WO2017061616A1

WO2017061616A1 - Bioabsorbable staple

Info

Publication number: WO2017061616A1
Application number: PCT/JP2016/080002
Authority: WO
Inventors: 広夫内田; 顕成檜; 花田　幸太郎
Original assignee: 国立大学法人名古屋大学; 国立研究開発法人産業技術総合研究所
Priority date: 2015-10-09
Filing date: 2016-10-07
Publication date: 2017-04-13
Also published as: JPWO2017061616A1; JP6823321B2

Abstract

Provided is a bioabsorbable staple (1) that is less likely to break when kept inside a living body. The staple (1) is made of a biodegradable metal material. The staple (1) comprises: two insertion parts (2) to be inserted into biological tissue; a bridge part (3) that extends over a site to be sutured; and connection parts (4) connecting the respective insertion parts (2) and the bridge part (3). The connection part (4) is formed in a shape including a curved part having no bend point. At least a portion of the bridge part (3) is located on the tip-end side of the insertion parts (2) than a line connecting the respective top parts (41, 41) of the connection parts (4).

Description

Bioabsorbable staple

The present invention relates to a bioabsorbable staple, and more particularly, to a staple that has a shape that does not have a bending point so that it is less likely to break due to corrosion when placed in a living body, and a suturing effect can be obtained over a long period of time. .

In surgical operations, thread has been used as a means for suturing wounds. However, in recent years, sutures can be sutured more quickly and easily. Further, postoperative suture failure is almost the same as that of hand stitching. As an alternative, staples are used. Staples are used in various surgical sites such as skin, blood vessels, intestinal tract, bones, muscles, and organs. In addition, it is used by a method depending on the suture location, such as puncturing and stitching from outside the body into the skin, or indwelling in the living body after suturing a blood vessel, intestinal tract, organ or the like in the living body.

Among the staples described above, staples that are indwelled in a living body include metals such as stainless steel, titanium, tantalum, and the like, and amorphous diamond-like carbon films formed on the surfaces of the metals, which are insoluble in the human body. (See Patent Document 1). In addition, a staple made of a metal material soluble in the human body in order to close a wound on the skin, fascia or internal organ is also known (see Patent Document 2).

JP-A-5-154189 Japanese Patent No. 5036697

As described in

Patent Documents

1 and 2, both insoluble and soluble in vivo are known as staples to be placed in the living body. By the way, since an insoluble material becomes a foreign body for a living body, when an insoluble material is left in the living body for a long time after the operation, an intractable infection may occur. For this reason, it is considered that the staples placed in the living body are desirably made of a material that is soluble in the living body. However, in actual medical practice, most of the staples placed in the living body are made of an insoluble material such as titanium, and there is a problem that staples made of a soluble material are hardly used.

The present invention has been made in order to solve the above-mentioned problems. As a result of extensive research, (1) when a staple made of a biodegradable metal material is placed in a living body, it is sutured from outside the living body. Unlike the case, the entire staple is gradually corroded by in vivo components. At that time, since the force for suturing the living tissue concentrates on the bent portion of the staple, it is easy to break at the bent portion. By forming the connecting part for connecting the parts into a shape including a curved part that does not have a bending point, the force for suturing the living tissue is dispersed and the force does not concentrate at a specific location, so the staple breaks (3) By forming at least a part of the erection part so as to be positioned on the distal end side of the insertion part with respect to the line connecting the top part and the top part of the connection part, two stitches are formed. It was newly found that the sutured part can be brought into close contact by being pressed down by the installation part in addition to the entrance part.

That is, an object of the present invention is to provide a bioabsorbable staple that is difficult to break when placed in a living body.

The present invention relates to the following bioabsorbable staples.

(1) A staple formed of a biodegradable metal material,
The staple includes two insertion portions to be inserted into a living tissue, an erection portion that straddles a suture site, and a connection portion that connects the insertion portion and the erection portion,
The connecting portion is formed in a shape including a curved portion having no bending point, and
A bioabsorbable staple in which at least a part of the erection part is located on a distal end side of the insertion part from a line connecting the top part and the top part of the connection part.
(2) The bioabsorbable staple according to (1), wherein all of the erection portions are located on a distal end side of the insertion portion with respect to a line connecting the top portions of the connection portions.
(3) The bioabsorbable staple according to (1) or (2), wherein the most curved portion of the connecting portion has a radius of curvature of 0.275 mm or more.
(4) The bioabsorbable staple according to any one of (1) to (3), wherein the biodegradable metal material is selected from an alloy containing magnesium as a main component.
(5) The bioabsorbable staple according to any one of (1) to (4), wherein the biodegradable metal material is coated with a biodegradable resin.

Since the connecting portion of the bioabsorbable staple is formed in a shape including a curved portion having no bending point, it is difficult to break even if it is placed in the living body. Therefore, the stitched portion can be adhered over a long period of time.

Further, since the connecting portion of the staple is formed in a shape including a curved portion that does not have a bending point, at least a part of the erection portion is arranged on the distal end side of the insertion portion with respect to a line connecting the top portion and the top portion of the connecting portion. It can form so that it may be located in. When stitched with the staple, the stitched portion can be brought into close contact with the installation portion in addition to the two insertion portions, so that the close-contact efficiency of the stitched portion can be increased.

FIG. 1 is a diagram illustrating at least one example of an embodiment of a staple 1. FIG. 2 is a diagram for explaining the “bending point”. FIGS. 3A to 3D are diagrams showing examples of shapes including a curved portion having no bending point. 4A to 4C are diagrams showing another example of the staple 1 embodiment. 5A and 5B are views showing shapes that are not included in the embodiment of the staple 1. 6A and 6B are diagrams for explaining the boundary between the erection part 3 and the connecting part 4, and FIG. 6C is a diagram illustrating another example of the erection part 3. FIG. 7 is a view showing still another example of the embodiment of the staple 1. FIG. 8 is a drawing-substituting photograph, FIG. 8A is Example 1, FIG. 8B is Example 2, FIG. 8C is Example 3, FIG. 8D is Example 4, and FIG. 8 (E) is a photograph of Example 5 after bending by 180 ° while pressing a wire against a stainless steel rod having a different diameter (curvature radius). FIG. 9 is a drawing-substituting photograph, FIG. 9A is a photograph of the staple produced in Example 6, FIG. 9B is a photograph of the staple produced in Comparative Example 1, and FIG. 9C is a puncture in the intestinal tract. FIG. 9D is a photograph of the staple of Comparative Example 1 punctured in the intestinal tract. FIG. 10 is a drawing-substituting photograph, FIG. 10 (A) is a photograph of a HE-stained section of a week after the operation of Example 7 (magnified 20 times), and FIG. 10 (B) is a week of the operation of Example 7 after one week. It is the photograph (200 time expansion) of the section | stain dye | stained HE. FIG. 10 (C) is a photograph of a HE-stained section 1 week after surgery in Comparative Example 2 (20-fold enlargement), and FIG. 10D is a photograph of a HE-stained section 1 week after surgery in Comparative Example 2 (200). Double magnification). FIG. 11 is a drawing-substituting photograph, FIG. 11 (A) is a photograph of a HE-stained section 2 times after the operation of Example 7 (magnification 40 times), and FIG. 11 (B) is 2 weeks after the operation of Example 7. It is the photograph (100 time expansion) of the section | stain dye | stained HE. FIG. 11 (C) is a photograph of a HE-stained section of Comparative Example 2 two weeks after surgery (magnification 40 times), and FIG. 11D is a photograph of a HE-stained section of Comparative Example 2 two weeks after surgery (100). Double magnification). FIG. 12 is a drawing-substituting photograph, FIG. 12 (A) is a photograph of a HE-stained section of 4 weeks after the operation of Example 7 (100 times magnification), and FIG. 12 (B) is 4 weeks after the operation of Example 7. It is the photograph (400 times expansion) of the section | stain dyed | stained HE. 12C is a photograph of a HE-stained section of Comparative Example 2 4 weeks after surgery (100 times magnification), and FIG. 12D is a photograph of a HE-stained section of Comparative Example 2 4 weeks after surgery (400). Double magnification).

Hereinafter, embodiments of the staple will be described in detail. FIG. 1 is a diagram illustrating an example of a staple embodiment. A staple 1 shown in FIG. 1 connects two insertion portions 2 to be inserted into a living tissue where suture is necessary by a surgical operation or the like, an erection portion 3 straddling the suture location, and the insertion portion 2 and the erection portion 3. Two connecting portions 4 are included.

The connecting part 4 is formed in a shape including a curved part having no bending point. In addition, in this application, as shown in FIG. 2, "bending point" means the bending center location 5 when a wire is bent around a specific location, and a smooth situation without the bending center location 5 continues. Different from the curved part. In the present application, since the “bending point” is not included, the force for bringing the sutured portion into close contact is less likely to be concentrated on the specific portion of the staple, and as a result, it is difficult to break even if it is corroded in vivo.

In addition, the “shape including a bending portion that does not have a bending point” in the present application refers to all shapes that do not include a bending point and can connect the insertion portion 2 and the erection portion 3 by including the bending portion. Means shape. For example, as shown in FIG. 3 (A), the whole connecting portion 4 is smoothly and continuously curved in the same direction, and as shown in FIG. 3 (B), part or all of the connecting portion 4 is curved. Includes a wavy portion, and the connecting portion 4 is curved in the same direction as a whole, and as shown in FIG. 3C, the connecting portion 4 includes a straight portion and a curved portion. In addition, although illustration is abbreviate | omitted, a linear part may be included in a part of connection part 4 of the shape shown to FIG. 3 (B). 3A to 3C are gradually curved from the insertion portion 2 toward the inside of the staple 1, but as shown in FIG. 3D, the connection portion 4 is gradually curved. It is also possible to first bend from the insertion portion 2 toward the outside of the staple 1 and then gradually bend toward the inside of the staple 1. Although not shown in the figure, the connection portion 4 having the shape shown in FIG. 3D is also partially or entirely wavy as shown in FIG. 3B, as shown in FIG. It may include a straight line portion. FIG. 3 is an illustration of a specific shape of the staple 1 of the present application, and is not limited to the example shown in FIG. As long as it is “a shape including a curved portion having no bending point”, a shape not shown may be used.

The staple 1 according to the embodiment is put into a stapler cartridge, and the staple 1 is pushed out to puncture a living tissue. Although the staple 1 having the shape shown in FIG. 3D can also be used, when the connecting portion 4 protrudes outside the staple 1, the insertion portion 2 is separated from the wall surface of the cartridge. Therefore, from the viewpoint of stability at the time of puncturing, as shown in FIGS. 3A to 3C, the connecting portion 4 is gradually curved from the insertion portion 2 toward the inside of the staple 1. Is preferred.

At least a part of the erection part 3 is located on the distal end 21 side of the insertion part 2 from the line (dotted line in FIG. 1) connecting the top part 41 of the one connection part 4 and the top part 41 of the other connection part 4. ing. In addition, in this application, a "top part" means the location which has the distance H most from the line | wire which connected the two front-end | tips 21 of the insertion part 2, as shown in FIG.

FIG. 1 shows an example in which all of the erection part 3 is located on the distal end 21 side of the insertion part 2 with respect to the line connecting the top part 41 and the top part 41, but the position of the erection part 3 and the top part 41 described above. There are no restrictions as long as the relationship is satisfied. FIG. 4 shows another example of the embodiment of the staple 1, and FIG. 4 (A) shows that the construction part 3 is formed in a wave shape, and one of the waves is opposite to the tip 21 from the line connecting the top parts 41. 4B, the erection part 3 is formed in a wave shape, and all of the waves protrude toward the tip 21 side from the line connecting the top parts 41, and FIG. An example is shown in which a plurality of waves protrude from the line connecting the top portions 41 to the side opposite to the tip 21. What is necessary is just to determine the shape of the construction part 3 suitably according to the shape of the location to sew.

FIG. 5 shows an example not included in the embodiment of the staple 1. In this technical field, a substantially U-shaped staple shown in FIG. 5A and a substantially U-shaped staple shown in FIG. 5B are known. However, in the staple of the shape shown in FIGS. 5A and 5B, any part of the erection part 3 is closer to the distal end 21 side of the insertion part 2 than the line connecting the top part 41 and the top part 41 of the connecting part 4. It is not included in the staple 1 embodiment because it is not located.

FIG. 6 is a diagram for explaining the boundary between the erection part 3 and the connection part 4. As shown in FIG. 6A, when the entire connecting portion 4 is smoothly curved in the same direction, the center point R of the virtual circle having an arc at two arbitrary points of the connecting portion 4 is a staple. 1 inside. Even when the connecting portion 4 includes a straight portion, R does not become outside the staple 1. On the other hand, since a part of the erection part 3 is on the tip 21 side from the line connecting the top part 41 and the top part 41, the center point R of the virtual circle having an arc of any two points is the part that is outside the staple 1. is there. What is necessary is just to define the boundary of the bridge | bridging part 3 and the connection part 4 as a location where the center point of a circular arc reverses. On the other hand, as shown in FIG. 6B, when the connecting portion 4 includes a wave-like portion, the center point R of the virtual circle is located both inside and outside the staple 1. In that case, what is necessary is just to define the last location where the center point of a circular arc reverses from the inner side of the staple 1 to the outer side as the boundary between the erection part 3 and the connection part 4. Since the boundary between the erection part 3 and the connection part 4 is defined as described above, for example, as shown in FIG. include.

FIG. 7 shows still another example of the embodiment of the staple 1. The insertion portion 2 of the staple 1 is substantially linear in order to make it easier to puncture a living tissue. Therefore, when the connecting portion 4 comes into contact with the living tissue after puncturing the insertion portion 2, the staple 1 is gradually bent from a substantially straight line, so that it is difficult to puncture the living tissue. Therefore, as shown in FIG. 7, at least a part of the erection part 3 is connected to the insertion part 2 and the connection part which are further on the tip 21 side of the insertion part 2 from the line connecting the top part 41 and the top part 41 of the connection part 4. 4 may be formed so as to be positioned closer to the distal end 21 side of the insertion portion 2 than the line 25 connecting the boundaries 24 of the four. In the case of the embodiment shown in FIG. 7, the erection part 3 is more likely to come into contact with the stitched portion, so that the adhesion efficiency of the stitched portion can be increased. The boundary between the insertion part 2 and the connection part 4 may be a place where the insertion part 2 begins to bend.

As described above, the staple 1 shown in each embodiment is characterized by having no bending point. However, in order to prevent a load from being applied to a specific portion of the staple 1, the curvature radius of the curved portion is increased. It is preferable to do. In the present application, the “curvature radius” means a radius of an imaginary circle having an arc at two arbitrary points of the curved portion of the connecting portion 4. The radius of curvature of the connecting portion 4 is preferably 0.1 mm or more, more preferably 0.275 mm or more, and still more preferably 0.4 mm or more. Moreover, it is preferable to also set the curvature radius similar to the above also about the boundary part of the connection part 4 and the installation part 3, and the connection part 4 and the insertion part 2. FIG. When the connecting portion 4 is wave-shaped, the amplitude may be reduced so as to have the above-described curvature radius. In addition, what is necessary is just to make it become the same curvature radius as the above also when the construction part 3 is made into a waveform.

In addition, there is no particular limitation on the stitching site where the staple 1 shown in each embodiment is used, and a staple having a size corresponding to the thickness of the stitching site may be used. The staple 1 has, for example, a vertical width (distance from the distal end of the insertion portion 2 to the erection portion 3) of 2 to 5 mm (a vertical width after puncturing the living tissue is 0.5 mm to 3 mm), and a horizontal width (puncture The distance between the insertion portion 2 and the insertion portion 2) can be exemplified by about 1 mm to 5 mm. However, as described above, the size may be appropriately adjusted according to the suture location.

The staple 1 shown in each embodiment is not particularly limited as long as it is a metal material that biodegrades when placed in the living body. For example, as the biodegradable metal material, pure magnesium or a magnesium alloy, pure calcium or a calcium alloy, pure zinc or a zinc alloy, or the like is used. Preferred is pure magnesium or a magnesium alloy. As a magnesium alloy, magnesium is a main component, H, C, N, O, Na, P, K, Ca, Fe, B, Al, Si, V, Cr, Mn, Zn. , Y, La, Ce, Nd, Sm, Gd, Tb, Dy, and Yb containing at least one element selected from rare earth elements.

Further, the staple 1 shown in each embodiment may be made of only a biodegradable metal material, but the biodegradable metal material may be coated with a biodegradable resin. By coating with a biodegradable resin, the progress of corrosion of the staple 1 when placed in the living body can be adjusted. The biodegradable resin is not particularly limited as long as it is enzymatically or non-enzymatically decomposed in vivo and the decomposed product does not exhibit toxicity. For example, polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone, polylactic acid-polycaprolactone copolymer, polyorthoester, polyphosphazene, polyphosphoric acid ester, polyhydroxybutyric acid, polymalic acid, poly Examples include α-amino acids, collagen, gelatin, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, hyaluronic acid, polyhydroxybutyrate valeric acid, polysalicylic acid, polypeptides, polysaccharides, chitin, and chitosan.

Further, the biodegradable metal material or the biodegradable resin coated with the biodegradable metal material may carry a physiologically active substance. The physiologically active substance is not particularly limited as long as it is supported on the surface of the biodegradable metal material or biodegradable resin. For example, the physiologically active substance may be dissolved in a solvent or the like and applied.

Physiologically active substance is not particularly limited as long as it is a known drug used for treatment or the like. For example, since a staple placed in the body is a foreign substance for a living body, post-operative inflammation or the like can be suppressed by carrying an anti-inflammatory agent, an antibiotic, an antiallergic agent, or the like. In addition, a hemostatic agent or the like may be carried if the suture site is a blood vessel, and an anticancer agent or the like may be carried if the suture site is cancer.

As described above, the manufacturing method of the staple 1 shown in each embodiment is not particularly limited as long as the connecting portion 4 is formed in a shape including a curved portion having no bending point. For example, a metal mold corresponding to at least the shapes of the connecting part 4 and the erection part 3 is produced, and a thin plate made of a biodegradable metal material may be press-molded. Or the metal mold | die of the shape of the insertion part 2, the connection part 4, and the installation part 3 should be produced, and the melted biodegradable metal material should just be injection-molded. In addition, you may make the front-end | tip part of the insertion part 2 into a taper shape in order to make it easy to puncture a biological tissue. In order to make the tip tapered, a press or injection molding mold may be adjusted, or a staple produced by pressing or the like may be sheared or ground.

The staple 1 shown in each embodiment may be set in a known stapler cartridge for living tissue. In addition, the staple 1 shown in each embodiment is connected when the connecting portion 4 is positioned on the distal end side of the insertion portion 2 with respect to the erection portion 3, so that the portion contacting the connecting portion 4 of the cartridge is linear. At least a part of the part is separated from the part. For this reason, if a conventional U-shaped portion that presses the staple of the stapler is used, the pressing force may concentrate on the top 41 of the connecting portion 4. Therefore, it is preferable that the pressing part of the stapler using the staple 1 shown in each embodiment has a shape that fits the connecting part 4 and the erection part 3.

Hereinafter, embodiments will be described in detail with reference to examples, but these examples are provided merely for reference of specific modes. These illustrations are intended to illustrate certain specific aspects of the staple 1 embodiment of the present application, but do not limit or limit the scope of the embodiments disclosed herein. .

<Examples 1 to 5>
[Production of alloy wire]
Magnesium (Mg), Neodymium (Nd), Yttrium (Y) and Zirconium (Zr) will be 95.6% Mg-3.0% Nd-1.0% Y-0.4% Zr by weight%. In addition, each pure metal was placed in a graphite crucible for high frequency induction heating and placed inside a high frequency coil in a high frequency melting furnace chamber. Next, after evacuating the chamber, it is filled with helium gas until atmospheric pressure is reached, the crucible is heated to 750 ° C., and after confirming that all the metal in the crucible has melted, it is held for 10 minutes. Immediately, the melt in the crucible was cast into a cylindrical copper mold that had been installed in front of the high-frequency coil. After cooling for a certain period of time, the above-mentioned cylindrical alloy ingot was obtained from this mold.

The obtained alloy ingot was hot-extruded under conditions of a temperature of 400 ° C., an extrusion ratio of 15 and an extrusion speed of 60 mm / min, and processed into a rod having an outer diameter of 17 mm. A billet (outer diameter 10 mm × length 25 mm) was cut out from this alloy bar, and hot extrusion was performed under the conditions of a temperature of 400 ° C. and an extrusion ratio of 28 to obtain an alloy wire having an outer diameter of 1.9 mm.

Next, the alloy wire was inserted into a drawing die and drawn at room temperature. The area reduction rate of the alloy wire cross section before and after the drawing process was adjusted to 30% or less, and after the drawing process, annealing was performed at 400 ° C. for 30 minutes. Then, drawing and annealing were repeated until the wire diameter of the alloy wire became 0.25 mm.

The obtained alloy wire having a wire diameter of 0.25 mm was cut to a length of 25 mm and bent 180 ° while being pressed against a stainless steel rod having the following diameter (curvature radius).
Example 1: Diameter 0.2 mm (curvature radius = 0.1 mm)
Example 2: Diameter 0.55 mm (curvature radius = 0.275 mm)
-Example 3: Diameter 0.8mm (curvature radius = 0.4mm)
Example 4: Diameter 1.0 mm (curvature radius = 0.5 mm)
Example 5: Diameter 1.5 mm (curvature radius = 0.75 mm)

8A is Example 1, FIG. 8B is Example 2, FIG. 8C is Example 3, FIG. 8D is Example 4, and FIG. 8E is Example 5. It is a photograph after bending 180 degrees. Three samples were prepared and bent with the above-mentioned curvature radius. As shown in Table 1, when the sample of Example 1 (alloy wire) was bent by 180 °, cracks were observed in the bent portion (not broken), but the samples of Examples 2 to 5 No cracks were observed in the bent part.

[Immersion experiment]
Next, an immersion experiment system simulating the inside of a living body was prepared, and the corrosion change when the samples of Examples 1 to 5 were immersed in the immersion experiment system was examined.
First, the samples of Examples 1 to 5 were immersed in a 0.5% nitric acid aqueous solution for 20 seconds, acid-washed, then subjected to ultrasonic washing for 1 minute each in the order of pure water and acetone, and dried.
Next, 10 ml of bovine serum (New Zealand; Thermo Fisher Scientific Gibco) was placed in a test tube to prepare an immersion experiment system. And the sample which performed the said process was put into the test tube, the test tube was hold | maintained in the thermostat kept at 37 degreeC, and the corrosion state was observed by immersion time 3,6,9h. The results are shown in Table 1. As the dipping time progressed, corrosion fracture occurred at the bent part, and this tendency was strongly observed as the radius of curvature decreased. However, no significant difference was observed when the radius of curvature was 0.4 mm or more.

[Puncture experiment]
<Example 6>
An alloy wire having a wire diameter of 0.25 mm obtained by the same procedure as described in Examples 1 to 5 above is 3 mm (distance connecting the left and right insertion portions 2 and the connecting portion 4 boundary 24) by pressing. × It was processed into a staple shape of 2.5 mm (length to the insertion portion 2 and the top portion 41 of the connecting portion 4). The tip of the staple insertion portion 2 was tapered at an angle of 45 degrees toward the inside of the staple with respect to the insertion direction. Moreover, the curvature radius of the connection part 4 was 0.5 mm. The length of the erection part 3 was 2.5 mm. Next, by pressing a stainless steel rod having a diameter of 0.5 mm against the machined staple erection part 3, the erection part 4 has a radius of curvature of 0.25 mm from the top part 41 of the coupling part 4 to the distal end 21 side of the insertion part 2. Staples having indentations were prepared. FIG. 9A is a photograph of the produced staple.

Next, the produced staple was punctured into the intestinal tract filled with pork. FIG. 9C is a photograph of staples punctured in the intestinal tract.

<Comparative Example 1>
In Example 6, the intestinal tract was punctured in the same manner as in Example 6 except that the stainless steel bar having a diameter of 0.5 mm was not pressed against the erection part 3 of the staple and the staple in the pressed state was changed to Comparative Example 1. FIG. 9B is a photograph of the staple of Comparative Example 1, and FIG. 9D is a photograph of the staple punctured in the intestinal tract.

As is clear from FIGS. 9A to 9D, it was confirmed that the staple having the erected portion positioned closer to the distal end side of the insertion portion than the top of the connecting portion was in close contact with the stitched portion. On the other hand, the staple of Comparative Example 1 stopped at the connecting portion, and the erection portion did not come into close contact with the stitched portion.
From the above results, when the connecting portion of the staple is formed into a shape including a curved portion that does not have a bending point, it is difficult to break in vivo, and further, the erection portion of the construction portion is connected to the line connecting the top portion and the top portion of the connecting portion. It has been clarified that at least a part is located on the distal end side of the insertion portion, so that the sutured portion can be adhered for a long period of time.

[Suture experiment in animal body]
<Example 7>
Instead of the raw material of Example 1, magnesium (Mg), rare earth (RE; misch metal containing Nd as a main component), and yttrium (Y) are 96% Mg-3.0% RE-1.0% by weight. An alloy wire was prepared in the same procedure as in Example 1 except that Y was used, and then a wire with a wire diameter of 0.25 mm was pressed into 3 mm (left and right insertion portions 2 and connecting portions 4). (Distance connecting the boundary 24) × 2.5 mm (the length from the insertion portion 2 to the top portion 41 of the connecting portion 4). The tip of the staple insertion portion 2 was tapered at an angle of 45 degrees toward the inside of the staple with respect to the insertion direction.
Next, using the prepared staples, sutures were performed in the animal body according to the following procedure, and pathological findings were examined.
(1) Three pigs were laparotomized under general anesthesia, and a small intestine machine suture was performed at 50 cm from the terminal ileum using a suture instrument (Ethicon (Johnson &Johnson); Powered ECHELON FLEX).
(2) After the operation, the abdomen was raised after 1 week, 2 weeks and 4 weeks, and the pathological findings around the sutured part were observed. The pathological findings were observed by visual observation around the sutured part and by HE staining. HE staining was performed according to the following procedure.
(A) The polished specimen was washed with water after resin removal.
(B) Immersion in Weigert's iron hematoxylin solution for 60 minutes.
(C) After washing with water, it was immersed in an eosin solution for 7 minutes.
(D) Dehydrated with ethanol, sealed with xylene, and sealed.

FIG. 10 (A) is a photograph of a HE-stained section 1 week after surgery (20 times magnification), FIG. 10B is a photograph of a HE-stained section 1 week after surgery (200 times magnification), and FIG. 11 (A). ) Is a photograph of a HE-stained section 2 weeks after surgery (40 times magnification), FIG. 11B is a photograph of a HE-stained section 2 weeks after surgery (100 times magnification), and FIG. A photograph of a 4-week HE-stained section (100 times magnification) and FIG. 12 (B) are photographs of a 4-week post-surgery HE-stained section (400 times magnification).

<Comparative Example 2>
Example except that titanium staple (Ethicon (Johnson &Johnson); ECR45W) was used instead of the staple of Example 7 and the small intestine machine was sutured at a position shifted from Example 7 (50 cm from the stomach pylorus). At the same time, small intestine suture was performed. The observation of the pathological findings was performed in the same procedure as in Example 7.

FIG. 10 (C) is a photograph of a HE-stained section 1 week after surgery (20 times magnification), FIG. 10D is a photograph of a HE-stained section 1 week after surgery (200 times magnification), and FIG. 11 (C). ) Is a photograph of a HE-stained section 2 weeks after surgery (40 times magnification), FIG. 11 (D) is a photograph of a HE-stained section 2 weeks after surgery (100 times magnification), and FIG. 12 (C) is after surgery. A photograph of a 4-week HE-stained section (100-fold magnification) and FIG. 12D are photographs of a 4-week post-surgery HE-stained section (400-fold magnification).

10A to 10D and macroscopic observation, the following pathological findings were obtained 1 week after the operation.
(A) In Example 7 (Mg staple) and Comparative Example 2 (Ti staple), inflammatory cell infiltration was observed around the metal, but the effect was limited to a relatively narrow range.
(B) In both Mg staple and Ti staple, the inflammation around the metal spread from the mucosa to the serosal surface. The degree of inflammation was similar.
(C) In the Ti staple, inflammation spread by neutrophils, eosinophils, and lymphocytes, mainly metal, was stronger.

From the results shown in FIGS. 11A to 11D and macroscopic observation, the following pathological findings were obtained at 2 weeks after the operation.
(D) Relatively strong inflammatory cell infiltration was observed in the entire specimen for both Mg staple and Ti staple. A spillover of inflammation was also observed at some distance from the metal piece.
(E) In both Mg staple and Ti staple, the inflammation around the metal spread from the mucosa to the serosal surface. The degree of inflammation was similar.
(F) Ti staples were more strongly affected by neutrophils, eosinophils and lymphocytes, mainly metal.

12 (A) to 12 (D) and macroscopic observation, the following pathological findings were obtained at 4 weeks after the operation.
(G) A relatively strong inflammatory cell infiltration was observed in the whole specimen as well as both the Mg staple and the Ti staple. In addition, a spillover of inflammation was also observed at a distance from the metal piece.
(H) In the Ti staple, the inflammation spread by neutrophils, eosinophils, and lymphocytes, mainly metal, was stronger.

From Example 7 and Comparative Example 2, in both the Mg staple and the Ti staple, the local inflammatory change accompanying the implantation of the metal piece remains only in the vicinity of the metal piece (only around) until one week after the operation. The degree of inflammation was similar in both cases. In the 4 weeks after the operation, both the Mg staple and the Ti staple showed a relatively strong inflammatory cell infiltration throughout the tissue, and inflammation was also observed at a relatively remote location from the metal piece. However, compared to Ti staples, Mg staples were found to have less inflammation spread by neutrophils, eosinophils, and lymphocytes. From the above results, it was confirmed that a biodegradable metal material is preferable as a material for staples placed in the living body.

When the staple of the embodiment disclosed in the present application is used, the stitched portion can be adhered for a long period of time. Therefore, it is useful for surgery in a medical institution.

Claims

A staple formed of a biodegradable metal material,
The staple includes two insertion portions to be inserted into a living tissue, an erection portion that straddles a suture site, and a connection portion that connects the insertion portion and the erection portion,
The connecting portion is formed in a shape including a curved portion having no bending point, and
A bioabsorbable staple in which at least a part of the erection part is located on a distal end side of the insertion part from a line connecting the top part and the top part of the connection part.
2. The bioabsorbable staple according to claim 1, wherein all of the erection portions are located on a distal end side of the insertion portion with respect to a line connecting the top portions of the connection portions.
The bioabsorbable staple according to claim 1 or 2, wherein the most curved portion of the connecting portion has a curvature radius of 0.275 mm or more.
The bioabsorbable staple according to any one of claims 1 to 3, wherein the biodegradable metal material is selected from an alloy containing magnesium as a main component.
The bioabsorbable staple according to any one of claims 1 to 4, wherein a periphery of the biodegradable metal material is coated with a biodegradable resin.