HRP20230834T1 - Postupci za proizvodnju personaliziranih krvnih žila - Google Patents
Postupci za proizvodnju personaliziranih krvnih žila Download PDFInfo
- Publication number
- HRP20230834T1 HRP20230834T1 HRP20230834TT HRP20230834T HRP20230834T1 HR P20230834 T1 HRP20230834 T1 HR P20230834T1 HR P20230834T T HRP20230834T T HR P20230834TT HR P20230834 T HRP20230834 T HR P20230834T HR P20230834 T1 HRP20230834 T1 HR P20230834T1
- Authority
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- Croatia
- Prior art keywords
- whole blood
- cell
- blood sample
- fgf
- concentration
- Prior art date
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- 238000000034 method Methods 0.000 title claims 22
- 210000004204 blood vessel Anatomy 0.000 title claims 5
- 210000004369 blood Anatomy 0.000 claims 18
- 239000008280 blood Substances 0.000 claims 18
- 239000000725 suspension Substances 0.000 claims 14
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 6
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 4
- 239000003146 anticoagulant agent Substances 0.000 claims 4
- 229940126864 fibroblast growth factor Drugs 0.000 claims 4
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims 3
- 229920002307 Dextran Polymers 0.000 claims 3
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 claims 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims 3
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 3
- 102000013275 Somatomedins Human genes 0.000 claims 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims 3
- 230000002785 anti-thrombosis Effects 0.000 claims 3
- 229960005070 ascorbic acid Drugs 0.000 claims 3
- 235000010323 ascorbic acid Nutrition 0.000 claims 3
- 239000011668 ascorbic acid Substances 0.000 claims 3
- 230000001413 cellular effect Effects 0.000 claims 3
- 230000007613 environmental effect Effects 0.000 claims 3
- 239000003102 growth factor Substances 0.000 claims 3
- 229960002897 heparin Drugs 0.000 claims 3
- 229920000669 heparin Polymers 0.000 claims 3
- 235000015097 nutrients Nutrition 0.000 claims 3
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims 2
- 108010055166 Chemokine CCL5 Proteins 0.000 claims 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims 2
- 108010063738 Interleukins Proteins 0.000 claims 2
- 102000015696 Interleukins Human genes 0.000 claims 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims 2
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 2
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 2
- 230000023555 blood coagulation Effects 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000012544 monitoring process Methods 0.000 claims 2
- 210000000440 neutrophil Anatomy 0.000 claims 2
- 102000005162 pleiotrophin Human genes 0.000 claims 2
- 102000003390 tumor necrosis factor Human genes 0.000 claims 2
- 102100032367 C-C motif chemokine 5 Human genes 0.000 claims 1
- 102000001327 Chemokine CCL5 Human genes 0.000 claims 1
- 125000002353 D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 108090000378 Fibroblast growth factor 3 Proteins 0.000 claims 1
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 claims 1
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 claims 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 claims 1
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 claims 1
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 claims 1
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 claims 1
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 claims 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 claims 1
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 claims 1
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 claims 1
- 108090000367 Fibroblast growth factor 9 Proteins 0.000 claims 1
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 claims 1
- 102000018710 Heparin-binding EGF-like Growth Factor Human genes 0.000 claims 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 claims 1
- 101001052035 Homo sapiens Fibroblast growth factor 2 Proteins 0.000 claims 1
- 102000014150 Interferons Human genes 0.000 claims 1
- 108010050904 Interferons Proteins 0.000 claims 1
- 108090000978 Interleukin-4 Proteins 0.000 claims 1
- 108090001007 Interleukin-8 Proteins 0.000 claims 1
- 102000004890 Interleukin-8 Human genes 0.000 claims 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 1
- 229960004676 antithrombotic agent Drugs 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 229940119744 dextran 40 Drugs 0.000 claims 1
- 238000002513 implantation Methods 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 229940079322 interferon Drugs 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- -1 neutrophil (NT)-6 Proteins 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 230000010412 perfusion Effects 0.000 claims 1
Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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Claims (20)
1. Postupak za proizvodnju personalizirane krvne žile, naznačen time, da obuhvaća stavljanje u doticaj površine bezstaničnog cjevastog postolja sa suspenzijom koja sadrži uzorak pune krvi od pojedinca kojemu je potrebna personalizirana krvna žila, pri čemu se uzorak pune krvi razrjeđuje u fiziološkoj otopini i pritom se stavljanje u doticaj izvršava u vremenu od 3 do 14 dana.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da stanična populacija u uzorku pune krvi nastanjuje bezstanično cjevasto postolje.
3. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da uzorak pune krvi sadrži jedan ili više nestaničnih faktora, pri čemu jedan ili više nestaničnih faktora pune krvi nastanjuje postolje, i time, da nestanični faktori potiču celularizaciju bezstaničnog cjevastog postolja i kompatibilnost domaćina krvne žile nakon usađivanja.
4. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da suspenzija koja sadrži uzorak pune krvi nadalje sadrži antitrombotički faktor.
5. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotički faktor sadrži sredstvo protiv zgrušavanja krvi.
6. Postupak prema patentnom zahtjevu 5, naznačen time, da sredstvo protiv zgrušavanja krvi sadrži heparin ili dekstran.
7. Postupak prema patentnom zahtjevu 6, naznačen time, da se heparin nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,5 IU/mL +/- 10% do 150 IU/mL +/- 10%, opcionalno pritom heparin se nalazi u nerazrijeđenom uzorku pune krvi ili u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 6,7 IU/mL +/- 10%.
8. Postupak prema patentnom zahtjevu 6, naznačen time, da dekstran je dekstran-40.
9. Postupak prema patentnom zahtjevu 6, naznačen time, da se dekstran nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 1 g/L +/- 10% do 55 g/L +/- 10%.
10. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotičko sredstvo sadrži askorbinsku kiselinu.
11. Postupak prema patentnom zahtjevu 10, naznačen time, da se askorbinska kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,2 μg/mL +/- 10% do 200 μg/mL +/- 10%, opcionalno pritom se koncentracija askorbinske kiseline nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 5 μg/mL +/- 10%.
12. Postupak prema patentnom zahtjevu 4, naznačen time, da antitrombotički faktor sadrži acetilsalicilnu kiselinu.
13. Postupak prema patentnom zahtjevu 12, naznačen time, da se acetilsalicilna kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 0,2 μg/mL +/- 10% do 200 μg/mL +/- 10%, opcionalno pritom se acetilsalicilna kiselina nalazi u suspenziji koja sadrži uzorak pune krvi na početku njezinog stavljanja u doticaj s površinom bezstaničnog cjevastog postolja, u koncentraciji od 5 μg/mL +/- 10%.
14. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da suspenzija koja sadrži uzorak pune krvi nadalje sadrži jednako ili više od prosječne fiziološke razine populacije faktora rasta odabranog iz skupine koju čine: stimulacijski faktor kolonije granulocita makrofaga (GM-CSF), interleukin (IL)-3, IL-4, neutrofin (NT)-6, pleiotrofin (HB-GAM), midkin (MK), inducirajući protein-10 interferona (IP-10), faktor krvnih pločica (PF)-4, monocitni kemotaktični protein-1 (MCP-1), RANTES (CCL-5, kemokin (C-C-motiv) ligand 5), IL-8, IGF, faktor rasta fibroblasta (FGF)-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8, FGF-9, transformacijski faktor rasta (TGF)-β, VEGF, trombocitni faktor rasta (PDGF)-A, PDGF-B, HB-EGF, faktor rasta hepatocita (HGF), faktor nekroze tumora (TNF)-α, faktor rasta nalik na inzulin (IGF)-1, i bilo koja njihova kombinacija ili bilo koje njihove kombinacije, poželjno gdje faktor rasta je faktor rasta fibroblasta (FGF)-2, opcionalno pritom gdje FGF-2 jest ljudski FGF-2.
15. Postupak prema patentnom zahtjevu 1, naznačen time, da je stavljanje u doticaj u vremenskom periodu od 3 do 9 dana, i opcionalno time, da je stavljanje u doticaj u vremenskom periodu od 4 do 9 dana.
16. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se uzorak pune krvi razrjeđuje u fiziološkoj otopini od najmanje 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, ili 200%, poželjno s time, da se uzorak pune krvi razrjeđuje 1:1.
17. Postupak prema patentnom zahtjevu 14, naznačen time, da se faktor rasta nadopunjava kao izolirana, pročišćena, i/ili sintetička molekula.
18. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da postupak nadalje obuhvaća nadziranje koncentracije nutrijenta u suspenziji, pri čemu nutrijent je D-glukoza, dok se koncentracija D-glukoze neprekidno ili regularno podešava u svrhu održavanja koncentracije D-glukoze na 3 mmol/L +/- 10% do 11 mmol/L +/- 10%, poželjno pritom se koncentracija D-glukoze održava na 5 mmol/L +/- 10% do 8 mmol/L +/- 10%.
19. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se neprekidno vrši perfuzija bezstaničnog cjevastog postolja suspenzijom, pri čemu se opcionalno vrši perfuzija bezstaničnog cjevastog postolja brzinom od 0,1 mL +/- 10% do 50 mL +/- 10% u minuti, dok se opcionalno vrši perfuzija bezstaničnog cjevastog postolja brzinom od 2 mL +/- 10% u minuti, gdje se opcionalno vrši perfuzija postolja sa zatvorenom recirkulacijom suspenzije, te, opcionalno, time, da neprekidno stavljanje u doticaj jest perfuzija koja se provodi uporabom bioreaktora.
20. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se bezstanično cjevasto postolje stavlja u doticaj sa suspenzijom koja sadrži uzorak pune krvi, i postupak nadalje obuhvaća nadziranje čitavog niza okolišnih parametara i/ili koncentracije nutrijenta za vrijeme proizvodnje personalizirane krvne žile, s time, da nadalje obuhvaća prilagođavanje čitavog niza okolišnih parametara, dok čitav niz okolišnih parametara uključuje temperaturu, pH vrijednost, kisik, i/ili CO2.
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US201862714200P | 2018-08-03 | 2018-08-03 | |
PCT/IB2019/056621 WO2020026212A2 (en) | 2018-08-03 | 2019-08-02 | Methods of preparing personalized blood vessels |
EP19779967.9A EP3830243B1 (en) | 2018-08-03 | 2019-08-02 | Methods of preparing personalized blood vessels |
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EP (2) | EP4194541B1 (hr) |
JP (2) | JP7208393B2 (hr) |
KR (1) | KR102530336B1 (hr) |
CN (1) | CN112805364A (hr) |
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CA (1) | CA3107918A1 (hr) |
DK (1) | DK3830243T3 (hr) |
ES (1) | ES2953744T3 (hr) |
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HR (1) | HRP20230834T1 (hr) |
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JPH02274244A (ja) * | 1989-04-14 | 1990-11-08 | Yasunori Morohoshi | 人工血管およびその製造法 |
US6376244B1 (en) | 1999-12-29 | 2002-04-23 | Children's Medical Center Corporation | Methods and compositions for organ decellularization |
ATE390152T1 (de) * | 2000-04-28 | 2008-04-15 | Baylor College Medicine | Dezellularisierte gefässprothesen |
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