WO2023199586A1 - Artificial skin with antimicrobial effect - Google Patents

Artificial skin with antimicrobial effect Download PDF

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Publication number
WO2023199586A1
WO2023199586A1 PCT/JP2023/004214 JP2023004214W WO2023199586A1 WO 2023199586 A1 WO2023199586 A1 WO 2023199586A1 JP 2023004214 W JP2023004214 W JP 2023004214W WO 2023199586 A1 WO2023199586 A1 WO 2023199586A1
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layer
collagen
silicone
artificial skin
silver
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French (fr)
Japanese (ja)
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一 松村
綾子 高見
綾乃 倉田
博 寺井
真理子 征矢
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株式会社ジーシー
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Publication of WO2023199586A1 publication Critical patent/WO2023199586A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/60—Materials for use in artificial skin

Definitions

  • the present invention relates to artificial skin that has an antibacterial effect.
  • the present invention was made in view of the above-mentioned circumstances, and an object of the present invention is to provide an artificial skin that can prevent the growth of bacteria.
  • One aspect of the present invention includes a collagen layer containing collagen as a main component, and a silicone layer containing silicone as a main component and covering one surface of the collagen layer, wherein between the collagen layer and the silicone layer, the silicone It is an artificial skin in which only the layer contains antibacterial agents.
  • FIG. 1 is a perspective view of an artificial skin according to an embodiment of the present invention.
  • FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating how to use the artificial skin of FIG. 1, and shows the state before the artificial skin is transplanted.
  • FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating how to use the artificial skin of FIG. 1, and shows the state after the artificial skin is transplanted.
  • FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating a method of using the artificial skin of FIG. 1, and shows the state after the formation of a dermis-like tissue.
  • FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating a method of using the artificial skin of FIG. 1, after the silicone layer is removed.
  • the artificial skin 1 is a sheet-like member, and includes a collagen layer 2 containing collagen as a main component and a silicone layer 3 containing silicone as a main component.
  • the artificial skin 1 has a two-layer structure consisting of a collagen layer 2 and a silicone layer 3 laminated in the thickness direction of the artificial skin 1, and the silicone layer 3 covers one surface of the collagen layer 2.
  • the artificial skin 1 is applied to the defect A in the skin or mucous membrane where the dermis B is missing (see FIG. 2A).
  • the size of the artificial skin 1 is designed according to the defect A to which it is applied.
  • Collagen layer 2 is a sponge made of crosslinked collagen and does not contain glycosaminoglycan. Collagen is crosslinked only by thermal crosslinking.
  • the collagen constituting the collagen layer 2 is a mixture of fibrotic atelocollagen and heat-denatured atelocollagen.
  • the silicone layer 3 has two first layers 4 made of silicone rubber and a second layer 5 arranged between the two first layers 4 and having a mesh structure.
  • the first layer 4 contains silver as an antibacterial agent 6, preferably 0.01% to 10% by weight of silver sulfate. Silver is supported in the first layer 4 in the form of particles and dispersed within the silicone.
  • the second layer 5 is made of a mesh sheet made of plastic such as PET (polyethylene terephthalate).
  • the tensile strength of the second layer 5 is higher than that of the first layer 4.
  • the artificial skin 1 has one or more drain holes 7 that penetrate the collagen layer 2 and the silicone layer 3 in the thickness direction.
  • the drain hole 7 is a passage through which exudate and hematoma accumulated in the defect A are drained from the body.
  • the drain hole 7 may have a shape other than a slit.
  • a base agent made of liquid silicone, a hardening agent, and silver as an antibacterial agent 6 (for example, 0.01 wt% to 10 wt% silver sulfate based on the total weight of the base agent, hardening agent, and silver sulfate) are added.
  • the resulting silicone mixture is formed into a sheet with a thickness of about 200 ⁇ m.
  • the mesh sheet 5 is embedded in a sheet-shaped silicone mixture, and then the silicone mixture is composited with an uncrosslinked collagen sponge. This yields a composite of silicone mixture and collagen sponge.
  • a drain hole 7 is drilled in the composite using a knife.
  • the artificial skin 1 is obtained by heat-treating the composite at about 110° C. in a vacuum to thermally crosslink the atelocollagen.
  • the artificial skin 1 is transplanted into the defect A of the skin or mucous membrane. Specifically, the artificial skin 1 is attached to the defect A so that the collagen layer 2 contacts the wound surface C, and the edges of the artificial skin 1 are attached to the defect A using sutures, staplers, etc. sutured to the surrounding skin. Since the artificial skin 1 has sufficient tensile strength due to the mesh sheet 5 within the silicone layer 3, the artificial skin 1 is prevented from tearing during suturing.
  • the collagen layer 2 within the defect A is maintained in a moist state by the silicone layer 3 covering the outside of the collagen layer 2.
  • the silicone layer 3 covering the outside of the collagen layer 2.
  • cells and capillaries invade the collagen layer 2 from around the defect A, and the cells construct a dermis-like tissue D in the defect A, while the collagen layer 2 is gradually absorbed by the living body.
  • the collagen layer 2 is gradually replaced with dermis-like tissue D.
  • exudate and hematoma accumulated in the defect A are discharged to the outside of the silicone layer 3 via the drain hole 7.
  • the silver contained in the silicone layer 3 comes into contact with the exudate, it releases silver ions, and the silver ions exert an antibacterial effect on the collagen layer 2 and/or the silicone layer 3.
  • the silicone layer 3 is removed by peeling from the surface of the dermis-like tissue D, and if necessary, a split-thickness skin graft is placed on the surface of the dermis-like tissue D. will be held.
  • the defect A where the artificial skin 1 has been transplanted is shielded from the outside by the silicone layer 3, and the silicone layer 3 prevents bacteria from entering the defect A from the outside.
  • the silicone layer 3 contains silver as the antibacterial agent 6, and silver ions released from the silver exhibit an antibacterial effect. Thereby, infection of the defective part A from the outside can be effectively prevented. Furthermore, the antibacterial action of silver ions released from silver can prevent the growth of bacteria on the collagen layer 2 and/or the silicone layer 3.
  • the antibacterial agent 6 contained in the silicone layer 3 can effectively suppress the growth of bacteria near the interface between the collagen layer 2 and the silicone layer 3.
  • the silicone layer 3 and the antibacterial agent 6 contained therein continue to stably exist outside the defect A throughout the period until the silicone layer 3 is removed. . Therefore, the antibacterial effect can continue to be stably exhibited throughout the period until the dermis-like tissue D is formed.
  • antibacterial agents such as silver can generally affect cells and tissues.
  • the antibacterial agent 6 is not contained in the collagen layer 2 but only in the outer silicone layer 3. Thereby, the antibacterial agent 6 can be prevented from affecting the formation of the dermis-like tissue D. Furthermore, after the dermis-like tissue D is formed, the antibacterial agent 6 is removed from the repaired defect A along with the silicone layer 3 and does not remain in the living body. Therefore, the influence of the antibacterial agent 6 on cells and tissues can be further suppressed.
  • the silicone layer 3 contains silver sulfate as the antibacterial agent 6, but instead may contain other types of silver commonly used as an antibacterial agent.
  • the silicone layer 3 may contain silver nitrate or silver sulfadiazine (SSD).
  • the silicone layer 3 may contain other types of antibacterial agents instead of or in addition to silver.
  • the second layer 5 is made of a mesh sheet made of plastic such as PET, but the second layer 5 is made of a mesh sheet made of another material having biocompatibility, flexibility, and high tensile strength. It may be a sheet.
  • the collagen layer 2 is made of fibrotic atelocollagen and heat-denatured atelocollagen, but the collagen constituting the collagen layer 2 may be other types of collagen commonly used in artificial skin.
  • the collagen may be atelocollagen that has not undergone either fibrosis or heat denaturation, or may be collagen from which telopeptide has not been removed.
  • the collagen of the collagen layer 2 is crosslinked only by thermal crosslinking, but the collagen may be crosslinked by other methods.
  • collagen may be crosslinked by chemical crosslinking with a crosslinking agent instead of or in addition to thermal crosslinking.
  • the artificial skin 1 has the drain hole 7, but the artificial skin 1 does not need to have the drain hole 7.
  • a user such as a doctor may make a drain hole in the artificial skin 1 using an instrument such as a scalpel.
  • the silicone layer 3 has the second layer 5 having a mesh structure, but it does not need to have the second layer 5.
  • the silicone layer 3 may be composed of only a single first layer 4.
  • the collagen layer 2 may appropriately contain additives such as glycosaminoglycan in addition to collagen as a main component.
  • the silicone layer 3 may contain arbitrary additives in addition to silicone and an antibacterial agent as main components.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

An artificial skin (1) comprises a collagen layer (2), which is mainly composed of collagen, and a silicone layer (3), which is mainly composed of silicone and covers one surface of the collagen layer (2). Of the collagen layer (2) and the silicone layer (3), only the silicone layer (3) contains an antimicrobial agent (6).

Description

抗菌効果を有する人工皮膚Artificial skin with antibacterial effect
　本発明は、抗菌効果を有する人工皮膚に関するものである。 The present invention relates to artificial skin that has an antibacterial effect.
　従来、コラーゲンスポンジを備える人工皮膚が知られている（例えば、特許文献１参照。）。皮膚の欠損部に移植されたコラーゲンスポンジに周囲から細胞が侵入し真皮様組織を構築することによって、欠損部が修復される。 Conventionally, artificial skin including a collagen sponge has been known (for example, see Patent Document 1). The defect is repaired by cells invading the collagen sponge from the surrounding area and building a dermis-like tissue.
特許第２６１０４７１号公報Patent No. 2610471
　欠損部では、皮膚のバリア機能が低下または損失しているので、細菌が増殖し易い。したがって、人工皮膚の移植において、欠損部における細菌の増殖防止が重要な課題の１つとなる。
　本発明は、上述した事情に鑑みてなされたものであって、菌の増殖を防止することができる人工皮膚を提供することを目的とする。 In the defect area, the barrier function of the skin is reduced or lost, making it easy for bacteria to grow. Therefore, in artificial skin transplantation, one of the important issues is preventing bacterial growth in the defect area.
The present invention was made in view of the above-mentioned circumstances, and an object of the present invention is to provide an artificial skin that can prevent the growth of bacteria.
　本発明の一態様は、コラーゲンを主成分とするコラーゲン層と、シリコーンを主成分とし、前記コラーゲン層の一方の表面を覆うシリコーン層とを備え、前記コラーゲン層および前記シリコーン層の内、該シリコーン層のみが抗菌剤を含む、人工皮膚である。 One aspect of the present invention includes a collagen layer containing collagen as a main component, and a silicone layer containing silicone as a main component and covering one surface of the collagen layer, wherein between the collagen layer and the silicone layer, the silicone It is an artificial skin in which only the layer contains antibacterial agents.
　本発明によれば、菌の増殖を防止することができるという効果を奏する。 According to the present invention, it is possible to prevent the proliferation of bacteria.
本発明の一実施形態に係る人工皮膚の斜視図である。FIG. 1 is a perspective view of an artificial skin according to an embodiment of the present invention. 図１の人工皮膚の使用方法を説明する皮膚または粘膜の欠損部の断面図であり、人工皮膚の移植前を示している。FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating how to use the artificial skin of FIG. 1, and shows the state before the artificial skin is transplanted. 図１の人工皮膚の使用方法を説明する皮膚または粘膜の欠損部の断面図であり、人工皮膚の移植後を示している。FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating how to use the artificial skin of FIG. 1, and shows the state after the artificial skin is transplanted. 図１の人工皮膚の使用方法を説明する皮膚または粘膜の欠損部の断面図であり、真皮様組織の形成後を示している。FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating a method of using the artificial skin of FIG. 1, and shows the state after the formation of a dermis-like tissue. 図１の人工皮膚の使用方法を説明する皮膚または粘膜の欠損部の断面図であり、シリコーン層の除去後を示している。FIG. 2 is a cross-sectional view of a defective part of the skin or mucous membrane, illustrating a method of using the artificial skin of FIG. 1, after the silicone layer is removed.
　以下に、本発明の一実施形態に係る人工皮膚について図面を参照して説明する。
　図１に示されるように、本実施形態に係る人工皮膚１は、シート状の部材であり、コラーゲンを主成分とするコラーゲン層２と、シリコーンを主成分とするシリコーン層３とを備える。人工皮膚１は、人工皮膚１の厚さ方向に積層されたコラーゲン層２およびシリコーン層３からなる２層構造を有し、シリコーン層３はコラーゲン層２の一方の表面を覆っている。 EMBODIMENT OF THE INVENTION Below, the artificial skin based on one embodiment of this invention is demonstrated with reference to drawings.
As shown in FIG. 1, the artificial skin 1 according to the present embodiment is a sheet-like member, and includes a collagen layer 2 containing collagen as a main component and a silicone layer 3 containing silicone as a main component. The artificial skin 1 has a two-layer structure consisting of a collagen layer 2 and a silicone layer 3 laminated in the thickness direction of the artificial skin 1, and the silicone layer 3 covers one surface of the collagen layer 2.
　人工皮膚１は、真皮Ｂが欠損した皮膚または粘膜の欠損部Ａを修復するために欠損部Ａに適用される（図２Ａ参照。）。人工皮膚１のサイズは、適用される欠損部Ａに応じて設計される。 The artificial skin 1 is applied to the defect A in the skin or mucous membrane where the dermis B is missing (see FIG. 2A). The size of the artificial skin 1 is designed according to the defect A to which it is applied.
　コラーゲン層２は、架橋されたコラーゲンからなるスポンジであり、グルコサミノグリカンを含まない。コラーゲンは、熱架橋のみによって架橋されている。
　コラーゲン層２を構成するコラーゲンは、線維化アテロコラーゲンと熱変性アテロコラーゲンとの混合物である。 Collagen layer 2 is a sponge made of crosslinked collagen and does not contain glycosaminoglycan. Collagen is crosslinked only by thermal crosslinking.
The collagen constituting the collagen layer 2 is a mixture of fibrotic atelocollagen and heat-denatured atelocollagen.
　シリコーン層３は、シリコーンゴムからなる２つの第１層４と、２つの第１層４の間に配置されメッシュ構造を有する第２層５とを有する。
　第１層４は、抗菌剤６として銀を含み、好ましくは、０．０１質量％～１０質量％の硫酸銀を含む。銀は、粒子の形態でシリコーン内に分散した状態で第１層４に担持される。 The silicone layer 3 has two first layers 4 made of silicone rubber and a second layer 5 arranged between the two first layers 4 and having a mesh structure.
The first layer 4 contains silver as an antibacterial agent 6, preferably 0.01% to 10% by weight of silver sulfate. Silver is supported in the first layer 4 in the form of particles and dispersed within the silicone.
　第２層５は、ＰＥＴ（ポリエチレンテレフタレート）等のプラスチック製のメッシュシートからなる。第２層５の引張強度は、第１層４の引張強度よりも高い。第２層５を設けることによって、人工皮膚１の引張強度を高め、人工皮膚１が使用中に破れることを防止することができる。 The second layer 5 is made of a mesh sheet made of plastic such as PET (polyethylene terephthalate). The tensile strength of the second layer 5 is higher than that of the first layer 4. By providing the second layer 5, the tensile strength of the artificial skin 1 can be increased and the artificial skin 1 can be prevented from tearing during use.
　人工皮膚１は、コラーゲン層２およびシリコーン層３を厚さ方向に貫通する１以上のドレーン孔７を有する。ドレーン孔７は、欠損部Ａに溜まる滲出液および血腫を体外に排出する通路である。図１の例において、同一方向に延びるスリットからなる複数のドレーン孔７が設けられている。ドレーン孔７は、スリット以外の形状であってもよい。 The artificial skin 1 has one or more drain holes 7 that penetrate the collagen layer 2 and the silicone layer 3 in the thickness direction. The drain hole 7 is a passage through which exudate and hematoma accumulated in the defect A are drained from the body. In the example of FIG. 1, there are provided a plurality of drain holes 7 consisting of slits extending in the same direction. The drain hole 7 may have a shape other than a slit.
　次に、人工皮膚１の製造方法について説明する。
　線維化アテロコラーゲンと熱変性アテロコラーゲンとを含む溶液を凍結乾燥することによって、これらアテロコラーゲン同士が架橋されていない未架橋のコラーゲンスポンジを得る。線維化アテロコラーゲンおよび熱変性アテロコラーゲンは、公知の方法（例えば、特許第２６１０４７１号公報に記載の方法）によって得られる。 Next, a method for manufacturing the artificial skin 1 will be explained.
By freeze-drying a solution containing fibrotic atelocollagen and heat-denatured atelocollagen, an uncrosslinked collagen sponge in which these atelocollagens are not crosslinked is obtained. Fibrillated atelocollagen and heat-denatured atelocollagen are obtained by known methods (for example, the method described in Japanese Patent No. 2610471).
　次に、液状のシリコーンからなる主剤と、硬化剤と、抗菌剤６である銀（例えば、主剤、硬化剤および硫酸銀の総重量に対して０．０１ｗｔ％～１０ｗｔ％の硫酸銀）とを混合し、得られたシリコーン混合物を、約２００μｍの厚さのシート状に成形する。次に、シート状のシリコーン混合物にメッシュシート５を埋め込み、次いで、シリコーン混合物を未架橋のコラーゲンスポンジと複合化させる。これにより、シリコーン混合物とコラーゲンスポンジとの複合体を得る。
　次に、刃物を使用して、複合体にドレーン孔７を開ける。
　次に、複合体を真空中にて約１１０℃で加熱処理してアテロコラーゲンを熱架橋することによって、人工皮膚１を得る。 Next, a base agent made of liquid silicone, a hardening agent, and silver as an antibacterial agent 6 (for example, 0.01 wt% to 10 wt% silver sulfate based on the total weight of the base agent, hardening agent, and silver sulfate) are added. The resulting silicone mixture is formed into a sheet with a thickness of about 200 μm. Next, the mesh sheet 5 is embedded in a sheet-shaped silicone mixture, and then the silicone mixture is composited with an uncrosslinked collagen sponge. This yields a composite of silicone mixture and collagen sponge.
Next, a drain hole 7 is drilled in the composite using a knife.
Next, the artificial skin 1 is obtained by heat-treating the composite at about 110° C. in a vacuum to thermally crosslink the atelocollagen.
　次に、人工皮膚１の使用方法について説明する。
　図２Ａおよび図２Ｂに示されるように、人工皮膚１は、皮膚または粘膜の欠損部Ａに移植される。具体的には、人工皮膚１は、コラーゲン層２が創面Ｃに接触するように欠損部Ａに貼り付けられ、人工皮膚１の縁部が、縫合糸またはステープラ等を使用して欠損部Ａの周囲の皮膚に縫合される。シリコーン層３内のメッシュシート５によって人工皮膚１は十分な引張強度を有するので、縫合時に人工皮膚１が裂けてしまうことが防止される。 Next, a method of using the artificial skin 1 will be explained.
As shown in FIGS. 2A and 2B, the artificial skin 1 is transplanted into the defect A of the skin or mucous membrane. Specifically, the artificial skin 1 is attached to the defect A so that the collagen layer 2 contacts the wound surface C, and the edges of the artificial skin 1 are attached to the defect A using sutures, staplers, etc. sutured to the surrounding skin. Since the artificial skin 1 has sufficient tensile strength due to the mesh sheet 5 within the silicone layer 3, the artificial skin 1 is prevented from tearing during suturing.
　人工皮膚１の移植後、コラーゲン層２の外側を覆うシリコーン層３によって欠損部Ａ内のコラーゲン層２は湿潤状態に維持される。湿潤状態において、図２Ｃに示されるように、欠損部Ａの周囲からコラーゲン層２へ細胞および毛細血管が侵入して細胞が欠損部Ａに真皮様組織Ｄを構築し、その一方で、コラーゲン層２は次第に生体に吸収される。これにより、コラーゲン層２が次第に真皮様組織Ｄに置換される。また、欠損部Ａに溜まる滲出液および血腫は、ドレーン孔７を経由してシリコーン層３の外側へ排出される。また、シリコーン層３に含まれる銀が滲出液に接触することによって銀イオンを放出し、銀イオンがコラーゲン層２および／またはシリコーン層３において抗菌効果を発揮する。 After the artificial skin 1 is transplanted, the collagen layer 2 within the defect A is maintained in a moist state by the silicone layer 3 covering the outside of the collagen layer 2. In the wet state, as shown in FIG. 2C, cells and capillaries invade the collagen layer 2 from around the defect A, and the cells construct a dermis-like tissue D in the defect A, while the collagen layer 2 is gradually absorbed by the living body. As a result, the collagen layer 2 is gradually replaced with dermis-like tissue D. Further, exudate and hematoma accumulated in the defect A are discharged to the outside of the silicone layer 3 via the drain hole 7. Furthermore, when the silver contained in the silicone layer 3 comes into contact with the exudate, it releases silver ions, and the silver ions exert an antibacterial effect on the collagen layer 2 and/or the silicone layer 3.
　図２Ｄに示されるように、真皮様組織Ｄが構築された後、シリコーン層３は、真皮様組織Ｄの表面から剥がすことによって除去され、必要に応じて真皮様組織Ｄの表面に分層植皮が行われる。 As shown in FIG. 2D, after the dermis-like tissue D is constructed, the silicone layer 3 is removed by peeling from the surface of the dermis-like tissue D, and if necessary, a split-thickness skin graft is placed on the surface of the dermis-like tissue D. will be held.
　この場合において、人工皮膚１が移植された欠損部Ａはシリコーン層３によって外部から遮蔽され、外部から欠損部Ａへの菌の侵入がシリコーン層３によって防止される。
　特に、シリコーン層３に抗菌剤６の銀が含まれ、銀から放出される銀イオンが抗菌作用を発揮する。これにより、外部からの欠損部Ａの感染を効果的に防止することができる。
　また、銀から放出される銀イオンの抗菌作用によって、コラーゲン層２および／またはシリコーン層３での菌の増殖を防止することができる。 In this case, the defect A where the artificial skin 1 has been transplanted is shielded from the outside by the silicone layer 3, and the silicone layer 3 prevents bacteria from entering the defect A from the outside.
In particular, the silicone layer 3 contains silver as the antibacterial agent 6, and silver ions released from the silver exhibit an antibacterial effect. Thereby, infection of the defective part A from the outside can be effectively prevented.
Furthermore, the antibacterial action of silver ions released from silver can prevent the growth of bacteria on the collagen layer 2 and/or the silicone layer 3.
　また、コラーゲン層とシリコーン層とからなる従来の人工皮膚の臨床現場での使用において、コラーゲン層とシリコーン層との間の界面付近で細菌が増殖し易いことが報告されている。本実施形態によれば、シリコーン層３に含まれる抗菌剤６によって、コラーゲン層２とシリコーン層３との間の界面付近での細菌の増殖を効果的に抑制することができる。 Furthermore, it has been reported that when conventional artificial skin consisting of a collagen layer and a silicone layer is used in a clinical setting, bacteria tend to grow near the interface between the collagen layer and the silicone layer. According to this embodiment, the antibacterial agent 6 contained in the silicone layer 3 can effectively suppress the growth of bacteria near the interface between the collagen layer 2 and the silicone layer 3.
　また、生体吸収されるコラーゲン層２とは異なり、シリコーン層３およびこれに含まれる抗菌剤６は、シリコーン層３が除去されるまでの期間ずっと、欠損部Ａの外側に安定的に存在し続ける。したがって、真皮様組織Ｄが形成されるまでの期間中ずっと抗菌作用を安定的に発揮し続けることができる。 Furthermore, unlike the collagen layer 2 which is bioabsorbed, the silicone layer 3 and the antibacterial agent 6 contained therein continue to stably exist outside the defect A throughout the period until the silicone layer 3 is removed. . Therefore, the antibacterial effect can continue to be stably exhibited throughout the period until the dermis-like tissue D is formed.
　また、一般に銀等の抗菌剤は、細胞および組織に影響する可能性がある。抗菌剤６は、コラーゲン層２には含まれず、外側のシリコーン層３のみに含まれる。これにより、抗菌剤６が真皮様組織Ｄの形成に影響することを防ぐことができる。さらに、真皮様組織Ｄが形成された後、抗菌剤６は、シリコーン層３と共に修復された欠損部Ａから除去され、生体に残らない。したがって、抗菌剤６の細胞および組織への影響をさらに抑制することができる。 Additionally, antibacterial agents such as silver can generally affect cells and tissues. The antibacterial agent 6 is not contained in the collagen layer 2 but only in the outer silicone layer 3. Thereby, the antibacterial agent 6 can be prevented from affecting the formation of the dermis-like tissue D. Furthermore, after the dermis-like tissue D is formed, the antibacterial agent 6 is removed from the repaired defect A along with the silicone layer 3 and does not remain in the living body. Therefore, the influence of the antibacterial agent 6 on cells and tissues can be further suppressed.
　上記実施形態において、シリコーン層３が、抗菌剤６として硫酸銀を含むこととしたが、これに代えて、抗菌剤として一般に使用される他の種類の銀を含んでいてもよい。例えば、シリコーン層３は、硝酸銀またはスルファジアジン銀（ＳＳＤ）を含んでいてもよい。
　また、シリコーン層３は、銀に代えて、またはこれに加えて、他の種類の抗菌剤を含んでいてもよい。 In the above embodiment, the silicone layer 3 contains silver sulfate as the antibacterial agent 6, but instead may contain other types of silver commonly used as an antibacterial agent. For example, the silicone layer 3 may contain silver nitrate or silver sulfadiazine (SSD).
Also, the silicone layer 3 may contain other types of antibacterial agents instead of or in addition to silver.
　上記実施形態において、第２層５が、ＰＥＴ等のプラスチック製のメッシュシートからなることとしたが、第２層５は、生体適合性、柔軟性および高い引張強度を有する他の材料からなるメッシュシートであってもよい。 In the above embodiment, the second layer 5 is made of a mesh sheet made of plastic such as PET, but the second layer 5 is made of a mesh sheet made of another material having biocompatibility, flexibility, and high tensile strength. It may be a sheet.
　上記実施形態において、コラーゲン層２が、線維化アテロコラーゲンおよび熱変性アテロコラーゲンからなることとしたが、コラーゲン層２を構成するコラーゲンは、人工皮膚において一般に使用される他の種類のコラーゲンであってもよい。例えば、コラーゲンは、線維化および熱変性のいずれもされていないアテロコラーゲンであってもよく、または、テロペプチドが除去されていないコラーゲンであってもよい。 In the above embodiment, the collagen layer 2 is made of fibrotic atelocollagen and heat-denatured atelocollagen, but the collagen constituting the collagen layer 2 may be other types of collagen commonly used in artificial skin. . For example, the collagen may be atelocollagen that has not undergone either fibrosis or heat denaturation, or may be collagen from which telopeptide has not been removed.
　上記実施形態において、コラーゲン層２のコラーゲンが熱架橋のみによって架橋されることとしたが、コラーゲンは他の方法によって架橋されてもよい。例えば、コラーゲンは、熱架橋に代えて、またはこれに加えて、架橋剤による化学架橋によって架橋されていてもよい。 In the above embodiment, the collagen of the collagen layer 2 is crosslinked only by thermal crosslinking, but the collagen may be crosslinked by other methods. For example, collagen may be crosslinked by chemical crosslinking with a crosslinking agent instead of or in addition to thermal crosslinking.
　上記実施形態において、人工皮膚１がドレーン孔７を有することとしたが、人工皮膚１は、ドレーン孔７を有していなくてもよい。この場合、医師等の使用者が、メス等の器具を使用して人工皮膚１にドレーン孔を開けてもよい。
　上記実施形態において、シリコーン層３がメッシュ構造の第２層５を有することとしたが、第２層５を有していなくてもよい。この場合、シリコーン層３は、単一の第１層４のみから構成されていてもよい。 In the above embodiment, the artificial skin 1 has the drain hole 7, but the artificial skin 1 does not need to have the drain hole 7. In this case, a user such as a doctor may make a drain hole in the artificial skin 1 using an instrument such as a scalpel.
In the above embodiment, the silicone layer 3 has the second layer 5 having a mesh structure, but it does not need to have the second layer 5. In this case, the silicone layer 3 may be composed of only a single first layer 4.
　上記実施形態において、コラーゲン層２は、主成分のコラーゲンに加えて、グルコサミノグリカン等の添加物を適宜含んでいてもよい。
　また、シリコーン層３は、主成分のシリコーンと抗菌剤に加えて、任意の添加物を含んでいてもよい。 In the embodiment described above, the collagen layer 2 may appropriately contain additives such as glycosaminoglycan in addition to collagen as a main component.
Further, the silicone layer 3 may contain arbitrary additives in addition to silicone and an antibacterial agent as main components.
　１　人工皮膚
　２　コラーゲン層
　３　シリコーン層
　４　第１層
　５　第２層
　６　銀、抗菌剤
　７　ドレーン孔
　Ａ　欠損部
　Ｂ　真皮
　Ｃ　創面
　Ｄ　真皮様組織  1 Artificial skin 2 Collagen layer 3 Silicone layer 4 First layer 5 Second layer 6 Silver, antibacterial agent 7 Drain hole A Defective area B Dermis C Wound surface D Dermis-like tissue

Claims (4)

  1. 　コラーゲンを主成分とするコラーゲン層と、
    　シリコーンを主成分とし、前記コラーゲン層の一方の表面を覆うシリコーン層とを備え、
    　前記コラーゲン層および前記シリコーン層の内、該シリコーン層のみが抗菌剤を含む、人工皮膚。     A collagen layer whose main component is collagen,
    a silicone layer containing silicone as a main component and covering one surface of the collagen layer;
    Of the collagen layer and the silicone layer, only the silicone layer contains an antibacterial agent.
  2. 　前記抗菌剤が、銀を含み、好ましくは、硫酸銀、硝酸銀およびスルファジアジン銀の中から選択される、請求項１に記載の人工皮膚。 Artificial skin according to claim 1, wherein the antimicrobial agent comprises silver, preferably selected from silver sulfate, silver nitrate and silver sulfadiazine.
  3. 　前記シリコーン層が、シリコーンを主成分とする第１層と、メッシュ構造を有する第２層とを含み、
    　前記第２層の引張強度が、前記第１層の引張強度よりも高い、請求項１または請求項２に記載の人工皮膚。     The silicone layer includes a first layer containing silicone as a main component and a second layer having a mesh structure,
    The artificial skin according to claim 1 or 2, wherein the second layer has a higher tensile strength than the first layer.
  4. 　前記コラーゲン層および前記シリコーン層を厚さ方向に貫通するドレーン孔を有する、請求項１または請求項２に記載の人工皮膚。 The artificial skin according to claim 1 or 2, having a drain hole that penetrates the collagen layer and the silicone layer in the thickness direction.
PCT/JP2023/004214 2022-04-14 2023-02-08 Artificial skin with antimicrobial effect WO2023199586A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989008465A1 (en) * 1988-03-09 1989-09-21 Terumo Kabushiki Kaisha Medical material permitting cells to enter thereinto and artificial skin
JPH05192363A (en) * 1991-11-07 1993-08-03 Terumo Corp Wound covering material
CN106853263A (en) * 2017-02-16 2017-06-16 深圳齐康医疗器械有限公司 A kind of artificial skin and preparation method thereof
US20220031446A1 (en) * 2018-09-19 2022-02-03 Shenzhen Tsingcare Medical Instruments Co., Ltd. Artificial dermis repair material and preparation method therefor

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989008465A1 (en) * 1988-03-09 1989-09-21 Terumo Kabushiki Kaisha Medical material permitting cells to enter thereinto and artificial skin
JPH05192363A (en) * 1991-11-07 1993-08-03 Terumo Corp Wound covering material
CN106853263A (en) * 2017-02-16 2017-06-16 深圳齐康医疗器械有限公司 A kind of artificial skin and preparation method thereof
US20220031446A1 (en) * 2018-09-19 2022-02-03 Shenzhen Tsingcare Medical Instruments Co., Ltd. Artificial dermis repair material and preparation method therefor

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