JP5259710B2 - ボツリヌス毒素の安定性が改善された薬学的液状組成物 - Google Patents
ボツリヌス毒素の安定性が改善された薬学的液状組成物 Download PDFInfo
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- JP5259710B2 JP5259710B2 JP2010515962A JP2010515962A JP5259710B2 JP 5259710 B2 JP5259710 B2 JP 5259710B2 JP 2010515962 A JP2010515962 A JP 2010515962A JP 2010515962 A JP2010515962 A JP 2010515962A JP 5259710 B2 JP5259710 B2 JP 5259710B2
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- Prior art keywords
- botulinum toxin
- polysorbate
- liquid composition
- methionine
- pharmaceutical
- 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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Description
(1)ボツリヌス毒素液状組成物の製造
安定化剤溶液を用いてボツリヌス毒素液を希釈し、最終的にボツリヌス毒素液の濃度を100ユニット/mLとなるようにボツリヌス毒素液状組成物を製造した。
製造されたボツリヌス毒素液状組成物を特定の温度で保管しながら一定期間ごとに1mLサンプリングを行った。サンプリングされた液状組成物1mLに注射用水9mLを入れて10倍に希釈し、希釈されたサンプルを4週齢ICR(Institute of Cancer Research、USA)雌マウス5匹に腹腔注射した(1匹当り0.3mLずつ、すなわち3ユニット/マウス)。腹腔注射後3日間観察しながら、死亡したマウスの数およびそれによる死亡率を確認した。マウスの死亡率が50%以上であれば、ボツリヌス毒素の活性が維持されるものと評価できる。
多様なボツリヌス毒素安定化剤候補を含むボツリヌス毒素液状組成物を製造し、25℃または37℃の温度で保管しながら、保管期間によるボツリヌス毒素液状組成物の安定性を測定した。ボツリヌス毒素安定化剤の選別実験による25℃での安定性実験結果を表1に示し、37℃での安定性実験結果を表2に示した。表1および表2において、HSAはヒト血清アルブミン(Human Serum Albumin)を意味し、PEG8000はポリエチレングリコール8000を意味する。
ボツリヌス毒素の安定化剤として様々な濃度のメチオニンとポリソルベート20を含む液状ボツリヌス毒素組成物の安定性実験を37℃の保管条件で実施した。以下の表3にはメチオニンの濃度変化によるボツリヌス毒素の安定性実験結果を示した。
ボツリヌス毒素の安定化剤としてメチオニンと様々な濃度のポリソルベート20を含む液状ボツリヌス毒素組成物の安定性実験を37℃の保管条件で行った。ポリソルベート20の濃度変化によるボツリヌス毒素の安定性実験結果は表4に示した。
ボツリヌス毒素の安定化剤として、メチオニンおよびポリソルベート20の多様な濃度を含む液状ボツリヌス毒素組成物によるボツリヌス毒素の安定性実験を37℃の保管条件で行った。表5および表6には、30日および60日保管時のメチオニンおよびポリソルベート20の多様な濃度条件(実施例12)におけるボツリヌス毒素の安定性実験結果(死亡率(%))を示した。前記実験のボツリヌス毒素液状組成物において、ボツリヌス毒素の濃度は100ユニット/mLであった。
ボツリヌス毒素を最も安定化させるメチオニンとポリソルベート20の濃度範囲においてpH5.5〜7.0のボツリヌス毒素液状組成物(実施例13)を製造し、ボツリヌス毒素の安定性実験を40℃の保管条件で行った。ボツリヌス毒素液状組成物のpHは塩酸(HCl)または水酸化ナトリウム(NaOH)を用いて調整し、ボツリヌス毒素の濃度は100ユニット/mLであった。表7にはボツリヌス毒素液状組成物のpHによるボツリヌス毒素の安定性実験結果を示した。
ボツリヌス毒素の安定化剤を選別する過程で、メチオニンとポリソルベート20の組み合わせだけでなく、イソロイシンとポリソルベート20の組み合わせもボツリヌス毒素を安定化させる効果を持たと確認されたので、メチオニン、イソロイシンおよびポリソルベート20の組み合わせによるボツリヌス毒素の安定性実験を37℃の保管条件で行った。前記実験のボツリヌス毒素液状組成物におけるボツリヌス毒素の濃度は100ユニット/mLであった。
Claims (6)
- ボツリヌス毒素、ポリソルベート20、およびメチオニンを含む薬学的液状組成物であって、前記ボツリヌス毒素の濃度は50〜100ユニット/mLであり、前記ポリソルベート20の濃度は0.1〜2.5mg/mLであり、前記メチオニンの濃度は、1〜100mMである、薬学的液状組成物。
- 前記ボツリヌス毒素は、ボツリヌス毒素血清型A、B、C、D、E、FおよびGよりなる群から選択される、請求項1記載の薬学的液状組成物。
- 前記ボツリヌス毒素は複合体化タンパク質を含有しない形態、または複合体化タンパク質を含有する複合体形態である、請求項1または2に記載の薬学的液状組成物。
- 前記薬学的組成物のpHは5.5〜7.0である、請求項1〜3のいずれか1項に記載の薬学的液状組成物。
- 前記薬学的液状組成物はイソロイシンをさらに含む、請求項1〜4のいずれか1項に記載の薬学的液状組成物。
- 前記ボツリヌス毒素の濃度は100ユニット/mLである、請求項1〜5のいずれか1項記載の薬学的液状組成物。
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PCT/KR2008/002975 WO2009008595A1 (en) | 2007-07-10 | 2008-05-28 | Pharmaceutical liquid composition of botulinum toxin with improved stability |
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EP (1) | EP2170400B1 (ja) |
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KR (1) | KR101087017B1 (ja) |
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CA (1) | CA2690773C (ja) |
ES (1) | ES2391798T3 (ja) |
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Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
US8168206B1 (en) * | 2005-10-06 | 2012-05-01 | Allergan, Inc. | Animal protein-free pharmaceutical compositions |
KR101087017B1 (ko) * | 2007-07-10 | 2011-12-09 | (주)메디톡스 | 보툴리눔 독소의 안정성이 개선된 약제학적 액상 조성물 |
US9161970B2 (en) | 2007-12-12 | 2015-10-20 | Allergan, Inc. | Dermal filler |
EP2248518B1 (en) | 2009-04-17 | 2013-01-16 | Merz Pharma GmbH & Co. KGaA | Formulation for stabilizing proteins, peptides or mixtures thereof. |
JP6043627B2 (ja) * | 2009-06-25 | 2016-12-14 | ルバンス セラピュティックス インク.Revance Therapeutics,Inc. | アルブミン非含有ボツリヌス毒素製剤 |
ES2639617T3 (es) * | 2010-10-12 | 2017-10-27 | Merz Pharma Gmbh & Co. Kgaa | Formulación adecuada para estabilizar proteínas, que carece de excipientes de mamíferos |
EP3241547B1 (en) | 2011-03-31 | 2020-05-20 | Medy-Tox Inc. | Lyophilized preparation of botulinum toxin |
EP2731590B1 (en) * | 2011-07-13 | 2018-05-23 | The Foundry, LLC | Methods and apparatus for delivering a therapeutic agent to nasopharyngeal mucosa targets |
US9480731B2 (en) | 2013-12-12 | 2016-11-01 | Medy-Tox, Inc. | Long lasting effect of new botulinum toxin formulations |
US10478498B2 (en) | 2014-06-20 | 2019-11-19 | Reform Biologics, Llc | Excipient compounds for biopolymer formulations |
US11357857B2 (en) | 2014-06-20 | 2022-06-14 | Comera Life Sciences, Inc. | Excipient compounds for protein processing |
WO2015196091A1 (en) | 2014-06-20 | 2015-12-23 | Reform Biologics, Llc | Viscosity-reducing excipient compounds for protein formulations |
KR102557798B1 (ko) * | 2014-12-23 | 2023-07-19 | 메르츠 파마 게엠베하 운트 코. 카가아 | 보툴리눔 독소 사전충전된 용기 |
US10406290B2 (en) | 2015-02-03 | 2019-09-10 | Merz Pharma Gmbh & Co. Kgaa | Botulinum toxin prefilled plastic syringe |
WO2017188618A1 (en) * | 2016-04-26 | 2017-11-02 | Korea Prime Pharm Co., Ltd. | A novel composition comprising botulinum toxin |
WO2017203038A1 (en) * | 2016-05-27 | 2017-11-30 | Ipsen Biopharm Limited | Liquid neurotoxin formulation stabilized with tryptophan or tyrosine |
WO2018038301A1 (en) | 2016-08-26 | 2018-03-01 | Hugel Inc. | Stabilized liquid formulation of botulinum toxin and preparation method thereof |
WO2018038585A1 (ko) * | 2016-08-26 | 2018-03-01 | 주식회사 에이비바이오 | 보툴리눔 독소 및 안정화제를 포함하는 액상 제형 및 이의 제조방법 |
RU2019110875A (ru) * | 2016-09-13 | 2020-10-15 | Аллерган, Инк. | Небелковые композиции клостридиального токсина |
KR101744900B1 (ko) * | 2017-01-20 | 2017-06-08 | 주식회사 대웅 | 보툴리눔 독소를 포함하는 안정한 액상 조성물 |
WO2018236873A1 (en) | 2017-06-19 | 2018-12-27 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR THE TREATMENT OF MICROBIAL INFECTION |
CN107540732B (zh) * | 2017-08-31 | 2020-07-14 | 青海省畜牧兽医科学院 | 一种d型肉毒毒素的仿生矿化加工方法及应用 |
WO2020111852A1 (ko) * | 2018-11-30 | 2020-06-04 | 주식회사 휴온스글로벌 | 보툴리눔 독소의 안정화 액상 조성물 |
KR102259423B1 (ko) * | 2018-11-30 | 2021-06-02 | 주식회사 휴온스바이오파마 | 보툴리눔 독소의 안정화 액상 조성물 |
JP2023521123A (ja) * | 2020-04-08 | 2023-05-23 | メディトックス インク. | 吐出速度調節が容易であり、安定したボツリヌム毒素事前充填の注射器剤形 |
KR102324855B1 (ko) * | 2020-05-20 | 2021-11-11 | 오스템임플란트 주식회사 | 보툴리눔 독소를 포함하는 약제학적 액상 조성물 |
US20230256064A1 (en) | 2020-07-23 | 2023-08-17 | Medytox Inc. | Cancer therapeutic agent |
KR102414997B1 (ko) | 2020-09-29 | 2022-06-29 | 주식회사 엘지생활건강 | 안정성이 개선된 재조합 보툴리눔 독소 경쇄 단백질 조성물 |
WO2022075785A1 (ko) | 2020-10-07 | 2022-04-14 | 주식회사 프로톡스 | 보툴리눔 독소의 진공 건조 방법 |
KR20230001254A (ko) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법 |
KR20230001260A (ko) | 2021-06-28 | 2023-01-04 | (주)메디톡스 | 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법 |
KR20230071072A (ko) * | 2021-11-15 | 2023-05-23 | (주)메디톡스 | 보툴리눔 독소 조성물 |
CN116440281A (zh) * | 2022-01-07 | 2023-07-18 | 重庆誉颜制药有限公司 | 一种肉毒毒素蛋白组合物 |
KR20240060314A (ko) * | 2022-10-28 | 2024-05-08 | 주식회사 파마리서치바이오 | 보툴리눔 독소를 포함하는 안정한 액상 제제 |
Family Cites Families (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US656730A (en) * | 1899-08-25 | 1900-08-28 | Farbenfabriken Of Elberfeld Company | Blue chrysazin dye and process of making same. |
IL107887A (en) * | 1992-12-08 | 2003-07-06 | Ambi Inc | Stabilized lanthionine containing bacteriocin compositions |
US5358708A (en) * | 1993-01-29 | 1994-10-25 | Schering Corporation | Stabilization of protein formulations |
GB9418092D0 (en) * | 1994-09-08 | 1994-10-26 | Red Cross Found Cent Lab Blood | Organic compounds |
US5756468A (en) * | 1994-10-13 | 1998-05-26 | Wisconsin Alumni Research Foundation | Pharmaceutical compositions of botulinum toxin or botulinum neurotoxin and methods of preparation |
US5512547A (en) | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
US5656730A (en) * | 1995-04-07 | 1997-08-12 | Enzon, Inc. | Stabilized monomeric protein compositions |
WO2000051829A2 (en) | 1999-03-01 | 2000-09-08 | Rexam Industries Corp. | Decorative sheet material with chlorinated polyolefin adhesive layer |
JP2000247903A (ja) | 1999-03-01 | 2000-09-12 | Chugai Pharmaceut Co Ltd | 長期安定化製剤 |
US20060269575A1 (en) * | 2000-02-08 | 2006-11-30 | Allergan, Inc. | Botulinum toxin pharmaceutical compositions formulated with recombinant albumin |
EP1398038B2 (en) * | 2000-02-08 | 2011-01-26 | Allergan, Inc. | Botulinum toxin pharmaceutical compositions |
US20030118598A1 (en) * | 2000-02-08 | 2003-06-26 | Allergan, Inc. | Clostridial toxin pharmaceutical compositions |
US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
US8632785B2 (en) * | 2000-02-08 | 2014-01-21 | Allergan, Inc. | Clostridial toxin pharmaceutical composition containing a gelatin fragment |
US7998929B2 (en) | 2000-09-01 | 2011-08-16 | Chugai Seikyaku Kabushiki Kaisha | Solution preparations stabilized over long time |
US7140371B2 (en) * | 2002-03-14 | 2006-11-28 | Allergan, Inc. | Surface topography method for determining effects of a botulinum toxin upon a muscle and for comparing botulinum toxins |
WO2004007520A2 (en) * | 2002-07-12 | 2004-01-22 | Medarex, Inc. | Methods and compositions for preventing oxidative degradation of proteins |
US6803046B2 (en) | 2002-08-16 | 2004-10-12 | Bracco International B.V. | Sincalide formulations |
US20060002862A1 (en) * | 2002-12-17 | 2006-01-05 | Medimmune Vaccines, Inc. | High pressure spray-dry of bioactive materials |
WO2004087059A2 (en) * | 2003-03-26 | 2004-10-14 | The University Of Texas | Covalent attachment of ligands to nucleophilic proteins guided by non-covalent binding |
DE10333317A1 (de) * | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
GB2416122A (en) * | 2004-07-12 | 2006-01-18 | Ipsen Ltd | Botulinum neurotoxin composition |
EP2266600B1 (en) * | 2004-07-26 | 2014-09-10 | Merz Pharma GmbH & Co. KGaA | Therapeutic composition with a botulinum neurotoxin |
DE102004043009A1 (de) * | 2004-09-06 | 2006-03-23 | Toxogen Gmbh | Transportprotein zum Einbringen chemischer Verbindungen in Nervenzellen |
US7399607B2 (en) * | 2004-09-22 | 2008-07-15 | Allergan, Inc. | Fluorescence polarization assays for determining clostridial toxin activity |
JP5006803B2 (ja) * | 2005-03-03 | 2012-08-22 | アラーガン、インコーポレイテッド | クロストリジウム・バクテリアの培地およびクロストリジウム毒素を得るための方法 |
DE102005019302A1 (de) * | 2005-04-26 | 2006-11-16 | Toxogen Gmbh | Carrier zum Targeting von Nervenzellen |
US8323666B2 (en) * | 2005-08-01 | 2012-12-04 | Allergan, Inc. | Botulinum toxin compositions |
KR101105871B1 (ko) * | 2005-09-27 | 2012-01-16 | 주식회사 엘지생명과학 | 인 난포자극호르몬의 안정한 용액 제형 |
US8168206B1 (en) * | 2005-10-06 | 2012-05-01 | Allergan, Inc. | Animal protein-free pharmaceutical compositions |
US8137677B2 (en) | 2005-10-06 | 2012-03-20 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
US8232265B2 (en) * | 2005-10-07 | 2012-07-31 | Board Of Trustees Of The University Of Alabama | Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients |
US20090324647A1 (en) * | 2005-10-11 | 2009-12-31 | Borodic Gary E | Albumin-Free Botulinum Toxin Based Pharmaceutical Compositions Containing a Hyaluronidase and Methods of Use |
US9486408B2 (en) * | 2005-12-01 | 2016-11-08 | University Of Massachusetts Lowell | Botulinum nanoemulsions |
PT3295955T (pt) * | 2005-12-01 | 2021-07-12 | Univ Massachusetts Lowell | Nanoemulsões botulínicas |
US20070264355A1 (en) * | 2005-12-14 | 2007-11-15 | Binary, Llc | Binary compositions and methods for sterilization |
CA2645073A1 (en) * | 2006-03-08 | 2007-09-13 | Nuviance, Inc. | Transdermal drug delivery compositions and topical compositions for application on the skin |
WO2008070538A2 (en) * | 2006-12-01 | 2008-06-12 | Anterios, Inc. | Micellar nanoparticles comprising botulinum toxin |
GB0700523D0 (en) * | 2007-01-11 | 2007-02-21 | Insense Ltd | The Stabilisation Of Proteins |
JP2009008595A (ja) * | 2007-06-29 | 2009-01-15 | Kenwood Corp | ナビゲーション装置、ナビゲーション方法、および、ナビゲーションプログラム |
KR101087017B1 (ko) * | 2007-07-10 | 2011-12-09 | (주)메디톡스 | 보툴리눔 독소의 안정성이 개선된 약제학적 액상 조성물 |
US8883146B2 (en) * | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
US8420081B2 (en) * | 2007-11-30 | 2013-04-16 | Abbvie, Inc. | Antibody formulations and methods of making same |
KR20090120222A (ko) * | 2008-05-19 | 2009-11-24 | (주)메디톡스 | 식물 유래 성분 함유 배지 및 가요성 폐쇄 용기를 이용하여클로스트리디움 보툴리눔 독소를 생산하는 방법 |
US9155772B2 (en) * | 2008-12-08 | 2015-10-13 | Philip Morris Usa Inc. | Soft, chewable and orally dissolvable and/or disintegrable products |
KR101135449B1 (ko) * | 2009-03-10 | 2012-04-13 | 한국과학기술연구원 | 헤파라나제 활성 측정용 이온 복합체 나노 입자 및 그 제조방법 |
KR101736775B1 (ko) * | 2009-06-30 | 2017-05-18 | (주)아모레퍼시픽 | 복분자 추출물을 함유하는 피부 주름 개선용 화장료 조성물 |
KR101303388B1 (ko) * | 2010-10-26 | 2013-09-03 | 한미사이언스 주식회사 | 지속형 인터페론 알파 결합체의 액상 제제 |
EP3241547B1 (en) * | 2011-03-31 | 2020-05-20 | Medy-Tox Inc. | Lyophilized preparation of botulinum toxin |
KR101135486B1 (ko) * | 2011-05-25 | 2012-04-13 | 함종욱 | 보툴리눔 에이형 독소의 액상제품 |
US20140120077A1 (en) * | 2012-10-28 | 2014-05-01 | Revance Therapeutics, Inc. | Compositions and Methods for Safe Treatment of Rhinitis |
EP3052137A4 (en) * | 2013-10-01 | 2017-05-17 | Dana-Farber Cancer Institute, Inc. | Methods for the identification, assessment, prevention, and treatment of neurological disorders and diseases using fndc5 |
US9480731B2 (en) * | 2013-12-12 | 2016-11-01 | Medy-Tox, Inc. | Long lasting effect of new botulinum toxin formulations |
WO2018039506A1 (en) * | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Engineered botulinum neurotoxin |
KR102463881B1 (ko) * | 2016-10-04 | 2022-11-07 | (주)메디톡스 | 보툴리눔 독소 함유 용액으로부터 보툴리눔 독소를 분리하는 방법 |
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2008
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RU2440825C2 (ru) | 2012-01-27 |
EP2170400B1 (en) | 2012-07-25 |
BRPI0813948B1 (pt) | 2019-08-06 |
KR20090005963A (ko) | 2009-01-14 |
US20190298813A1 (en) | 2019-10-03 |
CA2690773A1 (en) | 2009-01-15 |
US8617568B2 (en) | 2013-12-31 |
US10293034B2 (en) | 2019-05-21 |
US20140161783A1 (en) | 2014-06-12 |
US20160206710A1 (en) | 2016-07-21 |
US20100291136A1 (en) | 2010-11-18 |
JP2010532784A (ja) | 2010-10-14 |
RU2009148286A (ru) | 2011-06-27 |
EP2170400A4 (en) | 2010-09-08 |
KR101087017B1 (ko) | 2011-12-09 |
ES2391798T3 (es) | 2012-11-30 |
US20210379165A1 (en) | 2021-12-09 |
EP2170400A1 (en) | 2010-04-07 |
WO2009008595A1 (en) | 2009-01-15 |
CA2690773C (en) | 2013-09-17 |
US9220780B2 (en) | 2015-12-29 |
BRPI0813948B8 (pt) | 2021-05-25 |
BRPI0813948A2 (pt) | 2016-06-28 |
CN101687046B (zh) | 2012-12-26 |
CN101687046A (zh) | 2010-03-31 |
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