US0077993.37B2 (12) United States Patent (10) Patent No.: US 7,799,337 B2 Levin (45) Date of Patent: *Sep. 21, 2010 (54) METHOD FOR DIRECTED INTRANASAL (56) References Cited ADMINISTRATION OF ACOMPOSITION U.S. PATENT DOCUMENTS (76) Inventor: Bruce H. Levin, 125 Broome St., 3,105,854. A 10/1963 Druey Merion, PA (US) 19066 Continued (*) Notice: Subject to any disclaimer, the term of this ( ) patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U.S.C. 154(b) by 382 days. BE 1 OO9851. A 10, 1997 inplent is Subject to a terminal dis- (Continued) OTHER PUBLICATIONS (21) Appl. No.: 10/218,138 Goodman and Gilman's The Pharmacological Basis of Therapeutics, (22) Filed: Aug. 12, 2002 tenth edition, McGraw Hill publishing, pp. 278-281.* (65) Prior Publication Data (Continued) Primary Examiner—San-ming Hui US 2003/O133877 A1 Jul 17, 2003 y 9. ll. If, (74) Attorney, Agent, or Firm Panitch Schwarze Belisario & Related U.S. Application Data Nadel LLP (63) Continuation-in-part of application No. 09/737,302, (57) ABSTRACT filed on Dec. 15, 2000, now abandoned, and a continu riggerial o o E.2. E. Methods, kits, apparatus, and compositions for inhibiting a ation-in-part of application No. 09/118,615.filed on cerebral neurovascular disorder, a muscular headache, or Jul.17, 1998, now Pat No. 6.432.986, cerebral inflammation in a human patient are provided. The r s - 1s methods comprise intranasally administering to the patient a (60) Provisional application No. 60/117,398, filed on Jan. pharmaceutical composition comprising a local anesthetic, i. d'E' pysis, application S. Of . and preferably a long-acting local anesthetic ingredient. A Soo 1 6.hisdon Jul psya E. composition useful for practicing the methods of the inven cation No. 60,072,845, filed on ". 1998 ER: tion is described which comprises at least one local anesthetic sional application No. 60,084.559 filed on May 6 in a pharmaceutically acceptable carrier, wherein the compo 1998. sa- a-- s s sition is formulated for intranasal delivery. Cerebral neu rovascular disorders include migraine and cluster headache. (51) Int. Cl. Muscular headaches include tension headaches and muscle A6DF 3/00 (2006.01) contraction headaches. A kit comprising the composition and A61N L/30 (2006.01) an intranasal applicator and a method of systemically deliv A6M I/00 (2006.01) ering a pharmaceutically active agent to an animal are also (52) U.S. Cl. ........................... 424/434; 604/19, 604/27; included in the invention. Apparatus for directed intranasal 604/30 administration of the compositions of the invention and for (58) Field of Classification Search ................. 424/434, performing the methods of the invention are also described. 424/401; 600/120, 144 See application file for complete search history. 23 Claims, 8 Drawing Sheets US 7,799,337 B2 Page 2 U.S. PATENT DOCUMENTS EP O 754 453 A1 1, 1997 EP O 755 678 A1 1, 1997 3,260,258 A 7, 1966 Berman GB 2315 673. A 2, 1998 3,568,678 A 3/1971 Pourquier WO WO95/10276 4f1995 3,862,321 A 1/1975 Adams et al. WO WO95/21821 8, 1995 3,867.946 A 2/1975 Huddy WO WO96,32109 10, 1996 3,914,283 A 10, 1975 Okamoto et al. WO WO 97.15548 5, 1997 3,925,469 A 12/1975 Adams et al. WO WO97, 18855 * 5, 1997 3,988.475 A 10/1976 Manghisi WO WO97,23467 7/1997 4,073.917 A 2/1978 Sandberg et al. WO WO 97/38675 10, 1997 4,117,160 A 9, 1978 Molnar et al. WO WO98, 15275 A 4f1998 4,138.492. A 2f1979 Noverola WO WO 98,38998 9, 1998 4,147,804 A 4, 1979 Diamond et al. WO WO99,32103 7, 1999 4,147,805 A 4, 1979 Morrow 4,163,789 A 8, 1979 Mauri OTHER PUBLICATIONS 4,217,349 A 8, 1980 Katsube et al. 4,280,493 A 7, 1981 Council Frey, William H., II, Ph.D., “Bypassing the Blood-Brain Barrier to 4,298,603 A 11/1981 Chang et al. Deliver Therapeutic Agents to the Brain and Spinal Cord.” Jul.-Aug. 4,352,820 A 10, 1982 Scurlocket al. 2002 Issue of Drug Delivery Technology (Applicant received copy 4,379,161 A 4, 1983 Thominet et al. Jul. 15, 2002). 4,397,845. A 8, 1983 Allen 1996, Med. Sci. Bull. 19(4): 1. 4.495,174 A 1, 1985 Allcock et al. Aberg, 1972, Acta Pharmacol. Toxicol. 3 1:273-286. 4,551.453 A 11, 1985 Marsili Anthony, 1992, Clin. Neurol. NeuroSurg.94:297-301. 4,562,060 A 12/1985 Broberg et al. APS, 1978, Br. J. Clin. Pharmac. 6:63-68. 4,585,866 A 4, 1986 Fozard Ariéns, 1991, Eur, J. Clin. Pharmacol. 41(2):89-93. 4,622,219 A 1 1/1986 Haynes Ariéns, 1990, Pharmaceutisch Weekblad 125:(22)552-554. 4,632,940 A 12/1986 Chiarino et al. Ariéns, 1990, Schweiz Med. Wochenschr, 120(5) 131-134. 4,636,387 A 1, 1987 Allcock et al. Barth, 1984, Pain S269 (abstract - XP-002068058). 4,695,576 A 9, 1987 af Ekenstam et al. Barré, 1982, Headache 22(2):69-73. 4,727,145 A 2, 1988 Press Burm, et al., 1994, Br. J. Clin. Pharmacol. 38:125-129. 4,755,174 A 7, 1988 Milewski et al. Butterworth, et al., 1993, Anesthesiology 79(1):88-95. 4,819,619 A 4, 1989 Augustine et al. Caputi, 1997, Headache 37(3):174-179. 4,821,715 A 4/1989 Downing Clark, et al., 1991, J. Chromatog. 553:383-390. 4,833,149 A 5/1989 Press Clarkson, et al., 1985, Anesthesiology 62:396-405. 4,871,745 A 10, 1989 PreSS Courtney, et al., 1988, Biochim. Biophys. Acta 939:163-166. 4,886,493 A 12, 1989 Yee ............................ 604,516 Dejong, et al., 1981, Reg. Anesth. 6:99-103. 4.937,078 A 6, 1990 Mezei et al. Denson, et al., 1992, Reg. Anesth. 17:311-316. 5,008,289 A 4, 1991 Bernstein Du Pen, et al., 1992, Pain 49:293-300. 5,085,868 A 2f1992 Mattsson et al. Fozzard, et al., 1985, Card. Electrophys. Arrhythmias 51-57. 5,227,165 A 7, 1993 Domb et al. Gristwood, et al., 1994, Exp. Opin. Invest. Drugs 3(11): 1209-1212. 5,234,957 A 8, 1993 Mantelle Honerjäger, 1986, Basic Res. Cardiol. 81 (Suppl.):33-37. 5,332,576 A 7, 1994. Mantelle Kuhnert, et al., 1981, Fed. Proc. 40(31):684 Drug Disposition, 5,360,805. A 1 1/1994 Asket al. Abstract 2599. 5,387,587 A 2f1995 Hausler et al. Lee-Son; et al., 1992, Anesthesiology 77:324-335. 5,420,151 A 5/1995 Hammarberg et al. Luduena, et al., 1970, Heterocyclic Compounds 73(5), Abstract 5,428,006 A 6/1995 Bechgaard et al. 25314a. 5,527,293 A 6, 1996 Zamierowski Luduena, et al., 1972, Arch. Int. Pharmacodyn. 200:359-369. 5,578,315 A 11/1996 Chien et al. Maciewicz, 1988, Clin. J. Pain 4:11-16. 5,624,898 A 4/1997 Frey, II Mather, 1991, Br. J. Anaesth. 67:239-246. 5,639,772 A 6/1997 Hammarberg et al. Mazoit, 1993, Anesth Analg 77:477-482. 5,656,657 A 8/1997 Hammarberg et al. Moskowitz, 1993, Neurology 43 (Suppl. 3): S16-S20. 5,660,837 A 8/1997 Lundquist Niesel, 1990, Reg. Anaesth. 13(3):54-56 (abstract only). 5,667,799 A 9, 1997 Caldwell Reiz, et al., 1986, Br. J. Anaesth. 58:736-746. 5,676,635 A 10, 1997 Levin Reynolds, 1995, Int. J. Obst. Anesth. 4:93-108. 5,676,691 A 10, 1997 Friedman Robbins, 1995, Headache 35: 83-84. 5,676.955 A 10, 1997 Ansmann et al. Rowland, et al., 1995, Clin. Pharmacokin. 83-88. 5,726, 187 A 3, 1998 Gaster Rutten, et al., 1992, J. Pharm. Pharmacol. 44:355-358. 5,756.520 A 5, 1998 Asket al. Rutten, et al., 1991, Br. J. Anaesth, 67:247-256. 5,840,755 A 11/1998 Liedtke Rutten, et al., 1993, Chirality 5(7):485-491. 5,858.410 A 1, 1999 Muller Schlepper, 1989, European Heart Journal 10(Suppl):73-80. 5,939.425. A 8, 1999 Caruso Strichartz, 1988, Neural Physiology and Local Anesthetic Action pp. 5,964,223. A 10, 1999 Baran 25-45 in: Neural Blockade in Clinical Anesthesia and Management of 6,019,994 A 2/2000 Evetts Pain, J.B. Lippincott. 6,110,937 A 8/2000 Loughhead Testa, et al., 1990, Chirality 2:129-133. 6,180,603 B1 1/2001 Frey, II Vanhoutte, et al., 1991, Br. J. Pharmacol. 103: 1275-1281. 6,407,061 B1 6/2002 Frey, II Valenzuela, et al., 1994, Biophys. J. 66: A205 (abstract only 6.432,986 B2 8, 2002 Levin Tu-Pos383). 6,444,205 B2 9, 2002 Dinsmore et al. Wahedi, et al., 1990, Reg. Anaesth. 13(3):66-72 (abstract only). 6,491,940 B1 12/2002 Levin ......................... 424/434 Wang, et al., 1992, J. Gen. Physiol. 100: 1003-1020. Diamond, 1996, Jama 276(19): 1553. FOREIGN PATENT DOCUMENTS Gherardini, 1995, Acta Anaesthesiol. Scand. 39(6):765-768. Lane, 1996, J. Am. Med. Assoc. 276(19): 1553. EP T54060 10, 1995 Sachs, 1996, J. Am. Med. Assoc.276(19): 1553-1554. US 7,799,337 B2 Page 3 Scott, et al., 1989, Anesth. Analg. 69(5):563-569 (abstract only). Goadsby et al., 1987, Am J.