111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US008394406B2
`
`c12) United States Patent
`Chang et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,394,406 B2
`*Mar. 12, 2013
`
`(54) ONCE DAILY FORMULATIONS OF
`TETRACYCLINES
`
`(75)
`
`Inventors: Rong-Kun Chang, Rockville, MD (US);
`Arash Raoufinia, Springfield, VA (US);
`Niraj Shah, Owings Mills, MD (US)
`
`(73) Assignee: Supernus Pharmaceuticals, Inc.,
`Rockville, MD (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 12/926,934
`
`(22) Filed:
`
`Dec.17, 2010
`
`(65)
`
`Prior Publication Data
`
`US 2011/0288056 AI
`
`Nov. 24, 2011
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 12/155,676, filed on
`Jun. 6, 2008, which is acontinuationofapplicationNo.
`10/819,620, filed on Apr. 7, 2004, now Pat. No.
`7,749,532.
`
`(60) Provisional application No. 60/460,963, filed on Apr.
`7, 2003, provisional application No. 60/547,964, filed
`on Feb. 26, 2004.
`
`(51)
`
`Int. Cl.
`A61K 9154
`(2006.01)
`(52) U.S. Cl. ....................................................... 424/458
`(58) Field of Classification Search ........................ None
`See application file for complete search history.
`
`(56)
`
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`Primary Examiner- Paul Dickinson
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`Stephen B. Maebius; Sunit Talapatra
`ABSTRACT
`(57)
`Disclosed are once-daily formulations containing tetracy(cid:173)
`clines, especially doxycycline. Such formulations are useful,
`for instance, for the treatment of collagenase destructive
`enzyme-dependent diseases, such as periodontal disease and
`acne, and acute and chronic inflammatory disease states, such
`as rosacea and arthritis.
`21 Claims, 6 Drawing Sheets
`
`Doxycycline Monohydrate tR Pellets, 40 mg
`
`Report#: ARD3A16
`lot#: 801027 (CTM)
`110 - - - - - - - - - - - - - - - - - - - - - -
`
`100
`
`90.
`
`80 .
`
`70.
`
`60-
`
`50-
`
`40
`
`30-
`
`20-
`
`10.
`
`-&-Vessel1
`-a- Vessel2
`-6-Vessell
`'""""'*-Vesse14
`---*-Vessel S
`-9--- Vessel 6
`
`0~---------------------------------------~
`0
`10
`20
`30
`
`Time {Minutes)
`
`Dissolution profile for doxycycline monohydrate IR beads
`
`1
`
`

`

`US 8,394,406 B2
`Page 2
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