Claims for Patent: 6,399,086

Summary for Patent: 6,399,086

Title:	Pharmaceutical preparations for the controlled release of beta-lactam antibiotics
Abstract:	The present invention relates to a pharmaceutical controlled-release oral drug delivery system comprising as active ingredient at least one .beta.-lactam antibiotic agent, having a specific absorption site in the small intestine in combination with a polymeric matrix, optionally further containing additional pharmaceutically acceptable constituents, wherein at least 50% of the .beta.-lactam antibiotic agent are released from the matrix within from about 3 to about 4 hours from oral administration and the reminder of the pharmaceutical agent is released at a controlled rate. The drug delivery system according to the invention optionally further comprises a .beta.-lactamase inhibitor, preferably in combination with amoxicillin and/or amoxicillin trihydrate as the active ingredient. The polymeric matrix of the pharmaceutical controlled-release oral drug delivery system of the invention my be of hydrophilic and/or hydrophobic nature and the delivery system may further comprise pharmaceutically acceptable additive. The pharmaceutical controlled-release oral drug delivery system of the invention is preferably in dosage unit form.
Inventor(s):	Katzhendler; Ifat (Jerusalem, IL), Hoffman; Amnon (Jerusalem, IL), Friedman; Michael (Jerusalem, IL)
Assignee:	Yissum Research Development Company of the Hebrew University of Jerusalem (Jerusalem, IL)
Application Number:	09/313,101
Patent Claims:	1. A pharmaceutical controlled-release oral drug delivery system comprising as active ingredient at least one .beta.-lactam antibiotic agent having a specific absorption site in the small intestine in combination with a polymeric matrix, optionally further containing additional pharmaceutically acceptable constituents, wherein at least 50% up to but not more than 67.61.+-.5.78% of said .beta.-lactam antibiotic agent is released from said matrix within 3 to 4 hours from oral administration and the remainder of the pharmaceutical agent is released at a controlled rate. 2. A drug delivery system according to claim 1 wherein said .beta.-lactam antibiotic drug is selected from the group consisting of cephalosporins and penicillins, and pharmaceutically acceptable salts and derivatives thereof. 3. A drug delivery system according to claim 2 wherein said cephalosporin or derivative thereof is cefadroxil, cefalexin, cefaclor, cefprozil, cefuiroxime, cefoxitin, cefpodoxime, cefixime, cefuroxime axetil, or cefpodoxime proxetil. 4. A drug delivery system according to claim 2 wherein said penicillin is penicillin G, penicillin V, amoxicillin, ampicillin, nafcillin, oxacillin, cloxacillin or dicloxacillin, pharmaceutically acceptable salts thereof or pharmaceuticlly acceptable derivatives thereof. 5. A drug delivery system according to claim 4 wherein said .beta.-lactam antibiotic agent is amoxicillin trihydrate. 6. A drug delivery system according to claim 2 comprising a .beta.-lactamase inhibitor. 7. A drug delivery system according to claim 6 wherein said .beta.-lactamase inhibitor is clavulonic acid, sulbactam or pharmaceutically acceptable salts thereof. 8. A drug delivery system according to claim 7 wherein said active ingredient is amoxicillin and said .beta.-lactamase inhibitor is clavulonic acid. 9. A drug delivery system according to claim 1 wherein said polymeric matrix comprises a hydrophilic polymer. 10. A drug delivery system according to claim 9 wherein said polymer is selected from the group consisting of hydrophilic cellulose derivatives, hydrophilic polyacrylamide derivatives, proteins, alginates, arabinogalactane, chitosan and hydrophilic methacrylic acid derivatives. 11. A drug delivery system according to claim 10 wherein said hydrophilic cellulose derivative is selected from the group consisting of methyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose and hydroxyethyl methyl cellulose. 12. A drug delivery system according to claim 10 wherein said proteins are egg albumin, bovine albumin, human albumin or soy bean protein, in native or denatured form. 13. A drug delivery system according to claim 1 wherein said polymeric matrix comprises a hydrophobic polymer. 14. A drug delivery system according to claim 13 wherein said polymer is selected from the group consisting of hydrophobic cellulose derivatives, fats, hydrophobic polyacrylamide and polyamide derivatives and hydrophobic methacrylic acid derivatives. 15. A drug delivery system according to claim 14 wherein said hydrophobic cellulose derivative is ethyl cellulose. 16. A drug delivery system according to claim 14 wherein said fat is glycerol palmitostearate, beeswax, glycowax, castorwax, carnaubawax, glycerol monostearate or stearyl alcohol. 17. A drug delivery system according to claim 1 wherein said polymeric matrix comprises a mixture of hydrophilic polymers, a mixture of hydrophobic polymers or a mixture of hydrophilic and hydrophobic polymers. 18. A drug delivery system according to claim 17 wherein said hydrophilic polymer is selected from hydrophilic cellulose derivatives, proteins, alginates, arabinogalactane, chitosan and hydrophilic methacrylic acid derivatives and said hydrophobic polymer is selected from hydrophobic cellulose derivatives, waxes and hydrophobic methacrylic acid derivatives. 19. A drug delivery system according to claim 1 further comprising a pharmaceutically acceptable additive selected from salts, polyethylene glycol and surfactants. 20. A drug delivery system according to claim 1 in dosage unit form. 21. A drug delivery system according to claim 20 which is in the form of a mono- or double-layer tablet, a disintegrating granulated tablet, or a capsule, which may be coated with a pharmaceutically acceptable coating.

Details for Patent 6,399,086

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		2016-11-17
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2016-11-17
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2016-11-17
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2016-11-17
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2016-11-17