Claims for Patent: 8,202,540

Summary for Patent: 8,202,540

Title:	Method for controlled production of ultrafine microparticles and nanoparticles
Abstract:	The invention relates to superfine microparticles and nanoparticles and a process for their gentle preparation with exclusion of water or minimization of water and/or exclusion of plasticizers and/or reduced temperature load, in which a matrix material is subjected to a high-pressure homogenization process in an anhydrous or water-poor medium and/or at low temperatures, preferably room temperature (20.degree. C.) and in particular below the freezing point of water, which leads to a gentle particle reduction with minimization of the impairment of the chemical stability of the homogenized material.
Inventor(s):	Muller; Rainer H. (Berlin, DE), Krause; Karsten (Berlin, DE), Mader; Karsten (Berlin, DE)
Assignee:	Abbott GmbH & Co., KG (Wiesbaden, DE)
Application Number:	10/030,417
Patent Claims:	1. Process for the gentle preparation of superfine micro- and nanoparticles having a particle size, as average diameter of the number distribution, of 5.6 .mu.m or less, the method comprising: subjecting a matrix material comprising solid particles to a high-pressure homogenizing process in a piston-gap homogenizer in an anhydrous or water-reduced dispersion medium containing less than 50 wt. % of water in which the solid particles are suspended and at temperatures of 20.degree. C. or less, which leads to a gentle particle size reduction with minimization of the impairment of the chemical stability of the homogenized material, to form superfine micro- and nanoparticles. 2. Process according to claim 1, wherein the homogenized matrix material comprises at least one selected from the group consisting of drugs, pharmaceutical active ingredients, veterinary drugs, active ingredients, auxiliaries, additives for cosmetics, agricultural products, foodstuffs and preservatives. 3. Process according to claim 2, wherein the homogenized matrix material comprises at least one drug selected from the group consisting of ciclosporin, azodicarbonamide, paclitaxel, prednisolone, carbamazepine, taxol, morphine, diclofenac, ibuprofen, phenobarbital and cromoglycin. 4. Process according to claim 1, wherein the homogenized matrix material comprises at least one selected from the group consisting of synthetic, semi-synthetic or natural polymers, and natural macromolecules. 5. Process according to claim 4, wherein the homogenized matrix material comprises at least one selected from the group consisting of synthetic polymers, polylactide, polyglycolide, polylactide/-glycolide co-polymer, polyorthoester, polyhydroxybutyrate (PHB), polyhydroxyvaleriate (PHV), polyhydroxybutyrate/-valeriate co-polymer, polyacrylates, polymethacrylates, polyvinyl derivatives, block polymers of polyethylene glycol and polyesters, polyhydroxybutyric acid, polycyanoacrylates, polycarbonates and polycaprolacton. 6. Process according to claim 4, wherein the homogenized matrix material comprises at least one selected from the group consisting of natural macromolecules, alginates, albumin, serum albumin, human albumin, bovine albumin, collagen, casein, fibrin, tragacanth, xanthans, polysaccharides, chitin, dextrans and hyaluronic acid. 7. Process according to claim 1, wherein the homogenized matrix material comprises polymers or natural macromolecules loaded with drugs or active ingredients. 8. Process according to claim 7, wherein the homogenized matrix material comprises at least one polymer selected from the group consisting of polylactide, polyglycolide, polylactide/-glycolide co-polymer, polyorthoester, polyhydroxybutyrate (PHB), polyhydroxyvaleriate (PHV), and polyhydroxybutyrate/-valeriate co-polymer. 9. Process according to claim 7, wherein the homogenized matrix material comprises at least one selected from the group consisting of natural macromolecules, in particular alginates, albumin, preferably serum albumin, human albumin and bovine albumin, collagen, casein, fibrin, bentonite, tragacanth, xanthans, polysaccharides such as chitin, dextrans and hyaluronic acid. 10. Process according to claim 1, wherein the materials to be reduced in size are dispersed in a non-aqueous dispersion medium. 11. Process according to claim 10, wherein the materials to be reduced are dispersed in an oily medium. 12. Process according to claim 10, wherein the materials to be reduced are dispersed in liquid hydrocarbons. 13. Process according to claim 10, wherein the materials to be reduced are dispersed in at least one selected from the group consisting of polyethylene glycols (PEGs), PEG 100 to PEG 1000, anhydrous glycerol, anhydrous alcohols, methanol, ethanol, 1-propanol, isopropanol, n-butanol, 2-butanol, pentanol, hexanol, octanol, decanol, allyl alcohol, propargyl alcohol, ethanol, isopropanol butanol, and propylene glycols. 14. Process according to claim 10, characterized in that the materials to be reduced are dispersed in dimethyl sulfoxide. 15. Process according to claim 1, wherein the materials to be reduced are dispersed in a dispersion medium that contains a small or minimized proportion or proportion desired, for product-related reasons, of water. 16. Process according to claim 15, wherein the materials to be reduced are dispersed in a dispersion medium containing less than 5 wt. % water. 17. Process according to claim 15, wherein the materials to be reduced are dispersed in a dispersion medium which contains less than 10 wt. % water. 18. Process according to claim 15, wherein the materials to be reduced are dispersed in a dispersion medium comprising water and at least one dissolved substance selected from the group consisting of polymers, polyethylene glycols solid at room temperature, PEG 6000, cellulose derivatives, and hydroxypropyl methylcellulose (HPMC). 19. Process according to claim 1, wherein the process temperature is below the freezing point of water. 20. Process according to claim 1, wherein the process is carried out with the exclusion of oxygen. 21. Process according to claim 1, further comprising degassing the dispersion medium before use. 22. Process according to claim 1, wherein the particle size is less than 5 .mu.m. 23. Process according to claim 1, wherein the particle size is less than 1 .mu.m. 24. Process according to claim 1, wherein the homogenization process is conducted at temperatures below the freezing point of water. 25. Process according to claim 11, wherein the oily medium comprises at least one selected from the group consisting of medium chain triglycerides (MCT), peanut oil, avocado oil, cottonseed oil, safflower oil, long chain triglycerides (LCT), in particular soybean oil, triacetin and isopropyl myristate. 26. Process according to claim 12, wherein the liquid hydrocarbon comprises at least one selected from the group consisting of fluid paraffin, viscous paraffin, hexane and octane. 27. Process according to claim 16, wherein the dispersion medium contains less than 1 wt. % of water. 28. Process according to claim 1, wherein the process temperature is 4.degree. C. 29. Process according to claim 19, wherein the process temperature is below -20.degree. C. 30. Process according to claim 19, wherein the process temperature is below -50.degree. C. 31. Process according to claim 20, further comprising gassing the matrix material and medium with inert gases. 32. Process according to claim 31, wherein the inert gas comprises at least one selected from the group consisting of nitrogen and argon. 33. Process according to claim 20, wherein the homogenization process is conducted under a vacuum. 34. Process according to claim 1, wherein the homogenizing process is conducted in a piston-gap homogenizer in an anhydrous medium. 35. Process for the gentle preparation of superfine micro- and nanoparticles having a particle size, as average diameter of the number distribution, of 5.6 .mu.m or less, the method comprising: dispersing solid particles in an anhydrous or water-reduced dispersion medium containing less than 50 wt. % of water to form a pre-suspension; and subjecting the pre-suspension to a high-pressure homogenizing process in a piston-gap homogenizer to reduce the particle size without cavitation with minimization of the impairment of the chemical stability of the homogenized material, to form superfine micro- and nanoparticles. 36. Process for the gentle preparation of superfine micro- and nanoparticles having a particle size, as average diameter of the number distribution, of 5.6 .mu.m or less, the method comprising: dispersing solid particles comprising a drug, pharmaceutical active ingredient, or veterinary drug in an anhydrous or water-reduced dispersion medium containing less than 50 wt. % of water to form a pre-suspension; and subjecting the pre-suspension to a high-pressure homogenizing process in a piston-gap homogenizer to reduce the particle size without cavitation with minimization of the impairment of the chemical stability of the homogenized material, to form superfine micro- and nanoparticles comprising the drug, pharmaceutical active ingredient, or veterinary drug.

Details for Patent 8,202,540

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2019-07-13
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2019-07-13
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2019-07-13
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2019-07-13
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2019-07-13
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	06/11/2003		2019-07-13
Csl Behring Llc	ALBUMINAR, ALBUMINAR-20, ALBUMINAR-25, ALBUMINAR-5	albumin (human)	Injection	103955	03/17/2000		2019-07-13