JP2015066404A - Wound covering material - Google Patents
Wound covering material Download PDFInfo
- Publication number
- JP2015066404A JP2015066404A JP2013206393A JP2013206393A JP2015066404A JP 2015066404 A JP2015066404 A JP 2015066404A JP 2013206393 A JP2013206393 A JP 2013206393A JP 2013206393 A JP2013206393 A JP 2013206393A JP 2015066404 A JP2015066404 A JP 2015066404A
- Authority
- JP
- Japan
- Prior art keywords
- water
- copolymer
- wound dressing
- wound
- mass
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Abstract
Description
本発明は、創傷被覆材に関する。詳しくは、病原因子産生抑制効果を有する水溶性ポリリン酸化合物を徐々に放出すること(以下、徐放という)が可能な創傷被覆材に関する。 The present invention relates to a wound dressing. Specifically, the present invention relates to a wound dressing capable of gradually releasing a water-soluble polyphosphate compound having a pathogenic factor production inhibitory effect (hereinafter referred to as sustained release).
創傷被覆材は、外傷性の皮膚創傷及び採皮創等の創傷並びに疾患に伴う創傷部に対する創傷保護剤又は保護材料として用いるものであり、創傷部を乾燥状態に保ち、滲出液の流出を防いで痂皮形成することによって治癒するドライドレッシングタイプと、創傷部を常に湿潤状態に保ち、滲出液中に含まれる種々の治療促進因子により治癒するウェットドレッシングタイプに大別される。 The wound dressing is used as a wound protective agent or protective material for wounds such as traumatic skin wounds and skin wounds and wounds associated with diseases, and keeps the wound dry and prevents exudate from flowing out. The dry dressing type that heals by forming a scab in the skin and the wet dressing type that keeps the wound part moist always and heals by various treatment promoting factors contained in the exudate.
また近年では、創傷を負った際にヒトは種々の治癒促進因子を産生していることが明らかになってきたが、創傷が細菌に感染していると、細菌が出す病原因子によって、この治癒促進因子が分解され治癒が進まないことが明らかとなってきた。 In recent years, it has been clarified that humans produce various healing-promoting factors when wounded. When wounds are infected with bacteria, the pathogenic factors produced by the bacteria cause this healing. It has become clear that facilitating factors are degraded and healing does not proceed.
ドライドレッシングタイプの創傷被覆材として、例えば、スミスアンドネフューハル社からはメロリン(MELOLIN)の名称で知られる創傷被覆材が上市されている。該創傷被覆材は創傷接触面に多孔性ポリエステルフィルム、その外側にコットン/アクリル繊維から構成される吸収層、及び創傷被覆面から最も離れた外層にポリエステル不織布を有する、3層からなる絆創膏タイプである。この創傷被覆材では多孔性ポリエステルフィルムにより創傷部からの滲出液をすばやく吸収することで、創傷面への滲出液の固着を防ぎ、その外側に位置する吸収層で滲出液を吸収、保持して外部への漏れを防止し、外層のポリエステル不織布により創傷部が外部から保護されている。 As a dry dressing type wound dressing, for example, a wound dressing known by the name of MELOLIN is marketed by Smith & Nefuhar. The wound dressing is a three-layer adhesive plaster type having a porous polyester film on the wound contact surface, an absorbent layer composed of cotton / acrylic fibers on the outside, and a polyester nonwoven fabric on the outermost layer farthest from the wound dressing surface. is there. In this wound dressing material, the porous polyester film absorbs exudate from the wound part quickly, thereby preventing the exudate from adhering to the wound surface and absorbing and holding the exudate in the absorbent layer located outside the wound surface. Leakage to the outside is prevented, and the wound portion is protected from the outside by the polyester nonwoven fabric of the outer layer.
ドライドレッシングタイプの創傷被覆材は、滲出液の吸収、乾燥を迅速に行う為に、外部に対して開放型であるため、抗菌剤を用いることにより外部からの細菌の進入、感染の危険を回避する必要がある。例えば、特許文献1には、基材と粘着剤層から成り、粘着剤層に銀などの抗菌剤を含有する医療用テープが記載されている。特許文献2には、抗菌剤としてヨウ素―シクロデキストリン化合物を含有する粘着剤層が記載されている。しかし、創傷被覆材に抗菌剤を用いている為に、抗菌剤が治癒促進に有用な皮膚常在菌をも殺菌してしまい、良好な治癒効果が得られないという問題があった。また、熱傷(火傷)の場合は創傷面が細菌などに二次感染しやすく、その中でも緑膿菌などは感染しやすい細菌として知られているが、緑膿菌は多剤耐性であることが多く、抗菌剤によって有効に殺菌することが難しい。 The dry dressing type wound dressing is open to the outside in order to absorb exudate quickly and dry, so the use of antibacterial agents avoids the invasion of bacteria from outside and the risk of infection. There is a need to. For example, Patent Document 1 describes a medical tape that includes a base material and an adhesive layer, and the adhesive layer contains an antibacterial agent such as silver. Patent Document 2 describes an adhesive layer containing an iodine-cyclodextrin compound as an antibacterial agent. However, since an antibacterial agent is used for the wound dressing, the antibacterial agent sterilizes resident skin bacterium useful for promoting healing, and there is a problem that a good healing effect cannot be obtained. In addition, in the case of burns (burns), the wound surface is susceptible to secondary infection with bacteria, among which Pseudomonas aeruginosa is known as a susceptible infection, but Pseudomonas aeruginosa is multidrug resistant. Many are difficult to effectively sterilize with antibacterial agents.
ウェットドレッシングタイプの創傷被覆材については、例えば、特許文献3に、スチレン−イソプレン共重合体やスチレン−ブタジエン共重合体の様な疎水性有機ポリマーを、可塑化剤、例えばポリオレフィンの様な熱可塑性の疎水性ゲル中に親水性有機微粒子と共に混練して押し出し成形器にかけて、親水性ヒドロゲルを疎水性有機ポリマー中に分散させた吸収性非接着性ポリマー組成物を含む創傷被覆材が記載されている。また特許文献4には、ポリイソブチレンやポリイソプレン等のエラストマーと、ペクチン、ゼラチン、およびカルボキシメチルセルロース等の吸水性物質を含有する粘着剤層を有する創傷被覆材が記載されている。ウェットドレッシングタイプの創傷被覆材は、使用に先立って、十分に傷口の洗浄、殺菌を行う。殺菌後、傷口に創傷被覆材を貼り付けて、外部への水分の出入りを遮蔽して、閉鎖状態の中で、傷口からの滲出液中に含まれる治癒促進因子による治癒を促進させると共に、過剰の滲出液は疎水性有機ポリマーマトリックス中に分散された親水性のヒドロゲルによって吸収される。 For a wet dressing type wound dressing, for example, in Patent Document 3, a hydrophobic organic polymer such as a styrene-isoprene copolymer or a styrene-butadiene copolymer is used as a plasticizer, for example, a thermoplastic resin such as polyolefin. A wound dressing comprising an absorbent non-adhesive polymer composition in which a hydrophilic hydrogel is dispersed in a hydrophobic organic polymer by kneading together with hydrophilic organic fine particles in a hydrophobic gel of the present invention and passing through an extruder. . Patent Document 4 describes a wound dressing material having an adhesive layer containing an elastomer such as polyisobutylene and polyisoprene and a water-absorbing substance such as pectin, gelatin, and carboxymethylcellulose. The wet dressing type wound dressing sufficiently cleans and sterilizes the wound prior to use. After sterilization, a wound dressing is applied to the wound to shield the moisture from entering and exiting, and in a closed state, the healing by the healing factor contained in the exudate from the wound is promoted and excessive. The exudate is absorbed by a hydrophilic hydrogel dispersed in a hydrophobic organic polymer matrix.
ウェットドレッシングタイプの創傷被覆材においては、創傷部に滲出液中に含まれる治癒促進因子を阻害するような成分、例えば殺菌剤や抗菌剤等を含有させないことが好ましい。しかし、ウェットドレッシングタイプは滲出液が外部に流出しないように密閉している為に、傷口の洗浄、殺菌が不十分であると、細菌が繁殖して、病原因子(毒素)を産生し感染症を引き起こす虞があるという問題を抱えている。 In the wet dressing type wound dressing material, it is preferable that the wound part does not contain a component that inhibits a healing promoting factor contained in the exudate, such as a bactericidal agent or an antibacterial agent. However, since the wet dressing type is sealed so that exudate does not flow out, if the wound is not sufficiently washed and sterilized, bacteria will propagate and produce pathogenic factors (toxins) and infectious diseases Have the problem of causing
一方、特許文献5には、病原性細菌による病原性毒素の産出を抑えることによって、緑膿菌や黄色ブドウ球菌の様な多剤耐性菌にも有効な病原性因子産生抑制剤として、レブリン酸類、タングステン酸類、ベンゾイルアセトン類、ポリリン酸類が提案されている。 On the other hand, Patent Document 5 discloses levulinic acids as virulence factor production inhibitors effective against multidrug-resistant bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus by suppressing the production of pathogenic toxins by pathogenic bacteria. Tungstic acids, benzoylacetones, and polyphosphoric acids have been proposed.
上記の病原性因子産生抑制剤の中でも、水溶性のポリリン酸化合物は、レブリン酸やベンゾイルアセトン類の様な皮膚刺激性やタングステン酸類の様な経口毒性が無く、細菌感染した化膿創傷に対しても、感染症を抑制する可能性があることが期待される。しかし、水溶性ポリリン酸化合物を創傷部に噴霧後、前記ドライドレッシングタイプの創傷被覆材により創傷部を保護した場合、創傷部からの滲出液がすぐに蒸発、乾固するため、病原性因子産生抑制効果の発現が中断されてしまう。このため、病原性因子産生抑制効果を継続して維持する為には繰り返し水溶性ポリリン酸化合物を創傷部へ噴霧する必要があり、その都度、創傷被覆材を貼り換えなければならなかった。また、前記した親水性ヒドロゾルを疎水性有機ポリマーマトリックス中に分散したウエットドレッシングタイプの創傷被覆材に水溶性ポリリン酸化合物を適用した場合、水溶性ポリリン酸化合物が十分に放出されず、十分な治癒効果が期待できるものではなかった。 Among the above pathogenic factor production inhibitors, water-soluble polyphosphate compounds have no skin irritation such as levulinic acid or benzoylacetones or oral toxicity such as tungstic acids, and are effective against bacterially infected suppuration wounds. Are also expected to have the potential to control infections. However, after spraying a water-soluble polyphosphate compound onto the wound area, if the wound area is protected by the dry dressing type wound dressing, exudate from the wound area will immediately evaporate and dry, thus producing pathogenic factors. The expression of the inhibitory effect is interrupted. For this reason, in order to maintain the pathogenic factor production inhibitory effect continuously, it was necessary to spray a water-soluble polyphosphate compound repeatedly on a wound part, and the wound dressing had to be replaced each time. In addition, when a water-soluble polyphosphate compound is applied to a wet dressing type wound dressing in which the hydrophilic hydrosol described above is dispersed in a hydrophobic organic polymer matrix, the water-soluble polyphosphate compound is not sufficiently released and sufficient healing is achieved. The effect was not expected.
この様な理由から、水溶性ポリリン酸化合物を創傷表面に徐放することによって、皮膚常在菌を含む細菌を殺傷することなく細菌の毒素産生を継続して抑制することが可能な創傷被覆材の実現が望まれていた。 For these reasons, a wound dressing that can continuously suppress the production of toxins from bacteria without killing bacteria, including skin-resident bacteria, by gradually releasing a water-soluble polyphosphate compound onto the wound surface. Realization of was desired.
本発明は病原因子産生抑制効果を有する水溶性ポリリン酸化合物を徐放することが可能な創傷被覆材を提供することを課題とする。 An object of the present invention is to provide a wound dressing capable of gradually releasing a water-soluble polyphosphate compound having a pathogenic factor production inhibitory effect.
上記課題は、水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する創傷被覆層を有する創傷被覆材により達成された。 The above object has been achieved by a wound dressing having a wound dressing layer containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C.
本発明により、病原因子産生抑制効果を有する水溶性ポリリン酸化合物を徐放することが可能な創傷被覆材を提供することが可能となる。 According to the present invention, it is possible to provide a wound dressing capable of gradually releasing a water-soluble polyphosphate compound having a pathogenic factor production inhibitory effect.
以下、本発明をその好適な実施形態に即して詳細に説明する。なお、図面の説明において同一の要素には同一の符号を付し、重複する説明を省略する。また、図示の便宜上、図面の寸法比率は説明のものと必ずしも一致しない。 Hereinafter, the present invention will be described in detail with reference to preferred embodiments thereof. In the description of the drawings, the same elements are denoted by the same reference numerals, and redundant description is omitted. For the convenience of illustration, the dimensional ratios in the drawings do not necessarily match those described.
図1は、本発明の創傷被覆材の一実施形態を示す側面図であり、創傷被覆層4のみからなる創傷被覆材を示す。創傷被覆層4は水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃の熱可塑性ラテックスを含有する層である。図1の創傷被覆材により創傷部の全面を覆うようにして創傷部の皮膚表面に創傷被覆層4を粘着させると、創傷部からの滲出液を吸収して創傷被覆層4が膨潤すると共に、創傷被覆層4から水溶性ポリリン酸化合物が創傷部に徐放される。 FIG. 1 is a side view showing an embodiment of the wound dressing of the present invention, and shows a wound dressing consisting of only the wound dressing layer 4. The wound covering layer 4 is a layer containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. When the wound covering layer 4 is adhered to the skin surface of the wound portion so as to cover the entire surface of the wound portion with the wound dressing of FIG. 1, the exudate from the wound portion is absorbed and the wound covering layer 4 swells, The water-soluble polyphosphate compound is gradually released from the wound covering layer 4 to the wound part.
図2は、本発明の創傷被覆材の別の実施形態を示す側面図であり、バッキング層1と創傷被覆層4からなる創傷被覆材を示す。バッキング層1は、創傷被覆層4を外部からの異物や雑菌の進入から保護する層である。また、バッキング層1は、創傷被覆層4が吸収した滲出液の外部への滲出を防止すると共に、創傷被覆層4中の滲出液の水分の一部を、バッキング層1の外に排出する層である。この様なバッキング層1に用いられる材料として、例えば、特開平5−192386号公報に記載の多孔質ポリプロピレンフィルムや、特開平9−309968号公報に記載の多孔性ポリウレタンフィルム等の空孔を有するフィルム等の、いわゆる多孔性フィルムを用いることが好ましい。また、上記した作用を得るために、バッキング層1の厚さは10〜100μmの範囲が好ましい。 FIG. 2 is a side view showing another embodiment of the wound dressing of the present invention, and shows a wound dressing composed of a backing layer 1 and a wound dressing layer 4. The backing layer 1 is a layer that protects the wound covering layer 4 from the entry of foreign substances and germs from the outside. In addition, the backing layer 1 is a layer that prevents exudate absorbed by the wound covering layer 4 from escaping to the outside and discharges a part of the moisture of the exudate in the wound covering layer 4 to the outside of the backing layer 1. It is. Examples of the material used for such a backing layer 1 include pores such as a porous polypropylene film described in JP-A-5-192386 and a porous polyurethane film described in JP-A-9-309968. It is preferable to use a so-called porous film such as a film. In order to obtain the above-described action, the thickness of the backing layer 1 is preferably in the range of 10 to 100 μm.
図3は、本発明の創傷被覆材のまた別の実施形態を示す側面図であり、バッキング層1、接着剤層2、吸収層3及び創傷被覆層4からなる創傷被覆材の側面図である。吸収層3は接着剤層2を介してバッキング層1と接着されている。滲出液により膨潤した創傷被覆層4中の滲出液の一部はさらに吸収層3により吸収される。吸収層3に吸収された滲出液中の水分の一部は、バッキング層1の空孔からバッキング層1の外に排出される。吸収層3に用いられる材料として、織布、不織布、編布、高吸水性フィルムなどの滲出液吸収性の高い素材を用いることができるが、創傷被覆層4との接着性や滲出液吸収性などの点から不織布が最も好ましい。不織布の素材としては、綿、麻、絹、羊毛、パルプ、等の天然繊維、レーヨン、ポリエチレン、ポリプレピレンなどのポリエチレンテレフタレート等のポリエステル、ポリオレフィン、ポリアミド等の合成繊維を単独、または組み合わせて用いることが出来る。 FIG. 3 is a side view showing still another embodiment of the wound dressing of the present invention, and is a side view of a wound dressing comprising a backing layer 1, an adhesive layer 2, an absorbent layer 3 and a wound covering layer 4. . The absorbent layer 3 is bonded to the backing layer 1 via the adhesive layer 2. Part of the exudate in the wound covering layer 4 swollen by the exudate is further absorbed by the absorbent layer 3. Part of the moisture in the exudate absorbed by the absorbent layer 3 is discharged out of the backing layer 1 through the holes in the backing layer 1. As the material used for the absorbent layer 3, a material having high exudate absorbability such as woven fabric, non-woven fabric, knitted fabric, and super absorbent film can be used. Non-woven fabrics are most preferable from the viewpoints of the above. As the material of the nonwoven fabric, natural fibers such as cotton, hemp, silk, wool, and pulp, polyesters such as polyethylene terephthalate such as rayon, polyethylene, and polypropylene, and synthetic fibers such as polyolefin and polyamide may be used alone or in combination. I can do it.
不織布の製造方法については特に制限はなく、目的、用途に応じて、乾式法、湿式抄造法、メルトブローン法、スパンボンド法などで得られたウェブを、ウォータージェット法、ニードルパンチ法、ステッチボンド法などの物理的方法、サーマルボンド法などの熱による方法、レジンボンドなどの接着剤による方法で強度を発現させる方法を、適宜組み合わせて製造することができる。吸収層3とバッキング層1は接着剤層2によって接着される。接着剤層2に用いられる接着剤として、アクリル樹脂接着剤、ウレタン樹脂接着剤、天然または合成ゴム接着剤、酢酸ビニル樹脂接着剤など様々な接着剤を用いることができるが、ホットメルト接着が容易なアクリル樹脂接着剤やウレタン樹脂接着剤が好ましく用いられる。接着剤層の量は乾燥固形分として0.1〜5g/m2の範囲が好ましい。 There are no particular restrictions on the method for producing the nonwoven fabric, and the web obtained by the dry method, wet papermaking method, melt blown method, spun bond method, etc., depending on the purpose and application, water jet method, needle punch method, stitch bond method It is possible to produce a suitable combination of a physical method such as a thermal bond method, a thermal bond method, a heat bond method, or a resin bond adhesive method. The absorbent layer 3 and the backing layer 1 are bonded by the adhesive layer 2. Various adhesives such as an acrylic resin adhesive, a urethane resin adhesive, a natural or synthetic rubber adhesive, and a vinyl acetate resin adhesive can be used as the adhesive used for the adhesive layer 2, but hot melt bonding is easy. An acrylic resin adhesive or urethane resin adhesive is preferably used. The amount of the adhesive layer is preferably in the range of 0.1 to 5 g / m 2 as a dry solid content.
以下では、本発明の創傷被覆材の構成とその製造方法について更に詳細に説明する。
本発明において創傷被覆層が含有する水溶性ポリリン酸化合物とは、20℃の蒸留水に対する溶解度が1.0g/L以上のポリリン酸化合物を指す。本発明で用いられる水溶性ポリリン酸化合物の具体例として、下記一般式(1)で表される直鎖状の水溶性ポリリン酸化合物、または一般式(2)で表される環状の水溶性ポリリン酸化合物が安価であり、好ましく用いられる。
一般式(1) Mm+2PmO3m+1(ここで、Mはナトリウムまたはカリウム原子、mは2以上の整数を表す。)
一般式(2) MnPnO3n(ここで、Mはナトリウムまたはカリウム原子を表し、nは3以上の整数を表す。)
また、n及びmの上限は100以下であることが望ましいが、n及びmが7を超える水溶性ポリリン酸化合物は、通常、重合度の異なる水溶性ポリリン酸化合物の混合物として販売されているため、繰り返し安定した成分の水溶性ポリリン酸化合物を入手することが困難である。n及びmが3〜6の水溶性ポリリン酸化合物、例えば、三リン酸五ナトリウム、三リン酸五カリウム、四リン酸四ナトリウム、五リン酸七ナトリウムなどは、純度が高く安価なものを容易に入手することが出来ることから、本発明ではより好ましく用いられる。
Below, the structure of the wound-dressing material of this invention and its manufacturing method are demonstrated in detail.
In the present invention, the water-soluble polyphosphate compound contained in the wound covering layer refers to a polyphosphate compound having a solubility in distilled water at 20 ° C. of 1.0 g / L or more. Specific examples of the water-soluble polyphosphate compound used in the present invention include a linear water-soluble polyphosphate compound represented by the following general formula (1), or a cyclic water-soluble polyphosphate represented by the general formula (2). Acid compounds are inexpensive and are preferably used.
Formula (1) M m + 2 P m O 3m + 1 ( wherein, M is sodium or potassium atom, m represents an integer of 2 or more.)
Formula (2) M n P n O 3n ( where, M represents sodium or potassium atom, n represents an integer of 3 or more.)
Moreover, although it is desirable that the upper limit of n and m is 100 or less, water-soluble polyphosphate compounds in which n and m exceed 7 are usually sold as a mixture of water-soluble polyphosphate compounds having different degrees of polymerization. Therefore, it is difficult to obtain a water-soluble polyphosphate compound that is a component that is repeatedly stable. Water-soluble polyphosphoric acid compounds having n and m of 3 to 6, such as pentasodium triphosphate, pentapotassium triphosphate, tetrasodium tetraphosphate, heptasodium pentaphosphate, etc. are easy to purify and inexpensive. Therefore, it is more preferably used in the present invention.
本発明の水溶性ポリリン酸化合物とガラス転移温度が−29.5〜6.0℃の熱可塑性ラテックスの間には好ましい比率が存在し、水溶性ポリリン酸化合物は該熱可塑性ラテックスの乾燥固形分量に対して0.25〜25質量%の範囲であることが好ましく、より好ましくは0.5〜15質量%の範囲である。また本発明の創傷被覆層中に含有される水溶性ポリリン酸化合物の量は、0.25〜100g/m2の範囲であることが好ましく、より好ましくは1〜25g/m2の範囲である。 There is a preferred ratio between the water-soluble polyphosphate compound of the present invention and the thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C., and the water-soluble polyphosphate compound has a dry solid content of the thermoplastic latex. It is preferable that it is the range of 0.25-25 mass% with respect to this, More preferably, it is the range of 0.5-15 mass%. The amount of a wound dressing layer the water-soluble polyphosphate compound contained in the present invention is preferably in the range of 0.25~100g / m 2, more preferably in the range of 1 to 25 g / m 2 .
本発明において創傷被覆層が含有する熱可塑性ラテックスとは、詳細には熱可塑性樹脂微粒子の水分散物を指す。本発明に用いられるガラス転移温度(Tg)が−29.5〜6.0℃の熱可塑性ラテックスとして、スチレンブタジエン共重合体、スチレンイソプレン共重合体、アクリロニトリルクロロプレン共重合体、エピクロロヒドリンアリルグリシジルエーテル共重合体、アクリロニトリルブタジエン共重合体、アクリル酸エステル共重合体、スチレンアクリル酸エステル共重合体、アクリルウレタン共重合体、スチレンブタジエンビニルピリジン共重合体、エチレンプロピレン共重合体などの熱可塑性ラテックスが挙げられる。これらの熱可塑性ラテックスの中で、スチレンブタジエン共重合体、アクリロニトリルブタジエン共重合体、アクリル酸エステル共重合体、スチレンアクリル酸エステル共重合体などの熱可塑性ラテックスが好ましく用いられる。ガラス転移温度が−29.5〜6.0℃の熱可塑性ラテックスの具体例として、スチレンブタジエン共重合体としては、例えば、日本ゼオン株式会社製のSX1105(Tg=0℃)、JSR株式会社製スチレンブタジエンラテックス573(Tg=−9℃)、同696(Tg=−12℃)、アクリロニトリルブタジエン共重合体としては、例えば、日本ゼオン株式会社製のSX1503A(Tg=−20℃)、アクリル酸エステル共重合体としては、例えば、日本ゼオン株式会社製のSX1706A(Tg=0℃)、スチレンアクリル酸エステル共重合体としては、例えば、日本ゼオン株式会社製のSX1707A(Tg=−7℃)やJSR株式会社製のAE981A(Tg=−15℃)、同AE982(Tg=0℃)などが挙げられる。 In the present invention, the thermoplastic latex contained in the wound covering layer refers specifically to an aqueous dispersion of thermoplastic resin fine particles. As a thermoplastic latex having a glass transition temperature (Tg) of −29.5 to 6.0 ° C. used in the present invention, a styrene butadiene copolymer, a styrene isoprene copolymer, an acrylonitrile chloroprene copolymer, and epichlorohydrin allyl are used. Thermoplastics such as glycidyl ether copolymer, acrylonitrile butadiene copolymer, acrylic ester copolymer, styrene acrylic ester copolymer, acrylic urethane copolymer, styrene butadiene vinyl pyridine copolymer, ethylene propylene copolymer Latex. Among these thermoplastic latexes, thermoplastic latexes such as styrene butadiene copolymers, acrylonitrile butadiene copolymers, acrylic acid ester copolymers, and styrene acrylic acid ester copolymers are preferably used. As a specific example of the thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C., examples of the styrene butadiene copolymer include SX1105 (Tg = 0 ° C.) manufactured by Nippon Zeon Co., Ltd., and JSR Corporation. Examples of styrene butadiene latex 573 (Tg = -9 ° C.), 696 (Tg = -12 ° C.), and acrylonitrile butadiene copolymer include SX1503A (Tg = −20 ° C.) manufactured by Nippon Zeon Co., Ltd., and acrylic ester. Examples of the copolymer include SX1706A (Tg = 0 ° C.) manufactured by Nippon Zeon Co., Ltd., and examples of the styrene acrylate copolymer include SX1707A (Tg = −7 ° C.) manufactured by Nippon Zeon Co., Ltd. and JSR. AE981A (Tg = -15 ° C.) and AE982 (Tg = 0 ° C.) manufactured by the same company may be mentioned.
本発明の創傷被覆材の創傷被覆層は、水溶性ポリリン酸化合物をガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する水分散液と混合し、基材上(例えば、後述する保護剥離基材)に塗布した後、乾燥することにより得られる。本発明の創傷被覆層には、水溶性ポリリン酸化合物と前記した熱可塑性ラテックス以外に、pH調整剤、界面活性剤、増粘剤、消泡剤、無機顔料などを添加することが出来る。pH調整剤としては、硫酸、リン酸などの無機酸や、水酸化ナトリウム、水酸化カリウムなどの無機アルカリ化合物を用いることが出来る。界面活性剤としては、ラウリル硫酸ナトリウム、ドデシル硫酸ナトリウム等のアルキル硫酸塩、ポリオキシエチレンラウリルエ一テル硫酸ナトリウム、ポリオキシエチレンステアリルエ一テル硫酸ナトリウム等のポリオキシエチレンアルキルエーテル硫酸塩、ポリオキシエチレンステアリルエーテル酢酸塩、ポリオキシエチレンラウリルエーテル酢酸塩等のポリオキシエチレンアルキルエーテル酢酸塩などのアニオン系界面活性剤や、塩化ラウリルトリメチルアンモニウム、塩化アルコキシプロピルトリメチルアンモニウム、塩化ジアルキルジメチルアンモニウム、塩化ベンザルコニウム等のカチオン系の界面活性剤、アルキルジメチルアミノ酢酸ベタイン、アルキルジメチルアミンオキサイド、アルキルカルボキシメチルヒドロキシエチルイミダゾリニウムベタイン、アルキルアミドプロピルベタイン等の両性の界面活性剤、グリセリン脂肪酸エステル、プロピレングリコール脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシプロピレン-ポリオキシエチレンブロックコポリマー等の非イオン性の界面活性剤などを用いることが出来る。増粘剤として、例えば、グアーガム、アラビアガム、カラギーナン、タラガム、タマリンド、アルギン酸及びアルギン酸ナトリウム等の塩、キサンタンガム、デキストラン、サクシノグ、カードラン、プルラン、ジェランガム、キチン、キトサン、寒天、セルロースナノファイバー、メチルセロース、エチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、ポリビニルピドリドンなどの高分子増粘剤や膨潤性無機化合物であるペントナイト、スメクタイトなど天然の粘土化合物やヘクトライトの様な合成の粘土化合物を用いることが出来る。無機顔料としてはゼオライトや活性炭等を用いることが出来る。 The wound dressing layer of the wound dressing of the present invention is prepared by mixing a water-soluble polyphosphate compound with an aqueous dispersion containing a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. For example, it is obtained by drying after applying to a protective release substrate (to be described later). In addition to the water-soluble polyphosphate compound and the above-described thermoplastic latex, a pH adjuster, a surfactant, a thickener, an antifoaming agent, an inorganic pigment, and the like can be added to the wound covering layer of the present invention. As the pH adjuster, inorganic acids such as sulfuric acid and phosphoric acid, and inorganic alkali compounds such as sodium hydroxide and potassium hydroxide can be used. Surfactants include alkyl sulfates such as sodium lauryl sulfate and sodium dodecyl sulfate, polyoxyethylene alkyl ether sulfates such as sodium polyoxyethylene lauryl ether sulfate, sodium polyoxyethylene stearyl ether sulfate, polyoxyethylene Anionic surfactants such as polyoxyethylene alkyl ether acetates such as ethylene stearyl ether acetate and polyoxyethylene lauryl ether acetate, lauryltrimethylammonium chloride, alkoxypropyltrimethylammonium chloride, dialkyldimethylammonium chloride, benzalco chloride Cationic surfactants such as nium, alkyldimethylaminoacetic acid betaine, alkyldimethylamine oxide, alkylcarboxymethylhydroxyethyl Amphoteric surfactants such as midazolinium betaine and alkylamidopropyl betaine, nonionic surfactants such as glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxypropylene-polyoxyethylene block copolymer, etc. Can be used. Examples of thickeners include guar gum, gum arabic, carrageenan, tara gum, tamarind, alginic acid and sodium alginate, xanthan gum, dextran, succinog, curdlan, pullulan, gellan gum, chitin, chitosan, agar, cellulose nanofiber, methylcellulose Polymer clay thickeners such as ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and polyvinyl pyridone, and swellable inorganic compounds such as pentonite and smectite, and synthetics such as hectorite The clay compound can be used. As the inorganic pigment, zeolite, activated carbon or the like can be used.
本発明において創傷被覆層の乾燥固形分量は25〜500g/m2の範囲であることが好ましく、より好ましくは50〜250g/m2の範囲である。また創傷被覆層の全乾燥固形分量に対する熱可塑性ラテックスの比率は、75質量%を超える事が好ましく、85質量%を超える事がより好ましい。 Preferably dry solids content of the wound dressing layer is in the range of 25~500g / m 2 in the present invention, more preferably from 50 to 250 g / m 2. The ratio of the thermoplastic latex to the total dry solid content of the wound covering layer is preferably more than 75% by mass, more preferably more than 85% by mass.
本発明の創傷被覆材が有する創傷被覆層は、殺菌剤や抗菌剤を実質的に含有しないことが好ましい。ここで実質的にとは、例え創傷被覆層が殺菌剤や抗菌剤を含有しても、これらの作用が発現しない範囲であれば含有することが可能である事を意味する。具体的には殺菌剤や抗菌剤は、創傷被覆層の全乾燥固形分量に対して0.1質量%未満とすることが好ましく、更に0.01質量%未満とすることがより好ましく、特に好ましくは0.001質量%未満である。 It is preferable that the wound covering layer of the wound covering material of the present invention does not substantially contain a bactericidal agent or an antibacterial agent. “Substantially” means that even if the wound covering layer contains a bactericidal agent or an antibacterial agent, it can be contained as long as these effects are not exhibited. Specifically, the disinfectant or antibacterial agent is preferably less than 0.1% by mass, more preferably less than 0.01% by mass, particularly preferably relative to the total dry solid content of the wound covering layer. Is less than 0.001 mass%.
図4は、図1に示される創傷被覆材の製造方法を説明する為の側面図である。図1の創傷被覆材は水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する塗布液を、表面を離型処理した保護剥離基材5に塗布した後、加熱、乾燥し、保護剥離基材5を取り除くことで得られる。 FIG. 4 is a side view for explaining the method of manufacturing the wound dressing shown in FIG. The wound dressing of FIG. 1 is a protective release substrate 5 whose surface is subjected to a release treatment from a coating solution containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. It is obtained by removing the protective release substrate 5 by heating and drying.
保護剥離基材5としては、樹脂コートされた紙の表面に撥水加工を施した基材が好ましく用いられる。保護剥離基材に用いることの出来る基材として、例えば、ポリエチレンラミネート上質紙にシリコン層を設けた、王子タック株式会社製の剥離シート紙L7C、L8C、グラシン紙にシリコン層を設けた王子タック株式会社製の剥離シート紙G6B、G8W、ポリエチレンラミネートしたグラシンにシリコン層を設けた王子タック株式会社製の剥離シート紙GB80、GW64等が挙げられる。 As the protective release substrate 5, a substrate obtained by subjecting a resin-coated paper surface to a water repellent finish is preferably used. Examples of substrates that can be used as protective release substrates include release sheet papers L7C and L8C manufactured by Oji Tac Co., Ltd., which are provided with a silicon layer on polyethylene laminated fine paper, and Oji Tac Co., Ltd., which is provided with a silicon layer on glassine paper. Examples include release sheet papers G6B and G8W manufactured by company, and release sheet papers GB80 and GW64 manufactured by Oji Tac Co., Ltd. in which a silicone layer is provided on glassine laminated with polyethylene.
図5は、図2に示される創傷被覆材の製造方法を説明する為の側面図である。図2の創傷被覆材は水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する塗布液を、表面を離型処理した保護剥離基材5に塗布した後、加熱、乾燥して創傷被覆層4を形成し、該創傷被覆層4をバッキング層1と接触させ、加熱、乾燥して接着した後、保護剥離基材5を取り除くことで得られる。 FIG. 5 is a side view for explaining the method of manufacturing the wound dressing shown in FIG. The wound dressing of FIG. 2 is a protective release substrate 5 whose surface has been subjected to a release treatment from a coating solution containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. It is obtained by removing the protective release substrate 5 after applying to the substrate, heating and drying to form the wound covering layer 4, bringing the wound covering layer 4 into contact with the backing layer 1, heating, drying and bonding. It is done.
図6は、図3に示される創傷被覆材の製造方法を説明する為の側面図である。図3の創傷被覆材は水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する塗布液を、表面を離型処理した保護剥離基材5に塗布した後、保護剥離基材5上の創傷被覆層4が乾燥終了するまでの任意の時期に吸収層3を創傷被覆層4と接触させ、加熱、乾燥して接着した後、接着剤層2を介してバッキング層1を、例えばホットメルト接着した後、保護剥離基材5を取り除くことで得られる。 FIG. 6 is a side view for explaining the method of manufacturing the wound dressing shown in FIG. The wound dressing of FIG. 3 is a protective release substrate 5 whose surface is subjected to a release treatment from a coating solution containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. The adhesive layer 3 is brought into contact with the wound coating layer 4 at any time until the wound covering layer 4 on the protective release substrate 5 is dried, and heated, dried and bonded, and then the adhesive layer. For example, after the backing layer 1 is hot-melt bonded via 2, the protective release substrate 5 is removed.
本発明の創傷被覆材において、病原因子産生抑制効果を有する水溶性ポリリン酸化合物を徐放するとは、37℃の密封された容器中で、本発明の創傷被覆層1質量部を生理食塩水100質量部と接触後、少なくとも3日間以上の期間に渉って、1日当りに創傷被覆層が含有する水溶性ポリリン酸化合物の5質量%(創傷被覆層に最初に含まれる水溶性ポリリン酸化合物の全部の量を100質量%とする)以上の量が、生理食塩水中に放出され続けることを指す。 In the wound dressing of the present invention, the sustained release of the water-soluble polyphosphate compound having a pathogenic factor production inhibitory effect means that 1 part by mass of the wound dressing layer of the present invention is placed in physiological saline 100 in a sealed container at 37 ° C. 5% by mass of the water-soluble polyphosphate compound contained in the wound dressing layer per day over the period of at least 3 days after contact with the mass part (of the water-soluble polyphosphate compound initially contained in the wound dressing layer) This means that an amount equal to or greater than 100% by mass is continuously released into the physiological saline.
従来技術では、ウエットドレッシングタイプの創傷被覆材の親水性のヒドロゲルは通常、200℃以上の温度で加熱したゴムに固形の添加物として混練され、スリットから押し出し成型することにより形成される。この方法においては親水性のヒドロゲルに水溶性ポリリン酸化合物を封入することが可能であるものの、スリットから押し出し成型するために、生産性が高い製造方法とは言えなかった。また良好な徐放性も得られなかった。本発明者らは、生産性の観点から熱可塑性樹脂微粒子の水分散物である熱可塑性ラテックスと水溶性ポリリン酸化合物を混合し、水溶性ポリリン酸化合物の徐放性を有する創傷被覆層を検討した。しかし、水溶性ポリリン酸化合物、およびガラス転移温度が−29.5℃未満である熱可塑性ラテックスを用いて形成された創傷被覆層は、生理食塩水との接触により短期間の間に水溶性ポリリン酸化合物を創傷被覆層外に放出してしまい、良好な徐放性を得ることが出来なかった。この理由は、ガラス転移温度が−29.5℃未満である熱可塑性ラテックスの疎水性が比較的高く、水溶性ポリリン酸化合物の添加により、かかる熱可塑性ラテックスの分散安定性が低下する結果、水溶性ポリリン酸化合物は熱可塑性ラテックスから乖離しやすくなる為と推測される。また、水溶性ポリリン酸化合物、およびガラス転移温度が6.0℃超である熱可塑性ラテックスを用いて形成された創傷被覆層は、熱可塑性ラテックスの生理食塩水との接触によっても水溶性ポリリン酸化合物を創傷被覆層外に容易に放出しなかった。この理由は、ガラス転移温度が6.0℃超である熱可塑性ラテックスの親水性が比較的高く、水溶性ポリリン酸化合物と熱可塑性ラテックスの親和性が高まり、水溶性ポリリン酸化合物を容易に乖離し難くなる為と推測される。これに対し水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを用いて形成された創傷被覆層によって、良好な徐放性が得られることを見出したものが本発明である。この理由は、水溶性ポリリン酸化合物と熱可塑性ラテックスとの間で適度な親和性が保たれることにより、徐々に水溶性ポリリン酸化合物を乖離することが出来る為と推測される。 In the prior art, the hydrophilic hydrogel of a wet dressing type wound dressing is usually formed by kneading as a solid additive in rubber heated at a temperature of 200 ° C. or higher and extruding from a slit. In this method, it is possible to encapsulate a water-soluble polyphosphate compound in a hydrophilic hydrogel, but it cannot be said to be a production method with high productivity because it is extruded from a slit. Also, good sustained release was not obtained. From the viewpoint of productivity, the present inventors mixed a thermoplastic latex, which is an aqueous dispersion of thermoplastic resin particles, and a water-soluble polyphosphate compound, and examined a wound covering layer having a sustained release property of the water-soluble polyphosphate compound. did. However, a wound dressing layer formed using a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of less than −29.5 ° C. has a short time due to contact with physiological saline. The acid compound was released outside the wound covering layer, and good sustained release could not be obtained. This is because the thermoplastic latex having a glass transition temperature of less than −29.5 ° C. has a relatively high hydrophobicity, and the addition of a water-soluble polyphosphate compound decreases the dispersion stability of the thermoplastic latex. This is presumed to be because the functional polyphosphoric acid compound tends to be separated from the thermoplastic latex. Further, the wound covering layer formed using the water-soluble polyphosphate compound and the thermoplastic latex having a glass transition temperature of more than 6.0 ° C. can be obtained by contacting the water-soluble polyphosphate with the physiological saline of the thermoplastic latex. The compound did not release easily out of the wound dressing layer. This is because the thermoplastic latex having a glass transition temperature of over 6.0 ° C. has relatively high hydrophilicity, and the affinity between the water-soluble polyphosphate compound and the thermoplastic latex is increased, so that the water-soluble polyphosphate compound is easily separated. Presumably because it becomes difficult. On the other hand, it has been found that a good sustained release property can be obtained by a wound covering layer formed using a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. This is the present invention. The reason is presumed that the water-soluble polyphosphate compound can be gradually separated by maintaining an appropriate affinity between the water-soluble polyphosphate compound and the thermoplastic latex.
以下に、水溶性ポリリン酸化合物の徐放性を評価する方法を記載する。37℃の密封された容器中で、本発明の創傷被覆層1質量部を生理食塩水100質量部中に浸漬し、24時間後、48時間後、72時間接触後の生理食塩水の一部を試料溶液として採取し、生理食塩水中に含まれる水溶性ポリリン酸化合物の量を測定する。これにより0〜24時間、24時間〜48時間、48時間〜72時間の間に生理食塩水中に放出された水溶性ポリリン酸化合物量を求める。生理食塩水中に放出された水溶性ポリリン酸化合物量は、創傷被覆層1質量部が予め含有している水溶性ポリリン酸化合物量に対する質量%に換算する。生理食塩水中の水溶性ポリリン酸化合物の量は、例えば、原田雅章、藏源一郎著、「リン酸塩の分離と定量」(「体験“身近な科学”」(福岡教育大学出版2001年)の49〜55頁)に記載のカラムクロマトグラフィーにより求めることが出来る。試料溶液中の水溶性ポリリン酸化合物の量は、その種類に応じて、予めカラムクロマトグラフィー装置により分離された後、モリブデンブルー法によるリン酸濃度の定量分析法に従って測定することができる。具体的な測定方法の一例を以下に示す。 The method for evaluating the sustained release property of the water-soluble polyphosphate compound is described below. In a sealed container at 37 ° C., 1 part by mass of the wound covering layer of the present invention is immersed in 100 parts by mass of physiological saline, and part of the physiological saline after contact for 24 hours, 48 hours, and 72 hours Is collected as a sample solution, and the amount of the water-soluble polyphosphate compound contained in the physiological saline is measured. Thereby, the amount of the water-soluble polyphosphate compound released into the physiological saline during 0 to 24 hours, 24 hours to 48 hours, and 48 hours to 72 hours is determined. The amount of the water-soluble polyphosphate compound released into the physiological saline is converted to mass% with respect to the amount of the water-soluble polyphosphate compound contained in advance by 1 part by mass of the wound covering layer. The amount of the water-soluble polyphosphate compound in physiological saline is, for example, 49 of Masaaki Harada and Ichiro Sugen, “Separation and Quantification of Phosphate” (“Experience“ Family Science ”” (Fukuoka University of Education Press 2001). To page 55). The amount of the water-soluble polyphosphate compound in the sample solution can be measured according to the quantitative analysis method of the phosphoric acid concentration by the molybdenum blue method after being previously separated by a column chromatography apparatus according to the type. An example of a specific measurement method is shown below.
カラムクロマトグラフィー装置において、試料溶液中の各成分は、移動相(溶液)と呼ばれる溶液と混合されて、分離の為の固定相を入れたカラムを通過することによりそれぞれの成分に分離された後、定量分析される。図7は本発明の創傷被覆材に含まれる水溶性ポリリン酸化合物の徐放性を測定する為のカラムクロマトグラフィー装置の概念図である。移動相は、0.3molのKClと0.1質量%エチレンジアミン四酢酸二ナトリウム溶液(pH10.0)からなる溶液である。測定に先立って移動相は容器11中に収められている。また、固定相16は東ソー株式会社製の粒径10μmアニオン交換樹脂TSKgelSAX(商品名)である。固定相16は、直径が4mmで、長さが250mmの円筒形のカラム15内に予め充填されている。移動相(溶液)は容器11から送液ポンプ12を用いて1ミリリットル/分の流速で試料溶液導入部13に送液される。試料溶液は試料溶液を入れた容器14から試料溶液導入部13に導入される。試料溶液は、試料溶液導入部13を経て移動相と共に、カラム15に移動し、カラム15に充填されている固定相16のアニオン交換樹脂により一リン酸イオン(PO4 3−)、二リン酸イオン(P2O7 4−)、三リン酸イオン(P3O10 5−)、四リン酸イオン(P4O13 6−)、五リン酸イオン(P6O16 7−)等に分離される。固定相16を通過して分離された各リン酸イオンは、容器17から送液ポンプ18で0.5ミリリットル/分の流速で送られた下記のモリブデン試薬溶液と混合した後、140℃の加熱装置19で加熱することによりリンモリブデンへテロブルー錯体溶液が生成する。リンモリブデンへテロブルー錯体の830nmの吸光度を可視紫外分光光度計20、例えば株式会社島津製作所製紫外可視分光光度計UV−2600(商品名)を用いて測定し、検量線溶液の吸光度と比較することにより生理食塩水中に放出された水溶性ポリリン酸化合物の化学種及び放出量を定量することが出来る。 In a column chromatography device, each component in a sample solution is mixed with a solution called a mobile phase (solution) and separated into each component by passing through a column containing a stationary phase for separation. Quantitative analysis. FIG. 7 is a conceptual diagram of a column chromatography apparatus for measuring sustained release properties of a water-soluble polyphosphate compound contained in the wound dressing of the present invention. The mobile phase is a solution composed of 0.3 mol of KCl and 0.1% by mass of ethylenediaminetetraacetic acid disodium solution (pH 10.0). Prior to the measurement, the mobile phase is contained in the container 11. The stationary phase 16 is an anion exchange resin TSKgel SAX (trade name) manufactured by Tosoh Corporation. The stationary phase 16 is packed in advance in a cylindrical column 15 having a diameter of 4 mm and a length of 250 mm. The mobile phase (solution) is fed from the container 11 to the sample solution introduction unit 13 at a flow rate of 1 ml / min using the liquid feed pump 12. The sample solution is introduced from the container 14 containing the sample solution into the sample solution introduction unit 13. The sample solution moves to the column 15 together with the mobile phase through the sample solution introduction unit 13, and monophosphate ions (PO 4 3− ) and diphosphate by the anion exchange resin of the stationary phase 16 packed in the column 15. Ions (P 2 O 7 4− ), triphosphate ions (P 3 O 10 5− ), tetraphosphate ions (P 4 O 13 6− ), pentaphosphate ions (P 6 O 16 7− ), etc. To be separated. Each phosphate ion separated through the stationary phase 16 is mixed with the following molybdenum reagent solution sent from the container 17 by the liquid feed pump 18 at a flow rate of 0.5 ml / min, and then heated at 140 ° C. By heating with the apparatus 19, a phosphomolybdenum hetero blue complex solution is produced. The absorbance at 830 nm of the phosphomolybdenum heteroblue complex is measured using a visible ultraviolet spectrophotometer 20, for example, an ultraviolet-visible spectrophotometer UV-2600 (trade name) manufactured by Shimadzu Corporation, and compared with the absorbance of a calibration curve solution. Thus, the chemical species and release amount of the water-soluble polyphosphate compound released into the physiological saline can be quantified.
<モリブデン試薬溶液>
(1)モリブデン酸アンモニウム((NH4)6MoO24・4H2O))35.3gを1リットルビーカーで蒸留水200ミリリットルに溶かす。
(2)これに濃塩酸200ミリリットルを撹拌しながら加える。
(3)次に亜鉛粉末3gを少しずつ加える。
(4)さらに濃塩酸180ミリリットルを加え,冷却しながら濃硫酸400ミリリットルを加える。
(5)十分に冷えた後、1リットルメスフラスコに移し全量を1リットルとする。
<Molybdenum reagent solution>
(1) Ammonium molybdate ((NH 4) 6 MoO 24 · 4H 2 O)) 35.3g of dissolved in 200 ml of distilled water with one liter beaker.
(2) Add 200 ml of concentrated hydrochloric acid to this while stirring.
(3) Next, 3 g of zinc powder is added little by little.
(4) Add 180 ml of concentrated hydrochloric acid, and add 400 ml of concentrated sulfuric acid while cooling.
(5) After sufficiently cooling, transfer to a 1 liter volumetric flask to make the total volume 1 liter.
本発明の創傷被覆材の病原因子産生抑制効果は、本発明の創傷被覆材に一定株の緑膿菌を加えて、培養し、緑膿菌の菌数の変化及び緑膿菌により産生される毒素であるピオシアニン色素の生成量を測定することにより評価することができる。緑膿菌の培養と菌数測定方法および毒素(ピオシアニン色素)の定量方法を以下に示す。 The pathogenic factor production inhibitory effect of the wound dressing material of the present invention is produced by adding a certain strain of Pseudomonas aeruginosa to the wound dressing material of the present invention and culturing it, and then changing the number of Pseudomonas aeruginosa bacteria and It can be evaluated by measuring the amount of pyocyanin pigment that is a toxin. A method for culturing Pseudomonas aeruginosa and measuring the number of bacteria and a method for quantifying a toxin (pyocyanin pigment) are shown below.
<緑膿菌の測定方法>
シート状の創傷被覆材1gをガラスシャーレに入れ、120℃で15分間オートクレーブで滅菌後、緑膿菌培養液0.2ミリリットルを滴下し、シャーレに均一に液を広げた後、培養器に入れて、37℃48時間培養した緑膿菌培養試料を作成する。上記の緑膿菌培養試料を入れたシャーレに生理食塩水10ミリリットルを加えて振とう、遠心分離後、上澄み液を抽出し、光学顕微鏡により菌数を測定する。
<Method for measuring Pseudomonas aeruginosa>
1 g of sheet-shaped wound dressing is placed in a glass petri dish, sterilized in an autoclave at 120 ° C. for 15 minutes, 0.2 ml of Pseudomonas aeruginosa culture solution is added dropwise, and the solution is spread evenly on the petri dish and then placed in an incubator. Then, a culture sample of Pseudomonas aeruginosa cultured at 37 ° C. for 48 hours is prepared. 10 ml of physiological saline is added to the petri dish containing the Pseudomonas aeruginosa culture sample, shaken, centrifuged, the supernatant is extracted, and the number of bacteria is measured with an optical microscope.
<毒素生成量の測定方法>
上記の緑膿菌培養試料を入れた別のシャーレにクロロホルム(1ミリリットル)を加えて毒素(ピオシアニン色素)の490nmの抽出吸光度(OD490)測定により毒素生成量を定量する。吸光度の測定には可視紫外分光光度計、例えば株式会社島津製作所製紫外可視分光光度計UV−2600を用いることができる。
<Measurement method of toxin production>
Chloroform (1 milliliter) is added to another petri dish containing the above Pseudomonas aeruginosa culture sample, and the amount of toxin produced is quantified by measuring the extraction absorbance (OD 490 ) of the toxin (piocyanin dye) at 490 nm. For the measurement of absorbance, a visible ultraviolet spectrophotometer, for example, an ultraviolet-visible spectrophotometer UV-2600 manufactured by Shimadzu Corporation can be used.
以下、実施例により本発明を詳しく説明する。以下において、%表示は質量基準を意味する。 Hereinafter, the present invention will be described in detail by way of examples. In the following, “%” means mass basis.
下記の塗布液(1)〜(9)を作製した。ここで、10%三リン酸五ナトリウム、10%五リン酸七ナトリウム、および10%四リン酸四ナトリウムは、硫酸を用いてpH7.0に予め調整したものを使用した。 The following coating solutions (1) to (9) were prepared. Here, 10% trisodium pentaphosphate, 10% pentasodium pentaphosphate, and 10% tetrasodium tetraphosphate used in advance were adjusted to pH 7.0 with sulfuric acid.
<塗布液(1)>
日本ゼオン株式会社製の商品名Nipol SX1706A(アクリル酸エステル共重合体;固形分48質量%;Tg=0℃) 70.5質量部
10%三リン酸五ナトリウム 8.7質量部
蒸留水 20.8質量部
<Coating liquid (1)>
Product name Nipol SX1706A manufactured by Nippon Zeon Co., Ltd. (acrylic ester copolymer; solid content 48% by mass; Tg = 0 ° C.) 70.5 parts by mass 10% pentasodium triphosphate 8.7 parts by mass distilled water 20. 8 parts by mass
<塗布液(2)>
日本ゼオン株式会社製の商品名Nipol SX1706A(アクリル酸エステル共重合体;固形分48質量%;Tg=0℃) 67.0質量部
10%三リン酸五ナトリウム 16.8質量部
蒸留水 16.2質量部
<Coating liquid (2)>
Product name Nipol SX1706A manufactured by Nippon Zeon Co., Ltd. (acrylic ester copolymer; solid content 48% by mass; Tg = 0 ° C.) 67.0 parts by mass 10% pentasodium triphosphate 16.8 parts by mass distilled water 16. 2 parts by mass
<塗布液(3)>
日本ゼオン株式会社製の商品名Nipol SX1706A(アクリル酸エステル共重合体;固形分48質量%;Tg=0℃) 64.5質量部
10%三リン酸五ナトリウム 35.5質量部
蒸留水 1.0質量部
<Coating liquid (3)>
Product name Nipol SX1706A manufactured by Nippon Zeon Co., Ltd. (acrylic ester copolymer; solid content 48% by mass; Tg = 0 ° C.) 64.5 parts by mass 10% pentasodium triphosphate 35.5 parts by mass distilled water 1. 0 parts by mass
<塗布液(4)>
日本ゼオン株式会社製の商品名Nipol SX1706A(アクリル酸エステル共重合体;固形分48質量%;Tg=0℃) 67.0質量部
10%五リン酸七ナトリウム 16.8質量部
蒸留水 16.2質量部
<Coating liquid (4)>
Product name Nipol SX1706A manufactured by Nippon Zeon Co., Ltd. (acrylic ester copolymer; solid content 48% by mass; Tg = 0 ° C.) 67.0 parts by mass 10% heptasodium pentaphosphate 16.8 parts by mass distilled water 16. 2 parts by mass
<塗布液(5)>
日本ゼオン株式会社製の商品名Nipol SX1706A(アクリル酸エステル共重合体;固形分48質量%;Tg=0℃) 67.0質量部
10%四リン酸四ナトリウム 16.8質量部
蒸留水 16.2質量部
<Coating liquid (5)>
Product name Nipol SX1706A manufactured by Nippon Zeon Co., Ltd. (acrylic acid ester copolymer; solid content 48 mass%; Tg = 0 ° C.) 67.0 mass parts 10% tetrasodium tetraphosphate 16.8 mass parts distilled water 16. 2 parts by mass
<塗布液(6)>
日本ゼオン株式会社製の商品名Nipol SX1503(アクリロニトリルブタジエン共重合体;固形分42質量%;Tg=−20℃) 76.6質量部
10%三リン酸五ナトリウム 16.8質量部
蒸留水 6.6質量部
<Coating liquid (6)>
Product name Nipol SX1503 (acrylonitrile butadiene copolymer; solid content 42% by mass; Tg = −20 ° C.) 76.6 parts by mass 10% pentasodium triphosphate 16.8 parts by mass distilled water 6 parts by mass
<塗布液(7)>
日本ゼオン株式会社製の商品名Nipol LX426(スチレンブタジエン共重合体;固形分42質量%;Tg=−39℃) 64.4質量部
10%三リン酸五ナトリウム 16.8質量部
蒸留水 18.8質量部
<Coating liquid (7)>
Product name Nipol LX426 (styrene butadiene copolymer; solid content 42% by mass; Tg = −39 ° C.) 64.4 parts by mass 10% pentasodium triphosphate 16.8 parts by mass distilled water 18. 8 parts by mass
<塗布液(8)>
日本ゼオン株式会社製の商品名Nipol LX430(スチレンブタジエン共重合体;固形分42質量%;Tg=12℃) 65.8質量部
10%三リン酸五ナトリウム 16.8質量部
蒸留水 17.4質量部
<Coating liquid (8)>
Product name Nipol LX430 (styrene butadiene copolymer; solid content 42% by mass; Tg = 12 ° C.) 65.8 parts by mass 10% pentasodium triphosphate 16.8 parts by mass distilled water 17.4 Parts by mass
<塗布液(9)>
10%ポリアクリル酸ナトリウム(重合度25000) 90質量部
(和光純薬株式会社製ポリアクリル酸ナトリウム重合度2700〜7500を使用)
10%三リン酸五ナトリウム 10質量部
<Coating liquid (9)>
90% by mass of 10% sodium polyacrylate (polymerization degree 25000) (using sodium polyacrylate polymerization degree 2700-7500 manufactured by Wako Pure Chemical Industries, Ltd.)
10 mass parts of 10% pentasodium triphosphate
上記塗布液(1)〜(9)を、王子タック株式会社製の剥離シート紙L7C(商品名)の上に乾燥固形分量が100g/m2となるように塗布し、60℃で乾燥した後、剥離シート紙から創傷被覆層を剥離した。このようにして、塗布液(1)〜(6)からなる本発明の創傷被覆材(1)〜(6)及び、塗布液(7)〜(9)からなる比較例の創傷被覆材(7)〜(9)を得た。 The coating liquid (1) to (9), dry solid content was coated with a 100 g / m 2 on the Oji Tac Co. release sheet paper L7C (trade name), was dried at 60 ° C. The wound covering layer was peeled from the release sheet paper. In this way, the wound dressing (1) to (6) of the present invention comprising the coating liquids (1) to (6) and the wound dressing of the comparative example (7) comprising the coating liquids (7) to (9). ) To (9) were obtained.
<三リン酸五ナトリウムを内包するアルギン酸カルシウムヒドロゲルの作製>
10%三リン酸五ナトリウム水溶液10質量部と5%アルギン酸ナトリウム(富士化学工業株式会社製の商品名スノーアルギンSH)水溶液2質量部からなる水溶液(a)を用意した。ガラス容器に入れて1000rpmの回転数の攪拌羽根により攪拌されている2%塩化カルシウム溶液100質量部に口径5μmのマイクロシリンジから上記水溶液(a)を添加し、三リン酸五ナトリウムを内包するアルギン酸カルシウムヒドロゲルの分散液(b)を得た。上記分散液(b)を3000rpmの遠心分離機で5分間遠心分離した後、乾燥機中で、60℃で12時間乾燥し、三リン酸五ナトリウムを内包したアルギン酸カルシウムヒドロゲルの粉末を得た。光学顕微鏡を用いてこの粉末を観察し、平均粒径10μmの球状の粒子であることが分かった。この粉末の100質量部を600℃の電気炉で1時間加熱し、絶乾試料とし、質量を測定したところ60質量部の質量であった。また、絶乾燥試料1質量部に99質量部の蒸留水を加え、Mo(V)−Mo(VI)試薬1質量部を加えて100℃で40分加熱後、生成したリンモリブデンへテロブルー錯体の830nmの吸光度を可視紫外分光光度計、株式会社島津製作所製紫外可視分光光度計UV−2600を用いて測定し、絶乾試料60質量部中、50質量部が三リン酸五ナトリウムであること、すなわちアルギン酸カルシウムヒドロゲルの50質量%が三リン酸化合物からなることが分かった。
<Preparation of calcium alginate hydrogel containing pentasodium triphosphate>
An aqueous solution (a) comprising 10 parts by mass of a 10% aqueous solution of pentasodium triphosphate and 2 parts by mass of an aqueous solution of 5% sodium alginate (trade name Snow Algin SH manufactured by Fuji Chemical Industry Co., Ltd.) was prepared. Alginic acid containing pentasodium triphosphate by adding the aqueous solution (a) from a microsyringe having a diameter of 5 μm to 100 parts by mass of a 2% calcium chloride solution stirred in a glass container and stirred with a stirring blade having a rotation speed of 1000 rpm A dispersion (b) of calcium hydrogel was obtained. The dispersion (b) was centrifuged for 5 minutes in a 3000 rpm centrifuge and then dried in a dryer at 60 ° C. for 12 hours to obtain a calcium alginate hydrogel powder containing pentasodium triphosphate. This powder was observed using an optical microscope and found to be spherical particles having an average particle diameter of 10 μm. 100 parts by mass of this powder was heated in an electric furnace at 600 ° C. for 1 hour to prepare an absolutely dry sample, and the mass was measured to be 60 parts by mass. Further, 99 parts by mass of distilled water was added to 1 part by mass of the absolutely dry sample, 1 part by mass of Mo (V) -Mo (VI) reagent was added, and the mixture was heated at 100 ° C. for 40 minutes, and then the phosphomolybdenum heteroblue complex formed. 830 nm absorbance was measured using a visible ultraviolet spectrophotometer, UV-2600 made by Shimadzu Corporation, and 50 parts by mass of pentasodium triphosphate in 60 parts by mass of absolutely dry sample. That is, it was found that 50% by mass of the calcium alginate hydrogel was composed of a triphosphate compound.
<マイクロカプセルを混練した創傷被覆層の作製>
熱可塑性のスチレン−エチレン/プロピレン−スチレン共重合体ペレット(商品名:クラレ株式会社製セプトン2007)20質量部、液状エチレンプロピレンゴム(商品名:クラレ株式会社製LEPR)70質量部、を加圧ニーダーに入れ均一になるまで分散混合した後、上記のようにして作製した三リン酸五ナトリウムを内包したアルギン酸カルシウムカプセル粉末10質量部を加え、均一になるまで加圧混合を行った。そして、得られた混合物を100μmのギャップを有する押し出し成型機から王子タック株式会社製の剥離シート紙L7Cの上に塗布し、室温に冷却し、剥離シート紙から創傷被覆層を剥離して、乾燥固形分量が100g/m2の比較例の創傷被覆材の創傷被覆層(10)を得た。
<Preparation of wound covering layer kneaded with microcapsules>
20 parts by mass of thermoplastic styrene-ethylene / propylene-styrene copolymer pellets (trade name: Kuraray Co., Ltd. Septon 2007) and 70 parts by mass of liquid ethylene propylene rubber (trade name: Kuraray Co., Ltd. LEPR) are pressurized. After dispersing and mixing in a kneader until uniform, 10 parts by mass of calcium alginate capsule powder encapsulating pentasodium triphosphate prepared as described above was added, and pressure mixing was performed until uniform. Then, the obtained mixture was applied from an extrusion molding machine having a gap of 100 μm onto release sheet paper L7C manufactured by Oji Tac Co., Ltd., cooled to room temperature, the wound covering layer was peeled off from the release sheet paper, and dried. A wound dressing layer (10) of the wound dressing material of Comparative Example having a solid content of 100 g / m 2 was obtained.
本発明の創傷被覆材が有する創傷被覆層(1)〜(6)および比較例の創傷被覆材の創傷被覆層(7)〜(10)各1gを100gの生理食塩水を入れた蓋付きのガラス瓶にいれ、37℃で24時間、48時間、又は72時間静置後、生理食塩水10gを採取し、図7に記載のカラムクロマトグラフィー装置を用いてそれぞれの生理食塩水中に放出された水溶性ポリリン酸化合物の量を測定した。0〜24時間、24時間〜48時間、48時間〜72時間の間に生理食塩水中に放出された水溶性ポリリン酸化合物の量を表1に示す。表1に於いて、生理食塩水中に放出された水溶性ポリリン酸化合物量は、創傷被覆層1gが予め含有している水溶性ポリリン酸化合物量に対する質量%に換算して示した。創傷被覆材の創傷被覆層(1)〜(3)、(6)、(7)、(9)、(10)から生理食塩水中に放出された水溶性ポリリン酸化合物はすべて三リン酸五ナトリウムであった。また創傷被覆材の創傷被覆層(4)から生理食塩水中に放出された水溶性ポリリン酸化合物はすべて五リン酸七ナトリウムであり、創傷被覆材の創傷被覆層(5)から生理食塩水中に放出された水溶性ポリリン酸化合物はすべて四リン酸四ナトリウムであった。 The wound dressing layers (1) to (6) of the wound dressing material of the present invention and the wound dressing layers (7) to (10) of the wound dressing materials of the comparative examples are each equipped with a lid containing 100 g of physiological saline. After placing in a glass bottle and allowing to stand at 37 ° C. for 24, 48, or 72 hours, 10 g of physiological saline was collected, and the aqueous solution released into each physiological saline using the column chromatography apparatus shown in FIG. The amount of the functional polyphosphate compound was measured. Table 1 shows the amount of the water-soluble polyphosphate compound released into the physiological saline during 0 to 24 hours, 24 hours to 48 hours, and 48 hours to 72 hours. In Table 1, the amount of the water-soluble polyphosphate compound released into the physiological saline is shown in terms of mass% with respect to the amount of the water-soluble polyphosphate compound contained in 1 g of the wound covering layer in advance. The water-soluble polyphosphate compound released into the physiological saline from the wound dressing layers (1) to (3), (6), (7), (9) and (10) of the wound dressing is all pentasodium triphosphate Met. The water-soluble polyphosphate compound released from the wound dressing layer (4) of the wound dressing into the physiological saline is all pentasodium pentaphosphate and released from the wound dressing layer (5) of the wound dressing into the physiological saline. The water-soluble polyphosphate compound produced was tetrasodium tetraphosphate.
表1の結果から、水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃の熱可塑性ラテックスを含有する創傷被覆層(1〜6)を有することを特徴とする本発明の創傷被覆材は、生理食塩水との接触により水溶性ポリリン酸化合物を徐放していることが分かる。一方、水溶性ポリリン酸化合物、および−29.5〜6.0℃のガラス転移温度を有しない熱可塑性ラテックスを含有する創傷被覆層(7、8)を有する比較例の創傷被覆材、ならびに、水溶性ポリリン酸化合物、および水分散性でない熱可塑性樹脂から形成された創傷被覆層(9、10)を有する比較例の創傷被覆材は、水溶性ポリリン酸化合物を放出しなかったり、あるいは短時間で放出が終了してしまい、良好な徐放性を示さなかった。 From the results of Table 1, the present invention is characterized by having a wound covering layer (1-6) containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of -29.5 to 6.0 ° C. It can be seen that the wound dressing of the present invention slowly releases the water-soluble polyphosphate compound by contact with physiological saline. On the other hand, a wound dressing of a comparative example having a wound dressing layer (7, 8) containing a water-soluble polyphosphate compound and a thermoplastic latex having no glass transition temperature of −29.5 to 6.0 ° C., and The wound dressing material of the comparative example having the wound dressing layers (9, 10) formed from the water-soluble polyphosphate compound and the thermoplastic resin that is not water-dispersible does not release the water-soluble polyphosphate compound, or for a short time. In this case, the release was terminated, and good sustained release was not exhibited.
<緑膿菌の培養と菌数測定>
本発明の創傷被覆材の創傷被覆層(1)〜(3)1gおよび比較例の創傷被覆材の創傷被覆層(9)1gをガラスシャーレ入れ、120℃で15分間オートクレーブで滅菌後、緑膿菌培養液0.2ミリリットルを滴下し、シャーレに均一に液を広げた後、培養器に入れて、37℃で48時間培養した緑膿菌培養試料を各々6個づつ作製した。上記の各緑膿菌培養試料6個のうちの各3個のシャーレに生理食塩水10ミリリットルを加えて振とう、遠心分離上澄み抽出し、光学顕微鏡により菌数を測定した。それぞれの菌数の平均値を図8に示す。
<Culture and measurement of Pseudomonas aeruginosa>
1 g of the wound dressing layers (1) to (3) of the wound dressing material of the present invention and 1 g of the wound dressing layer (9) of the wound dressing material of the comparative example were placed in a glass petri dish, sterilized in an autoclave at 120 ° C. for 15 minutes, and then treated with green pus. After adding 0.2 ml of the fungus culture solution and spreading the solution uniformly in the petri dish, each was put into an incubator, and 6 Pseudomonas aeruginosa culture samples cultured at 37 ° C. for 48 hours were prepared. 10 milliliters of physiological saline was added to each of 3 petri dishes out of the above 6 Pseudomonas aeruginosa culture samples, shaken, centrifuged and extracted, and the number of bacteria was measured with an optical microscope. The average value of each number of bacteria is shown in FIG.
<毒素生成量の測定>
上記の各緑膿菌培養試料6個の内の菌数測定に用いた以外の残りの各3個の緑膿菌培養試料を入れたシャーレにクロロホルム(1ミリリットル)を加えて毒素(ピオシアニン色素)の490nmの抽出吸光度(OD490)測定により毒素生成量を定量した。吸光度の測定には可視紫外分光光度計、株式会社島津製作所製紫外可視分光光度計UV−2600を用いた。それぞれの毒素生成量の平均値を図9に示す。毒素生成量は創傷被覆層(9)の毒素生成量の平均値を100としたときの相対値で表した。
<Measurement of toxin production>
Chloroform (1 milliliter) was added to the petri dish containing the remaining 3 P. aeruginosa culture samples other than those used for the count of the 6 P. aeruginosa culture samples, and a toxin (pyocyanin dye) The amount of toxin produced was quantified by measuring the extraction absorbance (OD 490 ) at 490 nm. For the measurement of absorbance, a visible ultraviolet spectrophotometer, a UV-visible spectrophotometer UV-2600 manufactured by Shimadzu Corporation was used. The average value of each toxin production amount is shown in FIG. The toxin production amount was expressed as a relative value when the average value of the toxin production amount of the wound covering layer (9) was 100.
図8および図9の結果から、水溶性ポリリン酸化合物、およびガラス転移温度が−29.5〜6.0℃である熱可塑性ラテックスを含有する創傷被覆層を有することを特徴とする本発明の創傷被覆材は、水溶性ポリリン酸化合物を徐放することにより、緑膿菌を殺傷することなく、緑膿菌による毒素の産生を抑制していることが分かる。一方、水溶性ポリリン酸化合物を徐放しない比較例の創傷被覆材は緑膿菌による毒素の産生が生じていることが分かる。 From the results of FIGS. 8 and 9, the present invention has a wound covering layer containing a water-soluble polyphosphate compound and a thermoplastic latex having a glass transition temperature of −29.5 to 6.0 ° C. It can be seen that the wound dressing material suppresses the production of toxins by Pseudomonas aeruginosa without killing Pseudomonas aeruginosa by releasing the water-soluble polyphosphate compound gradually. On the other hand, it can be seen that in the wound dressing of the comparative example in which the water-soluble polyphosphate compound is not released slowly, toxin production by Pseudomonas aeruginosa occurs.
本発明の創傷被覆材は、傷口への細菌進入を阻止する作用を有する皮膚常在菌を殺傷することなく滲出液による治癒をおこなえることから、化膿創傷ではない通常の創傷に対しても治癒を促進する効果がある可能性がある。本発明の創傷被覆材は、創傷部からの滲出液との接触により徐放される水溶性ポリリン酸化合物の病原性因子産生抑制効果によって、創傷、特に、黄色ブドウ球菌や緑膿菌などに感染しやすい火傷などの化膿創傷に対して治癒を促進する効果がある可能性がある。近年、医療機関での感染症に対する予防技術の向上により、医療機関内での細菌感染の機会が減少している。しかし、感染予防が十分に行えない環境での創傷治療、例えば、野外、災害現場、戦場、医療設備の整備されていない発展途上国などでの緊急医療用の創傷被覆材として有望である。 The wound dressing of the present invention can heal even with normal wounds that are not purulent wounds, because it can heal with exudates without killing the skin resident bacteria that have the effect of preventing bacterial entry into the wound. There is a possibility of promoting the effect. The wound dressing of the present invention is capable of infecting wounds, particularly Staphylococcus aureus and Pseudomonas aeruginosa, by the effect of inhibiting the production of virulence factors by water-soluble polyphosphate compounds that are gradually released by contact with exudate from the wound. It may have an effect of promoting healing for purulent wounds such as burns that tend to occur. In recent years, opportunities for bacterial infection in medical institutions have decreased due to improvements in prevention techniques against infectious diseases in medical institutions. However, it is promising as a wound dressing for emergency medical treatment in an environment where infection prevention cannot be sufficiently performed, for example, in the field, disaster scene, battlefield, developing countries where medical facilities are not established.
1・・・バッキング層
2・・・接着剤層
3・・・吸収層
4・・・創傷被覆層
5・・・保護剥離基材
DESCRIPTION OF SYMBOLS 1 ... Backing layer 2 ... Adhesive layer 3 ... Absorbing layer 4 ... Wound covering layer 5 ... Protective peeling base material
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Cited By (2)
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JP2019069925A (en) * | 2017-10-11 | 2019-05-09 | 国立大学法人鳥取大学 | Wound healing promoting sheet and production method thereof as well as wound dressing comprising chitin nano fiber |
JPWO2020158778A1 (en) * | 2019-01-30 | 2021-11-25 | 富士フイルム株式会社 | Water-developable flexographic printing plate original plate, flexographic printing plate and photosensitive resin composition |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2019069925A (en) * | 2017-10-11 | 2019-05-09 | 国立大学法人鳥取大学 | Wound healing promoting sheet and production method thereof as well as wound dressing comprising chitin nano fiber |
JPWO2020158778A1 (en) * | 2019-01-30 | 2021-11-25 | 富士フイルム株式会社 | Water-developable flexographic printing plate original plate, flexographic printing plate and photosensitive resin composition |
JP7417553B2 (en) | 2019-01-30 | 2024-01-18 | 富士フイルム株式会社 | Water-developable flexographic printing plate precursor, flexographic printing plate and photosensitive resin composition |
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