Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs

Abstract

Embodiments of the present invention provide a method for treatment of respiratory disorders such as asthma, chronic obstructive pulmonary disease, and chronic sinusitis, including cystic fibrosis, interstitial fibrosis, chronic bronchitis, emphysema, bronchopulmonary dysplasia and neoplasia. The method involves administration, preferably oral, nasal or pulmonary administration, of anti-inflammatory and anti-proliferative drugs (rapamycin or paclitaxel and their analogues).

1 . A method for treating at least one of asthma, chronic obstructive pulmonary disease, and chronic sinusitis in a mammal comprising:
 administering a pharmaceutical formulation comprising an effective amount of a drug and an additive to said mammal via a balloon catheter into a body passage of the respiratory or sinus system, wherein said drug is chosen from rapamycin and paclitaxel.   
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method according to  claim 1 , wherein the asthma and chronic obstructive pulmonary disease to be treated is selected from the group consisting of chronic bronchitis, cystic fibrosis, interstitial fibrosis, nasal and sinus dysplasia, bronchopulmonary dysplasia and neoplasia, and emphysema. 
     
     
         5 . The method according to  claim 1 , wherein the additive enhances absorption of the drug into tissue of the body passage. 
     
     
         6 . (canceled) 
     
     
         7 . The method according to  claim 1 , wherein the drug is not enclosed in micelles or encapsulated in polymer particles. 
     
     
         8 . The method according to  claim 1 , wherein the pharmaceutical formulation does not include oil, a lipid, or a polymer. 
     
     
         9 . The method according to  claim 1 , wherein the additive is chosen from PEG fatty esters and alcohols, glycerol fatty esters, sorbitan fatty esters, PEG glyceryl fatty esters, PEG sorbitan fatty esters, sugar fatty esters, PEG sugar esters, vitamins and derivatives, aminoacids, multiaminoacids and derivatives, peptides, polypeptides, proteins, quaternary ammonium salts, organic acids, salts and anhydrides. 
     
     
         10 . The method according to  claim 1 , wherein the additive is chosen from p-isononylphenoxypolyglycidol, PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate , PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, octoxynol, monoxynol, tyloxapol; cystine, tyrosine, tryptophan, leucine, isoleucine, phenylalanine, asparagine, aspartic acid, glutamic acid, and methionine; acetic anhydride, benzoic anhydride, ascorbic acid, 2-pyrrolidone-5-carboxylic acid, sodium pyrrolidone carboxylate, ethylenediaminetetraacetic dianhydride, maleic and anhydride, succinic anhydride, diglycolic anhydride, glutaric anhydride, acetiamine, benfotiamine, pantothenic acid; cetotiamine; cycothiamine, dexpanthenol, niacinamide, nicotinic acid, pyridoxal 5-phosphate, nicotinamide ascorbate, riboflavin, riboflavin phosphate, thiamine, folic acid, menadiol diphosphate, menadione sodium bisulfite, menadoxime, vitamin B 12, vitamin K5, vitamin K6, and vitamin U; albumin, immunoglobulins, caseins, hemoglobins, lysozymes, immunoglobins, a-2-macroglobulin, fibronectins, vitronectins, firbinogens, lipases, benzalkonium chloride, benzethonium chloride, docecyl trimethyl ammonium bromide, sodium docecylsulfates, dialkyl methylbenzyl ammonium chloride, and dialkylesters of sodium sulfonsuccinic acid. 
     
     
         11 . The method according to  claim 1 , wherein the additive is a surfactant. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The method according to  claim 1 , wherein the additive is chosen from PEG-fatty acids and PEG-fatty acid mono and diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterols and derivatives thereof, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugars and derivatives thereof, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, fat-soluble vitamins and salts thereof, water-soluble vitamins and amphiphilic derivatives thereof, amino acid and salts thereof, oligopeptides, peptides and proteins, and organic acids and esters and anhydrides thereof. 
     
     
         15 - 22 . (canceled) 
     
     
         23 . The method according to  claim 14 , wherein the additive is chosen from PEG-20 sorbitan monolaurate, PEG-20 sorbitan monopalmitate, PEG-20 sorbitan monostearate, and PEG-20 sorbitan monooleate. 
     
     
         24 - 28 . (canceled) 
     
     
         29 . The method according to  claim 14 , wherein the additive is chosen from sorbitan monolaurate, sorbitan monopalmitate, sorbitan monooleate, and sorbitan monostearate. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . The method according to  claim 14 , wherein the additive is albumin. 
     
     
         34 - 38 . (canceled) 
     
     
         39 . The method according to  claim 1 , wherein the pharmaceutical formulation further comprises an additional drug. 
     
     
         40 . The method according to  claim 39 , wherein the additional drug is selected from the group consisting of corticosteroids, anticholinergics, beta-agonists, non-steroidal anti-inflammatory drugs, macrolide antibiotics, bronchodilators, leukotriene receptor inhibitors, cromolyn sulfate, and combinations thereof. 
     
     
         41 - 91 . (canceled) 
     
     
         92 . A device sized and configured for insertion into a passage of a respiratory system, the device comprising a layer overlying an exterior surface of the device, the layer comprising a water insoluble drug for the treatment of the respiratory system and an additive that enhances absorption of the drug into tissue of the respiratory system, wherein:
 the device is a balloon catheter;   the water insoluble drug is chosen from paclitaxel and rapamycin; and   the additive is chosen from from PEG-fatty acids and PEG-fatty acid mono and diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and derivatives thereof, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugars and derivatives thereof, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, fat-soluble vitamins and salts thereof, water-soluble vitamins and amphiphilic derivatives thereof, amino acid and salts thereof, oligopeptides, peptides and proteins, and organic acids and esters and anhydrides thereof.   
     
     
         93 . (canceled) 
     
     
         94 . The device according to  claim 92 , wherein the drug is not enclosed in micelles or encapsulated in polymer particles. 
     
     
         95 . The device according to  claim 92 , wherein the layer does not include oil, a lipid, or a polymer. 
     
     
         96 - 100 . (canceled) 
     
     
         101 . A method for treating a respiratory system comprising:
 inserting a balloon catheter comprising a coating layer into an airway, wherein the coating layer comprises a drug and an additive, wherein:   the drug is chosen from paclitaxel and rapamycin; and   the additive is chosen from from PEG-fatty acids and PEG-fatty acid mono and diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and derivatives thereof, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugars and derivatives thereof, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, fat-soluble vitamins and salts thereof, water-soluble vitamins and amphiphilic derivatives thereof, amino acid and salts thereof, oligopeptides, peptides and proteins, and organic acids and esters and anhydrides thereof;   inflating the balloon catheter and releasing the drug to a wall of the airway;   deflating the balloon; and   withdrawing the balloon catheter from the airway.   
     
     
         102 . The method according to  claim 101 , wherein the additive enhances absorption of the drug into tissue of the respiratory or sinus system. 
     
     
         103 - 109 . (canceled) 
     
     
         110 . The method according to  claim 101 , wherein the drug can be released to the wall of the airway prior to, during, or after an asthma attack.