Glue composition for lung volume reduction

Abstract

The present invention relates to methods and compositions for sealing localized regions of damaged lung tissue to reduce overall lung volume. The glue compositions provide a glue featuring an adhering moiety coupled to one or more other moieties including, for example, a cross-linkable moiety and/or one other adhering moiety. The methods and compositions of the invention find use, for example, in treating pulmonary conditions, such as emphysema.

What is claimed is: 
     
       1. A method of reducing lung volume in a lung of a subject in need thereof, comprising:
 administering an effective amount of a glue composition to a localized region of damaged lung tissue of the subject, wherein the glue composition comprises a polyvinylalcohol polymer and a cross-linker, such that the polymer and cross-linker form a hydrogel in the lung, thereby reducing lung volume in the lung of the subject. 
 
     
     
       2. The method of  claim 1 , wherein said lung tissue comprises epithelial lining fluid. 
     
     
       3. The method of  claim 1 , wherein said administering delivers said glue composition to a deep lung region. 
     
     
       4. The method of  claim 1 , wherein said method is performed with prior identification of said damaged lung tissue. 
     
     
       5. The method of  claim 1 , wherein said glue composition further comprises a sclerosing agent that damages epithelial cells within lung tissue. 
     
     
       6. The method of  claim 5 , wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum, streptokinase, and urokinase. 
     
     
       7. The method of  claim 1 , wherein said glue composition is less than 10 microns. 
     
     
       8. The method of  claim 1 , wherein said glue composition is less than 5 microns. 
     
     
       9. The method of  claim 1 , wherein said glue composition is less than 1 micron. 
     
     
       10. The method of  claim 1 , wherein said administering is carded out via inhalation. 
     
     
       11. The method of  claim 10 , wherein said inhalation is carried out via the mouth. 
     
     
       12. The method of  claim 1 , wherein said administering is carried out via trans-thoracic administration. 
     
     
       13. The method of  claim 1 , wherein said administering is carried out by placing a bronchoscope in a bronchi of a deep lung region. 
     
     
       14. The method of  claim 13 , further comprising placing a catheter through said bronchoscope to reach a subsegmental bronchi. 
     
     
       15. The method of  claim 14 , wherein said catheter comprises an expandable balloon-like structure. 
     
     
       16. The method of  claim 1 , wherein said subject is suffering from a pulmonary condition. 
     
     
       17. The method of  claim 16 , wherein said pulmonary condition is emphysema or chronic obstructive pulmonary disease. 
     
     
       18. A method of reducing lung volume in a lung of a subject in need thereof comprising:
 providing a glue composition comprising a cross-linkable moiety and a polyvinylalcohol; 
 administering said glue composition to a localized region of the lung tissue of the subject; and 
 cross-linking said cross-linkable moiety and said polyvinylalcohol to form a hydrogel, thereby reducing lung volume. 
 
     
     
       19. The method of  claim 18 , wherein said glue composition further comprises a sclerosing agent that damages epithelial cells within lung tissue. 
     
     
       20. The method of  claim 19 , wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum, streptokinase, and urokinase. 
     
     
       21. The method of claim 1, wherein the cross-linker is glutaraldehyde. 
     
     
       22. The method of claim 1, wherein the glue composition further comprises a rate modifier. 
     
     
       23. The method of claim 1, wherein the glue composition further comprises an anti-secretory agent. 
     
     
       24. The method of claim 23, wherein the anti-secretory agent is selected from the group consisting of anticholinergic moieties, atronie, and atropinic moieties. 
     
     
       25. A method of sealing air spaces in a localized region of lung tissue in a subject, comprising:
 administering an effective amount of a glue composition to the air spaces in the localized region of lung tissue of the subject, wherein the glue composition comprises a polyvinylalcohol polymer and a cross-linker, such that the polymer and cross-linker form a hydrogel in the lung, thereby sealing the air spaces in the localized region of lung tissue of the subject.   
     
     
       26. The method of claim 25, wherein the localized region is a site of damaged lung tissue. 
     
     
       27. The method of claim 25, wherein the air spaces are within alveoli. 
     
     
       28. The method of claim 26, wherein the air spaces are within enlarged alveoli distal to a terminal bronchiole. 
     
     
       29. The method of claim 26, wherein the air spaces were enlarged air spaces or over-inflated air spaces prior to said administering of the glue composition. 
     
     
       30. The method of claim 26, wherein the air spaces remain in a collapsed or deflated state after said administering of the glue composition. 
     
     
       31. The method of claim 26, wherein said lung tissue comprises epithelial lining fluid. 
     
     
       32. The method of claim 26, wherein said method is performed with prior identification of said damaged lung tissue. 
     
     
       33. The method of claim 25, wherein said administering delivers said glue composition to a deep lung region. 
     
     
       34. The method of claim 25, wherein said cross-linker comprises glutaraldehyde. 
     
     
       35. The method of claim 25, wherein said glue composition further comprises a sclerosing agent that damages epithelial cells within lung tissue. 
     
     
       36. The method of claim 25, wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum, streptokinase, and urokinase. 
     
     
       37. The method of claim 25, wherein said glue composition is less than 10 microns. 
     
     
       38. The method of claim 25, wherein said glue composition is less than 5 microns. 
     
     
       39. The method of claim 25, wherein said glue composition is less than 1 micron. 
     
     
       40. The method of claim 25, wherein said administering is carried out via inhalation. 
     
     
       41. The method of claim 40, wherein said inhalation is carried out via the mouth. 
     
     
       42. The method of claim 25, wherein said administering is carried out via trans-thoracic administration. 
     
     
       43. The method of claim 25, wherein said administering is carried out by placing a bronchoscope in a bronchi of a deep lung region. 
     
     
       44. The method of claim 43, further comprising placing a catheter through said bronchoscope to reach a subsegmental bronchi. 
     
     
       45. The method of claim 44, wherein said catheter comprises an expandable balloon-like structure. 
     
     
       46. The method of claim 25, wherein said subject is suffering from a pulmonary condition. 
     
     
       47. The method of claim 46, wherein said pulmonary condition is emphysema or chronic obstructive pulmonary disease. 
     
     
       48. A method of cross-linking damaged lung tissue of a subject, comprising:
 administering an effective amount of a glue composition to a localized region of damaged lung tissue of the subject, wherein the glue composition comprises a polyvinylalcohol polymer and a cross-linker, thereby cross-linking the damaged lung tissue of the subject.   
     
     
       49. The method of claim 48, wherein the damaged lung tissue is within an alveolus. 
     
     
       50. The method of claim 48, wherein the damaged lung tissue is within an enlarged alveolus distal to a terminal bronchiole. 
     
     
       51. A method for delivering a glue composition to a lung of a patient, the system comprising:
 advancing a delivery catheter through a bronchoscope in an airway of the lung of the patient to a localized treatment site of damaged lung tissue; and   injecting a glue composition through the delivery catheter to the localized treatment site, wherein the glue composition comprises a polyvinylalcohol polymer and a cross-linker, such that the polymer and cross-linker form a hydrogel in the lung upon administration, thereby delivering the glue composition to the lung of the patient.   
     
     
       52. The method of claim 51, wherein said catheter comprises an expandable balloon-like structure. 
     
     
       53. The method of claim 51, wherein the cross-linker is glutaraldehyde. 
     
     
       54. The method of claim 51, wherein said glue composition further comprises a sclerosing agent that damages epithelial cells within lung tissue. 
     
     
       55. The method of claim 54, wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum, streptokinase, and urokinase. 
     
     
       56. The method of claim 51, wherein said glue composition is less than 10 microns. 
     
     
       57. The method of claim 51, wherein said glue composition is less than 5 microns. 
     
     
       58. The method of claim 51, wherein said glue composition is less than 1 micron. 
     
     
       59. The method of claim 51, wherein said patient is suffering from a pulmonary condition. 
     
     
       60. The method of claim 59, wherein said pulmonary condition is emphysema or chronic obstructive pulmonary disease.