JP2020510022A - 安定化されたタンパク質結合カンナビノイド組成物 - Google Patents
安定化されたタンパク質結合カンナビノイド組成物 Download PDFInfo
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- JP2020510022A JP2020510022A JP2019548645A JP2019548645A JP2020510022A JP 2020510022 A JP2020510022 A JP 2020510022A JP 2019548645 A JP2019548645 A JP 2019548645A JP 2019548645 A JP2019548645 A JP 2019548645A JP 2020510022 A JP2020510022 A JP 2020510022A
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- composition
- cannabinoid
- plasma protein
- fatty acid
- protein
- 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.)
- Granted
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Classifications
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- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
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Abstract
Description
本出願は、米国特許法第119条下で、2017年3月9日に提出された米国仮出願62/469,022の利益を主張し、その内容及び開示は、参照によりその全体に組み込まれる。
本発明の実施形態は、カンナビノイドを含む改良された組成物を提供する。このような組成物を生成する方法もまた本明細書にて提供される。特に下記の本明細書に記載される組成物は含水組成物の場合に安定化する。組成物の安定化は、例えば、組成物の色及び/又はカンナビノイドの分解速度、及び/又は生物活性の保持を観察することにより測定することができる。
カンナビノイドの供給源として大麻樹脂及びハーブ大麻は、貯蔵中に効力を失い、効力の損失は主に、THCなどのカンナビノイドの損失(分解など)によるものであることが長い間認識されてきた。
1.1 リノール酸でのアルブミンの前処理
純粋なリノール酸を50%のエタノールに溶解して、150mMの濃度にした。1mLのリノール酸溶液を10mLの100mg/mL HSA(ヒト血清アルブミン)水溶液に加えた。エタノール濃度が5%未満のリノール酸−HSA溶液を1分間混合し、次いで攪拌せずに37℃で1時間インキュベートした。
工程1.1で調製したリノール酸−HSA溶液を元の濃度の10分の1に水で希釈し、HSA濃度を10mg/mLに削減し、エタノール濃度を約0.5%に削減した。
インキュベーション後、孔径10kDのPellicon XL50カセット(Ultracel)(Pellicon XL Ultra filtration Module Ultracel 10kDa 0.005m2、カタログ番号 PXCO10c50)を使用して、メルク社のCogent μscale装置でDI(脱イオン水)ろ過による洗浄サイクルで透析ろ過により、HSAに結合していないTHC及び脂肪酸の大部分を除去した。その後、リノール酸−THC−HSA複合体を100mlから50mlに該Cogent装置を用いて濃縮した。濃縮リノール酸−THC−HSA複合体試料を3回、300mLの水で洗浄し、最後に洗浄した試料を約20mLの体積に濃縮した。カンナビノイド及び血漿タンパク質のレベルを監視するため、及び3回の洗浄で十分な量の強固に結合した複合体が得られることを測定するために、いくつかの精製段階から試料を採取した。
添加リノール酸の添加を含まない対照THC−HSA組成物(「−L組成物」)は、上記の工程1.1〜1.3のとおり調製されたが、工程1.1のリノール酸の添加の工程は行わなかった。最終精製及び濃縮THC−HSA組成物は、66mg/mLの濃度のアルブミン及び1790ug/mLの濃度のTHCを含んでいた。
最終精製及び濃縮の対照THC−アルブミン複合体(「−L」、上記工程1.4の生産物)を含むバイアル及び最終精製及び濃縮のリノール酸−THC−アルブミン複合体(「+L」、上記工程1.3の生産物)を含む別のバイアルは同一条件下、4℃、暗所で保管した。
Claims (27)
- 脂肪酸−カンナビノイド−血漿タンパク質(FCP)組成物を製造するための方法であって、前記方法は:
少なくとも1つの脂肪酸及び少なくとも1つのカンナビノイドが血漿タンパク質又はその一部に結合しているFCP複合体を含む複合組成物が調製されるように、
血漿タンパク質又はそのペプチド部分を、少なくとも1つの脂肪酸を含む補助脂肪酸組成物と接触させること;及び
血漿タンパク質又はその一部を、少なくとも1つのカンナビノイドを含むカンナビノイド組成物と接触させること、
を含む、前記方法。 - 少なくとも1つの脂肪酸がリノール酸を含む、請求項1に記載の方法。
- 少なくとも1つの脂肪酸がリノール酸からなる、請求項1に記載の方法。
- カンナビノイド組成物が本質的に脂肪酸を含まない、請求項1〜3のいずれか一項に記載の方法。
- 複合組成物中の少なくとも80%の脂肪酸及び少なくとも80%のカンナビノイドが、血漿タンパク質又はその一部に結合するように、複合組成物を精製して、血漿タンパク質又はその一部を保持し、かつ血漿タンパク質又はその一部に結合していない脂肪酸又はカンナビノイドを除去することをさらに含む、請求項1に記載の方法。
- 複合組成物中の実質的にすべての脂肪酸及び実質的にすべてのカンナビノイドが、血漿タンパク質又はその一部に結合する、請求項5に記載の方法。
- 血漿タンパク質又はその一部への脂肪酸及び/又はカンナビノイドの結合が非共有結合である、請求項5に記載の方法。
- 非共有結合が、タンパク質−リガンド相互作用である、請求項7に記載の方法。
- 非共有結合が、血漿タンパク質又はその一部における疎水性タンパク質ポケットとの非特異的な親油性及び極性の相互作用を特徴とする、請求項7に記載の方法。
- 血漿タンパク質又はその一部を補助脂肪酸組成物と接触させることには、血漿タンパク質又はその一部を含む組成物を補助脂肪酸組成物と混合し、かつ該混合物をインキュベートすることを含む、請求項1に記載の方法。
- インキュベーションが、摂氏25度(℃)〜40℃の温度である、請求項10に記載の方法。
- インキュベーションが、含水アルコール媒体で行われる、請求項10に記載の方法。
- 含水アルコール媒体に含まれるアルコールがエタノールである、請求項12に記載の方法。
- 含水アルコール媒体の初期のアルコール濃度が2%〜10%である、請求項12に記載の方法。
- 血漿タンパク質又はその一部をカンナビノイド組成物と接触させることには、血漿タンパク質又はその一部を含む組成物をカンナビノイド組成物と混合し、かつ該混合物をインキュベートすることを含む、請求項1に記載の方法。
- インキュベーションが、摂氏25度(℃)〜40℃の温度である、請求項15に記載の方法。
- インキュベーションが、含水アルコール媒体で行われる、請求項15に記載の方法。
- 含水アルコール媒体に含まれるアルコールがエタノールである、請求項17に記載の方法。
- 含水アルコール媒体の初期のアルコール濃度が16%〜30%である、請求項17に記載の方法。
- 複合組成物が、含水媒体中で提供される、請求項1に記載の方法。
- 含水媒体が、水又は生理食塩水からなる、請求項20に記載の方法。
- 複合組成物を乾燥又は凍結乾燥することをさらに含む、請求項20に記載の方法。
- 少なくとも1つのカンナビノイドは:THCA、THC、CBDA、CBD、CBN、CBG、THCV、CBGA、CBC、HU−210、WIN55,212−2及びJWH−133からなる群の1つ又は2つ以上の組み合わせである、請求項1に記載の方法。
- 血漿タンパク質又はその一部は:アルブミン、リポタンパク質、糖タンパク質、並びにαグロブリン、βグロブリン及びγグロブリン、並びにそれらの1つ以上の混合物からなる群から選択される、請求項1に記載の方法。
- 血漿タンパク質又はその一部が組換え体である、請求項1に記載の方法。
- 請求項1の記載に従って製造されるFCP組成物。
- 血漿タンパク質に結合するカンナビノイドの安定性を改善するための方法であって、請求項1の記載に従ってFCP組成物を製造することを含む、前記方法。
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