Antibacterial coating skin staple and method for manufacturing same

Abstract

The present invention relates to a method for manufacturing an antibacterial coating skin staple, the method comprising the steps of: coating a steel wire with an antibacterial coating composition (S11); drying the steel wire (S12); cutting the coated steel wire (S13); and molding the cut steel wires (S14), wherein the antibacterial coating composition contains a mussel-derived adhesive protein.

Description

Antibacterial coated skin staple and method for manufacturing the same

[0001] The present invention relates to an antibacterial coating skin staple using an adhesive protein containing an antibacterial peptide and a method for producing the same.

[0002] In general, a skin stapler is an improved version of the conventional method of suturing incised skin areas during surgical or plastic surgery with sutures and needles. It refers to a device that sutures the skin using staples, which are suture materials.

[0003] Medical surgical staples are widely used for organ resection and anastomosis. Their advantage is that they can perform resection and anastomosis simultaneously, shortening surgical time and ensuring precise closure of the surgical site. Medical staples are divided into open staples, used through an open thoracotomy or laparotomy, and endoscopic staples, used in thoracoscopic and laparoscopic procedures.

[0004] The above-mentioned medical staple device is widely used in modern surgical operations as a device for tissue excision and suturing due to its advantages of faster recovery and less scarring than when using surgical sutures.

[0005] Medical staples consist of a main body and a pair of legs formed at each end of the main body, forming a "ㄷ" shape when viewed from the front. The tips of the legs are sharply pointed to reduce penetration resistance when penetrating living tissue.

[0006] The medical staples as described above are manufactured, for example, by bending the two ends of a straight steel wire with a circular cross-section in a direction approaching each other, and when the two ends are at a predetermined angle before becoming perpendicular to the center, cutting the two ends with a punch and moving the blade thereof relatively in the direction in which the two ends were bent in a direction perpendicular to the center, and then bending the two ends approximately perpendicular to the center.

[0007] The medical staples manufactured as described above are loaded one by one into a magazine and supplied to a medical stapler. The magazine is composed of a body support section that supports and guides the central part (body section) of the medical staple, a descending section that is hung from both ends of the body support section, and a guide section formed at the bottom of the descending section that guides the tip of the bent part (leg) of the medical staple, and is formed in the shape of an Ω when viewed from the front.

[0008] Additionally, a pusher is installed on the body support of the magazine, and the medical staples filled in the magazine are biased toward the anvil by this pusher.

[0009] These medical staplers are distributed in sterile packaging with sterilized magazines and staples. However, postoperative suture site infections can lead to prolonged hospital stays and readmissions. A meta-analysis reported that stapled sutures in orthopedic surgery are associated with a higher incidence of wound infections compared to sutures using thread. While staplers offer a short and relatively easy suturing time, they are also associated with a higher risk of wound infection compared to sutures.

[0010] Research is needed to reduce the risk of infection from medical staplers.

[0011] The present invention aims to provide an antibacterial coated skin staple capable of preventing patient infection at a medical suture site and a method for manufacturing the same.

[0012] In order to achieve the above purpose, the present invention,

[0013] Provided are an antibacterial coated skin staple and a method for manufacturing the same that can prevent patient infection at a medical suture site.

[0014] In an antibacterial coating skin staple formed by coating with an antibacterial coating composition,

[0015] The above antibacterial coating composition provides an antibacterial coating skin staple characterized by comprising a DOPA-substituted antibacterial mussel adhesive protein, DIWater, ethanol, and sodium bicarbonate.

[0016] The antimicrobial peptide in the above antimicrobial coating composition is characterized by being KLWKKWAKKWLKLWKA (SEQ ID NO: 1) or CYCRIPACIAGERRYGTCIYQGRLWAFCC (SEQ ID NO: 2).

[0017] The above DOPA-substituted antibacterial mussel adhesive protein is characterized by a concentration of 300 to 500 ppm.

[0018] The ratio of the DOPA-substituted mussel adhesive protein and the ethanol is characterized by being 7:3 to 6:4.

[0019] The above sodium bicarbonate is characterized in that it is mixed in an amount of 3 to 5 wt%.

[0020] The above DOPA-substituted mussel adhesive protein is characterized in that it is 0.03 to 0.05 wt%, the DIWater is 57.12 to 67.94 wt%, the ethanol is 29.12 to 38.08 wt%, and the 100 mM sodium bicarbonate is 2.91 to 4.76 wt%.

[0021] A method for manufacturing an antibacterial coated skin staple according to another embodiment of the present invention,

[0022] Step (S11) of coating the steel wire with an antibacterial coating composition;

[0023] Step of drying the above steel wire (S12),

[0024] Coated steel wire cutting step (S13),

[0025] Including a cut steel wire forming step (S14),

[0026] The antimicrobial peptide in the above antimicrobial coating composition is characterized by being KLWKKWAKKWLKLWKA (SEQ ID NO: 1) or CYCRIPACIAGERRYGTCIYQGRLWAFCC (SEQ ID NO: 2).

[0027] A method for manufacturing an antibacterial coated skin staple according to another embodiment of the present invention,

[0028] Steel wire cutting stage (S21),

[0029] Step of forming the cut steel wire into a skin staple shape (S22),

[0030] Step (S23) of coating the above skin staple with an antibacterial composition;

[0031] Including a step (S24) of drying the above skin staple,

[0032] The antimicrobial peptide in the above antimicrobial coating composition is characterized by being KLWKKWAKKWLKLWKA (SEQ ID NO: 1) or CYCRIPACIAGERRYGTCIYQGRLWAFCC (SEQ ID NO: 2).

[0033] In order to achieve the above-mentioned purpose, the present invention provides an antibacterial coated skin staple capable of preventing patient infection at a medical suture site and a method for manufacturing the same.

[0034] According to an embodiment of the present invention configured as described above, an antibacterial coated skin staple capable of preventing patient infection at a medical suture site and a method for manufacturing the same can be provided.

[0035] Figure 1 is a drawing showing a skin staple.

[0036] Figure 2 is a drawing showing a skin stapler.

[0037] Figure 3 is a flow chart showing a method for manufacturing an antibacterial coated skin staple according to the first embodiment.

[0038] Figure 4 is a flow chart showing a method for manufacturing an antibacterial coated skin staple according to a second embodiment.

[0039] Figure 5 is a drawing showing the results of an antibacterial test of an antibacterial coated skin staple according to an embodiment of the present invention.

[0040] The present invention is capable of various modifications and embodiments. Specific embodiments are illustrated in the drawings and described in detail in the detailed description. The effects and features of the present invention, as well as the methods for achieving them, will become clearer with reference to the embodiments described in detail below, along with the drawings. However, the present invention is not limited to the embodiments disclosed below and can be implemented in various forms.

[0041] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings. When describing with reference to the drawings, identical or corresponding components are given the same drawing reference numerals, and redundant descriptions thereof will be omitted.

[0042] In the following examples, terms such as first, second, etc. are not used in a limiting sense, but are used for the purpose of distinguishing one component from another. In the following examples, singular expressions include plural expressions unless the context clearly indicates otherwise. In the following examples, terms such as include or have mean that a feature or component described in the specification exists, and do not exclude in advance the possibility that one or more other features or components may be added. In the following examples, when a part such as a film, region, or component is said to be on or above another part, it includes not only the case where it is directly on the other part, but also the case where another film, region, component, etc. is interposed.

[0043] For convenience of explanation, the sizes of components in the drawings may be exaggerated or reduced. For example, the sizes and thicknesses of each component shown in the drawings are arbitrarily indicated for convenience of explanation, and thus the present invention is not necessarily limited to what is shown.

[0044] In some embodiments, where implementations are otherwise feasible, specific process sequences may be performed in a different order than described. For example, two processes described in succession may be performed substantially simultaneously, or in a reverse order from the described order.

[0045] In the following examples, when it is said that a film, region, component, etc. are connected, it includes not only cases where the films, regions, and components are directly connected, but also cases where other films, regions, and components are interposed between the films, regions, and components and thus indirectly connected. For example, when it is said in this specification that a film, region, component, etc. are electrically connected, it includes not only cases where the films, regions, and components are directly electrically connected, but also cases where other films, regions, and components are interposed between them and thus indirectly electrically connected.

[0046] FIG. 1 illustrates an antibacterial coated skin staple (100) according to one embodiment of the present invention, and FIG. 2 illustrates a medical suture device (a) and a skin staple cartridge (b) on which the antibacterial coated skin staple (100) of FIG. 1 is movably mounted.

[0047] As illustrated, the staple (100) used in the skin stapler is formed with a body and a pair of legs formed at both ends of the body, and is formed in an approximately “ㄷ” shape. The ends of the legs may be formed with sharp tips to reduce penetration resistance when penetrating living tissue. The skin staple (100) is mounted on the cartridge (b) of the skin stapler (a) of FIG. 2, and when it leaves the skin stapler (a), its both ends are bent inward to suture the skin. The skin staple (100) is formed of a steel wire having a circular cross-section. The antibacterial skin staple according to an embodiment of the present invention may be formed by forming a steel wire and then applying an antibacterial coating thereto, or by cutting and forming a steel wire after applying an antibacterial coating thereto.

[0048] Figures 3 and 4 are flow charts showing the manufacturing process of antibacterial coated skin staples.

[0049] FIG. 3 is a flow chart showing a method for manufacturing an antibacterial coated skin staple according to the first embodiment, which includes, as shown, a step of coating a steel wire with an antibacterial composition (S11), a step of drying the coating composition (S12), a step of cutting the coated steel wire (S13), and a step of forming the cut steel wire (S13).

[0050] The coating step is performed by spraying the antimicrobial composition onto the steel wire using a spray gun in two or more directions and allowing the spray gun to pass through the steel wire. In another embodiment, the coating step is performed by immersing the steel wire in the antimicrobial composition for a set period of time.

[0051] The antibacterial composition is composed of a DOPA-substituted antibacterial mussel adhesive protein, DI water, ethanol, and sodium bicarbonate. The DOPA-substituted antibacterial mussel adhesive protein is prepared at a concentration of 100 to 1,000 ppm, preferably 300 to 500 ppm, and mixed well with ethanol. At this time, the ratio of the mussel adhesive protein to ethanol is maintained at 8:2 to 5:5, and more preferably 7:3 to 6:4. Finally, 100 mM sodium bicarbonate is added to the mixed solution of the mussel adhesive protein and ethanol and mixed quickly. At this time, the ratio of 100 mM sodium bicarbonate to be added is 1 to 10%, and more preferably 3 to 5%.

[0052] The weight ratio (%) of each component is 0.03 to 0.05% of antibacterial mussel adhesive protein, 57.12 to 67.94% of DIWater, 29.12 to 38.08% of ethanol, and 2.91 to 4.76% of 100 mM sodium bicarbonate.

[0053] When an antibacterial coating composition is prepared at the above weight ratio, it is possible to coat a steel wire and prevent separation of the antibacterial coating composition after coating is completed.

[0054] In the coating composition drying step (S12), the steel wire that performed step S11 is dried at room temperature for a set time.

[0055] In the coated steel wire cutting step (S13), the coated steel wire is cut to a set length.

[0056] The ends of the cut steel wire are bent toward each other to form a bridge, and the tip of the bridge is formed into a sharp tip to reduce penetration resistance when penetrating living tissue, thereby completing the staple.

[0057] FIG. 4 is a flow chart showing a method for manufacturing an antibacterial coated skin staple according to a second embodiment, which includes, as shown, a steel wire cutting step (S21), a cut steel wire forming step (S22), a steel wire coating step with an antibacterial composition (S23), and a coating composition drying step (S24).

[0058] After cutting the steel wire to a set length (S21), the cut steel wire is shaped as in step S13 (S22), and then coated with an antibacterial composition (S23). The coating step is performed by immersing the steel wire in the antibacterial composition for a set period of time. After immersing for a set period of time, the steel wire is dried at room temperature (S24).

[0059] As described above, the antimicrobial skin staple according to an embodiment of the present invention is coated with an antimicrobial composition. The antimicrobial composition may be a mussel adhesive protein. An example of a commercially available substrate protein includes BV AMP sold by Biovit Co., Ltd. An optional third component is a biocompatible polymer (e.g., polyethylene glycol or polyvinyl alcohol), which may be added to the composition to enhance the coating process and improve physical or mechanical properties, such as viscosity.

[0060] Antimicrobial peptides are generally cationic, with a net charge as high as +9 in some instances. The mixed cationic and hydrophobic composition of antimicrobial peptides is typically rich in lipids such as phosphatidylglycerol or cardiolipin, making them well suited to interact with and disrupt microbial cell membranes, which provide an anionic surface (William C Wimley, Describing the Mechanism of Antimicrobial Peptide Action with the Interfacial Activity Model, ACS Chem Biol 2010; 5(10): 905-917).

[0061] Due to the contribution of electrostatic interactions, antimicrobial peptide binding to microbial membranes is significant, but binding to the neutral phosphatidylcholine / cholesterol / sphingomyelin-rich surfaces of animal cytoplasm is weak. After contact with AMP for more than 1 hour, the microbial cytoplasmic membrane structure is completely disrupted.

[0062] Antimicrobial peptides are amino acid chains produced as part of the innate immune system of living organisms in nature, and generally exhibit antibiotic activity against bacteria, viruses, and fungi. In particular, antimicrobial peptides disrupt bacterial cell membranes or form pores, causing loss of intracellular materials, and surfaces coated with antimicrobial adhesive proteins can prevent this type of microbial contamination by providing antimicrobial peptides that act only on the membrane surface of microorganisms and not on human cell membranes. The antimicrobial coating composition comprises a mussel adhesive protein functionalized with one or two antimicrobial peptides that can be recombinantly incorporated into the C-terminus, N-terminus, or both the C- and N-termini of the adhesive protein as the adhesive protein.

[0063] It is preferable that the antimicrobial peptide in the above antimicrobial coating composition uses KLWKKWAKKWLKLWKA (SEQ ID NO: 1) located at the N-terminus and CYCRIPACIAGERRYGTCIYQGRLWAFCC (SEQ ID NO: 2) located at the C-terminus.

[0064] The antimicrobial peptide of sequence number 1 has high antimicrobial activity against gram-positive bacteria, and the antimicrobial peptide of sequence number 2 has high antimicrobial activity against gram-negative bacteria, and only exhibits bacteriostatic activity against the gram-positive bacterium Staphylococcus aureus. (The International Journal of Biochemistry & Cell Biology 1999, 31, 645-651) Therefore, in the present invention, the two types of antimicrobial peptides were used to prevent patient infection from both gram-positive and gram-negative bacteria.

[0065] The antibacterial mussel adhesive protein can be enzymatically treated to convert tyrosine residues into DOPA residues, and after lyophilization, the antibacterial adhesive protein containing DOPA can be dissolved in distilled water. The DOPA-substituted antibacterial mussel adhesive protein is prepared at a concentration of 100 to 1,000 ppm, preferably 300 to 500 ppm, and mixed well with ethanol. At this time, the ratio of mussel adhesive protein to ethanol is maintained at 8:2 to 5:5, and more preferably 7:3 to 6:4. Finally, 100 mM sodium bicarbonate is added to the mixed solution of mussel adhesive protein and ethanol and mixed quickly. At this time, the ratio of 100 mM sodium bicarbonate is added at 1 to 10%, and more preferably 3 to 5%.

[0066] The weight ratio (%) of each component is 0.03 to 0.05% of antibacterial mussel adhesive protein, 57.12 to 67.94% of DIWater, 29.12 to 38.08% of ethanol, and 2.91 to 4.76% of 100 mM sodium bicarbonate.

[0067] FIG. 5 is a drawing showing the results of an antibacterial test of an antibacterial skin staple manufactured according to an embodiment of the present invention configured as described above.

[0068] This is the result of placing 20 antibacterial coated skin staples and 20 uncoated staples in a tube, adding cultured E. coli solution and Staphylococcus aureus respectively, mixing in a shaker, and checking the degree of bacterial death for 3 hours. In tube (a) containing uncoated staples, no bacteria were killed, while in tube (b) containing the skin staple of the present invention coated with an antibacterial composition, bacteria were killed.

Claims

1. In a skin staple coated with an antibacterial coating composition, The above antibacterial coating composition comprises a DOPA-substituted antibacterial mussel adhesive protein, DIWater, ethanol, and sodium bicarbonate, An antibacterial coated skin staple characterized in that the DOPA substituted mussel adhesive protein is 0.03 to 0.05 wt%, the DIWater is 57.12 to 67.94 wt%, the ethanol is 29.12 to 38.08 wt%, and the 100 mM sodium bicarbonate is 2.91 to 4.76 wt%.

2. In paragraph 1, An antibacterial coating skin staple characterized in that the above DOPA-substituted antibacterial mussel adhesive protein has a concentration of 300 to 500 ppm.

3. Step of coating the steel wire with an antibacterial coating composition (S11) Step of drying the above steel wire (S12), Coated steel wire cutting step (S13), Including a cut steel wire forming step (S14), The above antibacterial coating composition comprises a DOPA-substituted antibacterial mussel adhesive protein, DIWater, ethanol, and sodium bicarbonate, A method for manufacturing an antibacterial coated skin staple, characterized in that the DOPA substituted mussel adhesive protein is 0.03 to 0.05 wt%, the DIWater is 57.12 to 67.94 wt%, the ethanol is 29.12 to 38.08 wt%, and the 100 mM sodium bicarbonate is 2.91 to 4.76 wt%.

4. Steel wire cutting stage (S21), Step of forming the cut steel wire into a skin staple shape (S22), Step (S23) of coating the above skin staple with an antibacterial composition; Including a step (S24) of drying the above skin staple, The above antibacterial coating composition comprises a DOPA-substituted antibacterial mussel adhesive protein, DIWater, ethanol, and sodium bicarbonate, A method for manufacturing an antibacterial coated skin staple, characterized in that the DOPA substituted mussel adhesive protein is 0.03 to 0.05 wt%, the DIWater is 57.12 to 67.94 wt%, the ethanol is 29.12 to 38.08 wt%, and the 100 mM sodium bicarbonate is 2.91 to 4.76 wt%.

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