JP2016053037A - 新規方法 - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A61K39/00—Medicinal preparations containing antigens or antibodies
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Abstract
Description
e.水中油型エマルションをプレろ過し、
f.工程e)においてろ過された水中油型エマルションを減菌グレードフィルターに通してろ過する、工程を含む。
水相を、注射用水、リン酸塩緩衝食塩水およびTweenを混合することでタンク2に準備した。油相を、トコフェロールおよびスクアレンを混合することでタンク1に準備した。両相を均質性が得られるまで撹拌した。トコフェロールの酸化を避ける為に装置全体に窒素を流した。
サイズは、光の拡散に基づく方法である動的光散乱法によって測定した。Z-平均直径は装置全体に正圧をかけた方法と比較して供給に膜ポンプを使用した方法の方がより小さかった。この違いは方法の初め(パス1)では大きかったが、方法の最後(ろ過した製造品)では減少する傾向であった。加えて、システム全体が正圧下の状態で供給を行ったとき、サイズの変動性はまた、パスを加えると減少した。これは膜ポンプを使用した場合には起こらない。図1を参照。
装置全体に正圧をかけることによる混合装置への供給は、より小さな液滴サイズおよび改善されたろ過性を得ることを可能とする。さらに、ZAD、PDIおよびろ過性で得られた標準偏差が供給を膜ポンプにより行った方法と比較してより小さかったことから、装置全体に正圧をかけることによる混合装置への供給はまた、方法の再現性も改善している。
Claims (30)
- a)油相を含むタンク中に正圧をかけることによって、混合装置に油相を導入する工程を含む、水中油型エマルションを製造する方法。
- 工程b)水相を含むタンク中に正圧をかけることによって、先の混合装置に水相を導入することを含む、請求項1に記載の方法。
- 油相および/または水相を、約2から6bar、例えば約4から約5bar、例えば4.5barの圧力に調整した混合装置に導入する、請求項1または2に記載の方法。
- 工程a)およびb)を実質的に同時に行う、請求項2または3に記載の方法。
- 水相および油相を、約90:10、95:5または98.75:1.25(パーセント v/v)の比率で導入する、前記請求項のいずれか1項に記載の方法。
- 混合装置が高せん断力ホモジナイザーまたは高圧ホモジナイザーである、前記請求項のいずれか1項に記載の方法。
- 工程c)水中油型エマルションを形成するために油相および水相を混合することを含む、請求項2から6のいずれか1項に記載の方法。
- d)水中サブミクロン油型エマルションを形成するために工程c)の水中油型エマルションを高圧均質化する工程を更に含む、請求項7に記載の方法。
- 工程d)を2、3、4、5または6回行う、請求項8に記載の方法。
- 高圧均質化を約10000psiから約20000psi、約12000psiから約18000psi、約14000psiから約16000psiまたは約15000±1000psiで行う、請求項8または9に記載の方法。
- 工程d)が行われたそれぞれの回の後に、水中油型サブミクロンエマルションを、15℃から30℃、16℃から29℃、17℃から28℃、16℃から27℃または16℃から28℃に冷却する、請求項8から10のいずれか1項に記載の方法。
- e.水中油型エマルションをプレろ過し、
f.工程e)においてろ過された水中油型エマルションを減菌グレードフィルターに通してろ過する
工程を含む工程を更に含む、請求項8から11のいずれか1項に記載の方法。 - 水中油型エマルションが2%から8%(v/v)の油を含む、前記請求項に記載の方法。
- 水中サブミクロン油型エマルションが4%から6%(v/v)の油を含む、請求項に記載の方法。
- 水中油型エマルションが8%から12%(v/v)の油を含む、前記請求項のいずれか1項に記載の方法。
- 油相がスクアレンを含む、前記請求項のいずれか1項に記載の方法。
- 油相が界面活性剤を含む、前記請求項のいずれか1項に記載の方法。
- 界面活性剤がソルビタントリオレアート(SPAN85)である、請求項17に記載の方法。
- 油相がトコールを含む、前記請求項のいずれか1項に記載の方法。
- トコールがα-トコフェロールである、請求項19に記載の方法。
- 水相が水溶液および界面活性剤を含む、請求項2から20のいずれか1項に記載の方法。
- 界面活性剤がポリオキシエチレンソルビタンモノオレアート(TWEEN80、POLYSORBATE80)である、請求項21に記載の方法。
- 請求項1から22のいずれか1項に記載の方法によって製造された水中油型エマルション。
- 請求項23による水中油型エマルションおよび抗原を含む免疫原性組成物。
- 医療において使用するための請求項23に記載の水中油型エマルションまたは請求項24に記載の免疫原性組成物。
- 病気の予防および/または治療に使用するための請求項23に記載の水中油型エマルションまたは請求項24に記載の免疫原性組成物。
- 病気の予防および/または治療の薬剤の製造における請求項23に記載の水中油型エマルションまたは請求項24に記載の免疫原性組成物の使用。
- 請求項23に記載の水中油型エマルションまたは請求項24に記載の免疫原性組成物を哺乳類、例えば人に投与する工程を含む治療方法。
- i)請求項23に記載の水中油型エマルション;およびii)抗原を含むキット。
- 抗原がインフルエンザウイルス由来である請求項23に記載の免疫原性組成物または請求項29に記載のキット。
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GB201009671D0 (en) * | 2010-06-10 | 2010-07-21 | Glaxosmithkline Biolog Sa | Novel process |
AU2013229432A1 (en) | 2012-03-08 | 2014-10-16 | Novartis Ag | Adjuvanted formulations of booster vaccines |
MX2015002717A (es) | 2012-09-06 | 2015-05-15 | Novartis Ag | Vacunas combinadas con meningococo del serogrupo b y toxoides de difteria/tetanos/tosferina. |
EP3620172A1 (en) | 2012-10-12 | 2020-03-11 | GlaxoSmithKline Biologicals SA | Non-cross-linked acellular pertussis antigens for use in combination vaccines |
CA2894260A1 (en) | 2012-12-18 | 2014-06-26 | Glaxosmithkline Biologicals S.A. | Conjugates for protecting against diphtheria and/or tetanus |
WO2017214497A1 (en) | 2016-06-10 | 2017-12-14 | Clarity Cosmetics Inc. | Non-comedogenic hair and scalp care formulations and method for use |
EP4171629A1 (en) | 2020-06-29 | 2023-05-03 | GlaxoSmithKline Biologicals S.A. | Adjuvants |
MX2023002356A (es) | 2020-08-24 | 2023-03-22 | Sanofi Pasteur Inc | Vacunas contra la covid-19 con coadyuvantes en emulsion de escualeno que contiene tocoferol. |
US20240165224A1 (en) | 2021-03-26 | 2024-05-23 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
WO2023274860A1 (en) | 2021-06-28 | 2023-01-05 | Glaxosmithkline Biologicals Sa | Novel influenza antigens |
WO2023020993A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023020994A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023020992A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
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WO2011154443A1 (en) | 2011-12-15 |
CA2801983C (en) | 2020-06-30 |
CN102917689A (zh) | 2013-02-06 |
JP2013528195A (ja) | 2013-07-08 |
BR112012031487A2 (pt) | 2016-11-01 |
GB201009673D0 (en) | 2010-07-21 |
EP3858331A1 (en) | 2021-08-04 |
BR112012031487B1 (pt) | 2021-06-29 |
US20130079395A1 (en) | 2013-03-28 |
US20160106670A1 (en) | 2016-04-21 |
ES2871003T3 (es) | 2021-10-28 |
EP2579849A1 (en) | 2013-04-17 |
CA2801983A1 (en) | 2011-12-15 |
CN102917689B (zh) | 2015-07-22 |
JP6263511B2 (ja) | 2018-01-17 |
EP2579849B1 (en) | 2021-03-17 |
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