Claims for Patent: 5,503,851

Summary for Patent: 5,503,851

Title:	Microencapsulation of water-soluble medicaments
Abstract:	In a process for the microencapsulation of water-soluble active ingredients according to the principle of phase separation, which comprises the steps (a) Preparation of a solution of a biocompatible polymer in an organic solvent; (b) Addition of an aqueous solution of one or more active ingredients or dispersion of one or more solid active ingredients in the solution from stage (a); (c) Addition of a coacervation agent to the emulsion or dispersion from stage (b); (d) Introduction of the mixture from stage (c) into an excess of a hardening agent; (e) Collection and washing of the microcapsules, natural or synthetic esters of saturated C.sub.4 to C.sub.18 carboxylic acids and polyhydric alcohols are used as hardening agents.
Inventor(s):	Mank; Reinhard (Kiel-Russee, DE), Gustafsson; Jan (Kiel, DE), Horig; Joachim (Kiel-Kronshagen, DE), Kochling; Wolfgang (Tuttendorf, DE), Nerlich; Birgit (Kiel-Russee, DE)
Assignee:	Ferring Arzneimittel GmbH (Kiel, DE)
Application Number:	08/084,592
Patent Claims:	1. A process for the microencapsulation of water-soluble active ingredients according to the principle of phase separation which comprises the steps of: a) preparing a solution of a biocompatible polymer in an organic solvent; b) adding an aqueous solution of one or more active ingredients to or dispersing one or more solid active ingredients in the solution from stage (a); c) adding a coacervation agent to the emulsion or the dispersion from stage (b) forming microcapsules in the solution; d) introducing the mixture from stage (c) into an excess of a liquid, non-hydrogenated hardening agent; and e) separating the microcapsules from the hardening agent, collecting and washing the microcapsules to remove substantially all of the hardening agent, wherein liquid, non-hydrogenated natural or synthetic esters of saturated C.sub.4 to C.sub.18 carboxylic acids and polyhydric alcohols are used as hardening agent in an excess amount of up to 30 times the total volume of polymer solvent and coacervation agent. 2. A process according to claim 1, wherein esters of C.sub.8 to C.sub.18 fatty acids are used. 3. A process according to claim 1, wherein esters of C.sub.8 to C.sub.10 fatty acids are used. 4. A process according to claim 3, wherein esters of caprylic and/or capric acid are used. 5. A process according to claim 1, wherein esters of di- or trihydric alcohols are used. 6. A process according to claim 5, wherein esters of ethylene glycol, propylene glycol or glycerin are used. 7. A process according to claim 1, wherein esters are used in which the hydroxyl groups of the alcohols are esterified with the same or different fatty acids. 8. A process according to claim 1, wherein neutral oils or fatty oils are used as esters. 9. A process according to claim 8, wherein sesame oil or peanut oil are used as fatty oils. 10. A process according to claim 9, wherein biocompatible, biologically non-degradable or biologically degradable polymers are used. 11. A process according to claim 10, wherein poly-L-lactide, poly-D, L-lactide, lactide/glycolide copolymer or mixtures thereof are used as polymer. 12. A process according to claim 11, wherein a lactide/glycolide copolymer with a molar ratio of lactic acid to glycolic acid of 10:90 to 90:10 is used. 13. A process according to claim 1, wherein said hardening agent is used in an amount of 10 to 30 times the total volume of polymer solvent and coacervation agent. 14. A process according to claim 1, wherein the content of said hardening agent in the microcapsules is selectively changed by washing with a solvent and the active ingredient release is thereby controlled. 15. A process according to claim 14, wherein alcohols are used as said solvent. 16. A process according to claim 15, wherein isopropanol is used as said alcohol. 17. A process according to claim 1, wherein pharmaceutical active ingredients are used as said active ingredients. 18. A process according to claim 17, wherein amino acids, peptides, proteins or hormones are used as said pharmaceutical active ingredients. 19. A process according to claim 18, wherein gonadotropin-releasing-hormone (GnRH) or an analogue (agonist or antagonist), calcitonin, growth hormone or hormone for the release of growth hormone, somatostatin or an analogue, parathyroid hormone (PTH) or a short-chain analogue is used as said pharmaceutical active ingredient. 20. A process according to claim 1, wherein the same substance which is used as said hardening agent is also employed as said coacervation agent.

Details for Patent 5,503,851

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2013-04-02
Aimmune Therapeutics, Inc.	PALFORZIA	peanut (arachis hypogaea) allergen powder	Powder	125696	01/31/2020		2013-04-02