JP6862447B2 - ダニリキシンの静脈内注射用製剤 - Google Patents
ダニリキシンの静脈内注射用製剤 Download PDFInfo
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- JP6862447B2 JP6862447B2 JP2018527942A JP2018527942A JP6862447B2 JP 6862447 B2 JP6862447 B2 JP 6862447B2 JP 2018527942 A JP2018527942 A JP 2018527942A JP 2018527942 A JP2018527942 A JP 2018527942A JP 6862447 B2 JP6862447 B2 JP 6862447B2
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- danilixin
- lyophilized
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 238000012009 microbiological test Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000003843 mucus production Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- UPCXAARSWVHVLY-UHFFFAOYSA-N tris(2-hydroxyethyl)azanium;acetate Chemical compound CC(O)=O.OCCN(CCO)CCO UPCXAARSWVHVLY-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4462—Non condensed piperidines, e.g. piperocaine only substituted in position 3
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
ダニリキシンは、現在アメリカで慢性閉塞性肺疾患(Chronic Obstructive Pulmonary Disease:COPD)のための臨床試験で第2フェーズ中のCXCR2阻害剤である。ダニリキシンは米国特許第7,893,089号に記載されており、その特許は、引用することによりその全文を本明細書に組み込むものとする。国際公開第2015/071235号はダニリキシンの臭化水素酸塩形態に関するものである。ダニリキシンの化学名は、N−{4−クロロ−2−ヒドロキシ−3−[−3−ピペリジニルスルホニル]フェニル}−N’−(3−フルオロ−2−メチルフェニル)尿素であり、本明細書では、互換的にそのエナンチオマー:N−{4−クロロ−2−ヒドロキシ−3−[(3S)−3−ピペリジニルスルホニル]フェニル}−N’−(3−フルオロ−2−メチルフェニル)尿素とも称される。
1.適当な水性の緩衝液を取って混合しながら水溶性賦形剤を添加すること、
2.混合しながらダニリキシン臭化水素酸塩を所望の濃度まで添加すること、
3.必要に応じて1N NaOHまたは1N HClを加えてpHを約3.5〜4.5に調整すること、
4.溶液を適当なバイアルに充填し、その後凍結乾燥機へ投入すること。
先の工程は特定の順番で示されているものの、当業者であれば必要に応じて工程の順序を変更することができるものと理解されたい。
遊離塩基ダニリキシンのIV製剤および安定性
表Aは、遊離塩基ダニリキシンのIV製剤1つ当たりの成分およびそれぞれの量を示す。
ダニリキシンの凍結乾燥臭化水素酸塩のIV製剤
表Cは、ダニリキシンのHBr凍結乾燥製剤のIV製剤1つ当たりの成分およびそれぞれの量を示す。
凍結乾燥サイクル開発
多数の凍結乾燥サイクルは、最も効率的な乾燥サイクルを達成するそれらの能力で評価することができる。乾燥サイクルを達成するためによく評価する変数には、凍結速度、一次乾燥温度、時間および製品への圧力が含まれる。現在の凍結乾燥プロセスは、下表Dで見ることができる。
ダニリキシンの凍結乾燥された臭化水素酸塩のIV製剤の安定性
表Eは、例2で製剤化されたダニリキシンの安定性を示す。この例では、界面活性剤のない4%Captisol(登録商標)でのこの製剤の安定性を示す。安定性は次を含む複数の時点での不純物のパーセント(Imp%)として測定した:5℃、25℃、40℃、および50℃の様々な温度ならびに60%および75%の相対湿度(RH)で、1週間、2週間および4週間。
Claims (10)
- N−{4−クロロ−2−ヒドロキシ−3−[(3S)−3−ピペリジニルスルホニル]フェニル}−N’−(3−フルオロ−2−メチルフェニル)尿素の臭化水素酸塩;および1種以上の薬学的に許容可能な賦形剤を含んでなる静脈内投与用の医薬組成物であって、該薬学的に許容可能な賦形剤が、スルホブチルエーテル−β−シクロデキストリン(Captisol(登録商標))、マンニトールおよびクエン酸緩衝剤である、医薬組成物。
- 水性組成物である、請求項1に記載の医薬組成物。
- 3.5〜4.5の範囲のpHを有する、請求項1または2に記載の医薬組成物。
- pHが約4である、請求項1または2に記載の医薬組成物。
- 凍結乾燥されて凍結乾燥粉末を形成している、請求項1〜4のいずれか一項に記載の医薬組成物。
- 感染性疾患の治療のための、請求項1〜6のいずれか一項に記載の医薬組成物。
- 前記感染性疾患がウイルス性疾患である、請求項7に記載の医薬組成物。
- 前記感染性疾患がインフルエンザまたは呼吸器合胞体ウイルスである、請求項7に記載の医薬組成物。
- 前記感染性疾患がインフルエンザである、請求項7に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562260727P | 2015-11-30 | 2015-11-30 | |
US62/260,727 | 2015-11-30 | ||
PCT/IB2016/057220 WO2017093912A1 (en) | 2015-11-30 | 2016-11-30 | Formulations for intravenous injection of danirixin |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018535243A JP2018535243A (ja) | 2018-11-29 |
JP6862447B2 true JP6862447B2 (ja) | 2021-04-21 |
Family
ID=57543100
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018527942A Active JP6862447B2 (ja) | 2015-11-30 | 2016-11-30 | ダニリキシンの静脈内注射用製剤 |
Country Status (10)
Country | Link |
---|---|
US (2) | US20180369135A1 (ja) |
EP (1) | EP3383364A1 (ja) |
JP (1) | JP6862447B2 (ja) |
KR (1) | KR20180086423A (ja) |
CN (1) | CN108289840A (ja) |
AU (1) | AU2016364380B2 (ja) |
BR (1) | BR112018011138A2 (ja) |
CA (1) | CA3006865A1 (ja) |
RU (1) | RU2018123711A (ja) |
WO (1) | WO2017093912A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN114980896A (zh) * | 2019-08-07 | 2022-08-30 | 阿克里普斯一有限公司 | (6AS)-6-甲基-5,6,6A,7-四氢-4H-二苯并[de,g]喹啉-10,11-二醇的药物组合物 |
Family Cites Families (6)
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KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
TWI414517B (zh) | 2006-04-21 | 2013-11-11 | Smithkline Beecham Corp | Il-8受體拮抗劑 |
EP2742019B1 (en) * | 2011-08-08 | 2021-03-03 | Immunomet Therapeutics Inc. | N1-cyclic amine-n5-substituted phenyl biguanide derivatives and pharmaceutical composition comprising the same |
GB201320021D0 (en) * | 2013-11-13 | 2013-12-25 | Glaxosmithkline Ip Dev Ltd | Novel Compounds |
CN107072976A (zh) * | 2014-05-12 | 2017-08-18 | 葛兰素史克知识产权第二有限公司 | 用于治疗传染性疾病的包含Danirixin的药物组合物 |
CN104860919B (zh) * | 2015-03-26 | 2017-11-10 | 天津药物研究院有限公司 | 含哌啶的苯并咪唑衍生物及其制备方法和用途 |
-
2016
- 2016-11-30 EP EP16810066.7A patent/EP3383364A1/en not_active Withdrawn
- 2016-11-30 KR KR1020187014843A patent/KR20180086423A/ko unknown
- 2016-11-30 CN CN201680070059.5A patent/CN108289840A/zh active Pending
- 2016-11-30 AU AU2016364380A patent/AU2016364380B2/en not_active Expired - Fee Related
- 2016-11-30 WO PCT/IB2016/057220 patent/WO2017093912A1/en active Application Filing
- 2016-11-30 JP JP2018527942A patent/JP6862447B2/ja active Active
- 2016-11-30 RU RU2018123711A patent/RU2018123711A/ru not_active Application Discontinuation
- 2016-11-30 BR BR112018011138-4A patent/BR112018011138A2/pt not_active IP Right Cessation
- 2016-11-30 CA CA3006865A patent/CA3006865A1/en not_active Abandoned
- 2016-11-30 US US15/779,611 patent/US20180369135A1/en not_active Abandoned
-
2019
- 2019-12-03 US US16/701,729 patent/US10945947B2/en active Active
Also Published As
Publication number | Publication date |
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US20200206129A1 (en) | 2020-07-02 |
CN108289840A (zh) | 2018-07-17 |
EP3383364A1 (en) | 2018-10-10 |
US10945947B2 (en) | 2021-03-16 |
JP2018535243A (ja) | 2018-11-29 |
RU2018123711A (ru) | 2020-01-09 |
US20180369135A1 (en) | 2018-12-27 |
AU2016364380A1 (en) | 2018-05-31 |
WO2017093912A1 (en) | 2017-06-08 |
BR112018011138A2 (pt) | 2018-11-21 |
KR20180086423A (ko) | 2018-07-31 |
CA3006865A1 (en) | 2017-06-08 |
AU2016364380B2 (en) | 2019-06-20 |
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