US 2008O175887A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0175887 A1 Wang (43) Pub. Date: Jul. 24, 2008 (54) TREATMENT OF ASTHMA AND CHRONIC Mar. 2, 2007, provisional application No. 60/981,380, OBSTRUCTIVE PULMONARY DISEASE filed on Oct. 19, 2007, provisional application No. WITH ANT-PROLIFERATE AND 60/981,384, filed on Oct. 19, 2007. ANTI-NFLAMMATORY DRUGS Publication Classification (76) Inventor: Lixiao Wang, Medina, MN (US) (51) Int. Cl. A6IR 9/12 (2006.01) Correspondence Address: A63L/436 (2006.01) FINNEGAN, HENDERSON, FARABOW, GAR A6IP II/00 (2006.01) RETT & DUNNER A6M I5/00 (2006.01) LLP A6IF 2/82 (2006.01) 901 NEW YORKAVENUE, NW A6M 25/10 (2006.01) WASHINGTON, DC 20001-4413 A6M II/00 (2006.01) A63L/337 (2006.01) (21) Appl. No.: 11/942,459 (52) U.S. Cl. ........... 424/434; 514/291; 514/449; 424/43; 128/200.23; 128/203.15; 604/103.02; 623/1.42 (22) Filed: Nov. 19, 2007 (57) ABSTRACT Embodiments of the present invention provide a method for Related U.S. Application Data treatment of respiratory disorders such as asthma, chronic (60) Provisional application No. 60/860,084, filed on Nov. obstructive pulmonary disease, and chronic sinusitis, includ 20, 2006, provisional application No. 60/880,742, ing cystic fibrosis, interstitial fibrosis, chronic bronchitis, filed on Jan. 17, 2007, provisional application No. emphysema, bronchopulmonary dysplasia and neoplasia. 60/897.427, filed on Jan. 25, 2007, provisional appli The method involves administration, preferably oral, nasal or cation No. 60/903.529, filed on Feb. 26, 2007, provi pulmonary administration, of anti-inflammatory and anti sional application No. 60/926,850, filed on Apr. 30, proliferative drugs (rapamycin or paclitaxel and their ana 2007, provisional application No. 60/904,473, filed on logues). US 2008/0175887 A1 Jul. 24, 2008 TREATMENT OF ASTHMIA AND CHRONIC emphysema localized to the upper lung lobes are candidates OBSTRUCTIVE PULMONARY DISEASE for lung Volume reduction Surgery, where the upper lobes are WITH ANT-PROLIFERATE AND Surgically removed to restore the natural concavity and func ANTI-NFLAMMATORY DRUGS tion of the diaphragm. 0006 Acute exacerbation of asthma are often caused by CROSS REFERENCE TO RELATED spasm of the airways, or bronchoconstriction, causing Symp APPLICATIONS toms including Sudden shortness of breath, wheezing, and cough. Bronchospasm is treated with inhaled bronchodilators 0001. This application claims the benefit of priority under (anticholinergics such as ipratropium and beta-agonists Such 35 U.S.C. S 119 of U.S. Provisional Application No. 60/860, as albuterol). Patients inhale these medications into their 084, filed on Nov. 20, 2006, U.S. Provisional Application No. lungs as a mist, produced by either a nebulizer or a hand-held 607880,742, filed Jan. 17, 2007, U.S. Provisional Application meter dose (MDI) or dry powder (DPI) inhaler. Patients with No. 60/897,427, filed on Jan. 25, 2007, U.S. Provisional acute episodes may also be treated with oral or intravenous Application No. 60/903.529 filed on Feb. 26, 2007, U.S. steroids that serve to reduce the inflammatory response that Provisional Application No. 60/926,850 filed Apr. 30, 2007, exacerbates the condition. U.S. Provisional Application No. 60/904,473 filed Mar. 2, 0007 Asthma is a chronic respiratory disease character 2007, U.S. Provisional Application No. 60/981,380 filed Oct. ized by inflammation of the airways, excess mucus produc 19, 2007, and U.S. Provisional Application 60/981,384 filed tion and airway hyperresponsiveness, and a condition in Oct. 19, 2007, the disclosures of all of which are incorporated which airways narrow excessively or too easily respond to a by reference herein. stimulus. Asthma episodes or attacks cause narrowing of the airways, which make breathing difficult. Asthma attacks can FIELD OF THE INVENTION have a significant impact on a patient’s life, limiting partici 0002 The present invention relates to a method for treat pation in many activities. In severe cases, asthma attacks can ment of respiratory disorders such as asthma and chronic be life threatening. Presently, there is no know cure for obstructive pulmonary disease, including cystic fibrosis, asthma. interstitial fibrosis, chronic bronchitis, emphysema, bron 0008 According to the American Lung Association, there chopulmonary dysplasia and neoplasia. The method involves are approximately 20 million Americans with asthma in 2002. administration, preferably oral, nasal or pulmonary adminis Fourteen million of them were adults. Asthma resulted in tration, of anti-inflammatory and anti-proliferate drugs (rapa approximately 1.9 million emergency room visits in 2002. mycin or paclitaxel and their analogues). The estimated direct cost of asthma in the U.S. is S11.5 billions, which is spent on asthma medications, physician BACKGROUND OF THE INVENTION office visits, emergency room visits and hospitalizations. 0003 Chronic obstructive pulmonary disease (COPD) is a 0009. The causes of coronary heart disease and asthma are term used to classify two major airflow obstruction disorders: neointimal proliferation of Smooth muscle in arterial vessels chronic bronchitis and emphysema. Approximately 16 mil and in walls of airways. One aspect of the invention is to lion Americans have COPD, 80-90% of them were smokers deliverpaclitaxel or rapamycin and their analogues to the wall throughout much of their lives. COPD is a leading cause of of airways to treat the asthma and COPD. Drug coated stents death in the U.S., accounting for 122.283 deaths in 2003. The with these drugs have been approved for inhibiting the growth cost to the USA for COPD was approximately $20.9 billion in of the Smooth muscle cells in vascular arterial vessels. direct health care expenditures in 2003. Chronic bronchitis is 0010 Chronic sinusitis is an inflammation of the mem inflammation of the bronchial airways. The bronchial airways brane lining of one or more paranasal sinuses. Chronic sinusi connect the trachea with the lungs. When inflamed, the bron tis lasts longer than three weeks and often continues for chial tubes Secrete mucus, causing a chronic cough. Emphy months. In cases of chronic sinusitis, there is usually tissue sema is an overinflation of the alveoli, or air sacs in the lungs. damage. According to the Center for Disease Control (CDC), This condition causes shortness of breath. thirty seven million cases of chronic sinusitis are reported 0004. In emphysema, the alveolar sacs are overinflated as annually. a result of damage to the elastin skeleton of the lung. Inflam 0011 Chronic sinusitis is often difficult to treat success matory cells in emphysematous lung release elastase fully, however, as some symptoms persist even after pro enzymes, which degrade or damage elastin fibers within the longed courses of antibiotics. Steroid nasal sprays and pre lung matrix. Emphysema has a number of causes, including scribed Steroids are commonly used to treat inflammation in Smoking, exposure to environmental pollutants, alpha-one chronic sinusitis. When medical treatment fails, Surgery may antitrypsin deficiency, and aging. be the only alternative in treating chronic sinusitis. Presently, 0005. There are no therapies available today to halt the the most common Surgery done is functional endoscopic progression of COPD. Inhaled steroids have recently been sinus Surgery, in which the diseased and thickened tissues studied (Lung Health Study II) as a potential therapy to pre from the sinuses are removed to allow drainage. However, vent loss of lung function in emphysema patients. The study there is a need for better medicine for chronic sinusitis. concluded, however, that inhaled steroids failed to alter the 0012. The present invention provides a new method for decline in lung function over time. As patients lose lung treatment of respiratory disorders such as asthma, chronic function over time, they may become dependent on oxygen, obstructive pulmonary disease, and chronic sinusitis. The and eventually end up onventilators to assist with respiration. method involves administration, preferably oral, nasal or pull A relatively new treatment for patients with emphysema is monary administration, of anti-inflammatory and anti-prolif lung Volume reduction Surgery. Emphysema patients Suffer erate drugs (rapamycin or paclitaxel and their analogues). from air trapping in the lungs. This flattens the diaphragm, Embodiments of the present invention provides a pharmaceu impairing the ability to inhale and exhale. Patients with tical formulation comprising a drug for treatment of the res US 2008/0175887 A1 Jul. 24, 2008 piratory system, and an additive that enhances absorption of Sally, intrabronchially, transdermally, rectally, or via an the drug into tissue of body passages. impregnated vascular stent or balloon catheter into a body passage, wherein said drug is chosen from rapamycin and SUMMARY OF THE INVENTION analogues thereof and paclitaxel and analogues thereof. In 0013 Embodiments of the present invention are directed one aspect of this embodiment, the asthma and chronic to the treatment of respiratory disorders by intratracheal obstructive pulmonary disease to be treated is selected from administration of an effective amount of anti-inflammatory the group consisting of chronic bronchitis, cystic fibrosis, and anti-proliferate drugs (rapamycin or paclitaxel and their interstitial fibrosis, nasal and sinus dysplasia, bronchopulmo analogues). Respiratory disorders such as asthma, chronic nary dysplasia