JP2017522287A - 界面活性剤を含まない水中油エマルジョン及びその用途 - Google Patents
界面活性剤を含まない水中油エマルジョン及びその用途 Download PDFInfo
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- JP2017522287A JP2017522287A JP2016573130A JP2016573130A JP2017522287A JP 2017522287 A JP2017522287 A JP 2017522287A JP 2016573130 A JP2016573130 A JP 2016573130A JP 2016573130 A JP2016573130 A JP 2016573130A JP 2017522287 A JP2017522287 A JP 2017522287A
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- oil
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Abstract
Description
ミクロン粒子又はエマルジョン滴の粒子径分布の測定はレーザー粒度分析器を使用して行われ、具体的な測定工程は、5mgのミクロン粒子を50mLの脱イオン水に添加して、5min超音波処理して均一に分散させ、又は、50mLのエマルジョンを使用し、粒子懸濁液又はエマルジョンを試料セルに添加して、レーザー粒度分析器(Ma1vern Instruments、United Kingdom Coulter Co.,USA)を使用して測定することである。
1mgの粒子を秤量して、10mLの脱イオン水に添加し、5min超音波処理して均一に分散させた。1mLの懸濁液を吸い取って、アルミ箔に滴下し、アルミ箔において均一に広げ、自然乾燥させた。アルミ箔を導電性接着剤で試料台に貼り付け、真空条件において金粒子を蒸着し(サンプルの性質に応じて適当な条件とする)、その後、走査型電子顕微鏡で観察する。
水中油エマルジョンを少量吸い取って、スライドに滴下し、光学顕微鏡で観察する。
5mLの水中油エマルジョンを15mLの遠心分離管に入れ、2000gの遠心力の作用下で10min遠心分離後、分層状況を観察する。
Claims (10)
- 界面活性剤を含まない水中油エマルジョンであって、スクアレン又は/及びトコールを含む代謝可能な油相と、精製水、注射用水、グリセロール水溶液、緩衝食塩水溶液又は臨床的に使用可能な輸液剤のうちのいずれか1種又は少なくとも2種の組合せである水相と、水相に分散して生体適合性を有する、平均粒子径がナノ−ミクロンスケールの油水両親媒性の固体粒子とを含むことを特徴とする界面活性剤を含まない水中油エマルジョン。
- 前記トコールは、α−トコフェロール又はその誘導体であり、
好ましくは、前記油相は受容体に対して無毒で代謝作用によって変換可能な植物油、魚油、動物油又は合成油のいずれかを含み、好ましくは、ダイズ油、ミグリトール、中鎖油、魚油、ビタミンE、ビタミンEコハク酸エステル、ビタミンE酢酸エステル、サフラワー油、コーンオイル、サジー油、アマニ油、ピーナッツ油、椿油、ヒマワリ油、アーモンドオイル、ハトムギオイル、月見草油、ゴマ油、綿実油、ヒマシ油、低エルカ酸菜種油、オレイン酸エチル、オレイン酸、リノール酸エチル、ラウリン酸イソプロピル、ミリスチン酸イソプロピル、酪酸エチル、乳酸エチル、トリカプリルグリセリル又はカプリン酸トリグリセリドから選ばれるいずれか1種又は少なくとも2種の組合せであることを特徴とする請求項1に記載の水中油エマルジョン。 - 前記水相は注射用水、リン酸塩緩衝液、クエン酸緩衝液又はTris緩衝液のうちのいずれか1種又は少なくとも2種の組合せであり、
好ましくは、前記リン酸塩緩衝液、クエン酸緩衝液又はTris緩衝液のpH値が独立に5.0〜8.1、好ましくは6.0〜8.0であることを特徴とする請求項1又は2に記載の水中油エマルジョン。 - 前記水相は、ヒト抗原、非ヒト動物抗原、植物抗原、細菌抗原、真菌抗原、ウイルス抗原、寄生虫抗原又は腫瘍抗原のうちのいずれか1種又は少なくとも2種の組合せである単価又は多価抗原を含み、
好ましくは、前記抗原は、ニワトリ胚培養、細胞培養、キャリア体液、器官又は組織からの精製分離、組換え遺伝子発現又は化学合成によって得られ、好ましくは前記抗原は、弱毒化ワクチン、不活化ワクチン、スプリットワクチン、サブユニットワクチン、多糖結合ワクチン、組み換えワクチン又はDNAワクチン等から選ばれるいずれか1種又は少なくとも2種の組合せであり、
好ましくは、前記抗原は、季節性インフルエンザ株由来のウイルス抗原又は抗原性製剤を少なくとも三種類含み、更に、世界的流行の発生を引き起こし又は世界的流行の発生を引き起こす可能性があるインフルエンザウイルス株のウイルス抗原又は抗原性製剤を少なくとも1種含んでもよく、そのうち、世界的流行の発生を引き起こし又は世界的流行の発生を引き起こす可能性があるインフルエンザウイルス株は、
H1N1、H2N2、H3N2、H5N1、H7N7、H1N2、H9N2、H7N3、H10N7を含むヒトインフルエンザウイルスのA、B、C型と、
豚インフルエンザウイルスH1N1、H1N2、H3N1、H3N2と、
犬や馬インフルエンザウイルスH7N7、H3N8と、
鳥類インフルエンザウイルスH5N1、H7N2、H1N7、H7N3、H13N6、H5N9、H11N6、H3N8、H9N2、H5N2、H4N8、H10N7、H2N2、H8N4、H14N5、H6N5及びH12N5と、から選ばれる1種又は2種以上のインフルエンザウイルスの組合せであり、
好ましくは、前記水相には、好ましくはpH調節剤又は/及び緩衝剤、より好ましくは酢酸ナトリウム、乳酸ナトリウム、塩化ナトリウム、塩化カリウム、塩化カルシウム、ヒト血清アルブミン、必須アミノ酸、非必須アミノ酸、L−アルギニン塩酸塩、蔗糖、無水D−海藻糖、マンニトール、マンノース、澱粉又はゼラチンから選ばれるいずれか1種又は少なくとも2種の組合せである薬用補助物質を更に含むことを特徴とする請求項1〜3のいずれか1項に記載の水中油エマルジョン。 - 前記固体粒子は、アルミニウム塩、カルシウム塩、多糖、多糖誘導体又は高分子重合体から選ばれるいずれか1種又は少なくとも2種の混合物であり、
好ましくは、前記アルミニウム塩は水酸化アルミニウム又は/及びリン酸アルミニウムであり、
好ましくは、前記カルシウム塩はリン酸カルシウム又は/及び炭酸カルシウムであり、
好ましくは、前記多糖は、キトサン、アルギン酸、ゼラチン、澱粉、グルカン、コンニャクグルコマンナン、ヘパリン、ペクチン系多糖、ヒアルロン酸、コンドロイチン硫酸、キトサン塩、アルギン酸塩、ゼラチン塩、グルコース塩、コンニャクグルコマンナン塩、ヘパリン塩、ペクチン系多糖塩、ヒアルロン酸塩又はコンドロイチン硫酸塩から選ばれるいずれか1種又は少なくとも2種の組合せであり、好ましくはキトサン、アルギン酸塩、ゼラチン、澱粉又はグルカンのうちのいずれか1種又は少なくとも2種の組合せであり、
好ましくは、前記多糖誘導体は、多糖に対して四級化反応、カルボキシメチル化、ヒドロキシ化、アルキル化、アシル化、スルホン化、硝化又はハロゲン化等の誘導体化反応を行って得た多糖誘導体であり、好ましくは、バラキトサン、アルギン酸、ゼラチン、澱粉又はグルカンのうちのいずれか1種又は少なくとも2種の組合せに対して、四級化反応、カルボキシメチル化、ヒドロキシ化、アルキル化、アシル化、スルホン化、硝化又はハロゲン化等の誘導体化反応を行って得た多糖誘導体であり、
好ましくは、前記高分子重合体は、ポリ(α−ヒドロキシ酸)、ポリヒドロキシ酪酸、ポリカプロラクトン、ポリオルトエステル、ポリ無水物又はポリシアノアクリレート及びその共重合体であり、前記共重合体の共重合単量体は、ポリ(α−ヒドロキシ酸)、ポリヒドロキシ酪酸、ポリカプロラクトン、ポリオルトエステル、ポリ無水物又はポリシアノアクリレートのうちのいずれか1種又は少なくとも2種の組合せであることが好ましく、
好ましくは、前記高分子重合体は、ポリ(α−ヒドロキシ酸)及びその共重合体であり、好ましくはポリ(L−ラクチド)、ポリ(D,L−ラクチド)又はポリ(ラクチド−コ−グリコリド)、最も好ましくはポリ(ラクチド−コ−グリコリド)であり、
好ましくは、ポリ(ラクチド−コ−グリコリド)において、ラクチドとグリコリドのセグメントのモル比は10:90〜90:10であり、
好ましくは、前記固体粒子は、水酸化アルミニウム、リン酸アルミニウム、リン酸カルシウム、炭酸カルシウム、キトサン、アルギン酸塩、ポリ乳酸、ポリ乳酸−ヒドロキシ酢酸共重合体又はポリエチレングリコール−乳酸共重合体から選ばれるいずれか1種又は少なくとも2種の混合物であり、更に好ましくは水酸化アルミニウム、リン酸アルミニウム、リン酸カルシウム、ポリ乳酸、ポリ乳酸−ヒドロキシ酢酸共重合体又はポリエチレングリコール−乳酸共重合体から選ばれるいずれか1種又は少なくとも2種の混合物であり、最も好ましくはポリ乳酸−ヒドロキシ酢酸共重合体であることを特徴とする請求項1〜4のいずれか1項に記載の水中油エマルジョン。 - 固体粒子の表面に対して親水性修飾、疎水性修飾、被覆又はグラフト変性を行い、
好ましくは、前記固体粒子の表面又は内部にターゲット物質、蛍光マーカー、同位体マーカー、環境応答物質、サイトカイン、抗体又は免疫調節剤が吸着、結合又は包埋され、
好ましくは、前記環境応答物質は、pH感受性、熱感受性又は生物学的活性物質感受性基から選ばれ、
好ましくは、前記固体粒子の表面又は内部に抗原が吸着、結合又は包埋され、
好ましくは、前記固体粒子の平均粒子径は1nm〜10μm、好ましくは10nm〜5μmであり、
好ましくは、前記固体粒子の粒子径分布係数spanが1.0未満であり、
好ましくは、固体粒子の水相での質量濃度が0.1〜20wt%、好ましくは0.5〜10wt%、更に好ましくは1〜8wt%であることを特徴とする請求項1〜5のいずれか1項に記載の水中油エマルジョン。 - スクアレンである代謝可能な油相と、精製水、注射用水、グリセロール水溶液、緩衝食塩水溶液又は臨床的に使用可能な輸液剤のうちのいずれか1種又は少なくとも2種の組合せである水相と、水相に分散して生体適合性を有する、平均粒子径がナノ−ミクロンスケールのPLGA油水両親媒性の固体粒子とを含み、
好ましくは、前記水中油エマルジョンの油相と水相の体積比が1:100〜9:1、好ましくは1:50〜1:2であり、
好ましくは、前記水中油エマルジョンにおけるエマルジョン滴の平均粒子径が50nm〜300μm、好ましくは100nm〜100μmであり、
好ましくは、前記水中油エマルジョンは希釈剤、安定剤又は防腐剤のうちのいずれか1種又は少なくとも2種の組合せを含む薬用添加剤を更に含有することを特徴とする請求項1〜6のいずれか1項に記載の水中油エマルジョン。 - 界面活性剤を含まない免疫原性組成物であって、(1)抗原又は抗原組成物、及び(2)請求項1〜7のいずれか1項に記載の水中油エマルジョンからなるアジュバント組成物を含むことを特徴とする界面活性剤を含まない免疫原性組成物。
- 請求項1〜7のいずれか1項に記載の水中油エマルジョンのワクチンアジュバント、薬物送達又は徐放性担体としての用途。
- 免疫接種又は投与方法は、静脈内注射、脊髄腔注射、筋肉内注射、皮下注射、皮内注射、経呼吸器噴霧又は吸入、腹腔内注射、経鼻投与、眼内投与、経口投与、経直腸投与、経腟投与、局所投与又は経皮投与を含むことを特徴とする請求項9に記載の用途。
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JP (1) | JP6434995B2 (ja) |
CN (1) | CN104013955B (ja) |
WO (1) | WO2015192603A1 (ja) |
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11502192A (ja) * | 1994-12-27 | 1999-02-23 | デイミナコ・リミテッド | ワクチンのアジュバント |
JP2002522362A (ja) * | 1998-08-01 | 2002-07-23 | バイヤースドルフ・アクチエンゲゼルシヤフト | 水中油滴及び油中水滴型の微細に分散した乳化剤を含まない系 |
JP2002522364A (ja) * | 1998-08-01 | 2002-07-23 | バイヤースドルフ・アクチエンゲゼルシヤフト | 窒化ホウ素を含む水中油滴及び油中水滴型の微細に分散した乳化剤を含まない系 |
JP2009536653A (ja) * | 2006-05-09 | 2009-10-15 | ザ ヘンリー エム. ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | Hiv−1免疫原性組成物 |
JP2010527332A (ja) * | 2007-05-10 | 2010-08-12 | ノイブルク スキン ケア ゲーエムベーハー ウント コー カーゲー | 界面活性剤不含泡沫処方物 |
US20110052633A1 (en) * | 2009-09-02 | 2011-03-03 | National Health Research Institutes | Multi-phase emulsions based on amphiphilic block copolymers |
JP2011530526A (ja) * | 2008-08-06 | 2011-12-22 | ノバルティス アーゲー | 免疫原性組成物における使用のための微粒子 |
JP2014506916A (ja) * | 2011-03-02 | 2014-03-20 | ノバルティス アーゲー | より低用量の抗原および/またはアジュバントを有する混合ワクチン |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4031301A (en) * | 1975-09-10 | 1977-06-21 | The United States Of America As Represented By The Secretary Of The Army | Micro particle generation |
EP0382271B1 (en) * | 1989-02-04 | 1994-12-21 | Akzo Nobel N.V. | Tocols as adjuvant in vaccine |
US5849862A (en) * | 1995-06-07 | 1998-12-15 | Cytec Technology Corp. | Processes of spray drying polymer-containing dispersions, water-in-oil emulsions and water-in-oil microemulsions |
FR2783159B1 (fr) * | 1998-09-16 | 2000-11-17 | Oreal | Emulsion comprenant un compose epaississant hydrophile et un copolymere epaississant, compositions comprenant ladite emulsion, et utilisations |
JP3908565B2 (ja) * | 2002-02-27 | 2007-04-25 | 第一工業製薬株式会社 | 水中油型乳化組成物および乳化組成物の製造方法 |
JP5393978B2 (ja) * | 2004-04-05 | 2014-01-22 | ゾエティス・ピー・エルエルシー | マイクロ流動化された水中油型乳剤及びワクチン組成物 |
DE102005005205A1 (de) * | 2005-02-03 | 2006-08-10 | Basf Ag | Verwendung einer wässrigen Polymerdispersion als Bindemittel für cellulosische Fasern sowie zur Herstellung von Filtermaterialien |
GB0515906D0 (en) * | 2005-08-02 | 2005-09-07 | Chiron Srl | Mixtures of antigen and adjuvant |
CN101161238A (zh) * | 2007-11-20 | 2008-04-16 | 东南大学 | 一种基于磷脂的脂质纳米微囊及其制备方法 |
CN101783217A (zh) * | 2009-12-25 | 2010-07-21 | 上海纳米技术及应用国家工程研究中心有限公司 | 具有二氧化硅包覆的磁性微球的制备方法 |
CN103374143B (zh) * | 2012-04-28 | 2015-08-19 | 中国科学院过程工程研究所 | 一种超大孔聚合物微球及其制备方法 |
CN104013955B (zh) * | 2014-06-18 | 2016-02-24 | 中国科学院过程工程研究所 | 一种不含表面活性剂的水包油乳液及其用途 |
WO2017083774A1 (en) * | 2015-11-11 | 2017-05-18 | Onefocus Vision, Inc. | Accommodating lens with cavity |
-
2014
- 2014-06-18 CN CN201410272743.4A patent/CN104013955B/zh active Active
- 2014-11-26 US US14/909,593 patent/US20160175432A1/en not_active Abandoned
- 2014-11-26 WO PCT/CN2014/092290 patent/WO2015192603A1/zh active Application Filing
- 2014-11-26 JP JP2016573130A patent/JP6434995B2/ja active Active
- 2014-11-26 EP EP14895356.5A patent/EP3015114B1/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11502192A (ja) * | 1994-12-27 | 1999-02-23 | デイミナコ・リミテッド | ワクチンのアジュバント |
JP2002522362A (ja) * | 1998-08-01 | 2002-07-23 | バイヤースドルフ・アクチエンゲゼルシヤフト | 水中油滴及び油中水滴型の微細に分散した乳化剤を含まない系 |
JP2002522364A (ja) * | 1998-08-01 | 2002-07-23 | バイヤースドルフ・アクチエンゲゼルシヤフト | 窒化ホウ素を含む水中油滴及び油中水滴型の微細に分散した乳化剤を含まない系 |
JP2009536653A (ja) * | 2006-05-09 | 2009-10-15 | ザ ヘンリー エム. ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド | Hiv−1免疫原性組成物 |
JP2010527332A (ja) * | 2007-05-10 | 2010-08-12 | ノイブルク スキン ケア ゲーエムベーハー ウント コー カーゲー | 界面活性剤不含泡沫処方物 |
JP2011530526A (ja) * | 2008-08-06 | 2011-12-22 | ノバルティス アーゲー | 免疫原性組成物における使用のための微粒子 |
US20110052633A1 (en) * | 2009-09-02 | 2011-03-03 | National Health Research Institutes | Multi-phase emulsions based on amphiphilic block copolymers |
JP2014506916A (ja) * | 2011-03-02 | 2014-03-20 | ノバルティス アーゲー | より低用量の抗原および/またはアジュバントを有する混合ワクチン |
Non-Patent Citations (6)
Title |
---|
COLLOIDS AND SURFACES A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 2012, VOL. 413, P. 252-259, JPN6017041500, ISSN: 0003746888 * |
COLLOIDS AND SURFACES A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 2013, VOL. 439, P. 23-34, JPN6017041496, ISSN: 0003746886 * |
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2009, VOL. 371, P. 56-63, JPN6017041498, ISSN: 0003746887 * |
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2012, VOL. 428, P. 1-7, JPN6017041503, ISSN: 0003746889 * |
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2011, VOL. 59, P. 6137-6141, JPN6017041493, ISSN: 0003746885 * |
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2012, VOL. 375, P. 142-147, JPN6017041506, ISSN: 0003746890 * |
Cited By (5)
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JP7318250B2 (ja) | 2018-03-29 | 2023-08-01 | 東ソー株式会社 | 触媒内包ポリビニル樹脂微粒子、該微粒子組成物、触媒内包ポリビニル樹脂微粒子及び該微粒子組成物の製造方法 |
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JP7391959B2 (ja) | 2018-07-10 | 2023-12-05 | セキラス ピーティーワイ リミテッド | 凝集物の除去 |
JP7475733B2 (ja) | 2020-04-13 | 2024-04-30 | 四川大学 | マイクロエマルションに基づくワクチン送達システム、その製造方法及び使用 |
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EP3015114A4 (en) | 2016-11-30 |
EP3015114B1 (en) | 2023-07-12 |
EP3015114A1 (en) | 2016-05-04 |
US20160175432A1 (en) | 2016-06-23 |
CN104013955A (zh) | 2014-09-03 |
CN104013955B (zh) | 2016-02-24 |
JP6434995B2 (ja) | 2018-12-05 |
WO2015192603A1 (zh) | 2015-12-23 |
EP3015114C0 (en) | 2023-07-12 |
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