HRP20171973T1 - Metoda proizvodnje i analize priona - Google Patents

Metoda proizvodnje i analize priona Download PDF

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HRP20171973T1
HRP20171973T1 HRP20171973TT HRP20171973T HRP20171973T1 HR P20171973 T1 HRP20171973 T1 HR P20171973T1 HR P20171973T T HRP20171973T T HR P20171973TT HR P20171973 T HRP20171973 T HR P20171973T HR P20171973 T1 HRP20171973 T1 HR P20171973T1
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shear force
prion protein
maximum
conformation
liquid composition
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HRP20171973TT
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Thorsten Lührs
Felix DELUWEIT
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Senostic Gmbh
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
    • B01F31/83—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations comprising a supplementary stirring element
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
    • B01F27/05—Stirrers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
    • B01F27/05—Stirrers
    • B01F27/11—Stirrers characterised by the configuration of the stirrers
    • B01F27/117—Stirrers provided with conical-shaped elements, e.g. funnel-shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
    • B01F27/27—Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices
    • B01F27/272—Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices with means for moving the materials to be mixed axially between the surfaces of the rotor and the stator, e.g. the stator rotor system formed by conical or cylindrical surfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/80—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
    • B01F31/85—Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations with a vibrating element inside the receptacle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/453—Magnetic mixers; Mixers with magnetically driven stirrers using supported or suspended stirring elements
    • B01F33/4531—Magnetic mixers; Mixers with magnetically driven stirrers using supported or suspended stirring elements using an axis supported in several points for mounting the stirring element
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/453—Magnetic mixers; Mixers with magnetically driven stirrers using supported or suspended stirring elements
    • B01F33/4532—Magnetic mixers; Mixers with magnetically driven stirrers using supported or suspended stirring elements using a bearing, tube, opening or gap for internally supporting the stirring element
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/86—Mixing heads comprising a driven stirrer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/20—Measuring; Control or regulation
    • B01F35/22—Control or regulation
    • B01F35/221—Control or regulation of operational parameters, e.g. level of material in the mixer, temperature or pressure
    • B01F35/2214—Speed during the operation
    • B01F35/22142—Speed of the mixing device during the operation
    • B01F35/221422—Speed of rotation of the mixing axis, stirrer or receptacle during the operation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/40—Mounting or supporting mixing devices or receptacles; Clamping or holding arrangements therefor
    • B01F35/41—Mounting or supporting stirrer shafts or stirrer units on receptacles
    • B01F35/412—Mounting or supporting stirrer shafts or stirrer units on receptacles by supporting both extremities of the shaft
    • B01F35/4121—Mounting or supporting stirrer shafts or stirrer units on receptacles by supporting both extremities of the shaft at the top and at the bottom of the receptacle, e.g. for performing a conical orbital movement about a vertical axis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/40—Mounting or supporting mixing devices or receptacles; Clamping or holding arrangements therefor
    • B01F35/41—Mounting or supporting stirrer shafts or stirrer units on receptacles
    • B01F35/413—Mounting or supporting stirrer shafts or stirrer units on receptacles by means of clamps or clamping arrangements for fixing attached stirrers or independent stirrer units
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/44—Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0418—Geometrical information
    • B01F2215/0427—Numerical distance values, e.g. separation, position
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0418—Geometrical information
    • B01F2215/0431—Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0436—Operational information
    • B01F2215/0454—Numerical frequency values
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0436—Operational information
    • B01F2215/0477—Numerical time values
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0436—Operational information
    • B01F2215/0481—Numerical speed values

Claims (20)

1. Postupak proizvodnje prionskog proteina agregirane konformacije iz prionskog proteina nativne konformacije putem dovođenja proteina priona nativne konformacije u kontakt s prionskim proteinom agregirane konformacije u tekućem sastavu i podvrgavanje tekućeg sastava barem jednom ciklusu koji se sastoji od generiranja sile smicanja i faze odmora, naznačeno time da se sila smicanja primjenjuje na svaki element volumena tekućeg sastava i sastoji se od jedne uniformne jačine sile smicanja s intenzitetom raspona od maksimalno 10% vrijednosti sile smicanja.
2. Postupak prema zahtjevu 1, naznačeno time da je sila smicanja generirana putem rotiranja rotacijskog elementa postavljenog unutar odmaknute koaksijalne cijevi i prolaskom svakog elementa volumena između rotacijskog elementa i cijevi dok je rotacija kontrolirana do jedne brzine s rasponom od maksimalno 1% brzine.
3. Postupak prema zahtjevu 2, naznačeno time da je cijev dio zida cirkularnog križnog presjeka nositelja koji sadrži tekući sastav i da se rotacijski element rotira na osovini koja je koaksijalno postavljena unutar dijela zida nositelja.
4. Postupak prema zahtjevu 2, naznačeno time da je cijev fiksirana na rukav koji sadrži ležaj u kojem se osovina pričvršćena na rotacijski element rotira te svaki element volumena prolazi između rotacijskog elementa i cijevi dok je rotacija kontrolirana do jedne brzine s rasponom od maksimalno 1% brzine, te svaki element volumena izlazi kroz bar jedan izlaz postavljen između cijevi i rukava, a izlaz ima križni presjek koji odgovara barem križnom presjeku između cijevi i rotacijskog elementa.
5. Postupak prema zahtjevu 1, naznačeno time da je sila smicanja generirana putem ultrazvučnog uređaja i nositelja koji ima unutarnji volumen koji se produljuje samo za element volumena a koji je postavljen udaljeno od površine ultrazvučnog uređaja te paralelno s površinom isključivo, a u kojem je maksimalna ultrazvučna sila smicanja kontrolirana u rasponu od maksimalno 10% vrijednosti maksimuma.
6. Postupak prema zahtjevu 5, naznačeno time da ultrazvučni uređaj vibrira na svojoj rezonantnoj frekvenciji i da je cijeli unutarnji volumen nositelja postavljen na predeterminiranoj udaljenosti od ultrazvučnog uređaja i jednako udaljen između dva vibracijska čvora ultrazvučnog uređaja.
7. Postupak prema jednom od prethodnih zahtjeva za analizu uzorka koji je potekao od sisavca, naznačeno time da uzorak sadrži prionski protein agregirane konformacije a kod kojeg se primjenom sile smicanja zamjećuje povećanje prionskog proteina agregirane konformacije.
8. Postupak prema jednom od bilo kojih prethodnih zahtjeva, naznačeno time da su barem dva alikvota uzeta iz tekućeg sastava, čiji se alikvoti simultano primijenjuju s istom, ili svaki zasebno drugačijom, silom smicanja uniformnog intenziteta.
9. Postupak prema zahtjevu 8, naznačeno time da je spoj dodan prvom alikvotu tekućeg sastava, drugi alikvot ostaje bez dodanog spoja, te se daljnjom primjenom sile smicanja zamijećuje promjena u prvom alikvotu u odnosu na prionski protein agregirane konformacije u drugom alikvotu.
10. Postupak prema jednom od prethodnih zahtjeva, naznačeno time da je tekući sastav sadržan u nositelju reakcije (31), a nositelja reakcije (31) drži kontrolirani uređaj za pozicioniranje s mogućnošću njegova otpuštanja, a pozicioniran je u prvom položaju tokom generiranja sile smicanja te pozicioniran u drugom položaju koji je udaljen od prvog tokom faze odmora putem kontroliranog uređaja za pozicioniranje.
11. Upotreba uređaja kao kontroliranog generatora intenziteta sile smicanja u postupku prema jednom od bilo kojih prethodnih zahtjeva, a koji sadrži generator sile smicanja postavljen tako da vrši silu smicanja na svaki element volumena tekućeg sastava koji sadrži prionski protein nativne konformacije i prionski protein agregirane konformacije, naznačeno time da je generator sile smicanja kontroliran tako da generira silu smicanja koja se primjenjuje na svaki element volumena tekućeg sastava samo u jednom uniformnom intenzitetu sile smicanja koja je ograničena na intenzitet u rasponu od maksimalno 10% jednog intenziteta.
12. Upotreba prema zahtjevu 11, naznačeno time da generator sile smicanja sadrži cijev (20) i koaksijalni rotacijski element (1) postavljen duž longitudinalne osi cijevi (20) na udaljenosti od cijevi (20), rotacijski element (1) se kreće na ležajevima (3, 4) te je barem jedan otvor izlaza (21) postavljen između cijevi (1) i ležajeva (3,4), s time da otvor izlaza (21) ima presjek koji je barem veličine presjeka između rotacijskog elementa (1) i cijevi (20).
13. Upotreba prema zahtjevu 12, naznačeno time da je rotacijski element (1) učvršćen na jednom kraju koasijalne osovine (2), čija je osovina (2) postavljena na prvom ležaju (3) formiranim od polimerne cijevi niskog trenja (22) postavljene oko dijela osovine (2) i postavljenog unutar rukava (24), naznačeno time da je polimerna cijev niskog trenja (22) postavljena između ramena (23) osovine (2) i unutarnjeg ramena (25) rukava (24).
14. Upotreba prema zahtjevu 11, naznačeno time da generator sile smicanja sadrži ultrazvučni uređaj i nositelja s unutarnjim volumenom koji se proteže samo za element volumena koji je postavljen na udaljenosti od površine ultrazvučnog uređaja te je paralelno samo s površinskim dijelom, gdje je maksimalna ultrazvučna sila smicanja koja se može kontrolirati u rasponu od maksimalno 10% maksimuma sile smicanja.
15. Upotreba prema zahtjevu 14, naznačeno time da ultrazvučni uređaj ima površinu ultrazvučnog uređaja (40) koja tvori jedan zid transferne tekuće kupke, a visina transferne tekuće kupke okomite na površinu (40) je predodređena na jednu valnu duljinu ili inegralni višekratnik valne duljine ultrazvuka.
16. Upotreba prema jednom od zahtjeva 11 do 15, naznačeno time da uređaj sadrži kontrolirani aparat za pozicioniranje koji ima sredstva za stezanje (50) za držanje reakcijskog nositelja (31), koji aparat za pozicioniranje je prilagođen za pozicioniranje reakcijskog nositelja (31) na predeterminiranim pozicijama u odnosu na generator sile smicanja.
17. Upotreba prema zahtjevu 16, naznačeno time da je kontrolirani aparat za pozicioniranje prilagođen za opetovano pozicioniranje nositelja reakcije (31) na predeterminiranom prvom položaju u odnosu na generator sile smicanja tijekom faze u kojoj je sila smicanja generirana te za potonje uklanjanje reakcijskih nositelja (31) iz prve pozicije i pozicioniranje reakcijskih nositelja (31) na udaljenu drugu poziciju tijekom faze odmora.
18. Prionski protein agregirane konformacije koji se može dobiti postupkom prema zahtjevima 1 do 11, naznačeno time da je prionski protein agregirane konformacije jedna sekvenca amino kiselina.
19. Prionski protein agregirane konformacije prema zahtjevu 18, naznačeno time da ima homogeno agregirano stanje konformacije 13C-NMR.
20. Prionski protein agregirane konformacije prema bilo kojem od zahtjeva 18 i 19, naznačeno time da je agregirana konformacija otkrivena kao jedna proizvodna karika Western blot-a probavljenog proteina proteaze.
HRP20171973TT 2011-02-16 2017-12-20 Metoda proizvodnje i analize priona HRP20171973T1 (hr)

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Application Number Priority Date Filing Date Title
EP11154710A EP2489427A1 (en) 2011-02-16 2011-02-16 Device and method for production and analysis of prions
PCT/EP2012/052634 WO2012110570A1 (en) 2011-02-16 2012-02-15 Device and method for production and analysis of prions
EP12703832.1A EP2675555B1 (en) 2011-02-16 2012-02-15 Method for production and analysis of prions

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US20160354739A1 (en) 2016-12-08
US20140046025A1 (en) 2014-02-13
PT2675555T (pt) 2017-12-29
EP2675555B1 (en) 2017-09-20
EP2675555A1 (en) 2013-12-25
EP2489427A1 (en) 2012-08-22
US10449499B2 (en) 2019-10-22
NO2675555T3 (hr) 2018-02-17
HUE035632T2 (en) 2018-05-28
PL2675555T3 (pl) 2018-03-30
WO2012110570A1 (en) 2012-08-23
US9346864B2 (en) 2016-05-24

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