DK2723323T3 - Frysetørring af syntetisk liposomal pulmonært overfladeaktivt stof - Google Patents
Frysetørring af syntetisk liposomal pulmonært overfladeaktivt stof Download PDFInfo
- Publication number
- DK2723323T3 DK2723323T3 DK13716655.9T DK13716655T DK2723323T3 DK 2723323 T3 DK2723323 T3 DK 2723323T3 DK 13716655 T DK13716655 T DK 13716655T DK 2723323 T3 DK2723323 T3 DK 2723323T3
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- DK
- Denmark
- Prior art keywords
- freeze
- temperature
- mixture
- drying
- pulmonary surfactant
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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Claims (13)
1. Fremgangsmåde til fremstilling af et frysetørret syntetisk pulmonært overfladeaktivt stof med en mindsket eller elimineret kagelevitation under fremgangsmåden, fremgangsmåden omfattende: at tilvejebringe til et frysetørringskammer en præfrysetørringsblanding omfattende dipalmitoylphosphatidylcholin (DPPC), palmitoyloleoylphosphatidylglycerol (POPG), palmitinsyre og et syntetisk peptid med SEQ ID NO: 1 (KL4 polypeptid) dispergeret i et solvent med en organisk solvent i et område på mellem 3% (vol./vol.) og under 20% (vol./vol.) af den samlede volumen af præfrysetørringsblandingen hvor en resterende del er vand og/eller buffer, hvor præfrysetørringsblandingen fyldes i en beholder; at sænke en temperatur inden i frysetørringskammeret til at begynde at nedkøle og størkne præfrysetørringsblandingen i en frysefase hvor frysefasen omfatter at nedkøle præfrysetørringsblandingen til en første temperatur på -45°C eller under -45°C med en hastighed mellem 0,1 og 1,0°C pr. minut og at holde præfrysetørringsblandingen ved den første temperatur i en første tidsperiode tilstrækkelig til at størkne mindst 76% af solventen for at danne en første størknet blanding; at udføre en annealingfase forud for en primær tørringsfase og derved mindske eller eliminere kagelevitation af den første størknede blanding og i det frysetørrede syntetiske pulmonære overfladeaktive stof, hvor annealingfasen omfatter (i) at varme den første størknede blanding til en anden temperatur valgt til at mindske eller eliminere levitation af den første størknede blanding, (ii) at holde den første størknede blanding ved den anden temperatur i en anden tidsperiode tilstrækkelig til at mindske eller eliminere levitation af den første størknede blanding, og (iii) at nedkøle den første størknede blanding til en tredje temperatur på -45°C eller under -45°C med en hastighed mellem 0,1 til 1,0°C pr. minut for at danne en anden størknet blanding, hvor den anden størknede blanding holdes ved den tredje temperatur i en tredje tidsperiode tilstrækkelig til at fremme separation af optøet organisk solvent fra den anden størknede blanding og derved opnå en migration af den optøede organiske solvent til en grænseflade mellem beholderen og den anden størknede blanding; at udføre en primær tørringsfase ved et mindsket tryk på 30 mT eller højere, hvor den anden størknede blanding holdes ved den tredje temperatur i en fjerde tidsperiode tilstrækkelig til at fjerne mindst 5% af den organiske solvent, efterfulgt af at opvarme til en fjerde temperatur tilstrækkelig til at afholde den anden størknede blanding fra at levitere i beholderen og fastholde en struktur etableret under annealingfasen, og yderligere holdt ved den fjerde temperatur i en femte tidsperiode tilstrækkelig til at fjerne mindst 70% af solventen og derved danne en tredje størknet blanding; og at udføre en sekundær tørringsfase ved det mindskede tryk i en sjette tidsperiode tilstrækkelig til at fremstille det frysetørrede syntetiske pulmonære overfladeaktive stof med et residualsolventindhold på højst 2%; hvor det frysetørrede syntetiske pulmonære overfladeaktive stof har et specifikt overfladeareal på mindst 2,2 m2/g.
2. Fremgangsmåden ifølge krav 1, hvor et forhold mellem præfrysetørringsblandingens volumen i beholderen og beholderens volumen er fra 28% til 68%.
3. Fremgangsmåden ifølge krav 1, hvor et forhold mellem en højde af præfrysetørringsblandingen i beholderen og beholderens diameter er i området fra 0,3 til 0,8.
4. Fremgangsmåden ifølge krav 1, fremgangsmåden omfattende at tilvejebringe præfrysetørringsblandingen hvor den organiske solvent er i området fra 3% til 15%.
5. Fremgangsmåden ifølge krav 1, fremgangsmåden omfattende at tilvejebringe præfrysetørringsblandingen hvor den organiske solvent er i området fra 5% til 10%.
6. Fremgangsmåden ifølge krav 1, fremgangsmåden omfattende at tilvejebringe præfrysetørringsblandingen hvor den organiske solvent er i området fra 7% til 10%.
7. Fremgangsmåden ifølge et hvilket som helst af kravene 1-6, fremgangsmåden omfattende: at udføre frysefasen, hvor præfrysetørringsblandingen nedkøles til den første temperatur på - 50°C± 5°C med en hastighed mellem 0,1 og l,0°C/min; at udføre annealingfasen, hvor den første størknede blanding (i) opvarmes til den anden temperatur på - 22°C ± 5°C med en hastighed på 0,1 til l,0°C/min, (ii) holdes ved den anden temperatur i den anden tidsperiode mellem 3 og 8 timer, (iii) nedkøles til den tredje temperatur på - 50°C ± 5°C med en hastighed mellem 0,1 til l,0°C/min; og (iv) holdes ved den tredje temperatur i den tredje tidsperiode i 3 til 8 timer; at udføre den primære tørringsfase ved et tryk valgt fra området af 30mT til 200mT og en primær tørringstemperatur valgt fra området fra -25°C til 0°C øget fra - 50°C ± 5°C, og yderligere holdes ved den primære tørring i mindst 10 timer.
8. Fremgangsmåden ifølge et hvilket som helst af kravene 1-7, fremgangsmåden omfattende at udføre den sekundære tørringsfase ved et tryk valgt fra området fra 30mT til 200mT og temperatur på højst 46°C± 5°C.
9. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 8, hvor det specifikke overfladeareal er i området fra 3,7 m2/g til 2,2 m2/g.
10. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 8, hvor det frysetørrede syntetiske pulmonære overfladeaktive stof har porøsitet over 40 volumenprocent af et samlet areal af det frysetørrede syntetiske pulmonære overfladeaktive stof.
11. Frysetørret syntetisk pulmonært overfladeaktivt stof-sammensætning omfattende: et syntetisk polypeptid med SEQ ID NO: 1 (KL4 polypeptid), dipalmitoylphosphatidylcholin (DPPC), palmitoyloleoylphosphatidylglycerol (POPG) og palmitinsyre, hvor den frysetørrede syntetiske pulmonære overfladeaktive stof-sammensætning har et specifikt overfladeareal på mindst 2,2 m2/g.
12. Det frysetørrede syntetiske pulmonære overfladeaktive stof ifølge krav 11, hvor det specifikke overfladeareal er i området fra 3,7 m2/g til 2,2 m2/g.
13. Det frysetørrede syntetiske pulmonære overfladeaktive stof ifølge krav 11, hvor det frysetørrede syntetiske pulmonære overfladeaktive stof har porøsitet over 40 volumenprocent af et samlet areal af det frysetørrede syntetiske pulmonære overfladeaktive stof.
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| HUE026363T2 (en) * | 2012-03-28 | 2016-06-28 | Discovery Lab Inc | Lyophilization of pulmonary synthetic liposomal surfactant |
| WO2016080336A1 (ja) * | 2014-11-18 | 2016-05-26 | 国立研究開発法人物質・材料研究機構 | 多孔性粒子の製造方法 |
| KR101801566B1 (ko) * | 2014-12-30 | 2017-11-28 | 주식회사 삼양바이오팜 | 고분자 나노입자 동결건조물 및 그 제조방법 |
| EP3319597B1 (en) * | 2015-07-10 | 2021-02-17 | Byondis B.V. | Compositions comprising antibody-duocarmycin drug conjugates |
| IL288342B2 (en) | 2015-07-22 | 2024-02-01 | Nitto Denko Corp | Formulations and methods for lyophilic nanoparticulate forms |
| JP7012512B2 (ja) * | 2017-11-13 | 2022-01-28 | 清水建設株式会社 | 管理装置、製造システムおよび管理方法 |
| EP3727353A4 (en) * | 2017-12-21 | 2021-10-13 | Civitas Therapeutics, Inc. | SURFACTANT FORMULATIONS FOR INHALATION |
| CN108853061A (zh) * | 2018-10-09 | 2018-11-23 | 兆科药业（合肥）有限公司 | 一种人工合成肺表面活性剂药物组合物及与之的肠溶胶囊和其制备方法及用途 |
| WO2020142420A1 (en) * | 2018-12-31 | 2020-07-09 | Novus Therapeutics, Inc. | Novel surfactant-lipid alloy drug substance, methods of making the same, and pharmaceutical compositions comprising the same |
| US11287185B1 (en) | 2020-09-09 | 2022-03-29 | Stay Fresh Technology, LLC | Freeze drying with constant-pressure and constant-temperature phases |
| KR102545292B1 (ko) * | 2021-01-28 | 2023-06-16 | 인천대학교 산학협력단 | 마이크로캡슐 형성용 생체 적합 계면활성제 합성방법 |
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|---|---|---|---|---|
| BE751108R (fr) | 1969-06-06 | 1970-11-03 | Berliet Automobiles | Dispositif pour la mesure precise de la consommation specifiquedes moteurs a combustion |
| JPS59164724A (ja) * | 1983-03-10 | 1984-09-17 | Tokyo Tanabe Co Ltd | サ−フアクタント及びそれを含有する呼吸窮迫症候群治療剤 |
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| KR100449789B1 (ko) | 1996-01-24 | 2005-02-03 | 알타나 파마 아게 | 분말형폐계면활성제제의제조방법 |
| WO1997035882A1 (en) * | 1996-03-27 | 1997-10-02 | Ortho Pharmaceutical Corporation | Lyophilized pulmonary surfactant peptide compositions |
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| US7582312B2 (en) * | 2004-11-15 | 2009-09-01 | Discovery Laboratories, Inc. | Methods to produce lung surfactant formulations via lyophilization and formulations and uses thereof |
| EP2377554A1 (en) | 2005-07-22 | 2011-10-19 | Amgen, Inc | Concentrated protein lyophilates, methods and uses |
| EP1997502A1 (en) | 2007-06-01 | 2008-12-03 | CHIESI FARMACEUTICI S.p.A. | Reconstituted surfactants having improved properties |
| HUE026363T2 (en) * | 2012-03-28 | 2016-06-28 | Discovery Lab Inc | Lyophilization of pulmonary synthetic liposomal surfactant |
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