HRP20191631T1 - Novi spojevi gadolinij kelata za uporabu kod snimanja magnetskom rezonancom - Google Patents
Novi spojevi gadolinij kelata za uporabu kod snimanja magnetskom rezonancom Download PDFInfo
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- HRP20191631T1 HRP20191631T1 HRP20191631T HRP20191631T1 HR P20191631 T1 HRP20191631 T1 HR P20191631T1 HR P20191631 T HRP20191631 T HR P20191631T HR P20191631 T1 HRP20191631 T1 HR P20191631T1
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- Prior art keywords
- ceramidase
- acid
- mixture
- precursor
- inactive
- Prior art date
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- 229910052688 Gadolinium Inorganic materials 0.000 title 1
- 239000013522 chelant Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 title 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 title 1
- 238000002595 magnetic resonance imaging Methods 0.000 title 1
- 102000004201 Ceramidases Human genes 0.000 claims 19
- 108090000751 Ceramidases Proteins 0.000 claims 19
- 239000000203 mixture Substances 0.000 claims 15
- 230000001225 therapeutic effect Effects 0.000 claims 12
- 239000002253 acid Substances 0.000 claims 9
- 102000006772 Acid Ceramidase Human genes 0.000 claims 8
- 108020005296 Acid Ceramidase Proteins 0.000 claims 8
- 239000002243 precursor Substances 0.000 claims 8
- 238000002360 preparation method Methods 0.000 claims 8
- 238000000034 method Methods 0.000 claims 4
- 239000002671 adjuvant Substances 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 3
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 claims 2
- 102000010126 acid sphingomyelin phosphodiesterase activity proteins Human genes 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 2
- 238000011534 incubation Methods 0.000 claims 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 claims 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 claims 1
- 108010040721 Flagellin Proteins 0.000 claims 1
- 102000002579 Sphingosine N-acyltransferase Human genes 0.000 claims 1
- 108020004714 Sphingosine N-acyltransferase Proteins 0.000 claims 1
- 239000000443 aerosol Substances 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- 230000000468 autoproteolytic effect Effects 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 229920001983 poloxamer Polymers 0.000 claims 1
- 229920000447 polyanionic polymer Polymers 0.000 claims 1
- 229920005862 polyol Polymers 0.000 claims 1
- 150000003077 polyols Chemical class 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000002732 sphingomyelin phosphodiesterase inhibitor Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000006188 syrup Substances 0.000 claims 1
- 235000020357 syrup Nutrition 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
- A61K49/105—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA the metal complex being Gd-DTPA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
- A61K49/108—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA the metal complex being Gd-DOTA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Radiology & Medical Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Claims (15)
1. Postupak za proizvodnju terapeutskog pripravka, naznačen time, da obuhvaća:
dobivanje medija koji sadrži prekursor rekombinantne neaktivne kiseline ceramidaze;
inkubiranje medija pod uvjetima koji su djelotvorni za transformaciju dijela neaktivnog prekursora ceramidaze kiseline u aktivnu kiselinsku ceramidazu autoproteolitičkim cijepanjem, pri čemu se navedeno inkubiranje provodi pri pH od 4 do 6,5 i temperaturi od 30°C, 35°C ili 37°C tijekom 3 sata, te nadalje obuhvaća zagrijavanje navedenog medija pod uvjetima koji su djelotvorni za uklanjanje aktivnosti kiselinske sfingomilinaze; i
izoliranje inkubiranog medija kao smjese rekombinantne ceramidaze koja sadrži prekursor neaktivne kiseline ceramidaze i aktivnu kiselinsku ceramidazu, pri čemu mješavina ceramidaze nema aktivnost detektibilne kiselinske sfingomilinaze.
2. Postupak sukladno patentnom zahtjevu 1, naznačen time što navedeni medij osigurava:
osiguravanje stanica transformiranih s DNA koja kodira kiselinsku ceramidazu i kultiviranje transformiranih stanica pod uvjetima koji su učinkoviti za proizvodnju medija koji sadrži neaktivni prekursor kiselinske ceramidaze.
3. Terapeutski pripravak, naznačen time što sadrži:
smjesu rekombinantne ceramidaze koja sadrži:
neaktivni prekursor ceramidaze kiseline i
ceramidazu aktivne kiseline; i
farmaceutski prihvatljiv nosač, pri čemu mješavina ceramidaze nema detektabilnu aktivnost sfingomijelinaze kiseline.
4. Terapeutska kompozicija sukladno zahtjevu 3, naznačena time da mješavina ceramidaze sadrži 55 do 95 tež % neaktivnog kiselinskog prekursora ceramidaze i 45 do 5 tež% aktivne kiseline ceramidaze, 70 do 95 tež.% neaktivnog kiselinskog prekursora ceramidase i 30 do 5 tež% aktivne kiseline ceramidaze, ili 80 do 90 tež% neaktivnog kiselinskog prekursora ceramidaze i 20 do 10 tež% aktivne kiseline ceramidaze.
5. Terapeutski sastav sukladno zahtjevu 3, naznačen time, da nadalje sadrži:
adjuvans.
6. Postupak sukladno patentnom zahtjevu 1, naznačen time, što se navedeno inkubiranje provodi pri pH 4 i temperaturi od 37 ° C.
7. Postupak sukladno bilo kojem od prethodnih patentnih zahtjeva, naznačen time što se navedeno zagrijavanje provodi pri temperaturi od 60°C između 10 i 20 minuta.
8. Terapeutski pripravak sukladno zahtjevu 5, naznačen time što je navedeni adjuvans odabran iz skupine koja se sastoji od flagelina, Freundovog potpunog ili nepotpunog adjuvansa, aluminijevog hidroksida, lizolecitina, pluronskih poliola, polianiona, peptida, uljne emulzije, dinitrofenola, iskomatriksa i liposomske polikationske DNA čestice.
9. Terapeutska kompozicija sukladno zahtjevu 3, naznačena time, da navedena smjesa rekombinantne ceramidaze nadalje sadrži nukleinsku kiselinu koja kodira protein ceramidaze.
10. Terapeutski pripravak sukladno zahtjevu 3, naznačen time što je smjesa rekombinantne ceramidaze u obliku odabranom između tableta, kapsula, eliksira, suspenzija, otopine, disperzije ili sirupa.
11. Terapeutska smjesa sukladno zahtjevu 3, naznačena time što je rečena smjesa rekombinantne ceramidaze u obliku aerosola.
12. Terapeutski pripravak sukladno zahtjevu 3, naznačen time, da nadalje sadrži dodatno sredstvo odabrano između inhibitora kiselina sfingomijelinaza, inhibitora ceramidnih sintetaza, ili njihove kombinacije.
13. Terapeutski pripravak sukladno zahtjevu 3, naznačen time, da mješavina ceramidaze sadrži UniProt Q13510, UniProt Q9H715, UniProt Q96AS2, OMIM 228000, NCBI Gene 427, NCBI RefSeq NM_177924, NCBI RefSeq NM_004315, NCBI UniGene 427, Accession NCBI Q13510, Accession NCBI AAC73009, Accession NCBI AAC50907 ili njihovu kombinaciju.
14. Terapeutski pripravak sukladno zahtjevu 3, naznačen time da mješavina ceramidaze sadrži UniProt Q13510.
15. Terapeutski pripravak sukladno zahtjevu 3, naznačen time da mješavina ceramidaze sadrži NCBI RefSeq NP_808592.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15170658.7A EP3101012A1 (en) | 2015-06-04 | 2015-06-04 | New gadolinium chelate compounds for use in magnetic resonance imaging |
PCT/EP2016/062105 WO2016193190A1 (en) | 2015-06-04 | 2016-05-30 | New gadolinium chelate compounds for use in magnetic resonance imaging |
EP16726531.3A EP3303307B1 (en) | 2015-06-04 | 2016-05-30 | New gadolinium chelate compounds for use in magnetic resonance imaging |
Publications (1)
Publication Number | Publication Date |
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HRP20191631T1 true HRP20191631T1 (hr) | 2019-12-13 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20211467TT HRP20211467T1 (hr) | 2015-06-04 | 2016-05-30 | Novi spojevi gadolinijevih kelata za uporabu u magnetskoj rezonanciji |
HRP20191631 HRP20191631T1 (hr) | 2015-06-04 | 2019-09-11 | Novi spojevi gadolinij kelata za uporabu kod snimanja magnetskom rezonancom |
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HRP20211467TT HRP20211467T1 (hr) | 2015-06-04 | 2016-05-30 | Novi spojevi gadolinijevih kelata za uporabu u magnetskoj rezonanciji |
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Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
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EP3101012A1 (en) | 2015-06-04 | 2016-12-07 | Bayer Pharma Aktiengesellschaft | New gadolinium chelate compounds for use in magnetic resonance imaging |
KR102464647B1 (ko) * | 2016-11-28 | 2022-11-08 | 바이엘 파마 악티엔게젤샤프트 | 자기 공명 영상화에 사용하기 위한 높은 이완도 가돌리늄 킬레이트 화합물 |
BR112021007707A2 (pt) * | 2018-11-23 | 2021-07-27 | Bayer Aktiengesellschaft | formulação de meios de contraste e processo de preparação da mesma |
CN110396122B (zh) * | 2019-08-13 | 2020-10-27 | 牡丹江医学院 | 一种核磁共振造影剂、制备方法及其用于肿瘤诊断中的用途 |
KR102386595B1 (ko) * | 2019-10-29 | 2022-04-14 | 경북대학교 산학협력단 | 신규한 가돌리늄계 화합물, 이의 제조 방법, 및 이를 함유하는 mri 조영제 |
CN111393544A (zh) * | 2020-03-02 | 2020-07-10 | 合肥工业大学 | 一种具有靶向核磁共振造影和荧光成像功能的聚合物、制备方法及应用 |
CN114181233B (zh) * | 2021-11-24 | 2023-10-31 | 复旦大学 | 一种钆基T1磁共振造影剂FD-Gd-123及其制备方法和应用 |
CN114276309B (zh) * | 2021-12-24 | 2023-08-11 | 南京科技职业学院 | 一类含乙氧基芳环的钆磁共振造影剂及其制备方法与应用 |
WO2024046833A1 (de) | 2022-08-30 | 2024-03-07 | Bayer Aktiengesellschaft | Erzeugen von synthetischen radiologischen aufnahmen |
WO2024046831A1 (de) | 2022-08-30 | 2024-03-07 | Bayer Aktiengesellschaft | Erzeugen von synthetischen radiologischen aufnahmen |
WO2024046832A1 (de) | 2022-08-30 | 2024-03-07 | Bayer Aktiengesellschaft | Erzeugen von synthetischen radiologischen aufnahmen |
WO2024052156A1 (de) | 2022-09-05 | 2024-03-14 | Bayer Aktiengesellschaft | Erzeugen von künstlichen kontrastverstärkten radiologischen aufnahmen |
EP4335461A1 (en) | 2022-09-09 | 2024-03-13 | Bayer AG | Combinations of contrast agents |
WO2024063529A1 (ko) * | 2022-09-20 | 2024-03-28 | 주식회사 테라노큐어 | 신규 화합물 및 이를 포함하는 염증성 질환과 암에 대한 진단 및 치료에 사용되는 mri 조영제 |
WO2024083466A1 (de) | 2022-10-17 | 2024-04-25 | Bayer Aktiengesellschaft | Automatisches analysieren von radiologischen aufnahmen |
EP4360660A1 (en) | 2022-10-24 | 2024-05-01 | Bayer AG | Process for the preparation of a gadolinium contrast agent |
EP4369353A1 (de) | 2022-11-12 | 2024-05-15 | Bayer Aktiengesellschaft | Erzeugung von künstlichen kontrastmittelverstärkten radiologischen aufnahmen |
EP4369285A1 (de) | 2022-11-12 | 2024-05-15 | Bayer AG | Erzeugung von künstlichen kontrastmittelverstärkten radiologischen aufnahmen |
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