Drug coated balloon catheter for body lumens

Abstract

A balloon catheter for treating stenosis and / or cancer, preventing stenosis and / or cancer, or reducing recurrence of stenosis and / or cancer, or for treating benign prostatic hyperplasia (BPH) in a non-vascular body lumen; the balloon catheter includes: an elongated balloon; a coating covering an outer surface of the balloon, wherein the coating comprises one or more water soluble additives and a therapeutic agent of an initial drug loading amount; and a length control mechanism (600) that stretches and elongates the balloon during contraction, providing a smaller cross-sectional contraction profile of the balloon for tracking through a body cavity and post-treatment retrieval.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is a divisional application of Chinese patent application No. 202080030597.8 filed on February 21, 2020, the entire contents of which are incorporated herein by reference.

[0003] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 62 / 809,048, filed on February 22, 2019, and U.S. Provisional Patent Application Serial No. 62 / 859,396, filed on June 10, 2019, the disclosures of both of which are incorporated herein by reference in their entireties.

[0004] The disclosures of each of the following applications are incorporated herein by reference in their entirety: U.S. Patent Application Serial No. 16 / 135,436, which is a continuation-in-part of International Application No. PCT / US2018 / 03108, filed May 4, 2018, which claims the benefit of priority to U.S. Provisional Patent Application Serial No. 62 / 502,212, filed May 5, 2017. U.S. patent application serial number 16 / 135,436 is also a continuation-in-part application of U.S. patent application serial number 15 / 568,614 filed on October 23, 2017, which is a U.S. national phase filing under 35 U.S.C.371 from international application number PCT / US2016 / 028652 filed on April 21, 2016, which claims the benefit of priority of U.S. provisional patent application serial number 62 / 152,559 filed on April 24, 2015. U.S. Patent Application Serial No. 16 / 135,436 is also a continuation-in-part of U.S. Patent Application Serial No. 14 / 438,327, filed April 24, 2015, which was a U.S. national phase filing under 35 U.S.C. 371 from International Application No. PCT / US2013 / 064842, filed October 14, 2013, which claims the benefit of priority to U.S. Provisional Patent Application Serial No. 61 / 795,790, filed October 26, 2012. U.S. Patent Application Serial No. 16 / 135,472, which is a continuation-in-part of International Application No. PCT / US2018 / 03108, filed May 4, 2018, which claims the benefit of priority to U.S. Provisional Patent Application Serial No. 62 / 502,212, filed May 5, 2017. U.S. patent application serial number 16 / 135,472 is also a continuation-in-part application of U.S. patent application serial number 15 / 568,614 filed on October 23, 2017, which is a U.S. national phase filing under 35 U.S.C. 371 from international application number PCT / US2016 / 028652 filed on April 21, 2016, which claims the benefit of priority of U.S. provisional patent application serial number 62 / 152,559 filed on April 24, 2015.U.S. patent application serial number 16 / 135,472 is also a continuation-in-part application of U.S. patent application serial number 14 / 438,327 filed on April 24, 2015, which is a U.S. national phase filing under 35 U.S.C. 371 from international application number PCT / US2013 / 064842 filed on October 14, 2013, which claims the benefit of priority of U.S. provisional patent application serial number 61 / 795,790 filed on October 26, 2012. Technical Field

[0005] The present application relates to a drug-coated balloon catheter for body cavities and its use. Background Art

[0006] Benign prostatic hyperplasia is a noncancerous enlargement of the prostate gland that affects more than 50% of men over the age of 60. The prostate gland is the size and shape of a walnut early in life and weighs about 20 grams. Enlargement of the prostate gland appears to be a normal process. With age, the prostate gland gradually increases in size to twice or more times its normal size. As the prostate grows, it presses on the urethra and narrows it, causing prostatic urethral compression and urinary tract obstruction, which results in difficulty or inability to urinate.

[0007] Urethral stricture disease occurs in up to 0.6% of men in certain populations. Urethral stricture disease appears to be more common in the elderly population. Patients with urethral strictures experience moderate to severe complications such as lower urinary tract voiding symptoms or urinary retention, recurrent urinary tract infections, and the need for repeated urethral surgeries such as dilation, urethrotomy, or urethral reconstruction.

[0008] Ureteral strictures of the upper urinary tract are congenital or acquired. Most congenital ureteral strictures are located at the ureteropelvic junction. Most ureteral strictures are acquired and are usually iatrogenic. The most common cause of ureteral strictures is injury during endoscopic, open, or laparoscopic surgery.

[0009] Bladder neck strictures (e.g., stenosis or contracture) and urethral strictures are recognized complications of all prostate cancer treatments. Refractory bladder neck strictures are relatively rare overall; however, these are associated with significant morbidity, often requiring multiple interventions with associated complications and affecting quality of life. Bladder neck strictures and urethral strictures are complications after prostate cancer treatments such as radical prostatectomy (RP), radiation therapy, cryotherapy, and high-intensity focused ultrasound (HIFU).

[0010] Strictures in the digestive body cavity or gastrointestinal tract include esophageal strictures, achalasia strictures, biliary strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, and large intestinal strictures. The type of disease classifies the stricture as benign or malignant.

[0011] Biliary stricture, also called bile duct stricture, occurs when the bile duct becomes smaller or narrowed. The bile duct is the tube that carries bile from the liver to the small intestine. When the bile duct narrows, it makes it difficult to digest food. Biliary stricture can be caused by any injury to the bile duct, swelling, pancreatitis, intestinal damage, and cancer in the bile duct or pancreas. Symptoms of bile stricture include pain, fever, chills, itching, and nausea or vomiting.

[0012] Esophageal strictures are a common problem encountered in gastroenterology and can be caused by either malignant or benign lesions. Dysphagia is a symptom experienced by all patients. Most of these patients require palliative care to relieve dysphagia.

[0013] Gastrointestinal stricture is a narrowing of a portion of the intestine that causes problems by slowing or blocking the movement of food through that area. This stricture is caused by recurrent inflammation, cancer, Crohn's disease, and ulcerative colitis. Strictures include esophageal strictures, achalasia strictures, strictures in stents, bile strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, and large intestinal strictures.

[0014] Chronic obstructive pulmonary disease (COPD) is a term used to classify two major airflow obstruction diseases: chronic bronchitis and emphysema. About 16 million Americans have COPD, and 80% to 90% of them have been smokers at some point in their lives. COPD is the leading cause of death in the United States. Chronic bronchitis is an inflammation of the bronchial airways. The bronchial airways connect the trachea to the lungs. When inflamed, the bronchi secrete mucus, causing a chronic cough. Emphysema is an over-inflation of the alveoli, or air sacs, in the lungs. This condition causes shortness of breath.

[0015] Asthma is a chronic respiratory disease characterized by inflammation of the airways, excess mucus production, and airway hyperreactivity, and is a condition in which the airways are too narrow or too easily reactive to irritation. An asthma episode or attack causes the airways to narrow, which makes breathing difficult. Asthma attacks can have a significant impact on a patient's life, limiting participation in many activities. In severe cases, asthma attacks can be life-threatening. Currently, there is no known method for treating asthma.

[0016] Chronic sinusitis is an inflammation of the membrane lining of one or more paranasal sinuses. Chronic sinusitis lasts for more than 3 weeks and often lasts for months. In cases of chronic sinusitis, there is usually tissue damage. According to the Centers for Disease Control (CDC), 37 million cases of chronic sinusitis are reported each year.

[0017] Radiation (e.g., radiation therapy) is used as one of the treatment modalities for localized cancers. Localized cancers are the most commonly diagnosed cancers. Most patients are diagnosed at an early stage when they are potentially curable. Standard localized treatment options include active surveillance, radical prostatectomy (RP) for prostate cancer, and, generally for all cancer treatments, radiation therapy (RT). Radiation therapy can be delivered via external beam (EBRT) or brachytherapy (BT). The side effects associated with each treatment can vary greatly. Localized cancers include prostate cancer, urethral cancer, ureteral cancer, esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenum cancer, jejunal cancer, ileum cancer, colon cancer, rectal cancer, large intestine cancer, and lung cancer. Radiation therapy can cause damage, such as strictures, in adjacent healthy tissues. Strictures induced by radiation therapy can include strictures of the urethra, ureter, esophageal strictures, bile duct strictures, gastric strictures, small intestine strictures, duodenal strictures, jejunal strictures, ileal strictures, colon strictures, rectal strictures, and large intestine strictures. The treatment of radiation-induced strictures can be complex and difficult. Due to high survival rates, the number of prostate cancer survivors in the United States increases by 220,000 men each year, reaching nearly 2.8 million in 2015, placing a large number of men at risk for short-term or long-term side effects of radiation therapy used to treat prostate cancer. The development of urethral strictures as a side effect of radiation therapy for prostate cancer treatment is particularly problematic.

[0018] Anastomosis is the connection or opening between two fluid-carrying body structures. Surgical anastomosis is the anastomosis formed by connecting two fluid-carrying body structures together by surgical techniques. Anastomotic stricture is the stricture of anastomosis. Anastomotic stricture is a common complication of surgical anastomosis and various other surgical procedures. Anastomotic stricture is usually fibrotic and may be difficult to manage and treat. Anastomotic stricture may include a stricture in the anastomosis between two parts of the same body structure or between two different body structures, wherein the body structure may be the esophagus, bile duct, stomach, small intestine, duodenum, jejunum, ileum, colon, rectum, large intestine, colon, rectum, urethra, ureter or bladder neck. Anastomotic stricture may be colorectal stricture, post-gastric bypass stricture, ileocolic stricture, gastrointestinal stricture, J- cul-de-sac stricture or bladder neck stricture (e.g., stricture). Although balloon dilatation has been shown to be a safe and effective non-surgical method for managing anastomotic strictures, problems still exist, such as the need for repeated balloon dilatation due to refractory or recurrent anastomotic strictures.

[0019] Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Crohn's and ulcerative colitis-induced strictures are common complications of IBD and the surgical procedures used for their treatment. Over time, stricture rates in patients with IBD range from 34% to 70%. Some strictures are refractory or recurrent, requiring repeated endoscopic dilation for treatment.

[0020] Eosinophilic esophagitis (EoE) is a chronic inflammatory disease. Symptoms of the disease include dysphagia and food impaction, and are often the result of esophageal strictures. Repeated endoscopic dilation of fibrostenotic eosinophilic esophagitis strictures using bougies and balloon catheters is used to treat such strictures.

[0021] Barrett's disease, also known as Barrett's esophagus, is a condition in which there is an abnormal (metaplasic) change in the mucosal cells lining the lower esophagus (from the normal stratified squamous epithelium to a simple columnar epithelium) by scattered goblet cells that are normally only found in the colon. This change is considered a premalignant condition because it is associated with a high incidence of further transformation to esophageal adenocarcinoma, an often fatal cancer.

[0022] Various minimally invasive approaches for the treatment of various cancers, large colon polyps, and Barrett's esophagus are practiced worldwide. When patients prefer to avoid surgery, various minimally invasive approaches are preferred over surgery. Multiple randomized controlled trials and interim analyses have demonstrated the clinical and oncological safety and effectiveness of laparoscopic gastrectomy, robot-assisted gastrectomy, EMR (endoscopic mucosal resection), and ESD (endoscopic sub-mucosal dissection) in the treatment of various stages of cancer and Barrett's esophagus. EMR (endoscopic mucosal resection) and ESD (endoscopic sub-mucosal dissection) are safe and effective for the treatment of early superficial cancers such as esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenal cancer, jejunal cancer, ileal cancer, colon cancer, rectal cancer, colorectal cancer, ileocolonic cancer, and gastrointestinal cancer. EMR and ESD are safe and effective for the treatment of high-graded Barrett's esophagus. Laparoscopic gastrectomy, robotic-assisted gastrectomy, EMR, and ESD are feasible procedures with regard to clinical and oncological safety; however, recurrence of malignancy and refractory strictures have been noted in some patients. The local recurrence rate of cancer after minimally invasive treatment ranges from 2-20%, depending on the type and stage of cancer and the duration of follow-up. The incidence of strictures or stenoses after minimally invasive procedures is approximately 26%-70%. Repeated endoscopic balloon dilatations are required to treat refractory or recurrent strictures or stenoses. Summary of the invention

[0023] In various embodiments, the present invention provides a balloon catheter. The balloon catheter can be used to treat stenosis and / or cancer, prevent stenosis and / or cancer, or reduce the recurrence of stenosis and / or cancer in a non-vascular body cavity. The balloon catheter includes an elongated balloon. The balloon catheter includes a coating covering the outer surface of the balloon. The coating includes one or more water-soluble additives and an initial drug loading of a therapeutic agent. In some embodiments, the balloon catheter also includes a length control mechanism that stretches and elongates the balloon when the balloon is in a contracted state.

[0024] In various embodiments, the present invention provides a method for treating a target site in a non-vascular body cavity. The method can be a method for treating stenosis and / or cancer, preventing stenosis and / or cancer, or reducing the recurrence of stenosis and / or cancer, or for treating BPH at a target site in a non-vascular body cavity. The method includes inserting a balloon catheter into a target site in a non-vascular body cavity. The balloon catheter includes an elongated balloon. The balloon catheter also includes a coating covering the outer surface of the balloon. The coating includes one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflating the balloon after the inflation period. The method also includes removing the balloon catheter from the body cavity.

[0025] In various embodiments, the present invention provides a method for treating non-vascular stenosis induced by cancer treatment. The method includes inserting a balloon catheter into a target site in a body cavity including a non-vascular stenosis induced by cancer treatment, the balloon catheter including an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the location of the non-vascular stenosis induced by cancer treatment until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, cancer treatment is radiation therapy. In some embodiments, the stenosis is a urethral stenosis, a ureteral stenosis, an esophageal stenosis, an antral stenosis, a gastric stenosis, a small intestinal stenosis, a colon stenosis, a rectal stenosis, a large intestinal stenosis, a bladder neck stenosis, or a biliary tract stenosis. In some embodiments, cancer treatment is radiation therapy of the prostate, wherein the stenosis is a bladder neck stenosis. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting a balloon catheter into the stenosis or target site.

[0026] In various embodiments, the present invention provides a method for reducing the occurrence of non-vascular stenosis induced by cancer treatment or preventing non-vascular stenosis induced by cancer treatment, or reducing or preventing cancer recurrence. The method includes inserting a balloon catheter into a target site in a body cavity, wherein the target site is at, closest to, adjacent to, or far from the location of the cancer treatment being performed, and the balloon catheter includes an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes performing cancer treatment in the body cavity at, closest to, adjacent to, or far from the target site, and then inserting the balloon catheter into the target site. In some embodiments, non-vascular stenosis induced by cancer treatment is present at the target site, and the method further includes performing a stenotic incision at the target site, and then inserting the balloon catheter into the target site. In some embodiments, stricture incision includes needle knife electroincision, episiotomy, urethrotomy, direct vision internal urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic sub-mucosal dissection (ESD). In some embodiments, cancer treatment is radiation therapy. In some embodiments, the stricture is urethral stricture, ureteral stricture, esophageal stricture, antral stricture, gastric stricture, small intestinal stricture, colonic stricture, rectal stricture, large intestinal stricture, bladder neck stricture, or bile duct stricture. In some embodiments, the cancer treatment is radiation therapy of the prostate, wherein the stricture is bladder neck stricture. In some embodiments, the method includes using a scope that visualizes the insertion of a drug coated balloon catheter into and at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0027] In various embodiments, the present invention provides a method for treating non-vascular stenosis induced by surgical anastomosis. The method includes inserting a balloon catheter into a target site in a body cavity including a non-vascular stenosis induced by surgical anastomosis, the balloon catheter including an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the location of the non-vascular stenosis induced by surgical anastomosis until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the stenosis is a fibrotic stenosis. In some embodiments, the stenosis is an esophageal stenosis, a gastric stenosis, a small intestinal stenosis, a duodenal stenosis, a jejunal stenosis, an ileal stenosis, a colonic stenosis, a rectal stenosis, a large intestinal stenosis, a colorectal stenosis, a stenosis caused by gastric bypass, an ileocolonic stenosis, a gastrointestinal stenosis, a urethral stenosis, a ureteric stenosis, a J-pit ​​stenosis, or a bladder neck stenosis. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0028] In various embodiments, the present invention provides a method for reducing the occurrence of non-vascular stenosis induced by surgical anastomosis or preventing non-vascular stenosis induced by surgical anastomosis. The method includes inserting a balloon catheter into a target site in a body cavity, wherein the target site is the location of the surgical anastomosis performed, and the balloon catheter includes an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes forming a surgical anastomosis at the target site and then inserting the balloon catheter into the target site. In some embodiments, non-vascular stenosis induced by surgical anastomosis is present at the target site, and the method further includes performing a stenotic incision at the target site and then inserting the balloon catheter into the target site. In some embodiments, stricture incision includes needle knife electroresection, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD). In some embodiments, the stricture is fibrotic stricture. In some embodiments, the stricture is esophageal stricture, gallbladder stricture, stomach stricture, small intestine stricture, duodenal stricture, jejunal stricture, ileal stricture, colonic stricture, rectal stricture, large intestine stricture, colorectal stricture, stricture caused by gastric bypass, ileocolic stricture, gastrointestinal stricture, urethral stricture, ureteral stricture, J- cul-de-sac stricture, or bladder neck stricture. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter at a target site, inflation and contraction process, balloon diameter increase during inflation, balloon diameter reduction during contraction, yielding of the target site, released drugs on the wall of the target site after balloon contraction, or any combination thereof. The method may include flushing the target site with water or saline solution through a viewing instrument and then inserting a balloon catheter into the stenosis or target site.

[0029] In various embodiments, the present invention provides a method for treating non-vascular stenosis induced by inflammatory diseases. The method includes inserting a balloon catheter into a target site in a body cavity including a non-vascular stenosis induced by an inflammatory disease, the balloon catheter including an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the location of the non-vascular stenosis induced by the inflammatory disease until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the inflammatory disease is Crohn's disease. In some embodiments, the inflammatory disease is ulcerative colitis. In some embodiments, the stenosis is a small intestinal stenosis, a duodenal stenosis, a jejunal stenosis, an ileal stenosis, a colonic stenosis, a rectal stenosis, a large intestinal stenosis, a colorectal stenosis, an ileocolic stenosis, or a gastrointestinal stenosis. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0030] In various embodiments, the present invention provides a method for reducing the occurrence of non-vascular stenosis induced by inflammatory disease treatment or preventing non-vascular stenosis induced by inflammatory disease treatment. The method includes inserting a balloon catheter into a target site in a body cavity, wherein the target site is the location of the inflammatory disease treatment being performed, and the balloon catheter includes an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes performing inflammatory disease treatment at the target site and then inserting the balloon catheter into the target site. In some embodiments, the stenosis induced by inflammatory disease treatment is present at the target site, and the method further includes performing a strictotomy at the target site and then inserting the balloon catheter into the target site. In some embodiments, strictotomy includes electrocautery or endoscopic mucosal resection (EMR). In some embodiments, the inflammatory disease is Crohn's disease. In some embodiments, the inflammatory disease is ulcerative colitis. In some embodiments, the stenosis is small intestinal stenosis, duodenal stenosis, jejunal stenosis, ileal stenosis, colonic stenosis, rectal stenosis, large intestinal stenosis, colorectal stenosis, ileocolic stenosis, or gastrointestinal stenosis. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter in a target site, inflation and contraction processes, an increase in balloon diameter during inflation, a decrease in balloon diameter during contraction, the yielding of the target site, the released drug on the wall of the target site after balloon contraction, or any combination thereof. The method may include flushing the target site with water or saline solution by an observation instrument, and then inserting a balloon catheter into the stenosis or target site.

[0031] In various embodiments, the present invention provides a method for treating non-vascular stenosis induced by gastrectomy. The method includes inserting a balloon catheter into a target site in a body cavity including a non-vascular stenosis induced by gastrectomy, the balloon catheter including an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the location of the non-vascular stenosis induced by gastrectomy until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter into and at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after the balloon is deflated, or any combination thereof. The method may include flushing the target site with water or saline solution through an observation instrument, and then inserting the balloon catheter into the stenosis or target site.

[0032] In various embodiments, the present invention provides a method for reducing the occurrence of gastrectomy-induced non-vascular stenosis or preventing gastrectomy-induced non-vascular stenosis. The method includes inserting a balloon catheter into a target site in a body cavity, wherein the target site is the location of a gastrectomy performed, and the balloon catheter includes an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes performing a gastrectomy at the target site and then inserting the balloon catheter into the target site. In some embodiments, gastrectomy-induced non-vascular stenosis is present at the target site, and the method further includes performing a stricture incision at the target site and then inserting the balloon catheter into the target site. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0033] In various embodiments, the present invention provides a method for treating non-vascular stenosis induced by electrocautery, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD). The method includes inserting a balloon catheter into a target site in a body cavity including non-vascular stenosis induced by electrocautery, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD), the balloon catheter including an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the location of the electroincision-, urethrotomy-, direct vision urethrotomy (DVIU)-, EMR (endoscopic mucosal resection)-, or endoscopic submucosal dissection (ESD)-induced non-vascular stenosis until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, electroincision, episiotomy, endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) is used for the treatment of esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenal cancer, jejunal cancer, ileal cancer, colon cancer, rectal cancer, colorectal cancer, ileocolonic cancer, or gastrointestinal cancer. In some embodiments, electroresection, episiotomy, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are treatments for removing polyps from the colon, wherein stricture is colonic stricture. In some embodiments, electroresection, episiotomy, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are treatments for Barrett's esophagus and wherein stricture is esophageal stricture. In some embodiments, stricture is esophageal stricture, gallbladder stricture, small intestinal stricture, duodenal stricture, jejunal stricture, ileal stricture, colonic stricture, rectal stricture, colorectal stricture, ileocolic stricture or gastrointestinal stricture. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter in a target site, inflation and contraction process, balloon diameter increase during inflation, balloon diameter reduction during contraction, yielding of the target site, released drugs on the wall of the target site after balloon contraction or any combination thereof. The method may include flushing the target site with water or saline solution through a viewing instrument and then inserting a balloon catheter into the stenosis or target site.

[0034] In various embodiments, the present invention provides a method for reducing the occurrence of or preventing non-vascular stenosis induced by scalpel electroresection, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD). The method includes inserting a balloon catheter into a target site (e.g., a site to be resected) in a body cavity, wherein the target site is the site of the scalpel electroresection, episiotomy, urethrotomy, DVIU, EMR, or ESD performed, and the balloon catheter includes an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches the inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes performing acupuncture electroresection, episiotomy, urethrotomy, DVIU, EMR, or ESD at the target site, and then inserting the balloon catheter into the target site. In some embodiments, the target site includes non-vascular stenosis induced by acupuncture electroresection, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD), and the method further includes performing stenosis incision at the target site, and then inserting the balloon catheter into the target site. In some embodiments, electroresection, episiotomy, urethrotomy, direct urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) are used for the treatment of esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenal cancer, jejunal cancer, ileal cancer, colon cancer, rectal cancer, colorectal cancer, ileocolonic cancer, or gastrointestinal cancer. In some embodiments, electroresection, episiotomy, urethrotomy, direct urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) are used for the treatment of Barrett's esophagus and the position where the resected is esophageal stenosis. In some embodiments, the target site or the position to be resected is an esophageal position, a gallbladder position, a small intestine position, a duodenal position, a jejunal position, an ileal position, a colon position, a rectal position, a colorectal position, an ileocolonic position, or a gastrointestinal position. In some embodiments, the method includes using a scope that visualizes the insertion and placement of the drug coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof.The method may include flushing the target site with water or saline solution through a viewing instrument and then inserting a balloon catheter into the stenosis or target site.

[0035] In various embodiments, the present invention provides a method of treating bladder neck stenosis. The method includes inserting a balloon catheter into a target site in a body cavity including a bladder neck stenosis, the balloon catheter including an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating a balloon at the target site so that the coating contacts the wall of the body cavity at the location of the bladder neck stenosis until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the bladder neck stenosis is fibrotic. In some embodiments, the method includes using an observation instrument that visualizes the insertion and placement of a drug-coated balloon catheter into the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after the balloon deflates, or any combination thereof. The method may include flushing the target site with water or saline solution through an observation instrument, and then inserting the balloon catheter into the stenosis or target site.

[0036] In various embodiments, the present invention provides a method for reducing the occurrence of bladder neck stenosis induced by prostate cancer treatment or stricture incision or preventing prostate cancer treatment- or stricture incision-induced bladder neck stenosis. The method includes inserting a balloon catheter into a target site in a body cavity, wherein the target site is in the bladder neck and in, proximal to, proximal to, or distal to the location of prostate cancer treatment or stricture incision, and the balloon catheter includes an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method further includes performing prostate cancer treatment or stricture incision, and then inserting the balloon catheter into the target site. In some embodiments, stricture incision includes needle knife electroresection, episiotomy, urethrotomy, direct vision internal urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD). In some embodiments, the target site includes bladder neck stenosis induced by prostate cancer treatment or stricture incision, and the method further includes performing stricture incision and then inserting the balloon catheter into the target site. In some embodiments, prostate cancer treatment includes radical prostatectomy (RP), radiation therapy, cryotherapy, or high intensity focused ultrasound (HIFU). In some embodiments, bladder neck stenosis is fibrotic. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter in the target site, inflation and contraction process, balloon diameter increase during inflation, balloon diameter reduction during contraction, yielding of the target site, released drugs on the wall of the target site after balloon contraction, or any combination thereof. The method may include flushing the target site with water or saline solution through a viewing instrument and then inserting a balloon catheter into the stenosis or target site.

[0037] In various embodiments, the present invention provides a method for treating fibrostenotic esophageal strictures of eosinophilic esophagitis. The method includes inserting a balloon catheter into a target site in a body cavity comprising fibrostenotic esophageal strictures of eosinophilic esophagitis, the balloon catheter comprising an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating comprises one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the location of the fibrostenotic esophageal stricture of eosinophilic esophagitis until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0038] In various embodiments, the present invention provides a method for treating achalasia. The method includes inserting a balloon catheter into a target site in a body cavity including a lower esophageal sphincter, the balloon catheter including an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the location of the lower esophageal sphincter until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. In some embodiments, the method includes using an observation instrument that visualizes the insertion and placement of a drug-coated balloon catheter into the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after the balloon deflates, or any combination thereof. The method may include flushing the target site with water or saline solution through an observation instrument and then inserting the balloon catheter into the stenosis or target site.

[0039] In various embodiments, the present invention provides a method for treating benign prostatic hyperplasia (BPH). The method includes inserting a balloon catheter into a target site in a body cavity (i.e., the prostatic urethra). The balloon catheter includes an elongated balloon. The balloon catheter also includes a coating covering the outer surface of the balloon. The coating includes one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the location of the prostatic urethra until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity.

[0040] In various embodiments, the present invention provides a method for treating urethral strictures, which are trauma-induced strictures, idiopathic strictures, and / or iatrogenic strictures. The method includes inserting a balloon catheter into a target site in a body cavity that includes a urethral stricture. The balloon catheter includes an elongated balloon. The balloon catheter also includes a coating covering the outer surface of the balloon. The coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method also includes removing the balloon catheter from the body cavity.

[0041] In various embodiments, the present invention provides a method for treating a target site in a non-vascular body cavity. The method includes inserting an uncoated balloon catheter into a non-vascular body cavity to the target site. The method includes inflating the uncoated balloon catheter at the target site so that the target site contacts the wall of the body cavity until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the uncoated balloon after the inflation period. The method includes removing the uncoated balloon catheter from the body cavity. The method includes flushing the target site with water or saline. The method includes inserting the balloon catheter into the target site. The balloon catheter includes an elongated balloon, and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. The method further includes using a scope in a body lumen including the target site to visualize insertion of the drug-coated balloon catheter to the target site, inflation of the drug-coated balloon at the target site, deflation of the drug-coated balloon at the target site, or a combination thereof.

[0042] In various embodiments, the present invention provides a method for treating a target site in a non-vascular body cavity. The method includes performing acupuncture electroresection, episiotomy, urethrotomy, direct vision internal urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) on the target site. The method includes flushing the target site with water or saline. The method includes inserting a balloon catheter into the target site in the non-vascular body cavity. The balloon catheter includes an elongated balloon and a coating covering the outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent. The method includes inflating the balloon at the target site so that the coating contacts the wall of the body cavity at the target site until the balloon reaches an inflated balloon diameter for an inflation period. The method includes shrinking the balloon after the inflation period. The method includes removing the balloon catheter from the body cavity. The method further includes using a scope in a body lumen including the target site to visualize insertion of the drug-coated balloon catheter to the target site, inflation of the drug-coated balloon at the target site, deflation of the drug-coated balloon at the target site, or a combination thereof.

[0043] Various embodiments of the present invention provide methods for treating benign prostatic hyperplasia (BPH). The method includes inserting a first sheath including a pre-dilation balloon catheter into the urethra, the pre-dilation balloon catheter including a pre-dilation balloon. The method includes removing the first sheath from the urethra, leaving the pre-dilation catheter in the urethra. The method includes inserting a cystoscope into the urethra. The method includes using a cystoscope to visualize the placement of the pre-dilation balloon in the prostatic urethra. The method includes inflating the pre-dilation balloon to dilate the prostatic urethra with the pre-dilation balloon to form an initial commissurotomy of the prostatic urethra. The method includes contracting the pre-dilation balloon. The method includes using a cystoscope to verify that the pre-dilation balloon has produced an initial commissurotomy. The method includes removing the cystoscope from the urethra. The method includes reinserting the first sheath into the urethra above the pre-dilation balloon catheter. The method includes pulling the pre-dilation balloon into the first sheath. The method includes removing the first sheath including the pre-dilation balloon catheter from the urethra. The method includes inserting a second sheath including a drug-coated balloon catheter into the urethra, the drug-coated balloon catheter including a drug-coated balloon, the drug-coated balloon including a coating covering its outer surface, the coating including one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes removing the second sheath from the urethra, while leaving the drug-coated balloon catheter in the urethra. The method includes inserting a cystoscope into the urethra. The method includes using a cystoscope to visualize the placement of the drug-coated balloon in the prostatic urethra. The method includes inflating the drug-coated balloon so that the coating contacts the prostatic urethra. The method includes removing the cystoscope from the urethra. The method includes maintaining the drug-coated balloon in an inflated state for at least 5 minutes. The method includes deflated the drug-coated balloon. The method includes reinserting the second sheath into the urethra above the drug-coated balloon catheter. The method includes pulling the drug-coated balloon into the second sheath. The method also includes removing the second sheath including the drug-coated balloon catheter from the urethra.

[0044] In various embodiments, the present invention provides a method for treating benign prostatic hyperplasia (BPH). The method includes inserting a first sheath into the urethra. In one embodiment, the first sheath includes an optical device to allow visualization of proper placement during insertion. In another embodiment, the first sheath has an obturator to facilitate insertion. The method includes inserting a pre-expansion balloon catheter including a pre-expansion balloon into the first sheath until the pre-expansion balloon is in the prostatic urethra and then removing the first sheath. A guidewire can be used to facilitate sheath tracking. The method includes removing the first sheath. The method includes inserting a cystoscope into the urethra side by side with the pre-expansion balloon catheter. The method includes using a cystoscope to visualize the placement of the pre-expansion balloon in the prostatic urethra. The method includes inflating the pre-expansion balloon to expand the prostatic urethra with the pre-expansion balloon to form an initial commissure incision of the prostatic urethra. The method includes contracting the pre-expansion balloon. The method includes using a cystoscope to verify that the pre-expansion balloon has produced an initial commissure incision. The method includes removing the cystoscope from the urethra. The method includes reinserting the first sheath over the pre-dilation balloon and pulling the pre-dilation balloon into the first sheath. The method includes either removing the pre-dilation balloon from the first sheath and leaving the first sheath in place, wherein the first sheath is a second sheath; or removing the pre-dilation balloon and the first sheath from the urethra and inserting a second sheath containing a cystoscope or a tight plug into the urethra (e.g., wherein the second sheath is the same or different from the first sheath). If a second sheath is used, the method includes removing the cystoscope or the tight plug after the second sheath is properly positioned. A guidewire may be used to facilitate sheath tracking. The method includes inserting a drug-coated balloon catheter into the second sheath, the drug-coated balloon catheter including a drug-coated balloon, the drug-coated balloon including a coating covering its outer surface, the coating including one or more water-soluble additives and an initial drug loading of a therapeutic agent. The method includes removing the second sheath from the urethra. The method includes inserting a cystoscope into the urethra side by side with the drug-coated balloon catheter. The method includes using a cystoscope to visualize the placement of the drug-coated balloon in the prostatic urethra. The method includes inflating a drug-coated balloon so as to contact the coating with the prostatic urethra. The method includes removing a cystoscope from the urethra. The method includes maintaining the drug-coated balloon in an inflated state for at least 5 minutes. The method includes defusing the drug-coated balloon. The method includes inserting a second sheath over the drug-coated balloon and pulling the drug-coated balloon into the second sheath. The method includes removing a second sheath of a balloon catheter including a drug coating from the urethra.

[0045] In various embodiments, the present invention provides a method for treating radiation-induced stenosis. The method includes optionally pre-dilating the radiation-induced stenosis with a pre-dilation balloon having a nominal diameter smaller than the nominal diameter of the balloon catheter, or performing a strictotomy on the radiation-induced stenosis. The method includes optionally flushing the radiation-induced stenosis with water, a saline solution, or an aqueous solution including at least one water-soluble additive. The method includes inserting a balloon catheter into a target site in the radiation stenosis. The balloon catheter includes a balloon, and a coating covering the outer surface of the balloon. The coating includes at least one water-soluble additive and a therapeutic agent, wherein the initial drug loading is 1-6 micrograms of the therapeutic agent per square millimeter of the balloon. The therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, an mTOR inhibitor, or their analogs, and combinations thereof. The water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamide, N-nonanoyl-N-methylglycamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate, PEG caproate (ca proate), monocaprylin, monocaprin, monohexanoin, monolaurin, monocaprin, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine The present invention relates to a coating comprising a therapeutic agent, a thymine, a thymidine, a xanthine, a xanthosine, a xanthosine monophosphate, a caffeine, an allantoin, a (2-hydroxyethyl) urea, a N,N'-bis(hydroxymethyl) urea, a pentaerythritol ethoxylate, a pentaerythritol propoxylate, a pentaerythritol propoxylate / ethoxylate, a glycerol ethoxylate, a glycerol propoxylate, a trimethylolpropane ethoxylate, a pentaerythritol, a dipentaerythritol, a crown ether, a 18-crown-6, a 15-crown-5, a 12-crown-4, and a combination thereof. The weight of the therapeutic agent in the coating is about 0.05-20 to the total weight of the one or more water-soluble additives in the coating.The method includes inflating the balloon until the coating contacts the wall of the radiation-induced stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period. The method includes deflation of the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes. The method includes removing the balloon catheter from the radiation-induced stricture. The method includes optionally using a viewing instrument that visualizes the insertion and placement of the drug-coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after the balloon deflation, or any combination thereof. The stretch ratio at the treated site is about 1.0 to about 40. Radiation-induced strictures include urethral strictures, ureteral strictures, esophageal strictures, antral strictures, gastric strictures, small intestinal strictures, colonic strictures, rectal strictures, large intestinal strictures, or bile duct strictures.

[0046] In various embodiments, the drug coating on the balloon catheter can prevent or reduce the development of stenosis at the treatment site, can prevent or reduce the development of cancer or malignancy at the treatment site, can treat BPH, or a combination thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] The drawings illustrate generally, by way of example and not by way of limitation, various embodiments of the invention.

[0048] Figure 1A A balloon catheter having a neck section is shown according to various embodiments.

[0049] Figure 1B A balloon catheter with two neck sections is shown according to various embodiments.

[0050] Figure 1C A balloon catheter with three neck sections is shown according to various embodiments.

[0051] Figure 2 A double-neck drug-coated balloon catheter including a catheter shaft, a catheter tip, and a Tuohy Borst adapter according to various embodiments is shown (the balloon catheter includes a fixed wire, an over-the-wire, and a rapid exchange balloon catheter, details not shown). Figure 2 ), according to various embodiments.

[0052] Figure 3 is a perspective view of an embodiment of a balloon catheter according to the present invention (the balloon catheter includes a fixed wire, an integral exchange type, and a rapid exchange balloon catheter, the details are not shown in Figure 3 ), according to various embodiments.

[0053] Figures 4A-4C It is taken along line AA Figure 3 Cross-sectional views of various embodiments of a distal portion of a balloon catheter showing exemplary coatings according to various embodiments.

[0054] Figures 5A-5D A balloon catheter including an elongated rigid member is shown according to various embodiments.

[0055] Figure 6 An elongated rigid member acting as a spring is shown according to various embodiments.

[0056] Figures 7A-7C An integral exchange catheter with a balloon having one neck section is shown according to various embodiments. DETAILED DESCRIPTION

[0057] Reference will now be made in detail to certain embodiments of the disclosed subject matter, examples of which are partially illustrated in the accompanying drawings.While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the illustrated subject matter is not intended to limit the claims to the disclosed subject matter.

[0058] Throughout this document, values ​​expressed in range format should be interpreted in a flexible manner that includes not only the values ​​explicitly stated as range limits, but also all individual values ​​or subranges included in the range, as if each value and subrange were explicitly stated. For example, the range "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted as including not only about 0.1% to about 5%, but also 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 specified range. Unless otherwise specified, the expression "about X to Y" has the same meaning as "about X to about Y". Similarly, unless otherwise specified, the expression "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z".

[0059] In this document, unless the context clearly dictates otherwise, the terms "a", "an", or "the" are used to include one or more. Unless otherwise specified, the term "or" is used to refer to a non-exclusive "or". The expression "at least one of A and B" has the same meaning as "A, B, or A and B". Moreover, it should be understood that the words or terms used herein, and in the absence of any contrary qualifications, are for descriptive purposes only and have no limiting effect. Any use of section headings is intended to facilitate reading of the document and should not be construed as limiting; information related to a section heading may appear within or outside that particular section.

[0060] In the methods described herein, unless a time sequence or order of operations is clearly stated, the actions may be performed in any order without departing from the principles of the present invention. In addition, specified actions may be performed simultaneously unless the explicit claim language states that they are performed separately. For example, the requested action of performing X and the requested action of performing Y may be performed simultaneously within a single operation, and the resulting method will fall within the textual scope of the requested method.

[0061] As used herein, the term "about" can allow a certain degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of the specified limit of a specified value or range, and includes the exact specified value or range.

[0062] As used herein, the term "substantially" means majority, or predominantly, 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%.

[0063] One aspect of various embodiments of the present invention is to deliver therapeutic agents such as paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or their analogs to the wall of a body cavity to treat or prevent narrowing or stricture. These drugs can be considered anti-inflammatory or antiproliferative drugs. The narrowing can be in a vascular cavity (e.g., a vascular narrowing in a coronary artery or a peripheral artery) or the narrowing can be in a non-vascular cavity. The drug can be a water-insoluble drug.

[0064] The antimicrobial properties of various fatty acids and monoglycerides of C8-C12 fatty acids have been studied for many years. Studies have shown that both fatty acids and monoglycerides can inhibit the growth of many types of bacteria and viruses. The coating formulation of the present invention can include various fatty acids and monoglycerides of C8-C12 fatty acids, such as caprylic acid, monocaprilin, capric acid, monocaprin, lauric acid and monolaurin, as one of the additives for treating various diseases.

[0065] Non-vascular body lumen strictures, and related non-vascular diseases, such as benign prostatic hyperplasia (BPH), urethral strictures, ureteral strictures, prostate cancer, esophageal strictures, achalasia strictures, strictures in stents, biliary strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolic strictures, gastrointestinal strictures, J-pit ​​strictures, bladder neck strictures (stenosis), fibrostenotic eosinophilic esophagitis strictures, Crohn's disease (CD) Causes of ulcerative colitis (UC)-induced strictures, radiation-induced strictures, endoscopic resection (EMR and ESD)-induced strictures, surgically-related anastomotic strictures, achalasia strictures, gastrectomy-induced strictures, and asthma and chronic obstructive pulmonary disease (COPD) can include cancer, infection and inflammation caused by pathogens such as bacteria and viruses, radiation therapy, laparoscopic gastrectomy, robotic-assisted gastrectomy, EMR (endoscopic mucosal resection), ESD (endoscopic submucosal dissection), surgically created anastomoses, or inflammatory diseases. Various embodiments of the present invention provide for the delivery of coating formulations containing drugs and additives having properties of killing and inhibiting bacteria and viruses to strictures.

[0066] The present invention provides a new method for treating body cavity stenosis to have a long-term and lasting effect. The new method opens the cavity and prevents, reduces or minimizes restenosis and recurrent stenosis. The method includes delivering therapeutic agents such as anti-inflammatory and antiproliferative drugs (e.g., paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or their analogs) and one or more water-soluble additives to the target tissue.

[0067] Embodiments of the present invention provide a medical device coating formulation comprising a drug for treating stenosis in a non-vascular body lumen and an additive that enhances absorption of the drug into body lumen tissue. The additive may have antibacterial and antiviral properties. A balloon catheter comprises a coating covering an outer surface of the balloon, wherein the coating comprises one or more water-soluble additives and an initial drug loading of an antiproliferative therapeutic agent.

[0068] By coating the outer surface of the balloon catheter with a layer comprising a therapeutic agent and an additive, for example, it can be used to solve problems associated with using one or more therapeutic agents in a drug coating. For example, the additive can have a hydrophilic portion and a drug affinity portion. The drug affinity portion can be a hydrophobic portion and / or can have affinity for the therapeutic agent through hydrogen bonding and / or van der Waals interactions. Surprisingly, the additive comprising a hydrophilic portion and a drug affinity portion according to an embodiment of the present invention is combined with an antiproliferative therapeutic agent to form an effective drug delivery coating on a medical device without using oil and lipids, thereby avoiding the lipolysis dependence and other shortcomings of traditional oil-based coating formulations. In addition, the additive according to an embodiment of the present invention is conducive to rapid drug elution and excellent penetration of drugs into the tissue of the disease location. Therefore, the coating according to an embodiment of the present invention provides an improved rate and / or degree of absorption of antiproliferative therapeutic agents in non-vascular lesion tissues or non-vascular body cavities. In an embodiment of the present invention, the coated device delivers the antiproliferative therapeutic agent to non-vascular tissues in a very short deployment time of less than 10 minutes and less than 2 minutes, and reduces the re-narrowing and reoccurrence of non-vascular body cavity stenosis.

[0069] Various embodiments of the present invention relate to a medical device for delivering a therapeutic agent to a narrowed blood vessel or non-vascular body cavity, the device comprising a layer covering the outer surface of the medical device. The device comprises a balloon catheter, a fixed wire balloon catheter, an integral exchange balloon catheter, a rapid exchange balloon catheter, an infusion balloon catheter, a spaced double balloon, a cutting balloon catheter, a scoring balloon catheter, or an infusion catheter (e.g., a distal perforated drug infusion tube, a perforated balloon, a spaced double balloon, a porous balloon, or a dripping balloon (weeping balloon)). The balloon catheter comprises an elongated balloon having a middle portion with a narrowed diameter. The balloon catheter comprises at least one neck segment on the balloon, which comprises a diameter smaller than the main diameter, and at least one neck segment divides the balloon into at least two main segments, each having a diameter equal to or different from the main diameter. In some embodiments, the balloon catheter comprises a cylindrical balloon without a neck segment. In addition, non-vascular cavity or non-vascular stenosis comprises one of esophagus, airway, antrum, trachea, colon, bile duct, stomach, small intestine, duodenum, jejunum, ileum, rectum, large intestine, urinary tract, prostate, urethra, ureter and other non-vascular cavity.Vascular cavity comprises artery, vein or any cavity with blood.Non-vascular cavity comprises those cavities without blood.Balloon catheter shaft and balloon material can be made of polyether-amide block copolymer, polyamide, nylon, polyethylene terephthalate or its combination.Balloon catheter shaft can comprise rigid material such as stainless steel, polycarbonate, titanium, polyetheretherketone (PEEK), any other rigid biocompatible material, or its combination.

[0070] In some embodiments, the additive is at least one of a surfactant and a compound. The coating covering the exterior of the medical device may include one or more water-soluble additives. The coating covering the exterior of the medical device 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).

[0071] The medical device may further include a dimethyl sulfoxide solvent layer, wherein the dimethyl sulfoxide solvent layer covers an outer surface of the medical device.

[0072] The device is capable of releasing the therapeutic agent and additives and delivering the therapeutic agent to the tissue in about 0.1 to 10 minutes. The concentration of the therapeutic agent in the layer can be 1 to 20 μg / mm when the balloon is inflated to the nominal diameter. 2 The concentration of the therapeutic agent in this layer may be 2 to 10 μg / mm 2 .

[0073] In some embodiments, the additive can enhance the release of the therapeutic agent from the balloon. The additive can enhance the penetration and absorption of the therapeutic agent in the tissue. The additive can have a water and ethanol solubility of at least 1 mg / mL and the therapeutic agent can be water-insoluble.

[0074] The layer covering the outer surface of the medical device may include a therapeutic agent and at least two additives, wherein each additive includes a hydrophilic portion and a drug affinity portion, wherein 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 wherein 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 a mixture of these polar organic solvents and water. In another aspect of this embodiment, the device further includes a top layer to reduce the loss of the drug during transport through the body to the target tissue, and the top layer covers the surface of the layer covering the outer surface of the medical device.

[0075] In some embodiments, the additive reduces the crystal size and particle count of the therapeutic agent, and wherein the additive is water soluble, while the therapeutic agent is not water soluble. The additive may have an acid, ester, ether, or alcohol fatty chain, wherein the fatty chain may be directly inserted into the lipid membrane structure of the tissue. The additive may penetrate into and rearrange the lipid membrane structure of the tissue. The additive may have one or more functional groups that have affinity for the drug through hydrogen bonding and / or van der Waals interactions. In some embodiments, the additive can be at least one of a surfactant and a compound, and wherein the compound has a molecular weight of 50-750 g / mol (e.g., 50 g / mol or higher, or less than, equal to, or greater than 75 g / mol, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725 g / mol, or 750 g / mol or less). The compound may have more than four hydroxyl groups. In some embodiments, the compound having more than four hydroxyl groups has a melting point of 120° C. or less, and the compound is an alcohol or ester. In some embodiments, the therapeutic agent is not water soluble.

[0076] Medical device coatings for drug delivery to non-vascular tissues or non-vascular stenosis can be prepared from a mixture. The coating can be prepared from a mixture comprising an organic phase containing drug particles dispersed therein and an aqueous phase containing a water-soluble additive. The water-soluble additive can be selected from polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polypeptide, water-soluble surfactant, water-soluble vitamin and protein. The preparation of the mixture can include homogenization under high shear conditions and optionally under pressure.

[0077] The coating covering the outer surface of the medical device may consist essentially of a therapeutic agent and an additive. The coating covering the outer surface of the medical device may consist essentially of a therapeutic agent, a water-soluble first additive, and a water-soluble second additive. The coating covering the outer surface of the medical device may consist essentially of a therapeutic agent and one or more water-soluble additives (e.g., a water-soluble first additive, a water-soluble second additive, and a water-soluble third additive).

[0078] In some embodiments, the method of treating a stricture in a non-vascular body lumen comprises inserting a balloon catheter comprising a coating into a body stricture, wherein the stricture is a urethral stricture, a benign prostatic hyperplasia (BPH) stricture, a ureteral stricture, an esophageal stricture, an achalasia stricture, a biliary stricture, a gastric stricture, a small intestinal stricture, a duodenal stricture, a jejunal stricture, an ileal stricture, a colonic stricture, a rectal stricture, a stricture in a stent, a large intestinal stricture, an antral stricture, a colorectal stricture, a stricture after gastric bypass surgery, an ileocolic stricture, a gastrointestinal stricture, a J-pit ​​stricture, a bladder neck stricture One of a stricture (e.g., stenosis), a fibrostenotic eosinophilic esophagitis stricture, a stricture induced by Crohn's disease (CD) and ulcerative colitis (UC), a radiation-induced stricture, an endoscopic resection (EMR and ESD)-induced stricture, an achalasia stricture, a gastrectomy-induced stricture, and an anastomotic stricture associated with a surgical procedure, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the stricture, deflated the balloon; and removing the balloon catheter, wherein the residual drug can be about 1% to 70% of the total drug load on the balloon catheter. In one aspect of this embodiment, the additive enhances absorption of the drug into non-vascular body cavity tissues.

[0079] Some drugs considered particularly useful for the airways, sinuses, and other nasal cavities for use in various embodiments are corticosteroids such as budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, mometasone furoate, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, betamethasone, triamcinolone acetonide, and the like.

[0080] Various embodiments relate to methods for treating a stenosis in a non-vascular body lumen and may include flushing the lumen with water, saline solution, or an aqueous solution of an additive as described herein, inserting a balloon catheter comprising a coating into the body lumen, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the body lumen, deflation of the balloon, and removal of the balloon catheter. The method for treating a stenosis in a non-vascular body lumen may include injecting water, saline solution, or an aqueous solution comprising at least one of the additives described herein, inserting a balloon catheter comprising a coating into the stenosis in the non-vascular body lumen, wherein the stenosis in the non-vascular body lumen is one of a urethral stenosis, a ureteral stenosis, an esophageal stenosis, an achalasia stenosis, a stenosis in a stent, an antral stenosis, a gastric stenosis, a small intestinal stenosis, a duodenal stenosis, a jejunal stenosis, an ileal stenosis, a rectal stenosis, a large intestinal stenosis, and a biliary tract stenosis, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the stenosis in the non-vascular body lumen, deflation of the balloon, and removal of the balloon catheter. In one aspect of this embodiment, the additive enhances absorption of the drug into the non-vascular body lumen tissue. In another aspect of this embodiment, the additive comprises a hydrophilic portion and a drug affinitive portion, wherein the drug affinitive 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. In another aspect of this embodiment, the drug is selected from paclitaxel, docetaxel, taxol and analogs thereof and rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus and analogs thereof. In another aspect of this embodiment, the additive is selected from PEG-fatty acids and PEG-fatty acid mono- and diesters, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterols and their derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugars and their derivatives, polyethylene glycol alkylphenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, fat-soluble vitamins and their salts, water-soluble vitamins and their amphiphilic derivatives, amino acids and their salts, oligopeptides, peptides and proteins, and organic acids and their esters and anhydrides. In another aspect of this embodiment, the drug can be released to the walls of the airways before, during or after an asthma attack. In another aspect of this embodiment, the drug can be released to the walls of the esophagus. In another aspect of this embodiment, the drug can be released to the walls of the sinuses. In another aspect of this embodiment, the drug can be released to the walls of the bile duct. In another aspect of this embodiment, the drug can be released to the walls of the urinary tract, prostate, urethra and ureteral cavities. In yet another aspect of this embodiment, the drug can be released to the wall of the stomach, small intestine, duodenum, jejunum, ileum, colon, rectum or large intestine. In another embodiment of this embodiment, the drug can be released to the wall of a non-vascular stenosis in the stent.

[0081] In various embodiments, the present invention provides a method for treating a body cavity, comprising inserting a balloon catheter (e.g., any of the balloon catheters described herein) into a target site in the body cavity. The method comprises inserting Figure 1A , 1B , 1C, 2, 3, 5A-5D or 7A-7C into a target site in a body cavity. The method may include inserting the balloon catheter and a viewing instrument into the target site in the body cavity, the balloon catheter and the viewing instrument being inserted side by side or the balloon catheter being in the cavity of the viewing instrument. The viewing instrument may be an endoscope, an enteroscope, a colonoscope, a sigmoidoscope, a proctoscope, an anoscope, a nasal mirror, a bronchoscope, or a cystoscope. The viewing instrument may be used to ensure that the balloon catheter is properly positioned in the target cavity. The method may include flushing the body cavity with water, a saline solution, or an aqueous solution including at least one water-soluble additive before, during, or after inserting the balloon into the target site. The method includes inflating the balloon until the coating contacts the narrow wall in the body cavity at the target site and the balloon reaches an inflated balloon diameter for an inflation period. Feature (a), or (b), or (c), or (a) and (b), or (a) and (c), or (b) and (c), or (a) and (b) and (c): (a) the ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter is about 1.0 to about 40; or (b) the inflation comprises inflating the balloon to a pressure equal to or greater than the nominal pressure of the balloon catheter, and the stretch ratio is about 1.0 to about 40; or (c) the inflation comprises inflating to a pressure greater than the nominal pressure of the balloon catheter, and the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b) and (c). The method comprises deflation of the balloon after the inflation period. The method also comprises removing the balloon catheter from the stenosis in the body cavity.

[0082] In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0083] In some embodiments, the balloon is inflated until the coating contacts the wall of the stenosis and the stenosis is dilated, while delivering the drug to the stenosis. In some embodiments, the balloon is inflated until the coating contacts the wall of the stenosis, and the inflation dilates the stenosis to increase its diameter, such that contact with the stenosis can provide circumferential delivery of the drug to the wall of the stenosis. In some embodiments, the portion of the balloon that includes the drug (e.g., in embodiments that include less than 100% of the surface area coated with the drug) can contact the stenosis uniformly. In other embodiments, various portions of the balloon surface are in non-uniform contact with the stenosis.

[0084] The inflated diameter of the balloon can be any suitable diameter reached during or throughout the inflation period, thereby achieving a desired ratio of the inflated balloon diameter at the target site to the untreated diameter of the body cavity. The inflated diameter of the balloon can correspond to the pressure used to inflate the balloon during the inflation period. The inflation pressure can be in the range of the nominal inflation pressure to the rated burst pressure. The nominal pressure is the pressure at the nominal diameter of the inflated balloon catheter. The nominal diameter is the diameter of the balloon catheter at the nominal pressure and is indicated on the product label. 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 constraints from the stenosis. In some embodiments, the inflation pressure of the balloon during the inflation period can be higher or lower than the nominal pressure, and the inflated diameter of the balloon can be higher or lower than the nominal diameter of the balloon accordingly.

[0085] In various embodiments, the present invention provides a method for treating a body cavity. The method includes 1) reloading the balloon catheter into an observation instrument (e.g., a cystoscope). The method includes 2) inserting the observation instrument-balloon catheter assembly into the body cavity. The method includes 3) inflating the balloon to an initial pressure (e.g., 0.5atm, 1atm, or 1.5atm) and maintaining the initial pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 4) using an increment of 0.5, 1, or 1.5atm from the previous pressure, inflating to the next higher pressure, and maintaining a higher pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 5) repeating the steps of 4) until the cavity tissue, such as prostate tissue, yields. The method includes 6) keeping the balloon inflated for 1 minute to 7 days, or 1 minute to 1 day, or 1-10 minutes to release the drug into the tissue and prevent bleeding. The method includes 7) contracting the balloon catheter. The method includes 8) removing the observation instrument-balloon catheter assembly from the body cavity. In this embodiment, a scope may be used to ensure proper placement of the balloon catheter prior to and / or during inflation.

[0086] In various embodiments, the present invention provides a method for treating a body cavity. The method includes 1) inserting a flexible observation instrument and a balloon catheter (in a sheath) side by side into the body cavity. The method includes 2) removing the sheath from the top of the balloon and inflating to an initial pressure (e.g., 0.5atm, 1atm, or 1.5atm) and maintaining the initial pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 3) using an increment of 0.5, 1, or 1.5atm from the previous pressure, inflating to the next higher pressure, and maintaining a higher pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 4) repeating the steps of 3) until the body cavity tissue yields. The method includes 5) keeping the balloon inflated for 1 minute to 7 days, or 1 minute to 1 day, or 1-10 minutes to release the drug into the tissue and prevent bleeding. The method includes 6) contracting the balloon catheter. The method includes 7) pulling the balloon catheter back into the sheath. The method includes 8) removing the observation instrument and balloon catheter / sheath from the body cavity. In this embodiment, a scope may be used to ensure proper positioning of the balloon prior to and / or during inflation.

[0087] In various embodiments, the present invention provides a method for treating a body cavity. The method includes 1) inserting a flexible observation instrument into the body cavity. The method also includes 2) inserting a balloon catheter and an observation instrument side by side in the body cavity. The method includes 3) inflating to an initial pressure (e.g., 0.5atm, 1atm, or 1.5atm) and maintaining the initial pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 4) using an increment of 0.5, 1, or 1.5atm from the previous pressure, inflating to the next higher pressure, and maintaining a higher pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 5) repeating the steps of 4) until the body cavity tissue yields. The method includes 6) keeping the balloon inflated for 1 minute to 7 days, 1 minute to 1 day, or 1-10 minutes to release the drug into the tissue and prevent bleeding. The method includes 7) contracting the balloon catheter. The method includes 8) removing the observation instrument and the balloon catheter assembly from the body cavity. In this embodiment, the observation instrument can be used to ensure that the balloon catheter is properly placed before and / or during inflation.

[0088] In various embodiments, the present invention provides a method for treating a body cavity. The method includes 1) inserting a flexible observation instrument into the body cavity and placing a guide wire. The method also includes 2) inserting a balloon catheter above the guide wire and placing the observation instrument side by side in the body cavity. The method includes 3) inflating to an initial pressure (e.g., 0.5atm, 1atm, or 1.5atm) and maintaining the initial pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 4) using an increment of 0.5, 1, or 1.5atm from the previous pressure, inflating to the next higher pressure, and maintaining a higher pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 5) repeating the steps of 4) until the body cavity tissue yields. The method includes 6) keeping the balloon inflated for 1 minute to 7 days, 1 minute to 1 day, or 1-10 minutes to release the drug into the tissue and prevent bleeding. The method includes 7) shrinking the balloon catheter. The method includes 8) removing the observation instrument, guide wire, and balloon catheter assembly from the body cavity. In this embodiment, the scope can be used to ensure that the balloon catheter is properly positioned before and / or during inflation. In some embodiments, the method includes using a scope that visualizes the insertion and placement of the drug-coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method can include flushing the target site with water or saline solution through the scope and then inserting the balloon catheter into the stenosis or target site.

[0089] In various embodiments, the present invention provides a method for treating benign prostatic hyperplasia. The method includes 1) inserting a balloon catheter sheath assembly and an observation instrument (e.g., a cystoscope). The method includes 2) placing the observation instrument and the proximal edge of the balloon side by side near the external sphincter. The method includes 3) removing the sheath from the balloon and inflating to an initial pressure (e.g., 0.5 atm, 1 atm, or 1.5 atm) and maintaining the initial pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 4) using an increment of 0.5, 1, or 1.5 atm from the previous pressure, inflating to the next higher pressure, and maintaining a higher pressure until the pressure no longer decreases, for 1-2 minutes. The method includes 5) repeating the steps of 4) until the prostate tissue yields and forms a commissurotomy. The method includes 6) keeping the balloon inflated for 1 minute to 7 days, 1 minute to 1 day, or 1-10 minutes to release the drug into the tissue and prevent bleeding. The method includes 7) contracting the balloon catheter. The method includes 8) removing the observation instrument and the balloon catheter assembly from the body cavity. Feature (a), or (b), or (c), or (a) and (b), or (a) and (c), or (b) and (c), or (a) and (b) and (c): (a) the ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter is about 1.0 to about 40; or (b) the inflation comprises inflating the balloon to a pressure equal to or greater than the nominal pressure of the balloon catheter, and the stretch ratio at the target site is about 1.0 to about 40; or (c) the inflation comprises inflating to a pressure greater than the nominal pressure of the balloon catheter, and the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b) and (c).

[0090] Various embodiments of the present disclosure relate to treating stenosis in a body cavity by delivering an effective amount of a therapeutic agent such as an anti-inflammatory and antiproliferative drug (e.g., rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, paclitaxel, taxol, docetaxel, or their analogs) to a target tissue. Stenosis in a body cavity includes vascular stenosis, nonvascular stenosis, urethral stenosis, ureteral stenosis, esophageal stenosis, achalasia stenosis, stenosis in a stent, sinus stenosis, biliary tract stenosis, gastric stenosis, small intestinal stenosis, duodenal stenosis, jejunal stenosis, ileal stenosis, colonic stenosis, rectal stenosis, and large intestinal stenosis. Embodiments of the present disclosure relate to a method for treating at least one of vascular and nonvascular cavity stenosis, benign prostatic hyperplasia (BPH), urethral narrowing, prostate cancer, asthma, and chronic obstructive pulmonary disease (COPD). Treatment is intended for various animals, such as premature infants to adults.

[0091] The drug on the balloon catheter coating can be released into the target body cavity. The multi-segment continuous balloon with a neck section with a smaller diameter mechanically anchors the balloon in the body cavity, so it prevents the balloon from sliding in the body cavity. If the balloon slips or moves away from the target lesion location, the target site may be missed and the healthy cavity may be damaged.

[0092] In various embodiments, the present invention has advantages, at least some of which are unexpected. For example, coating the outer surface of a balloon catheter with a layer comprising a therapeutic agent and an additive having a hydrophilic portion and a drug affinity portion can be used to treat the disorders disclosed herein. The drug affinity portion is a hydrophobic portion and / or has affinity for the therapeutic agent through hydrogen bonding and / or van der Waals interactions. Surprisingly, additives according to embodiments of the present invention, which include a hydrophilic portion and a drug affinity portion, are combined with therapeutic agents to form an effective drug delivery coating on a medical device. In addition, additives according to embodiments of the present invention can be advantageous for rapid drug elution and excellent penetration of drugs into tissues at diseased locations. Therefore, coatings according to embodiments of the present invention can provide an increased rate and / or degree of absorption of therapeutic agents in diseased tissues or body cavities. In embodiments of the present invention, the coated device can deliver therapeutic agents to tissues in a very short deployment time of less than 10 minutes (e.g., less than 2 minutes), and can reduce restenosis and recurrence of stenosis of body cavities, for example, compared to other balloon catheters lacking such neck segments or neck segment structures.

[0093] In various embodiments, the balloon catheter of the present invention is compatible with flexible or rigid viewing instruments that allow visualization of the treatment area, allowing more accurate and more effective placement than other balloon catheters. The viewing instrument can be an endoscope, an enteroscope, a colonoscope, a sigmoidoscope, a proctoscope, an anoscope, a rhinoscope, a bronchoscope, or a cystoscope. In various embodiments, the balloon catheter of the present invention is self-guiding because the neck section of the balloon catheter guides the balloon catheter to the appropriate position (e.g., with the neck section of the balloon catheter, such as the most distal neck section, in the bladder neck) during inflation, even if the balloon catheter is slightly out of position when it is initially inflated.

[0094] Balloon catheter and method of using the same

[0095] In various embodiments, the present invention provides a balloon catheter for delivering a therapeutic agent to a target site of a body cavity. The balloon catheter may include an elongated balloon having a plurality of main sections or body sections and at least one neck section having a diameter less than the diameter of the main section. The balloon catheter may include an elongated balloon having a main diameter, such as a plurality of main sections having a main diameter or having an average diameter equal to the main diameter. The multi-segmented balloon with a smaller diameter neck section mechanically anchors the balloon in the body cavity; therefore, it can prevent the balloon from sliding in the body cavity. If the balloon slides away from the targeted lesion position, it may be missed and may damage the position of a healthy cavity. The balloon catheter may include at least one neck section on the balloon having a diameter less than the main diameter. The balloon catheter may also include a coating covering the outer surface of the balloon. The coating may include one or more water-soluble additives and an initial drug loading of a therapeutic agent (e.g., paclitaxel, taxol, docetaxel, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, their analogs, and combinations thereof). In a method of using a balloon catheter, feature (a), or (b), or (c), or (a) and (b), or (a) and (c), or (b) and (c), or (a) and (b) and (c): (a) the ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter is about 1.0 to about 40; or (b) inflation includes inflating the balloon to a pressure equal to or greater than the nominal pressure of the balloon catheter, and the stretch ratio at the target site is about 1.0 to about 40; or (c) inflation includes inflation to a pressure greater than the nominal pressure of the balloon catheter, and the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b), and (c).

[0096] The major diameter of the balloon may be the diameter of the major section of the balloon when the balloon is inflated. In some embodiments, the inflation pressure used to determine the major diameter may be any pressure that eliminates any folded or creased areas of the balloon and achieves the tautness of the balloon. The inflation pressure used to determine the major diameter may be a pressure such that the inflated balloon has a shape and size corresponding to the desired shape and size of the balloon during the intended treatment of the body cavity. The inflation pressure used to determine the major diameter may 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.

[0097] In one embodiment, the drug-coated balloon includes two main sections at both ends with the same diameter, a neck section with a smaller diameter between the two main sections, and two cones at the proximal and distal balloon bodies. The drug-coated balloon may include three main sections with the same diameter and two neck sections with a smaller diameter, and two cones at the proximal and distal balloon bodies, wherein the three main sections and the two neck sections are arranged alternately, and the neck sections are adjacent to the main sections with a larger diameter. The drug-coated balloon may include four main sections with a larger diameter, three neck sections with a smaller diameter, and two cones at the proximal and distal balloon bodies, wherein the four main sections with a larger diameter and the three neck sections are arranged alternately, and the neck sections are adjacent to the main sections with a larger diameter. The drug-coated balloon may include five main sections with a larger diameter, four neck sections with a smaller diameter, and two cones at the proximal and distal balloon bodies, wherein the five main sections with a larger diameter and the four neck sections are arranged alternately, and the neck sections are adjacent to the main sections with a larger diameter. The balloon catheter may include at least one neck section on the balloon having a diameter smaller than the balloon diameter of the main section. The balloon catheter may include an elongated (e.g., cylindrical) balloon with multiple sections having different diameters. There are features (a), or (b), or (c), or (a) and (b), or (a) and (c), or (b) and (c), or (a) and (b) and (c): (a) the ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter is about 1.0 to about 40; or (b) the inflation includes inflating the balloon to a pressure equal to or greater than the nominal pressure of the balloon catheter, and the stretch ratio at the target site is about 1.0 to about 40; or (c) the inflation includes inflating to a pressure greater than the nominal pressure of the balloon catheter, and the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b), and (c). A multi-segmented balloon with a smaller neck increases the friction between the balloon and the body cavity; thus it prevents the balloon from sliding in the body cavity.

[0098] The drug-coated balloon catheter can be a medical device for treating benign prostatic hyperplasia (BPH). The balloon catheter can expand the prostatic urethra and can include a catheter shaft for inserting the urethra and a compliance, semi-compliant or non-compliant balloon for inflation in the prostatic urethra. The balloon can be coated with a therapeutic agent, which is delivered to prostatic tissue and the prostatic urethra when the balloon is inflated. Any suitable method can be used to place the balloon in the prostate, such as by a separate positioning balloon in the bladder, a positioning balloon in the bulbous urethra, a marker band on or under the balloon visible by fluoroscopy, or the catheter shaft can be an observation instrument (such as a cystoscope) compatibility, allowing placement by direct visualization, or the catheter can be side by side with the observation instrument. For example, several possible catheter designs allow direct visualization of the balloon during placement and inflation. A design is cystoscope compatibility, in which the catheter is reloaded through a working channel. Once after passing through a cystoscope, a Touhy Borst adapter and a one-way stopcock can be connected to the catheter shaft to allow inflation of the balloon. Another design may include a multi-lumen catheter with a lumen in the center of the shaft that allows the optics of a rigid cystoscope to be inserted and positioned next to the proximal edge of the balloon.

[0099] In some embodiments, when treating the prostate, the size of the balloon catheter should be such that the main body section of the catheter is located between the bladder neck sphincter (at the outlet of the bladder) and the external sphincter. In other embodiments, the main body section of the catheter is located above the external sphincter, placed through the prostate, and one or more body sections pass through the bladder neck sphincter and are located in the bladder. In these embodiments, preferably, the neck region of the balloon catheter is aligned with the bladder neck. As discussed herein, an observation instrument equipped with visualization can be used to appropriately determine the size of the balloon catheter and place the balloon catheter.

[0100] In some embodiments where the balloon catheter includes a soft tip, Coude tip, etc., the tip can be used to assist in device insertion and tracking through the urethra. In other embodiments, the balloon catheter includes a lumen or channel designed to allow insertion and tracking through the urethra to the target site or prostate.

[0101] Achalasia stricture is a rare disease that makes it difficult for food and liquids to pass from the esophagus into the stomach. In some embodiments, when treating achalasia stricture, Figure 1AThe size of the balloon catheter shown in should be designed so that the proximal body section of the catheter is located in the atonic stenosis and above the lower esophageal sphincter. In these embodiments, the neck area of ​​the balloon catheter can be aligned with the lower esophageal sphincter neck. As discussed herein, being equipped with a visual observation instrument can be used to appropriately determine the size of the balloon catheter and place the balloon catheter. In the embodiment in which the balloon catheter comprises a soft tip, the tip can be inserted into the sphincter (for example, the lower esophageal sphincter) or the stomach to help place the balloon catheter in the desired position.

[0102] Balloon catheters can relieve lower urinary tract symptoms (LUTS) caused by BPH by directly expanding prostate tissue. Using a balloon with a ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter of 1.0 to 40, or using a balloon with a stretch ratio at the target site of 1.0 to 40, expanding the prostate can produce a joint cut in the natural plane, which separates the cross-section in the transition zone of the prostate. At the same time, drugs can be released from the coating into the prostate tissue, which can, for example, prevent the prostate from enlarging and the newly formed opening from narrowing again.

[0103] In various embodiments, during inflation of the balloon in the body lumen (e.g., during practice of the methods of the invention), the nominal balloon diameter of the catheter (e.g., the diameter typically achieved at the nominal pressure) can be such that the ratio of the nominal balloon diameter to the untreated diameter of the body lumen at the treated location is any suitable ratio, such as 1.0, 1.1, 1.2, 1.3, or 1.4 to 40 (e.g., 1, or greater than, less than, or equal to 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.10, 2.11, 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26, 2.27, 2.28, 2.29, 3.3, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.5 , 1.7, 1.8, 1.9, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 or less, or any value therebetween), or a combination thereof. 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 reached, or may limit the inflated balloon from forming a "dog bone" shape. The nominal balloon diameter at a predetermined pressure (e.g., 2 atm, 3 atm, 6 atm, or 9 atm) may be different for balloons of different diameters for various diseases. For example, for 6 mm, 8 mm, 10 mm, 12 mm, and 14 mm balloon catheters inflated at 4 atm, 5 atm, 6 atm, 8 atm, or 12 atm, the nominal diameter of the urethral stricture balloon may be 6 mm, 8 mm, 10 mm, 12 mm, and 14 mm, and the balloon length may be 20 mm, 25 mm, 30 mm, 35 mm, 40 mm, 45 mm, and 50 mm. The nominal diameter of the BPH stenosis balloon can be 25mm, 30mm, 35mm, 40mm, and 45mm, and the balloon length is 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm, 55mm, and 60mm balloon catheter, and the nominal pressure is 2atm, 3atm, 4atm, 6atm, or 9atm inflation. Table 1 illustrates the example of the ratio of the nominal balloon size, nominal pressure, and minimum balloon diameter to the untreated cavity diameter for treating the stenosis of various diseases. The nominal pressure is the pressure required to make the balloon reach the nominal diameter indicated on its label in the unconstrained pressure ramp test. The nominal diameter is the required diameter indicated on the product label. All physicians purchase balloons and select the balloons used according to the nominal diameter. The rated burst pressure is the maximum pressure to which a balloon can be inflated with very high confidence that it will not rupture, a labeling requirement for balloon catheters, calculated from statistical analysis of the pressures observed when the balloon ruptures in an unrestrained pressure ramp test.

[0104] Table 1. Examples of nominal balloon sizes, nominal pressures, and ratios of minimum balloon diameter to untreated lumen diameter for treating stenoses in various disease states, assuming an untreated target site diameter of 3 mm.

[0105]

[0106] In various embodiments, the balloon catheter can be sufficient so that at a predetermined pressure (e.g., nominal pressure), the balloon can have any suitable ratio of the inflated balloon catheter diameter to the untreated diameter of the body cavity at the treated location; for example, at a pressure of about 1 atm (304 kPa) to about 30 atm (3040 kPa) (e.g., about 1 atm or less, or less than, equal to, or greater than about 4 atm, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 28, or about 30 atm or greater).

[0107] Unless otherwise stated, stretch ratio is defined in this article as the ratio of the nominal diameter of sacculus to the untreated diameter of body cavity in the region processed by balloon catheter. The untreated diameter of the body cavity at the target site is the diameter before the balloon expansion coated with medicine, and is also the diameter before any pre-expansion method (such as performed on the same day) carried out during the same procedure, such as the diameter before using pre-expansion sacculus or cutting technology such as DVIU or hot knife. The nominal diameter of the sacculus for determining stretch ratio is the diameter that sacculus reaches under nominal pressure in an unrestricted environment. Untreated cavity diameter is the mean diameter of the target site (for example, the mean diameter of the cavity or stenosis (stricture), stenosis (stenosis) or lesions at the target site). For urinary tract, for example, for stenosis in the urethra, the untreated body cavity diameter will be the mean diameter of the narrow position in the urethra before the balloon expansion coated with medicine (and before any pre-expansion or cutting such as DVIU). For strictures in the urethra or prostatic urethra, the untreated lumen diameter at the target site can be the untreated lumen diameter (e.g., urination diameter) at the target site during urination, particularly in cases where the untreated lumen diameter at the target site is zero or close to zero in the absence of urination. For BPH and prostatic urethra, the untreated lumen diameter will be the average diameter of the prostatic urethra at the treated location. The inflated balloon diameter can be the actual diameter of the balloon after inflation, which in some embodiments can be equal to, less than, or greater than the nominal diameter of the balloon. In various embodiments, the stretch ratio of the balloon catheter of the present invention makes it more effective in treating non-vascular cavities than other catheters. During the implementation of the method of the present invention, the stretch ratio can be selected to achieve any suitable ratio of the desired ratio of the actual inflated balloon diameter to the untreated lumen diameter within the pressure range used during the method.In various embodiments, the stretch ratio of the balloon can be about 1.0 to about 40, or about 4 to about 40, or less than, equal to, or greater than about 1.1, 1.2, 1.3, 1.31, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or about 40 or more; such stretch ratios can result in an inflated balloon diameter that is greater than or equal to about 1.0 during inflation. The desired ratio of the untreated lumen diameter at the pressure used during the stretching can be the same, similar, or different than the stretching ratio, such as from about 1.0 to about 40, or from about 4 to about 40, or less than, equal to, or greater than about 1.1, 1.2, 1.3, 1.31, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or about 40 or more.

[0108] In various embodiments, the method includes measuring the body cavity stenosis to be treated. The distal and proximal healthy tissue diameters and the length of the stenosis can be evaluated to select the drug-coated balloon to be used. The physician will select the balloon based on the untreated diameter of the body cavity stenosis and achieve a stretch ratio of 1.0 to 40 or 4 to 40. The physician can then inflate the balloon to at least the nominal pressure, and in some cases, the balloon can be inflated to exceed the nominal pressure until the rated burst pressure of the balloon. The pressure range used during the inflation period can be referred to as the working pressure range of the drug-coated balloon. In some cases, the method may include exceeding the rated burst pressure of the balloon. Because the nominal diameter of the balloon is determined without any contraction, the inflated diameter of the balloon in the stenosis during the treatment will be approximately the same as the nominal diameter or less than or greater than the nominal diameter. At the burst pressure, above or below the burst pressure, the inflated diameter of the balloon may be less than the nominal diameter, equal to the nominal diameter, or may exceed the nominal diameter. For example, the body cavity stenosis can be measured to have an untreated diameter of 10 mm. The physician may select a drug-coated balloon with a nominal diameter of 14 mm, a nominal pressure of 6 atm, and a rated burst pressure of 10 atm. The stretch ratio is 1.4. The physician will inflate the balloon to at least 6 atm, and in some cases to 8 atm or 10 atm, and in some cases to more than 10 atm, to achieve the desired inflated balloon diameter during treatment.

[0109] In various embodiments, the balloon catheter has one or more neck segments separating one or more main segments, and the construction of at least one neck segment or one or more neck segments of the balloon catheter of the present invention allows the balloon catheter to remain in place to dilate the stenosis and deliver the drug more consistently and effectively during treatment compared to other balloon catheters lacking such neck segments or neck segment constructions.

[0110] In various embodiments, the balloon catheter can be equipped with a sheath. The catheter assembly and a viewing instrument (e.g., a cystoscope) are inserted transurethrally into the prostatic urethra, and they are placed side by side near the external sphincter. Using real-time video input from the viewing instrument, the external sphincter can be located. Adjacent to the external sphincter and in the prostatic urethra, a balloon can be placed. Balloon expansion, drug release, and balloon contraction can be visualized by the viewing instrument.

[0111] In various embodiments, the balloon catheter can be assembled with the cystoscope by reassembling the shaft through the working channel and connecting the Tuohy Borst and one-way stopcock at the proximal end. The cystoscope-catheter assembly is inserted transurethrally into the prostatic urethra. Using real-time video input from the cystoscope, the external sphincter can be located. The balloon can be placed adjacent to the external sphincter and within the prostatic urethra.

[0112] In some embodiments, when treating the prostate, it is preferred to place the proximal balloon waist in the external sphincter so that the external sphincter is not expanded. It is also preferred to size the balloon so that when the balloon waist is in the external sphincter, the balloon neck (e.g., the distal-most balloon neck) is aligned with the bladder neck. This arrangement provides a holding force so that the balloon does not slip during expansion. If the balloon neck cannot be aligned with the bladder neck, it may be preferred to slowly inflate the balloon so that the prostate can yield when the balloon is inflated.

[0113] Once properly placed, the balloon is inflated, such as using an inflation device with a pressure gauge. The balloon can be inflated slowly, which allows the prostate tissue to yield and reduces the tendency of the balloon to slide into the bladder proximally and reverse distally. Although the single-necked or multi-necked shape of the balloon can prevent balloon movement by aligning the most distal neck with the bladder neck, in some abnormal cases, such as those with median lobe enlargement (e.g., about 10-15% of cases), the neck of the balloon may not remain aligned with the neck of the bladder during inflation, and additional techniques may help to further prevent balloon migration. In some instances, inflation at a rate of about 0.5-1atm / min can prevent balloon movement. As the tissue yields, the balloon pressure drops accordingly, allowing additional fluid to be instilled into the balloon without increasing pressure. When the pressure stabilizes for about 1-2 minutes, the pressure can be increased in increments of 0.5 or 1atm and maintained in a similar manner. The pressure can be continuously increased according to this method of increasing pressure, which allows the pressure to be stabilized after the pressure drops, and the pressure continues to be increased until the commissure incision or split is achieved. Alternatively, very slow inflation can prevent the balloon from migrating to achieve commissure incision or prostate splitting. Once the commissure incision or prostatic urethra and prostate splitting are observed and confirmed by video input from the observation instrument, mechanical decompression can be achieved. The balloon can remain inflated for about 1 minute to 7 days, 1 minute to 1 day, or 1-10 minutes to allow the drug in the coating to be delivered to the tissue. Once the treatment is completed, the balloon can be deflated, and the catheter and observation instrument can be removed from the patient's body cavity.

[0114] In some embodiments, when treating the prostate, it may be desirable to pre-dilate the stenosis. In this embodiment, the pre-dilation catheter can be shorter and / or smaller in diameter than the drug-coated balloon treatment catheter, and there may be no drug coating. In this scheme, the pre-dilation catheter is placed so that the proximal waist of the balloon is in the external sphincter, and the neck area is aligned with the bladder neck. The balloon is slowly inflated as described herein to help yield the prostate while preventing the balloon from sliding. Once inflated, the pre-dilution balloon is contracted and removed, and the drug-coated treatment balloon is inserted. The proximal waist of the treatment balloon is aligned with the external sphincter. If the prostate is properly pre-dilated, it is not necessary to align the balloon neck with the bladder neck, because the balloon does not slide as easily as in a body cavity that is not pre-dilated. In some embodiments, before treatment with a drug-coated balloon, other stenosis as described herein can be pre-dilated with a non-drug-coated balloon catheter.

[0115] The drug-coated balloon catheter can include an elongated balloon body with multiple main sections, two cones at the distal and proximal ends of the balloon body, an inflation cavity and a line cavity, wherein the balloon body includes at least two main sections with a larger diameter and at least one neck section with a smaller diameter, wherein the main section with a larger diameter and the neck section are alternately and adjacently arranged. Except for any neck section on the balloon, any tapered section (e.g., cone) between the neck section and the main section with the main diameter, and any tapered or shaped section at the longitudinal end of the balloon, the elongated balloon can have a generally cylindrical shape. The elongated balloon can have any suitable cross-section taken perpendicular to the longitudinal direction of the balloon, such as a circular (e.g., cylindrical balloon), an elliptical, a curved, an asymmetric shape, or a polygon (e.g., a pentagon, a hexagon, a heptagon, an octagon, etc.) or a combination thereof. The so-called diameter of a non-cylindrical balloon can be the maximum dimension perpendicular to the longitudinal direction, or the average dimension perpendicular to the longitudinal direction.

[0116] The balloon can be formed of any suitable material, such as a non-compliant or semi-compliant biocompatible material. In some embodiments, the balloon can be made by blow molding to achieve the desired geometry. In some embodiments, the balloon can include a material that does not interact with the drug coating, or a material such as nylon (e.g., any suitable nylon, such as nylon 6,6 or nylon 12), polyether block amide (PEBA), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyester, polyurethane, derivatives thereof, or combinations thereof.

[0117] The balloon can have any suitable size. The balloon can be designed to fit in the prostatic urethra, while the distal section of the balloon is placed in the bladder. The main diameter and nominal balloon diameter can range from about 5 mm to about 50 mm, 25 mm to 45 mm, at least 10 mm, at least 15 mm, at least 20 mm, at least 30 mm, such as about 5 mm or less, or less than, equal to, or greater than about 6 mm, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 34, 36, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or about 50 mm or more; the main section diameter can be independently within any one of these ranges or specific sizes. The balloon can have a length of about 20 mm to about 160 mm, 40 mm to about 80 mm, or about 20 mm or less, or less than, equal to, or greater than about 22 mm, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78 mm, or about 80 mm or more. The balloon length and diameter can be selected based on the patient's unique prostate anatomy.

[0118] The balloon may include at least one neck segment. A neck segment is a segment of the balloon having a diameter smaller than the main nominal diameter of the balloon. The neck segment diameter may be about 2 mm to about 35 mm, about 5 mm to about 35 mm, 10 mm to about 35 mm, or about 2 mm or less, or less than, equal to, or greater than about 3 mm, 4, 5, 6, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34 mm, or about 35 mm or greater. At least one neck segment can have a diameter that is independently about 5% to about 99% of the main diameter, such as about 20% to about 99%, or about 5% or less, or less than, equal to, or greater than about 10%, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98, or about 99% or more. In some embodiments, the neck segment diameter is 35% to 75% of the diameter of the main segment of the balloon. In some embodiments, where the main segment of the balloon has a nominal diameter of 30 to 40 mm, the neck segment will have a diameter of 12 to 20 mm. In some embodiments, if the neck diameter is too close to the diameter of the main segment, its ability to prevent the balloon from sliding may be reduced. In some embodiments, the balloon neck can be directly connected to the catheter shaft, which can produce separation between adjacent lobes. In some embodiments, separation between adjacent balloon lobes can be achieved by individually connecting two adjacent balloons to catheters in close proximity, such as separating the two balloons by a distance of 0 mm, or less than, equal to, or greater than 1 mm, 2, 3, 4, 5, 6, 7, 8, 9, or approximately 10 mm or greater.

[0119] The neck segment can be a rigid or semi-rigid neck segment so that the diameter of the neck segment (e.g., the portion of the neck segment having the diameter of the neck segment) remains substantially stationary during balloon inflation. The neck segment can include a substantially non-elastic (e.g., non-compliant or minimally non-compliant) portion of the balloon, a reinforced portion of the balloon, or a combination thereof. The neck segment can include a non-elastic material surrounding the periphery of the neck segment, such as a suture or monofilament or multifilament of nylon, polyamide, aramid, ultra-high molecular weight polyethylene (UHMWPE), polyester, aromatic polyester, polyethylene terephthalate (PET), or a combination thereof.

[0120] In some embodiments, the balloon neck segment can be semi-compliant and expand at a different rate than the main balloon body. The compliance of the neck segment can be greater than, less than, or equal to the compliance of the balloon body. Table 2 illustrates example measurements of a balloon having a neck segment that expands more than the balloon body. Over a test pressure range of 1-5atm, the expansion rate of the neck diameter can be higher than the expansion rate of the diameter of the main body segment. Over a test pressure range of 1-5atm, the expansion rate of the neck diameter can be 1.1-10 times the diameter of the main body segment (main diameter), such as 2-6 times the main diameter. The expansion rate of the neck diameter is 12.38% / atm. The expansion rate of the body diameter is 2.4% / atm. The difference in expansion rate is 9.98% / atm. Table 3 illustrates example measured inflation of a balloon having a neck segment that expands less than the balloon body when inflated from 2 atmospheres to 4 atmospheres. In the test pressure range of 2-4 atm, the expansion rate of the neck diameter may be less than the expansion rate of the diameter of the body section.

[0121] Table 2: Example measurements for balloons with a neck section that is more inflated than the balloon body

[0122]

[0123] Table 3: Example measurements for balloons with a neck section that is smaller than the balloon body

[0124]

[0125] The neck segment is capable of creating a wedge of tissue between the larger diameter segments of the balloon that can hold the balloon in place. The larger segments of the balloon cannot overcome the tissue barrier created in the neck segment, so the balloon with the neck segment prevents, reduces or minimizes balloon migration during inflation. The balloon neck segments can be placed at different locations along the balloon, the number can be more or less than two (e.g., 1, 2, 3, 4 or more), and the diameter can vary. The neck segment placement can be designed to promote the maximum increase in traction while still maintaining therapeutic efficacy.

[0126] The neck segment may include a central narrow portion having the smallest diameter of the neck segment, and an adjacent portion that may have a varying diameter and that occurs between the central narrow portion and the portion of the balloon having the main diameter. When the diameter of the neck segment is referred to herein, it refers to the diameter of the central narrow portion having the smallest diameter, not the tapered segment, unless otherwise specified. The tapered segment of the balloon may be rigid, flexible (e.g., elastic), or a combination thereof. The neck segment, as measured including a central narrow portion and a tapered portion (e.g., a cone) adjacent thereto, can have any suitable length, such as from about 1% to about 50% of the balloon length, or about 1% or less, or less than, equal to, or greater than about 2%, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48%, or about 50% or more, or from about 0.5 mm to about 40 mm, or about 0.5 mm or less, or less than, equal to, or greater than about 1 mm, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, or about 40 mm.

[0127] In some embodiments, the balloon can include one neck segment and no other neck segment, such that the balloon includes two main segments separated by one neck segment. One neck segment can have any suitable location on the balloon, such as approximately centered relative to the length of the balloon, or off-center relative to the length of the balloon. One neck segment can be off-center relative to the length of the balloon and can be at the distal end of the balloon. Figure 1A 0047] An embodiment of a balloon comprising a neck section that is off-center relative to the length of the balloon is illustrated in FIG.

[0128] In some embodiments, the balloon can include two neck segments and no other neck segment, so that the balloon includes three lobes separated by two neck segments. The two neck segments can have approximately the same diameter, or one of the neck segments can have a smaller diameter than the other neck segment. The positions of the two neck segments can be symmetrical or asymmetrical relative to the center of the balloon length. The three main segments can have approximately equal lengths or can have different lengths. Figure 1B The diagram illustrates an embodiment of a balloon catheter having two neck segments and three main segments, wherein the positions of the neck segments are symmetrical about the center of the balloon length, and wherein the three main segments of the balloon have approximately the same length. During use, the distal neck segment (e.g., the neck segment on the distal end of the balloon catheter that is first inserted into the body) can anchor and position the balloon at the bladder neck, while the proximal neck segment can be placed in the prostatic urethra. In some embodiments, the distal main segment of the balloon catheter may not contain a therapeutic agent.

[0129] In some embodiments, the balloon can include three necks and no other neck segments, so that the balloon includes four segments separated by three necks. The three neck segments can be arranged in any suitable manner along the length of the balloon. The four main segments formed by the three neck segments can have equal or different lengths. The three neck segments can have equal diameters or different diameters. In some embodiments, two of the neck segments have an equal diameter that is less than the diameter of the other neck segment. Figure 1C An embodiment of a balloon catheter having three neck segments and four main segments each having approximately equal length is illustrated, wherein two of the neck segments have equal diameters that are smaller than the diameter of the other neck segment.

[0130] The balloon catheter can be a fixed wire balloon catheter (fixed wire balloon catheter). The outer shaft can be coupled to the proximal balloon neck, the distal end of the tapered wire can be coupled to the distal neck of the balloon, and the proximal end of the wire and the outer shaft can be coupled to the hub (e.g., valve, connector, or adapter) at the proximal end of the balloon catheter. The balloon catheter can be a movable wire catheter. The outer shaft is coupled to the proximal balloon neck, the distal end of the tapered wire is coupled to the distal neck of the balloon, and the proximal end of the wire is free to move relative to the hub of the proximal end of the balloon catheter. The balloon catheter can be an integral exchange balloon catheter (over-the-wire balloon catheter). The balloon catheter can be a rapid exchange balloon catheter (rapidexchange balloon catheter). The balloon catheter can include a catheter shaft on the longitudinal end of the balloon (e.g., on the proximal end of the balloon, inserted into the body after the insert at the distal end), and the catheter shaft includes a lumen for delivering air, liquid, or a combination thereof to the inside of the balloon. The catheter shaft can include a thermoplastic material that is thermally connected (e.g., connected by heating or melting) to the balloon, such as a high-hardness material, such as a material similar or identical to the balloon material, such as polyurethane, polyamide, nylon (e.g., nylon 6,6 or nylon 12), polyether block amide (PEBA), or a combination thereof. In some embodiments, the catheter shaft can be an observation instrument (e.g., a cystoscope). High-hardness materials can help prevent, reduce, or minimize crushing, and can allow pushability and flexibility. The size of the catheter shaft outer diameter can be customized to allow the working channel of a standard cystoscope to pass through, or the diameter is small enough to be assembled side by side with the cystoscope in the body cavity. A fluid connection between the inner cavity and the balloon interior can be included, such as a hole in the catheter shaft below the balloon connection point, to allow the balloon to be inflated by instilling a medium through the inner cavity.

[0131] In some embodiments, the balloon can be inflated through a single inflation channel or cavity that communicates with the proximal catheter and inflates all main sections and the neck section of the balloon simultaneously. In some embodiments, the balloon can be inflated through separate channels or cavities that communicate with different sections of the balloon, such as one cavity for the proximal main section of the balloon, a second cavity for the neck section, and a third cavity for the distal main section of the balloon. Any suitable combination of inflation cavities or channels and communication locations within the balloon can be used to generate a suitable pressure or pressures for performing the method.

[0132] In some embodiments, the catheter shaft can include an elongated rigid component, such as a rod, mandrel, or wire, that is longitudinally aligned with the catheter shaft. Figures 5A-5D The diagram illustrates a balloon catheter that includes an elongated rigid component, core wire 505 . Figure 5A An embodiment of balloon inflation is illustrated and Figure 5B The illustration shows a balloon in a non-expanded state. At the proximal end of the shaft, a core wire 505 is connected to a catheter shaft 501 under a strain relief 508. The core wire 505 extends distally in the catheter shaft 501. In some embodiments, the catheter shaft is made of a 72D PEBA polymer. The shaft 501 is made of a material that exhibits a certain amount of elasticity when under tension. Below the balloon 503, the core wire 505 is covered by a hypotube 510. The hypotube 510 provides lateral strength to the core wire 505 so that it does not buckle when the balloon 503 is inflated. Near the distal end of the catheter, the hypotube 510 and the core wire 505 are coupled to a tip 502. A tip extrusion 506 connects the tip 502 to the hypotube 510 and the core wire 505. The space between shaft 501 and core wire 505 is the inflation chamber of balloon 503, and the interior of balloon 503 is in fluid communication with Luer hub 507. Although this embodiment can be used with any suitable balloon of the present invention, Figure 5A and 5B A balloon 503 is shown having a neck, with polyethylene fibers 504 used to reinforce the neck. Figure 5C Illustration Figure 5A A cross-sectional view of a deflated balloon is shown illustrating balloon 504, hypotube 510, and core wire 505. Figure 5D Illustration Figure 5B , showing the shaft 501 and the core wire 505.

[0133] The elongated rigid component can have a cross-sectional profile of a cylindrical, conical, rectangular, hexagonal or other shape, and can be made of metal or a relatively incompressible non-metallic material. The elongated component can extend from the proximal side of the balloon to the distal side of the balloon, or from a position of the balloon proximal to the proximal side to the distal side of the balloon. The elongated component can float freely in the central cavity of the catheter shaft, can be placed in a dedicated cavity in a multi-lumen catheter shaft, or can extend longitudinally outside the main catheter shaft. The elongated component can be anchored at a single point, two points or more than two points along the catheter shaft. The elongated component can be anchored by directly heat fusing it to the catheter shaft, bonding it or chemically bonding it to the catheter shaft, swaging or crimping it to one or more parts of the catheter, overmolding or by any other suitable method. The elongated component can be reinforced along its entire length or along certain parts (such as below the balloon) to prevent buckling; for example, the elongated metal component can be a reinforcing wire. The reinforcement can be constructed of any rigid material, such as stainless steel, Nitinol (i.e., nickel-titanium alloy), steel, tungsten, iridium, superalloys (e.g., containing elements such as nickel (Ni), chromium (Cr), aluminum (Al), titanium (Ti), tungsten (W), niobium (Nb), tantalum (Ta), or cobalt (Co)), PEEK, or combinations thereof, and can have any suitable cross-sectional shape. In some embodiments, the reinforcement is cylindrical, rectangular, hexagonal, or a tube having any suitable outer profile. The elongated component can be configured within the reinforcement tube, such as Figure 5C As shown, or arranged along the outside of the reinforcement tube.

[0134] like Figure 5A and 5BAs shown, catheter can include balloon length control mechanism, it makes balloon (when it is in contracted state) stretch and stretch, this provides balloon less cross-sectional contraction profile, so that tracking (tracking) by body cavity and take out after treatment.When balloon inflation, length control mechanism can allow balloon total length to shorten and inflate to predetermined inflation diameter and length (for example, as produced in molding or forming process) of balloon.In one embodiment, the power produced by balloon inflation can be transmitted from the distal end of balloon, for example, via the balloon being attached to the metal component of elongation or via the connection between catheter tip and the metal component of elongation, by catheter shaft by the rigid metal component of elongation return to the catheter shaft close to balloon, as via the connection between the metal component of elongation and catheter shaft close to the proximal end of balloon or the proximal end of balloon.This power will allow the transmission of catheter shaft to act as spring when catheter shaft material works in the elastic region of the stress-strain curve of catheter shaft material. During balloon inflation, as the catheter shaft stretches under tension due to balloon inflation, energy can be stored in the catheter shaft material and can be released by the catheter shaft during deflation to press against the elongated metal component to stretch the balloon. In some embodiments, a spring oriented longitudinally along the catheter shaft can be used to store and release the force of the balloon length-control mechanism. Figure 6 An embodiment of a spring 600 is illustrated, which may be used as Figures 5A-5D An alternative to the core wire 505 shown. Figure 6 , spring 600 has spring section 601 and silk section 602.In some embodiments, spring section 601 can be located at the proximal end of catheter shaft.Spring can be located in the cavity in catheter shaft, outside cavity but in catheter shaft or outside catheter shaft.Spring can be in balloon, or can be located and separated from balloon, for example, adjacent to the proximal end of balloon, or its combination.Compared with the length of inflation balloon, the elongated length of contracted balloon can be about 0.1mm longer to about 100mm longer, or less than, equal to or greater than about 0.1mm longer, 0.2, 0.4, 0.6, 0.8, 1, 1.5, 1, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90 or about 100mm longer or larger. The catheter shaft can include various materials to achieve the desired amount of force to extend the balloon, such as polyamide, nylon (e.g., nylon 6,6 or nylon 12), polyether block amide (PEBA) (e.g., 35D PEBA, 55D PEBA or 72D PEBA), polyurethane, silicone, rubber, another thermoplastic polymer, or a combination thereof. The catheter shaft can be uniform in composition, or can include a combination of materials distributed along one or more portions of the catheter shaft to produce a desired elongation force. Different materials can produce different elastic strains and different forces applied to the elongated rigid metal component so that the balloon is extended. The catheter shaft can be an extruded catheter shaft.

[0135] Catheter shaft, balloon or its combination can comprise single or multiple mark along its length to help place and align / calibrate with certain anatomical structures.Mark can have any suitable orientation, for example along the circumferential direction or longitudinal direction of catheter shaft or balloon.Mark on catheter shaft or balloon can be used to help place balloon in treatment area, indicate that balloon has been fully recovered in sheath, or equipment is positioned in patient's anatomical structure.Can use endoscope, cystoscope or naked eye to visualize the mark on catheter shaft, or mark can comprise radioactive identifiable component such as radiopaque material.Mark can be produced by polymer heat bonding on the surface of catheter shaft with identifiable color, via pad printing (pad print), via laser marking or via any other method. Figure 5A and 5B The diagram illustrates an embodiment of a balloon recapture marker 509 and a placement marker 511. When a balloon catheter includes a sheath covering the balloon, the balloon recapture marker 509 can be used. When the sheath covers the balloon, the marker 509 can be positioned just proximal to the proximal end of the sheath. After the user advances the catheter to the desired location, removes the sheath, and inflates the balloon, the user may wish to later advance the sheath so that it covers the balloon for removal. In this case, after deflation, the user would advance the sheath distally until the recapture marker 509 is visible. The placement marker 511 can be used to help the user place the catheter in a body cavity. For example, Figure 5A and 5B As shown, when a single neck balloon is used for BPH treatment, a placement mark that can be positioned just proximal to the proximal end of the balloon can be placed just proximal to the external sphincter. In various embodiments, the user can see the mark 511 through the viewing instrument, and when the mark is just proximal to the external sphincter, the user can be sure that the balloon is properly placed.

[0136] In various embodiments, the catheter shaft can have a separate lumen that creates a passage for urine to flow from the bladder through the catheter shaft and out through the exterior of the device. This embodiment can allow the drug-coated balloon catheter to remain in place for a period of time, such as 0.1 to about 7 days, while preventing bleeding as the tissue heals into a new configuration. The drug-coated balloon can be used not only for dilation and drug delivery, but can also be used as a Foley catheter or urinary catheter.

[0137] The catheter shaft at the end (e.g., the proximal end) that remains outside the body may include a hub (e.g., a valve, connector, or adapter) that provides a connection to the inner cavity of the catheter shaft. During inflation, the hub (e.g., when closed, or all the time) can prevent fluid or air from flowing back from the balloon. The hub may include any suitable valve, such as a Tuohy Borst adapter. The Tuohy Borst adapter is a compression seal that can be placed over the catheter shaft and tightened to provide a liquid-tight / air-tight connection to the inner cavity of the catheter shaft. A one-way stopcock can allow control of the fluid flow into the balloon and can be connected to the inflation device via a standard Luer.

[0138] The proximal side of the catheter shaft may include a hub or any other connection manifold to connect and inject fluid, air or other gas through the catheter to inflate the balloon, allow a guide wire to pass, allow urine to drain, or make any other suitable connection to the catheter shaft. The connection to the hub or connection manifold can be made via 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 can be made of any suitable biocompatible material, such as polycarbonate, acrylonitrile butadiene styrene, nylon, Silicone, any other polymeric material capable of being molded, or a combination thereof. The hub can be connected to the catheter in any suitable manner, such as using an adhesive (e.g., a cyanoacrylate adhesive, a silicone adhesive, an epoxy resin, any other adhesive suitable for the substrate, or a combination thereof) or using a chemical bond. The hub or manifold can be over-molded onto the catheter shaft to fuse it directly to the catheter shaft. The catheter shaft can include a strain relief component at the joint between the catheter shaft and the hub or manifold. The strain relief component can help prevent kinking. The strain relief component can include a polyolefin, PET, FEP, another heat shrink material, or a combination thereof. The strain relief component can be a heat shrink. The strain relief component can be a flexible molded material that interfaces with the hub (e.g., the strain relief component can be connected to the hub).

[0139] At the distal end that is first inserted into the body, the balloon catheter may include a catheter tip at the longitudinal end of the balloon. The catheter tip may facilitate passage of the balloon through the urethra. The tip may be an atraumatic tip that helps prevent damage to the urethra during insertion therein. The tip may be a Coude atraumatic tip. The atraumatic Coude tip is designed to facilitate passage of the catheter through the bends in the male urethra while preventing damage to the urethral wall during tracking. It may be a low durometer biocompatible material that is overmolded onto the catheter shaft or adhesively bonded to the shaft. For example, the Coude tip may be made of Or liquid silicone rubber.

[0140] In some embodiments, the catheter can include an insertion sheath that covers the balloon (e.g., a coated and folded / pleated balloon) during insertion and can be completely removed from the body during treatment. The sheath can be designed to couple with an obturator or dilator to facilitate reinsertion of the sheath into the body cavity. The sheath can include one material or more than one material. The sheath can have a laminated structure in which several different layers of material are combined together to form the sheath, or can be constructed using simple extrusion or coextrusion. In one embodiment, the sheath includes an inner layer, the inner layer includes a fluoropolymer, such as PTFE or FEP, an intermediate reinforcement layer, including a braided or coiled silk monofilament such as stainless steel, Nitinol, PEEK, or other material, and an outer layer includes a polymer such as Nylon, polyurethane or another thermoplastic material. The hardness (durometer) of the outer sheath material and the pitch (pitch) of the braided or coiled reinforcement can be uniform or can vary along the length of the sheath. The tight plug (obturator) can be an extruded tube or can be molded into a specific geometric shape and can include various types of materials, such as LDPE, HDPE, PE, PEBA, nylon, silicone, polyurethane or other biocompatible materials. The distal tip (inserted into the body) of the tight plug (obturator) can include a taper, a radius or some combinations that are convenient for passing through the body cavity. The sheath and the tight plug (obturator) can have a central connection of overmolded (over-molded), swaged (swaged), crimped (crimped) or adhesively bonded (adhesively-bonded), which allows them to interface together. Alternatively, the tight plug (obturator) can be flared outwards at the proximal side to produce a grasping feature (grasping feature) and produce an interference connection with the sheath. After treatment, an obturator and sheath can be inserted through the body cavity into the proximal side of the balloon. Once in place, the obturator can be separated from the sheath, and the sheath can be replaced over the deflated balloon to facilitate the removal of the balloon catheter.

[0141] Figure 2An embodiment of a balloon catheter including a catheter shaft, catheter tip, and Tuohy Borst adapter / stopcock assembly is illustrated. All materials may be biocompatible. The balloon is coated with a paclitaxel solution but may be coated with any multitude of other drugs or biologics that may promote improvement of BPH symptoms. Only the two main sections of the proximal end of the balloon are coated with drug, as the distal section is in the bladder during use.

[0142] The balloon catheter may include an inflation device including a pressure gauge or pressure sensor, the inflation device being fluidly connected to a catheter shaft connected to the balloon catheter.

[0143] Figure 1A , 1B The balloons shown in 1C and 2 are blow molded in a mold including a main section and a neck section. A tube of balloon material is inserted into the mold having the desired shape. The tube of balloon material may be pre-stretched. The balloon mold has a shape that corresponds to Figure 1A , 1B , 1C or 2. This will include a proximal cone, at least one body segment, at least one neck segment, at least one more body segment and a distal cone. The balloon material can be polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, Any of polyurethanes and block copolymers of polyethers and polyesters. The tube and mold are heated to a temperature above the glass transition temperature of the tube of the balloon material and pressurized with a gas, air, fluid, etc., causing the tube material to take the shape of the mold. The formed balloon is then cooled, trimmed, and then ready for connection to a catheter.

[0144] In one embodiment, the balloon is inflated under low pressure and the neck section reinforcement is connected to one or more neck regions. The neck section reinforcement is used to control the expansion of the neck section during balloon expansion. The neck section can be the substantially inelastic part of the balloon, the reinforcement part of the balloon, or a combination thereof. The neck section can include the inelastic material surrounding the neck section periphery, such as such material, such as steel, stainless steel, nitinol, tungsten, aluminum, copper, silver, gold, platinum, iridium, super alloys containing elements (including nickel (Ni) chromium (Cr), aluminum (Al), titanium (Ti), molybdenum (Mo), tungsten (W), niobium (Nb), tantalum (Ta) and cobalt (Co)), nylon, polyamide, aramid, ultra-high molecular weight polyethylene (UHMWPE), polyester, aromatic polyester, polyethylene terephthalate (PET) or the suture thread or monofilament or multifilament of its combination. In some embodiments, the polymer material is in the form of a strand or filament and is wrapped multiple times around the neck segment and then held in place by using a continuous bead of glue or adhesive, two or more spots of glue or adhesive, heat welding, adhesive bonding after plasma treatment, or adhesive bonding to an adhesive layer. The adhesive layer, which is a separate layer applied to the balloon prior to the fiber attachment process, can improve the adhesion of the fiber adhesive or glue to the outer surface of the one or more balloon necks.

[0145] The main sections of the balloon can be formed to have the same or similar diameters. In some embodiments, the diameters of the various main sections can differ from each other by as much as 30% when measured with the nominal balloon diameter. Figure 1A , 1B In , 1C and 2, the main sections of the balloon are shown to have equal diameters, i.e., the diameter of each main section is constant. In reality, at higher pressures, the diameter of the main sections will bend slightly outward, because the diameter of the middle portion of the main section may have a slightly larger diameter than the edge of the main section near the balloon cone and / or near the neck section.

[0146] For a balloon having a neck and a main section (e.g. Figure 1A , 1B , 1C and 2) and wherein the balloon does not have any neck segment (such as Figure 3 In some embodiments (shown in Figure 1), after the balloon catheter is assembled, the balloon can be coated with at least one water-soluble additive and a drug, as discussed herein. In some embodiments where the balloon has multiple main sections, the distal main section may not be coated. The balloon can be coated according to the methods discussed herein. If a sheath is used, it can be placed over the balloon after the balloon is coated. The catheter is then packaged, sterilized, and labeled as known in the art.

[0147] Embodiments of the present invention relate to balloon catheters with rapid drug release coatings and methods for preparing such coated devices. Therapeutic agents according to embodiments of the present invention do not require delayed or long-term release, and instead, for example, therapeutic agents and additives are released in a very short period of time to provide a therapeutic effect when in contact with tissue. An object of embodiments of the present invention is to promote rapid and effective absorption of drugs by target tissues during temporary device deployment at a target site.

[0148] The drug coating can cover any suitable proportion of the outer surface of the balloon (e.g., the proportion of the balloon surface that achieves the major diameter during inflation to nominal pressure, excluding the neck and end taper), such as from about 1% to about 100%, or from about 50% to about 100%, to about 80% to about 100%, or about 10% or less, 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% or more.

[0149] The drug coating may include a water-soluble additive, for example, selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglycamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate. rate), PEG caproate, monocaprylin, monocaprin, monocaprylin, monolaurin, monocaprin, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil The water-soluble additive may include a first water-soluble additive which is a surfactant such as PEG sorbitan monolaurate, PEG sorbitan monooleate, or a combination thereof. The water-soluble additive 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 drug coating may include both the first water-soluble additive and the second water-soluble additive. In some embodiments, the distal end of the balloon may be free of a therapeutic agent.

[0150] In various embodiments, the present invention provides a method for treating a body cavity. The body cavity can be a vascular body cavity or a non-vascular body cavity. The method can include inserting a balloon catheter (e.g., any embodiment of the balloon catheter described herein) into a target site in the body cavity. The method can include inflating the balloon until (e.g., at least until) the coating contacts the stenotic wall in the body cavity at the target site and the balloon reaches an inflated balloon diameter for an inflation period. Feature (a), or (b), or (c), or (a) and (b), or (a) and (c), or (b) and (c), or (a) and (b) and (c): (a) the ratio of the inflated balloon diameter at the target site to the untreated body cavity diameter is about 1.0 to about 40; or (b) the inflation comprises inflating the balloon to a pressure equal to or greater than the nominal pressure of the balloon catheter, and the stretch ratio at the target site is about 1.0 to about 40; or (c) the inflation comprises inflating to a pressure greater than the nominal pressure of the balloon catheter, and the nominal diameter of the balloon catheter is less than the inflated balloon diameter; or (d) a combination of (a), (b), and (c). The method may include deflation of the balloon after the inflation period. The method may include removing the balloon catheter from the stenosis in the body cavity.

[0151] Various embodiments provide methods for treating strictures of benign prostatic hyperplasia (BPH), urethral strictures, ureteral strictures, prostate cancer, esophageal strictures, biliary strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolic strictures, gastrointestinal strictures, J-pit ​​strictures, bladder neck strictures (e.g., strictures), fibrostenotic eosinophilic esophagitis strictures, strictures induced by Crohn's disease (CD) and ulcerative colitis (UC), radiation-induced strictures, strictures induced by endoscopic resection (EMR and ESD), surgically related anastomotic strictures, achalasia strictures, strictures induced by gastrectomy, asthma, or chronic obstructive pulmonary disease (COPD). The method is a method for treating strictures in a body cavity, such as urethral strictures, benign prostatic hyperplasia (BPH) strictures, ureteral strictures, esophageal strictures, antral strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, and bile duct strictures. The strictures in the body cavity can be benign prostatic hyperplasia (BPH) strictures, urethral strictures (structure), or esophageal strictures. The method can be a method for treating benign prostatic hyperplasia, prostate cancer, or a combination thereof, wherein the body cavity is the prostate.

[0152] The method may include flushing the body cavity with water, saline solution, or an aqueous solution including at least one water-soluble additive before, during, or after inserting the balloon into the target site.

[0153] The body cavity may be a prostate, wherein inserting the balloon catheter includes placing the balloon catheter in the prostate using a scope (e.g., flexible or rigid, such as a cystoscope). The balloon catheter may include a scope, and the method may include using a video input from the scope to locate the target site. The method may include using a video input from the scope to place the balloon catheter at the target site.

[0154] The body cavity may be a prostate, the balloon may have a plurality of main sections separated by one or more necks, and inserting the balloon catheter may include positioning one of the balloon catheter main sections in the prostate and positioning a second main section of the balloon catheter in the bladder.

[0155] Inserting may include positioning at least one neck segment of the balloon in the bladder neck. At least one neck segment of the balloon catheter may be a distal neck segment, and inserting may include positioning the distal neck segment in the bladder neck. The balloon catheter may include a proximal neck segment, and inserting may include positioning the proximal neck segment in the prostatic urethra.

[0156] The inflation period can be any suitable inflation period, for example, from about 0.1 minute to about 10 minutes, from about 0.5 minute to about 2 minutes, or about 0.1 minute or less, or about 0.2 minutes, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or about 10 minutes or more.

[0157] Inflation can include increasing the pressure within the balloon at any suitable rate (e.g., this can exclude periods where the pressure drops due to tissue yielding and the pressure can be maintained during these times), such as from about 0.1 atm / min to about 10 atm / min, or from about 0.5 to about 1.5 atm / min, or about 0.1 atm / min or less, or less than, equal to, or greater than about 0.2 atm / min, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or about 10 atm / min or greater.

[0158] Inflation can include observing the pressure within the balloon, such as by a pressure gauge. During yielding of the stenosis, which can result in a decrease in pressure, inflation can include allowing the pressure within the balloon to stabilize and maintaining the stable pressure in the balloon during a stabilization period during tissue yielding, and then resuming increasing the pressure in the balloon until the desired inflated diameter is reached. The stabilization period can be any suitable period, such as about 0.1 minute to about 10 minutes, about 0.5 minutes to about 2 minutes, or about 0.1 minutes or less, or about 0.2 minutes, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or about 10 minutes or more.

[0159] like Figure 3 As shown, in one embodiment, the medical device is a balloon catheter. The balloon catheter can be any suitable catheter for the desired purpose, including conventional balloon catheters known to those of ordinary skill in the art. For example, the balloon catheter 10 can include an expandable, inflatable balloon 12 (at the distal end of the catheter 10), a handle assembly 16 (at the proximal end of the catheter 10), and an elongated flexible member 14 extending between the proximal and distal ends. The handle assembly 16 can be connected to and / or receive one or more suitable medical devices, such as an inflation medium source (e.g., air, saline, or contrast media). The flexible member 14 can be a tube made of a suitable biocompatible material and having one or more lumens therein. At least one of the lumens is configured to receive an inflation medium and pass such medium to the balloon 12 to inflate it. The balloon catheter can be a rapid exchange or integral exchange catheter and made of any suitable biocompatible material. The material of the balloon 12 can include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, One or more of polyurethanes and block copolymers of polyethers and polyesters.

[0160] In one embodiment, the present invention provides a balloon catheter for delivering a therapeutic agent to a tissue, such as a vascular tissue or a non-vascular tissue. The device includes a layer applied to the outer surface of the balloon catheter. The layer includes a therapeutic agent and one or more additives. The additives can be any suitable additive. The layer can include one additive, or the layer can include more than one additive, such as a water-soluble first additive and a water-soluble second additive. For example, Figure 4AAs shown in the embodiment depicted in FIG, the balloon 12 is coated with a layer 20 comprising a therapeutic agent and an additive. In some embodiments, the layer consists essentially of the therapeutic agent and the additive, for example, the layer includes only the therapeutic agent and the additive without any other substantially significant components. In some embodiments, the device may optionally include an adhesive layer. For example, as Figure 4B In the depicted embodiment, the balloon 12 is coated with an adhesive layer 22. A layer 24 including therapeutic agents and additives covers the adhesive layer. The adhesive layer, which is a separate layer located below the drug coating, improves the adhesion of the drug coating 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 medical device, the adhesive layer can prevent differential loss of the components and maintain the ratio of drug to additive in the coating during transport to the target site of therapeutic intervention. In addition, the adhesive layer can serve to promote the rapid release of the coating components from the surface of the device when in contact with tissue at the target site. In other embodiments, the device may include a top layer. For example, as Figure 4C In the depicted embodiment, the balloon 12 is coated with an adhesive layer 22, a layer 26 including therapeutic agents and additives covering the adhesive layer, and a top layer 28. The top layer can reduce the loss of the drug layer before the drug layer contacts the target tissue, such as during delivery of the balloon 12 to the site of therapeutic intervention or during the first moments of inflation of the balloon 12, before the coating 20 is pressed into direct contact with the target tissue.

[0161] Embodiments of the present invention relate to treating strictures in body cavities by delivering an effective amount of a therapeutic agent such as an anti-inflammatory and anti-proliferative drug (e.g., paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or their analogs, or a combination thereof. Stenosis in body cavities includes vascular strictures, urethral strictures, ureteral strictures, esophageal strictures, achalasia strictures, strictures in stents, antral strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, and bile duct strictures. Embodiments of the present invention relate to methods for treating at least one of vascular stenosis, benign prostatic hyperplasia (BPH), urinary tract problems, prostate cancer, colorectal stenosis, post-gastric bypass stenosis, ileocolic stenosis, gastrointestinal stenosis, J-pit ​​stenosis, bladder neck stenosis (e.g., stenosis), fibrostenotic eosinophilic esophagitis stenosis, Crohn's disease (CD) and ulcerative colitis (UC) induced stenosis, radiation induced stenosis, endoscopic resection (EMR and ESD) induced stenosis, surgically related anastomotic stenosis, achalasia stenosis, gastrectomy induced stenosis, asthma, and chronic obstructive pulmonary disease (COPD). According to an embodiment, the method involves delivering a therapeutic agent such as an anti-inflammatory and antiproliferative drug (e.g., rapamycin, paclitaxel, or their analogs) via a coated medical device, such as a balloon catheter. The therapeutic agent can be coated on the medical device alone or with one or more additives.

[0162] In one embodiment, the invention relates to a method for treating a stricture in a body lumen comprising inserting a balloon catheter comprising a coating into the stricture, wherein the stricture is a urethral stricture, a ureteral stricture, an esophageal stricture, an antral stricture, an achalasia stricture, a stricture in a stent, a stomach stricture, a small intestinal stricture, a duodenal stricture, a jejunal stricture, an ileal stricture, a colonic stricture, a rectal stricture, a large intestinal stricture, a colorectal stricture, a stricture after gastric bypass, an ileocolic stricture, a gastrointestinal stricture, a J-pit ​​stricture, a bladder neck stricture (e.g., a stricture), a fibrostenotic eosinophilic esophagitis stricture, a Crohn's disease (CD ) and one of ulcerative colitis (UC) induced strictures, radiation induced strictures, endoscopic resection (EMR and ESD) induced strictures, surgically related anastomotic strictures, achalasia strictures, gastrectomy induced strictures, and biliary strictures, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the stricture, deflation of the balloon; and removing the balloon catheter, wherein the residual drug can be about 1 to 70% of the total drug load on the balloon catheter, wherein the drug in the wall of the body cavity can be about 0.1 to 25% of the total drug load on the balloon catheter. In one aspect of this embodiment, the additive enhances absorption of the drug into the tissue of the stricture in the body cavity.

[0163] In one embodiment, the present invention relates to a method for treating a stenosis of a body cavity, comprising inserting a balloon catheter comprising a coating into a body cavity, wherein the body cavity is one of the esophagus, airway, antrum, trachea, colon, bile duct, stomach, small intestine, duodenum, jejunum, ileum, rectum, large intestine, urinary tract, prostate, urethra, ureter, and other cavities, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the body cavity, deflated the balloon; and removing the balloon catheter, wherein the residual drug can be about 1 to 70% of the total loaded drug on the balloon catheter, wherein the drug in the wall of the body cavity can be about 0.1 to 25% of the total loaded drug on the balloon catheter. In one aspect of this embodiment, the additive enhances the absorption of the drug into the tissue of the body cavity. In another aspect of this embodiment, the additive comprises a hydrophilic portion and a drug affinitive portion, wherein the drug affinitive 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.

[0164] In one embodiment, the present invention relates to a balloon catheter for delivering a therapeutic agent to a target site of a body lumen stenosis, the balloon catheter comprising a coating covering the outer surface of the balloon, wherein the coating comprises an initial drug loading amount of a therapeutic agent, and one or more water-soluble additives; the therapeutic agent is selected from paclitaxel, docetaxel, taxol, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, and their analogs, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N- Octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceride, monocapric glyceride, monolauric glyceride, monocapric glyceride, monocaprylic glyceride, monomyristic glyceride, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose e), aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthosine, xanthosine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof.

[0165] In one embodiment of the balloon catheter, the one or more water-soluble additives promote rapid release of the therapeutic agent from the balloon, and whereby the rapid release comprises a residual drug amount of the therapeutic agent remaining on the balloon after the balloon is inflated at a target site in a body cavity for an inflation period of about 0.1 minutes to 10 minutes and then removed from the body cavity.

[0166] In one embodiment of the balloon catheter, the ratio of the weight of the therapeutic (e.g., hydrophobic) agent in the coating to the total weight of one or more additives in the coating can be from about 0.05 to about 20, from about 0.1 to about 10, from about 0.1 to about 5, from about 0.5 to about 8, from about 0.5 to about 3, from about 2 to about 6, or about 0.05 or less, or less than, equal to, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 or more. In one embodiment of the balloon catheter, the ratio of the weight of the therapeutic agent in the coating to the total weight of one or more water-soluble additives in the coating (e.g., the total weight of the first and second water-soluble additives or the first, second, and third water-soluble additives in the coating) is about 0.05 to about 20, about 0.1 to about 10, about 0.1 to about 5, about 0.5 to about 8, about 0.5 to about 3, about 2 to about 6, or about 0.05 or less, or less than, equal to, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 or more.

[0167] In one embodiment, the present invention relates to a method for treating stenosis in a body cavity, the method comprising flushing the body cavity with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the stenosis in the body cavity, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon. The coating comprises at least one water-soluble additive, and an initial drug loading amount of a therapeutic agent; the therapeutic agent is selected from paclitaxel, docetaxel, taxol, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, their analogs, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galactosylceramide ... clocerebrosides), lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate, PEG caproate e), monocaprylic acid glyceryl, monocapric acid glyceryl, monocaproic acid glyceryl, monolauric acid glyceryl, monocapric acid glyceryl, monocaprylic acid glyceryl, monomyristic acid glyceryl, monopalmitolein, monooleic acid glyceryl, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N' -bis(hydroxymethyl)urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; inflating the balloon until the coating contacts the wall of the stenosis in the body cavity at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflation of the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the stenosis in the body cavity. The inflated balloon catheter diameter can be such that the ratio of the inflated balloon diameter to the untreated diameter of the treated body cavity can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated site can be about 1.0 to about 40, or about 4 to about 40.Optionally, inflating may include inflating to a pressure equal to or greater than a nominal pressure of the balloon catheter.

[0168] After removal, the balloon may have a residual amount of drug thereon. Any suitable amount of residual drug may remain after removal, for example, greater than, equal to, or less than about 90 wt%, 88, 86, 84, 82, 80, 78, 76, 74, 72, 70, 68, 66, 64, 62, 60, 58, 56, 54, 52, 50, 48, 46, 44, 42, 40, 38, 36, 34, 32, 30, 28, 26, 24, 22, 20, 18, 16, 14, 12, 10, 8, 6, 4, 3, 2, 1 wt%, or about 0 wt%.

[0169] In one embodiment, the present invention relates to a method for treating at least one of benign prostatic hyperplasia and prostate cancer, the method comprising flushing the prostate with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the prostate, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon. The coating may include one or more water-soluble additives, and an initial drug loading amount of a therapeutic agent; inflating the balloon until the coating contacts the wall of the benign prostatic hyperplasia or prostate cancer at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflate the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and remove the balloon catheter from the prostate. The ratio of the inflated balloon diameter to the untreated diameter of the body cavity can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0170] In one embodiment, the present invention relates to a method for treating a urethral stricture, the method comprising flushing the urethral stricture with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the urethral stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and an initial drug loading amount of a therapeutic agent; and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the urethral stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the urethral stricture. The ratio of the inflated balloon diameter to the untreated diameter of the urethra at the location of the stricture can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated site can be about 1.0 to about 40, or about 4 to about 40. After dilation, the diameter of the urethral stricture can be 6.7 mm or greater, such as about 6.7 mm to about 50 mm, or about 6.7 mm to about 20 mm, or less than, equal to, or greater than about 6.7, 6.8, 6.9, 7.0, 7.2, 7.4, 7.6, 7.8, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45 mm, or about 50 mm or greater. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0171] In one embodiment, the present invention is directed to a method for treating esophageal strictures such as achalasia strictures, the method comprising, optionally, before, during or after inserting a balloon catheter, flushing the esophageal stricture with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting the balloon catheter into a target site in the esophageal stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon (at its nominal diameter); and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the esophageal stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the esophageal stricture. The ratio of the balloon diameter to the untreated diameter of the esophagus at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some embodiments, the balloon catheter performance is equal to or similar to those given in Table 4, with a slower growth rate at higher pressures. Compliance is the percentage change in balloon diameter from nominal diameter to rated burst pressure (RBP) diameter, calculated as: diameter @ RBP - diameter @ nominal pressure) / diameter @ nominal pressure) * 100%. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0172] Table 4: Examples of performance of balloon catheters for the treatment of esophageal and gastrointestinal strictures

[0173] Nominal diameter(mm) Rated bursting pressure diameter (mm) Nominal pressure (atm) Rated burst pressure(atm) Compliance (%) 4 6 3 12 50 6 8 3 10 30 8 10 3 9 25 10 12 3 8 20 12 15 3 8 17 15 18 3 7 20 18 20 3 6 11 20 23 3 6 15 23 25 3 6 9 30 34 2 4 13 35 40 2 4 14 40 45 2 4 12

[0174] In one embodiment, the present invention is directed to a method for treating esophageal strictures such as achalasia strictures, the method comprising, optionally before, during, or after inserting a balloon catheter, flushing the esophageal stricture with water, a saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting the balloon catheter into a target site in the esophageal stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon (at its nominal diameter); and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the esophageal stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the esophageal stricture. The ratio of the inflated balloon diameter to the untreated diameter of the esophagus at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. In some embodiments, the balloon catheter performance is equal to or similar to those given in Table 5, and a single balloon catheter has the ability to achieve a wide range of balloon diameters at relatively high working pressures compared to conventional compliance balloons. The balloons in Table 5 have a unique feature, namely, there are three increased balloon diameters at three increased inflation pressure stages. The nominal inflation diameter is the diameter of stage I. For each stage of pressure increase, the diameter increases by about 0.5-4mm, preferably 0.75-3mm, and most preferably 0.9-2mm. For example, a balloon with a diameter of 15 mm at pressure I (3 atm) will have a diameter of 16.5 mm at pressure II (4.5 atm) and a diameter of 18 mm at pressure III (7 atm).

[0175] Table 5: Examples of performance of balloon catheters for the treatment of esophageal and gastrointestinal strictures.

[0176]

[0177] In one embodiment, the present invention relates to a method for treating gastrointestinal strictures, including gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, or biliary strictures, the method comprising flushing the gastrointestinal stricture with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the gastrointestinal stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon (at its nominal diameter); and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the esophageal stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the esophageal stricture. The inflated balloon catheter diameter can be such that the ratio of the balloon diameter to the untreated diameter of the esophagus at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. In some embodiments, the balloon catheter has the same or similar properties as given in Tables 4 and 5, with a slowed growth rate at higher pressures, and a single balloon catheter has the ability to achieve a wide range of balloon diameters at high working pressures.

[0178] In various embodiments, a drug coated balloon catheter for treating esophageal strictures, achalasia strictures, gastrointestinal strictures including gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolonic strictures, gastrointestinal strictures, J-pouch strictures, bladder neck strictures (e.g., strictures), fibrostenotic eosinophilic esophagitis strictures, Crohn's disease (CD) and ulcerative colitis (UC) induced strictures, radiation-induced strictures, endoscopic resection (EMR and ESD)-induced strictures, surgery-related anastomotic strictures, achalasia strictures, gastrectomy-induced strictures, and biliary strictures, has a catheter design that is a fixed wire, wire-guided, over-the-wire catheter, or a rapid exchange design catheter.

[0179] In one embodiment, the present invention is directed to a method for treating sinus stenosis, the method comprising: flushing the sinus stenosis with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the sinus stenosis, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, the initial drug loading being 1-6 micrograms of the therapeutic agent per square millimeter of the balloon (at its nominal diameter); the therapeutic agent being selected from budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, mometasone furoate, and the like. furoate, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, betamethasone, triamcinolone acetonide, paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, analogs thereof, and combinations thereof;The water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octanoyl- tonoyl)-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceryl, monocapric glyceryl, monocaprylic glyceryl, monolauric glyceryl, monocapric glyceryl, monocaprylic glyceryl, monomyristic glyceryl, monopalmitoleic glyceryl esters (monopalmitolein), monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis (hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate , glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ether, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the sinus stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the sinus stenosis. ;

[0180] In some embodiments, it may be desirable to pre-expand a targeted area of ​​a body cavity, such as the prostatic urethra or any other target site, before using a drug-coated balloon. In some embodiments, the pre-expanded balloon is selected to be slightly shorter and / or have a slightly smaller nominal diameter than the treatment balloon. If the pre-expanded balloon is shorter than the treatment balloon, it will be more likely that the entire pre-expanded area or region is treated by the treatment balloon. In some embodiments, the size of the pre-expanded balloon can be customized to be substantially the same as the treatment balloon, so that the nominal diameter and length of the pre-expanded balloon are substantially matched with the nominal diameter and length of the treatment balloon. In some embodiments, it may be desirable to directly treat the targeted area of ​​the body cavity without pre-expanding. In some embodiments, the method includes using an observation instrument that visualizes the insertion and placement of a pre-expanded balloon catheter in the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, or any combination thereof.

[0181] Embodiments of the present invention relate to balloon catheters with rapid drug release coatings and methods for preparing such coated devices. Therapeutic agents according to embodiments of the present invention do not require delayed or long-term release, and instead, for example, therapeutic agents and additives are released in a very short period of time to provide a therapeutic effect when in contact with tissue. An object of embodiments of the present invention is to promote rapid and effective absorption of drugs by target tissues during temporary device deployment at a target site.

[0182] In various embodiments, the balloon catheter can have one or more (e.g., 2) neck segments along the balloon body. The neck segment has a nominal diameter smaller than the nominal balloon body diameter (e.g., the latter is 1.5-2.5 times the former) and can be any suitable length, e.g., about 10-20 mm long. The neck segment can separate the balloon symmetrically or can cause certain balloon body segments to be longer than other segments. The nominal balloon diameter can be 6-45 mm and the working length is 20-160 mm.

[0183] exist Figure 1A In one embodiment, a balloon having a neck section is shown. Balloon 100 has waist 101, cone 102, first body section 103, neck 104, second body section 105, cone 106, and waist 107. When assembled into a balloon catheter, waists 101 and 107 will be connected or coupled (or otherwise) to a catheter shaft (not shown), as is known in the art. During inflation, waists 101 and 107 are not inflated because they are connected to the catheter shaft. Sections 102, 103, 104, 105, and 106 can all be inflated simultaneously through a single inflation point that is in communication with the catheter shaft and an external Luer hub. In Figure 1BIn one embodiment, a balloon having two neck sections is shown. Balloon 120 has a waist 121, a cone 122, a first body section 123, a first neck 124, a second body section 125, a second neck 126, a third body section 127, a cone 128, and a waist 129. When assembled into a balloon catheter, waists 121 and 129 will be connected or coupled (or otherwise) to the catheter shaft as is known in the art. During inflation, waists 121 and 129 are not inflated because they are connected to the catheter shaft. Sections 122, 123, 124, 125, 126, 127, and 128 can all be inflated simultaneously via a single inflation point in communication with the catheter shaft and an external Luer hub. Although neck sections 124 and 126 are shown as being the same diameter in the current inflated state, they can be the same or different diameters with the same or different compliances. In Figure 1C In one embodiment, a balloon with three neck sections is shown. Balloon 140 has waist 141, cone 142, first body section 143, first neck 144, second body section 145, second neck 146, third body section 147, third neck 148, fourth body section 149, cone 150 and waist 151. When assembled into a balloon catheter, waists 141 and 151 will be connected or coupled (or other means) to the catheter shaft as known in the art. During inflation, waists 141 and 151 are not inflated because they are connected to the catheter shaft. Sections 142, 143, 144, 145, 146, 147, 148, 149 and 150 can all be inflated simultaneously through a single inflation point that is connected to the catheter shaft and an external Luer hub. Although neck sections 144, 146, and 148 are shown as having different diameters in the present inflated state, they may be the same or different diameters with the same or different compliances.

[0184] like Figure 2As shown, in one embodiment, the medical device is a balloon catheter, a fixed wire balloon catheter, a moveable wire catheter, an over-the-wire balloon catheter, a rapid exchange balloon catheter, including conventional balloon catheters known to those of ordinary skill in the art. For example, the balloon catheter 160 may include an expandable, inflatable balloon 162 (at the distal end of the catheter 160), a handle assembly 161 (at the proximal end of the catheter 160), an elongated flexible member 164 extending between the proximal and distal ends, and an anti-damage Coude tip 163 at the distal end. The handle assembly 161 may be connected to and / or receive one or more suitable medical devices, such as an inflation medium source (e.g., air, water, saline, or contrast medium). The flexible member 164 may be a tube made of a suitable biocompatible material and having one or more lumens therein. At least one of the lumens is configured to receive an inflation medium and pass such a medium to the balloon 162 to inflate it. The balloon catheter may be a fixed wire or rapid exchange or integral exchange catheter and may be made of any suitable biocompatible material. The material of the balloon 162 may include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, One or more of polyurethane and block copolymers of polyether and polyester. Figure 2 In one embodiment, a balloon with two neck sections is shown. Balloon 162 has waist 165, cone 166, first body section 167, first neck 168, second body section 169, second neck 170, third body section 171, cone 172 and waist 173. When assembled into the balloon catheter, as known in the art, waist 165 and 173 will be connected or combined (or other means) to the catheter shaft. During inflation, waist 165 and 173 are not inflated because they are connected to the catheter shaft. Sections 166, 167, 168, 169, 170, 171 and 172 can all be inflated simultaneously through a single inflation point communicated with the catheter shaft and an external Luer hub. Although neck sections 168 and 170 are shown as being the same diameter in the current inflation state, they can be the same or different diameters with the same or different compliances.

[0185] like Figure 3As shown, in one embodiment, the medical device is a balloon catheter. The balloon catheter can be any suitable catheter for the desired purpose, including a fixed wire balloon catheter, a moveable wire catheter, an over-the-wire balloon catheter, a rapid exchange balloon catheter, including conventional balloon catheters known to those of ordinary skill in the art. For example, the balloon catheter 10 can include an expandable, inflatable balloon 12 (at the distal end of the catheter 10), a handle assembly 16 (at the proximal end of the catheter 10), and an elongated flexible member 14 extending between the proximal and distal ends. The handle assembly 16 can be connected to and / or receive one or more suitable medical devices, such as a source of inflation medium (e.g., air, saline or contrast medium). The flexible member 14 can be a tube made of a suitable biocompatible material and having one or more lumens therein. At least one of the lumens is configured to receive an inflation medium and pass this medium to the balloon 12 to inflate it. The balloon catheter 10 may be a rapid exchange or integral exchange catheter and may be made of any suitable biocompatible material. The material of the balloon 12 may include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, One or more of polyurethanes and block copolymers of polyethers and polyesters.

[0186] like Figures 7A-7C As shown in , in one embodiment, the medical device is a unit exchange balloon catheter or a rapid exchange balloon catheter. Fig. 7A A side view is shown. Figure 7B Illustration Fig. 7A Cross-section view of the central axis. Figure 7C Illustration from Fig. 7AThe cross-sectional view of the balloon of the catheter 700. The balloon catheter 700 may include an expandable, inflatable balloon (at the distal end of the catheter 700). The balloon 711 may have a proximal cone section 706, a first body section 707, a neck section 708, a second body section 709 and a distal cone section 710. The balloon catheter 700 may have a handle or Luer assembly 705, which is communicated by passage 704 to inflate the balloon 711 and allow a guide wire to be placed by passage 703. The handle assembly 705 may be connected to and / or receive one or more suitable medical devices, such as a source of inflation medium (e.g., air, water, saline or contrast medium). Flexible members 701 and 702 may be made of suitable biocompatible materials and have a tube with one or more cavities therein. An outer flexible member or extrusion 701 is placed above the top of the flexible member or extrusion 702 and terminates at the proximal balloon junction. The inner flexible member or extrusion 702 passes the entire length of the balloon catheter 700 below the balloon 711 and terminates at the distal end of the catheter in the form of a flexible rounded tip. The material of the balloon 711 may include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, One or more of polyurethanes, block copolymers of polyethers and polyesters, or combinations thereof.

[0187] In one embodiment, the present invention provides a medical device for delivering a therapeutic agent to a diseased tissue or stenosis, such as vascular tissue or non-vascular tissue. The device includes a layer applied to the outer surface of a balloon catheter. The layer includes a therapeutic agent and one or more additives. The additives can be any suitable additive. The layer can include one additive, or the layer can include more than one additive, such as a water-soluble first additive and a water-soluble second additive. For example, Figure 4A As shown in the embodiment depicted in FIG, the balloon 12 is coated with a layer 20 comprising a therapeutic agent and an additive. In some embodiments, the layer consists essentially of the therapeutic agent and the additive, for example, the layer includes only the therapeutic agent and the additive without any other substantially significant components. In some embodiments, the device may optionally include an adhesive layer. For example, as Figure 4BIn the depicted embodiment, shown, the balloon 12 is coated with an adhesive layer 22. A layer 24 including therapeutic agents and additives covers the adhesive layer. The adhesive layer, which is a separate layer located below the drug coating, improves the adhesion of the drug coating to the outer surface of the medical device and protects the coating integrity. For example, if the drug and additive have different adhesion to the medical device, the adhesive layer can prevent the difference loss of the components and maintain the ratio of the drug to the additive in the coating during transportation to the target site of therapeutic intervention. In addition, the adhesive layer can play a role in promoting the rapid release of the coating components from the device surface when in contact with the tissue at the target site. In other embodiments, the device can include a top layer. The top layer can reduce the loss of the drug layer before the drug layer contacts the target tissue, for example, during the delivery of the balloon 12 to the treatment intervention site or during the first moment of the balloon 12 inflation, before the coating 20 is pressed into direct contact with the target tissue.

[0188] Embodiments of the invention are directed to treating stenosis in non-vascular body lumens by delivering an effective amount of a therapeutic agent such as an anti-inflammatory and anti-proliferative drug (e.g., rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, paclitaxel, taxol, docetaxel, or their analogs). Stenosis in non-vascular body lumens includes urethral strictures, ureteral strictures, esophageal strictures, antral strictures, achalasia strictures, strictures in stents, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolic strictures, gastrointestinal strictures, J-pouch strictures, bladder neck strictures (e.g., strictures), fibrostenotic eosinophilic esophagitis strictures, Crohn's disease (CD) and ulcerative colitis (UC) induced strictures, radiation induced strictures, endoscopic resection (EMR and ESD) induced strictures, surgically related anastomotic strictures, achalasia strictures, gastrectomy induced strictures, and biliary strictures. Embodiments of the present invention relate to methods of treating at least one of benign prostatic hyperplasia (BPH), prostate cancer, asthma, and chronic obstructive pulmonary disease (COPD). According to various embodiments, the method includes delivering therapeutic agents such as anti-inflammatory and anti-proliferative drugs (e.g., rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, paclitaxel, taxol, docetaxel, or their analogs) via a coated balloon catheter. The anti-inflammatory and anti-proliferative drugs can be coated on the medical device alone or with one or more additives.

[0189] A method for treating a stenosis in a non-vascular body lumen comprises inserting a balloon catheter comprising a coating into a body lumen, wherein the coating comprises a drug and an additive, inflating the balloon catheter and releasing the drug to the wall of the non-vascular body lumen, deflated the balloon; and removing the balloon catheter, wherein the residual drug can be about 1 to 70% of the total loaded drug on the balloon catheter, wherein the drug in the wall of the body lumen can be about 0.1 to 25% of the total loaded drug on the balloon catheter. The method may include flushing the body lumen with water, saline solution, or an aqueous solution comprising at least one water-soluble additive before, during, or after inserting the balloon into the target site. In one aspect of this embodiment, the additive enhances absorption of the drug into the non-vascular body lumen tissue. In another aspect of this embodiment, the additive comprises a hydrophilic portion and a drug affinity portion, wherein the drug affinity portion is at least one of a hydrophobic portion, a portion having affinity for the therapeutic agent by hydrogen bonding, and a portion having affinity for the therapeutic agent by van der Waals interactions.

[0190] A balloon catheter for delivering a therapeutic agent to a target site in a non-vascular body cavity may include a coating covering the outer surface of the balloon, wherein the coating includes an initial drug loading amount of a therapeutic agent, and one or more water-soluble additives; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, and their analogs, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6 -ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric glyceryl oleyl esters, PEG8 caprylic / capric glycerides, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceride, monocapric glyceride, monocaprylic glyceride, monolauric glyceride, monocapric glyceride, monocaprylic glyceride, monomyristic glyceride, monopalmitolein, monooleic glyceride, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame Butame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof.

[0191] The non-vascular body lumen can be one of the esophagus, airway, antrum, trachea, colon, bile duct, stomach, small intestine, duodenum, jejunum, ileum, rectum, large intestine, urinary tract, prostate, urethra, ureter, and other non-vascular lumens.

[0192] In some embodiments, the one or more water-soluble additives can promote rapid release of the therapeutic agent from the balloon, and whereby the rapid release comprises a residual drug amount of the therapeutic agent remaining on the balloon after the balloon is inflated at a target site in a non-vascular body lumen for an inflation period of about 0.1 minutes to 10 minutes and then removed from the non-vascular lumen.

[0193] The ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more additives in the coating can be about 0.05 to about 20, about 0.1 to about 10, about 0.1 to about 5, about 0.5 to about 8, about 0.5 to about 3, about 2 to about 6, or about 0.05 or less, or less than, equal to, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 or more. The ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating (e.g., the total weight of the first and second water-soluble additives or the first, second, and third water-soluble additives in the coating) can be about 0.05 to about 20, about 0.1 to about 10, about 0.1 to about 5, about 0.5 to about 8, about 0.5 to about 3, about 2 to about 6, or about 0.05 or less, or less than, equal to, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 or more.

[0194] The initial drug load may be 1 microgram to 20 micrograms of therapeutic agent per square millimeter of balloon (i.e., surface area per nominal diameter of the balloon), or about 2 to about 6 micrograms, or about 1 microgram or less, or less than, equal to, or greater than about 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or about 20 micrograms or more. The amount of residual drug may be 70% or less of the initial drug load.

[0195] The method for treating a stenosis in a non-vascular body lumen comprises flushing the non-vascular body lumen with water, a saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the stenosis in the non-vascular body lumen, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon. The coating comprises at least one water-soluble additive, and an initial drug loading amount of a therapeutic agent; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, and their analogs, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galactosylceramide ... rebrosides), lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octanoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceryl monophosphate, monocaprylate, monocaprylate, monomyristic acid, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) ) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; inflating the balloon until the coating contacts the wall of the stenosis in a non-vascular body lumen at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the stenosis in the non-vascular body lumen. In some embodiments, the balloon diameter is 10 mm at a nominal inflation pressure of 6 atm. The ratio of the inflated balloon diameter to the untreated diameter of the target site of the body lumen can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40.Optionally, inflating may include inflating to a pressure equal to or greater than a nominal pressure of the balloon catheter.

[0196] After removal, the balloon may have a residual amount of drug thereon. Any suitable amount of residual drug may remain after removal, such as greater than, equal to, or less than about 70 wt%, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5 wt%, or about 0 wt%.

[0197] The ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more additives in the coating can be about 0.05 to about 20, about 0.1 to about 10, about 0.1 to about 5, about 0.5 to about 8, about 0.5 to about 3, about 2 to about 6, or about 0.05 or less, or less than, equal to, or greater than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or about 20 or more.

[0198] In various embodiments, the coating may include one or more water-soluble additives, and an initial drug loading of a therapeutic agent; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucamide, N-nonanoyl-N-methylglucamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, ceramide cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric acid Glycerides, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylin, monocaprylin, monocaprylin, monolaurin, monocaprin, monocaprin, monocaprylin, monomyristyl glyceride, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine The invention also includes the following: adenine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthosine, xanthosine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof.

[0199] In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0200] A method of treating at least one of benign prostatic hyperplasia and prostate cancer may include optionally flushing the prostate with water, saline solution, or an aqueous solution including at least one water-soluble additive; inserting a balloon catheter into a target site in the prostate, the balloon catheter including a balloon and a coating covering the outer surface of the balloon; and positioning the balloon body in the prostate and over the external urethral sphincter so that the balloon neck is in the bladder neck when the balloon is inflated. The method may include inflating the balloon until the coating contacts the wall of the benign prostatic hyperplasia or prostate cancer at the target site, the enlarged prostate is divided and the commissure is cut, and the balloon reaches an inflated balloon diameter for an inflation period; deflate the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and remove the balloon catheter from the prostate. The ratio of the inflated balloon diameter to the untreated body cavity diameter at the target site can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. Optionally, inflation may include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. In some embodiments, the method includes using a scope that visualizes insertion and placement of the drug-coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0201] A method of treating an achalasia stenosis comprises optionally flushing the achalasia stenosis with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter at a target site in the esophagus, the balloon catheter comprising a balloon and a coating covering an outer surface of the balloon; positioning the balloon body in the esophagus and above the esophageal sphincter such that when the balloon is inflated, the balloon neck is in the lower esophageal sphincter and the distal segment of the balloon is in the upper end of the stomach. The method may comprise inflating the balloon until the coating contacts the wall of the achalasia stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the esophagus. The ratio of the inflated balloon diameter to the untreated body cavity diameter at the target site may be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated site may be about 1.0 to about 40, or about 4 to about 40. In some cases, the achalasia stenosis can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. The balloon catheter can include one or more necks, such as Figures 1A-1C and Figure 2In various embodiments, the neck of the balloon can be positioned in the lower esophageal sphincter, with one or more balloon lobes distal to the neck in the stomach and one or more balloon lobes proximal to the neck in the esophagus.

[0202] The method for treating urethral stricture comprises flushing the urethral stricture with water, saline solution, or an aqueous solution including at least one water-soluble additive; inserting a balloon catheter into a target site in the urethral stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and an initial drug loading amount of a therapeutic agent; and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the urethral stricture at the target site, and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the urethral stricture. The ratio of the inflated balloon diameter to the untreated diameter of the body cavity at the site of the urethral stricture can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated site can be about 1.0 to about 40, or about 4 to about 40. After dilation, the diameter of the urethral stricture can be 6.7 mm or greater, such as about 6.7 mm to about 50 mm, or about 6.7 mm to about 20 mm, or less than, equal to, or greater than about 6.7, 6.8, 6.9, 7.0, 7.2, 7.4, 7.6, 7.8, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45 mm, or about 50 mm or greater. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0203] In one embodiment, after removal, the balloon has an amount of residual drug thereon that is less than about 70% of the initial drug load.

[0204] The method for treating esophageal stricture comprises optionally flushing the esophageal stricture with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the esophageal stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methyl Glucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG 8 Caprylate, PEG caprate, PEG caproate, caprylic acid glyceryl, capric acid glyceryl, caproic acid glyceryl, lauric acid glyceryl, capric acid glyceryl, capric acid glyceryl, caprylic acid glyceryl, myristic acid glyceryl, palmitoleic acid glyceryl, oleic acid glyceryl, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis( The invention relates to a method of coating a stenosis of the esophagus and a stenosis of the esophagus. The method comprises the following steps: coating the stenosis of the esophagus and a stenosis of the esophagus. The method comprises the following steps: coating the stenosis of the esophagus and a stenosis of the esophagus. The method comprises the following steps: first, coating the stenosis of the esophagus and a stenosis of the esophagus. The stenosis of the esophagus and a stenosis of the esophagus. The method comprises the following steps: first, coating the stenosis of the esophagus and a stenosis of the esophagus. The stenosis of the esophagus and a stenosis of the esophagus. The stenosis of the esophagus and a stenosis of the esophagus.The ratio of the inflated balloon diameter to the untreated diameter of the esophagus at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated luminal diameter and the balloon can achieve an expansion ratio of 0.7, 0.8, 0.9 or more. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0205] Eosinophilic esophagitis (EoE) is a chronic inflammatory disease. Symptoms of the disease include dysphagia and food impaction, and are often the result of esophageal stricture or narrowing. Repeated endoscopic dilatation of esophageal fibrostenotic eosinophilic esophagitis strictures using bougies and balloon catheters is required to treat esophageal strictures in EoE.

[0206] A method for treating esophageal strictures in eosinophilic esophagitis comprises optionally flushing the esophageal stricture with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the esophageal stricture, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N- Methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG8 Caprylate, PEG caprate, PEG caproate, monocaprylin, monocaprylin, monocaprylin, monolaurin, monocaprin, monocaprin, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) ) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and a ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the esophageal stricture at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the esophageal stricture of eosinophilic esophagitis.The ratio of the inflated balloon diameter to the untreated diameter of the esophagus at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated luminal diameter and the balloon can achieve an expansion ratio of 0.7, 0.8, 0.9 or more. In some cases, the esophageal stricture can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter.

[0207] Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). CD- and UC-induced strictures are common complications of IBD and its related surgical procedures. Over time, stricture rates can range from 34% to 70%. Some strictures are refractory or recurrent. Using current state-of-the-art techniques, repeated endoscopic dilations are required to treat refractory or recurrent strictures.

[0208] A method for treating inflammatory intestinal strictures in Crohn's disease (CD) and ulcerative colitis (UC) comprises optionally flushing the inflammatory intestinal stricture with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter at a target site in the treatment of inflammatory intestinal strictures, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl- D-Glucosamide, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride , PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylin, monocaprylin, monocaprylin, monolaurin, monocaprin, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N , N'-bis(hydroxymethyl)urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and a ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating of about 0.05-20; inflating the balloon until the coating contacts the wall of the inflammatory intestinal stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the inflammatory intestinal stenosis.The ratio of the inflated balloon diameter to the untreated diameter of the inflammatory bowel at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated luminal diameter and the balloon can achieve an expansion ratio of 0.7, 0.8, 0.9 or more. In some cases, the stenosis can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. Inflammatory bowel strictures of Crohn's disease (CD) and ulcerative colitis (UC) include small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolonic strictures, gastrointestinal strictures, and J-pit ​​strictures. Although balloon dilatation has been shown to be a safe and effective non-surgical method for treating inflammatory bowel strictures in Crohn's disease (CD) and ulcerative colitis (UC), problems still exist. Stenosis can be refractory or recurrent strictures, and using the technology of the prior art, repeated balloon dilatation is required. In another embodiment, the method for treating inflammatory bowel strictures in Crohn's disease (CD) and ulcerative colitis (UC) includes performing stricture incision before balloon dilatation of a drug coating. Stricture incision can include endoscopic mucosal resection, endoscopic submucosal dissection, needle knife electroresection and electrocautery. In some embodiments, the method includes using an observation instrument, which visualizes the insertion and placement of a drug-coated balloon catheter in a target site, inflation and contraction processes, an increase in balloon diameter during inflation, a decrease in balloon diameter during contraction, yielding of the target site, a released drug on the wall of the target site after balloon contraction, or any combination thereof. The method can include flushing the target site with water or saline solution through an observation instrument, and then inserting a balloon catheter into the stenosis or target site.

[0209] The method for treating radiation-induced stenosis comprises optionally flushing the radiation-induced stenosis with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the radiation stenosis, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N- Methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG 8 Caprylate, PEG caprate, PEG caproate, caprylic acid glyceryl, capric acid glyceryl, caproic acid glyceryl, lauric acid glyceryl, capric acid glyceryl, capric acid glyceryl, caprylic acid glyceryl, myristic acid glyceryl, palmitoleic acid glyceryl, oleic acid glyceryl, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) The invention relates to a method of treating a stenotic injury of a patient suffering from a stenotic injury of at least one of the following types of injuries: inflating the balloon until the coating contacts the wall of a radiation-induced stenosis at a target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is from 0.1 minute to 10 minutes; and removing the balloon catheter from the radiation-induced stenosis.The ratio of the inflated balloon diameter to the untreated diameter of the irradiated body lumen at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases, the radiation-induced stricture can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. Radiation-induced strictures include any stricture induced by radiation damage caused by the treatment of cancer. Radiation strictures can include urethral strictures, ureteral strictures, esophageal strictures, antral strictures, gastric strictures, small intestinal strictures, colonic strictures, rectal strictures, large intestinal strictures, and bile duct strictures. In another embodiment, a method for treating radiation strictures includes performing a stricture cut prior to dilation of a drug-coated balloon. Stricture incision can include urethrotomy, endoscopic mucosal resection, endoscopic submucosal stripping, needle knife electroresection, direct visual internal urethrotomy (DVIU) and electrocautery. In some embodiments, the method includes using a viewing instrument, which visualizes the insertion and placement of a drug-coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method can include flushing the target site with water or saline solution through a viewing instrument, and then inserting a balloon catheter into the stenosis or target site.

[0210] The method for treating surgical anastomotic stenosis comprises optionally flushing the surgical anastomotic stenosis with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the surgical anastomotic stenosis, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonano ... N-acetyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, P EG8 caprylate, PEG caprate, PEG caproate, caprylic acid glyceryl, capric acid glyceryl, caproic acid glyceryl, lauric acid glyceryl, capric acid glyceryl, caprylic acid glyceryl, myristic acid glyceryl, palmitoleic acid glyceryl, oleic acid glyceryl, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) The invention relates to a method of coating a surgical anastomotic stenosis comprising: coating the coating with a water-soluble agent selected from the group consisting of urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and a ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the surgical anastomotic stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is from 0.1 minute to 10 minutes; and removing the balloon catheter from the surgical anastomotic stenosis.The ratio of the inflated balloon diameter to the untreated diameter of the body lumen at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated lumen diameter and the balloon can achieve an expansion ratio of 0.7, 0.8, 0.9 or more. In some cases, anastomatic stenosis can be pre-dilated with an uncoated balloon, which can have a nominal diameter smaller than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. Surgical anastomotic stenosis includes any stenosis that is surgically connected between two fluid-carrying body stenosis. Surgical anastomosis is a surgical technique used to establish a new connection between two fluid-carrying body stenosis. Anastomotic stenosis is a common complication of various surgical procedures. Most of these strictures are fibrotic and difficult to manage. Anastomotic strictures include esophageal strictures, bile strictures, gastric strictures, small intestinal strictures, duodenal strictures, jejunal strictures, ileal strictures, colonic strictures, rectal strictures, large intestinal strictures, colorectal strictures, strictures after gastric bypass, ileocolonic strictures, gastrointestinal strictures, urethral strictures, ureteral strictures, J- cul-de-sac strictures, and bladder neck strictures (stenosis). Balloon dilatation has been shown to be a safe and effective non-surgical method for managing surgical anastomotic strictures. Anastomotic strictures can be refractory or recurrent strictures that require repeated balloon dilatation using prior art techniques. In another embodiment, a method for treating surgical anastomotic strictures includes performing stricture incision prior to drug-coated balloon dilatation. Stricture incisions can include urethrotomy, endoscopic mucosal resection, endoscopic submucosal dissection, needle knife electroresection, direct vision internal urethrotomy (DVIU) and electrocautery. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0211] Bladder neck stenosis (stricture or contracture) is a recognized complication of many prostate cancer treatments. Refractory bladder neck stenosis is relatively rare overall; however, they are associated with significant morbidity, often requiring multiple interventions with associated complications and impacting quality of life. These bladder neck stenosis diseases are often complications following prostate cancer treatments, including radical prostatectomy (RP), radiation therapy, cryotherapy, and high-intensity focused ultrasound (HIFU), and may develop after prostate treatment or may develop due to other conditions.

[0212] A method for treating bladder neck stenosis (stricture or contracture) comprises optionally flushing the bladder neck stenosis with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the bladder neck stenosis, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonano ... N-acetyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate , PEG8 caprylate, PEG caprate, PEG caproate, monocaprylin, monocapric glyceryl, monocaprylin, monolaurin, monocapric glyceryl, monocaprylin, monomyristyl glyceryl, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'- bis(hydroxymethyl)urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and a ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating of about 0.05-20; inflating the balloon until the coating contacts the wall of the bladder neck stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the bladder neck stenosis.The ratio of the inflated balloon diameter to the untreated diameter of the bladder neck at the location of the stenosis can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated luminal diameter and the balloon may achieve an expansion ratio of 0.7, 0.8, 0.9 or more. In some cases, the stenosis can be pre-dilated with an uncoated balloon, which may have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. Bladder neck stenosis includes any stenosis of the surgical connection between the bladder and the prostate or urethral cavity. Bladder neck stenosis is a common complication of various surgical procedures, including radical prostatectomy (RP), radiation therapy, cryotherapy, and high-intensity focused ultrasound (HIFU). Most of these strictures are fibrotic and difficult to manage. Bladder neck stenosis may be a refractory or recurrent stricture, which requires repeated balloon dilatation using prior art techniques. In another embodiment, the method for treating bladder neck stenosis comprises performing stricture incision prior to drug-coated balloon dilation. Stricure incision may include urethrotomy, endoscopic mucosal resection, endoscopic submucosal dissection, needle knife electrourethrotomy, direct visual internal urethrotomy (DVIU) and electrocautery.

[0213] EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection) in the treatment of various stages of cancer and Barrett's esophagus. Needle knife, EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection) are used to treat early superficial cancers. Cancers include esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenal cancer, jejunal cancer, ileal cancer, colon cancer, rectal cancer, colorectal cancer, ileocolonic cancer, and gastrointestinal cancer. EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection) are used to treat high-graded Barrett's esophagus. EMR and ESD are feasible procedures in terms of clinical efficacy and safety; however, recurrence of malignant tumors and refractory strictures have been noted in some patients. The local recurrence rate of cancer after treatment ranges from 2-20%, depending on the type and stage of cancer and the follow-up time. The recurrence rate of stricture or stenosis is about 26%-70%. Using the technology of the prior art, repeated endoscopic balloon dilatation is needed to treat refractory or recurrent strictures or stenosis. In various embodiments, after EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection), the present invention uses the expansion of a drug-coated balloon to reduce the recurrence of malignant tumors or cancer. In various embodiments, after EMR (endoscopic mucosal resection) or ESD (endoscopic submucosal dissection), the present invention uses the expansion of a drug-coated balloon to reduce the need for repeated balloon dilatation of strictures.

[0214] A method is provided for reducing stenosis and cancer recurrence after surgical procedures of needle knife, EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection).The method comprises performing endoscopic resection of a cancerous area of ​​a body cavity using a needle knife, EMR (endoscopic mucosal resection) and ESD (endoscopic submucosal dissection); optionally flushing the resected body cavity with water, saline solution or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the resected body cavity, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof , and combinations thereof; water-soluble additives selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic acid / caprylic acid glyceryl monooleate, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2 -hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and a ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the resected body cavity at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the resected body cavity.The ratio of the inflated balloon diameter to the untreated diameter of the body cavity can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases, the stenosis can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. The length of the drug-coated balloon is greater than the length of the resected body cavity, so that the resected area is completely covered by the drug formulation after balloon inflation. The length of the drug-coated balloon is 1 to 2 mm longer than the length of the resected body cavity. Sometimes two drug-coated balloons can be overlapped to cover a longer length of lesions. Cancers can include esophageal cancer, gallbladder cancer, gastric cancer, small intestine cancer, duodenal cancer, jejunal cancer, ileal cancer, colon cancer, rectal cancer, colorectal cancer, ileocolonic cancer, and gastrointestinal cancer, especially those early-stage cancers. As the area and depth of resection of the body cavity increase, the recurrence of cancer and stenosis may increase. In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug-coated balloon catheter at the target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0215] A method for reducing the recurrence of stricture, colon polyps, or Barrett's esophagus after surgical procedures such as needle knife, EMR (endoscopic mucosal resection), and ESD (endoscopic submucosal dissection) includes first performing endoscopic resection of colon polyps or Barrett's (esophagus) areas of a body cavity using needle knife, EMR (endoscopic mucosal resection), or ESD (endoscopic submucosal dissection); optionally flushing the resected body cavity with water, saline solution, or an aqueous solution including at least one water-soluble additive; inserting a balloon catheter into a target site in the resected body cavity, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble second additive, and a therapeutic agent, with an initial drug loading of 1-6 micrograms of the therapeutic agent per square meter. The balloon is sized in mm square; the therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or their analogs, and combinations thereof; the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamide, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl- D-sphingosine, N-octonoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceride, monocapric glyceride, monolauric glyceride, monocapric glyceride, monocaprylic glyceride, monomyristic glyceride, monopalmitolein, monooleic glyceride, creatine, creatinine, agmatine, citrulline, guanidine , sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the resected body cavity at the target site and the balloon reaches the inflated balloon diameter for an inflation period; defl ucing the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the resected body cavity. The ratio of the inflated balloon diameter to the untreated diameter of the body cavity can be about 1.0 to about 40, or about 4 to about 40; the stretch ratio at the treated location can be about 1.0 to about 40, or about 4 to about 40. In some cases where severe stenosis is present, it may not be possible to inflate the balloon to the untreated cavity diameter and the balloon can achieve an expansion ratio of 0.7, 0.8, 0.9 or more. In some cases, the stenosis can be pre-dilated with an uncoated balloon, which can have a smaller nominal diameter than the treatment balloon. Optionally, inflation can include inflation to a pressure equal to or greater than the nominal pressure of the balloon catheter. The length of the drug-coated balloon is greater than the length of the resected body cavity, so that the resected area is completely covered by the drug formulation after balloon inflation. The length of the drug-coated balloon is 1 to 2 mm longer than the length of the resected lumen. As the area and depth of the resected lumen increase, the recurrence of polyps or Barrett's esophagus and stricture increases.

[0216] A method for treating sinus stenosis comprises flushing the sinus stenosis with water, saline solution, or an aqueous solution comprising at least one water-soluble additive; inserting a balloon catheter into a target site in the sinus stenosis, the balloon catheter comprising a balloon and a coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and a therapeutic agent, wherein the initial drug loading is 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; the therapeutic agent is selected from budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, mometasone furoate, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, betamethasone, triamcinolone acetonide), paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, analogs thereof, and combinations thereof;The water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, cerabroside, sphingomyelin, galaclocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octanoyl- tonoyl)-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceryl, monocapric glyceryl, monocaprylic glyceryl, monolauric glyceryl, monocapric glyceryl, monocaprylic glyceryl, monomyristic glyceryl, monopalmitoleic glyceryl esters (monopalmitolein), monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis (hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate , glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof; and the ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the wall of the sinus stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; deflating the balloon after the inflation period, wherein the inflation period is 0.1 minutes to 10 minutes; and removing the balloon catheter from the sinus stenosis. ;

[0217] In some embodiments, the method includes using a scope that visualizes the insertion and placement of a drug coated balloon catheter at a target site, the inflation and deflation process, the increase in balloon diameter during inflation, the decrease in balloon diameter during deflation, the yielding of the target site, the released drug on the wall of the target site after balloon deflation, or any combination thereof. The method may include flushing the target site with water or saline solution through a scope and then inserting the balloon catheter into the stenosis or target site.

[0218] additive

[0219] In various embodiments, the additive has two parts. One part is hydrophilic, and the other part is a drug affinity part. The drug affinity part is a hydrophobic part and / or has affinity to the therapeutic agent by hydrogen bonding and / or van der Waals interactions. The drug affinity part of the additive can be combined with lipophilic drugs, such as paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors or their analogs, and combinations thereof. The hydrophilic part accelerates diffusion and improves drug penetration into tissues. The hydrophilic part can promote rapid movement of drugs away from medical devices by preventing hydrophobic drug molecules from agglomerating with each other and agglomerating on the device during deployment at the target site, thereby improving the drug solubility in the interstitial space, and / or accelerating the drug lumen to reach the lipid bilayer of the cell membrane of the target tissue through the polar head group. The additive of an embodiment of the present invention has two parts, which together serve to promote rapid release of the drug from the device surface and uptake by the target tissue during deployment (by accelerating the contact of the drug with tissues for which the drug has a high affinity), while preventing premature release of the drug from the device surface prior to device deployment at the target site.

[0220] In embodiments of the present invention, the therapeutic agent is rapidly released and rapidly absorbed after the medical device is brought into contact with the tissue. For example, certain embodiments of the device of the present invention include a drug-coated balloon that delivers a therapeutic agent such as a lipophilic antiproliferative drug (such as paclitaxel or rapamycin) to non-vascular tissues by simple, direct pressure contact at high drug concentrations during inflation and expansion of the balloon non-vascular body balloon. The lipophilic drug is retained, for example, in the target tissue at the target site, where it inhibits hyperplasia and restenosis and also allows epithelial growth. In these embodiments, the coating formulation of the present invention not only promotes the rapid release of the drug from the balloon surface during deployment and transmits the drug to the target tissue, but also prevents the drug from diffusing out of the device during transportation through the curved anatomical structure before reaching the target site and prevents the drug from being expelled from the device during the initial stage of balloon inflation before pressing the drug coating into the surface that directly contacts the body cavity.

[0221] The additive according to certain embodiments has a drug affinity part and a hydrophilic part. The drug affinity part is a hydrophobic part and / or has affinity for therapeutic agents through hydrogen bonding and / or van der Waals interactions. The drug affinity part can include aliphatic and aromatic organic hydrocarbons, such as benzene, toluene and alkanes, etc. These parts are insoluble in water. They can combine both hydrophobic drugs (which share structural similarities with each other) and lipids of cell membranes. The drug affinity part can include functional groups that can form hydrogen bonds with drugs and with themselves. The hydrophilic part can include hydroxyl, amine, amide, carbonyl, carboxylic acid and anhydride, diethyl ether, ethylene glycol, polyethylene glycol, ascorbic acid, amino acids, amino alcohols, glucose, sucrose, sorbitan, glycerol, polyols, phosphates, sulfates, organic salts and molecules substituted therewith, etc. One or more hydroxyl groups, carboxyl groups, acids, amides or amine groups, for example, can be advantageous because they easily replace hydrogen bonds to polar head groups and water molecules of surface proteins of cell membranes and can be used to remove this barrier between hydrophobic drugs and cell membrane lipids. These moieties can be dissolved in water and polar solvents. The additives of embodiments of the present invention have components for combining drugs and promoting the rapid movement of the drug away from the medical device during deployment to the target tissue.

[0222] The additive in the embodiment of the present invention can be a surfactant and a compound with one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties. The surfactant includes ionic, nonionic, aliphatic and aromatic surfactants. The compound with one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties is selected from amino alcohols, hydroxycarboxylic acids and anhydrides, diethyl ether, ethylene glycol, amino acids, peptides, proteins, sugars, glucose, sucrose, sorbitan, glycerol, polyols, phosphates, sulfates, organic acids, esters, salts, vitamins and substituted molecules thereof.

[0223] As is well known in the art, the terms "hydrophilic" and "hydrophobic" are relative terms. For use as additives in accordance with exemplary embodiments of the present invention, compounds include a polar or charged hydrophilic portion and a nonpolar hydrophobic (lipophilic) portion.

[0224] An empirical parameter commonly used in medicinal chemistry to characterize the relative hydrophilicity and hydrophobicity of a drug compound is the partition coefficient, P, i.e., the ratio of the concentrations of the unionized compound in the two phases of a mixture of two immiscible solvents (usually octanol and water) such that P = ([solute] octanol / [solute] water). The higher the log P, the more hydrophobic the compound is, while the lower the log P, the more hydrophilic the compound is. The Lipinski rule states that a drug compound with a log P < 5 may be more membrane permeable. For the purposes of certain embodiments of the present invention, for example, the additive has a log P that is less than the log P of the drug to be formulated (as an example, the log P of paclitaxel is 7.4). A greater difference in log P between the drug and the additive may promote phase separation of the drug. For example, if the log P of the additive is much lower than the log P of the drug, the additive may accelerate the release of the drug from the surface of the device to which the drug may otherwise be tightly adhered in an aqueous environment, thereby accelerating the delivery of the drug to the tissue during simple deployment at the intervention site. In certain embodiments of the present invention, the log P of the additive is negative. In other embodiments, the log P of the additive is less than the log P of the drug. While the octanol-water partition coefficient, P, or log P, of a compound can be used as a measure of relative hydrophilicity and hydrophobicity, it is only a rough criteria that may be useful in defining suitable additives for use in embodiments of the invention.

[0225] Suitable additives that can be used in embodiments of the present invention include, but are not limited to, organic and inorganic pharmaceutical excipients, natural products and derivatives thereof (such as sugars, vitamins, amino acids, peptides, proteins and fatty acids), low molecular weight oligomers, surfactants (cations, anions, nonionicity and ionicity) and mixtures thereof. The additives as described herein that can be used in the present invention are provided only for exemplary purposes, and are not intended to encompass everything. Many other additives can be used for purposes of the present invention.

[0226] Surfactants

[0227] Surfactant can be any surfactant suitable for pharmaceutical composition.This surfactant can be cationic, anionic, zwitterionic or nonionic.Mixtures of surfactants are also within the scope of various embodiments of the present invention, because they are combinations of surfactants and other additives.Surfactant often has one or more long aliphatic chains such as fatty acids, and these one or more long aliphatic chains can be directly inserted into the lipid bilayer of cell membrane to form the part of lipid structure, and other components of surfactant loosen lipid structure and enhance drug penetration and absorption simultaneously.Contrast agent iopromide does not have these characteristics.

[0228] An empirical parameter often used to characterize the relative hydrophilicity and hydrophobicity of surfactants is the hydrophilic-lipophilic balance value ("HLB" value). Surfactants with lower HLB values ​​are more hydrophobic and have greater solubility in oils, while surfactants with higher HLB values ​​are more hydrophilic and have greater solubility in aqueous solutions. Using the HLB value as a rough standard, hydrophilic surfactants are generally considered to be those compounds with an HLB value greater than about 10, as well as anionic, cationic or zwitterionic compounds for which the HLB measurement is generally not applicable. Similarly, hydrophobic surfactants are compounds with an HLB value less than about 10. In certain embodiments of the present invention, higher HLB values ​​are used because increased hydrophilicity can promote the release of hydrophobic drugs from the surface of the device. In one embodiment, the HLB of the surfactant additive is higher than 10. The additive HLB can be higher than 14. Alternatively, surfactants with lower HLB can be used to prevent drug loss before device deployment at the target site, for example, in a top layer above a drug layer with a very hydrophilic additive.

[0229] The HLB value of a surfactant is only a rough standard that is generally used to achieve the formulation of, for example, industrial, pharmaceutical, and cosmetic emulsions. For many important surfactants, including several polyethoxylated surfactants, it has been reported that the HLB values ​​can vary by up to about 8 HLB units, depending on the empirical method chosen to determine the HLB value (Schott, J. Pharm. Sciences, 79 (1), 87-88 (1990)). Keeping these inherent difficulties in mind and using the HLB value as a standard, as described herein, surfactants having the appropriate hydrophilicity or hydrophobicity for use in embodiments of the present invention can be identified.

[0230] PEG-fatty acids and PEG-fatty acid mono- and diesters

[0231] Although polyethylene glycol (PEG) itself is not used as a surfactant, numerous PEG-fatty acid esters have useful surfactant properties. Among PEG-fatty acid monoesters, lauric acid, oleic acid and stearic esters are most suitable for embodiments of the present invention. The example of hydrophilic surfactant includes PEG-8 laurate, PEG-8 oleate, PEG-8 stearate, PEG-9 oleate, PEG-10 laurate, PEG-10 oleate, PEG-12 laurate, PEG-12 oleate, PEG-15 oleate, PEG-20 laurate and PEG-20 oleate. The HLB value is 4-20.

[0232] Polyethylene glycol fatty acid diesters are also suitable for use as surfactants in the compositions of the present invention. Hydrophilic surfactants include PEG-20 dilaurate, PEG-20 dioleate, PEG-20 distearate, PEG-32 dilaurate and PEG-32 dioleate. HLB values ​​are 5-15.

[0233] In general, mixtures of surfactants are also useful in embodiments of the present invention, including mixtures of two or more commercial surfactants and mixtures of a surfactant with another additive or additives.Several PEG-fatty acid esters are commercially available as mixtures or mono- and diesters.

[0234] Polyethylene glycol glycerol fatty acid ester

[0235] The hydrophilic surfactant may include PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, PEG-40 glyceryl laurate, PEG-20 glyceryl oleate, and PEG-30 glyceryl oleate.

[0236] Alcohol-oil transesterification products

[0237] Many surfactants with varying degrees of hydrophobicity or hydrophilicity can be prepared by the reaction of alcohol or polyols with various natural and / or hydrogenated oils. The most common, the oil used is castor oil or hydrogenated castor oil, or edible vegetable oils such as corn oil, olive oil, peanut oil, palm kernel oil, apricot kernel oil or almond oil. Alcohol includes glycerol, propylene glycol, ethylene glycol, polyethylene glycol, sorbitol, and pentaerythritol. Among the surfactants of these alcohol-oil transesterifications, the hydrophilic surfactant is PEG-35 castor oil (Incrocas-35), PEG-40 hydrogenated castor oil (Cremophor RH 40), PEG-25 trioleate (TAGAT TM TO), PEG-60 corn oil glycerides (Crovol M70), PEG-60 almond oil (Crovol A70), PEG-40 palm kernel oil (Crovol PK70), PEG-50 castor oil (Emalex C-50), PEG-50 hydrogenated castor oil (Emalex HC-50), PEG-8 caprylic acid monoglyceride / capric acid monoglyceride (Labrasol), and PEG-6 caprylic acid monoglyceride / capric acid monoglyceride (Softigen767). For example, this class of hydrophobic surfactants includes PEG-5 hydrogenated castor oil, PEG-7 hydrogenated castor oil, PEG-9 hydrogenated castor oil, PEG-6 corn oil (Labrafil TM M 2125 CS), PEG-6 almond oil (Labrafil TMM 1966 CS), PEG-6 almond oil (Labrafil TM M 1944 CS), PEG-6 olive oil (Labrafil TM M 1980 CS), PEG-6 peanut oil (Labrafil TM M 1969 CS), PEG-6 hydrogenated palm kernel oil (Labrafil TM M 2130 BS), PEG-6 palm kernel oil (Labrafil TM M 2130 CS), PEG-6 triolein (Labrafil TM b M 2735 CS), PEG-8 corn oil (Labrafil TM WL 2609 BS), PEG-20 corn oil glycerides (Crovol M40), and PEG-20 almond glycerides (Crovol A40).

[0238] Polyglycerol fatty acid

[0239] The polyglycerol esters of fatty acids are also suitable surfactants for embodiments of the present invention. In polyglycerol fatty acid esters, hydrophobic surfactants especially include polyglycerol oleate (Plurol Oleique), polyglycerol-2 dioleate (Nikkol DGDO), polyglycerol-10 trioleate, polyglycerol stearate, polyglycerol laurate, polyglycerol myristate, polyglycerol palmitate, and polyglycerol linoleate. Hydrophilic surfactants include polyglycerol-10 laurate (Nikkol Decaglyn 1-L), polyglycerol-10 oleate (Nikkol Decaglyn 1-O), and polyglycerol-10 monooleate, polyglycerol-10 dioleate (CaproI TM PEG 860), polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, polyglyceryl-10 linoleate, polyglyceryl-6 stearate, polyglyceryl-6 laurate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, and polyglyceryl-6 linoleate. Polyglyceryl polyricinoleate (Polymuls) is also a surfactant.

[0240] Propylene glycol fatty acid esters

[0241] Esters of propylene glycol and fatty acids are suitable surfactants for use in embodiments of the present invention. In this class of surfactants, hydrophobic surfactants include propylene glycol monolaurate (Lauroglycol FCC), propylene glycol ricinoleate (Propymuls), propylene glycol monooleate (Myverol P-06), propylene glycol dicaprylate / dicaprate (Captex TM 200), and propylene glycol dicaprylate (Captex TM 800).

[0242] Sterols and sterol derivatives

[0243] Sterols and derivatives of sterols are suitable surfactants for use in embodiments of the present invention. Derivatives include polyethylene glycol derivatives. A surfactant of this class is PEG-24 cholesteryl ether (Solulan C-24).

[0244] Polyethylene glycol sorbitan fatty acid esters

[0245] A variety of PEG-sorbitan fatty acid esters are available and suitable for use as surfactants in embodiments of the present invention. Among the PEG-sorbitan fatty acid esters, surfactants include PEG-20 sorbitan monolaurate (Tween-20), PEG-20 sorbitan monopalmitate (Tween-40), PEG-20 sorbitan monostearate (Tween-60), PEG-20 sorbitan monooleate (Tween-80). In some embodiments, laurates are used because they have short lipid chains compared to oleates, thereby improving drug absorption.

[0246] Polyethylene glycol alkyl ether

[0247] Ethers of polyethylene glycols and alkyl alcohols are suitable surfactants for use in embodiments of the present invention. Ethers include PEG-3 oleyl ether (Volpo 3) and PEG-4 lauryl ether (Brij 30).

[0248] Sugar and its derivatives

[0249] Sugar derivatives are suitable surfactants for use in embodiments of the present invention. This class of surfactants includes sucrose monopalmitate, sucrose monolaurate, decanoyl-N-methylglucamide, n-decyl-β-D-glucopyranoside, n-decyl-β-D-maltopyranoside, n-dodecyl-β-D-glucopyranoside, n-dodecyl-β-D-maltoside, heptanoyl-N-methylglucamide, n-heptyl-β-D-glucopyranoside, n-heptyl-β-D-thioglucopyranoside, n-hexyl-β-D-glucopyranoside, nonanoyl-N-methylglucamide, n-nonyl-β-D-glucopyranoside, octanoyl-N-methylglucamide, n-octyl-β-D-glucopyranoside, and octyl-β-D-thioglucopyranoside.

[0250] Polyethylene glycol alkylphenol

[0251] Several PEG-alkylphenol surfactants are available, such as PEG-10-100 nonylphenol and PEG-15-100 octylphenol ether, tyloxapol, octylphenol polyether, octylphenol polyether-9, nonoxynol ether, and are suitable for use in embodiments of the present invention.

[0252] Polyoxyethylene-polyoxypropylene (POE-POP) block copolymer

[0253] POE-POP block copolymers are a unique class of polymeric surfactants. The unique structure of the surfactant, in which the hydrophilic POE and hydrophobic POP portions are in well-defined proportions and positions, provides a wide variety of surfactants suitable for use in embodiments of the present invention. These surfactants are available under various trade names, including Synperonic PE series (ICI), Pluronic TM series (BASF), Emkalyx, Lutrol (BASF), Supronic, Monolan, Pluracare and Plurodac. The generic term for these polymers is "Poloxamers" (CAS 9003-11-6). These polymers have the formula: HO(C2H4O) a (C3H6O) b (C2H4O) a H, wherein "a" and "b" represent the number of polyoxyethylene and polypropylene units, respectively.

[0254] This class of hydrophilic surfactants includes Poloxamers 108, 188, 217, 238, 288, 338 and 407. This class of hydrophobic surfactants includes Poloxamers 124, 182, 183, 212, 331 and 335.

[0255] Sorbitan fatty acid esters

[0256] Sorbitan esters of fatty acids are suitable surfactants for use in embodiments of the present invention. Among these esters, hydrophobic surfactants include sorbitan monolaurate (Arlacel 20), sorbitan monopalmitate (Span-40), and sorbitan monooleate (Span-80), sorbitan monostearate.

[0257] Sorbitan monopalmitate, an amphiphilic derivative of vitamin C (which has vitamin C activity), can have two important functions in a solubilizing system. First, it has effective polar groups that can adjust the microenvironment. These polar groups are the same groups that make vitamin C itself (ascorbic acid) one of the most water-soluble organic solid compounds available: ascorbic acid can be dissolved in water at about 30 wt / wt% (very close to the solubility of, for example, sodium chloride). Second, when the pH is increased, a portion of the ascorbyl palmitate is converted into a more soluble salt, such as sodium ascorbyl palmitate.

[0258] Ionic surfactants

[0259] Ionic surfactants include cationic surfactants, anionic surfactants and zwitterionic surfactants, which are suitable hydrophilic surfactants for embodiments of the present invention. Ionic surfactants include quaternary ammonium salts, fatty acid salts and bile salts. Specifically, ionic surfactants include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, dodecyltrimethylammonium bromide, sodium lauryl sulfate, dialkylmethylbenzyl ammonium chloride, edrophonium chloride, dofen bromide, dialkyl esters of sodium sulfosuccinate, dioctyl sodium sulfosuccinate, sodium cholate, and sodium taurocholate. They are soluble in both organic solvents (e.g., ethanol, acetone, and toluene) and water. This is particularly useful for medical device coatings because it simplifies preparation and coating processes and has good adhesion properties. Water-insoluble drugs are often dissolved in organic solvents.

[0260] Some surfactants described herein are very stable when heated. They still exist after the ethylene oxide sterilization process. The surfactant does not react with drugs such as paclitaxel or rapamycin during the sterilization process. Hydroxyl, ester, amino groups are used because they are unlikely to react with drugs, while amine and acid groups often react with paclitaxel or rapamycin during sterilization. In addition, the surfactant additive improves the integrity and quality of the coating so that the particles do not fall off during processing. When the surfactant described herein is formulated with paclitaxel, it is empirically protected from premature release of the drug during the device delivery process, while promoting rapid release and elution of paclitaxel during the very brief deployment time of 0.2 to 10 minutes at the target site. Drug absorption by tissues at the target site is empirically unexpectedly high.

[0261] Compounds having one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties

[0262] Compounds having one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties include 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, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol , dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, N-acetylglucosamine, N-octyl-D-glucosamine, C6-ceramide, dihydro-C6-ceramide, cerebrosides, sphingomyelins, galactocerebrosides, lactocerebrosides, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-capryl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglycerides, PEG caprylate, PEG8 caprylic / capric glycerides (e.g. PEG caprylate, PEG caproate, glyceryl monocaprylate, glyceryl monocaprate, glyceryl monocaproate, glyceryl monolaurate, glyceryl monocaprate, glyceryl monocaproate, glyceryl monomyristate, glyceryl monopalmitate, and glyceryl monooleate.

[0263] Compounds having one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties include amino alcohols, hydroxycarboxylic acids, esters, anhydrides, hydroxyketones, hydroxylactones, hydroxyesters, phosphate sugars, sulfate sugars, diethyl ethers, ethylene glycols, amino acids, peptides, proteins, sorbitan, glycerol, polyols, phosphates / esters, sulfates / esters, organic acids, esters, salts, vitamins, combinations of amino alcohols and organic acids, and substituted molecules thereof. Hydrophilic compounds having one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties having a molecular weight of less than 5,000-10,000 are used in certain embodiments. In other embodiments, the molecular weight of the additive having one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester moieties is less than 1000-5,000, or less than 750-1,000, or less than 750. In these embodiments, the molecular weight of the additive is less than the molecular weight of the drug to be delivered. In addition, the molecular weight of the additive is higher than 80, because molecules with a molecular weight less than 80 evaporate very easily and will not remain in the coating of the medical device. Small molecules can diffuse rapidly. They can easily release themselves from the delivery balloon, thereby accelerating the release of the drug, and they can diffuse away from the drug when the drug binds to the tissue of the body cavity.

[0264] In certain embodiments, additives with more than four hydroxyl groups are used, for example, in the case of high molecular weight additives. Macromolecules diffuse slowly. If the molecular weight of the additive or compound is high, for example, if the molecular weight is higher than 800, higher than 1000, higher than 1200, higher than 1500 or higher than 2000, the macromolecules will elute too slowly from the surface of the medical device to release the drug within 2 minutes. If these macromolecules contain more than four hydroxyl groups, they have increased hydrophilic properties, which is necessary for relatively large molecules to release drugs quickly. Increased hydrophilicity helps the coating elute from the balloon, accelerates the release of the drug, and improves or promotes the movement of the drug through the water barrier and the polar head groups of the lipid bilayer to penetrate the tissue. In one embodiment, hydroxyl groups are used as hydrophilic moieties because it is unlikely to react with water-insoluble drugs such as paclitaxel or rapamycin. In some embodiments, the compound with more than four hydroxyl groups has a melting point of 120° C. or less.

[0265] In some embodiments, the compound having more than four hydroxyl groups has three adjacent hydroxyl groups, and the three adjacent hydroxyl groups are all on one side of the molecule in the stereo configuration. For example, sorbitol and xylitol have three adjacent hydroxyl groups that are all on one side of the molecule in the stereo configuration, while galactitol is not. This difference affects the physical properties of the isomers such as melting temperature. The stereo configuration of the three adjacent hydroxyl groups can enhance drug binding. This will bring improved compatibility of water-insoluble drugs and hydrophilic additives, as well as improved tissue uptake and absorption of the drug.

[0266] Some of the compounds described herein with one or more hydroxyl, amine, carbonyl, carboxyl or ester moieties are very stable when heated. They still exist after the ethylene oxide sterilization process and do not react with water-insoluble drugs paclitaxel or rapamycin during sterilization. On the other hand, L-ascorbic acid and its salts and diethanolamine do not have to still exist after the sterilization process, and they react with paclitaxel. Therefore, different sterilization methods are adopted for L-ascorbic acid and diethanolamine. For example, hydroxyl, ester and amide groups are used because they are unlikely to react with therapeutic agents such as paclitaxel or rapamycin. Sometimes, amine and acid groups do react with paclitaxel, for example, according to experience, benzoic acid, gentisic acid, diethanolamine and ascorbic acid are unstable during ethylene oxide sterilization, heating and aging processes, and react with paclitaxel. When the compounds described herein are formulated with paclitaxel, a top coating may be advantageous to prevent premature drug loss during the device delivery process before deployment at the target site, because hydrophilic small molecules are sometimes very easy to release drugs. The compounds herein rapidly elute the drug from the balloon during deployment at the target site. Surprisingly, when the coating contains these additives, although some drug is lost during transport from the device to the target site, based on experience, the drug uptake by the tissue is unexpectedly high after only 0.2-10 minutes of deployment, for example, when the additive is a hydroxylactone such as ribonolactone and gluconolactone.

[0267] Fat-soluble vitamins and their salts

[0268] Vitamins A, D, E and K in their various forms and provitamin forms are considered fat-soluble vitamins, and in addition to these, several other vitamins and vitamin sources or close relatives are also fat-soluble and have polar groups and relatively high octanol-water partition coefficients. Clearly, compounds of this general class have a history of safe use and a high benefit / risk ratio, making them useful as additives in embodiments of the present invention.

[0269] The following examples of fat-soluble vitamin derivatives and / or sources can also be used as additives: alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, tocopherol acetate, ergosterol, 1-alpha-hydroxycholecalciferol, vitamin D2, vitamin D3, alpha-carotene, beta-carotene, gamma-carotene, vitamin A, fursultiamine, hydroxymethylriboflavin, octylthiamine, propylthiamine, riboflavin, benzoylethylenethiamine, dihydrovitamin K1, dihydronaphthoquinone diacetate, naphthoquinone dibutyrate, naphthoquinone disulfate, naphthoquinone, vitamin K1, vitamin K1 oxide, vitamin K2 and vitamin K--S (II). Folic acid is also of this type, and although it is water-soluble at physiological pH, it can be formulated in free acid form. Other derivatives of fat-soluble vitamins that can be used in embodiments of the present invention can be easily obtained by well-known chemical reactions with hydrophilic molecules.

[0270] Water-soluble vitamins and their amphiphilic derivatives

[0271] A variety of different forms of vitamin B, C, U, pantothenic acid, folic acid and some menadione-related vitamins / original vitamins are considered to be water-soluble vitamins. These can also be conjugated or compounded with hydrophobic moieties or multivalent ions to form amphiphilic forms with relatively high octanol-water partition coefficients and polar groups. Again, the compound can have low toxicity and high benefit / risk ratio, so that they can be used as additives in embodiments of the present invention. The salts of these compounds can also be used as additives in the present invention. The examples of water-soluble vitamins and derivatives include but are not limited to acetylthiamine, benfotiamine, pantothenic acid, cimetropium, cyclothiamine, dexpanthenol, nicotinamide, nicotinic acid, 5-pyridoxal phosphate, ascorbic acid nicotinamide, riboflavin, riboflavin phosphate, thiamine, folic acid, menadione phosphate, sodium menadione bisulfite, menadoxine, vitamin B12, vitamin K5, vitamin K6, vitamin K6 and vitamin U. In addition, as mentioned above, folic acid is water-soluble as salt in a wide pH range including physiological pH.

[0272] Compounds in which there is an amino group or other basic group can be easily modified by a simple acid-base reaction with an acid containing a hydrophobic group, such as a fatty acid (especially lauric acid, oleic acid, myristic acid, palmitic acid, stearic acid or 2-ethylhexanoic acid), a low solubility amino acid, benzoic acid, salicylic acid or an acidic fat-soluble vitamin (such as riboflavin). Other compounds can be obtained by reacting the acid with another group on the vitamin, such as a hydroxyl group, to form a bond, such as an ester bond. Derivatives of water-soluble vitamins containing an acidic group can be generated in a reaction with a reactant containing a hydrophobic group, such as stearylamine or riboflavin, such as to produce compounds that can be used in embodiments of the present invention. The connection of a palmitate chain to vitamin C produces ascorbyl palmitate.

[0273] Amino acids and their salts

[0274] Alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, glycine, histidine, proline, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine, and derivatives thereof are other useful additives in embodiments of the present invention.

[0275] Certain amino acids (in their zwitterionic form and / or in salt form with monovalent or multivalent ions) have polar groups, relatively high octanol-water partition coefficients, and can be used i...

Claims

1. A balloon catheter for treating stenosis and / or cancer, preventing stenosis and / or cancer, or reducing the recurrence of stenosis and / or cancer in a non-vascular body cavity, or for treating benign prostatic hyperplasia (BPH), the balloon catheter comprising: elongated saccule; a coating covering an outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; and A length control mechanism stretches and elongates the balloon when the balloon is in the deflated state.

2. The balloon catheter of claim 1, wherein the length control mechanism stores energy during inflation of the balloon, and wherein the stored energy is used to elongate the balloon once the balloon is in the deflated state.

3. The balloon catheter of claim 2, wherein energy for the length control mechanism during inflation of the balloon is stored in the catheter shaft.

4. The balloon catheter of any one of claims 1-3, wherein the balloon catheter comprises an elongated rigid component from a distal end of the elongated balloon to at least a proximal end of the elongated balloon.

5. The balloon catheter of claim 4, wherein the elongated rigid component is disposed inside or outside a reinforcing tube, the reinforcing tube being continuous or discontinuous along a section of the elongated rigid component.

6. The balloon catheter of any one of claims 4-5, wherein the distal end of the elongated rigid member is mechanically coupled to the distal end of the elongated balloon such that as the balloon is inflated, force is transmitted in a proximal direction along the elongated rigid member.

7. The balloon catheter of any one of claims 4 to 6, wherein the distal end of the elongated rigid component is connected to the distal end of the elongated balloon, or wherein the distal end of the elongated rigid component is connected to the catheter tip.

8. The balloon catheter of any one of claims 4-7, wherein the balloon catheter comprises a catheter shaft, wherein the proximal end of the elongated rigid component is connected to the catheter shaft at or proximal to the proximal end of the elongated balloon.

9. The balloon catheter of any one of claims 4-8, wherein the balloon catheter comprises an elastic member connected to the proximal end of the elongated rigid component, so that when the elongated rigid component moves in the proximal direction, force is stored in the elastic member, and so that when the force is released from the elastic member, the force is applied from the elastic member to the elongated rigid component in the distal direction.

10. The balloon catheter of any one of claims 1-9, wherein the therapeutic agent is selected from the group consisting of paclitaxel, docetaxel, taxol, their analogs, rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, mTOR inhibitors, their analogs, and combinations thereof.

11. The balloon catheter of any one of claims 1 to 10, wherein the water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucamide, N-nonanoyl-N-methylglucamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, sphingosine, sphingomyelin, galactosylsphingosine, lactosylsphingosine, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octanoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG 8 caprylic / capric glyceride, PEG caprylate, PEG 8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceryl, monocapric glyceryl. , monocaproin, monolaurin, monocaprin, monocaprylin, monocaprylin, monomyristicin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof.

12. The balloon catheter of any one of claims 1-11, wherein the water-soluble additive is selected from the group consisting of pentaerythritol ethoxylate, pentaerythritol propoxylate, and combinations thereof.

13. A method for treating stenosis and / or cancer, preventing stenosis and / or cancer, or reducing the recurrence of stenosis and / or cancer, or treating benign prostatic hyperplasia (BPH) at a target site in a non-vascular body lumen, the method comprising: A balloon catheter is inserted into a target site in a non-vascular body cavity, wherein the balloon catheter comprises elongated saccule, and a coating covering an outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; inflating the balloon at the target site so that the coating contacts the wall of the body lumen at the target site until the balloon reaches an inflated balloon diameter for an inflation period; deflation of the balloon after the inflation period; and Remove the balloon catheter from the body cavity.

14. The method of claim 13, wherein the method is a method of treating cancer therapy-induced non-vascular stenosis, wherein the target site in the body lumen comprises the cancer therapy-induced non-vascular stenosis.

15. The method of claim 13, wherein the method is a method of treating radiation-induced non-vascular stenosis, wherein the target site in the body lumen comprises the radiation-induced non-vascular stenosis.

16. The method of claim 13, wherein the method is a method of reducing the occurrence of radiation-induced non-vascular stenosis or preventing radiation-induced non-vascular stenosis, wherein the target site in the body lumen includes the radiation-induced non-vascular stenosis.

17. The method of claim 13, wherein the method is a method for reducing the occurrence of cancer therapy-induced non-vascular stenosis or preventing cancer therapy-induced non-vascular stenosis, or reducing or preventing cancer recurrence, wherein the target site is at, proximal to, adjacent to, or distal to the location of the cancer treatment being performed.

18. The method of claim 13, wherein the method is a method of treating surgical anastomosis-induced non-vascular stenosis, wherein the target site in the body cavity comprises the surgical anastomosis-induced non-vascular stenosis.

19. The method of claim 13, wherein the method is a method of reducing the occurrence of surgical anastomosis-induced non-vascular stenosis or preventing surgical anastomosis-induced non-vascular stenosis, wherein the target site includes the location of the surgical anastomosis performed.

20. The method of claim 13, wherein the method is a method of treating inflammatory disease-induced non-vascular stenosis, wherein the target site in the body lumen comprises the inflammatory disease-induced non-vascular stenosis.

21. The method of claim 13, wherein the method is a method of reducing the occurrence of inflammatory disease treatment-induced non-vascular stenosis or preventing inflammatory disease treatment-induced non-vascular stenosis, wherein the target side in the body lumen includes the location where the inflammatory disease treatment is performed.

22. The method of claim 13, wherein the method is a method of treating gastrectomy-induced non-vascular stenosis, wherein the target site in the body cavity comprises the gastrectomy-induced non-vascular stenosis.

23. The method of claim 13, wherein the method is a method of reducing the occurrence of gastrectomy-induced non-vascular stenosis or preventing gastrectomy-induced non-vascular stenosis, wherein the target site in the body cavity comprises the location of the performed gastrectomy.

24. The method of claim 13, wherein the method is a treatment method for non-vascular stenosis induced by electrocautery, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD), wherein the target site includes non-vascular stenosis induced by electrocautery, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD).

25. The method of claim 13, wherein the method is a method for reducing the occurrence of or preventing non-vascular stenosis induced by electrocautery, episiotomy, urethrotomy, direct vision urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD), wherein the target site in the body cavity includes the location where the electrocautery, episiotomy, urethrotomy, DVIU, EMR, or ESD is performed.

26. The method of claim 13, wherein the method is a method of treating bladder neck stenosis, wherein the target site in the body cavity comprises the bladder neck stenosis.

27. The method of claim 13, wherein the method is a method of reducing the occurrence of or preventing prostate cancer treatment or stricture incision-induced bladder neck stenosis, wherein the target site in the body cavity is in the bladder neck and is at, proximal to, adjacent to, or distal to the site of the prostate cancer treatment or stricture incision.

28. The method of claim 13, wherein the method is a method of treating esophageal fibrostenotic strictures in eosinophilic esophagitis, wherein the target site in the body cavity comprises esophageal fibrostenotic strictures in eosinophilic esophagitis.

29. The method of claim 13, wherein the method is a method of treating achalasia, wherein the target site in the body cavity comprises the lower esophageal sphincter.

30. The method of claim 13, wherein the method is a method of treating benign prostatic hyperplasia (BPH), wherein the target site in the body cavity comprises the prostatic urethra.

31. The method of claim 13, wherein the method is a method of treating urethral strictures, wherein the urethral strictures are trauma-induced strictures, idiopathic strictures, and / or iatrogenic strictures, and wherein the target site in the body cavity comprises the trauma-induced strictures, idiopathic strictures, and / or iatrogenic strictures.

32. The method of any one of claims 13-31, further comprising flushing the body cavity with water, saline solution, or an aqueous solution including at least one water-soluble additive prior to inserting the balloon into the target site.

33. The method of any of claims 13-32, further comprising using a viewing instrument within the non-vascular lumen to properly position the balloon catheter, visualize inflation of the balloon, visualize deflation of the balloon, visualize yielding of the target site, visualize a therapeutic agent being released on the wall of the target site, or a combination thereof.

34. The method of any one of claims 13-33, further comprising pre-dilating the target site with another balloon catheter before inserting the drug-coated balloon into the target site.

35. The method of any one of claims 13-34, wherein the balloon catheter is the balloon catheter of any one of claims 1-12.

36. A method of treating a target site in a non-vascular body lumen, the method comprising: inserting an uncoated balloon catheter into a non-vascular body lumen to a target site; inflating the uncoated balloon catheter at the target site so as to contact the wall of the body lumen at the target site until the balloon reaches an inflated balloon diameter for an inflation period; deflation of the uncoated balloon after the inflation period; removing the uncoated balloon catheter from the body cavity; Irrigate the target area with water or saline; Insert the balloon catheter into the target area. The balloon catheter includes elongated saccule, and a coating covering an outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; inflating the balloon at the target site so that the coating contacts the wall of the body lumen at the target site until the balloon reaches an inflated balloon diameter for an inflation period; deflate the balloon after the inflation period; Removing the balloon catheter from the body cavity; and A scope is used in a body lumen including a target site to visualize insertion of a drug-coated balloon catheter to the target site, inflation of the drug-coated balloon at the target site, deflation of the drug-coated balloon at the target site, or a combination thereof.

37. A method of treating a target site in a non-vascular body lumen, the method comprising: Perform electrosurgical resection, episiotomy, urethrotomy, direct visual urethrotomy (DVIU), endoscopic mucosal resection (EMR), or endoscopic submucosal dissection (ESD) on the target site; Irrigate the target area with water or saline; A balloon catheter is inserted into a target site in a non-vascular body cavity, wherein the balloon catheter comprises elongated saccule, and a coating covering an outer surface of the balloon, wherein the coating includes one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; inflating the balloon at the target site so that the coating contacts the wall of the body lumen at the target site until the balloon reaches an inflated balloon diameter for an inflation period; deflate the balloon after the inflation period; Removing the balloon catheter from the body cavity; and A scope is used in a body lumen including a target site to visualize insertion of a drug-coated balloon catheter to the target site, inflation of the drug-coated balloon at the target site, deflation of the drug-coated balloon at the target site, or a combination thereof.

38. A method for treating benign prostatic hyperplasia (BPH), the method comprising: inserting a first sheath including a pre-dilation balloon catheter into the urethra, the pre-dilation balloon catheter including a pre-dilation balloon; The first sheath is removed from the urethra, leaving the pre-dilated catheter in the urethra; Inserting a cystoscope into the urethra; Use a cystoscope to facilitate visualization of the placement of the predilation balloon in the prostatic urethra; inflating a pre-dilation balloon so as to dilate the prostatic urethra with the pre-dilation balloon to form an initial commissure incision of the prostatic urethra; deflate the pre-dilation balloon; Use a cystoscope to verify that the predilatation balloon has produced an initial commissure incision; Remove the cystoscope from the urethra; Re-insert the first sheath into the urethra over the predilation balloon catheter; Pull the pre-dilation balloon into the first sheath; removing the first sheath including the pre-dilated balloon catheter from the urethra; inserting a second sheath comprising a drug-coated balloon catheter into the urethra, the drug-coated balloon catheter comprising a drug-coated balloon, the drug-coated balloon comprising a coating covering an outer surface thereof, the coating comprising one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; removing the second sheath from the urethra, leaving the drug-coated balloon catheter in the urethra; Inserting a cystoscope into the urethra; Use a cystoscope to visualize placement of the drug-coated balloon in the prostatic urethra; inflating the drug-coated balloon so that the coating contacts the prostatic urethra; Remove the cystoscope from the urethra; Maintaining the drug-coated balloon in the inflated state for at least 5 minutes; deflate the drug-coated balloon; reinserting the second sheath into the urethra over the drug-coated balloon catheter; pulling the drug-coated balloon into the second sheath; and The second sheath including the drug-coated balloon catheter is removed from the urethra.

39. A method for treating benign prostatic hyperplasia (BPH), the method comprising: inserting the first sheath into the urethra; inserting a pre-dilation balloon catheter including a pre-dilation balloon into the first sheath; Remove the first sheath; Insert the cystoscope into the urethra alongside the predilated balloon catheter; Use a cystoscope to facilitate visualization of the placement of the predilation balloon in the prostatic urethra; inflating a pre-dilation balloon so as to dilate the prostatic urethra with the pre-dilation balloon to form an initial commissure incision of the prostatic urethra; deflate the pre-dilation balloon; Use a cystoscope to verify that the predilatation balloon has produced an initial commissure incision; Remove the cystoscope from the urethra; Inserting a first sheath over the predilated balloon in the urethra; Pull the pre-dilation balloon into the first sheath; or removing the pre-dilation balloon from the first sheath while leaving the first sheath in place, wherein the first sheath is the second sheath, or removing the pre-dilation balloon and the first sheath from the urethra and inserting the second sheath into the urethra; inserting a drug-coated balloon catheter into the second sheath, the drug-coated balloon catheter comprising a drug-coated balloon, the drug-coated balloon comprising a coating covering an outer surface thereof, the coating comprising one or more water-soluble additives and an initial drug loading amount of a therapeutic agent; Remove the second sheath from the urethra; A cystoscope is inserted into the urethra alongside a drug-coated balloon catheter; Use a cystoscope to visualize placement of the drug-coated balloon in the prostatic urethra; inflating the drug-coated balloon so that the coating contacts the prostatic urethra; Remove the cystoscope from the urethra; Maintaining the drug-coated balloon in the inflated state for at least 5 minutes; deflate the drug-coated balloon; inserting a second sheath over the drug-coated balloon in the urethra; pulling the drug-coated balloon into the second sheath; and The second sheath including the drug-coated balloon catheter is removed from the urethra.

40. A method of treating radiation-induced stenosis, comprising: optionally pre-dilatating the radiation-induced stenosis with a pre-dilatation balloon having a nominal diameter smaller than the nominal diameter of the balloon catheter, or performing a strictotomy on the radiation-induced stenosis; optionally flushing the radiation-induced stenosis with water, saline solution, or an aqueous solution including at least one water-soluble additive; A balloon catheter is inserted into the target site of the stenosis. The balloon catheter includes balloon, and A coating covering the outer surface of the balloon, wherein the coating comprises at least one water-soluble additive, and The therapeutic agent, wherein the initial drug loading is 1-6 micrograms of the therapeutic agent per square millimeter of the balloon; in The therapeutic agent is selected from paclitaxel, taxol, docetaxel, rapamycin, sirolimus, zotarolimus, tacrolimus, everolimus, mTOR inhibitors, or analogs thereof, and combinations thereof, The water-soluble additive is selected from N-acetylglucosamine, N-octyl-D-glucosamine, N-nonanoyl-N-methylglucosamine, N-octanoyl-N-methylglutamine, C6-ceramide, dihydro-C6-ceramide, sphingosine, sphingomyelin, galactosylsphingosine, lactosylsphingosine, N-acetyl-D-sphingosine, N-hexanoyl-D-sphingosine, N-octanoyl-D-sphingosine, N-lauroyl-D-sphingosine, N-palmitoyl-D-sphingosine, N-oleoyl-D-sphingosine, PEG caprylic / capric diglyceride, PEG8 caprylic / capric glyceride, PEG caprylate, PEG8 caprylate, PEG caprate, PEG caproate, monocaprylic glyceryl, monocapric glyceryl, monocapric glyceryl, monocaprylic glyceryl, monolauric acid glycerides, monocaprin, monocaprylin, monomyristin, monopalmitolein, monoolein, creatine, creatinine, agmatine, citrulline, guanidine, sucralose, aspartame, hypoxanthine, theobromine, theophylline, adenine, uracil, uridine, guanine, thymine, thymidine, xanthine, xanthine, xanthine monophosphate, caffeine, allantoin, (2-hydroxyethyl) urea, N,N'-bis(hydroxymethyl) urea, pentaerythritol ethoxylate, pentaerythritol propoxylate, pentaerythritol propoxylate / ethoxylate, glycerol ethoxylate, glycerol propoxylate, trimethylolpropane ethoxylate, pentaerythritol, dipentaerythritol, crown ethers, 18-crown-6, 15-crown-5, 12-crown-4, and combinations thereof, and The ratio of the weight of the therapeutic agent in the coating to the total weight of the one or more water-soluble additives in the coating is about 0.05-20; inflating the balloon until the coating contacts the walls of the radiation-induced stenosis at the target site and the balloon reaches an inflated balloon diameter for an inflation period; After the inflation period, the balloon is deflated, wherein the inflation period is 0.1 minutes to 10 minutes; balloon catheter removal from radiation-induced strictures; optionally using a scope that visualizes insertion and placement of the drug coated balloon catheter at the target site, the inflation and deflation process, increase in balloon diameter during inflation, decrease in balloon diameter during deflation, yielding of the target site, released drug on the wall of the target site after balloon deflation, or any combination thereof; in The stretch ratio at the treated location is from about 1.0 to about 40, and Radiation-induced strictures include urethral strictures, ureteric strictures, esophageal strictures, antral strictures, gastric strictures, small intestinal strictures, colonic strictures, rectal strictures, large intestinal strictures, or bile duct strictures.

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