阅读说明：本技术 一种药物膜层可降解的胃肠吻合钉及其制备方法 (Gastrointestinal anastomosis nail with degradable drug film layer and preparation method thereof ) 是由 曹键 程兆俊 叶颖江 姜可伟 杨晓东 白晶 邵怡 于 2020-07-22 设计创作，主要内容包括：本发明公开了一种药物膜层可降解的胃肠吻合钉及其制备方法,胃肠吻合钉由可降解金属钉基体和载药膜层构成。可降解胃肠吻合钉为U型钉,金属钉基体由镁合金丝材制钉获得,所述镁合金丝材具有上下两个平行面；载药膜层由含有药物分子的多孔氧化膜构成。本发明的胃肠吻合钉可有效降低制备和使用过程中断钉的风险,同时配合药物使用,可抑制吻合部位可能残留的肿瘤细胞增殖,降低复发风险或促进吻合口愈合,降低吻合口漏的发生。(The invention discloses a gastrointestinal anastomosis nail with a degradable drug film layer and a preparation method thereof. The degradable gastrointestinal anastomosis nail is a U-shaped nail, and the metal nail substrate is made of magnesium alloy wires which are provided with an upper parallel surface and a lower parallel surface; the drug-loaded membrane layer is composed of a porous oxide membrane containing drug molecules. The gastrointestinal anastomosis nail can effectively reduce the risk of nail breakage in the preparation and use processes, can inhibit the proliferation of tumor cells possibly remaining in an anastomosis part by matching with medicines, reduces the recurrence risk or promotes the healing of an anastomosis, and reduces the occurrence of anastomotic leakage.)

1. The utility model provides a medicine rete degradable stomach intestine anastomosis nail which characterized in that, includes degradable metal nail base member and medicine carrying film layer, and wherein, the surface of metal nail base member is provided with porous oxide film, and medicine carrying film layer deposit is on porous oxide film's surface.

2. The drug film degradable gastrointestinal staple of claim 1, wherein the metal staple substrate is a magnesium alloy substrate.

3. The drug film degradable gastrointestinal anastomosis nail according to claim 1, wherein the porous oxide film has a thickness of 3 to 8 μm and a pore diameter of 50 to 100 nm.

4. The gastrointestinal anastomosis nail with the degradable drug film layer according to claim 1, wherein the drug in the drug-loaded film layer is one of fluorouracil, vascular endothelial growth factor or basic fibroblast growth factor, and drug molecules of the drug are deposited in nano-pores of the oxide film to form the drug-loaded film layer.

5. The gastrointestinal anastomosis nail with the degradable drug film layer according to claim 1, wherein a nail tip of the gastrointestinal anastomosis nail is provided with a bevel, and an included angle X between the bevel and a nail leg is 30-45 degrees.

6. The gastrointestinal staple with a degradable drug film layer according to claim 1, wherein the gastrointestinal staple has an oval-like cross section and is provided with two parallel surfaces, and the central angle Y corresponding to the parallel surfaces is 60-90 degrees.

7. A preparation method of a gastrointestinal anastomosis nail with a degradable drug film layer is characterized by comprising the following steps:

carrying out hot extrusion on the magnesium alloy ingot at the temperature of 360-420 ℃ to obtain a magnesium alloy rod;

performing multi-pass drawing deformation on the obtained magnesium alloy rod, and performing annealing treatment at the temperature of 200-300 ℃ to obtain a magnesium alloy wire with the diameter of 0.2-0.4 mm;

precisely hot rolling the obtained magnesium alloy wire with the reduction proportion of 10-20% of the diameter to obtain the magnesium alloy wire with an ellipse-like section;

carrying out continuous anodic oxidation treatment on the magnesium alloy wire with the similar elliptical section obtained in the step 3);

making nails from the magnesium alloy wire processed in the step 4) to obtain magnesium alloy gastrointestinal anastomosis nails;

cleaning, drying and sterilizing the magnesium alloy gastrointestinal anastomosis nail;

immersing the magnesium alloy gastrointestinal anastomosis nail obtained in the step 6) in a medicinal solution, and taking out, drying and sterilizing after ultrasonic oscillation is carried out for a set time to obtain the gastrointestinal anastomosis nail coated with a medicinal film layer.

8. The method for preparing a gastrointestinal anastomosis nail with a degradable drug film layer according to claim 7, wherein the magnesium alloy ingot does not contain non-human body essential elements, and in the step 1), the extrusion ratio of hot extrusion is 20: 1.

9. The method for preparing a gastrointestinal anastomosis nail degradable by a drug film according to claim 7, wherein the hot rolling temperature in the step 3) is 100 ℃, the processing time per unit length of wire in the anodic oxidation treatment of the step 4) is 10min, and the ultrasonic oscillation time in the step 7) is 1 hour.

10. The method for preparing a gastrointestinal anastomosis nail degradable by a drug film layer according to claim 7, wherein the drug in the drug solution is one of fluorouracil, vascular endothelial growth factor or basic fibroblast growth factor, and the drug molecules are deposited in the nano-micropores of the oxide film formed in the step 4).

Technical Field

The invention relates to the technical field of medical instruments, in particular to a gastrointestinal anastomosis nail with a degradable drug film layer and a preparation method thereof.

Background

Staples are common medical devices used for suturing tissues or organs in clinical place of manual staples, especially in suturing surgery after partial removal of the gastrointestinal tract. At present, the most commonly used anastomotic nail for the anastomat is made of a titanium alloy material, the chemical property of the anastomotic nail is stable, the mechanical property of the anastomotic nail is excellent, but the titanium anastomotic nail cannot be degraded and permanently remained in a body, and certain influence can be caused on the postoperative life of a patient. For example, long-term retention of titanium staples can interfere with medical imaging, cause local inflammatory reactions, and the like.

In the actual postoperative recovery of gastrointestinal surgery, the anastomosis nail only needs to be mechanically supported for 1-2 weeks, long-term retention is not needed, and the gastrointestinal part has low requirements on the mechanical properties of the anastomosis nail. Therefore, the prior art proposes that magnesium staples are adopted to replace titanium staples, and magnesium is used as a major element necessary for a human body, has better biocompatibility, can be gradually degraded in a human body environment, and cannot cause adverse effects after being stored for a long time.

Chinese patent ZL201610592979.5 provides a degradable anastomosis nail and a production process, solves the problems of a titanium anastomosis nail, realizes the self degradation and discharge of the anastomosis nail after operation, but contains silver element in the components, has uncertainty on the influence of a human body, and can cause premature failure due to excessively high degradation rate of the anastomosis nail in acid environments such as stomach and intestine.

Chinese patent 'CN 201911005516.4' provides an in vivo degradable anastomosis nail, the components of which are all essential elements for human body, thereby avoiding the influence of other elements on human body, but no effective measure for improving corrosion resistance is provided, and the risk of premature degradation failure exists in gastrointestinal environment.

Meanwhile, due to the physical and chemical properties of the magnesium alloy, the magnesium alloy wire is easy to break in the bending process. Even if the fracture does not occur, the bent part is easy to degrade preferentially after being implanted into the human body environment due to stress concentration, so that the failure is caused. Also, the gastrointestinal anastomosis is generally performed after the gastrointestinal tumor is removed, so that the staples having the function of inhibiting the proliferation of residual tumor cells or promoting the healing of the anastomotic orifice will be advantageous for the recovery of the patient.

In order to solve the defects in the prior art, the development of the degradable gastrointestinal anastomosis staple with the degradation rate and the functionality meeting the clinical requirements has important significance.

Disclosure of Invention

Aiming at the problems in the prior art, the invention aims to provide a gastrointestinal anastomosis nail with a degradable drug film layer, which has a certain tumor inhibiting effect and meets the requirements of clinical degradation rate and functionality. The invention also aims to provide a preparation method of the staple, which can effectively reduce stress concentration in the preparation and use processes and improve the corrosion resistance of the staple.

In order to achieve the purpose, the gastrointestinal anastomosis nail with the degradable drug film layer comprises a degradable metal nail base body and a drug-loaded film layer, wherein a porous oxide film is arranged on the surface of the metal nail base body, and the drug-loaded film layer is deposited on the surface of the porous oxide film.

Further, the metal nail base body is a magnesium alloy base body.

Furthermore, the thickness of the porous oxide film is 3-8 μm, and the diameter of the film pores is 50-100 nm.

Furthermore, the drug in the drug-loaded membrane layer is one of fluorouracil, vascular endothelial growth factor or basic fibroblast growth factor, and drug molecules of the drug-loaded membrane layer are deposited in nano-pores of the oxide membrane to form the drug-loaded membrane layer.

Furthermore, the nail tip of the gastrointestinal anastomosis nail is provided with an inclined plane, and the included angle X between the inclined plane and the nail leg is 30-45 degrees.

Furthermore, the section of the gastrointestinal anastomosis nail is similar to an ellipse, and is provided with two parallel surfaces, and the central angle Y corresponding to the parallel surfaces is 60-90 degrees.

A preparation method of the gastrointestinal anastomosis nail with the degradable drug film layer comprises the following steps:

1) carrying out hot extrusion on the magnesium alloy ingot at the temperature of 360-420 ℃ to obtain a magnesium alloy rod;

2) performing multi-pass drawing deformation on the obtained magnesium alloy rod, and performing annealing treatment at the temperature of 200-300 ℃ to obtain a magnesium alloy wire with the diameter of 0.2-0.4 mm;

3) precisely hot rolling the obtained magnesium alloy wire with the reduction proportion of 10-20% of the diameter to obtain the magnesium alloy wire with an ellipse-like section;

4) carrying out continuous anodic oxidation treatment on the magnesium alloy wire with the similar elliptical section obtained in the step 3);

5) making nails from the magnesium alloy wire processed in the step 4) to obtain magnesium alloy gastrointestinal anastomosis nails;

6) cleaning, drying and sterilizing the magnesium alloy gastrointestinal anastomosis nail;

7) immersing the magnesium alloy gastrointestinal anastomosis nail obtained in the step 6) in a medicinal solution, and taking out, drying and sterilizing after ultrasonic oscillation is carried out for a set time to obtain the gastrointestinal anastomosis nail coated with a medicinal film layer.

Further, in the step 1), the extrusion ratio of hot extrusion is 20: 1.

Further, in the step 3), the rolling temperature of the hot rolling is 100 ℃.

Further, in the anodizing treatment of the step 4), the treatment time per unit length of the wire rod is 10 min.

Further, the ultrasonic oscillation time in the step 7) is 1 hour.

Further, the magnesium alloy ingot does not contain elements which are not essential to human bodies.

Further, the drug in the drug solution is one of fluorouracil, vascular endothelial growth factor or basic fibroblast growth factor, and the drug molecules are deposited in the nano-micropores of the oxide film formed in step 4).

The invention has the following beneficial effects:

(1) the magnesium alloy wire material is an ellipse-like wire material, so that the problem of stress concentration at a bent part when the existing round wire is used for making nails and performing anastomosis is greatly reduced, the nail breakage phenomenon in the preparation or use process and the problem of preferential degradation of the stress concentration part after implantation are avoided, and the effective service cycle of the anastomosis nails is ensured.

(2) The invention adopts a continuous anodic oxidation process, so that the surface of the anastomosis nail is provided with a uniform oxide film, the integral corrosion resistance can be effectively improved, the rapid degradation in the gastrointestinal environment is avoided, and meanwhile, a storage space is provided for the medicine.

(3) The drug-loaded film layer can be gradually degraded to release drugs after being implanted into a human body, and has a certain inhibiting effect on residual tumor cells after operation or can promote healing of anastomotic stoma according to different drugs selected by the film layer.

(4) The magnesium alloy containing no non-human body essential elements is used as the raw material of the anastomosis nail, has excellent biocompatibility and safety, can be automatically degraded and discharged in the human body environment, and solves the problem and negative influence of long-term retention of the titanium alloy anastomosis nail.

Drawings

FIG. 1 is a schematic view of an intestinal staple construction;

FIG. 2 is a schematic cross-sectional view of an intestinal staple;

fig. 3 is a schematic view of the micro-morphology of the drug-loaded film layer of the gastrointestinal anastomosis nail.

Labeled as:

the nail comprises a metal nail base body 1, a medicine carrying film layer 2, an inclined plane 3 and a parallel plane 4.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.

The following detailed description of embodiments of the invention refers to the accompanying drawings. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.

As shown in fig. 1, fig. 2 and fig. 3, the gastrointestinal anastomosis nail with a degradable drug film layer comprises a degradable metal nail base body 1 and a drug-loaded film layer 2, wherein a porous oxide film is arranged on the surface of the metal nail base body, and the drug-loaded film layer is deposited on the surface of the porous oxide film.

In the invention, the gastrointestinal anastomosis nail is a U-shaped nail, and the whole gastrointestinal anastomosis nail is of a U-shaped structure. The metal nail matrix is a magnesium alloy matrix, and the components of the metal nail matrix do not contain elements which are not necessary for a human body except inevitable impurities. The porous oxide film arranged on the surface of the metal nail substrate is a nano film, the thickness of the porous oxide film is 3-8 mu m, and the diameter of the film hole is 50-100 nm. The surface of the membrane is provided with nano micropores, so that the deposition of drug molecules can be facilitated to form a drug-loaded membrane layer.

The drug in the drug-loaded membrane layer 2 is one of fluorouracil, vascular endothelial growth factor or basic fibroblast growth factor, and drug molecules of the drug are deposited in nano-membrane pores of the oxide membrane to form the drug-loaded membrane layer 2.

In order to facilitate use, the nail tip of the gastrointestinal anastomosis nail is provided with an inclined surface 3, the included angle X between the inclined surface 3 and the nail leg is 30-45 degrees, and the arrangement of the inclined surface 3 is beneficial to puncturing human muscle or other tissues so as to enable a wound to be anastomosed and fixed. Meanwhile, the section of the gastrointestinal anastomosis nail is set to be similar to an ellipse, the gastrointestinal anastomosis nail is provided with two parallel surfaces 4, the central angle Y corresponding to the parallel surfaces is 60-90 degrees, and the problem of stress concentration caused by bending during nail making and operation can be effectively reduced by arranging the two parallel surfaces 4.