JP2023008832A - 薬学的組成物及びその使用 - Google Patents
薬学的組成物及びその使用 Download PDFInfo
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- JP2023008832A JP2023008832A JP2022090666A JP2022090666A JP2023008832A JP 2023008832 A JP2023008832 A JP 2023008832A JP 2022090666 A JP2022090666 A JP 2022090666A JP 2022090666 A JP2022090666 A JP 2022090666A JP 2023008832 A JP2023008832 A JP 2023008832A
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
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- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
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- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
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- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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- 239000002076 α-tocopherol Substances 0.000 description 1
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A—HUMAN NECESSITIES
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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Abstract
Description
8wt%~30wt%の量で存在する以下の式(I)の有効成分又は薬学的に許容可能なその塩若しくは溶媒和物と、
を含む薬学的組成物を対象とする。
を含む薬学的組成物が以下に詳細に開示される。
ALP001E:ALP001Eの調製は、米国特許出願公開第2019/0345118号明細書を参照可能である。
アセトン:溶媒として使用される。
エチルアルコール(200プルーフ)(Ethyl Alcohol 200 Proof):溶媒として使用される。
ヒプロメロース酢酸エステルコハク酸エステル(Hypromellose Acetate Succinate):ALP001Eの固体分散体における分散剤として又はキャリアとして使用される。
ヒドロキシステアリン酸マクロゴール15(Macrogol 15 Hydroxystearate):薬剤の溶解度及び吸収を改善するだけでなく、製品の安定性にも関連する。それは主に、12-ヒドロキシステアリン酸のモノエステル及びジエステルと、12-ヒドロキシステアリン酸をエトキシ化によって得られるマクロゴールの混合物である。また、それは、α-ヒドロ-ω-ヒドロキシポリ(オキシ-1、2-エタンジイル)との12-ヒドロキシオクタデカン酸ポリマー、12-ヒドロキシステアリン酸ポリエチレングリコールコポリマー、ヒドロキシステアリン酸マクロゴール15、15-ヒドロキシステアリン酸ポリエチレングリコール及び12-ヒドロキシステアリン酸ポリエチレングリコール660として知られている。
製剤A~Hの成分を以下の表1に列記する。製剤A~Hのための噴霧乾燥の製造プロセスのパラメータを以下の表2に列記する。
製剤A~Hの得られた粉末の特性を測定し、結果を以下の表3に列記する。測定方法を以下に簡潔に説明する。
in vitro溶出試験を、溶出溶媒として0.25%のw/vSDSを含む900mLのリン酸バッファpH6.8を用いて75rpm(無限大において250rpm)でUSP溶出装置タイプ2(パドル)を用いて、37±0.5℃で実施した。in vitro溶出試験のためのパラメータを以下の表4に列記し、結果を以下の表5に列記する。
製剤の溶解度を測定する方法を簡潔に説明する。
簡潔には、4~10歳で体重9~12kgの3匹の健康な研究用ビーグル犬を用いた。薬物動態試験は、静脈内ボーラス(IVボーラス)群及び経口群を有する。
本明細書に開示されているすべての構成を任意の組合せで組み合わせてもよい。本明細書で開示されている各構成は、同一、均等又は同様の目的を果たす代替構成に置き換えられ得る。したがって、特に明記しない限り、開示される各構成は、均等又は同様の構成の一般的な一連の例に過ぎない。
Claims (20)
- 前記分散剤の前記可溶化剤に対する重量比は、3.0~20.0の範囲である、請求項1に記載の薬学的組成物。
- 前記式(I)の前記有効成分又は前記薬学的に許容可能なその塩若しくは溶媒和物が、9wt%~28wt%の量で存在する、請求項1に記載の薬学的組成物。
- 前記式(I)の前記有効成分又は前記薬学的に許容可能なその塩若しくは溶媒和物が、10wt%~28wt%の量で存在する、請求項3に記載の薬学的組成物。
- 前記式(I)の前記有効成分又は前記薬学的に許容可能なその塩若しくは溶媒和物が、14.5wt%~20wt%の量で存在する、請求項4に記載の薬学的組成物。
- 前記分散剤が、40wt%~88wt%の量で存在する、請求項1に記載の薬学的組成物。
- 前記分散剤が、60wt%~85wt%の量で存在する、請求項6に記載の薬学的組成物。
- 前記分散剤が、70wt%~80wt%の量で存在する、請求項7に記載の薬学的組成物。
- 前記可溶化剤が、2wt%~20wt%の量で存在する、請求項1に記載の薬学的組成物。
- 前記可溶化剤が、5wt%~13wt%の量で存在する、請求項9に記載の薬学的組成物。
- 前記可溶化剤が、5wt%~10wt%の量で存在する、請求項10に記載の薬学的組成物。
- 経口薬学的組成物である請求項1に記載の薬学的組成物。
- 前記分散剤が、ヒプロメロース酢酸エステルコハク酸エステルを含む、請求項1に記載の薬学的組成物。
- 前記可溶化剤が、ヒドロキシステアリン酸マクロゴール15を含む、請求項1に記載の薬学的組成物。
- 前記式(I)の前記有効成分又は前記薬学的に許容可能なその塩若しくは溶媒和物が10wt%~28wt%の量で存在し、前記分散剤が60wt%~85wt%の量で存在し、かつ前記可溶化剤が5wt%~13wt%の量で存在する、請求項1に記載の薬学的組成物。
- 前記分散剤がヒプロメロース酢酸エステルコハク酸エステルを含み、前記可溶化剤がヒドロキシステアリン酸マクロゴール15を含む、請求項15に記載の薬学的組成物。
- 前記式(I)の前記有効成分又は前記薬学的に許容可能なその塩若しくは溶媒和物が14.5wt%~20wt%の量で存在し、前記分散剤が70wt%~80wt%の量で存在し、かつ前記可溶化剤が5wt%~10wt%の量で存在する、請求項1に記載の薬学的組成物。
- 前記分散剤がヒプロメロース酢酸エステルコハク酸エステルを含み、前記可溶化剤がヒドロキシステアリン酸マクロゴール15を含む、請求項17に記載の薬学的組成物。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011518208A (ja) * | 2008-04-22 | 2011-06-23 | アボツト・プロダクツ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | 難透過性医薬品活性成分のための改善された製剤 |
JP2015536978A (ja) * | 2012-11-07 | 2015-12-24 | エスケー バイオファーマスティカルズ カンパニー リミテッド | 難溶性薬物の固体分散体およびその製造方法 |
WO2018079984A1 (ko) * | 2016-10-25 | 2018-05-03 | 주식회사 에스텍파마 | 두타스테리드와 타다라필을 함유하는 속효성 복합정제 |
JP2018538325A (ja) * | 2015-12-18 | 2018-12-27 | ナトコ ファーマ リミテッド | フェニルアミノピリミジン誘導体を含む医薬組成物 |
JP2020506226A (ja) * | 2017-01-24 | 2020-02-27 | 昊運股▲フン▼有限公司Alphala Co., Ltd | アミド化合物およびその使用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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FI20080355A0 (fi) * | 2008-05-09 | 2008-05-09 | Atacama Labs Oy | Prosessi metforminia käsittävien tablettien valmistamiseksi |
WO2016090240A1 (en) * | 2014-12-04 | 2016-06-09 | Astex Pharmaceuticals, Inc. | Pharmaceutical compositions for increasing the bioavailability of poorly soluble drugs |
WO2017066488A1 (en) * | 2015-10-13 | 2017-04-20 | Charleston Laboratories, Inc. | Treating pain using a composition comprising an opioid and an antiemetic |
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Publication number | Priority date | Publication date | Assignee | Title |
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JP2011518208A (ja) * | 2008-04-22 | 2011-06-23 | アボツト・プロダクツ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | 難透過性医薬品活性成分のための改善された製剤 |
JP2015536978A (ja) * | 2012-11-07 | 2015-12-24 | エスケー バイオファーマスティカルズ カンパニー リミテッド | 難溶性薬物の固体分散体およびその製造方法 |
JP2018538325A (ja) * | 2015-12-18 | 2018-12-27 | ナトコ ファーマ リミテッド | フェニルアミノピリミジン誘導体を含む医薬組成物 |
WO2018079984A1 (ko) * | 2016-10-25 | 2018-05-03 | 주식회사 에스텍파마 | 두타스테리드와 타다라필을 함유하는 속효성 복합정제 |
JP2020506226A (ja) * | 2017-01-24 | 2020-02-27 | 昊運股▲フン▼有限公司Alphala Co., Ltd | アミド化合物およびその使用 |
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