JP6403738B2 - デンプンを使用する経口ワクチン速溶性剤型 - Google Patents
デンプンを使用する経口ワクチン速溶性剤型 Download PDFInfo
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- JP6403738B2 JP6403738B2 JP2016176393A JP2016176393A JP6403738B2 JP 6403738 B2 JP6403738 B2 JP 6403738B2 JP 2016176393 A JP2016176393 A JP 2016176393A JP 2016176393 A JP2016176393 A JP 2016176393A JP 6403738 B2 JP6403738 B2 JP 6403738B2
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Description
FDDFを、Zydis(登録商標)錠剤の一般に知られている調製に従って調製した。Zydis(登録商標)錠剤を、200mgのゼラチンを3.3mlの水と組み合わせ、混合物を60℃まで30分かけて加熱することによって調製した。溶液を、加熱する間覆って、蒸発を最小限に留めた。続いて、溶液を、冷水浴中で約25℃まで冷却した。これに続いて、150mgのマンニトールを、撹拌しながら添加した。インフルエンザ抗原A/Panama/2007/99H3N2のストック溶液を添加して、体積を5mlとし、したがって、各錠剤が、1μgのインフルエンザを含有した。インフルエンザ添加後のマトリックス形成剤の最終濃度は、4%ゼラチン(w/v)および3%マンニトール(w/v)であった。処方を、実施例1と同じ条件下でプロセスし、すなわち、溶解、冷却、凍結、凍結乾燥を行った。凍結乾燥した錠剤を、実施例1と同じように検査した。凍結乾燥した錠剤を、表面の欠陥について検査した。主要な欠陥は見出されず、錠剤は未変化であった。(錠剤を37℃の精製水100μl中に置くことによる)分散試験を、Zydis(登録商標)錠剤に対して実施し、錠剤は、10秒未満のうちに溶解した。
FDDFを、比較例1に従って調製し、ただし、ブリスターポケット中に注入する前に、アルギン酸ナトリウムマイクロカプセル化A/Panama/2007/99H3N2インフルエンザウイルスを、処方に添加し、したがって、各錠剤が、1μgのインフルエンザを含有した。最終的な量を達成するために、錠剤1つ当たり3つのマイクロカプセル化インフルエンザビーズを添加した。続いて、溶液を、実施例1と同じ条件下でプロセスし、すなわち、溶解、冷却、凍結、凍結乾燥を行った。凍結乾燥した錠剤を、実施例1と同じように検査した。
FDDFを、比較例1に従って調製し、ただし、ブリスターポケット中に注入する前に、PLGAマイクロカプセル化A/Panama/2007/99H3N2インフルエンザウイルスを、処方に添加し、したがって、各錠剤が、1μgのインフルエンザを含有した。最終的な量を達成するために、計10μlのPLGAビーズを、20μlのFDDF混合物に添加して、錠剤1つ当たり10μlのマイクロカプセル化インフルエンザビーズの量を達成した。続いて、溶液を、実施例1と同じ条件下でプロセスし、すなわち、溶解、冷却、凍結、凍結乾燥を行った。凍結乾燥した錠剤を、実施例1と同じように検査した。
A. in vitroにおける試験
抗原によるチャレンジに対するT細胞の性質および抗体応答は、抗原と接触したことによる活性化の状態および単核球/マクロファージ/樹状細胞により産生されるサイトカインにより定まる。特定のタイプのT細胞およびB細胞の応答を推進するために、アジュバントおよび送達ビヒクルにより、これらの応答を操作する。例えば、これらの細胞によるIL-12の賦活は、補体結合抗体、食細胞の活性化およびCTLの産生により特徴付けられるTh1免疫応答の促進と関連がある主要な決定因子である。IL-4は、Th2応答の主要な推進力であり、一方、IL-6は、TGFベータと一緒になって、粘膜IgA応答の主要な推進力となる。
抗原に対するT細胞応答を推進するためには、クラスII MHCの上方制御が、抗原の提示の増強における必須のステップとなる。上方制御は、その特定の応答の速度または程度を活性化するかまたは増加させるプロセスである。
CD25は、IL-2についての受容体の一部である。この分子の上方制御は、活性化の賦活に対する急性応答であり、高まった活性化状態、および抗原提示細胞として機能するための用意ができていることの指標となる。
CD86は、(細胞媒介型免疫に必要な)ヘルパーT細胞および細胞傷害性T細胞の両方に影響を与える共刺激因子である。CD86は、ヘルパーT細胞および細胞傷害性T細胞の両方の応答を活性化させるために必要な、重要な意味をもつ第2のシグナルをもたらす。CD86は通常、休止状態の抗原提示細胞上では非常に低いレベルで発現し、免疫応答を発生させるためには、その上方制御は、そのような細胞がT細胞と生産的に相互作用するのを可能にする点で重要な意味をもつ事象である。
T細胞応答を賦活し、T細胞応答の性質に影響を及ぼす点で重要な意味をもつサイトカイン応答を、サイトカインのプロファイルにより評価する。
1. 実施例1および比較例1〜3の試験
5種の処方のうちの1つを投与した動物群のそれぞれ、および未治療の動物群(陰性対照)において、第14、28および59日にマウスから採取した血液試料を、インフルエンザ特異的IgGの存在について検討した。図1のグラフは、異なる処方を用いた1、2および3回の免疫化の後のインフルエンザウイルスに対する抗体レベルを示す。全てのグラフが、群平均エンドポイント力価(EPT)±SEMを示す(n=8/群)。
マクロファージ培養物を使用する実施例2に示したin-vitroにおける研究の結果に基づいて、特定の処方を選択して、マウスにおいて、in-vivoにおけるチャレンジ研究を行った。選択した処方は、F8(キサンタンガムを含有する)、F7(ポロキサマー188を含有する)、F10(コーンスターチを含有する)、F4(HPデンプンを含有する)、およびF12(米デンプンを含有する)であった。
各群のマウスの体重を、チャレンジ後の7日間モニターした。結果を、図6に示す。
- 立毛
- 猫背の姿勢
- 一定しない呼吸
- 運動に影響を受ける
- 涙目
Claims (37)
- (a)免疫原性量の抗原調製物、
(b)少なくとも1つの免疫応答強化マトリックス形成剤、および
(c)少なくとも1つの追加のマトリックス形成剤
を含む速溶性経口固体ワクチン剤型であって、
少なくとも1つの免疫応答強化マトリックス形成剤がデンプンであり、少なくとも1つの追加のマトリックス形成剤がマンニトールとゼラチンとの組み合わせであり、ゼラチンが2.5重量%〜65重量%の量で存在し、マンニトールが5重量%〜80重量%の量で存在し、前記剤型が前記抗原調製物内の抗原の口腔内での取込みを促進し、アジュバントをさらに含む、速溶性経口固体ワクチン剤型。 - デンプンが、2重量%〜90重量%の量で存在する、請求項1に記載の速溶性経口固体ワクチン剤型。
- デンプンが、未改質デンプン、改質デンプンおよびそれらの組合せからなる群から選択される、請求項1に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから60秒以内に崩壊する、請求項1に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから30秒以内に崩壊する、請求項4に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから10秒以内に崩壊する、請求項5に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから5秒以内に崩壊する、請求項6に記載の速溶性経口固体ワクチン剤型。
- 凍結乾燥により調製される、請求項1に記載の速溶性経口固体ワクチン剤型。
- ゼラチンが、3重量%〜55重量%の量で存在し、マンニトールが、7重量%〜65重量%の量で存在し、デンプンが、7重量%〜75重量%の量で存在する、請求項1に記載の速溶性経口固体ワクチン剤型。
- 少なくとも1つの追加のマトリックス形成剤が、さらにガムを含む、請求項1に記載の速溶性経口固体ワクチン剤型。
- ガムが、キサンタンガムである、請求項10に記載の速溶性経口固体ワクチン剤型。
- 界面活性剤をさらに含む、請求項1に記載の速溶性経口固体ワクチン剤型。
- 界面活性剤が、Tween80およびポロキサマーからなる群から選択される、請求項12に記載の速溶性経口固体ワクチン剤型。
- 粘膜接着性物質をさらに含む、請求項1に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことによって患者に投与すると、免疫応答が誘導される、請求項1に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことが、舌の上もしくは下、または口腔内頬側もしくは咽頭の領域中に置くことである、請求項15に記載の速溶性経口固体ワクチン剤型。
- (a)免疫原性量の不活性化インフルエンザウイルス、
(b)少なくとも1つの免疫応答強化マトリックス形成剤、および
(c)少なくとも1つの追加のマトリックス形成剤
を含む速溶性経口固体ワクチン剤型であって、
少なくとも1つの免疫応答強化マトリックス形成剤がデンプンであり、少なくとも1つの追加のマトリックス形成剤がマンニトールとゼラチンとの組み合わせであり、ゼラチンが2.5重量%〜65重量%の量で存在し、マンニトールが5重量%〜80重量%の量で存在し、前記剤型が前記不活性化インフルエンザウイルスの口腔内での取込みを促進し、アジュバントをさらに含む、速溶性経口固体ワクチン剤型。 - デンプンが、2重量%〜90重量%の量で存在する、請求項17に記載の速溶性経口固体ワクチン剤型。
- デンプンが、未改質デンプン、改質デンプンおよびそれらの組合せからなる群から選択される、請求項17に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから60秒以内に崩壊する、請求項17に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから30秒以内に崩壊する、請求項20に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから10秒以内に崩壊する、請求項21に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置かれてから5秒以内に崩壊する、請求項22に記載の速溶性経口固体ワクチン剤型。
- 凍結乾燥により調製される、請求項17に記載の速溶性経口固体ワクチン剤型。
- ゼラチンが、3重量%〜55重量%の量で存在し、マンニトールが、7重量%〜65重量%の量で存在し、デンプンが、7重量%〜75重量%の量で存在する、請求項17に記載の速溶性経口固体ワクチン剤型。
- 少なくとも1つの追加のマトリックス形成剤が、さらにガムを含む、請求項17に記載の速溶性経口固体ワクチン剤型。
- ガムが、キサンタンガムである、請求項26に記載の速溶性経口固体ワクチン剤型。
- 界面活性剤をさらに含む、請求項17に記載の速溶性経口固体ワクチン剤型。
- 界面活性剤が、Tween80およびポロキサマーからなる群から選択される、請求項28に記載の速溶性経口固体ワクチン剤型。
- 粘膜接着性物質をさらに含む、請求項17に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことによって患者に投与すると、インフルエンザ特異的IgG応答が誘導される、請求項17に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことが、舌の上もしくは下、または口腔内頬側もしくは咽頭の領域中に置くことである、請求項31に記載の速溶性経口固体ワクチン剤型。
- 免疫応答を必要とする人の口腔中に置くことにより、患者において免疫応答を誘導するための、請求項1に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことが、舌の上もしくは下、または口腔内頬側もしくは咽頭の領域中に置くことである、請求項33に記載の速溶性経口固体ワクチン剤型。
- インフルエンザ特異的抗体応答を必要とする人の口腔中に置くことにより、患者においてインフルエンザ特異的抗体応答を誘導するための、請求項17に記載の速溶性経口固体ワクチン剤型。
- 口腔中に置くことが、舌の上もしくは下、または口腔内頬側もしくは咽頭の領域中に置くことである、請求項35に記載の速溶性経口固体ワクチン剤型。
- インフルエンザ特異的抗体応答が、IgG応答である、請求項35に記載の速溶性経口固体ワクチン剤型。
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Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6061859B2 (ja) * | 2010-10-08 | 2017-01-18 | アール.ピー. シェーラー テクノロジーズ エルエルシー | デンプンを使用する経口ワクチン速溶性剤型 |
US9668970B2 (en) * | 2013-12-02 | 2017-06-06 | Intelgenx Corp. | Film dosage form with extended release mucoadhesive particles |
US11033493B2 (en) | 2013-12-02 | 2021-06-15 | Intelgenx Corp. | Film dosage form with extended release mucoadhesive particles |
US10272038B2 (en) | 2013-12-02 | 2019-04-30 | Intelgenx Corp. | Film dosage form with extended release mucoadhesive particles |
TWI745278B (zh) * | 2014-10-10 | 2021-11-11 | 以色列商艾畢克生物實驗有限公司 | 發泡性降低之疫苗組合物 |
CN104530489B (zh) * | 2015-02-05 | 2017-07-07 | 湖南尔康制药股份有限公司 | 一种速溶于水的淀粉成膜组合物 |
CN109224191A (zh) * | 2018-07-23 | 2019-01-18 | 西安交通大学医学院第附属医院 | 一种用于静脉输液用的无菌输液港辅助植入装置 |
US11523988B2 (en) * | 2018-11-29 | 2022-12-13 | Catalent U.K. Swindon Zydis Limited | Oral dispersible vaccine comprising virosomes |
DK3791395T3 (da) | 2019-07-31 | 2021-09-13 | Catalent Uk Swindon Zydis Ltd | Densitetsgennemstrømningsmåler til dosering af farmaceutisk formulering |
IL301250A (en) | 2020-09-17 | 2023-05-01 | Catalent Uk Swindon Zydis Ltd | Surfactant use with high molecular weight fish gelatin-based dosage formulations to improve flow properties |
WO2022074127A2 (en) | 2020-10-08 | 2022-04-14 | Catalent U.K. Swindon Zydis Limited | Stable oral dispersible formulation for epinephrine and salts or solvates thereof |
US11672761B2 (en) | 2020-11-16 | 2023-06-13 | Orcosa Inc. | Rapidly infusing platform and compositions for therapeutic treatment in humans |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1548022A (en) | 1976-10-06 | 1979-07-04 | Wyeth John & Brother Ltd | Pharmaceutial dosage forms |
US5079018A (en) * | 1989-08-14 | 1992-01-07 | Neophore Technologies, Inc. | Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs |
IT1250421B (it) | 1991-05-30 | 1995-04-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato con proprieta' bio-adesive. |
JPH08508247A (ja) * | 1993-03-11 | 1996-09-03 | セクレテック,インク. | 粘膜表面への免疫原の輸送における重合的粘膜付着体 |
GB9517062D0 (en) * | 1995-08-18 | 1995-10-25 | Scherer Ltd R P | Pharmaceutical compositions |
WO1997013531A1 (en) * | 1995-10-13 | 1997-04-17 | Zynaxis, Inc. | Solid, orally administrable viral vaccines and methods of preparation |
GB9700878D0 (en) * | 1997-01-17 | 1997-03-05 | Scherer Ltd R P | Dosage forms and method for ameliorating male erectile dysfunction |
US5976577A (en) * | 1997-07-11 | 1999-11-02 | Rp Scherer Corporation | Process for preparing fast dispersing solid oral dosage form |
EP1579851A3 (en) * | 1997-08-29 | 2009-09-02 | Corixa Corporation | Rapid release encapsulated bioactive agents for inducing or potentiating an immune response and methods of use thereof |
US20040265377A1 (en) * | 1997-10-27 | 2004-12-30 | Harry Seager | Solid dispersing vaccine composition for oral delivery |
GB9722682D0 (en) | 1997-10-27 | 1997-12-24 | Scherer Ltd R P | Pharmaceutical products |
GB9901819D0 (en) * | 1999-01-27 | 1999-03-17 | Scherer Corp R P | Pharmaceutical compositions |
GB9908014D0 (en) * | 1999-04-08 | 1999-06-02 | Scherer Corp R P | Pharmaceutical compositions |
EP2345721A1 (en) | 1999-11-12 | 2011-07-20 | Fibrogen, Inc. | Recombinant gelatin in vaccines |
EP1120109A3 (en) * | 2000-01-24 | 2002-07-10 | Pfizer Products Inc. | Rapidly disintegrating and fast dissolving solid dosage form |
GB0020089D0 (en) | 2000-08-15 | 2000-10-04 | Smithkline Beecham Biolog | Vaccine Composition |
US6509040B1 (en) | 2001-06-22 | 2003-01-21 | R.P. Scherer Corporation | Fast dispersing dosage forms essentially free of mammalian gelatin |
DE60307082T4 (de) * | 2002-05-07 | 2015-04-30 | Ferring B.V. | In der mundhöhle dispergierbare phamarzeutische zusammensetzung mit desmopressin |
GB0210397D0 (en) * | 2002-05-07 | 2002-06-12 | Ferring Bv | Pharmaceutical formulations |
KR20050052467A (ko) * | 2002-08-12 | 2005-06-02 | 다이나박스 테크놀로지 코퍼레이션 | 면역조절 조성물, 이의 제조방법 및 이의 이용방법 |
MXPA05005528A (es) | 2002-11-26 | 2006-04-05 | Alk Abello As | Producto farmaceutico de alergeno. |
US8012505B2 (en) * | 2003-02-28 | 2011-09-06 | Alk-Abello A/S | Dosage form having a saccharide matrix |
WO2004096193A1 (en) * | 2003-05-02 | 2004-11-11 | Warner-Lambert Company Llc | Fast dissolving orally consumable films containing a modified starch for improved heat and moisture resistance |
CA2537900A1 (en) * | 2003-09-03 | 2005-04-28 | Dendritherapeutics, Inc. | Multiplex vaccines |
US7972621B2 (en) * | 2004-06-03 | 2011-07-05 | R.P. Scherer Technologies, Llc | Process for formulating fast dispersing dosage forms comprising at least one fish gelatin selected on the basis of molecular weight |
RU2008117396A (ru) * | 2005-10-04 | 2009-11-10 | Альк-Абелло А/С (Dk) | Твердая вакцинная композиция |
US20070166239A1 (en) * | 2006-01-13 | 2007-07-19 | Haixiang Lin | Mucosal immunogenic substances comprising a polyinosinic acid - polycytidilic acid based adjuvant |
US20110129438A1 (en) | 2006-06-28 | 2011-06-02 | James Robert Swartz | Immunogenic protein constructs |
CA2696764A1 (en) * | 2007-08-20 | 2009-02-26 | Fraunhofer Usa, Inc. | Prophylactic and therapeutic influenza vaccines, antigens, compositions, and methods |
US20090226522A1 (en) * | 2008-02-28 | 2009-09-10 | Howes Simon A M | Process to minimize polymorphism |
JP2011526888A (ja) * | 2008-07-01 | 2011-10-20 | ザ・ジョンズ・ホプキンス・ユニバーシティ | 治療薬を標的送達するための経口速溶性薄膜 |
US20120034253A1 (en) * | 2008-09-25 | 2012-02-09 | Fraunhofer Usa, Inc. | Influenza Vaccines, Antigens, Compositions, and Methods |
KR101074271B1 (ko) * | 2009-06-25 | 2011-10-17 | (주)차바이오앤디오스텍 | 불쾌한 맛을 효과적으로 은폐한 경구용 속용 필름 |
US8545879B2 (en) * | 2009-08-31 | 2013-10-01 | Wilmington Pharmaceuticals, Llc | Fast disintegrating compositions of meloxicam |
PL2493457T3 (pl) * | 2009-10-30 | 2018-01-31 | Ix Biopharma Ltd | Szybko rozpuszczalna stała postać dawkowana |
GB201009273D0 (en) | 2010-06-03 | 2010-07-21 | Glaxosmithkline Biolog Sa | Novel vaccine |
US20130108762A1 (en) * | 2010-07-08 | 2013-05-02 | Xiaoqun Mo | Confection with gelatin complex |
JP6061859B2 (ja) * | 2010-10-08 | 2017-01-18 | アール.ピー. シェーラー テクノロジーズ エルエルシー | デンプンを使用する経口ワクチン速溶性剤型 |
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