JP2020527987A - ヒアルロン酸−カルシウム及びポリリシンを含む創傷被覆材及びその製造方法 - Google Patents
ヒアルロン酸−カルシウム及びポリリシンを含む創傷被覆材及びその製造方法 Download PDFInfo
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- JP2020527987A JP2020527987A JP2020502959A JP2020502959A JP2020527987A JP 2020527987 A JP2020527987 A JP 2020527987A JP 2020502959 A JP2020502959 A JP 2020502959A JP 2020502959 A JP2020502959 A JP 2020502959A JP 2020527987 A JP2020527987 A JP 2020527987A
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- Prior art keywords
- calcium
- wound dressing
- hyaluronic acid
- polylysine
- pll
- 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.)
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Classifications
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
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Abstract
Description
以下、実施例を通じて本発明を更に詳しく説明するが、下記実施例は単なる例示であって、本発明の範囲を何ら限定するものではない。
ヒアルロン酸5gを精製水450mlに加え、2時間攪拌した。CaCl21.1gを精製水50mlに溶解させて、前記溶液に加え、室温で3時間ゆっくり攪拌してヒアルロン酸カルシウム塩を生成した。次に、全10ml体積の製造液に下記表1に示す量でそれぞれpH8.4に調整したHAとPLLの混合液を、0〜4℃で6〜10時間安定化した後、−10〜−20℃で10〜12時間冷凍し、凍結乾燥させてHA−PLLフォーム状創傷被覆材(以下、「HA−PLLパッド」または「HA−Ca−PLLパッド」と呼ばれる場合もある)を製造し、フォームが形成されるかどうかを観察した。その結果は下記表1に示す通りである。表1において比較例1および2は、PLL無しでカルシウム塩で置換されたHAだけで製造したパッドである。
実施例2の組成の混合液に0.8%になるように塩化ナトリウムを添加してプレフィールドシリンジに入れ、液体状創傷被覆材の試料を準備した。
実施例2の組成の混合液を10cm×10cmの大きさの型枠に注型し、40℃のインキュベータで12時間〜16時間放置してフィルム状創傷被覆材を製造した。
前記実施例2、5、比較例1および2で製造したパッドのカルシウム置換率を、以下のような手順に従って、EDTAによるCa定量法で測定した。
1cm×1cm(横×縦)の大きさに切断した試験片に、それぞれ血液と抗凝固剤(クエン酸ナトリウム、3.8w/v%)を9:1の体積比で混合した。混合液100μlを滴下し、0.2MCaCl2水溶液10μlを添加して10分間37℃のインキュベータで凝固させた後、凝固に関与しない血液を再び蒸留水12.5mlに溶出した。その溶出液1mlを採取して540nmの波長で吸光度[AB]を測定し、蒸留水1mlをとり、540nmの波長で吸光度[AW]を測定した。血液溶出液に含まれている蒸留水の吸光度の影響を排除するために、下記式1に基づいて血液凝固特性(吸光度)を計算した。
37℃インキュベータでの血液凝固時間をそれぞれ1、2、3、5、および10分間凝固させた試料を用いたことを除いては、実験例4と同様の方式で血液溶出液の吸光度を測定して血液凝固速度を評価し、その結果を図6および7に示した。図6は、HA含有量が0.5%である場合、PLL含有量に応じた吸光度(O.D.)の計算結果を示すグラフであり、図7は、HA含有量が1.0%である場合、PLL含有量に応じた吸光度(O.D.)の計算結果を示すグラフである。
血液の吸収速度を、1cm×1cm(横×縦)大きさのヒアルロン酸−カルシウム及びポリリシン含有パッドに100μlの血液を滴下した後、完全に吸収されるまでの時間で評価し、そこから止血用パッドとしての適合性を判断した。対照群として、市販されているAlgi DermとRegenPack二つの製品について、同一の方式で比較実験を行った。その結果を下記の表4及び図8に示した。図8は、HA含有量が0.5%であるフォーム状パッドの血液滴下後5秒以内に撮影した写真である。
*血液吸収速度の指標は、血液が完全に吸収される時間に応じて、次のような基準に基づいて評価した:1:10秒以内;2:30秒以内;3:1分以上。
カルシウムとPLLが血液凝固に及ぼす影響を調べるため、実施例と同様の方法でヒアルロン酸カルシウム塩(HA−Ca)、ヒアルロン酸ナトリウム塩(HA−Na)、ヒアルロン酸−カルシウム及びポリリシン(HA−Ca−PLL)、およびヒアルロン酸−ナトリウムおよびポリリシン(HA−Na−PLL)含有フォーム状パッドを製造し、実験例2による方式で血液溶出液の吸光度を測定し、その結果を図9に示した。
ヒアルロン酸カルシウム塩(HA−Ca)、ヒアルロン酸ナトリウム塩(HA−Na)、ヒアルロン酸−カルシウム及びポリリシン(HA−Ca−PLL)、およびヒアルロン酸−ナトリウムおよびポリリシン(HA−Na−PLL)含有パッドの止血性能を、それぞれマウス(mouse)という肝門脈損傷モデルを用いた方法で評価した。麻酔された8週齢の雄マウスを、肝門脈がよく見えるように腹部の中央を切開した。18G針で血管に穴を開けてから、出血部位に1cm×1cm大きさの試験片を覆って止血されるまでの時間(clooting time)を測定した。止血作用を示すと言われているカルボキシメチルセルロース(CMC)を、ヒアルロン酸ナトリウム塩と混合して作成されたパッド(HA−CMC)を、比較例として追加して実験を行った。その結果を図10に示した。
前記実施例で製造された創傷被覆材の癒着防止性能を評価するために、ラット盲腸/腹壁擦過傷モデルを用いた。実験動物としては、7週齢雄Sprague−Dawley rat(SLC、Japan)を各群当たり5匹ずつ使用した。癒着を誘発させるために、実験動物にKetamine−HClを腹腔に注射(0.1ml/100g)して麻酔した後、腹部を除毛して70%エタノールで消毒した後、4−5cm程度を中央線に沿って開腹した。その後、盲腸を取り出して1.2cm×1.2cm大きさの滅菌ガーゼを用いて出血が起こるほどに漿膜に損傷を加え、向かい合う腹腔膜に同一の大きさで試薬用スプーンを用いて損傷を加えた。両損傷面を当接するようにして摩擦損傷部位から1cm離れた2ヶ所を5−0ナイロン縫合糸で固定することで、癒着の形成を促進した。
本発明によるHA及びPLLを含むフォーム状創傷被覆材と比較するために、架橋剤を使用してHAとPLLを架橋させてパッドを製造した。
37℃インキュベータでの血液凝固時間をそれぞれ1、2、3、5、および10分間凝固させた試料を用いたことを除いては、実験例2と同様の方式で血液溶出液の吸光度を測定して血液凝固速度を評価し、その結果を図6および7に示した。図6は、HA含有量が0.5%である場合、PLL含有量に応じた吸光度(O.D.)の計算結果を示すグラフであり、図7は、HA含有量が1.0%である場合、PLL含有量に応じた吸光度(O.D.)の計算結果を示すグラフである。
Claims (11)
- ヒアルロン酸−カルシウム及びポリリシンを含む、創傷被覆材。
- ヒアルロン酸−カルシウムとポリリシンを4:1〜1:1.5の重量比で含む、請求項1に記載の創傷被覆材。
- ヒアルロン酸−カルシウムとポリリシンを2:1〜4:3の重量比で含む、請求項1に記載の創傷被覆材。
- ヒアルロン酸−カルシウムとポリリシンを2:1〜1:1.5の重量比で含む、請求項1に記載の創傷被覆材。
- 前記ヒアルロン酸の分子量が2×106〜3×106Daである、請求項1に記載の創傷被覆材。
- 液体状、フォーム状又はフィルム状を呈する、請求項1に記載の創傷被覆材。
- 請求項1から請求項6のいずれか一項に記載の創傷被覆材を製造する方法であって、
(1)pHを8.4以上に調整したヒアルロン酸カルシウム塩の水溶液を、pHを8.4以上に調整したポリリシン水溶液と混合するステップ、および
(2)前記ステップ(1)で得られる混合液から創傷被覆材を得ること
を含む、創傷被覆材の製造方法。 - 前記ステップ(2)において、ヒアルロン酸カルシウム塩の水溶液及びポリリシン水溶液のpHをそれぞれ8.4〜9.0の範囲に調節する、請求項7に記載の創傷被覆材の製造方法。
- 前記ステップ(2)の混合液から液体状創傷被覆材を得る、請求項7に記載の創傷被覆材の製造方法。
- 前記ステップ(2)において、混合液を凍結乾燥させてフォーム状創傷被覆材を得る、請求項7に記載の創傷被覆材の製造方法。
- 前記ステップ(2)において、混合液を基材上に塗布するか、あるいは型枠に注型し、乾燥させてフィルム状創傷被覆材を得る、請求項7に記載の創傷被覆材の製造方法。
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EP (1) | EP3659631B1 (ja) |
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KR (2) | KR20190012120A (ja) |
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Families Citing this family (18)
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GB0808376D0 (en) | 2008-05-08 | 2008-06-18 | Bristol Myers Squibb Co | Wound dressing |
GB0817796D0 (en) | 2008-09-29 | 2008-11-05 | Convatec Inc | wound dressing |
GB201020236D0 (en) | 2010-11-30 | 2011-01-12 | Convatec Technologies Inc | A composition for detecting biofilms on viable tissues |
ES2748519T3 (es) | 2010-12-08 | 2020-03-17 | Convatec Technologies Inc | Accesorio de sistema de exudado de heridas |
US10207031B2 (en) | 2010-12-08 | 2019-02-19 | Convatec Technologies Inc. | Integrated system for assessing wound exudates |
GB201115182D0 (en) | 2011-09-02 | 2011-10-19 | Trio Healthcare Ltd | Skin contact material |
GB2497406A (en) | 2011-11-29 | 2013-06-12 | Webtec Converting Llc | Dressing with a perforated binder layer |
MX2015007771A (es) | 2012-12-20 | 2015-09-04 | Convatec Technologies Inc | Procesamiento de fibras celulosicas quimicamente modificadas. |
UY37178A (es) | 2016-03-30 | 2017-10-31 | Convatec Technologies Inc | Detección de infección microbiana en heridas |
AU2017243601A1 (en) | 2016-03-30 | 2018-11-22 | Acib Gmbh | Detecting microbial infection in wounds |
ES2882336T3 (es) | 2016-07-08 | 2021-12-01 | Convatec Technologies Inc | Sistema flexible de presión negativa |
EP3481348A4 (en) | 2016-07-08 | 2020-02-26 | ConvaTec Technologies Inc. | FLUID COLLECTION APPARATUS |
AU2017292028B2 (en) | 2016-07-08 | 2023-03-02 | Convatec Technologies Inc. | Fluid flow sensing |
US11331221B2 (en) | 2019-12-27 | 2022-05-17 | Convatec Limited | Negative pressure wound dressing |
US11771819B2 (en) | 2019-12-27 | 2023-10-03 | Convatec Limited | Low profile filter devices suitable for use in negative pressure wound therapy systems |
CN113174092B (zh) * | 2021-05-17 | 2022-10-25 | 西安交通大学 | 透明质酸-ε-聚赖氨酸盐酸盐的聚离子复合物、制备方法及应用 |
KR20230017722A (ko) | 2021-07-28 | 2023-02-06 | 주식회사 타임바이오 | 제대혈간세포 유래 엑소좀을 포함하는 창상 치료 또는 창상 치료 촉진용 조성물 |
EP4398914A1 (en) * | 2021-09-08 | 2024-07-17 | Ariel Scientific Innovations Ltd. | Methods of treating non-bleeding wounds, chronic wounds, inflammatory pain and nociceptive pain |
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- 2018-07-25 CN CN201880049648.4A patent/CN110997019A/zh active Pending
- 2018-07-25 WO PCT/KR2018/008397 patent/WO2019022493A1/ko unknown
- 2018-07-25 KR KR1020180086517A patent/KR20190012120A/ko not_active Application Discontinuation
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- 2023-08-10 KR KR1020230104897A patent/KR102667393B1/ko active IP Right Grant
- 2023-11-08 US US18/504,742 patent/US20240066179A1/en active Pending
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CN110997019A (zh) | 2020-04-10 |
EP3659631A4 (en) | 2021-04-14 |
EP3659631A1 (en) | 2020-06-03 |
JP6868314B2 (ja) | 2021-05-12 |
KR102667393B1 (ko) | 2024-05-20 |
KR20230125136A (ko) | 2023-08-29 |
US20210228768A1 (en) | 2021-07-29 |
US20240066179A1 (en) | 2024-02-29 |
WO2019022493A1 (ko) | 2019-01-31 |
KR20190012120A (ko) | 2019-02-08 |
EP3659631B1 (en) | 2023-08-30 |
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