JP7404242B2 - カンナビノイドを含む放出調節組成物 - Google Patents
カンナビノイドを含む放出調節組成物 Download PDFInfo
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- JP7404242B2 JP7404242B2 JP2020536959A JP2020536959A JP7404242B2 JP 7404242 B2 JP7404242 B2 JP 7404242B2 JP 2020536959 A JP2020536959 A JP 2020536959A JP 2020536959 A JP2020536959 A JP 2020536959A JP 7404242 B2 JP7404242 B2 JP 7404242B2
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- 239000008380 degradant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- SSQJFGMEZBFMNV-PMACEKPBSA-N dexanabinol Chemical compound C1C(CO)=CC[C@@H]2C(C)(C)OC3=CC(C(C)(C)CCCCCC)=CC(O)=C3[C@H]21 SSQJFGMEZBFMNV-PMACEKPBSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- MAMJNXVNGGBHFN-UHFFFAOYSA-N docosa-1,3,5,7,9,11-hexaene Chemical compound CCCCCCCCCCC=CC=CC=CC=CC=CC=C MAMJNXVNGGBHFN-UHFFFAOYSA-N 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- OYHQOLUKZRVURQ-AVQMFFATSA-N linoelaidic acid Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-AVQMFFATSA-N 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008252 pharmaceutical gel Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229940093426 poloxamer 182 Drugs 0.000 description 1
- 229940106032 poloxamer 335 Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 1
- 229960003015 rimonabant Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- LGUDZTGJDWUGDV-HXUWFJFHSA-N win 55212 Chemical compound C([C@H]1CC(=O)C=2C=CC=C3C(C(=O)C=4C5=CC=CC=C5C=CC=4)=C(N1C3=2)C)N1CCOCC1 LGUDZTGJDWUGDV-HXUWFJFHSA-N 0.000 description 1
Classifications
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Description
によって定義される溶媒を含む。
によって定義される溶媒を含む医薬製剤を含む、経口医薬剤形又は医薬組成物に関する。経口医薬剤形又は医薬組成物は、放出調節形態である。
に従って定義される溶媒を含み、シェルが放出調節剤を含む、前記経口医薬組成物に関する。
本発明による製剤は、カンナビクロメン(CBC)、カンナビクロメン酸(CBCV)、カンナビジオール(CBD)、カンナビジオール酸(CBDA)、カンナビジバリン(CBDV)、カンナビジバリン酸(CBDVA)、カンナビゲロール(CBG)、カンナビゲロールプロピル変異体(CBGV)、カンナビシクロール(CBL)、カンナビノール(CBN)、カンナビノールプロピル変異体(CBNV)、カンナビトリオール(CBO)、テトラヒドロカンナビノール(THC)、テトラヒドロカンナビノール酸(THCA)、テトラヒドロカンナビバリン(THCV)及びテトラヒドロカンナビバリン酸(THCVA)からなる群から選択される少なくとも1つのカンナビノイドを含む。このリストは、網羅的ではなく、参照のために本出願で同定されるカンナビノイドを単に詳述している。これまでに、100種類を超える様々なカンナビノイドが同定され、これらのカンナビノイドは、フィトカンナビノイド、エンドカンナビノイド及びシントカンナビノイド等の様々な群に分けることができる。好ましくは、本発明で用いられるカンナビノイドは、フィトカンナビノイド及びエンドカンナビノイドからなる群から選択される少なくとも1つである。フィトカンナビノイド及びエンドカンナビノイドは、合成的に生成され得るか、又はこれらの天然源から高度に精製され得る。
本発明による製剤は、式(I)
によって定義される溶媒を含む。
本発明による製剤は、少なくとも1つのポロキサマーを含む。
によって定義される。
本発明による経口医薬剤形又は医薬組成物は放出調節剤を含む。
製剤は更に香味剤、例えば、ペパーミントを含み得る。
本発明によるIV型経口製剤が室温及び室圧で固体であること、即ち、製剤が20℃及び1atmで固体であることが好ましい。このような製剤は、典型的には、製造中流体であり、室温で固体であり、37℃で再び流体になる。本発明の目的のために、ゲルは、固体とみなされる。
によって定義される溶媒;及び任意で酸化防止剤からなる。
25質量%のカンナビジオール、
34質量%のポロキサマー124、
15質量%のポロキサマー188及び
26質量%のプロピレングリコール
を含む。
25質量%のカンナビジオール、
34質量%のポロキサマー124、
15質量%のポロキサマー188及び
26質量%のジアセチン
を含む。
25質量%のカンナビジオール、
25質量%のポロキサマー124、
25質量%のポロキサマー407及び
25質量%のプロピレングリコール
を含む。
25質量%のカンナビジオール、
35質量%のポロキサマー124、
20質量%のポロキサマー188及び
20質量%のプロピレングリコール
を含む。
35質量%のカンナビジオール、
28質量%のポロキサマー124、
16質量%のポロキサマー188及び
22質量%のプロピレングリコール
を含む。
12.5質量%のカンナビジオール、
38質量%のポロキサマー124、
19質量%のポロキサマー188及び
30質量%のプロピレングリコール
を含む。
25質量%のカンナビジオール、
27質量%のポロキサマー188及び
48質量%のジアセチン
を含む。
30質量%のカンナビジオール、
27質量%のポロキサマー188及び
43質量%のジアセチン
を含む。
25質量%のカンナビジオール、
27質量%のポロキサマー188及び
48質量%のトリアセチン
を含む。
25質量%のカンナビジオール、
27質量%のポロキサマー188及び
48質量%のプロピレングリコール
を含む。
25質量%のカンナビジオール、
35質量%のポロキサマー124、
20質量%のポロキサマー188及び
20質量%のクエン酸トリエチル
を含む。
25質量%のカンナビジオール、
27質量%のポロキサマー188及び
48質量%のクエン酸トリエチル
を含む。
25質量%のカンナビジバリン、
27質量%のポロキサマー188及び
48質量%のクエン酸トリエチル
を含む。
25質量%のカンナビジバリン、
35質量%のポロキサマー124、
20質量%のポロキサマー188及び
20質量%のプロピレングリコール
を含む。
20質量%のカンナビジバリン、
35質量%のポロキサマー124、
25質量%のポロキサマー188及び
20質量%のトリアセチン
を含む。
25質量%のカンナビジバリン、
35質量%のポロキサマー124、
20質量%のポロキサマー188及び
20質量%のクエン酸トリエチル
を含む。
組成物は、治療法における使用のため、好ましくは小児てんかんにおける使用のためのものである。
「カンナビノイド」は、エンドカンナビノイド、フィトカンナビノイド、及びエンドカンナビノイドでもフィトカンナビノイドでもないもの、以下「シントカンナビノイド」を含む化合物の一群である。
1.1.再水和(RH)手順
クラス3の無色透明ガラスバイアルに、室温(RH-RT)で20mLの注射用水を添加することによるか、又は37℃(RH-37)で20mLの注射用水を添加することによって、少なくとも1つのカンナビノイド、少なくとも1つの溶媒及び少なくとも1つのポロキサマーを含むIV型経口医薬製剤(OPF)を再水和した。バイアルを10秒間ボルテックスした。
OPFの粘度、均一性及び透明性を視覚的に確認した。
再水和後、製剤を、均一性並びに粒子及び/又は再水和していないOPFの存在について視覚的に確認する。泡の存在は、カンナビノイドを再水和するために十分なポロキサマーを使用していることを示す。
再水和流体におけるカンナビノイドの放出を以下のように試験した:再水和したOPFをHPLC分析にかけた。装置:可変波長UV検出器又はダイオードアレイ検出器を備えるHPLCシステム。カラム:Ace C18-AR150×4.6mm、3μm。プレカラム:Ace C18-ARガードカートリッジ。移動相:アセトニトリル:0.25%酢酸(62%:38%)。カラム温度:38℃。流速:1.0ml分-1。検出:220nm。注入量:10μl。ランタイム25分。試料調製:試験試料を約0.15mg/mLの近似濃度で三連で正確に調製する。試料は、関連の物質又は分解物の正確な定量を確実にするように高濃度で調製され得る。0.1mLの再水和したOPFを10mLのエタノールで希釈した。10μLをHPLCシステムに注入した。
CBD:合成、植物由来CBD含有ワックス及び植物由来再結晶化CBD(CBD-r)。植物由来CBDV及び合成CBDV。
Lutrol L44(BASF社、ポロキサマー124:P124)、Lutrol F68(BASF社、ポロキサマー188:P188)、Lutrol F87(BASF社、ポロキサマー237:P237)、Lutrol F108(BASF社、ポロキサマー338:P338)、Lutrol F127(BASF社、ポロキサマー407、P407)、グリセロール(Sigma社:gly)、ジアセチン(Sigma社:di)、トリアセチン(Sigma社:tri)、プロピレングリコール(Sigma社:PG)、エタノール(Fischer社)、プロピレングリコールジアセテート(Sigma社:PGDA)、クエン酸トリエチル(Sigma社:TEC)。
別段記載されない限り、製剤は全て以下の方法を用いて製造した。添加剤及びカンナビノイドを容器に秤量し、溶融するまで加熱する。冷却した後、ゲルをカプセル又はバイアルに質量で充填する。ゲルの粘度は、HPMC、ゼラチン及び軟ゼラチンカプセルへの充填の柔軟性を可能にする温度の関数である。
OPFの安定性をIHC指針Q1A~Q1Fに従って実施した。試料を25℃±2℃/60%RH±5%、30℃±2℃/65%RH±5%RH及び40℃±2℃/75%RH±5%で貯蔵した。OPFの安定性を上記の化学分析及び外観によって評価した。化学分析を上記の安定性を示すHPLC法によって行った。6回の反復実験を行った場合、6ヶ月の時点を除き、各時点の反復実験の数は3であった。試料の調製:0.1mLの再水和したOPFを10mLのエタノールで希釈し、10μLをHPLCシステムに注入した。
IV型製剤(150mg/カプセル):30% w/w CBD;5% w/w P124;40% w/w P188及び25% w/w クエン酸トリエチル。
以下の医薬製剤を、本試験の医薬組成物での使用のために調製した。
30% w/w CBD;5% w/w P124;40% w/w P188;及び25% w/wクエン酸トリエチル。
15%酢酸フタル酸セルロース(CAP)、3%プロピレングリコール、1% Tween 80、40.5%エタノール、40.5%アセトン。
放出調節剤を含む医薬組成物の溶解を、75rpmのパドル設定を有するUSP2装置によって測定した。第1の実施例において、上記の放出調節コーティングカプセルを0.1M HCl溶液(pH1.1)に入れた。第2の実施例において、上記の放出調節コーティングカプセルを3%Labrasolを含有するリン酸緩衝液(pH6.8)に入れた。反復実験の数は6であった。上記溶液から採取されたアリコート中のCBDの濃度を、設定時間間隔で測定した。これは、pH1.1及び6.8でのカプセルの溶解を示している。前述のHPLC法を用いてCBDを定量した。試験の結果を以下のTable 4(表5)に示す。
本発明によるIV型製剤がI型及びIII型製剤と比較して改善されたバイオアベイラビリティを示すことを例示するために、比較を行い、各製剤のバイオアベイラビリティを測定した。バイオアベイラビリティ試験の結果を以下のTable 5(表6)に表す。
ビーグル犬(Charles River UK社から提供)に15mg/kgの標的レベルで経口カプセル用量を投与した。使用したカプセルは、サイズ「0」のゼラチンカプセルであり、動物には、各カプセルの投与後、100mLの水フラッシュを行った。各サンプリング時間に採取した血液量は2mLであり、主として頸静脈から採取された。時折、橈側皮静脈の試料を採取した。サンプリング時間は投与から0.5、1、1.5、2、2.5、3、4、5、6、8、12及び24時間後であった。イヌ血漿中のCBD、6-OH CBD、THC及び11 OH THCの決定を、タンデム質量分析検出を用いた逆相液体クロマトグラフィーによるタンパク質沈殿によって行った。CBDのLLOQは1ng/mLであり、代謝物は全て0.5ng/mLのLLOQを有していた。
ジアセチンを質量で秤量してバイアルに入れ、次いでP124を上部に直接入れた。P188を秤量し、ジアセチン及びP124を含有する容器に添加した。最後に、所望される量のCBDを秤量し、容器に添加し、ボルテックスしながら溶融するまで加熱して(100℃)、均一なゲルを確保する。冷却した後(30~40℃)、ゲルをカプセル又はバイアルに質量で充填する。ゲルの粘度は、HPMC、ゼラチン及び軟ゼラチンカプセルへの充填の柔軟性を可能にする温度の関数である。室温で、CBDの用量が低いゲルは固体であるが、CBDが高充填された製剤はゲルのままであった。
IV型ゲル(125mg/g):12.5% w/w CBD;38% w/w P124;19% w/w P188;及び30% w/w ジアセチン。放出=99.3%。外観=固体ゲル。
IV型ゲル(250mg/g):25% w/w CBD;34% w/w P124;15% w/w P188;及び26% w/w ジアセチン。放出=97.4%。外観=透明ゲル。
III型(i)SEDDS(250mg/g):15質量%の油、45質量%の水溶性界面活性剤及び40質量%の親水性共溶媒と共に配合したCBD。
III型(ii)SEDDS(250mg/g):31質量%の油、45質量%の水溶性界面活性剤及び24質量%の親水性共溶媒と共に配合したCBD。
Claims (26)
- 医薬製剤を含むコア、及び
メタクリル酸とメタクリレートとのコポリマー、メタクリル酸とエチルアクリレートとのコポリマー、ヒドロキシプロピルメチルセルロースアセテートスクシネート(HPMC-AS)、ヒドロキシプロピルメチルセルロースフタレート(HPMCP)、ポリビニルアセテートフタレート(PVAP)、メチルビニルエーテルと無水マレイン酸とのコポリマー、酢酸フタル酸セルロース(CAP)、酢酸酪酸セルロース(CAB)、酢酸トリメリト酸セルロース(CAT)、酢酸コハク酸セルロース(CAS)、エチルセルロース、メチルセルロース、シェラック、ジェランガム、ゼイン、アルギン酸及びワックスからなる群から選択される少なくとも1つの放出調節剤を含むシェル
を含む経口医薬組成物であって、
前記医薬製剤が、
少なくとも1つのカンナビノイドであって、医薬製剤に対して10~50質量%の量で存在する、カンナビノイド、
ポロキサマー124及びポロキサマー188であって、ポロキサマーの総量が医薬製剤に対して30~60質量%の量で存在する、ポロキサマー124及びポロキサマー188、並びに
ジアセチン、プロピレングリコール、トリアセチン、モノアセチン、プロピレングリコールジアセテート、クエン酸トリエチル及びこれらの混合物からなる群から選択される溶媒であって、医薬製剤に対して20~50質量%の量で存在する、溶媒
を含み、
前記医薬製剤が、2質量%未満の油を含み、油がトリグリセリド、ジグリセリド、モノグリセリド、脂肪酸及び脂肪酸エステルから選択される、経口医薬組成物。 - 放出調節剤が、ヒドロキシプロピルメチルセルロースアセテートスクシネート(HPMC-AS)、ヒドロキシプロピルメチルセルロースフタレート(HPMCP)及び酢酸フタル酸セルロース(CAP)からなる群から選択される、請求項1に記載の経口医薬組成物。
- 溶媒が、プロピレングリコール、プロピレングリコールジアセテート、クエン酸トリエチル及びこれらの混合物からなる群から選択される、請求項1又は2に記載の経口医薬組成物。
- 溶媒が、プロピレングリコール、クエン酸トリエチル及びこれらの混合物からなる群から選択される、請求項1~3のいずれか一項に記載の経口医薬組成物。
- 溶媒がクエン酸トリエチルである、請求項1~4のいずれか一項に記載の経口医薬組成物。
- 溶媒が、医薬製剤に対して20~30質量%の量で存在する、請求項1~5のいずれか一項に記載の経口医薬組成物。
- カンナビノイドが、カンナビクロメン(CBC)、カンナビクロメン酸(CBCV)、カンナビジオール(CBD)、カンナビジオール酸(CBDA)、カンナビジバリン(CBDV)、カンナビゲロール(CBG)、カンナビシクロール(CBL)、カンナビノール(CBN)、カンナビトリオール(CBO)、テトラヒドロカンナビノール(THC)、テトラヒドロカンナビノール酸(THCA)、テトラヒドロカンナビバリン(THCV)及びテトラヒドロカンナビバリン酸(THCVA)、並びにこれらの組み合わせからなる群から選択される、請求項1~6のいずれか一項に記載の経口医薬組成物。
- カンナビノイドが、カンナビジオール(CBD)又はカンナビジバリン(CBDV)である、請求項1~7のいずれか一項に記載の経口医薬組成物。
- カンナビノイドが、合成であるか又は植物源から再結晶されたものである、請求項1~8のいずれか一項に記載の経口医薬組成物。
- カンナビノイドが、医薬製剤に対して20~30質量%の量で存在する、請求項1~9のいずれか一項に記載の経口医薬組成物。
- 更に、酸化防止剤を含む、請求項1~10のいずれか一項に記載の経口医薬組成物。
- 酸化防止剤が、ブチル化ヒドロキシトルエン、ブチル化ヒドロキシアニソール、α-トコフェロール(ビタミンE)、アスコルビン酸、アスコルビン酸ナトリウム、エチレンジアミン四酢酸、システイン塩酸塩、クエン酸、クエン酸ナトリウム、重硫酸ナトリウム、メタ重亜硫酸ナトリウム、レシチン、没食子酸プロピル、硫酸ナトリウム、モノチオグリセロール及びこれらの混合物からなる群から選択される、請求項11に記載の経口医薬組成物。
- 酸化防止剤が、α-トコフェロール(ビタミンE)、モノチオグリセロール、アスコルビン酸、クエン酸及びこれらの混合物からなる群から選択される、請求項12に記載の経口医薬組成物。
- 医薬製剤がトリグリセリド、ジグリセリド、モノグリセリド、脂肪酸及び脂肪酸エステルを含まない、請求項1~13のいずれか一項に記載の経口医薬組成物。
- 医薬製剤が20℃及び1atmで固体である、請求項1~14のいずれか一項に記載の経口医薬組成物。
- 粘膜付着性ゲル剤、錠剤、散剤、液体ゲルカプセル剤、固体カプセル剤、経口液剤、顆粒剤又は押出物からなる群から選択される経口剤形である、請求項1~15のいずれか一項に記載の経口医薬組成物。
- 医薬製剤がコアのみに存在し、放出調節剤がシェルのみに存在する、請求項1~16のいずれか一項に記載の経口医薬組成物。
- 液体ゲルカプセル及び固体カプセルからなる群から選択される経口剤形である、請求項1~17のいずれか一項に記載の経口医薬組成物。
- 治療法における使用のための、請求項1~18のいずれか一項に記載の経口医薬組成物。
- 治療対象が18歳未満である、請求項19に規定の使用のための経口医薬組成物。
- ドラベ症候群、レノックスガストー症候群、ミオクローヌス発作、若年性ミオクローヌスてんかん、難治性てんかん、統合失調症、若年性けいれん、ウェスト症候群、乳児けいれん、難治性乳児けいれん、結節性硬化症、脳腫瘍、神経因性疼痛、大麻使用障害、心的外傷後ストレス障害、不安、早期精神病、アルツハイマー病及び自閉症からなる群から選択される疾患又は障害の治療における使用のための、請求項1~18のいずれか一項に記載の経口医薬組成物。
- 脱力、欠神又は部分発作の治療における使用のための、請求項1~18のいずれか一項に記載の経口医薬組成物。
- カンナビノイドがCBDV及び/又はCBDAである、自閉症スペクトラム障害並びに多動性障害の治療における使用のための、請求項1~18のいずれか一項に記載の経口医薬組成物。
- ドラベ症候群、レノックスガストー症候群、ミオクローヌス発作、若年性ミオクローヌスてんかん、難治性てんかん、統合失調症、若年性けいれん、ウェスト症候群、乳児けいれん、難治性乳児けいれん、結節性硬化症、脳腫瘍、神経因性疼痛、大麻使用障害、心的外傷後ストレス障害、不安、早期精神病、アルツハイマー病及び自閉症からなる群から選択される疾患又は障害の治療のための医薬の製造における、請求項1~18のいずれか一項に記載の経口医薬組成物の使用。
- 脱力、欠神又は部分発作の治療のための医薬の製造における、請求項1~18のいずれか一項に記載の経口医薬組成物の使用。
- 自閉症スペクトラム障害又は多動性障害の治療のための医薬の製造における、請求項1~18のいずれか一項に記載の経口医薬組成物の使用であって、カンナビノイドがCBDV及び/又はCBDAである、使用。
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EP3272340A1 (en) * | 2016-07-22 | 2018-01-24 | Capsugel Belgium NV | Acid resistant capsules |
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AU2016203127A1 (en) | 2005-11-07 | 2016-06-02 | Murty Pharmaceuticals, Inc | An improved oral gastrointestinal dosage form delivery system of cannabinoids and/or standardized marijuana extracts |
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RU2020125295A3 (ja) | 2022-02-03 |
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