An embolic coil made of shape memory gel based on light curing

Abstract

The present invention discloses an embolic spring coil prepared based on a photocurable shape memory gel, and the preparation process thereof comprises: (1) preparing a photocurable gel precursor solution: the photocurable gel precursor solution comprises, by weight, 45 to 55 parts of 4-acryloylmorpholine (ACMO), 7 to 17 parts of benzyl methacrylate (BMA), 10 to 15 parts of tert-butyl acrylate (tBA), 0.5 to 1 part of a photoinitiator, and 20 to 30 parts of a cross-linking agent; (2) preparing an embolic spring coil mold, embedding a capillary silicone tube into a groove of the embolic spring coil mold, so that the capillary silicone tube matches the embolic spring coil mold; then injecting the photocurable gel precursor solution obtained in step (1) into the capillary silicone tube, cross-linking and curing under ultraviolet light, and obtaining the embolic spring coil after peeling. The embolic spring coil provided by the present invention has good mechanical properties, adhesion and shape memory effect.

Description

Technical Field

[0001] The invention relates to the technical field of medical devices, and in particular to an embolic spring coil prepared based on a light-cured shape memory gel. Background Art

[0002] Aneurysm is a hidden and fatal vascular disease, and its correct identification is of great significance for treatment. In recent decades, traditional open surgery has been transformed into minimally invasive surgery to treat such vascular diseases. Under the guidance of interventional imaging equipment, endovascular embolization can be an effective means of treating aneurysms. However, since aneurysms have different shapes and sizes, existing metal coils with fixed sizes are difficult to adapt to all types of aneurysms. Therefore, there is an increasing demand for related biomaterials and coil production for personalized aneurysm embolization.

[0003] For complex malformed aneurysms, liquid embolic agents can be used as an alternative to solid coils, such as ethylene-vinyl alcohol copolymer (EVOH) in dimethyl sulfoxide (DMSO) solution (Onyx), which is approved by the US Food and Drug Administration for aneurysm embolization. However, it has safety risks in use, has certain cytotoxicity, and has a complicated preparation procedure. Hydrogel-based coils are considered to be a more biocompatible solution. For example, shear-thinning nanocomposite hydrogel coils made of gelatin and silicate nanoparticles exhibit hemostatic activity similar to that of metal coils. However, due to its shear-thinning properties, it can only weakly adhere to vascular tissue, which may cause unnecessary migration under high-speed blood flow impact. Alginate-based hydrogels based on silk and tantalum nanopowders also have similar problems. At the same time, it is reported that alginate hydrogels and many photocurable hydrogels with high water content are fragile and brittle because their mechanical moduli are usually only a few hundred to a few thousand Pa, which makes them difficult to pre-molded into complex 3D structures. For example, CN116392643A discloses a degradable hydrogel spring coil based on zinc-iron-copper alloy, which has better mechanical properties than existing gel spring coils, and also improves the degradability and biocompatibility of the spring coil itself, but its complicated production steps cannot meet the needs of personalized customization. CN218754163U discloses a metal spring coil, which uses a rod-shaped object as a support and is wound to make a metal wire. This method is not suitable for materials with low toughness, which are prone to breakage and bending when winding and bending, or cannot be applied to materials in the original liquid / sol state. Summary of the invention

[0004] In view of the technical problem that the fixed-shape coils in the prior art cannot fully adapt to complex application scenarios, the present invention provides an embolic coil prepared by a shape memory gel based on light curing. Compared with the existing hydrogel coils, the embolic coils provided by the present invention have better mechanical properties and adhesion; compared with metal coils, there is no need to use the rigidity of metal to maintain the shape, nor is there a need to use a support winding method to prepare samples, and no metal artifacts will be caused in postoperative CT imaging, thereby improving image quality.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] In one aspect, the present invention provides an embolic spring coil prepared based on a light-cured shape memory gel, wherein the preparation process of the embolic spring coil comprises the following steps:

[0007] (1) preparing a photocurable gel precursor solution: the photocurable gel precursor solution comprises, by weight, 45 to 55 parts of 4-acryloylmorpholine (ACMO), 7 to 17 parts of benzyl methacrylate (BMA), 10 to 15 parts of tert-butyl acrylate (tBA), 0.5 to 1 part of a photoinitiator and 20 to 30 parts of a crosslinking agent;

[0008] (2) preparing an embolization spring coil mold, embedding a capillary silicone tube into the groove of the embolization spring coil mold, so that the capillary silicone tube matches the embolization spring coil mold; then injecting the photocurable gel precursor solution obtained in step (1) into the capillary silicone tube, cross-linking and curing under ultraviolet light, and obtaining the embolization spring coil after peeling.

[0009] As a preferred embodiment, the mass fraction of 4-acryloylmorpholine (ACMO) is 50 parts;

[0010] Preferably, the mass fraction of benzyl methacrylate (BMA) is 12.5 parts;

[0011] Preferably, the mass fraction of tert-butyl acrylate (tBA) is 11.5 parts.

[0012] As a preferred embodiment, in step (1), the photoinitiator is diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO).

[0013] As a preferred embodiment, in step (1), the crosslinking agent is trifunctional aliphatic polyurethane acrylate (TAPUA);

[0014] Preferably, the mass fraction of the cross-linking agent is 25 parts.

[0015] As a preferred embodiment, in step (1), the photocurable gel precursor solution further comprises 20 to 40 parts of barium sulfate powder; in the technical solution of the present invention, the addition of barium sulfate can be used for X-ray development.

[0016] As a preferred embodiment, in step (1), the preparation method of the photocurable gel precursor solution is: mixing the components evenly to obtain the photocurable gel precursor solution.

[0017] In certain specific embodiments, in step (2), the capillary silicone tube is a commercial capillary silicone tube with an inner diameter of 0.3 mm and an outer diameter of 0.8 mm. In the technical solution of the present invention, the shape and size of the embolization spring coil mold are customized according to the usage scenario through 3D printing technology, and it is used in conjunction with the capillary silicone tube to prepare a spring coil with a fine structure and maintain the same wire diameter as the capillary silicone tube, which is helpful for the introduction of the microcatheter during surgery.

[0018] As a preferred embodiment, in step (2), the wavelength of the ultraviolet light is 365-405 nm;

[0019] Preferably, the cross-linking and curing time is 2 to 5 seconds.

[0020] In the technical solution of the present invention, the embolic spring coil has a permanent shape. At room temperature of about 20°C, it can form a temporary shape under the action of external force, such as being stretched into a linear shape; when triggered by external thermal stimulation (about 38°C, i.e., human body temperature), it can return to a permanent shape.

[0021] In another aspect, the present invention provides an embolic spring coil obtained by the above preparation method.

[0022] The above technical solution has the following advantages or beneficial effects:

[0023] The invention uses 4-acryloylmorpholine (ACMO), benzyl methacrylate (BMA) and tert-butyl acrylate (tBA) as monomers to form a gel skeleton structure of an embolization spring coil through a polymerization reaction.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] (1) The embolic coil provided by the present invention has a gel curing reaction that can be completed within a few seconds under ultraviolet light irradiation, and the preparation method is simple and efficient;

[0026] (2) The preparation method provided by the present invention can be combined with 3D printing to customize the shape and size, adapting to a variety of complex usage scenarios, and its wire diameter can be as low as 0.3 mm, adapting to a variety of commercial microcatheters, which has unique advantages in the use scenario of complex aneurysms and reduces the surgical risks caused by shape mismatch during embolization;

[0027] (3) The embolic coil provided by the present invention triggers the shape memory effect at body temperature and has a rapid response time, which can be completed within a few seconds. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a flow chart of the preparation of the embolic coil in Example 1 of the present invention.

[0029] Figure 2 Schematic diagram of the shape memory of the embolic spring coil in Example 1 of the present invention. DETAILED DESCRIPTION

[0030] The following embodiments are only some embodiments of the present invention, rather than all embodiments. Therefore, the detailed description in the embodiments of the present invention provided below is not intended to limit the scope of the present invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work belong to the protection scope of the present invention.

[0031] In the present invention, unless otherwise specified, all equipment and raw materials can be purchased from the market or are commonly used in the industry. The methods in the following embodiments are all conventional methods in the art unless otherwise specified.

[0032] Embodiment 1:

[0033] like Figure 1 As shown, this embodiment provides an embolic spring coil prepared based on a light-cured shape memory gel, and the preparation process includes the following steps:

[0034] (1) weighing 5 g of 4-acryloylmorpholine (ACMO), 1.25 g of benzyl methacrylate (BMA), 1.15 g of tert-butyl acrylate, 2.5 g of trifunctional aliphatic polyurethane acrylate (TAPUA) and 0.5 g of diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), and mixing them uniformly to form a gel precursor solution;

[0035] (2) Based on the shape and size of the aneurysm analyzed after preoperative imaging, the corresponding Omega-shaped coil mold is designed, the corresponding mold is 3D printed, and then a capillary silicone tube with an inner diameter of 0.3 mm and an outer diameter of 0.8 mm is embedded in the groove of the mold so that the capillary silicone tube has the same shape as the groove of the mold;

[0036] (3) injecting the glue precursor solution into the capillary silicone tube, and then irradiating it under a UV lamp with a wavelength of 405 nm and a power of 50 W for 5 seconds for cross-linking and curing;

[0037] (4) After the gel is formed, the capillary silicone tube is stretched into a straight line, and then the formed gel filaments are peeled off from the capillary silicone tube with a scalpel to obtain the embolization spring coil.

[0038] The wire diameter of the embolic spring coil prepared in this embodiment is 0.3 mm, and its shape memory process is as follows: Figure 2 As shown: The spring coil has a permanent shape as shown in the figure. Under the action of external force at 20°C, it can be stretched into a linear shape, and under thermal stimulation at 38°C, it can spontaneously recover from the linear shape to the permanent shape.

[0039] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An embolic coil prepared based on a light-cured shape memory gel, characterized in that: The preparation process of the embolic coil comprises the following steps: (1) Preparing a photocurable gel precursor solution: The photocurable gel precursor solution comprises, by weight, 45-55 parts of 4-acryloylmorpholine, 7-17 parts of benzyl methacrylate, 10-15 parts of tert-butyl acrylate, 0.5-1 parts of a photoinitiator and 20-30 parts of a crosslinking agent; the photoinitiator is diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide; the crosslinking agent is trifunctional aliphatic polyurethane acrylate; (2) preparing an embolic spring coil mold, embedding a capillary silicone tube into the groove of the embolic spring coil mold, so that the capillary silicone tube matches the embolic spring coil mold; then injecting the photocurable gel precursor solution obtained in step (1) into the capillary silicone tube, cross-linking and curing under ultraviolet light, and obtaining the embolic spring coil after peeling.

2. The embolic coil according to claim 1, characterized in that: In step (1), the mass fraction of the 4-acryloylmorpholine is 50 parts.

3. The embolic coil according to claim 1, characterized in that: In step (1), the mass fraction of benzyl methacrylate is 12.5 parts.

4. The embolic coil according to claim 1, characterized in that: In step (1), the mass fraction of tert-butyl acrylate is 11.5 parts.

5. The embolic coil according to claim 1, characterized in that: In step (1), the mass fraction of the cross-linking agent is 25 parts.

6. The embolic coil according to claim 1, characterized in that: In step (1), the photocurable gel precursor solution further includes 20 to 40 parts of barium sulfate powder.

7. The embolic coil according to claim 1, characterized in that: In step (1), the preparation method of the photocurable gel precursor solution is: mixing the components evenly to obtain the photocurable gel precursor solution.

8. The embolic coil according to claim 1, characterized in that: In step (2), the wavelength of the ultraviolet light is 365-405 nm.

9. The embolic coil according to claim 1, characterized in that: In step (2), the cross-linking and curing time is 2 to 5 s.

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