JP6823321B2 - Bioabsorbable staple - Google Patents

Description

The present invention relates to a bioabsorbable staple, and particularly to a staple having a shape having no bending point, which makes it difficult for breakage due to corrosion to occur when placed in a living body and provides a suturing effect for a long period of time. ..

Threads have been used as a means of suturing wounds during surgery, but in recent years they can be sutured faster and easier, and postoperative suture failure is almost the same as hand-sewn. Staples are used as a non-existent means. Staples are used in various surgical sites such as skin, blood vessels, intestinal tract, bones, muscles or organs. Further, it is used by a method according to the sutured portion, such as piercing and suturing into the skin or the like from outside the body, or suturing a blood vessel, intestinal tract, organ or the like in the living body and then indwelling in the living body.

Among the above staples, as staples to be indwelled in a living body, metals such as stainless steel, titanium and tantalum, and staples insoluble in the human body in which an amorphous diamond-like carbon film is formed on the surface of the metal are known. (See Patent Document 1). Staples made of a metal material soluble in the human body for closing wounds on the skin, fascia or internal organs are also known (see Patent Document 2).

Japanese Unexamined Patent Publication No. 5-154189 Japanese Patent No. 5036697

As described in Patent Documents 1 and 2, both insoluble and soluble staples in vivo are known as staples to be indwelled in vivo. By the way, since an insoluble material becomes a foreign substance to a living body, if the insoluble material is left in the living body for a long period after surgery, an intractable infectious disease may occur. Therefore, it is considered desirable that the staples to be indwelled in the living body are made of a material soluble in the living body. However, in the actual medical field, most of the staples to be indwelled 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 rarely used.

The present invention has been made to solve the above problems, and as a result of intensive research, (1) when staples made of a biodegradable metal material are placed in a living body, they are sutured from outside the living body. Unlike the case, the entire staple is gradually corroded by biodegradable components. At that time, since the force for suturing the living tissue is concentrated on the bent part of the staple, it is easy to break at the bent part, and (2) the erection straddling the two insertion parts of the staple and the sutured part. By forming the connecting part for connecting the parts into a shape including the curved part having no bending point, the force for suturing the living tissue is dispersed and the force is not concentrated at a specific place, so that the staple breaks. (3) By forming at least a part of the erection part so as to be located on the tip side of the insertion part from the line connecting the tops of the connection part, two stitches are stabbed. It was newly found that the sutured part can be brought into close contact by pressing with the erection part in addition to the entrance part.

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

The present invention relates to the bioabsorbable staples shown below.

(1) Staples made of biodegradable metal material
The staple includes two insertion portions to be inserted into a living tissue, an erection portion straddling a sutured portion, and a connecting portion connecting 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 portion is located on the tip side of the insertion portion from the line connecting the tops of the connection portion.
(2) The bioabsorbable staple according to (1) above, wherein all of the erection portions are located on the tip side of the insertion portion from the line connecting the tops of the connection portions.
(3) The bioabsorbable staple according to (1) or (2) above, 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) above, 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) above, 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 a living body. Therefore, the sutured portion can be in close contact for a long period of time.

Further, since the connecting portion of the staple is formed in a shape including a curved portion having no bending point, at least a part of the erection portion is on the tip side of the insertion portion from the line connecting the top and the top of the connecting portion. It can be formed to be located in. When sutured with the staple, the sutured portion can be brought into close contact with the erection portion in addition to the two insertion portions, so that the adhesion efficiency of the sutured portion can be improved.

FIG. 1 is a diagram illustrating at least one example of an embodiment of staple 1. FIG. 2 is a diagram for explaining a “bending point”. 3 (A) to 3 (D) are views showing an example of a shape including a curved portion having no bending point. 4 (A) to 4 (C) are views showing another example of the embodiment of staple 1. 5 (A) and 5 (B) are views showing shapes not included in the embodiment of staple 1. 6 (A) and 6 (B) are diagrams for explaining the boundary between the erection portion 3 and the connecting portion 4, and FIG. 6 (C) is a diagram showing another example of the erection portion 3. FIG. 7 is a diagram showing still another example of the embodiment of staple 1. 8 is a drawing substitute photograph, FIG. 8 (A) is Example 1, FIG. 8 (B) is Example 2, FIG. 8 (C) is Example 3, and FIG. 8 (D) is Example 4. 8 (E) is a photograph of Example 5 after bending 180 ° while pressing a wire rod against stainless steel rods having different diameters (radius of curvature). 9 is a drawing substitute photograph, FIG. 9 (A) is a photograph of the staple prepared in Example 6, FIG. 9 (B) is a photograph of the staple prepared in Comparative Example 1, and FIG. 9 (C) is a puncture in the intestinal tract. A photograph of the staple of Example 6 and FIG. 9 (D) is a photograph of the staple of Comparative Example 1 punctured in the intestinal tract. 10 (A) is a drawing substitute photograph, FIG. 10 (A) is a photograph of a HE-stained section of Example 7 one week after the operation (magnified 20 times), and FIG. 10 (B) is one week after the operation of Example 7. It is a photograph (200 times magnification) of the HE-stained section of. FIG. 10 (C) is a photograph of the HE-stained section of Comparative Example 2 one week after the operation (magnified 20 times), and FIG. 10 (D) is a photograph of the HE-stained section of Comparative Example 2 one week after the operation (200). Double magnification). FIG. 11 is a drawing-substituting photograph, FIG. 11 (A) is a photograph of a HE-stained section 2 weeks after the operation of Example 7 (magnified 40 times), and FIG. 11 (B) is a photograph 2 weeks after the operation of Example 7. It is a photograph (100 times magnification) of the section which was stained with HE. FIG. 11 (C) is a photograph of the HE-stained section of Comparative Example 2 2 weeks after the operation (magnified 40 times), and FIG. 11 (D) is a photograph of the HE-stained section of Comparative Example 2 2 weeks after the operation (100). Double magnification). 12A and 12B are photographs of substitute drawings, FIG. 12A is a photograph of a HE-stained section of Example 7 4 weeks after the operation (enlarged 100 times), and FIG. 12B is a photograph of the section 4 weeks after the operation of Example 7. It is a photograph (400 times magnification) of the section which was stained with HE. FIG. 12 (C) is a photograph (100-fold magnification) of the HE-stained section of Comparative Example 2 4 weeks after the operation, and FIG. 12 (D) is a photograph (400) of the HE-stained section of Comparative Example 2 4 weeks after the operation. Double magnification).

The embodiments of staples will be described in detail below. FIG. 1 is a diagram illustrating an example of an embodiment of staples. The staple 1 shown in FIG. 1 connects two puncture portions 2, an erection portion 3 straddling the suture portion, and the puncture portion 2 and the erection portion 3 to be pierced into a biological tissue at a portion requiring suturing by surgery or the like. Includes two connecting parts 4.

The connecting portion 4 is formed in a shape including a curved portion having no bending point. In the present application, as shown in FIG. 2, the “bending point” means a bending center portion 5 when the wire rod is bent around a specific portion, and a smooth phase having no bending center portion 5 continues. It is different from the curved part. In the present application, since the "bending point" is not included, it becomes difficult for the force for adhering the sutured portion to concentrate on the specific portion of the staple, and as a result, it becomes difficult to break even if it is corroded in the living body.

Further, the "shape including a curved portion having no bending point" in the present application means all cases in which the insertion portion 2 and the erection portion 3 can be connected by including the curved portion without including the bending point. Means shape. For example, as shown in FIG. 3A, the entire connecting portion 4 is smoothly and continuously curved in the same direction, and as shown in FIG. 3B, a part or all of the connecting portion 4 is formed. There is a shape in which the connecting portion 4 includes a wavy portion and the connecting portion 4 is curved in the same direction as a whole, and a shape in which the connecting portion 4 includes a straight portion and a curved portion as shown in FIG. 3C. Although not shown, a straight line portion may be included in a part of the connecting portion 4 having the shape shown in FIG. 3 (B). Further, the connecting portion 4 having a shape shown in FIGS. 3A to 3C is gradually curved from the insertion portion 2 toward the inside of the staple 1, but as shown in FIG. 3D, the insertion portion 4 is inserted. It may be curved from the inlet 2 toward the outside of the staple 1 first, and then gradually curved toward the inside of the staple 1. Further, although not shown, in the case of the connecting portion 4 having the shape shown in FIG. 3 (D), a part or the whole is a wavy portion as shown in FIG. 3 (B), as shown in FIG. 3 (C). It may include a straight line portion. Note that FIG. 3 is an example of the specific shape of the staple 1 of the present application, and is not limited to the example shown in FIG. A shape (not shown) may be used as long as it is a "shape including a curved portion having no bending point".

The staple 1 according to the embodiment is placed in a stapler cartridge, and the staple 1 is extruded and punctured into a living tissue. Although the staple 1 having the shape shown in FIG. 3D can be used, if the connecting portion 4 protrudes to the outside of the staple 1, the insertion portion 2 is separated from the wall surface of the cartridge. Therefore, from the viewpoint of stability during puncture, as shown in FIGS. 3A to 3C, the connecting portion 4 has a shape in which the connecting portion 4 is gradually curved inward from the puncturing portion 2 to the staple 1. Is preferable.

At least a part of the erection portion 3 is located on the tip 21 side of the insertion portion 2 from the line connecting the top 41 of one connecting portion 4 and the top 41 of the other connecting portion 4 (dotted line in FIG. 1). ing. In the present application, as shown in FIG. 1, the “top” means a portion having the longest distance H from the line connecting the two tips 21 of the insertion portion 2.

FIG. 1 shows an example in which all of the erection portion 3 is located on the tip 21 side of the insertion portion 2 from the line connecting the top portion 41 and the top portion 41, but the positions of the above-mentioned erection portion 3 and the top portion 41 are shown. There are no particular restrictions as long as the relationship is satisfied. FIG. 4 shows another example of the embodiment of staple 1, in FIG. 4 (A), the erection portion 3 is formed in a wave shape, and one of the waves is opposite to the tip 21 from the line connecting the top 41. Projected to the side, FIG. 4 (B) forms the erection portion 3 in a wavy shape, all of the waves project toward the tip 21 side from the line connecting the tops 41, and FIG. 4 (C) shows the erection portion 3 in a wavy shape. An example is shown in which a plurality of waves are formed and protrude from the line connecting the top 41 to the side opposite to the tip 21. The shape of the erection portion 3 may be appropriately determined according to the shape of the portion to be sewn.

Further, FIG. 5 shows an example not included in the embodiment of staple 1. In the art, the substantially U-shaped staples shown in FIG. 5 (A) and the substantially U-shaped staples shown in FIG. 5 (B) are known. However, in the staples having the shapes shown in FIGS. 5A and 5B, any part of the erection portion 3 is on the tip 21 side of the insertion portion 2 from the line connecting the top portions 41 and the top portions 41 of the connecting portion 4. Since it is not located, it is not included in the embodiment of staple 1.

FIG. 6 is a diagram illustrating a boundary between the erection portion 3 and the connecting portion 4. As shown in FIG. 6A, when the entire connecting portion 4 is smoothly curved in the same direction, the center points R of the virtual circle having any two points of the connecting portion 4 as arcs are staples. It will be inside 1. 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 portion 3 is on the tip 21 side of the line connecting the top 41 and the top 41, the center point R of the virtual circle having any two points as an arc is the portion outside the staple 1. is there. The boundary between the bridging portion 3 and the connecting portion 4 may be defined as a location where the center point of the arc is inverted. On the other hand, as shown in FIG. 6B, when the connecting portion 4 includes the wavy portion, the center point R of the virtual circle is located both inside and outside the staple 1. In that case, the last point where the center point of the arc is inverted from the inside to the outside of the staple 1 may be defined as the boundary between the erection portion 3 and the connecting portion 4. Since the boundary between the erection portion 3 and the connecting portion 4 is defined as described above, for example, as shown in FIG. 6C, the erection portion 3 has a substantially U-shaped shape according to the embodiment of the staple 1. include.

FIG. 7 shows yet another example of the staple 1 embodiment. The puncture portion 2 of the staple 1 is substantially linear in order to facilitate puncture into the living tissue. Therefore, when the connecting portion 4 comes into contact with the living tissue after the puncture portion 2 is punctured, the staple 1 gradually bends from a substantially straight line, making it difficult to puncture the staple 1 into the living tissue. Therefore, as shown in FIG. 7, at least a part of the erection portion 3 is connected to the insertion portion 2 which is the tip 21 side of the insertion portion 2 further than the line connecting the top 41 and the top 41 of the connection portion 4. It may be formed so as to be located on the tip 21 side of the insertion portion 2 from the line 25 connecting the boundary 24 of 4. In the case of the embodiment shown in FIG. 7, since the erection portion 3 is more likely to come into contact with the sewn portion, the adhesion efficiency of the sewn portion can be improved. The boundary between the insertion portion 2 and the connecting portion 4 may be a place where the insertion portion 2 begins to bend.

As described above, the staple 1 shown in each embodiment is characterized in that it does not have a bending point, but in order to prevent a load from being applied to a specific portion of the staple 1, the radius of curvature of the curved portion is increased. It is preferable to do so. In the present application, the "radius of curvature" means the radius of a virtual circle having an arc at any two 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, still more preferably 0.4 mm or more. Further, it is preferable that the boundary portion between the connecting portion 4 and the erection portion 3 and the connecting portion 4 and the insertion portion 2 has the same radius of curvature as described above. When the connecting portion 4 has a wavy shape, the amplitude may be reduced so as to have the above-mentioned radius of curvature. Even when the erection portion 3 has a wavy shape, the radius of curvature may be the same as described above.

Further, there is no particular limitation on the stitched portion where the staple 1 shown in each embodiment is used, and a staple having a size corresponding to the thickness or the like of the stitched portion may be used. The size of the staple 1 is, for example, a vertical width (distance from the tip of the insertion portion 2 to the erection portion 3) of 2 to 5 mm (the vertical width after puncturing the living tissue is 0.5 mm to 3 mm) and a horizontal width (stab). The distance between the insertion portion 2 and the insertion portion 2) can be exemplified by about 1 mm to 5 mm, but as described above, the size may be appropriately adjusted according to the stitched portion.

The staple 1 shown in each embodiment is not particularly limited as long as it is a metal material that biodegrades when placed in a living body. For example, as the biodegradable metal material, pure magnesium or magnesium alloy, pure calcium or calcium alloy, pure zinc or zinc alloy and the like are used. A pure magnesium or magnesium alloy is preferred. The magnesium alloy contains magnesium as a main component and is an essential element in the body composed of H, C, N, O, Na, P, K, Ca, Fe, B, Al, Si, V, Cr, Mn, Zn, or Sc. , Y, La, Ce, Nd, Sm, Gd, Tb, Dy, Yb, preferably 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, or the periphery of the biodegradable metal material may be coated with a biodegradable resin. By coating with a biodegradable resin, the progress of corrosion of staple 1 when placed in a living body can be adjusted. The biodegradable resin is not particularly limited as long as it is enzymatically or non-enzymatically decomposed in a living body and the decomposed product does not show toxicity. For example, polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone, polylactic acid-polycaprolactone copolymer, polyorthoester, polyphosphazene, polyphosphate ester, polyhydroxybutyrate, polyapple acid, poly. Examples thereof include α-amino acids, collagen, gelatin, laminin, heparan sulfate, fibronectin, bitronectin, 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 a biodegradable metal material or a biodegradable resin. For example, the physiologically active substance may be dissolved in a solvent or the like and applied.

The physiologically active substance is not particularly limited as long as it is a known drug used for treatment or the like. For example, since staples placed in the body are foreign substances to the living body, postoperative inflammation and the like can be suppressed by carrying an anti-inflammatory agent, an antibiotic, an antiallergic agent and the like. Further, if the sutured part is a blood vessel, a hemostatic agent or the like may be carried, and if the sutured part is cancer, an anticancer agent or the like may be carried.

As described above, the staple 1 shown in each embodiment is not particularly limited in the manufacturing method as long as the connecting portion 4 is formed in a shape including a curved portion having no bending point. For example, a mold corresponding to at least the shapes of the connecting portion 4 and the erection portion 3 may be produced, and a thin plate made of a biodegradable metal material may be press-molded. Alternatively, a mold having the shape of the insertion portion 2, the connecting portion 4, and the erection portion 3 may be produced, and the melted biodegradable metal material may be injection-molded. The tip portion of the insertion portion 2 may be tapered in order to facilitate puncture into the living tissue. In order to taper the tip, a mold for pressing or injection molding may be adjusted, or a stap made by pressing or the like may be sheared or ground.

The staple 1 shown in each embodiment may be used by being set in a known stapler cartridge for living tissue. In the staple 1 shown in each embodiment, since the connecting portion 4 is located closer to the tip end side of the insertion portion 2 than the erection portion 3, the staple 1 is connected when the portion abutting on the connecting portion 4 of the cartridge has a linear shape. At least a part of the part will be separated from the part. Therefore, if a conventional U-shaped portion for pressing the stapler of the stapler is used, the pressing force may be concentrated on the top 41 of the connecting portion 4. Therefore, it is preferable that the pressing portion of the stapler using the staple 1 shown in each embodiment has a shape suitable for the connecting portion 4 and the erection portion 3.

An embodiment will be specifically described below with reference to the embodiment, but the embodiment is provided merely as a reference for the specific embodiment. These examples are for explaining specific specific embodiments of the staple 1 embodiment of the present application, but do not represent limiting or limiting the scope of the embodiments disclosed in the present application. ..

<Examples 1 to 5>
[Making alloy wire]
Magnesium (Mg), Neodium (Nd), Yttrium (Y) and Zirconium (Zr) are added to 95.6% Mg-3.0% Nd-1.0% Y-0.4% Zr by weight. Each pure metal was placed in a graphite crucible for high frequency induction heating and installed inside the high frequency coil in the high frequency melting furnace chamber. Next, after evacuating the inside of the chamber, it is filled with helium gas until it reaches atmospheric pressure, the crucible is heated to 750 ° C., and after confirming that all the metal in the crucible is melted, it is held for 10 minutes, and then held. Immediately, the melt in the crucible was cast into a cylindrical type copper mold previously installed in front of the high frequency coil. After cooling for a certain period of time, a columnar alloy ingot was obtained from this mold.

The obtained alloy ingot was hot-extruded under the conditions of a temperature of 400 ° C., an extrusion ratio of 15, and an extrusion speed of 60 mm / min, and processed into a bar having an outer diameter of 17 mm. Then, a billet (outer diameter 10 mm × length 25 mm) was cut out from this alloy rod and hot-extruded 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 surface reduction rate of the cross section of the alloy wire before and after the drawing process was adjusted to be 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 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 (radius of curvature).
Example 1: Diameter 0.2 mm (radius of curvature = 0.1 mm)
Example 2: Diameter 0.55 mm (radius of curvature = 0.275 mm)
Example 3: Diameter 0.8 mm (radius of curvature = 0.4 mm)
Example 4: Diameter 1.0 mm (radius of curvature = 0.5 mm)
Example 5: Diameter 1.5 mm (radius of curvature = 0.75 mm)

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

[Immersion experiment]
Next, an immersion experimental system imitating 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 experimental system was investigated.
First, the samples of Examples 1 to 5 were immersed in a 0.5% aqueous nitric acid solution for 20 seconds, acid-cleaned, and then ultrasonic-cleaned in the order of pure water and acetone for 1 minute each and dried.
Next, 10 ml of bovine serum (from New Zealand; Gibco manufactured by Thermo Fisher Scientific) was placed in a test tube to prepare an immersion experimental system. Then, the sample subjected to the above treatment was placed in a test tube, the test tube was held in a constant temperature bath kept at 37 ° C., and the corrosion state was observed at immersion times 3, 6 and 9 hours. The results are shown in Table 1. Corrosion fracture occurred at the bent portion as the immersion time progressed, and this tendency was more strongly observed as the radius of curvature became smaller. 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 in Examples 1 to 5 is pressed to 3 mm (distance connecting the boundary 24 between the left and right insertion portions 2 and the connecting portion 4) ×. It was processed into a staple shape of 2.5 mm (the length from the insertion portion 2 to the top 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. The radius of curvature of the connecting portion 4 was set to 0.5 mm. The length of the erection portion 3 was 2.5 mm. Next, by pressing a stainless steel rod having a diameter of 0.5 mm against the erection portion 3 of the processed staple, the erection portion 4 has a radius of curvature of 0.25 mm from the top 41 of the connecting portion 4 to the tip 21 side of the insertion portion 2. A staple having a dent was prepared. FIG. 9A is a photograph of the staples produced.

Next, the prepared staples were 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, a stainless steel rod having a diameter of 0.5 mm was not pressed against the erection portion 3 of the staples, and the staples in a pressed state were used as Comparative Example 1, and the staples were punctured in the same manner as in Example 6. 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 staples in which the erection portion is located on the tip end side of the insertion portion from the top of the connecting portion are in close contact with the sutured 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 sutured portion.
From the above results, if the connecting portion of the staple is formed into a shape including a curved portion having no bending point, it becomes difficult to break in the living body, and further, the erection portion is formed from a line connecting the tops of the connecting portions. It was clarified that the sutured portion can be adhered for a long period of time by locating at least a part on the tip side of the insertion portion.

[Suture experiment in animal body]
<Example 7>
Instead of the raw materials of Example 1, magnesium (Mg), rare earth (RE; misch metal containing Nd as a main component), and yttrium (Y) were added in 96% by weight% Mg-3.0% RE-1.0%. An alloy wire rod was produced in the same procedure as in Example 1 except that it was used so as to be Y, and then a wire rod having a wire diameter of 0.25 mm was pressed to 3 mm (left and right insertion portions 2 and connecting portion 4). It was processed into a staple shape of (distance connecting the boundaries 24) x 2.5 mm (the length from the insertion portion 2 to the top 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, the staples were sutured in the animal body according to the following procedure to examine the pathological findings.
(1) Three pigs were laparotomized under general anesthesia, and a site 50 cm from the terminal ileum was sutured mechanically in the small intestine using a suture device (manufactured by Ethicon (Johnson &Johnson); Powered ECHELON FLEX).
(2) After the operation, the animals were bred for 1 week, 2 weeks, and 4 weeks, and then the abdomen was opened, and the pathological findings around the sutured part were observed. Pathological findings were observed by macroscopic observation around the sutured part and HE staining. HE staining was performed by the following procedure.
(A) The polished specimen was deresined and then washed with water.
(B) Immersed in Weigert 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, permeable with xylene, and then sealed.

FIG. 10 (A) is a photograph of the HE-stained section one week after the operation (20-fold magnification), FIG. 10 (B) is a photograph of the HE-stained section one week after the operation (200-fold magnification), and FIG. 11 (A). ) Is a photograph of a HE-stained section 2 weeks after surgery (40-fold magnification), FIG. 11 (B) is a photograph of a HE-stained section 2 weeks after surgery (100-fold magnification), and FIG. 12 (A) is postoperative. A 4-week HE-stained section photograph (100-fold magnification) and FIG. 12 (B) are a 4-week postoperative HE-stained section photograph (400-fold magnification).

<Comparative example 2>
Examples except that a titanium staple (manufactured by Ethicon (Johnson &Johnson); ECR45W) was used instead of the staple of Example 7 and the small intestine was mechanically sutured at a position shifted from Example 7 (50 cm from the gastric pylorus). At the same time as 7, the small intestine was sutured. The pathological findings were observed in the same procedure as in Example 7.

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

From FIGS. 10 (A) to 10 (D) and macroscopic observation, the following pathological findings were obtained one week after the operation.
(A) Infiltration of inflammatory cells was observed around the metal in both Example 7 (Mg staple) and Comparative Example 2 (Ti staple), but the effect was limited to a relatively narrow range.
(B) Inflammation around the metal of both Mg staples and Ti staples extended from the mucosa to the serosal surface. The degree of inflammation was similar.
(C) Ti staples had a stronger inflammatory spread due to neutrophils, eosinophils, and lymphocytes, mainly in metals.

From FIGS. 11 (A) to 11 (D) and macroscopic observation, the following pathological findings were obtained 2 weeks after the operation.
(D) Relatively strong inflammatory cell infiltration was observed in both Mg staples and Ti staples throughout the specimen. Inflammation spread was also observed at some distance from the metal pieces.
(E) Inflammation around the metal of both Mg staples and Ti staples extended from the mucosa to the serosal surface. The degree of inflammation was similar.
(F) Ti staples had a stronger inflammatory spread due to neutrophils, eosinophils, and lymphocytes, mainly in metals.

From FIGS. 12 (A) to 12 (D) and macroscopic observation, the following pathological findings were obtained at 4 weeks after the operation.
(G) Both Mg staples and Ti staples showed relatively strong inflammatory cell infiltration throughout the specimen. Inflammation spread was also observed in places that were some distance from the metal pieces. (H) Ti staples had a stronger inflammatory spread due to neutrophils, eosinophils, and lymphocytes, mainly in metals.

From Example 7 and Comparative Example 2, in both Mg staples and Ti staples, the local inflammatory changes associated with the implantation of the metal pieces remained in the immediate vicinity (only around) of the metal pieces until one week after the operation. The degree of inflammation was similar in both cases. Then, within 4 weeks after the operation, relatively strong inflammatory cell infiltration was observed in both Mg staples and Ti staples in the whole tissue, and inflammation was also observed in a place relatively distant from the metal piece. However, it was clarified that the inflammatory spread by neutrophils, eosinophils and lymphocytes was weaker in Mg staples than in Ti staples. From the above results, it was confirmed that a biodegradable metal material is preferable as a staple material to be indwelled in a living body.

By using the staples of the embodiment disclosed in the present application, the stitched portions can be brought into close contact with each other for a long period of time. Therefore, it is useful for surgery in medical institutions.

Claims (4)

Staples made of biodegradable metal material
The staple includes two insertion portions to be inserted into a living tissue, an erection portion straddling a sutured portion, and a connecting portion connecting the insertion portion and the erection portion.
The connecting portion is formed in a shape including a curved portion having no bending point, and
At least a part of the erection part is located on the tip side of the insertion part from the line connecting the tops of the connection part .
The most curved portion of the connecting portion is a bioabsorbable staple having a radius of curvature = 0.275 mm or more . The bioabsorbable staple according to claim 1, wherein all of the erection portions are located on the tip end side of the insertion portion from the line connecting the top portions of the connection portion. The bioabsorbable staple according to claim 1 or 2 , 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 3 , wherein the biodegradable metal material is coated with a biodegradable resin.