JP7190760B2 - 神経学的、筋肉、および不妊の疾患または症状の治療のための安定化無定形炭酸カルシウム - Google Patents
神経学的、筋肉、および不妊の疾患または症状の治療のための安定化無定形炭酸カルシウム Download PDFInfo
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Description
発明の背景
安定化ACC:
医薬組成物および投与の経路
神経筋疾患または症状
補助的生殖技術:
細胞成長を高めるための方法:
例
例1.SC-DRG共培養におけるACCの効果
例3-健全な骨格筋細胞におけるACC調製物の効果
例4.デュシェンヌ型筋ジストロフィ-筋細胞株におけるACCの効果を評価する-インビトロ試験
例5.一次mdxマウス細胞におけるカルシウム源の効果
例6.マウスにおける筋ジストロフィ-に対するACCの効果を評価する-インビボ試験
例7.MDXマウスにおける筋ジストロフィ-に対するACC消費の効果を評価する
例8.ACC補充培地における胚発達の向上
例14.
例17.
例18.細胞培養培地サプリメントとして製剤化された10%TP-1%クエン酸ACC(10%三リン酸および1%クエン酸によって安定化されたACC)の調製
例19.
例20.
例21.細胞培養培地サプリメントとして製剤化されたACCの調製
例23.精子運動率向上のためのACC
例24.スイムアップ実験における精子運動率に対するACCの効果
例25.スイムアップ実験における精子運動率に対するACC濃度の効果
精子の運動率におけるACC濃度の効果を、各ACCについて3種の異なるサンプルを用いてスイムアップ実験によって試験した。結果を表21にまとめて示す。
例26ACCはインビトロで卵巣を維持する。
Claims (6)
- インビトロ受精のための方法であって、(a)哺乳動物卵母細胞をインビトロ受精させ、(b)胚をインビトロ培養することを含み、ここでステップ(a)、ステップ(b)、または両ステップ(a)および(b)は少なくとも1種類の安定化剤によって安定化された無定形炭酸カルシウム(ACC)を含む細胞培養培地で実施される、上記方法。
- 前記胚を少なくとも1種類の安定化剤によって安定化されたACCを含む細胞培養培地においてインビトロ培養することを含み、これによって胚発達を高める、請求項1に記載の方法。
- ステップ(a)の前に、少なくとも1種類の安定化剤によって安定化されたACCを含む細胞培養培地における卵母細胞のインビトロ成熟のステップをさらに含む、請求項1または2に記載の方法。
- 前記卵母細胞、または胚が、ヒトまたは非ヒト哺乳動物の卵母細胞、または胚である、請求項1~3のいずれか一項に記載の方法。
- 前記非ヒト哺乳動物が、家畜動物、家庭用愛玩動物、げっ歯類、および霊長類からなる群から選択される、請求項4に記載の方法。
- 前記少なくとも1種類の安定化剤が、ポリリン酸、リン酸化アミノ酸、有機酸、リン酸化、ホスホン酸化、硫酸化、またはスルホン酸化有機化合物、ヒドロキシカルボン酸のリン酸または硫酸エステル、ビスホスホネ-ト、サッカライドおよびそれらの誘導体、タンパク質、ペプチド、リン酸化タンパク質、リン酸化ペプチド、天然および合成バイオポリマ-およびそれらの誘導体、ならびにそれらのいずれかの組み合わせから選択される、請求項1~5のいずれか一項に記載の方法。
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WO2018078616A1 (en) | 2016-10-25 | 2018-05-03 | Amorphical Ltd | Amorphous calcium carbonate for treating a leukemia |
CN114144075A (zh) * | 2019-07-23 | 2022-03-04 | 艾玛菲克有限公司 | 用于改善运动性能的无定形碳酸钙 |
BR112022018055A2 (pt) * | 2020-03-11 | 2022-10-18 | Amorphical Ltd | Carbonato de cálcio amorfo para tratamento de acidose. |
IT202200010592A1 (it) * | 2022-05-23 | 2023-11-23 | Neilos S R L | “Composizione nutraceutica o farmaceutica per l’infertilità maschile” |
IT202200010583A1 (it) * | 2022-05-23 | 2023-11-23 | Neilos S R L | “Composizione nutraceutica o farmaceutica per l’infertilità maschile” |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070006332A1 (en) | 2003-08-20 | 2007-01-04 | Northern Sydney Area Health Service | Methods for enhancing embryo viability |
JP2010505818A (ja) | 2006-10-05 | 2010-02-25 | ベン グリオン ユニバーシティ オブ ザ ネゲブ リサーチ アンド ディベロップメント オーソリティ | 甲殻類の胃石成分を含む組成物とその使用 |
WO2014122658A1 (en) | 2013-02-11 | 2014-08-14 | Amorphical Ltd. | Amorphous calcium carbonate for accelerated bone growth |
JP2015500333A (ja) | 2011-12-13 | 2015-01-05 | アモーフィカル リミテッド. | カルシウム吸収不良及び代謝性骨障害を治療するための非晶質炭酸カルシウム |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4757017A (en) | 1984-09-14 | 1988-07-12 | Mcw Research Foundation, Inc. | In vitro cell culture system |
EP1048724A1 (en) * | 1999-04-27 | 2000-11-02 | Transgene S.A. | Human myoblast cell lines and their uses |
EP1670902A4 (en) * | 2003-09-08 | 2008-05-07 | Univ Texas | METHOD AND COMPOSITION FOR ENHANCING IN VITRO EMBRYONIC DEVELOPMENT BY ENRICHING A CULTURE MEDIUM COMPRISING PROSTAGLANDIN OR PROSTAGLANDIN ANALOGUE |
AU2005247198B2 (en) | 2004-05-26 | 2011-09-22 | Ben-Gurion University Of The Negev Research And Development Authority | Orally-administrable compositions comprising stable amorphous calcium carbonate |
US20080039531A1 (en) * | 2005-06-13 | 2008-02-14 | Alfred Stracher | Compositions, and kits comprising targeted aldehyde or acetal protease inhibitor compounds for treating muscle disorders |
RU2462458C2 (ru) * | 2006-02-10 | 2012-09-27 | Байомарин Ига Лимитед | Лечение миодистрофии дюшена |
CN104530208B (zh) * | 2007-10-22 | 2018-12-14 | 艾玛菲克有限公司 | 包含磷酸化氨基酸、合成的磷酸化肽和胃石蛋白的稳定的无定形碳酸钙 |
BR112015002505B1 (pt) | 2012-08-07 | 2021-07-20 | Amorphical Ltd. | Método para preparar carbonato de cálcio amorfo(acc), suspensão de acc estabilizada, pó de acc estável e uso de uma suspensão ou pó |
JP6860473B2 (ja) | 2014-07-31 | 2021-04-14 | アモーフィカル リミテッド. | 非晶質炭酸カルシウムの液体および半固体の非水性製剤 |
RU2748976C2 (ru) | 2015-06-04 | 2021-06-02 | Аморфикал Лтд. | Композиции аморфного карбоната кальция для ингаляции, подъязычного или трансбуккального введения |
CN108778295A (zh) | 2016-01-18 | 2018-11-09 | 艾玛菲克有限公司 | 作为细胞培养基补充剂的稳定的无定形碳酸钙 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070006332A1 (en) | 2003-08-20 | 2007-01-04 | Northern Sydney Area Health Service | Methods for enhancing embryo viability |
JP2010505818A (ja) | 2006-10-05 | 2010-02-25 | ベン グリオン ユニバーシティ オブ ザ ネゲブ リサーチ アンド ディベロップメント オーソリティ | 甲殻類の胃石成分を含む組成物とその使用 |
JP2015500333A (ja) | 2011-12-13 | 2015-01-05 | アモーフィカル リミテッド. | カルシウム吸収不良及び代謝性骨障害を治療するための非晶質炭酸カルシウム |
WO2014122658A1 (en) | 2013-02-11 | 2014-08-14 | Amorphical Ltd. | Amorphous calcium carbonate for accelerated bone growth |
Non-Patent Citations (1)
Title |
---|
Journal of materials chemistry B,2015年11月23日,Vol.4,p.376-386 |
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KR20180109941A (ko) | 2018-10-08 |
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RU2757419C2 (ru) | 2021-10-15 |
AU2017208953B2 (en) | 2022-11-03 |
IL260548A (ja) | 2018-09-20 |
EP3405201A4 (en) | 2019-06-26 |
US10758566B2 (en) | 2020-09-01 |
JP2019501947A (ja) | 2019-01-24 |
US20190030068A1 (en) | 2019-01-31 |
JP6873389B2 (ja) | 2021-05-19 |
US11207347B2 (en) | 2021-12-28 |
IL260548B2 (en) | 2024-04-01 |
EP3405201B1 (en) | 2023-05-17 |
IL260548B1 (en) | 2023-12-01 |
EP4257141A2 (en) | 2023-10-11 |
ES2952537T3 (es) | 2023-11-02 |
WO2017125918A1 (en) | 2017-07-27 |
RU2018129457A (ru) | 2020-02-20 |
BR112018014520A2 (pt) | 2018-12-11 |
CN108778296A (zh) | 2018-11-09 |
JP2023029914A (ja) | 2023-03-07 |
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