mixture of PCL and contrast agent powder. The micro-cilia were made by stretching PCL fibers and wound on the surface of the device to improve the roughness of the surface, so that blood coagulation could be promoted, and thrombosis could be more easily induced. The embolization device manufactured in this example has a spherical A structure with a cross-sectional diameter of 0.25 mm, and a B structure with a cross-sectional diameter of 0.15 mm and a length of 0.15 mm.

[0075] The device may be used to block blood flow in the vasculature during embolization procedures and may be delivered through a 2 F catheter.

Example 3

[0076] The example provides a polymer-based embolization device used in vascular embolization surgery and a preparation method thereof, the method comprising:

[0077] 1) preparing a mold with a bead-like groove;

[0078] 2) preparing polymer fiber filaments with the diameter of 0.2 mm by adopting a conventional hot melting extrusion technology;

[0079] 3) treating the polymer fiber filaments with an iopamidol solution to obtain polymer fiber filaments containing iopamidol; and

[0080] 3) placing the polymer fiber filament containing iopamidol into the mold at a forming temperature, closing the mold and pressurizing to form and solidify the polymer fiber filament, removing the polymer fiber filament from the mold to obtain the polymer fiber filament with a bead-like structure, spirally winding the bead-like polymer fiber filament on a rod-shaped support, and carrying out heat treatment to fix the shape to obtain a polymer helix with the bead-like structure; and then manually weaving micro-cilia (diameter 10 m or so) on the device surface, where the micro-cilia were made by stretching monofilament fibers.

[0081] The embolization device released itself in a free space as a helix coil, and released in a limited space according to the spatial pattern to form randomly; and the used polymer was PCL or polyethylene terephthalate. The micro-cilia were made by stretching polymer fibers and wound on the surface of the device to increase the roughness of the surface, so that blood coagulation could be promoted, and thrombosis could be more easily induced. The embolization device manufactured in this example has a spherical A structure with a cross-sectional diameter of 0.2 mm, and a B structure with a cross-sectional diameter of 0.1 mm and a length of 0.1 mm.

[0082] The device may be used to block blood flow in the vasculature during embolization procedures and may be delivered through a 2 F catheter.