Methods for Treating Airway Stenosis or Stenosis

Abstract

A method for treating recurrent airway stenosis or stenosis in a body cavity includes inserting a scope and a drug-coated balloon catheter into a target site containing the recurrent airway stenosis or stenosis in the body cavity. The method includes inflating the balloon to an inflated diameter such that the coating contacts the interior surface of the body cavity at the target site. The method includes deflating the balloon and withdrawing the scope and balloon catheter from the target site.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 279,776, filed November 16, 2021, the disclosure of which is incorporated herein by reference in its entirety. [Background technology]

[0002] background Chronic rhinosinusitis (CRS) is an inflammation of the membranes lining one or more of the sinuses. Chronic sinusitis lasts longer than three weeks and often lasts for several months. With chronic sinusitis, there is usually tissue damage. According to the Centers for Disease Control and Prevention, there are 37 million cases of chronic sinusitis reported annually in the United States.

[0003] Chronic rhinosinusitis (CRS) is considered a widespread and common disease - many studies cite a prevalence of 10-15% (see, for example, Adam S. DeConde et al., Am J Rhinol Allergy 30, 134-139, 2016). Chronic rhinosinusitis with nasal polyps (CRSwNP) and nasal polyps (NP) account for approximately 25-30% of CRS. CRSwNP is an inflammatory condition of the nose and paranasal sinuses of unknown etiology, which appears in 2%-4% of the adult population. In the United States, direct costs for the management of CRS are currently $10-13 billion per year or approximately $2600 per patient per year. The highest direct costs are associated with patients with recurrent polyposis after surgery. Surgery is expensive, increasing up to $11,000 in the United States (EPOS 2020). Surgery and medications are recommended for refractory CRS (patients whose CRS symptoms persist despite appropriate treatment). Recurrence of CRSwNP after surgery is common, occurring in as many as 60% of patients (50% of these patients have previously undergone surgery) (see Adam S. DeConde et al., Am J Rhinol Allergy 30, 134-139, 2016).

[0004] Asthma is a chronic respiratory disease characterized by inflammation of the airways, excessive mucus production, airway hyperresponsiveness, and airways that are too narrow or too easily responsive to stimuli. Asthma episodes or attacks cause airway smooth muscle contraction, narrowing the airways and making breathing difficult. Asthma attacks can have a significant impact on a patient's life and can limit participation in many activities. In severe cases, asthma attacks can be life-threatening. Of the more than 35 million people with asthma in the United States, approximately 5-10% suffer from severe asthma. Currently, there is no known cure for asthma.

[0005] CRS is associated with asthma, with a prevalence of asthma in CRS patients of approximately 25% compared to 5% in the general population. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often also have asthma under the concept of "integrated airway disease," a combination of both diseases that is one of the most difficult to treat. The efficacy of CRSwNP treatment, whether medical or surgical, in asthma is less controversial today, since several studies have shown that medical and / or surgical treatment of CRSwNP improves asthma.

[0006] Chronic obstructive pulmonary disease (COPD) is a term used to classify two major airflow obstruction disorders: chronic bronchitis and emphysema. Approximately 16 million Americans have COPD, and approximately 80-90% of them have been smokers for most of their lives. COPD is the leading cause of death in the United States. Chronic bronchitis is inflammation of the bronchial airways. The bronchial airways connect the trachea to the lungs. When inflamed, the bronchi secrete mucus, causing chronic coughing. Emphysema is the over-expansion of the alveoli, or air sacs, in the lungs. This condition causes shortness of breath.

[0007] Mucus can accumulate in the lungs, clogging the airways and reducing airflow. Airway plugs can contain viscous high molecular weight glycoproteins. These proteins are overproduced by goblet cells and submucosal glands in the airways of the lungs. If the mucus plug is in the large upper airways, such as the main bronchi, intermediate bronchi, or lobar bronchi, the condition can lead to the patient becoming short of breath or dying, as seen in chronic bronchitis, asthma, and cystic fibrosis.

[0008] Unregulated localized production of IL-5, IL-6, IL-4, IL-13, IL-23 and / or ILC2 in the airways may contribute to airway eosinophilia in patients with severe eosinophilic asthma. IL-5, IL-6, IL-4, IL-13, IL-23, eosinophils and other targeted cells in the airways may be responsible for airway inflammation in asthma patients. A variety of humanized monoclonal antibodies have been developed that target these cells for the treatment of severe asthma. These biologics require annual or lifelong administration, and cessation of treatment leads to disease recurrence.

[0009] Airway restenosis is one of the most difficult pathologies to treat in the field of otorhinolaryngology and pulmonology. It may be at the level of the supraglottis, glottis, subglottis, trachea, main bronchus, intermediate trunk bronchus or lobar bronchus. Among the wide range of etiologies, e.g., congenital, traumatic, inflammatory and idiopathic, trauma after long-term intubation and tracheotomy is still considered the most common cause of airway stenosis development in both pediatric and adult populations. Benign stenosis or restenosis forms the most benign form of airway restenosis and includes airway restenosis associated with post-intubation tracheal stenosis, post-tracheotomy tracheal restenosis, post-tuberculous infection, transplant-related and idiopathic restenosis. There are various methods to relieve symptoms in patients with airway restenosis, including mechanical debulking, rigid bronchoscopic dilation, stent placement and balloon dilation. These procedures can be used to provide relief of the stenosis or narrowed airway segment, but the narrowing often recurs, necessitating subsequent repeat procedures. Summary of the Invention

[0010] Summary of the Invention The present invention provides a method for treating recurrent airway stenosis or stenosis in an airway lumen. The method includes inserting a scope and a balloon catheter into a target site of recurrent airway stenosis or stenosis in an airway lumen. The balloon catheter includes an elongated balloon. The balloon catheter also includes a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the lumen at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site.

[0011] The present invention provides a method for treating recurrent airway stenosis or stenosis in an airway body cavity. The method includes damaging, expanding and / or removing the stenosis or stenosis at a target site in the body cavity. The method includes flushing the target site with a flushing composition comprising water and / or saline. The method includes inserting a scope and a balloon catheter into the target site. The balloon catheter includes an elongated balloon. The balloon catheter also includes a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes hydrating and / or soaking the coating with the flushing composition at the target site. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to expansion, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0012] The present invention provides a method of treating chronic rhinosinusitis with nasal polyps (CRSwNP). The method includes removing at least one nasal polyp at a target site in a body cavity. The method includes inserting a scope and a balloon catheter into the target site in the body cavity. The balloon catheter includes an elongated balloon and a coating layer covering an outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0013] The present invention provides a method for treating laryngeal stenosis and / or subglottic stenosis or stenosis. The method includes damaging, expanding and / or removing laryngeal stenosis and / or subglottic stenosis or stenosis at a target site in a body cavity. The method includes inserting a scope and a balloon catheter into a target site in a body cavity. The balloon catheter includes an elongated balloon and a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0014] The present invention provides a method for treating severe asthma. The method includes inserting a scope and a balloon catheter into a target site in a body cavity including the trachea, main bronchus, intermediate trunk bronchus, and / or lobar bronchus. The balloon catheter includes an elongated balloon and a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. The method may include treating more than one treatment site. The method may include at least one drug-coated balloon catheter, two drug-coated balloon catheters, or more than two drug-coated balloon catheters. In embodiments involving treatment of more than one treatment site, multiple treatments can be performed simultaneously or a time delay, such as a time delay of 1-6 weeks, can occur between treatments. For example, in some embodiments, the bronchi in the upper lung can be treated with a first treatment, and untreated bronchi in another part of the lung can be treated with a subsequent (e.g., second) treatment. An asthmatic episode or attack can cause narrowing of the airway due to smooth muscle contraction in the airway. In various embodiments, the drug released from the drug-coated balloon can reduce the amount of smooth muscle cells in the airway, for example, by 5%-50%. Before inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0015] The present invention provides a method for reducing severe asthma exacerbations and / or hospitalizations. The method includes inserting a scope and a balloon catheter into a target site in a body cavity including the trachea, main bronchus, intermediate trunk bronchus, and / or lobar bronchus. The balloon catheter includes an elongated balloon and a coating layer covering the exterior surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the interior surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. In various embodiments, the drug released from the drug-coated balloon can reduce the concentration of smooth muscle cells in the airways by, for example, 5% to 50%, leading to a reduction in severe asthma exacerbations and / or hospitalizations and a reduction in smooth muscle contraction in the airways. Prior to expansion, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0016] The present invention provides a method for reducing the concentration of bronchial smooth muscle cells in a patient with severe asthma. The method includes inserting a scope and a balloon catheter into a target site containing bronchial smooth muscle cells in a body cavity. The balloon catheter includes an elongated balloon and a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0017] The present invention provides a method of treating chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. The method includes removing at least one nasal polyp at a first target site in a first body cavity. The method includes inserting a first scope and a first balloon catheter into a first target site in a first body cavity. The first balloon catheter includes a first elongated balloon. The first balloon catheter also includes a first coating layer covering an exterior surface of the first balloon. The first coating layer includes one or more first additives and an initial drug loading amount of a first therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the first balloon to a first inflated diameter such that the first coating layer contacts the interior surface of the first body cavity at the first target site. The method includes deflating the first balloon. The method also includes withdrawing the first scope and the first balloon catheter from the first target site. The method includes inserting a second scope and a second balloon catheter into a second target site in a second body cavity, including the trachea and / or bronchi. The second balloon catheter includes a second elongated balloon. The second balloon catheter also includes a second coating layer covering the exterior surface of the second balloon. The second coating layer includes one or more second additives and an initial drug loading amount of a second therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the second balloon to an inflated diameter such that the coating contacts the interior surface of the second body cavity at the second target site. The method includes deflating the second balloon. The method also includes withdrawing the second scope and the second balloon catheter from the second target site. In various embodiments, the second target site includes a bronchi, such as a main bronchi, an intermediate trunk bronchi, and / or a lobar bronchi. In various embodiments, the asthma is severe asthma.In various embodiments, simultaneous treatment of CRSwNP and asthma can advantageously result in a synergistic total treatment effect that is greater than the total treatment effect of treating CRSwNP and asthma separately. Prior to inflation, the coating on the first and / or second drug-coated balloon is hydrated and / or soaked to activate the coating.

[0018] The present invention provides a method for reducing the concentration of eosinophils, IL-4, IL-5, IL-6, IL-13, IL-23 and / or ILC2 in the airways, such as in patients with severe asthma. The balloon catheter includes an elongated balloon and a coating layer covering the exterior surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the interior surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0019] The present invention provides a method for treating a mucus plug in an airway. The method may optionally include removal of the mucus plug. The method includes inserting a scope and a balloon catheter into a target site containing a mucus plug in an airway body cavity. The balloon catheter includes an elongated balloon and a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. In various embodiments, the drug released from the drug-coated balloon can reduce the concentration of goblet cells in the airway and prevent or reduce the production of a viscous mucus plug in the airway. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0020] The present invention provides a method for reducing the concentration of goblet cells in an airway. The method includes inserting a scope and a balloon catheter into a target site in a body cavity that contains one or more goblet cells. The balloon catheter includes an elongated balloon and a coating layer covering the outer surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the inner surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. The drug released from the drug-coated balloon can reduce the concentration of goblet cells in the airway. Prior to inflation, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0021] The present invention provides a method for reducing the concentration of one or more mucins in an airway. Mucins are gel-forming glycoproteins in mucus plugs. Mucins are produced by mucus overproduction and hypersecretion in chronically inflamed airways. The method includes inserting a scope and a balloon catheter into a target site in a body cavity including the trachea, main bronchus, intermediate bronchus, and / or lobar bronchus. The balloon catheter includes an elongated balloon and a coating layer covering the exterior surface of the balloon. The coating layer includes one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method includes inflating the balloon to an inflated diameter such that the coating contacts the interior surface of the body cavity at the target site. The method includes deflating the balloon. The method also includes withdrawing the scope and balloon catheter from the target site. Prior to expansion, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0022] In various embodiments, the present invention provides a minimally invasive method for the treatment or prevention of recurrent stenosis or stenosis of the frontal sinus, ethmoid sinus, sphenoid sinus, maxillary sinus, nasal cavity, supraglottis, glottis, subglottis, trachea, main bronchi, intermediate trunk bronchi or lobar bronchi. The method includes inserting a catheter with an expandable body through a body lumen containing the recurrent stenosis or stenosis such that the expandable body is inside the stenosis or stenosis. The catheter with an expandable body may include a balloon catheter, a drug-coated catheter, a drug-eluting stent and / or a drug-eluting stent crimped to a drug-coated balloon. The catheter includes an expandable body with a coating layer or more than one layer including a therapeutic agent and one or more additives covering the outer surface of the expandable body of the catheter. The one or more additives are selected from one or more water-insoluble additives, slightly water-insoluble additives, partially water-soluble additives, water-soluble additives or combinations thereof. The method includes expanding the body to a specific diameter for a period of time to contact the coating layer with the stenosis or stricture in the body lumen. The method includes contracting the expanded body after a period of time and withdrawing the catheter from the treated stenosis or stricture. In some embodiments, the method further includes performing a surgical procedure for tissue expansion, resection or removal prior to insertion of the balloon catheter into the target site. Prior to expansion, the coating on the drug-coated balloon is hydrated and / or soaked to activate the coating.

[0023] An embodiment of the present invention provides a medical device coating formulation comprising a therapeutic agent or drug for the treatment of stenosis or narrowing in an airway body cavity and an additive that promotes the absorption of the drug into the tissue of the body cavity. An embodiment provides a coating covering an expandable portion of a catheter with a single or multiple layers that contain a single or multiple therapeutic agents. In an embodiment, the layer that contacts the expandable portion of the catheter does not have a therapeutic agent, and all or a substantial portion of the coating is formulated with a component that allows it to be transferred to the stenosis or narrowing upon expansion of the catheter. The cause of the stenosis or narrowing may include infection and inflammation caused by pathogens such as bacteria and viruses. In an embodiment, the coating may include an additive that has antibacterial and antiviral properties. In an embodiment, the layer of the coating that contains the therapeutic agent contains a drug that is crystalline, amorphous, or a combination thereof. In an embodiment, the layer of the coating that contains the therapeutic agent has at least one hydrophilic component and at least one hydrophobic component. In an embodiment, the coating layer includes a component that enhances the adhesion of the coating to the luminal surface of the expanded stenosis or narrowing. In some embodiments, the coating is formulated so that upon catheter expansion, the coating is transferred to the stenosis or stenosis as particles, condensed particles, dissolved substances, or combinations thereof. In some embodiments, the size of the transferred particles or condensed particles is small, less than 10 μm, or more preferably less than 5 μm.

[0024] In various embodiments, the present invention provides a catheter including an expandable elongate body portion for use in dilating recurrent airway stenosis or restenosis. In some embodiments, the elongate body is a cylindrical balloon. In some embodiments, the elongate body is a balloon having a shape or longitudinal profile that prevents the balloon from moving within the body cavity in which it is inflated.

[0025] Some embodiments of the present invention relate to balloon catheters with rapid drug release coatings and methods of use thereof for the treatment of airway stenosis or stenosis. The therapeutic agents according to some embodiments of the present invention do not require delayed or prolonged release; rather, the therapeutic agents and additives are released in the short term to provide a rapid therapeutic effect. The objective of some embodiments of the present invention is to facilitate rapid and efficient uptake of the drug by the target tissue during temporary device placement at the target site.

[0026] Various conventional treatments for severe asthma or chronic rhinosinusitis with nasal polyps (CRSwNP) require annual retreatment or continued retreatment for the patient's lifetime to avoid recurrence of the treated condition. However, in various embodiments of the present invention, the method can be effective to avoid recurrence of the treated condition for the patient's entire lifetime or for 3, 5, or 10 years, etc. [Brief description of the drawings]

[0027] Generally, the drawings illustrate by way of illustration, not by way of limitation, certain embodiments of various inventions.

[0028] [Figure 1A] According to various embodiments, a balloon catheter having one neck section is described.

[0029] [Figure 1B] According to various embodiments, a balloon catheter having two neck sections is described.

[0030] [Figure 1C] According to various embodiments, a balloon catheter having three neck sections is described.

[0031] [Diagram 2]Various embodiments of a dual-necked drug-coated balloon catheter are described that include a catheter shaft, a catheter tip, and a Tuohy-Borst adapter (balloon catheters include fixed-wire, over-the-wire, and rapid-exchange balloon catheters, which are not detailed in FIG. 2).

[0032] [Diagram 3] FIG. 3 is a perspective view of one embodiment of a balloon catheter of the present invention, according to various embodiments (balloon catheters include fixed-wire, over-the-wire, and rapid-exchange balloon catheters, not shown in detail in FIG. 3).

[0033] [Figure 4A-4C] 4A-4D are cross-sectional views of various embodiments of the distal portion of the balloon catheter of FIG. 3 taken along line AA, showing examples of coating layers according to various embodiments.

[0034] [Diagram 5] According to various embodiments, a drug coated balloon catheter over a guidewire is described.

[0035] [Figure 6] 1 hour paclitaxel concentrations in treated tissues according to various embodiments are described.

[0036] [Figure 7] 1 depicts paclitaxel concentration versus time according to various embodiments.

[0037] [Figure 8A] Test article treatment sites are depicted 28 days after treatment according to various embodiments.

[0038] [Figure 8B] Control article treatment sites after 28 days according to various embodiments are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Detailed Description of the Invention Details regarding particular embodiments of the disclosed subject matter are now described. While the disclosed subject matter will be described in conjunction with numbered claims, it is understood that the illustrated subject matter is not intended to limit the scope of the claims to the disclosed subject matter.

[0040] Throughout this document, values ​​expressed in the form of ranges should be interpreted in a flexible manner to include not only the numerical values ​​expressly set forth as limiting the range, but also all individual numerical values ​​or subranges contained within the range as if each numerical value and subrange were expressly set forth. For example, the range "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only exactly about 0.1% to about 5%, but also the individual values ​​(e.g., 1%, 2%, 3% and 4%) and subranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the range indicated. The description "about X to Y" has the same meaning as "about X to about Y" unless otherwise specified. Similarly, the description "about X, Y or about Z" has the same meaning as "about X, about Y or about Z" unless otherwise specified.

[0041] As used herein, the singular terms "a," "an," and "an" are used to include one or more than one, unless the context clearly indicates otherwise. The term "or" includes a non-exclusive "or" unless otherwise specified. The phrase "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B." Furthermore, it is understood that any phrases or terms used herein and not otherwise defined are for purposes of description only and not limitation. Any use of section headings is intended to aid in the interpretation of this document and should not be construed as limiting; information associated with a section heading may appear within or outside of a particular section.

[0042] In the methods described herein, the operations may be performed in the particular order described herein. Alternatively, in any embodiment disclosed herein, certain operations may be performed in any order without departing from the principles of the invention, unless a temporal or operational order is specified. Furthermore, certain operations may be performed simultaneously, unless the terms in the claims recite them separately or unless the plain meaning of the claims requires it. For example, a claimed operation to perform X and a claimed operation to perform Y may be performed simultaneously in one operation, and the resulting method will fall within the literal scope of the claimed method.

[0043] As used herein, the term "about" allows for a degree of variation in a value or range, e.g., within 10%, within 5%, or within 1% of a stated value or the limits of a stated range, and includes the exactly stated value or range.

[0044] As used herein, the term "substantially" refers to a majority or majority, such as at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99% or at least about 99.999% or more or 100%. As used herein, the term "substantially free" can mean free of the substance or an insignificant amount such that the amount of the substance present does not affect the properties of the composition containing the substance, e.g., from about 0 wt% to about 5 wt%, or from about 0 wt% to about 1 wt%, or about 5 wt% or less, or about 4.5 wt%, 4 wt%, 3.5 wt%, 3 wt%, 2.5 wt%, 2 wt%, 1.5 wt%, 1 wt%, 0.9 wt%, 0.8 wt%, 0.7 wt%, 0.6 wt%, 0.5 wt%, 0.4 wt%, 0.3 wt%, 0.2 wt%, 0.1 wt%, 0.01 wt%, or about 0.001 wt% of the composition is the substance.

[0045] Methods for Treating Recurrent Airway Stenosis or Stenosis in an Airway Lumen - Patent application The present invention provides a method for treating recurrent airway stenosis or stenosis in airway lumen. The method can open the lumen and prevent, reduce or minimize re-narrowing of the lumen and recurrent stenosis or restenosis. The method can prevent stenosis or stenosis recurrence or cause recurrence to occur less frequently and / or cause recurrence to be less severe compared to conventional treatment. Treatment can be performed on a variety of animals and humans, including premature infants to adults. In various embodiments, the present invention provides a minimally invasive method for treating or preventing recurrent stenosis of the upper and lower airways.

[0046] The cavity may be any suitable airway cavity that contains at least one recurrent stenosis or stricture. The cavity may include the frontal sinus, ethmoid sinus, sphenoid sinus, maxillary sinus, nasal cavity, supraglottis, glottis, subglottis, trachea, main bronchi, intermediate bronchi and / or lobar bronchi.

[0047] The recurrent stenosis or stenosis may be caused by any suitable condition. The recurrent stenosis or stenosis may be idiopathic. The recurrent stenosis or stenosis may be caused by a surgical procedure. The recurrent stenosis or stenosis may be caused by a congenital condition, trauma, inflammation, post-intubation tracheal stenosis, post-tracheotomy tracheal restenosis, post-tuberculous infection, transplant-related restenosis, repeated medication procedures, surgical removal, electrocautery, laser ablation, cryoablation, mechanical debulking, rigid bronchoscopic dilation, stent placement and / or balloon dilation. The recurrent stenosis or stenosis may be caused by bronchial smooth muscle cells, IL-4, IL-5, IL-6, IL-13, IL-23, ILC2, mucus plug, goblet cells, fibrosis, cystic fibrosis and / or one or more mucins. Stenosis or stenosis can include CRS stenosis, CRSwNP stenosis, nasal stenosis, severe asthma, comorbidities of CRSwNP, comorbidities of severe asthma stenosis, subglottic stenosis and / or stenosis, laryngeal stenosis, tracheal stenosis, bronchial stenosis, airway anastomosis stenosis and / or radiation-induced airway stenosis. In treating severe asthma, the method can reduce or weaken the smooth muscle in the wall of the treated bronchial airway to prevent or reduce recurrence of severe asthma. In various embodiments, the method can include at least two treatments of the trachea, main bronchi, intermediate trunk bronchi or lobar bronchi, and can include treatment of CRSwNP and severe asthma with one method. CRSwNP and severe asthma can be comorbidities, and treatment of one can benefit the other. Treatment of CRSwNP can reduce or eliminate recurrence of severe asthma, and vice versa.

[0048] The airway stenosis or narrowing may include chronic rhinosinusitis with nasal polyps (CRSwNP). The airway stenosis or narrowing may include laryngeal stenosis and / or subglottic stenosis or narrowing. The airway stenosis or narrowing may be narrowing or narrowing induced by repeated medication treatments, intubation, tracheotomy, tuberculosis infection, surgical removal, electrocautery, laser ablation, cryoablation, mechanical debulking, rigid bronchoscopic dilation, stent placement, and / or balloon dilation.

[0049] The method may include hydration and / or soaking of the coating prior to inflation of the drug-coated balloon. Hydration and / or soaking can be performed outside the body (e.g., using saline, water, or a combination thereof), during passage to the target site while in the body cavity, at the target site, or a combination thereof. Hydration and / or soaking during passage to the target site while in the body cavity or at the target site may include hydration and / or soaking with a flushing composition, a natural fluid that is native to the body cavity that is not added externally, or a combination thereof. In various embodiments, for lung tissue treatment, the method may include pre-soaking the coating prior to insertion into the target site. In various embodiments, for nasal tissue or other non-pulmonary tissue treatment, the method may include pre-soaking the coating prior to insertion into the target site, flushing the target site prior to insertion of the drug-coated balloon into the target site, or a combination thereof.

[0050] The method may include flushing the target site with a flushing composition comprising water and / or saline. The method may include inserting a scope and a balloon catheter into the target site. Flushing can be performed before and / or during insertion of the scope and balloon catheter into the target site. The balloon catheter may include an elongated balloon. The balloon catheter may also include a coating layer covering the exterior surface of the balloon. The coating layer may include one or more additives and an initial drug loading amount of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. The method may include hydrating and / or soaking the coating with the flushing composition at the target site. The method may include expanding the balloon to an inflated diameter such that the coating contacts the interior of the body cavity at the target site. The method may include deflating the balloon. The method may include withdrawing the scope and balloon catheter from the target site.

[0051] In various embodiments of the method, the method does not include damaging, dilating and / or removing the stenosis or stenosis prior to insertion of the drug-coated balloon catheter. In other embodiments that include damaging, dilating and / or removing the stenosis or stenosis prior to insertion of the drug-coated balloon catheter, the damaging, dilating and / or removing of the stenosis or stenosis can be performed using any suitable method. The damaging, dilating and / or removing of the stenosis or stenosis can include surgical removal, electrocautery, laser ablation, cryoablation, radiofrequency ablation, mechanical debulking, rigid bronchoscope dilation, knife cutting, open internal stenosis resection, use of an uncoated balloon for stenosis or stenosis dilation, or a combination thereof. The damaging, dilating and / or removing of the stenosis or stenosis can include inserting a pre-dilatation balloon into the body cavity at the target site prior to insertion of the drug-coated balloon catheter, inflating the pre-dilatation balloon and removing the pre-dilatation balloon. In some embodiments, the pre-dilatation balloon catheter has a cutting or scouring element on the balloon that is used to break up the calcified plaque. In some embodiments, the pre-dilation catheter may be shorter and / or smaller in diameter than the drug-coated balloon treatment catheter. In this scenario, the pre-dilation catheter is positioned so that the center of the balloon body coincides with the center of the stenosis or stenosis. Once inflated, the pre-dilation balloon is deflated and removed, and the drug-coated treatment balloon is inserted. The size of the drug-coated balloon is selected to have a larger balloon diameter and balloon length than the pre-dilation balloon catheter, ensuring that the drug coating contacts the entire lumen wall of the pre-dilated stenosis or stenosis.

[0052] The method includes inserting a balloon catheter through the nasal or oral cavity and tracking recurrent airway stenosis or stenosis. Inserting the scope and balloon catheter may include inserting the balloon catheter through a lumen of the scope. Inserting the scope and balloon catheter may include inserting the balloon catheter and the scope side-by-side. The method may include positioning the proximal end of the balloon of the scope and balloon catheter at or near the target site. The scope may be any scope suitable for use in a body cavity that includes the target site, such as an endoscope, a nasal laryngoscope, a nasal scope, a bronchoscope, a cystoscope, or combinations thereof. The scope may be a rigid scope or a flexible scope. The method may include visualizing placement of the balloon catheter at the target site with the scope. The method may include visualizing indentation and expansion of the target site with the scope. The method may include visualizing inflation with the scope. The method may include visualizing inflation of the balloon during inflation using the scope by the physician / user. The method may include the physician / user using a scope to visualize the balloon pushing inside the lumen as it expands, expanding the lumen wall. The method may include the physician / user using a scope to visualize apposition of the drug-coated balloon to the lumen to confirm completion and / or using a scope to prevent over-inflation of the treated lumen. The method may include the physician / user using a scope to visualize the degree of drug coverage of the target site after deflation via observation of drug deposited on the lumen wall to ensure completion.

[0053] Various embodiments of the method do not include flushing the target site before and / or during the balloon catheter insertion into the target site.In other embodiments that include flushing the target site before and / or during the balloon catheter insertion into the target site, the method can include inserting a balloon catheter through the nasal or oral cavity and flushing the target site before capturing recurrent airway stenosis or stenosis.The flushing composition can include water, saline or a combination thereof.In some embodiments, flushing can be performed before, during or after the balloon catheter is inserted into the target site. Hydration and / or soaking with the flushing composition may be performed for any suitable time, such as from about 0.1 minutes to about 20 minutes, or from about 0.1 minutes to about 10 minutes, or from about 0.1 minutes to about 5 minutes, or less than 20 minutes and from 0.1 minutes, 0.2 minutes, 0.3 minutes, 0.4 minutes, 0.5 minutes, 0.6 minutes, 0.7 minutes, 0.8 minutes, 0.9 minutes, 1 minute, 1.5 minutes, 2 minutes, 2.5 minutes, 3 minutes, 3.5 minutes, 4 minutes, 4.5 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 12 minutes, 14 minutes, 16 minutes, 18 minutes, or 19 minutes or more. In embodiments of the method that do not include flushing of the target site, the balloon catheter may be flushed or soaked prior to insertion (e.g., soaked and / or hydrated outside the body prior to insertion).

[0054] In some embodiments, the balloon is inflated until the coating layer contacts the wall of the stenosis or stenosis, the stenosis or stenosis is expanded, and the drug is transferred to the stenosis or stenosis at the same time.In some embodiments, the balloon is inflated until the coating layer contacts the wall of the stenosis or stenosis, the stenosis or stenosis is expanded and increases in diameter, so that the contact with the stenosis or stenosis can provide complete circumferential transfer of the drug to the wall of the stenosis or stenosis.In some embodiments, the part of the balloon that contains the drug (e.g., in embodiments that include less than 100% of the surface area covered with the drug) can be in uniform contact with the stenosis or stenosis.In other embodiments, the contact between various parts of the balloon surface and the stenosis or stenosis is non-uniform.

[0055] The inflated diameter of the balloon can be any suitable diameter achieved during or throughout the inflation period such that a desired ratio of inflated balloon diameter to body lumen diameter is achieved. The desired ratio can be in the range of 0.5 to 2.0 or greater than 0.5 and less than or equal to 0.75, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0. The inflated diameter of the balloon can be proportional to the pressure used to inflate the balloon during the inflation period. In some embodiments, the inflation pressure can be the nominal pressure of the balloon and the inflated diameter of the balloon can be approximately equal to the nominal diameter of the balloon or can be less than the nominal diameter of the balloon due to stenosis or restriction from a stenosis. In some embodiments, the inflation pressure of the balloon during the inflation period can be greater than or less than the nominal pressure and the inflated diameter of the balloon can correspond to, be greater than, or be less than the nominal diameter of the balloon.

[0056] The inflation may be performed sufficiently to achieve a particular stretch ratio. The stretch ratio is defined herein, unless otherwise specified, as the ratio of the nominal diameter of the balloon to the lumen diameter of the area to be treated with the balloon catheter. The nominal diameter of the balloon is the diameter of the balloon that is achieved at the nominal pressure in an unconstrained environment. The lumen diameter is the average diameter of the luminal stenosis or narrowing or lesion. The inflated balloon diameter is the actual diameter of the balloon after inflation, which in some embodiments may be equal to, smaller than, or larger than the nominal diameter of the balloon. In various embodiments, the stretch ratio allows the balloon catheter of the present invention to treat airway narrowing and narrowing more effectively than other catheters. During the practice of the method of the present invention, the stretch ratio may be selected to be any suitable ratio that achieves the desired ratio of the actual inflated balloon diameter to the lumen diameter at the range of pressures used during the method. In various embodiments, the stretch ratio of the balloon can be about 1.01 to about 20, 1.31 to 20, or about 1.01 to about 15, or about 1.1 to about 10, 1.2 to 10, 1.3 to 10, 1.31 to 10, 1.4 to 10, 1.5 to 10, 1.6 to 10, 1.7 to 10, 1.8 to 10, 2 to 10, 2.2 to 10, 2.5 to 10, or about 1.0 to about 40 (e.g., 40 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, or 38 or more); such stretch ratios are dependent on the pressure used during inflation. The force can result in a desired ratio of inflated balloon diameter to lumen diameter and can be the same as, similar to, or different from a stretch ratio such as about 1.01 to about 20, 1.31 to 40, or about 1.01 to about 15, or about 1.1 to about 10, 1.2 to 10, 1.3 to 10, 1.31 to 10, 1.4 to 10, 1.5 to 10, 1.6 to 10, 1.7 to 10, 1.8 to 10, 2 to 10, 2.2 to 10, 2.5 to 10, or about 1.0 to about 40 (e.g., 40 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, or 38 or more).

[0057] The inflation may be performed at least until the target site is indented and expanded. The inflation may be performed to provide a ratio of inflated diameter to nominal body lumen diameter at the target site of about 1.0 to about 20, such as 20 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 or more. The inflation may be performed to provide a ratio of inflated diameter to nominal body lumen diameter at the target site of about 1.0, 1.1, 1.2, or 1.31 to 10. The inflation may be performed to inflate the balloon to a pressure equal to or greater than the nominal pressure of the balloon. The inflation may be performed to provide a stretch ratio of inflated diameter of the balloon to nominal body lumen diameter at the target site of about 1.0 to about 20. The inflation can be performed such that the ratio of inflated diameter of the balloon to the nominal body lumen diameter at the target site is about 1.0, 1.1, 1.2 or 1.31 to 10 or about 1.0 to about 20, such as 20 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 or more. The inflation can be performed such that the ratio of inflated diameter to the nominal body lumen diameter at the target site is about 1.0 to 20 and such that the ratio of inflated diameter of the balloon to the nominal body lumen diameter at the target site is about 1.0 to about 20. The inflation can be performed such that the balloon is inflated to a pressure that exceeds the nominal pressure of the balloon and the nominal inflated diameter of the balloon is less than the inflated diameter.Cases (a) or (b) or (c) or (a) and (b) or (a) and (c) or (b) and (c) or (a) and (b) and (c) may exist: (a) the ratio of inflated balloon diameter to body lumen diameter at the target site is about 1.0 to about 40 (e.g., 40 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 or 38 or more); or (b) inflation causes the balloon to expand to a pressure equal to or greater than the nominal pressure of the balloon catheter. to a pressure of at least about 1.0 to about 40, wherein the stretch ratio of the nominal diameter of the balloon catheter to the diameter of the body lumen at the target site is about 1.0 to about 40 (e.g., 40 or less and 1, 1.1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, or 38 or more); or (c) the inflation includes inflating to at least a nominal pressure of the balloon catheter, wherein the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b), and (c). The inflation may include monitoring the pressure within the balloon (e.g., via a pressure gauge external to the patient). Inflating may include inflating the balloon to a first pressure, stabilizing the pressure within the balloon for a stabilization period while maintaining the balloon at the first pressure, and then resuming increasing the pressure in the balloon until the inflated diameter is achieved.

[0058] The method may include maintaining the inflated diameter for a suitable period of time. Maintaining the inflated diameter may include maintaining the inflated diameter at or above a particular desired diameter. The inflated diameter may be increased under consistent inflation pressure as long as the stenosis or stenosis collapses. The method may include maintaining the inflated diameter for 1 minute to 7 days, 1 minute to 1 day, 1 minute to 10 minutes or less than 7 days and 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 12 minutes, 14 minutes, 16 minutes, 18 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 1 day, 2 days, 3 days, 4 days, 5 days or more than 6 days. The method may include maintaining the expanded diameter for a period of time sufficient for a drug to be released into tissue at the target site and / or to prevent or reduce bleeding.

[0059] Balloon catheter The balloon catheter may include an elongated balloon. The balloon catheter may also include a coating layer covering the exterior surface of the balloon. The coating layer may include one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof.

[0060] Balloon catheters may include fixed wire balloon catheters, over-the-wire balloon catheters, rapid exchange balloon catheters, perfusion balloon catheters, double space balloons, cutting balloon catheters, scouring balloon catheters or infusion catheters (e.g., distal perforated drug infusion tubes, perforated balloons, double space balloons, porous balloons or wettable balloons).

[0061] The elongated balloon can have a length of about 20 mm to about 300 mm, or about 20 mm to about 160 mm, or less than about 300 mm, and about 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, 50 mm, 55 mm, 60 mm, 65 mm, 70 mm, 75 mm, 80 mm, 85 mm, 90 mm, 95 mm, 100 mm, 105 mm, 110 mm, 115 mm, 120 mm, 125 mm, 130 mm, 135 mm, 140 mm, 145 mm, 150 mm, 175 mm, 200 mm, 225 mm, 250 mm, 275 mm, or 290 mm or more.

[0062] The balloon may include a major diameter that is a nominal inflated diameter (e.g., nominal diameter) of at least 1 mm, or at least 5 mm, or at least 10 mm, or at least 13 mm, or at least 15 mm, or at least 20 mm, or at least 30 mm, or at least 35 mm, or 1-50 mm, 1-40 mm, or 1-30 mm, or 50 mm or less, and 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 8 mm, 10 mm, 12 mm, 14 mm, 16 mm, 18 mm, 20 mm, 22 mm, 24 mm, 26 mm, 28 mm, 30 mm, 32 mm, 34 mm, 36 mm, 38 mm, 40 mm, 42 mm, 44 mm, 46 mm, or 48 mm or more. For a balloon that includes a neck, the major diameter is the diameter of the large section of the balloon. The nominal diameter is determined by the nominal inflation pressure of the balloon, which is typically the diameter achieved at the nominal pressure in an unconstrained environment.

[0063] In some embodiments, the inflation pressure used to determine the major diameter can be any pressure that eliminates folded or wrinkled areas of the balloon and achieves tension on the balloon. The inflation pressure used to determine the major diameter can be such that the inflated balloon has a shape and size that corresponds to the desired shape and size of the balloon during treatment of the intended body cavity. The inflation pressure used to determine the major diameter can be the nominal pressure of the balloon such that the nominal diameter of the balloon catheter is equal to the major diameter of the balloon. In some embodiments, the inflated diameter of the balloon at the target site during inflation to the nominal pressure is equal to the nominal diameter; however, during actual use, some stenosis may prevent the nominal diameter from being achieved or may constrain the inflated balloon to form a "dog-bone" configuration. The balloon nominal diameter at the planned pressure (e.g., 2 atm, 3 atm, 6 atm, or 9 atm) may be different for balloons of different diameters for different diseases. For example, the nominal diameter of a sinus stenosis or stenosis balloon is 6mm, 8mm, 10mm, 12mm and 14mm for 6mm, 8mm, 10mm, 12mm and 14mm balloon catheters at 4atm, 5atm, 6atm, 8atm or 12atm inflation and balloon length 20mm, 25mm and 30mm. The nominal diameter of an airway stenosis or stenosis balloon is 25mm and 30mm for 2atm, 3atm, 4atm, 6atm or 9atm inflation and balloon length 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm, 55mm and 60mm balloon catheters. The nominal pressure is the pressure required to bring the balloon to its labeled nominal diameter in a non-restrictive pressure ramp test. The nominal diameter is the desired diameter that is labeled on the product. All physicians purchase and select balloons according to the nominal diameter. The rated burst pressure is the highest pressure to which the balloon can be inflated with a high degree of confidence that it will not burst, and is a required labeling requirement for balloon catheters, calculated from a statistical analysis of the pressure observed when the balloon bursts in an unrestrained pressure ramp test.

[0064] Examples of balloon catheter properties for treating recurrent airway stenosis or stenosis are shown in Table 1.

[0065] [Table 1]

[0066] In one embodiment, the balloon catheter has properties equal to or similar to those in Table 2, and is a single balloon catheter with the ability to achieve a wide range of balloon diameters at relatively high working pressures compared to conventional compliant balloons. The balloons in Table 2 have the unique property of three balloon diameter increases at three inflation pressure increases. The nominal inflated diameter is the diameter at Stage I. The diameter increase is about 0.5-4 mm, preferably 0.75-3 mm, and most preferably 0.9-2 mm, over all pressure stages. For example, a balloon with a diameter of 15 mm at Pressure I (3 atm) has a diameter of 16.5 mm at Pressure II (4.5 atm) and a diameter of 18 mm at Pressure III (7 atm).

[0067] [Table 2]

[0068] In various embodiments, the balloon catheter can be sufficient such that at a planned pressure (e.g., nominal pressure), for example, from about 1 atmosphere (about 101 kPa) to about 30 atmospheres (about 3040 kPa) (e.g., less than about 1 atmosphere or less than about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 28, or less than about 30 atmospheres), the balloon can have any suitable ratio of inflated balloon catheter diameter to body lumen diameter at the site of treatment.

[0069] The balloon catheter may include an elongated balloon and no other balloons, hi other embodiments, the balloon catheter may include more than one balloon.

[0070] The balloon may be substantially free of a neck section between the proximal and distal ends of the balloon. In other embodiments, the balloon may include at least one neck section on the balloon that includes a diameter smaller than the main diameter of the balloon when the balloon is inflated, and the at least one neck section divides the balloon into at least two main sections, each having a constant diameter. The neck section may include a central narrow section having a minimum diameter of the neck section and adjacent sections that may have various diameters and are between the central narrow section and the portion of the balloon having the main diameter. During inflation, the neck section in combination with the at least two main sections may together secure the balloon to a target site in the body cavity, helping to avoid slippage, thereby helping to avoid damage to healthy or unintended body cavities. In various embodiments, the one or more neck sections may allow the balloon catheter to remain more consistently and effectively during the procedure and deliver drugs for dilatation of stenosis or strictures, as compared to other balloon catheters that lack such neck sections or neck section placement. When the diameter of the neck section is described herein, it refers to the diameter of the central narrow portion having the smallest diameter, and not the tapered section, unless otherwise specified. The tapered section of the balloon can be rigid, flexible (e.g., elastic), or a combination thereof. The diameter of the at least two main sections can be equal to the main diameter of the elongated balloon, or at least one neck section has a diameter that is about 5% to about 99% of the diameter of at least one of the at least two main sections. At least one neck section can independently have a diameter that is about 5 mm to about 35 mm, or 1 mm to 40 mm, or 40 mm or less, and 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 8 mm, 10 mm, 12 mm, 14 mm, 16 mm, 18 mm, 20 mm, 22 mm, 24 mm, 26 mm, 28 mm, 30 mm, 32 mm, 34 mm, 36 mm, or 38 mm or more. The one neck section can be at any suitable location on the balloon, such as approximately centered relative to the balloon length or off-center relative to the balloon length. The one neck section can be off-center relative to the balloon length and can be at the distal end of the balloon.An embodiment of a balloon that includes one neck section that is off-center relative to the balloon length is depicted in FIG. 1A.

[0071] The diameter of the at least one neck section may remain substantially stationary during inflation of the balloon such that the neck section diameter remains substantially stationary during inflation of the balloon. The neck section may be a rigid or semi-rigid neck section. The at least one neck section may comprise a substantially inelastic (e.g., non-compliant or minimally compliant) portion of the balloon, a reinforced portion of the balloon, or a combination thereof. The at least one neck section may comprise an inelastic material around the neck section. The inelastic material may comprise a suture or a monofilament or multifilament of such material, such as nylon, polyamide, aromatic polyamide, ultra-high molecular weight polyethylene (UHMWPE), polyester, aromatic polyester, polyethylene terephthalate (PET), or a combination thereof.

[0072] The diameter of the at least two main sections can be from about 1 mm to about 50 mm, from about 1 mm to about 35 mm, from about 1 mm to about 30 mm, from about 1 mm to about 20 mm, or from about 5 mm to about 45 mm or less than 50 mm and from 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 8 mm, 10 mm, 12 mm, 14 mm, 16 mm, 18 mm, 20 mm, 22 mm, 24 mm, 26 mm, 28 mm, 30 mm, 32 mm, 34 mm, 36 mm, 38 mm, 40 mm, 42 mm, 44 mm, 46 mm, or 48 mm or more.

[0073] At least one neck section can be about 1% to about 50% or less than about 50% and more than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46% or 48% of the balloon length.

[0074] The at least one neck section may be one neck section and the balloon may not include the other neck section such that the balloon includes two main sections separated by one neck section. The at least one neck section may be two neck sections and the balloon may not include the other neck section. The two neck sections may have approximately the same diameter. One of the two neck sections may have a smaller diameter than the other neck section. The two neck sections may be located symmetrically or asymmetrically with respect to the center of the balloon length. The three main sections may have approximately the same length or may have different lengths. FIG. 1B describes an embodiment of a balloon catheter with two neck sections and three main sections, where the neck sections are located symmetrically with respect to the center of the balloon length and where the three main sections of the balloon have approximately the same length.

[0075] The balloon catheter may include three main sections separated by two neck sections. At least one neck section may be a three neck section, where the balloon does not include other neck sections. The three neck sections may be arranged to provide four main sections separated by three neck sections. The three neck sections may be arranged in any suitable manner along the length of the balloon. The four main sections formed by the three neck sections may have equal or different lengths. The three neck sections may have equal or different diameters. In some embodiments, two of the neck sections have equal diameters that are smaller than the diameters of the other neck sections. FIG. 1C illustrates an embodiment of a balloon catheter having three neck sections and four main sections, each having approximately equal lengths, where two of the neck sections have equal diameters that are smaller than the diameters of the other neck sections.

[0076] In some embodiments, the balloon neck section is semi-compliant and may expand at a different rate than the main balloon body. The neck section compliance may be higher, lower or equal to the compliance of the balloon body. Table 3 lists exemplary dimensions for a balloon having a neck section that expands more than the balloon body. The expansion rate of the neck diameter may be higher than the expansion rate of the main body section diameter at a test pressure range of 1-5 atmospheres. The expansion rate of the neck diameter may range from 1.1 to 10 times the main body section diameter (main diameter), for example, 2 to 6 times the main diameter, at a test pressure range of 1-5 atmospheres. The expansion rate of the neck diameter may be 12.38% per atmosphere. The expansion rate of the body diameter may be 2.4% per atmosphere. The difference in expansion rates may be 9.98% per atmosphere. Table 4 lists exemplary dimensions for a balloon having a neck section that expands less than the balloon body when inflated at 2 atmospheres to 4 atmospheres. The expansion rate of the neck diameter may be less than the expansion rate of the main body section diameter at a test pressure range of 2 atmospheres to 4 atmospheres.

[0077] [Table 3]

[0078] [Table 4]

[0079] The neck section can create a wedge of tissue between the larger diameter sections of the balloon that can keep the balloon in place. The larger section of the balloon cannot overcome the tissue barrier created by the neck section, and thus, a balloon with a neck section can prevent, reduce or minimize migration during inflation. The neck section placement can be designed such that the balloon facilitates maximum increase in static friction while maintaining treatment efficacy.

[0080] The balloon catheter may include a catheter shaft at a longitudinal end of the balloon, the catheter shaft including a lumen for delivering gas, liquid, or a combination thereof to the interior of the balloon. The balloon catheter may include an atraumatic coupe tip.

[0081] The balloon catheter may be a fixed-wire balloon catheter. The balloon catheter may be an over-the-wire balloon catheter. The balloon catheter may be a rapid-exchange balloon catheter. The outer shaft may be coupled to a proximal balloon neck (e.g., the proximal end of the balloon that is inserted into the body after distal end insertion), with a distal end of a tapered wire coupled to the distal neck of the balloon and a proximal end of the wire coupled to a hub (e.g., a valve, connector, or adapter) at the proximal end of the balloon catheter and the outer shaft. The balloon catheter may be a moveable wire catheter. The outer shaft is coupled to a proximal balloon neck, with a distal end of the tapered wire coupled to the distal neck of the balloon, and the proximal end of the wire is free to move relative to the hub at the proximal end of the balloon catheter. The balloon catheter may be an over-the-wire balloon catheter. The balloon catheter may be a rapid-exchange balloon catheter. The balloon catheter may include a catheter shaft at a longitudinal end of the balloon (e.g., the proximal end of the balloon that is inserted into the body after distal end insertion), with the catheter shaft including a lumen for delivering air, liquid, or a combination thereof to the interior of the balloon. The catheter shaft may comprise a thermoplastic material, such as a high durometer material, thermally bonded (e.g., bonded by heating or melting) to the balloon, such as a material similar or identical to the balloon material, such as polyamide, nylon (e.g., nylon 6,6 or nylon 12), polyether block amide (PEBA), 70D polyether block amide (PEBA), 72D polyether block amide (PEBA), 74D polyether block amide (PEBA), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyester, polyurethane, derivatives thereof, or combinations thereof. In some embodiments, the catheter shaft may be a scope (e.g., a cystoscope). The high durometer material may help prevent, reduce, or minimize shattering and may allow for pushability and flexibility. The catheter shaft outer diameter may be sized to allow passage through the working channel of the scope.A fluid connection between the lumen and the interior of the balloon may be included, such as a hole in the catheter shaft below the balloon attachment point to allow inflation of the balloon by injection of a medium through the lumen.

[0082] The catheter shaft at the end that remains outside the body (e.g., the proximal end) may include a hub (e.g., a valve, connector, or adapter) that provides a connection to the lumen of the catheter shaft. During inflation, the hub (e.g., when closed or at all times) may prevent backflow of fluid or air from the balloon. The hub may include any suitable valve, such as a Touhy-Borst adapter. A Touhy-Borst adapter is a compression sealing device that can cover and clamp the catheter shaft to provide a fluid-tight / air-tight connection to the catheter shaft lumen. A one-way stopcock allows for control of the flow rate to the balloon and may be connected to an inflation device via a standard luer.

[0083] The proximal side of the catheter shaft may include a hub or any other connection manifold for connection through the catheter to inject fluids, air or other gases to inflate the balloon, allow passage of a guidewire, allow urine drainage, or any other suitable connection to the catheter shaft. Connection to the hub or connection manifold may be through any suitable one or more connections, such as a single female or male Luer hub or a Luer manifold with multiple channels. The hub or manifold may be made of any suitable material, such as polycarbonate, acrylonitrile butadiene styrene, nylon, Pebax, etc. (登録商標)The hub may be constructed of any suitable biocompatible material, such as cellulose, silicone, any other polymeric material that can be molded, or a combination thereof. The hub may be connected to the catheter in any suitable manner, such as using an adhesive (e.g., cyanoacrylate adhesive, silicone adhesive, epoxy, any other adhesive suitable for the substrate, or a combination thereof) or using chemical bonding. The hub or manifold may be overmolded onto the catheter shaft and fused directly to the catheter shaft. The catheter shaft may include a strain relief member at the connection between the catheter shaft and the hub or manifold. The strain relief member may help prevent kinking. The strain relief member may include polyolefin, PET, FEP, other heat shrink materials, or a combination thereof. The strain relief member may be heat shrunk. The strain relief member may be a flexible molding that interfaces with the hub (e.g., the strain relief member may be connected to the hub).

[0084] The balloon catheter may include a catheter tip at the distal end that is inserted into the body first at the longitudinal end of the balloon. The catheter tip may facilitate passage of the balloon through the body cavity. The tip may be an atraumatic tip that helps prevent damage to the body cavity during insertion. The tip may be a coude atraumatic tip. An atraumatic coude tip is designed to facilitate passage of the catheter through bends in the body cavity while preventing damage to the cavity wall during tracking. The tip may be a low durometer biocompatible material overmolded onto the catheter shaft or adhesively bonded to the shaft. For example, the coude tip may be made of Pebax. (登録商標) Or it may be formed from liquid silicone rubber.

[0085] FIG. 2 illustrates an embodiment of a balloon catheter including a catheter shaft, catheter tip, and a Touhy-Borst adapter / plug assembly. All materials may be biocompatible. The balloon is coated with a paclitaxel solution, but may be coated with any of a number of other drugs or biologics that may promote improvement of BPH symptoms. In FIG. 2, only the proximal two main sections of the balloon are coated with drug.

[0086] The balloon catheter may include an inflation device including a pressure gauge or pressure sensor that is fluidly connected to a catheter shaft that is connected to the balloon catheter. The gauge or sensor may be used to monitor and / or monitor the pressure of the balloon during inflation.

[0087] The balloons shown in Figures 1A, 1B, 1C and 2 may be blown into a mold containing a main section and a neck section. A tube of balloon material is blown into a mold having the desired shape. The balloon material tube may be pre-stretched. The balloon mold has a shape corresponding to the balloon shown in FIG. 1A, 1B, 1C or 2. For a balloon catheter with one neck, it includes a proximal cone, at least one main body section, at least one neck section, at least one further main body section and a distal cone. The balloon material may be polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, Pebax, etc. (登録商標)The balloon catheter shaft may be made of any of the following materials: polyurethane and block copolymers of polyether and polyester. The tube and mold are heated to a temperature above the glass transition temperature of the tube of balloon material and pressurized with gas, air, fluid, etc., so that the material of the tube takes the shape of the mold. The formed balloon is then cooled and trimmed, and is ready for connection to the catheter. The balloon catheter shaft may be made of any other semi-flexible to non-flexible polymer, including polyether-amide block copolymers, polyamide, nylon, polyester, polyethylene terephthalate, or blends thereof. The balloon catheter shaft may be made using rigid materials, such as stainless steel, polycarbonate, titanium, PEEK (polyether ether ketone), or any other rigid biocompatible material. The balloon catheter shaft may include polyamide, nylon (e.g., nylon 6,6 or nylon 12), polyether block amide (PEBA) (e.g., 35D PEBA, 55D PEBA, 72D PEBA, or 74D PEBA), polyurethane, silicone, rubber, other thermoplastic polymers, or combinations thereof. The catheter shaft may be homogenous in composition or may include a combination of materials distributed over one or more portions of the catheter shaft. The catheter shaft may be an extruded catheter shaft. In some embodiments, the catheter shaft may include an elongated rigid portion, such as a rod, mandrel, or wire, aligned longitudinally with the catheter shaft.

[0088] After the balloon is attached to the catheter, the balloon can be inflated at low pressure and a neck section reinforcement can be attached to the neck region. The neck section reinforcement is used to control the expansion of the neck section during balloon inflation. The neck section can be a substantially inelastic portion of the balloon, a reinforced portion of the balloon, or a combination thereof. The neck section can include an inelastic material wrapped around the neck section, such as a suture or a monofilament or multifilament of such material, such as steel, stainless steel, nitinol, tungsten, aluminum, copper, silver, gold, platinum, iridium, nickel (Ni), chromium (Cr), aluminum (Al), titanium (Ti), molybdenum (Mo), tungsten (W), niobium (Nb), tantalum (Ta) and cobalt (Co), nylon, polyamide, aromatic polyamide, ultra-high molecular weight polyethylene (UHMWPE), polyester, aromatic polyester, polyethylene terephthalate (PET), or a combination thereof. In some embodiments, the polymeric material is in the form of a thread or fiber that is wrapped around the neck section several times and then secured in place using two or more points of glue or adhesive.

[0089] The main sections of the balloon may be formed with the same or similar diameters. In some embodiments, the diameters of the various main sections may differ from each other by as much as 30% when measured at the nominal balloon diameter. In Figures 1A, 1B, 1C and 2, the main sections of the balloon are shown with equal diameters, i.e., the diameter of each main section is constant. In practice, at higher pressures, the diameter of the main sections curves slightly in that the diameter of the central part of the main section may be slightly larger than the end of the main section near the balloon cone and / or near the neck section.

[0090] In embodiments in which the balloons shown in Figures 1A, 1B, 1C and 2 have a neck and main section and in which the balloon shown in Figure 3 does not have any neck section, after the balloon catheter is assembled, the balloon may be coated with at least one water soluble additive and drug as described herein. In some embodiments in which the balloon has multiple main sections, the distal main section may not be coated. The balloon may be coated in the manner described herein. If a sheath is used, it may be placed over the balloon after the balloon is coated. The catheter may then be packaged, sterilized and labeled as known in the art.

[0091] The balloon catheter may be any suitable catheter for a desired application, including conventional balloon catheters known to those of skill in the art. For example, as shown in FIG. 3, the balloon catheter 10 may include an expandable, inflatable balloon 12 at a distal end of the catheter 10, a handle assembly 16 at a proximal end of the catheter 10, and an elongated flexible section 14 extending between the proximal and distal ends. The handle assembly 16 may be connected to and / or receive one or more suitable medical devices, such as a source of inflation media (e.g., air, saline, or contrast media). The flexible section 14 may be a tube made of a suitable biocompatible material and having one or more lumens. At least one of the lumens is configured to receive an inflation media and pass such media through the balloon 12 for inflation thereof. The balloon catheter may be a rapid exchange or over-the-wire catheter and may be made of any suitable biocompatible material. Materials for the balloon 12 include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, Pebax, and the like. (登録商標) , polyurethanes and block copolymers of polyether and polyester.

[0092] After deflation and withdrawal from the target site, the balloon catheter may contain a residual drug amount that is less than 100 wt% of the initial drug load. After deflation and withdrawal from the target site, the balloon catheter may contain a residual drug amount that is less than about 70 wt% of the initial drug load or about 0 wt% to about 99 wt%, or 1 wt% to 90 wt%, 5 wt% to 90 wt%, 10 wt% to 90 wt%, or 99 wt% or less of the initial drug load and 0 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 22 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 37 wt%, 38 wt%, 39 wt%, 40 wt%, 41 wt%, 42 wt%, 43 wt%, 44 wt%, 45 wt%, 46 wt%, 47 wt%, 48 wt%, 49 wt%, 50 ... %, 20wt%, 25wt%, 30wt%, 35wt%, 40wt%, 45wt%, 50wt%, 55wt%, 60wt%, 65wt%, 70wt%, 72wt%, 74wt%, 76wt%, 78wt%, 80wt%, 81wt%, 82wt%, 83wt%, 84wt%, 85wt%, 86wt%, 87wt%, 88wt%, 89wt%, 90wt%, 91wt%, 92wt%, 93wt%, 94wt%, 95wt%, 96wt%, 97wt% or 98wt% or more.

[0093] The initial drug load is about 1 microgram to about 20 micrograms of therapeutic agent per square millimeter of the balloon, or about 2 to about 6 micrograms of therapeutic agent per square millimeter of the balloon, or about 20 micrograms / mm 2 Less than or equal to about 1 microgram / mm 2 , 2 micrograms / mm 2 , 3 micrograms / mm 2 , 4 micrograms / mm 2 , 5 micrograms / mm 2 , 6 micrograms / mm 2 , 7 micrograms / mm 2 , 8 micrograms / mm 2 , 9 micrograms / mm 2 , 10 micrograms / mm 2 , 11 micrograms / mm 2 , 12 micrograms / mm 2 , 13 micrograms / mm2 , 14 micrograms / mm 2 , 15 micrograms / mm 2 , 16 micrograms / mm 2 , 17 micrograms / mm 2 , 18 micrograms / mm 2 , 19 micrograms / mm 2 It could be more than that.

[0094] The weight ratio of the therapeutic agent in the coating layer to the total weight of the one or more additives in the coating layer can be about 0.05 to about 20, about 0.5 to about 8, about 2 to about 6 or about 20 or less and about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or 19 or more. The drug coating may be any suitable percentage of the balloon's exterior surface (e.g., percentage of the balloon surface taken at its major diameter during inflation to nominal pressure, excluding the neck and end cones), such as about 1% to about 100%, or about 50% to about 100%, to about 80% to about 100%, or less than about 10%, or less than, equal to, or greater than 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or about 100%. Can be covered.

[0095] The balloon catheter may further include a sheath covering the elongate balloon. The method may include removing the sheath prior to inflation.

[0096] The catheter shaft, balloon, or combination thereof may include single or multiple markings along their length to aid in placement and alignment with a particular anatomical structure. The markings may have any suitable orientation, such as circumferential or longitudinal along the catheter shaft or balloon. Markings on the catheter shaft or balloon may be used to aid in balloon placement at a target site, indicate when the balloon is fully retracted into the sheath, or to place the device within the patient's anatomy. The markings on the catheter shaft may be visible using a scope or with the naked eye, or may include a radiologically identifiable component, such as a radiopaque material. The markings may be made of a thermally bonded polymer, by pad printing, laser marking, or any other method, on the surface of the catheter shaft in a distinguishable color.

[0097] 4A-4C are cross-sections taken along line AA of various embodiments of the distal balloon partial catheter of FIG. 3, showing examples of coating layers. In some embodiments, the balloon may optionally include an adhesive layer. For example, as shown in the embodiment depicted in FIG. 4A, balloon 12 is coated with layer 20 containing therapeutic agents and additives. In some embodiments, the layer consists essentially of therapeutic agents and additives, e.g., the layer contains only therapeutic agents and additives without any other materially significant elements. In some embodiments, the device may optionally include an adhesive layer. For example, as shown in the embodiment depicted in FIG. 4B, balloon 12 is coated with adhesive layer 22. Layer 24 containing therapeutic agents and additives covers the adhesive layer. The adhesive layer separating the layers below the drug coating layer helps adhere the drug coating layer to the outer surface of the medical device and protects the integrity of the coating. For example, if the drug and additive have different adhesion to the balloon, the adhesive layer can prevent abnormal loss of these components during delivery to the target site for therapeutic intervention and maintain the drug-to-additive ratio in the coating. Additionally, the adhesive layer may function to facilitate rapid release of the coating layer components from the device surface upon contact with tissue at the target site. In other embodiments, the device may include a top layer. For example, as shown in the embodiment depicted in FIG. 4C, balloon 12 is coated with adhesive layer 22, layer 26 containing therapeutic agents and additives that cover the adhesive layer, and top layer 28. The top layer may reduce loss of the drug layer before the drug layer contacts the target tissue, for example during transportation of balloon 12 to the intervention site or during the initial moment of inflation of balloon 12 before coating layer 20 is pressed into direct contact with the target tissue.

[0098] Therapeutic Agents The balloon catheter may include a coating layer covering the outer surface of the balloon. The coating layer may include one or more additives and an initial drug loading amount of a therapeutic agent. The coating layer may be a single layer or the coating layer may include two or more layers. The coating layer may include one therapeutic agent or more than one therapeutic agent. The therapeutic agent may be in direct contact with the outer balloon surface, and the balloon may include a coating between the therapeutic agent and the outer balloon surface, such as a layer including one or more additives.

[0099] The therapeutic agent may be a hydrophobic therapeutic agent, an anti-inflammatory drug, and / or an anti-proliferative drug. The therapeutic agent may be in any suitable physical state, such as molecular distribution, crystalline form, or cluster form. The therapeutic agent may include lipophilic substantially water-insoluble drugs, such as paclitaxel, rapamycin, daunorubicin, doxorubicin, rapachone, vitamins D2 and D3, and their analogs and derivatives. The therapeutic agent may include paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, mTOR inhibitors (i.e., a group of drugs that inhibit the mechanistic target of rapamycin), analogs thereof (i.e., analogs of any of the above members), or combinations thereof. The therapeutic agent may be in any suitable form, such as crystalline, partially crystalline, amorphous, partially amorphous, or combinations thereof. In some embodiments, the therapeutic agent may have a particle size of 0.2 microns to 10 microns, or preferably 0.5 microns to 5 microns. In some embodiments, the therapeutic agent is at least 75 wt% crystalline or at least 90 wt% crystalline. In other embodiments, the drug is substantially amorphous with little or no molecular orientation. Techniques for determining whether a drug is crystalline or amorphous include powder x-ray diffraction (pXRD), modulated differential scanning calorimetry (mDSC), or confocal Raman spectroscopy.

[0100] In some embodiments, the one or more additives may partially or completely encapsulate the therapeutic agent, for example, the particle size of the therapeutic agent encapsulated in the one or more additives may be from 0.7 microns to 15 microns.

[0101] Therapeutic agents may include budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, mometasone furoate, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, betamethasone, triamcinolone acetonide, or combinations thereof. Therapeutic agents may include bronchodilators or vasoconstrictors. Therapeutic agents may include terbutaline, albuterol, ipratropium, pirbuterol, epinephrine, salmeterol, levalbuterol, formoterol, or combinations thereof.

[0102] In various embodiments, combinations of therapeutic agents can be used. Different drug combinations have different therapeutic mechanisms and therefore can have additive effects. For example, therapeutic agents can include combinations of paclitaxel and rapamycin, combinations of paclitaxel and active vitamin D, combinations of paclitaxel and rapachone, combinations of rapamycin and active vitamin D, combinations of rapamycin and rapachone or combinations thereof. In various embodiments, the additive effect of therapeutic agents can reduce the dose of one or more therapeutic agents, and reduce or prevent complications caused by high doses of one or more therapeutic agents.

[0103] In various embodiments, the therapeutic agent is a polymer-encapsulated drug particle.

[0104] Additives The balloon catheter may include a coating layer covering the outer surface of the balloon. The coating layer may include one or more additives and an initial drug load of a therapeutic agent.

[0105] The one or more additives may include one or more water insoluble additives. The one or more additives may include one or more slightly water insoluble and / or partially water insoluble additives. The one or more additives may include one or more water soluble additives. The one or more additives may include a) one or more water soluble additives and b) one or more water insoluble or partially water insoluble additives.

[0106] The one or more additives may be pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, N-acetylglucosamine, N-octyl-D-gluconamide, N-nonanoyl-N-methylglucamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerebroside, sphingomyelin, galacrocerebroside, lactate, Cerebrosides, N-Acetyl-D-Sphingosine, N-Hexanoyl-D-Sphingosine, N-Octanoyl-D-Sphingosine, N-Lauroyl-D-Sphingosine, N-Palmitoyl-D-Sphingosine, Sphingosine, Polyethylene Glycol (PEG) Caprylic / Capric Diglyceride, PEG-8 Caprylic / Capric Glyceride, PEG Caprylate, PEG-8 Caprylate, PEG Caprate, PEG Caprate The glyceryl monophosphate may be selected from the group consisting of glyceryl monocaprylate, glyceryl monocaprate, glyceryl monocaproate, monolaurin, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthosine, xanthosine monophosphate, caffeine, allantoin, (2-hydroxyethyl)urea, N,N'-bis(hydroxymethyl)urea, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof. The one or more additives may include pentaerythritol ethoxylate, pentaerythritol propoxylate, or a combination thereof. The one or more additives may include butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), derivatives thereof, and / or combinations thereof. The one or more additives may include a polymer. In various embodiments, the therapeutic agent may include a polymer-encapsulated drug particle.

[0107] The coating layer covering the outside of the balloon may include one or more water-soluble additives (e.g., a water-soluble first additive, a water-soluble second additive, and a water-soluble third additive). The water-soluble additives may include a first water-soluble additive that is a surfactant, such as PEG sorbitan monolaurate, PEG sorbitan monooleate, or a combination thereof. The water-soluble additives may include a second water-soluble additive that is a compound having one or more moieties that are hydroxyl, amine, carbonyl, carboxyl, or ester, such as sorbitol, sorbitan, xylitol, gluconolactone, or a combination thereof. The coating layer may include both a first water-soluble additive and a second water-soluble additive. In some embodiments, the distal end of the balloon may not include a therapeutic agent.

[0108] In some embodiments, the additive is a surfactant and at least one compound.

[0109] In some embodiments, the coating with the therapeutic agent has at least one water-soluble component and at least one water-insoluble or partially water-soluble component, and the coating releases the balloon to an aqueous medium within 30 seconds without condensation particles or individual particles larger than 20 μm. In some embodiments, the released coating has particles or condensation particles smaller than 10 μm or preferably particles smaller than 5 μm.

[0110] In some embodiments, the one or more additives can enhance the release of the therapeutic agent from the balloon. The additives can enhance the penetration and absorption of the therapeutic agent in tissue. The additives can have a water and ethanol solubility of at least 1 mg / mL, and the therapeutic agent can be water insoluble.

[0111] The coating covering the balloon surface may include a therapeutic agent and at least two additives, each of which includes a hydrophilic portion and a drug affinity portion, where the drug affinity portion is at least one of a hydrophobic portion, a portion having affinity for the therapeutic agent through hydrogen bonding, and a portion having affinity for the therapeutic agent through van der Waals interactions, and each additive is soluble in a polar organic solvent and soluble in water. In one aspect of this embodiment, the polar organic solvent is selected from methanol, ethanol, isopropanol, acetone, dimethylformamide, tetrahydrofuran, methyl ethyl ketone, dimethyl sulfoxide, acetonitrile, ethyl acetate, and chloroform, and mixtures of these polar organic solvents with water. In another aspect of this embodiment, the balloon further includes a top layer covering the surface of the layer covering the outer surface of the balloon to reduce drug loss during transport through the body to the target tissue.

[0112] The one or more additives can facilitate rapid drug elution at the site of the stenosis or stenosis and excellent penetration of the drug into the tissue. Thus, coatings according to certain embodiments of the invention provide enhanced rate and / or extent of absorption of the antiproliferative therapeutic agent at the airway stenosis or stenosis. In certain embodiments of the invention, the coated device delivers the antiproliferative therapeutic agent to the airway stenosis or stenosis during very short deployment times of less than 10 minutes, less than 2 minutes, reducing restenosis and recurrence of stenosis of non-vascular body lumens.

[0113] The additives, such as water insoluble or slightly or partially water insoluble additives, may be selected from cholesteryl acetate, cholesteryl phenylacetate, cholesteryl laurate, cholesteryl palmitate, cholesteryl stearate, cholesteryl n-valerate, cholesteryl benzoate, cholesteryl heptanoate, cholesteryl decylate, cholesteryl caproate, cholesteryl oleate, cholesteryl oleyl carbonate, cholesteryl linoleate, cholesteryl pelargonate, cholesteryl erucate, cholesteryl caprylate, 5-α-cholestane, 5α-cholestan-3-one. The water-insoluble or slightly or partially water-insoluble first additive having an alkyl fatty group is selected from the group consisting of alkyl glyceryl ethers, monoglycerides of C8-C12 fatty acids, alkyl alcohols, alkyl ethers, alkyl esters, caprylic acid, monocaprylin, capric acid, monocapric acid, lauric acid, dodecylglycerol, butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienol, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid. , alpha-linolenic acid, gamma-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di- or triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, alpha tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobees, niosomes and derivatives and combinations thereof.

[0114] Additives such as water soluble second additives include polyethylene glycol (PEG)-cholesteryl sebacate, polyoxyethanyl α-tocopheryl sebacate, methylated polyethylene glycol cholesterol (mPEG cholesterol), polyethylene glycol cholesterol, PEG amide ester cholesterol, PEG amide ether cholesterol, mPEG amide ester cholesterol, PEG amide ether cholesterol, DSPE-PEG-cholesterol, PEGylated phospholipids, methylated PEGylated phospholipids, PEG capryl / Capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG caprate, PEG caproate, PEG-20 sorbitan monolaurate (Tween-20), PEG-20 sorbitan monopalmitate (Tween-40), PEG-20 sorbitan monostearate (Tween-60), PEG-20 sorbitan monooleate (Tween-80), PEG laurate, PEG oleate, PEG stearate, PEG glyceryl laurate, and PEG-30 glyceryl oleate.

[0115] In some embodiments, the one or more additives include a first additive that includes a water-insoluble or slightly or partially water-insoluble additive that includes at least one alkyl aliphatic group or cholesteryl group with a molecular weight of 50 to 750. One or more of the additives, such as the water-insoluble additives, in the coating may have a lower melting temperature than the pure form. One or more of the additives, such as the water-insoluble additives, in the coating may have a lower crystallinity than the pure form. One or more of the additives, such as the water-soluble additives, may be more hydrophilic or water-soluble than the water-insoluble or slightly or partially water-insoluble additives in the coating. The water-soluble additives may include polyethylene glycol (-(CH2CHO)-) units with a molecular weight ranging from 750 to 100,000 or 750 to 50,000 or 750 to 10,000. EXAMPLES

[0116] The device used was a 0.035" guidewire compatible over-the-wire catheter with a tapered atraumatic tip. The distal end of the catheter had a semi-compliant inflatable balloon coated with a proprietary coating containing the drug paclitaxel and a carrier that facilitates drug transfer to the airway wall upon inflation. The drug coating only coated the balloon body. The device had two radiopaque marker bands that indicated the drug coated working length of the balloon under fluoroscopy. The device was provided sterile and is intended for single use only. Figure 5 illustrates the device and Table 5 summarizes the device specifications.

[0117] [Table 5]

[0118] The amount of drug applied to the surface of the maximum DCB (12.9 mg for 18 × 65 DCB) was 333 mg paclitaxel / adult male (175 mg paclitaxel / m 2 and male body surface area 1.9 m 2 This is estimated to be approximately 30 times lower than a typical chemotherapy systemic injection dose of 1.5 μg paclitaxel / mm of balloon surface. 2 Table 6 details the drug delivery amount per balloon size.

[0119] [Table 6]

[0120] Two preclinical studies are described in Examples 1 and 2. A total of 10 sheep were treated with the device to explore product design feasibility and procedural safety in these anatomical structures.

[0121] Short-term preclinical study #1 was a short-term study conducted in one surviving sheep to determine short-term drug transfer and to further refine bronchoscopic access techniques, device compatibility and tissue sampling methods.

[0122] Long-term preclinical study #2 was a long-term (28-day) study in 9 sheep to evaluate gross pathology at the treatment site, plasma, treatment site and organ pharmacokinetics, and to evaluate the overall health of the animals during the 28-day survival phase of the study. Animal safety, device performance, and treatment course were combined with the animals' overall health, weight gain over time, treatment site, plasma, downstream and organ paclitaxel pharmacokinetics, gross pathology and histology, etc. The results and conclusions from these studies are summarized in Examples 1 and 2 herein. In Examples 1 and 2, the drug-coated balloons were soaked prior to treatment to activate the drug coating.

[0123] Examples 3 and 4 describe short-term and long-term studies in nasal tissues of five live sheep. In Examples 3 and 4, the nasal treatment site was flushed with a solution that was saline or water, a balloon catheter was inserted into the nasal treatment site, the balloon catheter was soaked at the site to hydrate and activate the drug coating at the treatment site, and then inflated. The drug-coated catheter was inflated at the target site for 3-5 minutes.

[0124] Example 1. Short-term preclinical study #1 Acute drug transfer was measured in acute preclinical study #1. Figure 6 shows the 1-hour paclitaxel drug concentration in treated tissues. Figure 6 shows that paclitaxel can be successfully delivered to the trachea and bronchi on a drug-coated balloon.

[0125] Example 2. Long-term preclinical study #2 Overall health of the animal (moribund) All evaluations suggested that the general health of the animals remained good throughout the study period. There were no deaths or major adverse events affecting animal health or welfare.

[0126] Treatment site (tracheobronchial) paclitaxel pharmacokinetics Animals were sacrificed on days 7, 14, and 28. At the time of sacrifice, one animal from each time point was used for pharmacokinetic data and each treatment site in the tracheobronchial tree was excised and assayed for paclitaxel by HPLC-MS.

[0127] FIG. 7 shows that paclitaxel is delivered to tissues at the time of treatment, and then the paclitaxel concentration decreases over time. In Examples 1 and 2, the drug-coated balloon catheters were immersed and / or hydrated in water or saline solution outside the body for 90 seconds, and then the balloon catheters were inserted into the target sites of the trachea and bronchial airways. The target sites of the trachea and bronchial airways were not flushed. On day 28, low levels of paclitaxel were present in the tissues at the treatment sites. In the treated tissues, T max 1 hour, C max The mean tissue drug level was 3.4 ng / g on day 28. The data shown in Figure 7 are summarized in Table 7.

[0128] [Table 7]

[0129] Day 28 focal and non-target organ histopathology FIG. 12A depicts an SEM image of a test article treated site 28 days after treatment. FIG. 12B depicts an SEM image of a control article treated site 28 days after treatment. There was no thrombosis, no epithelial loss, no submucosal hemorrhage, and no necrosis at the treatment sites. The airway lumen remained patent without airway wall collapse. As expected after paclitaxel treatment, submucosal inflammation, smooth muscle loss, submucosal fibrosis, and adventitial fibrosis were more common in test animals than in control animals. This is consistent with a healing response after paclitaxel exposure. Under SEM, airways from test animals were >90% covered with ciliated epithelial cells at 28 days, compared to 51%-90% coverage in airways from control animals.

[0130] No microscopic morphologic abnormalities were observed in the heart, liver, spleen, kidney, or downstream lung tissues. All of these tissues appeared normal, with no device-related findings during gross necropsy breadloafing and histopathologic evaluation.

[0131] Overall Preclinical Study Conclusions The following conclusions were drawn from preclinical studies: drug was successfully delivered to the treatment site; drug concentrations at the treatment site decreased over time to low levels at 28 days; drug concentrations in non-target organs were below the limit of quantification at 28 days; drug concentrations in plasma were below the limit of quantification at 7 days; there were no gross or histologic findings of tracheobronchial tree toxicity due to the treatment; in all test animals, the tracheobronchial tree remained patent and the test animals were able to behave normally as indicated by animal findings; and the performance of the DCB was acceptable and capable of tracking, inflation, deflation, and withdrawal for all treatments. No major safety concerns have arisen in any of the preclinical studies performed to date with overdosing of 10-12 treatments per animal, and no device-related adverse reactions have been identified.

[0132] Acute preclinical studies: nasal tissue Acute drug transfer in nasal tissue was measured using 10x30 balloon. Table 8 shows the 2-hour paclitaxel drug concentration in treated tissue (nasal side (Tx2)). Table 8 shows that paclitaxel can be successfully delivered to nasal tissue on drug-coated balloon.

[0133] [Table 8]

[0134] Long-term preclinical trials: nasal tissue Table 9 shows the results of the chronic preclinical studies. Nasal cavity Tx1 was the superior nasal cavity, nasal cavity Tx2 was the lateral nasal cavity, and nasal cavity Tx3 was the anterior and inferior nasal cavity.

[0135] [Table 9]

[0136] The terms and expressions used herein are used for the purpose of description and not limitation, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described herein or portions thereof, but rather it is recognized that various modifications are possible within the scope of certain embodiments of the present invention.Thus, although the present invention has been specifically disclosed by specific embodiments and optional features, it should be understood that modifications and variations of the concepts disclosed herein may be employed by those skilled in the art, and such modifications and variations are considered to be within the scope of certain embodiments of the present invention.

[0137] Exemplary embodiments The following are examples of embodiments, the numbering of which should not be construed as implying importance:

[0138] Embodiment 1 is a method for treating recurrent airway stenosis or stenosis in an airway cavity, comprising: The scope and balloon catheter are inserted into a target site for recurrent airway stenosis or stenosis in an airway lumen, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site The present invention provides a method, comprising:

[0139] Embodiment 2 provides the method of embodiment 1, further comprising damaging, dilating and / or removing a stenosis or stricture at a target site in a body cavity prior to insertion of the scope and balloon catheter to the target site.

[0140] Embodiment 3 provides the method of embodiment 2, wherein damaging, dilating and / or removing the stenosis or stenosis prior to inserting the drug-coated balloon catheter is inserting a pre-dilation balloon into the body cavity at the target site, inflating the pre-dilation balloon and removing the pre-dilation balloon.

[0141] Embodiment 4 provides the method of any of embodiments 2-3, wherein the damaging, dilating and / or removing comprises surgical removal, electrocautery, laser ablation, cryoablation, radiofrequency ablation, mechanical debulking, rigid bronchoscopic dilatation, knife cutting, open internal stenosis tomography, use of an uncoated balloon for stenosis or stenosis dilatation, or a combination thereof.

[0142] In a fifth embodiment, prior to expansion, Flushing the target site with a flushing composition comprising water and / or saline to hydrate and / or soak the coating at the target site with the flushing composition; or The coating is hydrated and / or soaked with saline, water and / or natural fluids naturally present in the body cavity that are not added exogenously, where the hydration and / or soaking is performed outside the body, in the body cavity where the balloon catheter is en route to the target site, at the target site, or a combination thereof; or Combinations of these The method of any one of embodiments 1 to 4 is provided, comprising:

[0143] Embodiment 6 provides the method of embodiment 5, wherein the hydration and / or soaking is carried out for 0.1 minutes to 5 minutes.

[0144] Embodiment 7 provides the method of any of embodiments 5-6, wherein flushing is performed before and / or during insertion of the scope and balloon catheter into the target site.

[0145] Embodiment 8 is flushing the target site with a flushing composition comprising water and / or saline to hydrate and / or soak the coating at the target site with the flushing composition; or performing ex vivo hydration and / or soaking of the drug coating with a flushing composition comprising water and / or saline prior to inserting the drug-coated balloon at the target site (optionally wherein the method does not include flushing at the target site); The method of any of embodiments 5 to 7 further comprises:

[0146] Example 9 provides the method of any of Examples 1-8, wherein the one or more additives include one or more water-insoluble additives.

[0147] Embodiment 10 provides the method of any of embodiments 1-9, wherein the one or more additives include one or more slightly water-insoluble and / or partially water-insoluble additives.

[0148] Example 11 provides the method of any of Examples 1-10, wherein the one or more additives include one or more water-soluble additives.

[0149] Embodiment 12 is a method for preparing a composition comprising the steps of: one or more water soluble additives; One or more water-insoluble or partially water-insoluble additives The method of any one of embodiments 1 to 11 is provided, comprising:

[0150] Embodiment 13 is a method for treating a vascular endothelial disorder in which the one or more additives are selected from the group consisting of pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, N-acetylglucosamine, N-octyl-D-gluconamide, N-nonanoyl-N-methylglucamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerebroside, sphingomyelin, galacrocerebroside, lactocerebroside, N-acetylglucosamine ... Tyl-D-Sphingosine, N-Hexanoyl-D-Sphingosine, N-Octanoyl-D-Sphingosine, N-Lauroyl-D-Sphingosine, N-Palmitoyl-D-Sphingosine, Sphingosine, Polyethylene Glycol (PEG) Caprylic / Capric Diglyceride, PEG-8 Caprylic / Capric Glyceride, PEG Caprylate, PEG-8 Caprylate, PEG Caprate, PEG Caproate, Glyceryl Monocaprylate, Glyceryl Monocaprate , Glyceryl monocaproate, Monolaurin, Monocaprin, Monocaprylin, Monomyristin, Monopalmitolein, Monoolein, Creatine, Creatinine, Agmatine, Citrulline, Guanidine, Sucralose, Aspartame, Hypoxanthine, Theobromine, Theophylline, Adenine, Uracil, Uridine, Guanine, Thymine, Thymidine, Xanthine, Xanthosine, Xanthosine Monophosphate, Caffeine, Allantoin, (2-Hydroxyethyl)urea, N,N 13. The method of any of embodiments 1-12, wherein the hydroxyl group is selected from the group consisting of 1'-bis(hydroxymethyl)urea, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), derivatives thereof, and combinations thereof.

[0151] Embodiment 14 provides the method of any of embodiments 1-13, wherein the one or more additives include pentaerythritol ethoxylate, pentaerythritol propoxylate, or a combination thereof.

[0152] Embodiment 15 provides the method of any of embodiments 1 to 14, wherein the balloon has a major diameter that is a nominal inflated diameter of at least 1 mm, or at least 15 mm, or at least 20 mm, or at least 30 mm, or at least 35 mm.

[0153] Embodiment 16 provides the method of any of embodiments 1 to 15, wherein the balloon catheter is an elongated balloon and does not include other balloons.

[0154] Example 17 provides the method of any of Examples 1 to 16, wherein the balloon catheter comprises more than one balloon.

[0155] Example 18 provides the method of any of examples 1 to 17, wherein the balloon is substantially free of a neck section between the proximal and distal ends of the balloon.

[0156] Embodiment 19 provides the method of any of embodiments 1 to 18, wherein the balloon includes at least one neck section on the balloon that includes a diameter smaller than the balloon main diameter when the balloon is inflated, the at least one neck section dividing the balloon into at least two main sections, each having a constant diameter.

[0157] Embodiment 20 provides the method of embodiment 19, wherein a diameter of the at least two main sections is equal to a main diameter of the elongate balloon or the at least one neck section has a diameter that is about 5% to about 99% of the diameter of at least one of the at least two main sections.

[0158] Example 21 provides the method of any of Examples 19-20, wherein at least one neck section independently has a diameter between about 5 mm and about 40 mm.

[0159] Example 22 provides the method of any of Examples 19 to 21, wherein the diameter of at least one neck section remains substantially constant during inflation of the balloon.

[0160] Example 23 provides the method of any of examples 19 to 22, wherein at least one neck section comprises a substantially inelastic portion of the balloon, a reinforced portion of the balloon, or a combination thereof.

[0161] Example 24 provides the method of any of examples 19-23, wherein at least one neck section includes a non-elastic material around the neck section.

[0162] Example 25 provides the method of example 24, wherein the non-elastic material comprises ultra-high molecular weight polyethylene, nylon, polyamide, or a combination thereof.

[0163] Example 26 provides the method of any of Examples 19-25, wherein the diameter (eg, expanded diameter) of the at least two major sections is from about 5 mm to about 45 mm.

[0164] Embodiment 27 provides a method of any of embodiments 19 to 26, wherein at least one neck section is about 1% to about 50% of the balloon length.

[0165] Embodiment 28 provides the method of any of embodiments 19 to 27, wherein the at least one neck section is one neck section and the balloon does not include other neck sections.

[0166] Example 29 provides the method of any of examples 19 to 28, wherein the at least one neck section is two neck sections and the balloon does not include any other neck section.

[0167] Example 30 provides the method of example 29, wherein the two neck sections have approximately the same diameter.

[0168] Example 31 provides the method of any of Examples 29-30, wherein one of the two neck sections has a smaller diameter than the other neck section.

[0169] Example 32 provides a method of any of examples 29 to 31, wherein the two neck sections are positioned symmetrically relative to the center of the balloon length.

[0170] Example 33 provides the method of any of examples 29 to 32, wherein the balloon catheter includes three main sections separated by two neck sections.

[0171] Example 34 provides the method of any of examples 29 to 33, wherein the at least one neck section is three neck sections, and wherein the balloon does not include other neck sections.

[0172] Example 35 provides the method of example 34, wherein the three neck sections are arranged to provide four main sections separated by the three neck sections.

[0173] Embodiment 36 provides the method of any of embodiments 1 to 35, wherein the elongate balloon has a length of about 20 mm to about 300 mm.

[0174] Embodiment 37 provides any of the methods of embodiments 1 to 36, wherein the balloon catheter comprises a catheter shaft at a longitudinal end of the balloon, the catheter shaft comprising an inner lumen for delivering gas, liquid or a combination thereof to the interior of the balloon.

[0175] Embodiment 38 provides the method of any of embodiments 1 to 37, wherein the balloon catheter comprises an atraumatic coupe tip.

[0176] Embodiment 39 provides the method of any of embodiments 1 to 38, wherein the balloon catheter comprises a residual drug amount, after deflation and withdrawal from the target site, that is less than 100 wt% of the initial drug load.

[0177] Embodiment 40 provides the method of any of embodiments 1 to 39, wherein the balloon catheter comprises a residual drug amount, after deflation and withdrawal from the target site, that is about 70 wt% or less of the initial drug load.

[0178] Embodiment 41 provides the method of any of embodiments 1-40, wherein the initial drug loading is about 1 microgram to about 20 micrograms of therapeutic agent per square millimeter of the balloon, measured when the balloon is at its nominal inflated diameter.

[0179] Embodiment 42 provides the method of any of embodiments 1-41, wherein the initial drug load is about 2 to about 6 micrograms of therapeutic agent per square millimeter of the balloon, measured when the balloon is at its nominal inflated diameter.

[0180] Embodiment 43 provides the method of any of embodiments 1-42, wherein the weight ratio of the therapeutic agent in the coating layer to the total weight of the one or more additives in the coating layer is about 0.05 to about 20.

[0181] Embodiment 44 provides the method of any of embodiments 1-43, wherein the ratio of the weight of the therapeutic agent in the coating layer to the total weight of the one or more additives in the coating layer is about 0.5 to about 8.

[0182] Embodiment 45 provides the method of any of embodiments 1-44, wherein the ratio of the weight of the therapeutic agent in the coating layer to the total weight of the one or more additives in the coating layer is about 2 to about 6.

[0183] Embodiment 46 provides the method of any of embodiments 1 to 45, wherein the balloon catheter has an expansion ratio of about 1.0 to about 20.

[0184] Embodiment 47 provides the method of any of embodiments 1 to 46, wherein the balloon catheter further comprises a sheath covering the elongate balloon, and the method comprises removing the sheath prior to inflation.

[0185] Embodiment 48 provides the method of any of embodiments 1 to 47, wherein inserting the scope and the balloon catheter comprises inserting the balloon catheter through a lumen of the scope.

[0186] Embodiment 49 provides the method of any of embodiments 1 to 48, wherein inserting the scope and the balloon catheter comprises inserting the balloon catheter and the scope side-by-side.

[0187] Embodiment 50 provides a method of any of embodiments 1 to 49, comprising positioning a proximal end of the scope and balloon at or near the target site.

[0188] Embodiment 51 provides the method of any of embodiments 1 to 50, wherein the scope is an endoscope, a nasal laryngoscope, a nasal speculum, a bronchoscope, a cystoscope, or a combination thereof.

[0189] Example 52 provides a method of any of Examples 1 to 51, comprising visualizing the placement of the balloon catheter at the target site with a scope.

[0190] Example 53 provides the method of any of Examples 1 to 52, wherein the expansion is performed at least until the target site collapses and expands.

[0191] Embodiment 54 provides the method of any of embodiments 1 to 53, wherein the expansion is performed such that the ratio of expanded diameter to normal lumen diameter at the target site is about 1.0 to about 20.

[0192] Embodiment 55 provides the method of any of embodiments 1 to 54, wherein the inflation is performed such that the ratio of the inflation diameter to the nominal body lumen diameter at the target site is about 1.0, 1.1, 1.2, or 1.31 to 10.

[0193] Example 56 provides the method of any of Examples 1 to 55, wherein the inflation is performed such that the balloon is inflated to a pressure equal to or greater than the nominal pressure of the balloon.

[0194] Embodiment 57 provides a method of any of embodiments 1 to 56, wherein the inflation is performed such that the stretch ratio of the inflated diameter of the balloon at the target site to the normal body lumen diameter is about 1.0 to about 20.

[0195] Embodiment 58 provides a method of any of embodiments 1 to 57, wherein the inflation is performed such that the stretch ratio of the inflated diameter of the balloon at the target site to the normal body lumen diameter is about 1.0, 1.1, 1.2, or 1.31 to 10.

[0196] Embodiment 59 provides a method of any of embodiments 1 to 58, wherein the inflation is performed such that the ratio of inflated diameter to normal body lumen diameter at the target site is about 1.0 to 20 and the stretch ratio of inflated diameter of the balloon to normal body lumen diameter at the target site is about 1.0 to about 20.

[0197] Embodiment 60 provides the method of any of embodiments 1 to 59, wherein the balloon is inflated to a pressure greater than the nominal pressure of the balloon and the nominal inflated diameter of the balloon is less than the inflated diameter.

[0198] Example 61 provides the method of any of examples 1 to 60, wherein the inflation includes monitoring the pressure within the balloon.

[0199] Embodiment 62 provides the method of any of embodiments 1 to 61, wherein the inflation includes inflating the balloon to a first pressure, stabilizing the pressure in the balloon for a stabilization period while maintaining the first pressure in the balloon, and then resuming increasing the pressure in the balloon until the inflated diameter is achieved.

[0200] Example 63 provides the method of example 62, which includes visualizing the indentation and dilation of the target site with a scope.

[0201] Example 64 provides a method of any of examples 1 to 63, comprising visualizing the expansion with a scope.

[0202] Embodiment 65 provides the method of any of embodiments 1 to 64, comprising maintaining the inflated diameter by maintaining the balloon inflated for between 1 minute and 7 days.

[0203] Embodiment 66 provides the method of any of embodiments 1 to 65, comprising maintaining the inflated diameter by maintaining the balloon inflated for between 1 minute and 1 day.

[0204] Embodiment 67 provides the method of any of embodiments 1 to 66, comprising maintaining the inflated diameter by maintaining the balloon inflated for 1 minute to 10 minutes.

[0205] Embodiment 68 provides the method of any of embodiments 1 to 67, comprising maintaining the expanded diameter for a period of time sufficient to release a drug into tissue at the target site and / or prevent or reduce bleeding.

[0206] Embodiment 69 provides the method of any of embodiments 1 to 68, wherein the body cavity includes the frontal sinus, ethmoid sinus, sphenoid sinus, maxillary sinus, nasal cavity, supraglottis, glottis, subglottis, trachea, main bronchi, intermediate bronchi and / or lobar bronchi.

[0207] Embodiment 70 provides the method of any of embodiments 1 to 69, wherein the recurrent stenosis or stenosis is idiopathic.

[0208] Embodiment 71 is directed to a method for treating a tracheal stenosis, comprising administering to a patient a tracheal stenosis, ... stenosis, nasal stenosis, severe asthma, comorbidities of CRSwNP, comorbidities of severe asthma stenosis, subglottic stenosis and / or stenosis, laryngeal stenosis, tracheal stenosis, bronchial stenosis, airway anastomotic stenosis, radiation induced airway stenosis, bronchial smooth muscle cells, IL-4, IL-5, IL-6, IL-13, IL-23, ILC2, mucus plugs, goblet cells, fibrosis, cystic fibrosis and / or one or more mucins.

[0209] Embodiment 72 provides the method of any of embodiments 1 to 71, wherein the airway stenosis or stenosis comprises tracheal and / or bronchial stenosis or stenosis.

[0210] Embodiment 73 provides the method of any of embodiments 1-72, wherein the airway stenosis or stenosis comprises chronic rhinosinusitis with nasal polyps (CRSwNP).

[0211] Embodiment 74 provides the method of any of embodiments 1 to 73, wherein the airway stenosis or stenosis comprises laryngeal stenosis and / or subglottic stenosis or stenosis.

[0212] Embodiment 75 provides the method of any of embodiments 1 to 74, wherein the airway stenosis or stenosis is stenosis or stenosis induced by repeated medication procedures, intubation, tracheotomy, tuberculosis infection, surgical removal, electrocautery, laser ablation, cryoablation, mechanical debulking, rigid bronchoscopy dilation, stent placement, and / or balloon dilation.

[0213]

[0036] Embodiment 76 further comprises damaging, dilating and / or removing a stenosis or constriction at a target site in a body lumen prior to insertion of the scope and balloon catheter to the target site, wherein: The method is for treating chronic rhinosinusitis with nasal polyps (CRSwNP), wherein the airway stenosis or constriction is CRSwNP-induced stenosis or constriction. The method of any one of embodiments 1 to 75 is provided.

[0214]

[0043] Embodiment 77 further includes damaging, dilating and / or removing a stenosis or constriction at a target site in a body cavity prior to insertion of the scope and balloon catheter to the target site, wherein: The method is a method of treating laryngeal stenosis and / or subglottic stenosis or stenosis, wherein the airway stenosis or stenosis is stenosis or stenosis induced by laryngeal stenosis and / or subglottic stenosis or stenosis; The method of any one of embodiments 1 to 76 is provided.

[0215] Embodiment 78 provides the method of any of embodiments 1 to 77, wherein the pre-dilatation balloon is substantially free of a drug coating.

[0216] Embodiment 79 is a method for treating recurrent airway stenosis or stenosis in an airway lumen, comprising: Lesions, dilations and / or removal of stenoses or strictures at a target site in a body cavity; The scope and balloon catheter are inserted into the target site, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; hydrating and / or soaking the coating with a flushing composition at the target site; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; where, prior to expansion, the drug coating is soaked and / or hydrated to activate the coating; A method is provided.

[0217] Embodiment 80 is a method for treating chronic rhinosinusitis with nasal polyps (CRSwNP), comprising: removing at least one nasal polyp at a target site in the body cavity; The scope and balloon catheter are inserted into a target site in a body cavity, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; where, prior to expansion, the drug coating is soaked and / or hydrated to activate the coating; A method is provided.

[0218] Embodiment 81 is a method for treating laryngeal stenosis and / or subglottic stenosis or stenosis, comprising: Lesions, dilations and / or removal of laryngeal and / or subglottic stenosis or strictures at a target site in a body cavity; The scope and balloon catheter are inserted into a target site in a body cavity, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, methods are provided in which the drug coating is soaked and / or hydrated prior to expansion to activate the coating.

[0219] Embodiment 82 is a method for treating severe asthma, comprising the steps of: The scope and balloon catheter are inserted into a target site in a body cavity including the trachea, main bronchus, intermediate bronchus, and / or lobar bronchus, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, a method is provided in which the drug-coated balloon is soaked and / or hydrated outside the body prior to inflation to activate the coating.

[0220] Embodiment 83 is a method for reducing severe asthma exacerbations and / or hospitalizations, comprising: The scope and balloon catheter are inserted into a target site in a body cavity including the trachea, main bronchus, intermediate bronchus, and / or lobar bronchus, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, a method is provided in which the drug-coated balloon is soaked and / or hydrated outside the body prior to inflation to activate the coating.

[0221] Embodiment 84 is a method for reducing the concentration of bronchial smooth muscle cells in a patient with severe asthma, comprising: A scope and a balloon catheter are inserted into a target site in a body cavity, the target site including bronchial smooth muscle cells, wherein the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, a method is provided in which the drug-coated balloon is soaked and / or hydrated outside the body prior to inflation to activate the coating.

[0222] Embodiment 85 is a method for reducing eosinophils, IL-4, IL-5, IL-6, IL-13, IL-23 and / or ILC2 in the airways, comprising: The scope and balloon catheter are inserted into a target site in a body cavity including the trachea, main bronchus, intermediate bronchus, and / or lobar bronchus, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, methods are provided in which the drug coating is soaked and / or hydrated prior to expansion to activate the coating.

[0223] Embodiment 86 is a method for treating mucus plugs in an airway, comprising: Removes mucus plugs from target sites in body cavities; The scope and balloon catheter are inserted into the target site, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, methods are provided in which the drug coating is soaked and / or hydrated prior to expansion to activate the coating.

[0224] Embodiment 87 is a method for reducing the concentration of goblet cells in the airways, comprising: A scope and a balloon catheter are inserted into a target site in a body cavity that includes one or more goblet cells, wherein the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, methods are provided in which the drug coating is soaked and / or hydrated prior to expansion to activate the coating.

[0225] Embodiment 88 relates to a method for reducing the concentration of one or more mucins in the airways, comprising: The scope and balloon catheter are inserted into a target site in a body cavity including the trachea, main bronchus, intermediate bronchus, and / or lobar bronchus, where the balloon catheter Long and thin balloons and a coating layer covering the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the balloon to an expanded diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site Including; Here, methods are provided in which the drug coating is soaked and / or hydrated prior to expansion to activate the coating.

[0226] Embodiment 89 is a method for treating chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma, comprising: removing at least one nasal polyp at a first target site in the first body cavity; A first scope and a first balloon catheter are inserted into a first target site in a first body cavity, where the first balloon catheter a first elongated balloon; a first coating layer covering the exterior surface of the first balloon, wherein the first coating layer comprises one or more first additives and an initial drug loading amount of a first therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; which includes; inflating the first balloon to a first inflated diameter such that the first coating layer contacts the interior of the first body cavity at the first target site; Deflate the first balloon; withdrawing the first scope and the first balloon catheter from the first target site; A second scope and a second balloon catheter are inserted into a second target site in a second body cavity including the trachea and / or bronchus, where the second balloon catheter a second elongated balloon; and a second coating layer overlying the exterior surface of the second balloon, wherein the second coating layer comprises one or more second additives and an initial drug loading amount of a second therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof. which includes; inflating the second balloon to an expanded diameter such that the coating contacts the interior of the second body cavity at the second target site; Deflate the second balloon; Withdraw the second scope and the second balloon catheter from the target site; Optionally, the treatment is repeated at a third target site in the trachea and / or bronchi that is different from the second target site. Including; Here, methods are provided in which the first and / or second drug coated balloons are soaked and / or hydrated prior to inflation of the first and / or second drug coated balloons to activate the coating.

[0227] Embodiment 90 provides the method of embodiment 89, wherein the time between the second target site treatment and the third target site treatment is 1 to 6 weeks.

[0228] Embodiment 91 provides the method of embodiment 89, wherein the second target site includes a bronchus.

[0229] Embodiment 92 provides the method of embodiment 91, wherein the bronchi include main bronchi, intermediate bronchi and / or lobar bronchi.

[0230] Embodiment 93 provides the method of any of embodiments 89 to 92, wherein the asthma is severe asthma.

[0231] Embodiment 94 provides any method or combination of embodiments 1 to 93 configured to allow the use or selection of all described elements or options as desired.

Claims

1. A balloon catheter for treating recurrent airway stenosis or stenosis in an airway cavity, comprising: Long, thin balloons and a coating layer overlying the exterior surface of the balloon, wherein the coating layer comprises one or more additives and an initial drug load of a therapeutic agent selected from paclitaxel, docetaxel, taxol, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, analogs thereof, and combinations thereof; A balloon catheter comprising: inserting the scope and the balloon catheter into a target site for recurrent airway stenosis or stenosis in an airway cavity; inflating the balloon to an inflated diameter such that the coating contacts the interior of the body cavity at the target site; Deflate the balloon; and Withdraw the scope and balloon catheter from the target site A balloon catheter for use in a method comprising:

2. A balloon catheter as claimed in claim 1, characterized in that the method comprises hydrating and / or soaking the coating on the drug-coated balloon prior to inflation to activate the coating layer.

3. A balloon catheter of claim 2, wherein the method further comprises flushing the target site with a flushing composition comprising water and / or saline, and hydrating and / or soaking the coating layer at the target site with the flushing composition.

4. A balloon catheter of claim 2, wherein the method further comprises performing ex vivo hydration and / or soaking of the coating layer with a flushing composition comprising water and / or saline prior to inserting the drug-coated balloon into the target site.

5. A balloon catheter as claimed in claim 4, wherein the method does not include flushing at the target site.

6. The balloon catheter of claim 2, wherein the hydration and / or immersion is carried out for 0.1 to 5 minutes.

7. A balloon catheter as claimed in claim 1, wherein the method further comprises at least one of damaging, dilating and removing a stenosis or narrowing at a target site in a body cavity prior to insertion of the scope and balloon catheter into the target site.

8. 8. The balloon catheter of claim 7, wherein the damaging, dilating and removing comprises surgical removal, electrocautery, laser ablation, cryoablation, radiofrequency ablation, mechanical debulking, rigid bronchoscopic dilatation, knife cutting, open internal strictureotomy, use of an uncoated balloon for stenosis or stricture dilatation, or a combination thereof.

9. One or more additives one or more water-insoluble additives; one or more slightly water-insoluble and / or partially water-insoluble additives, one or more water-soluble additives or combinations of these The balloon catheter of claim 1 , comprising:

10. The one or more additives may be pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, N-acetylglucosamine, N-octyl-D-gluconamide, N-nonanoyl-N-methylglucamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerebroside, sphingomyelin, galacrocerebroside, lactocerebroside, N-acetyl-D- Sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, sphingosine, polyethylene glycol (PEG) caprylic / capric diglyceride, PEG-8 caprylic / capric glyceride, PEG caprylate, PEG-8 caprylate, PEG caprate, PEG caproate, glyceryl monocaprylate, glyceryl monocaprate, Glyceryl monocaproate, monolaurin, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthosine, xanthosine monophosphate, caffeine, allantoin, (2-hydroxyethyl)urea, N 2. The balloon catheter of claim 1, wherein the hydroxybenzoate is selected from the group consisting of, N'-bis(hydroxymethyl)urea, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), derivatives thereof, and combinations thereof.

11. 10. The balloon catheter of claim 1, wherein the one or more additives comprise pentaerythritol ethoxylate, pentaerythritol propoxylate, or a combination thereof.

12. 10. The balloon catheter of claim 1, wherein the elongated balloon has a length of about 20 mm to about 300 mm, and the balloon has a major diameter that is a nominal inflated diameter of 1 mm to 50 mm.

13. 2. The balloon catheter of claim 1, wherein the balloon includes at least one neck section on the balloon that includes a diameter smaller than the main diameter of the balloon when the balloon is inflated, the at least one neck section dividing the balloon into at least two main sections.

14. 10. The balloon catheter of claim 1, wherein the initial drug load is from about 1 microgram to about 20 micrograms of therapeutic agent per square millimeter of the balloon, measured when the balloon is at its nominal inflated diameter.

15. Insertion of a scope and balloon catheter Inserting a balloon catheter through the lumen of the scope or Inserting the balloon catheter and scope side by side The balloon catheter of claim 1 , comprising:

16. 2. The balloon catheter of claim 1, wherein the scope is an endoscope, a rhinolaryngoscope, a nasoscope, a bronchoscope, a cystoscope, or a combination thereof.

17. Expansion the ratio of expanded diameter to normal body lumen diameter at the target site is about 1.0 to about 20; the ratio of expanded diameter to normal lumen diameter at the target site is about 1.0, 1.1, 1.2, or 1.31 to 10; The balloon is inflated to a pressure above the balloon's nominal pressure, a stretch ratio of the inflated diameter of the balloon at the target site to the normal body lumen diameter of about 1.0 to about 20; or combinations of these The balloon catheter of claim 1, wherein:

18. 2. The balloon catheter of claim 1, wherein the body cavity includes at least one of the frontal sinus, ethmoid sinus, sphenoid sinus, maxillary sinus, nasal cavity, supraglottis, glottis, subglottis, trachea, main bronchus, bronchus intermedius, and lobar bronchus, and / or the airway stenosis or narrowing includes tracheal and / or bronchial stenosis or narrowing.

19. 2. The balloon catheter of claim 1, wherein the airway stenosis or narrowing is stenosis or narrowing induced by at least one of repeated medication treatments, intubation, tracheotomy, tuberculosis infection, surgical removal, electrocautery, laser ablation, cryoablation, mechanical debulking, rigid bronchoscopic dilation, stent placement, balloon dilation, bronchial smooth muscle cells, eosinophils, IL-4, IL-5, IL-6, IL-13, IL-23, ILC2, mucus plugs, goblet cells, fibrosis, cystic fibrosis, and one or more mucins.

20. A method for treating recurrent airway stenosis or stenosis in an airway body cavity, wherein the stenosis is laryngeal stenosis and / or subglottic stenosis or stenosis, wherein the method further comprises at least one of damaging, expanding, and removing the laryngeal stenosis and / or subglottic stenosis or stenosis at a target site in the body cavity; or A method of treating severe asthma using a balloon catheter, wherein the target site includes at least one of the main bronchus, the intermediate bronchus, and the lobar bronchus; or a balloon catheter for at least one of treating severe asthma, reducing exacerbations and hospitalizations, wherein the target site comprises at least one of the trachea, main bronchi, intermediate bronchi, and lobar bronchi, wherein the method does not comprise flushing the target site, and wherein the method comprises activating the coating by hydrating and / or soaking the coating outside the body; or A method of using a balloon catheter to reduce the concentration of bronchial smooth muscle cells in a patient with severe asthma, wherein the target site comprises bronchial smooth muscle cells in a body cavity; or A method in which a balloon catheter reduces the concentration of at least one of eosinophils, IL-4, IL-5, IL-6, IL-13, IL-23, and ILC2 in the airways, wherein the target site includes at least one of the trachea, main bronchi, intermediate bronchi, and lobar bronchi; or the recurrent airway stenosis or narrowing in the airway cavity comprises a mucus plug in the airway, and wherein the balloon catheter further comprises removing the mucus plug from the target site in the cavity prior to inflation; or A method in which a balloon catheter reduces the concentration of goblet cells in an airway lumen, wherein the target site contains one or more goblet cells; or a balloon catheter for reducing the concentration of one or more mucins in the airway, wherein the target site includes at least one of the trachea, main bronchi, intermediate bronchi, and lobar bronchi; 16. The balloon catheter of any one of claims 1, 2 and 15.

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