Claims (13)
1. Postupak za proizvodnju skupine čestica neke tvari u proizvodnom aranžmanu, pri čemu navedene čestice imaju unaprijed određene veličine, a uključuju korake:
miješanje unutar mlaznice za raspršivanje (101, 201, 301) i pod uvjetima protoka struje otopine (102, 202) u kojoj je navedena tvar otopljena ili dispergirana strujom tekućine (103, 203) koja je u potkritičnom stanju ili još poželjnije u superkritičnom stanju, odabire se udio navedenog protoka tekućine i toka otopine kako bi se potaknula nukleracija i stvaranje čestica navedene tvari u navedenoj smjesi;
omogućavanje jednog ili više sredstava za nadopunjavanje (107, 207), koja utječu na karakteristike veličina navedenih čestica, navedenom toku tekućine (103, 203);
prolazak navedene smjese u obliku spreja (204) kroz ispusni otvor (109, 209, 309) navedene mlaznice za prskanje (101, 201, 301) u komoru za prikupljanje čestica (105, 205); i
odvajanje i sakupljanje unutar navedene komore za prikupljanje čestica (105, 205) navedenih čestica iz navedene smjese.1. A procedure for the production of a group of particles of a substance in a production arrangement, wherein said particles have predetermined sizes, and include steps:
mixing within the spray nozzle (101, 201, 301) and under the conditions of the flow of the solution stream (102, 202) in which said substance is dissolved or dispersed by the liquid stream (103, 203) which is in a subcritical state or even more preferably in a supercritical state, the proportion of said liquid flow and solution flow is selected to encourage nucleation and particle formation of said substance in said mixture;
providing one or more replenishment means (107, 207), which affect the size characteristics of said particles, to said fluid flow (103, 203);
passing said mixture in the form of a spray (204) through the discharge opening (109, 209, 309) of said spray nozzle (101, 201, 301) into the particle collection chamber (105, 205); and
separation and collection within said particle collection chamber (105, 205) of said particles from said mixture.
2. Postupak prema patentnom zahtjevu 1, naznačen time što je omjer navedenog toka tekućine i navedenog toka otopine pri miješanju te omjer i vrsta spomenutih sredstava za nadopunu odabran radi održavanja faze s jednim fluidom nakon spomenutog miješanja. 2. The method according to patent claim 1, indicated by the fact that the ratio of the specified liquid flow and the specified solution flow during mixing and the ratio and type of the mentioned replenishment agents are selected to maintain a phase with one fluid after the mentioned mixing.
3. Postupak prema bilo kojem od zahtjeva 1-2, naznačen time što
izvođenje niza obuhvaća podkorake:
a) skupljanje navedene smjese nakon što se u toj tvari isprazni tijekom navedenog koraka odvajanja i sakupljanja,
b) odvajanje navedene tekućine od otapala navedene otopine u funkciji odvajanja (120), i
c) recirkuliranje (106, 206) navedene tekućine odvojene u koraku (b) do navedene struje tekućine (103).3. The method according to any one of claims 1-2, characterized in that
sequence execution includes substeps:
a) collection of the specified mixture after it is emptied into that substance during the specified step of separation and collection,
b) separation of said liquid from the solvent of said solution in the function of separation (120), i
c) recirculating (106, 206) said liquid separated in step (b) to said liquid stream (103).
4. Postupak prema zahtjevu 3, naznačen time da navedena recirkulirana tekućina sadrži barem jedno od navedenih sredstava za nadopunu.4. The method according to claim 3, characterized in that said recirculated liquid contains at least one of said replenishment agents.
5. Postupak prema bilo kojem od zahtjeva 1-4, naznačen time da se
navedeni koraci miješanja i prolaska izvode u dvije ili više zasebnih i u osnovi identičnih mlaznica (401a, b ...) koje pripadaju navedenom proizvodnom aranžmanu sa
a) najmanje dvije navedene mlaznice za raspršivanje koje se nalaze u spreju s istom komorom za prikupljanje čestica (405) i / ili
b) dvije ili više komora za prikupljanje čestica (505a, b...), pri čemu svaka od ovih komora za prikupljanje čestica (505a, b...) sadrži barem jednu mlaznicu za raspršivanje (501a, b ...)
i opcionalno pokretanje stvaranja čestica u navedene dvije ili više mlaznica za raspršivanje istovremeno. 5. The method according to any one of claims 1-4, characterized in that
said mixing and passing steps are performed in two or more separate and essentially identical nozzles (401a, b ...) belonging to said production arrangement with
a) at least two of said spray nozzles located in a spray with the same particle collection chamber (405) and/or
b) two or more particle collection chambers (505a, b...), each of these particle collection chambers (505a, b...) containing at least one spray nozzle (501a, b...)
and optionally initiating particle generation in said two or more spray nozzles simultaneously.
6. Postupak prema bilo kojem od zahtjeva 1-5, naznačen time da je unaprijed određeni srednji promjer navedenih čestica navedene šarže odabran da bude ≤ 20 µm ili ≤ 10 µm i / ili raspodjela veličine navedenih čestica u navedenoj skupini je na način da je ≥ 80 % navedenih čestica veličine s razmakom koji ima širinu od ≤ 20 µm.6. The method according to any one of claims 1-5, characterized in that the predetermined mean diameter of said particles of said batch is chosen to be ≤ 20 µm or ≤ 10 µm and/or the size distribution of said particles in said group is such that ≥ 80 % of the specified particle size with a gap having a width of ≤ 20 µm.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-6, naznačen time što volumetrijska brzina protoka barem jednog od spomenutih ili više sredstava za nadopunu pri njegovom miješanju s navedenim protokom tekućine daje koncentraciju u navedenom toku tekućine koji nije zasićen i odabire se u intervalu od 0.01 do 20% volumetrijske brzine protoka navedenog strujanja tekućine. 7. A method according to any one of claims 1-6, characterized in that the volumetric flow rate of at least one of said or more replenishing agents when mixed with said liquid flow provides a concentration in said liquid flow that is not saturated and is selected in interval from 0.01 to 20% of the volumetric flow rate of the specified liquid flow.
8. Postupak prema bilo kojem od zahtjeva 1-7, naznačen time da je najmanje jedno od spomenutih ili više sredstava za nadopunjavanje tekućina pod atmosferskim pritiskom i sobnom temperaturom (25°C).8. The method according to any one of claims 1-7, characterized in that at least one of the mentioned or more liquid replenishing means is at atmospheric pressure and room temperature (25°C).
9. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-8, naznačen time što barem jedno od spomenutih ili više sredstava za nadopunjavanje potiče nukleaciju i stvaranje čestica navedene tvari u navedenoj smjesi, npr. je antiotapalo za spomenutu tvar. 9. The method according to any one of patent claims 1-8, characterized in that at least one of said or more replenishing agents promotes the nucleation and formation of particles of said substance in said mixture, e.g. is an antisolvent for said substance.
10. Postupak prema bilo kojem od zahtjeva 1-9, naznačen time da barem jedno od spomenutih ili više sredstava za nadopunjavanje promovira solubilizaciju navedene tvari, npr. je otapalo za navedenu tvar. 10. The method according to any one of claims 1-9, characterized in that at least one of said or more replenishing agents promotes solubilization of said substance, e.g. is a solvent for said substance.
11. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačen time što je navedeno miješanje započeto spajanjem navedenog strujanja tekućine i navedenog toka otopine pod kutom odabranim u intervalu od 30° -150°, a prednost je 90°. 11. The method according to any one of claims 1-10, characterized in that said mixing is started by connecting said liquid flow and said solution flow at an angle selected in the interval of 30°-150°, preferably 90°.
12. Postupak prema bilo kojem od zahtjeva 1-11, naznačen time, da
A) navedeni dio za raspršivanje (201, 301) obuhvaća
a) dva unutarnja transportna vodova za navedenu otopinu i navedenu tekućinu (202, 203, 203, 303), koja su unutarnja cjevovoda koaksijalna barem u svojim gornjim dijelovima, a na njihovim se nizvodnim krajevima (238, 234) međusobno spajaju u jedan
b) aparat za miješanje (214, 314) koji slijedi i/ili se podudara sa
c) navedeni otvor za raspršivanje (209,309) i
a1) donji dio (238, 342) jednog od navedena dva unutrašnja transportna cjevovoda (210, 212, 310, 312) je cilindričan koji omogućava cilindrični protok na mjestu spajanja s drugim unutarnjim transportnim kanalom, a donji dio (234,334) drugog od navedenog dva unutarnja transportna cjevovoda je oblika diska pružajući prstenasti tok koji je radijalno usmjeren prema sredini koji se poklapa s osi navedenog cilindričnog protoka, pri čemu se kut spajanja između dva unutarnja transportna voda bira u intervalu od 30° - 150°,
b1) navedeni sloj za miješanje (214, 314) je prstenasti koji sadrži prstenasti gornji kraj na kraju spajanja dvaju unutarnjih transportnih kanala (210, 212, 310, 312) i prstenasti krajnji dio nizvodno, i
c1) navedeni otvor za raspršivanje (209) je prstenast i povezuje u smjeru uzvodno s navedenim prstenastim krajnjim dijelom navedenog rasporeda miješanja, i
B) izvođenje spomenutog koraka miješanja u spomenutom uređenju miješanja i navedenog koraka prolaska u navedenom ispusnom vodu s tim da navedeni tok otopine ulazi u navedeni sloj miješanja kroz unutarnji vod (212, 312) od dva unutarnja transportna voda i navedeni fluid tekućine kroz vanjski (210, 310) dva navedena cjevovoda za unutarnji transport.12. The method according to any one of claims 1-11, characterized in that
A) said dispersing part (201, 301) comprises
a) two internal transport lines for the specified solution and the specified liquid (202, 203, 203, 303), which are coaxial internal pipelines at least in their upper parts, and at their downstream ends (238, 234) they connect to one another
b) a mixing apparatus (214, 314) following and/or coinciding with
c) said spray opening (209,309) and
a1) the lower part (238, 342) of one of the two internal transport pipelines (210, 212, 310, 312) is cylindrical, which enables cylindrical flow at the point of connection with the other internal transport channel, and the lower part (234, 334) of the other of the two the internal transport pipeline is disc-shaped providing an annular flow which is directed radially towards the center which coincides with the axis of said cylindrical flow, whereby the angle of connection between the two internal transport lines is chosen in the interval of 30° - 150°,
b1) said mixing bed (214, 314) is annular comprising an annular upper end at the end of the junction of the two inner transport channels (210, 212, 310, 312) and an annular downstream end, and
c1) said spray orifice (209) is annular and connects upstream to said annular end portion of said mixing arrangement, and
B) carrying out said mixing step in said mixing arrangement and said passage step in said discharge conduit with said solution stream entering said mixing layer through an inner conduit (212, 312) of two inner transport conduits and said liquid fluid through an outer (210 , 310) two mentioned pipelines for internal transport.
13. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-12, naznačen time što su navedene čestice dobivene u navedenim koracima razdvajanja i sakupljanja ugrađene kao sastojak u farmaceutski pripravak koji sadrži terapeutski aktivnu tvar koja je možda kombinirana s prijenosnikom ili aditivom.13. The method according to any one of patent claims 1-12, characterized in that said particles obtained in said separation and collection steps are incorporated as an ingredient in a pharmaceutical preparation containing a therapeutically active substance that may be combined with a carrier or additive.