JP2013501043A - 経口投与可能な医薬製剤 - Google Patents
経口投与可能な医薬製剤 Download PDFInfo
- Publication number
- JP2013501043A JP2013501043A JP2012523416A JP2012523416A JP2013501043A JP 2013501043 A JP2013501043 A JP 2013501043A JP 2012523416 A JP2012523416 A JP 2012523416A JP 2012523416 A JP2012523416 A JP 2012523416A JP 2013501043 A JP2013501043 A JP 2013501043A
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- JP
- Japan
- Prior art keywords
- insulin
- type
- pharmaceutical formulation
- aminocaproic acid
- casein
- 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.)
- Pending
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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Abstract
Description
目的は、インスリン、プロテアーゼ阻害物質および高分子量天然タンパク質の組み合わせによって達成された。プロテアーゼ阻害物質とタンパク質の両方が腸壁を通過でき、適当な担体分子が同様に、ペプチド性質のインスリンを通過させられるように、両方が、腸の担体を有することが重要である。
雄性ウィスターラット(チャールズ−リバー研究所、ブダペスト、ハンガリー)を実験に用いた。実験前に、動物を16時間餓えさせた。実験は、朝の8〜9時の間に開始した。1グループ当たり4匹として、2 x 6のグループをランダムに作成した。以下の通り、フィーディングプローブを介して動物を前処理した:グループ1:1 g/kgのε−アミノカプロン酸;グループ2:0.1 U/kgのインスリン;グループ3:0.1 U/kgのインスリンおよび1 g/kgのε−アミノカプロン酸;グループ4:1.0 U/kgのインスリン;グループ5:1.0 U/kgのインスリンおよび1 g/kgのε−アミノカプロン酸;ならびにグループ6:溶媒。第1の6グループに対する処置から15分後および第2の6グループに対する処置から60分後の動脈血から血糖値および結晶インスリン値を決定した。得られた結果を第1表にまとめる。
健康な雄性ウィスターラット(230-250 g)の十二指腸内に、標準カゼインを加えたε−アミノカプロン酸−ヒト組換えインスリン混合物を与えた。測定の終点は、インスリン-アセプラミン製剤(水性懸濁液)の投与後15分および60分の時点で、グルコースオキシダーゼ法で測定される血糖およびラジオイムノアッセイで測定される血漿インスリンであった。
データ:平均±標準偏差、グループ当たり=8。統計:t-検定+ANOVA後のボンフェローニ補正。
インビトロ安定性は、天然インスリンと比較した場合の、タンパク質分解酵素の存在下でのインスリン−アセプラミン混合物の基本製剤(primitive formulation)の生分解を意味する(逆相HPLC試験の結果)。
ストレプトゾシンの単回静脈内投与によって、雄性スプラーグ−ドーリーラット(230-250 g)に実験的糖尿病を誘発した。10日後、15 mmol/l以上の空腹時(12時間の飢餓状態の後)血糖値を有する動物を用いて実験を継続した。動物に、経口または非経口(s.c.)でインスリン(10 IU/kg)を投与し、次いで、血糖値(第2表のデータ)および血漿インスリン免疫反応性(第3表のデータ)を測定した。
本発明の医薬製剤の排出半減期は、ラットにおいて約40分である。
本発明の医薬製剤は、亜慢性毒性を示さない。
Claims (12)
- バイオテクノロジーによって生産されたヒト組換えインスリンおよび/または修飾インスリンまたはその類縁体および/または誘導体、プロテアーゼインヒビターならびに高分子量天然タンパク質の組み合わせを含む経口投与可能な医薬製剤。
- ヒトインスリンが、B28位がAsp、Lys、Leu、ValまたはAlaであり、B29位がLysまたはProであるアナログであるか;またはdes(B28-B30)、des(B27)もしくはdes(B30)ヒトインスリンである請求項1に記載の医薬製剤。
- プロテアーゼインヒビターが、ε−アミノカプロン酸である請求項1に記載の医薬製剤。
- 高分子量天然タンパク質が、カゼインである請求項1または2に記載の医薬製剤。
- 40〜100 IUのヒト組換えインスリン、100〜1000 mgのε−アミノカプロン酸および1〜100 mgのカゼインを含む請求項1〜4のいずれか1つに記載の医薬製剤。
- 哺乳動物の1型および2型糖尿病の治療に適した経口投与可能な医薬製剤の製造のための、治療有効量のバイオテクノロジーによって生産されたヒト組換えインスリンおよび/または修飾インスリンまたはその類縁体および/または誘導体、ε−アミノカプロン酸およびカゼインの組み合わせの使用。
- 医薬的に許容しうる担体および添加物と混合された、40〜100 IUのバイオテクノロジーによって生産されたヒト組換えインスリンおよび/または修飾インスリンまたはその類縁体および/または誘導体、100〜1000 mgのε−アミノカプロン酸および1〜100 mgのカゼインが、経口投与可能な投与剤形に製剤される、経口投与可能な医薬製剤の製造方法。
- 哺乳動物の1型および2型糖尿病の治療のための請求項1〜5のいずれか1つに記載の医薬製剤の使用。
- 妊娠中の糖尿病の治療のための請求項1〜5のいずれか1つに記載の医薬製剤の使用。
- 患者が、治療有効量のバイオテクノロジーによって生産されたヒト組換えインスリンおよび/または修飾インスリンまたはその類縁体および/または誘導体、ε−アミノカプロン酸およびカゼインを含む経口投与可能な医薬製剤を投与される、哺乳動物の1型および2型糖尿病の治療方法。
- 患者が、40〜100 IUのヒト組換えインスリン、100〜1000 mgのε−アミノカプロン酸および1〜100 mgのカゼインを含む医薬製剤を投与される、哺乳動物の1型および2型糖尿病の治療方法。
- バイオアベイラビリティが、30 %以上である請求項1〜5のいずれか1つに記載の医薬製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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HU0900482A HUP0900482A2 (en) | 2009-08-03 | 2009-08-03 | Pharmaceutical formulation for oral administration |
HUP0900482 | 2009-08-03 | ||
PCT/IB2010/053499 WO2011015984A1 (en) | 2009-08-03 | 2010-08-02 | Orally administerable pharmaceutical preparation containing insulin |
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JP2013501043A true JP2013501043A (ja) | 2013-01-10 |
JP2013501043A5 JP2013501043A5 (ja) | 2013-07-25 |
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JP2012523416A Pending JP2013501043A (ja) | 2009-08-03 | 2010-08-02 | 経口投与可能な医薬製剤 |
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EP (1) | EP2461820A1 (ja) |
JP (1) | JP2013501043A (ja) |
KR (1) | KR20120088660A (ja) |
CN (1) | CN102791282A (ja) |
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CN109008910A (zh) * | 2011-06-29 | 2018-12-18 | 拉尼医疗有限公司 | 用于使用可吞服药物递送装置递送到肠道内腔中的治疗药剂制剂 |
CA3067713A1 (en) * | 2017-06-28 | 2019-01-03 | Helmholtz Zentrum Munchen - Deutsches Forschungszentrum Fur Gesundheit Und Umwelt (Gmbh) | Method for determining the risk to develop type 1 diabetes |
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- 2010-08-02 EP EP10757272A patent/EP2461820A1/en not_active Withdrawn
- 2010-08-02 US US13/387,212 patent/US20120129769A1/en not_active Abandoned
- 2010-08-02 AU AU2010280418A patent/AU2010280418B2/en not_active Expired - Fee Related
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- 2010-08-02 MX MX2012001461A patent/MX2012001461A/es not_active Application Discontinuation
- 2010-08-02 UA UAA201202346A patent/UA106506C2/uk unknown
- 2010-08-02 WO PCT/IB2010/053499 patent/WO2011015984A1/en active Application Filing
- 2010-08-02 RU RU2012109006/15A patent/RU2012109006A/ru unknown
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- 2010-08-02 BR BR112012002413A patent/BR112012002413A2/pt not_active IP Right Cessation
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AU2010280418B2 (en) | 2015-04-09 |
UA106506C2 (uk) | 2014-09-10 |
HUP0900482A2 (en) | 2011-03-28 |
KR20120088660A (ko) | 2012-08-08 |
CN102791282A (zh) | 2012-11-21 |
HU0900482D0 (en) | 2009-10-28 |
BR112012002413A2 (pt) | 2016-03-01 |
MX2012001461A (es) | 2012-05-22 |
CA2769620A1 (en) | 2011-02-10 |
EP2461820A1 (en) | 2012-06-13 |
ZA201201519B (en) | 2013-05-29 |
IL217856A0 (en) | 2012-03-29 |
US20120129769A1 (en) | 2012-05-24 |
WO2011015984A1 (en) | 2011-02-10 |
RU2012109006A (ru) | 2013-09-10 |
AU2010280418A1 (en) | 2012-03-22 |
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