JP6370002B2 - ヒアルロン酸の製造方法及び前記製造方法で製造されたヒアルロン酸を含む癒着防止用組成物 - Google Patents
ヒアルロン酸の製造方法及び前記製造方法で製造されたヒアルロン酸を含む癒着防止用組成物 Download PDFInfo
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- 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
- A61L27/58—Materials at least partially resorbable by the body
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/042—Polysaccharides
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
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Description
(a)ストレプトコカスディスカラクティーエ9103菌株を炭素源及び窒素源が含まれた培地で培養する段階;及び
(b)前記(a)段階で培養された培養物からヒアルロン酸を回収する段階を含む製造方法でもある。
分子量による癒着防止効果実験
SDラット(female,SPF,(株)オリエントバイオ)を吸込み式で麻酔して、手術する間継続して麻酔した。四肢を手術台に固定して、腹部の毛を剃刀で取除き消毒後ハサミで腹部を開腹した。盲腸を取出して荒いガーゼで血痕がガーゼにつく程に傷を明渡し、盲腸があった位置の腹壁又は同じ方法で盲腸と内腹膜壁との癒着が起こる条件を作った。試料を処理後縫合して、2週間飼育後開腹して、癒着の如何を確認した。試料は平均分子量300万Daのヒアルロン酸と400万Da及び600万Daのヒアルロン酸をリン酸ナトリウム緩衝溶液に溶かして使用し、無菌状態を維持した。
高分子ヒアルロン酸生産のための基本培養条件
-72℃の冷凍機で保管されたストレプトコカスディスカラクティーエID9103菌株培養液4mlを急速解凍して、5.2%ブレインハートインフュージョン個体培地に塗抹して37で24時間培養後、縦横1cm2の面積で生育されたコロニーを切り出して、3%のトドフュイトブロス(Todd-Hewitt broth)滅菌液体培地(heart,infusion 0.31%,neopeptone 2%,dextropse 0.2%,Disodium phosphate 0.04%,sodium carbonate 0.25%;BD社,米国)40mlに接種した。
高分子ヒアルロン酸生産性及び分子量
窒素源は微生物の代謝において重要な役割をし、ヒアルロン酸の生産にも影響を及ぼすものとして知られている。従って、基本的に使用される窒素源であるペプトン類を含み、アミノ酸類の変更を通じて、得ようとする400万乃至600万Daのヒアルロン酸の生産に寄与できると判断された。
ヒアルロン酸の体内分解速度比較実験
体内でヒアルロン酸を分解する酵素であるヒアルロニダーゼ(hyaluronidase)を利用して、300万Da、400万Da及び600万Daのヒアルロン酸に対する分解速度比較実験を行った。分解速度比較実験は粘度測定値(cP)を利用し、ヒアルロニダーゼ混合前後の粘度測定は、値の差を通じてヒアルロン酸の分解程度を比較した。粘度測定はBrookfield Difital Viscometer LVDV-1+(Brookfield,USA)で実施し、spindle 31,0.3RPM,25で測定した。その結果を表2と図2に示す。
Claims (4)
- ストレプトコカスディスカラクティーエ9103菌株(KCTC11818BP)を培地で培養する段階を含む、体内低分解速度を有するヒアルロン酸の製造方法であって、
前記ヒアルロン酸の分子量は350万Da乃至1000万Daであり、
前記培地は、ブドウ糖、酵母エキス、カゼインペプトン、グルタミン、グルコン酸ナトリウム、蓚酸、硫酸マグネシウム、リン酸一水素二カリウム、塩化ナトリウム、アセト酸ナトリウム、塩化二鉄、及びアンモニウムモリブデンを含み、かつ、下記(a)〜(c)の一以上の条件を満たすことを特徴とする前記製造方法。
(a)前記カゼインペプトンの代わりにカゼイン酵素加水分解物を含む
(b)前記グルタミンの代わりにアルギニンを含む
(c)前記ブドウ糖の代わりに麦芽糖を含む - 前記培地が、さらに亜鉛イオンを含む、請求項1に記載の製造方法。
- 前記ヒアルロン酸の分子量は400万Da乃至600万Daであることを特徴とする、請求項1に記載の製造方法。
- 前記ヒアルロン酸が架橋されていない、請求項1〜3のいずれかに記載の製造方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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KR1020130029876A KR101598329B1 (ko) | 2013-03-20 | 2013-03-20 | 히알루론산의 제조방법 및 상기 제조방법으로 제조된 히알루론산을 포함하는 유착방지용 조성물 |
KR10-2013-0029876 | 2013-03-20 | ||
PCT/KR2014/002364 WO2014148847A1 (ko) | 2013-03-20 | 2014-03-20 | 히알루론산의 제조방법 및 상기 제조방법으로 제조된 히알루론산을 포함하는 유착방지용 조성물 |
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Publication Number | Publication Date |
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JP2016515821A JP2016515821A (ja) | 2016-06-02 |
JP6370002B2 true JP6370002B2 (ja) | 2018-08-08 |
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JP2016504255A Active JP6370002B2 (ja) | 2013-03-20 | 2014-03-20 | ヒアルロン酸の製造方法及び前記製造方法で製造されたヒアルロン酸を含む癒着防止用組成物 |
Country Status (6)
Country | Link |
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US (1) | US20160009828A1 (ja) |
EP (1) | EP2977460B1 (ja) |
JP (1) | JP6370002B2 (ja) |
KR (1) | KR101598329B1 (ja) |
CN (1) | CN105324486B (ja) |
WO (1) | WO2014148847A1 (ja) |
Families Citing this family (5)
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ITUA20164153A1 (it) | 2016-06-07 | 2017-12-07 | Jointherapeutics S R L | Composizioni polisaccaridiche impiegabili nella riparazione tissutale |
WO2018106924A1 (en) | 2016-12-09 | 2018-06-14 | Cummins Inc. | Spark plug for an internal combustion engine having a combustion pre-chamber |
KR102489403B1 (ko) * | 2018-10-29 | 2023-01-17 | 엠앤에이치바이오 주식회사 | 신규한 스트렙토코커스 속 ubc-u46 균주 및 이를 이용한 히알루론산 생산 방법 |
EP3797800A1 (en) * | 2019-05-02 | 2021-03-31 | Institut National De La Sante Et De La Recherche Medicale - Inserm | Hyaluronic acid hydrogels with prolonged antimicrobial activity |
KR102546437B1 (ko) * | 2021-03-15 | 2023-06-21 | 금오공과대학교 산학협력단 | 생체적합성 고분자를 포함하는 파우더형 유착방지제 및 그의 제조방법 |
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US4141973A (en) * | 1975-10-17 | 1979-02-27 | Biotrics, Inc. | Ultrapure hyaluronic acid and the use thereof |
US5496726A (en) * | 1993-04-16 | 1996-03-05 | Lucky Limited | Streptococcus zooepidemicus medium and process for preparing hyaluronic acid |
JP3632197B2 (ja) * | 1996-10-15 | 2005-03-23 | チッソ株式会社 | 高分子量ヒアルロン酸もしくはその塩の製造法 |
CN1101405C (zh) | 1997-08-22 | 2003-02-12 | 电气化学工业株式会社 | 透明质酸凝胶的制备方法、用此方法制得的透明质酸及包含这种凝胶的医用材料 |
DE60014400T2 (de) | 1999-07-28 | 2005-10-06 | United States Surgical Corp., Norwalk | Antiadhäsionsschicht aus hyaluronsäure |
AU2003252566A1 (en) * | 2002-08-19 | 2004-03-03 | Kolon Ind. Inc. | Microorganism producing hyaluronic acid and purification method of hyaluronic acid |
KR20090012439A (ko) | 2007-07-30 | 2009-02-04 | 주식회사 핸슨바이오텍 | 기관 유착 방지 특성을 갖는 히알루론산 및카르복시메칠셀룰로즈 복합체 유도체 필름 및 겔 및 그제조방법 |
EP2031053A1 (en) * | 2007-08-31 | 2009-03-04 | The University Of Queensland | Production of HA |
WO2010010631A1 (ja) * | 2008-07-25 | 2010-01-28 | 電気化学工業株式会社 | ヒアルロン酸の製造方法 |
KR101087969B1 (ko) * | 2008-10-31 | 2011-12-01 | 일동제약주식회사 | 미생물 배양에 의한 히알우론산을 생산하는 방법 |
KR101062068B1 (ko) * | 2008-12-01 | 2011-09-02 | 포항공과대학교 산학협력단 | 유착방지용 조성물 |
WO2010125069A1 (en) * | 2009-04-28 | 2010-11-04 | Pharmasurgics In Sweden Ab | Hyaluronic acid for preventing post surgical adhesions |
KR101074467B1 (ko) | 2009-05-08 | 2011-10-17 | 주식회사 휴메딕스 | 히알루론산 및 l-아르기닌을 함유하는 유착방지제 |
KR101132114B1 (ko) * | 2009-09-15 | 2012-04-05 | 일동제약주식회사 | 히알루론산의 분자량을 조절하는 방법 |
WO2011109130A1 (en) * | 2010-03-01 | 2011-09-09 | Tautona Group Lp | Threads of hyaluronic acid and methods of use thereof |
KR101091072B1 (ko) | 2010-03-04 | 2011-12-08 | 신효산업 주식회사 | 2단 빨대 |
KR101227248B1 (ko) | 2010-04-14 | 2013-01-28 | 원제돈 | 다용도 압력 조리장치 |
CN101912633A (zh) * | 2010-08-03 | 2010-12-15 | 孙伟庆 | 一种透明质酸海绵及其制备方法 |
WO2012057381A1 (ko) * | 2010-10-29 | 2012-05-03 | 주식회사 휴메딕스 | 히알루론산 및 l-아르기닌을 함유하는 유착방지제 |
TW201313261A (zh) * | 2011-08-26 | 2013-04-01 | Lg Life Sciences Ltd | 防沾黏劑及使用該防沾黏劑之預防沾黏之方法 |
KR101322227B1 (ko) * | 2011-09-30 | 2013-10-28 | 일동제약주식회사 | 스트렙토코커스 디스갈락티애 id9103 균주 및 이를 이용한 히알루론산 생산 방법 |
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- 2013-03-20 KR KR1020130029876A patent/KR101598329B1/ko active IP Right Grant
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- 2014-03-20 WO PCT/KR2014/002364 patent/WO2014148847A1/ko active Application Filing
- 2014-03-20 EP EP14767484.0A patent/EP2977460B1/en active Active
- 2014-03-20 CN CN201480029053.4A patent/CN105324486B/zh active Active
- 2014-03-20 JP JP2016504255A patent/JP6370002B2/ja active Active
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- 2015-09-21 US US14/859,975 patent/US20160009828A1/en not_active Abandoned
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Publication number | Publication date |
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WO2014148847A8 (ko) | 2015-10-22 |
CN105324486B (zh) | 2020-09-01 |
KR20140115149A (ko) | 2014-09-30 |
JP2016515821A (ja) | 2016-06-02 |
CN105324486A (zh) | 2016-02-10 |
EP2977460A1 (en) | 2016-01-27 |
EP2977460A4 (en) | 2016-11-16 |
KR101598329B1 (ko) | 2016-02-29 |
WO2014148847A1 (ko) | 2014-09-25 |
EP2977460B1 (en) | 2019-05-08 |
US20160009828A1 (en) | 2016-01-14 |
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