Claims (16)
1. Metoda za kontrolu veličine i/ili morfoloških karakteristika čestica za proizvodnju skupine čestica tvari u proizvodnom aranžmanu, pri čemu navedene čestice imaju unaprijed određene veličine i/ili morfologiju, naznačena time što sadrži korake:
i) miješanja unutar mlaznice za raspršivanje (101, 201) i pod uvjetima protoka, tekućina s tekućom otopinom (102, 202) u kojoj je ta tvar otopljena ili dispergirana strujom tekućine (103, 203), vrste otapala u navedenoj tekućoj otopini, vrste tekućine i omjer volumena navedene tekuće otopine u odnosu na volumen navedene tekućine odabrane za promicanje nukleacije i stvaranja čestica navedene tvari u navedenoj smjesi,
ii) prolaska 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
iii) odvajanje i sakupljanje unutar navedene komore za prikupljanje čestica (105, 205) navedenih čestica iz navedene smjese, pri čemu je navedeno otapalo tekućina, a navedeni fluid je vodena tekućina u subkritičnom stanju.1. A method for controlling the size and/or morphological characteristics of particles for the production of a group of particles of a substance in a production arrangement, wherein said particles have predetermined sizes and/or morphology, characterized by the fact that it contains steps:
i) mixing within the spray nozzle (101, 201) and under flow conditions, the liquid with the liquid solution (102, 202) in which the substance is dissolved or dispersed by the liquid stream (103, 203), the type of solvent in said liquid solution, the type liquid and the ratio of the volume of the said liquid solution in relation to the volume of the said liquid chosen to promote the nucleation and formation of particles of the said substance in the said mixture,
ii) passing said mixture in the form of a spray (204) through the outlet opening (109, 209, 309) of said spray nozzle (101, 201, 301) into the particle collection chamber (105, 205) and
iii) separation and collection within said particle collection chamber (105, 205) of said particles from said mixture, wherein said solvent is a liquid, and said fluid is an aqueous liquid in a subcritical state.
2. Metoda sukladno zahtjevu 1, naznačena time što se navedeni fluid i navedeno otapalo mogu miješati jedan s drugim, što ne uzrokuje razdvajanje faza na tekućinu /tekuću fazu nakon miješanja.2. The method according to claim 1, characterized in that said fluid and said solvent can be mixed with each other, which does not cause phase separation into a liquid/liquid phase after mixing.
3. Metoda u skladu s bilo kojim od zahtjeva 1 do 2, naznačena time što se volumetrijske brzine protoka navedenog toka otopine (102, 202, 302) na gornjem dijelu smjese za miješanje (114, 214, 314) nalaze u intervalu 0,01-20%, primjerice ≥ 0,1% i / ili ≤ 15%, brzine protoka navedenog strujanja tekućine (103, 203, 303).3. A method according to any one of claims 1 to 2, characterized in that the volumetric flow rates of said solution stream (102, 202, 302) on the upper part of the mixing mixture (114, 214, 314) are in the interval 0.01 -20%, for example ≥ 0.1% and / or ≤ 15%, of the flow rate of the specified liquid flow (103, 203, 303).
4. Metoda prema bilo kojem od zahtjeva 1-3, naznačena time što je koncentracija navedene tvari u navedenoj tekućoj otopini je ispod koncentracije zasićenja navedene tvari, obično ≤ 80% i / ili ≥ 1%, navedene koncentracije zasićenja pri tlaku I temperature primijenjenim pri miješanju.4. The method according to any one of claims 1-3, characterized in that the concentration of the specified substance in the specified liquid solution is below the saturation concentration of the specified substance, usually ≤ 80% and / or ≥ 1%, of the specified saturation concentration at the pressure and temperature applied at mixing.
5. Metoda prema bilo kojem od zahtjeva 1-4, naznačena time što se koraci (i) i (ii) izvode istovremeno u dvije ili više odvojene i u osnovi identične mlaznice za prskanje (401a, b ...) koje pripadaju navedenom proizvodnom uređenju koje sadrži barem jednu komoru za skupljanje čestica (405, 505a, b ...) s a) najmanje dvije navedene mlaznice za raspršivanje u komunikaciji s istom komorom za prikupljanje čestica (405) i / ili b) sa svakom od navedenih komora za prikupljanje čestica (505a, b ...) koja sadrži najmanje jednu mlaznicu za raspršivanje (501a, b ...).5. The method according to any one of claims 1-4, characterized in that steps (i) and (ii) are carried out simultaneously in two or more separate and essentially identical spray nozzles (401a, b ...) belonging to said production arrangement comprising at least one particle collection chamber (405, 505a, b ...) with a) at least two of said spray nozzles in communication with the same particle collection chamber (405) and/or b) with each of said particle collection chambers (505a, b ...) containing at least one spray nozzle (501a, b ...).
6. Metoda u skladu s bilo kojim od patentnih zahtjeva 1-5, naznačena time što je unaprijed određeni srednji promjer navedenih čestica skupina čestica odabran da bude ≤ 20 µm ili ≤ 10 µ m i / ili je raspodjela veličine navedenih čestica u toj skupini ≥ 80% navedenih čestica ima veličine s razmakom širine ≤ 20 µm.6. The method according to any one of claims 1-5, characterized in that the predetermined mean diameter of said particles of the group of particles is chosen to be ≤ 20 µm or ≤ 10 µm and/or the size distribution of said particles in that group is ≥ 80 % of the mentioned particles have sizes with a gap width ≤ 20 µm.
7. Metoda u skladu s bilo kojim od patentnih zahtjeva 1-6, naznačena time što je spomenuto miješanje započeto spajanjem navedenog protoka tekućine i navedeni tok otopine pod kutom odabranim u intervalu od 30 ° -150 °.7. A method according to any one of claims 1-6, characterized in that said mixing is initiated by connecting said liquid flow and said solution flow at an angle selected in the interval of 30°-150°.
8. Metoda u skladu s bilo kojim od patentnih zahtjeva 1-7, naznačena time što
A) navedena mlaznica za raspršivanje (201, 301) sadrži
a) dva unutarnja transportna cjevovoda za navedenu tekuću otopinu i navedenu tekućinu (202, 203, 203, 303), koji su unutrašnji transportni cjevovodi koaksijalni barem u svojim uzvodnim dijelovima, a na donjim nizovima (238, 234) stapaju se jedno s drugim
b) aparat za miješanje (214, 314) koji slijedi i/ili se podudara sa
c) ispusnim otvorom (209, 309), gdje
a1) nizvodni dio (238, 342) jednog od navedena dva unutrašnja transportna cjevovoda (210, 212, 310, 312) je cilindrični koji omogućava cilindrični protok na mjestu spajanja s drugim unutarnjim transportnim vodom, a donji dio (234, 334) drugog od navedena dva unutrašnja transportna cjevovoda je oblikovan na način da osigurava prstenasti tok koji je usmjeren radijalno prema van iz središta koje se podudara sa osi navedenog cilindričnog protoka, pri čemu je kut spajanja između navedena dva unutrašnja transportna vodiča odabran u intervalu od 30 ° - 150 °,
b1) navedeni sklop za miješanje (214, 314) je prstenasti sklop koji sadrži prstenasti gornji dio pri spajanju navedenih dvaju vodova za unutarnji transport (210, 212, 310, 312) i prstenastog dijela nizvodno, i
c1) navedeni otvor za raspršivanje (209) je prstenast i komunicira u smjeru uzvodno s navedenim prstenastim završetkom navedenog rasporeda miješanja, i
B) izvođenje koraka (i) u navedenom rasporedu miješanja i koraka (ii) u navedenom otvoru za raspršivanje.8. A method according to any one of claims 1-7, characterized in that
A) said spray nozzle (201, 301) comprises
a) two internal transport pipelines for said liquid solution and said liquid (202, 203, 203, 303), which internal transport pipelines are coaxial at least in their upstream parts, and merge with each other on the lower rows (238, 234)
b) a mixing apparatus (214, 314) following and/or coinciding with
c) discharge opening (209, 309), where
a1) the downstream 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 pipeline, and the lower part (234, 334) of the other said two internal transport pipelines is shaped in such a way as to provide an annular flow which is directed radially outward from the center which coincides with the axis of said cylindrical flow, wherein the connection angle between said two internal transport conductors is selected in the interval of 30 ° - 150 ° ,
b1) said mixing assembly (214, 314) is an annular assembly comprising an annular upper part at the junction of said two internal transport lines (210, 212, 310, 312) and an annular downstream part, and
c1) said spray orifice (209) is annular and communicates upstream with said annular end of said mixing arrangement, and
B) performing step (i) in said mixing arrangement and step (ii) in said spray orifice.
9. Metoda iz patentnog zahtjeva 8, naznačena time što je unutarnji dio (212) od navedena dva unutrašnja transportna cjevovoda (210, 212) na svom nizvodnom kraju (238) cilindričan, a vanjski (210) je na svojem nizvodnom kraju (234) u obliku diska.9. The method from claim 8, characterized in that the inner part (212) of the two inner transport pipelines (210, 212) is cylindrical at its downstream end (238), and the outer part (210) is cylindrical at its downstream end (234) in the form of a disc.
10. Metoda iz patentnog zahtjeva 8, naznačena time što su navedena dva kanala za unutarnji transport koaksijalna prema svojoj točki spajanja.10. The method of claim 8, characterized in that said two internal transport channels are coaxial to their connection point.
11. Postupak u skladu s bilo kojim od patentnih zahtjeva 8-10, naznačen time što prolazi navedeni tok otopine kroz unutarnji (212, 312) od dva unutrašnja transportna kanala (210, 212, 310, 312) koji su koaksijalni u svom gornjem toku i navedenom toku tekućine preko vanjskog dijela (210, 310), dva navedena unutrašnja transportna kanala (210, 212, 310, 312).11. The method according to any one of claims 8-10, characterized in that said solution flow passes through the inner (212, 312) of two inner transport channels (210, 212, 310, 312) which are coaxial in their upper flow. and said liquid flow over the outer part (210, 310), two said internal transport channels (210, 212, 310, 312).
12. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-11, naznačen time što su navedene čestice dobivene u koraku (iii) ugrađene kao sastojak u farmaceutskoj formulaciji koja sadrži terapeutski aktivnu tvar po mogućnosti u kombinaciji s nosačem ili aditivom, a prednost je da je navedena tvar terapeutski aktivna tvar.12. The method according to any of patent claims 1-11, characterized in that said particles obtained in step (iii) are incorporated as an ingredient in a pharmaceutical formulation containing a therapeutically active substance, preferably in combination with a carrier or additive, and the advantage is that the specified substance is a therapeutically active substance.
13. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-12, naznačen time što je tlak uzvodno i nizvodno od navedene mlaznice za raspršivanje > 1 bar i ≤ 30 bara.13. The method according to any one of claims 1-12, characterized in that the pressure upstream and downstream of said spray nozzle is > 1 bar and ≤ 30 bar.
14. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-13, naznačen time što pad tlaka preko navedene mlaznice za prskanje iznosi ≤ 30 bara.14. The method according to any one of claims 1-13, characterized in that the pressure drop across said spray nozzle is ≤ 30 bar.
15. Postupak u skladu s patentnim zahtjevom 14, naznačen time što navedeni pad tlaka preko navedene mlaznice za prskanje iznosi ≥ 1,25 bara.15. The method according to claim 14, characterized in that said pressure drop across said spray nozzle is ≥ 1.25 bar.
16. Postupak u skladu s bilo kojim od patentnih zahtjeva 1-15, naznačen time što navedeni fluid ima sadržaj vode ≥ 50% (v/v), poželjno sadržaj vode ≥ 90% (v/v).16. The method according to any one of patent claims 1-15, characterized in that said fluid has a water content ≥ 50% (v/v), preferably a water content ≥ 90% (v/v).