Delivery catheter and method of disease treatment

Abstract

Embodiments of the invention provide devices and methods for at least one disease by delivering an effective amount of energy and / or a formulation to tissue on or near a body lumen. The formulation may include at least one of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, or a combination thereof of one or more ingredients. The delivered amount of formulation and / or energy may be effective to damage or damage tissue, nerves, and / or nerve endings to relieve disease symptoms.

Description

[0001] Cross Reference to Related Applications

[0002] This application is a continuation of divisional application number 202080046425.X, filed on June 25, 2020, entitled “Delivery Catheter and Disease Treatment Method.”

[0003] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 866,266, filed on June 25, 2019, U.S. Patent Application No. 16 / 563,235, filed on September 6, 2019, and U.S. Patent Application No. 16 / 690,992, filed on November 21, 2019, the disclosures of which are incorporated by reference herein in their entireties. TECHNICAL FIELD

[0004] The present application relates to a delivery catheter for delivering a chemical agent and / or energy, and a method of treating at least one disease, for example by treating at least two different target tissues in one procedure. BACKGROUND

[0005] Hypertension, or high blood pressure, is a major global health problem. It is estimated that 30 to 40 percent of adults worldwide suffer from this disease. Moreover, its prevalence is expected to increase, particularly in developing countries. The diagnosis and treatment of hypertension remains suboptimal, and most patients struggle to properly control their blood pressure.

[0006] Benign prostatic hyperplasia is a non-cancerous enlargement of the prostate that affects more than 50% of men over 60 years of age. At an early stage in life, the prostate is about the size of a walnut and weighs about 20 grams. Over time, the prostate enlarges and is considered normal. With age, the prostate gradually enlarges to at least twice its original size. The growth of the prostate causes an increase in pressure against the adjacent urethra, causing this latter organ to narrow and eventually leading to urinary tract obstruction, making urination difficult.

[0007] Chronic obstructive pulmonary disease (COPD) is associated with two major airflow obstruction disorders: chronic bronchitis and emphysema. Chronic bronchitis results from inflammation of the bronchial airways. Bronchial airways connect the trachea with the lungs. Emphysema is a disease caused by over-inflation of the alveoli or air sacs of the lungs. This condition causes shortness of breath. Approximately 16 million Americans suffer from COPD, most of whom (80-90%) are life-long smokers. COPD is a leading cause of death in the United States.

[0008] Asthma is a chronic respiratory disease characterized by excessive narrowing of the airways and caused by airway inflammation, excess mucus secretion, and airway hyperresponsiveness. This airway narrowing causes breathing difficulties and can significantly impact a patient's life, limiting participation in many activities. In severe cases, asthma attacks can be life threatening. To date, there is no known cure for asthma.

[0009] Chronic sinusitis (CS) is caused by inflammation of the membrane lining in one or more of the paranasal sinuses and is often associated with significant tissue damage. There are approximately 37 million cases of CS reported to the Centers for Disease Control and Prevention (CDC) each year.

[0010] Diabetes is a metabolic condition, or combination of conditions, in which an individual experiences high concentrations of blood glucose. The condition results from either insufficient production of insulin in the body or cells that cannot respond appropriately to insulin. Glycated hemoglobin (HbAlc) is a marker of plasma glucose concentration and is used clinically to diagnose diabetes. In humans, normal HbAlc levels are typically < 6.0%, prediabetes HbAlc levels range from 6.0-6.4%, and diabetes HbAlc levels exceed 6.5%.

[0011] Diabetes is one of the leading causes of death and disability in the United States and other developed countries. It is associated with long-term complications that affect nearly every part of the body. For example, it is associated with blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage.

[0012] In the United States, diabetes affects approximately 8% of the population and results in expenditures of nearly $250 billion.

[0013] Diabetes is generally classified as type 1 (also known as insulin-dependent diabetes mellitus or juvenile diabetes), type 2 (also known as non-insulin-dependent diabetes mellitus, adult-onset diabetes, or obesity-related diabetes), or gestational diabetes, where type 1 patients cannot produce sufficient insulin, type 2 patients cannot respond appropriately to insulin, and gestational diabetes is a condition that develops in late pregnancy in women.

[0014] Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of all cases. It is often associated with old age, obesity, family history, previous history of gestational diabetes, and inactive physical activity. It is also more prevalent in certain ethnic groups. Type 2 diabetes is also known as insulin-resistant diabetes because the pancreas typically produces sufficient amounts of insulin, but the body cannot respond to it appropriately. Symptoms associated with type 2 diabetes include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores.

[0015] The liver is critical for maintaining normal glucose homeostasis, producing glucose during fasting and storing glucose after meals. However, these liver processes are dysregulated in type 1 and type 2 diabetes, and this imbalance leads to hyperglycemia in both the fasting and postprandial states. Net hepatic glucose production is the sum of glucose flux from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis, and other pathways. Glucose levels are sensed by neurons and glial cells in the central nervous system (CNS) that express glucose transporters (GLUTs) and by peripheral tissues such as taste buds, gut, and carotid body. In the liver, glucose levels are also sensed at the portal vein. Activation of sympathetic efferent nerves increases glucose production and inhibits glycogen production.

[0016] To measure fasting blood glucose, a blood sample can be taken after an overnight fast. A fasting blood glucose level below 100 mg / dL (5.6 mmol / L) is normal. A fasting blood glucose level of 100-125 mg / dL (5.6-6.9 mmol / L) is considered pre-diabetic. A measurement of 126 mg / dL (7 mmol / L) or higher in two separate tests is considered to indicate diabetes. Diabetic patients have fasting blood glucose levels in the range of 126 mg / dL to 400 mg / dL or even higher, or in the range of 126 mg / dL to 300 mg / dL, or in the range of 126 mg / dL to 250 mg / dL. The liver acts as the body's glucose (or fuel) storage and helps keep circulating blood glucose levels and other body fuels stable and constant. The liver stores and makes glucose according to the body's needs. The need to store or release glucose is signaled by insulin and glucagon. During meals, the liver stores sugar or glucose as glycogen for later use when the body needs it. High levels of insulin and suppressed glucagon levels during meals promote the storage of glucose as glycogen. When not eating - especially overnight or between meals - the body must make its own sugar. The liver supplies sugar or glucose by converting glycogen into glucose in a process called glycogenolysis. The liver can also make necessary sugar or glucose by collecting amino acids, waste products, and fat byproducts. This process is called gluconeogenesis. As the body's glycogen stores become lower and lower, the body begins to conserve sugar supplies for organs that always need sugar. These organs include: the brain, red blood cells, and parts of the kidney. To supplement the limited sugar supply, the liver makes a substitute fuel from fat, which is called ketones. This process is called ketogenesis. The hormonal signal to start ketogenesis is low levels of insulin. Ketones are burned as fuel by muscles and other body organs, while sugar is left for organs that need it.

[0017] Glucagon, epinephrine, norepinephrine, Cortisol, and growth hormone help maintain blood glucose levels and raise blood glucose. Diabetics have high concentrations of glucagon, epinephrine, norepinephrine, Cortisol, and growth hormone. Glucagon is made by islet cells (alpha cells) in the pancreas, controls the production of glucose and another fuel, ketones, in the liver. Glucagon is released at night and between meals and is important to maintain the body's glucose and fuel balance. It signals the liver to break down its starch or glycogen stores and helps form new glucose units and ketone units from other substances. It also promotes the breakdown of fat in fat cells. Epinephrine and norepinephrine are very similar. Both are neurotransmitters and both increase blood pressure and blood glucose levels. Epinephrine (adrenaline) is released from nerve endings and the adrenal glands and acts directly on the liver to promote the production of glucose (by glycogen breakdown). Epinephrine also promotes the breakdown and release of fat nutrients that enter the liver and are converted to glucose and ketones. Cortisol is a steroid hormone also secreted from the adrenal glands. It makes fat and muscle cells resistant to the effects of insulin and increases the glucose produced by the liver. Normally, Cortisol counteracts the effects of insulin. Under stress or if synthetic Cortisol is used as a drug (e.g., with prednisone therapy or cortisone injections), Cortisol levels rise and cause insulin resistance. When a patient has type 2 diabetes, this means they can need to take more medication or insulin to control blood glucose. Growth hormone is released from the pituitary gland, which is part of the brain. Like Cortisol, growth hormone counteracts the effects of insulin on muscle and fat cells. High levels of growth hormone cause resistance to the effects of insulin.

[0018] Obesity is another major health problem, particularly in developed countries. It is a complex, multifactorial, and chronic condition characterized by an excess of body fat resulting from an imbalance between energy expenditure and caloric intake. While the cause of this imbalance is not fully understood, genetics and / or acquired physiological events and environmental factors are thought to contribute. Adverse health effects associated with obesity and particularly morbid obesity have become more firmly established in recent years. Such adverse effects include, but are not limited to, cardiovascular disease, diabetes, hypertension, arthritis, and sleep apnea. Generally speaking, as a patient's body mass index (BMI) increases, the likelihood of suffering adverse effects associated with obesity also increases.

[0019] Metabolic syndrome is a serious health condition that affects up to one-third of American adults and puts them at higher risk for cardiovascular disease, type 2 diabetes, stroke, and diseases related to the buildup of fat in the walls of arteries. It is a cluster of conditions that often occur together. These conditions include high blood pressure, high blood sugar, excess fat around the waist, and abnormal cholesterol or triglyceride levels. The National Institutes of Health guidelines define metabolic syndrome as having three or more of the following characteristics (including the ones you are taking medication to control): large waist (measured waist circumference of at least 35 inches (89 centimeters) for women and 40 inches (102 centimeters) for men), high triglyceride levels (150 milligrams per deciliter (mg / dL) or 1.7 millimoles per liter (mmol / L), or higher amounts of such fats found in the blood), low "good" or HDL cholesterol (high-density lipoprotein (HDL) cholesterol less than 40 mg / dL (1.04 mmol / L) for men or less than 50 mg / dL (1.3 mmol / L) for women), elevated blood pressure (130 / 85 millimeters of mercury (mm Hg) or higher), elevated fasting blood glucose (100 mg / dL (5.6 mmol / L) or higher).

[0020] Nonalcoholic fatty liver disease is another health problem that occurs when the liver has difficulty breaking down fat, causing it to build up in the liver tissue of people who drink little or no alcohol. It is normal for the liver to contain some fat. However, if more than 5% to 10% of the liver's weight is fat, it is called fatty liver (steatosis). Nonalcoholic fatty liver disease (NAFLD) is common and, for most people, does not cause signs and symptoms and complications. But in some people with nonalcoholic fatty liver disease, the accumulated fat can cause inflammation and scarring of the liver. This more serious form of nonalcoholic fatty liver disease is sometimes called nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. In the most severe cases, nonalcoholic fatty liver disease progresses to liver failure. NASH is associated with dyslipidemia, low high-density lipoprotein (HDL) (men <40 mg / dL or women <50 mg / dL), hypertriglyceridemia (>150 mg / dL), hypercholesterolemia (>200 mg / dL), and triglyceride (TG) / HDL >5.0. Resolution of NASH is associated with a decrease in TG and TG / HDL ratio.

[0021] The spleen is a major filter of blood-borne pathogens and a key organ for iron metabolism and red blood cell homeostasis. The spleen also plays an important role in immune responses to inflammatory conditions, including rheumatoid arthritis (RA), cancer, myocardial infarction, and atherosclerosis. The autonomic nervous system regulates immunity or responses to inflammatory stimuli by upregulating sympathetic transmission to the spleen, which mobilizes monocytes to sites of tissue injury and releases cytokines that modulate inflammatory responses. SUMMARY

[0022] Embodiments of the present invention relate to a delivery catheter for delivering a chemical agent and / or energy, and a method of treating at least one disease, such as by treating at least two different target tissues in one procedure. The at least one disease can include hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral artery disease (PAD), end-stage renal disease, digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), or a combination thereof. The delivery catheter can deliver an effective amount of energy or / and chemical agent to a target tissue in the body to alleviate disease symptoms, such as reducing blood pressure for hypertension, reducing blood glucose level and AIC for diabetes, reducing body weight for obesity, reducing restenosis for coronary and peripheral diseases, reducing liver fat for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and reducing pain for cancer and arthritis. The energy can be radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound energy, or a combination thereof. The target tissue can include a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, or a distal end of a right main renal artery branch), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a urinary lumen. The delivery catheter can include a radiofrequency catheter, a cryoablation catheter, a microwave catheter, a laser catheter, an ultrasound catheter, a high intensity focused ultrasound catheter, or a combination thereof. The delivery catheter can include a combination of a balloon and an infusion catheter, and other delivery devices. The agent delivered by the delivery catheter can include one or more components of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, and a combination thereof. The delivery of the agent to a target tissue in the body by chemical infusion from the delivery catheter can improve safety and effectiveness of the treatment.

[0023] Various embodiments of the present application provide a method of treating at least one disease, including treating at least two different target tissues in at least two different body lumens. The method includes performing a treatment procedure on a body lumen as a first body lumen. The treatment procedure includes inserting a delivery catheter into the body lumen. The delivery catheter includes a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon. The treatment procedure includes inflating the balloon to center the distal end of the shaft in the body lumen. The treatment procedure includes denervating or ablating a target tissue of the body lumen with the delivery catheter, including delivering an amount of energy or a chemical agent to the target tissue effective to injure or impair the target tissue to relieve a symptom of the disease. The treatment procedure includes deflating the balloon. The treatment procedure also includes removing the delivery catheter from the body lumen. The method also includes performing the treatment procedure on a second body lumen different from the first body lumen.

[0024] A method of treating at least one disease including treating at least two different target tissues in at least two different body lumens using a delivery catheter can be a method of treating metabolic syndrome. The method can include treating first, second, third, and fourth target tissues all different from each other and each located in a first, second, third, and fourth body lumen, respectively. The first body lumen can include a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, or a distal end of a right main renal artery branch), a renal vein, a pulmonary artery, a vascular lumen, a celiac artery, a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, a right hepatic artery, a left hepatic artery, a splenic artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, a non-vascular lumen, an esophagus, a digestive lumen, a stomach, a duodenum, a jejunum, or a combination thereof. The second body lumen can include a right main renal artery, a left main renal artery, a right renal branch artery, a left renal branch artery, a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, a right hepatic artery, a left hepatic artery, a splenic artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The third body lumen can include a splenic artery, a gastric artery, a left gastric artery, or a combination thereof. The fourth body lumen can include a gastroduodenal artery, a gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissue can reduce body weight, reduce hypertension, reduce AIC, reduce blood glucose levels, reduce body waist adipose tissue, or a combination thereof.

[0025] A method of treating at least one disease comprising treating at least two different target tissues in at least two different body lumens using a delivery catheter can be a method of treating hypertension. The method can comprise treating first, second, third, and fourth target tissues that are all different from each other and are located in first, second, third, and fourth body lumens, respectively. The first body lumen can comprise a renal artery, e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof. The second body lumen can comprise a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, a right hepatic artery, a left hepatic artery, a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen can comprise a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The fourth target tissue can comprise a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissues can reduce blood pressure.

[0026] A method of treating at least one disease comprising treating at least two different target tissues in at least two different body lumens using a delivery catheter can be a method of treating diabetes. The method can comprise treating first, second, third, and fourth target tissues that are all different from each other and are located in first, second, third, and fourth body lumens, respectively. The first body lumen can comprise a common hepatic artery, a proper hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second body lumen can comprise a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, or a distal end of a right main renal artery branch), a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen can comprise a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The fourth body lumen can comprise a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissues can reduce blood glucose levels, reduce AIC, or a combination thereof.

[0027] A method of treating at least one disease comprising treating at least two different target tissues in at least two different body lumens using a delivery catheter can be a method of treating obesity. The method can comprise treating first, second, third, and fourth target tissues that are all different from each other and are located in first, second, third, and fourth body lumens, respectively. The first body lumen can comprise a common hepatic artery, a proper hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second body lumen can comprise a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of the left main renal artery branch, or a distal end of the right main renal artery branch), a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen can comprise a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The fourth body lumen can comprise a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissues can reduce body weight, reduce body mass index, or a combination thereof.

[0028] A method of treating at least one disease comprising treating at least two different target tissues in at least two different body lumens using a delivery catheter can be a method of treating nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or a combination thereof. The method can comprise treating first, second, third, and fourth target tissues that are all different from each other and are located in first, second, third, and fourth body lumens, respectively. The first body lumen can comprise a common hepatic artery, a proper hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second body lumen can comprise a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of the left main renal artery branch, or a distal end of the right main renal artery branch), a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen can comprise a splenic artery, a right gastric artery, a left gastric artery, or a combination thereof. The fourth body lumen can comprise a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right inferior phrenic artery, a left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissues can reduce fat in the liver.

[0029] In various embodiments, the present disclosure provides a method of treating a disease. The method comprises inserting a delivery catheter into a body lumen, wherein the delivery catheter comprises a catheter shaft, at least one spray hole, and at least one marker band. The method comprises spraying a formulation through the at least one spray hole, wherein the amount of formulation delivered is effective to injure or damage a target tissue to relieve a symptom of the disease. The method comprises optionally removing the formulation from the tissue. The method further comprises withdrawing the delivery catheter from the body lumen.

[0030] In various embodiments, the present application provides a method of treating a disease. The method includes inserting a centering balloon delivery catheter into a body lumen, where the balloon delivery catheter includes at least one centering balloon and a catheter shaft, at least one injection needle, and at least one marker band. The method includes inflating the centering balloon to center the delivery catheter shaft in the body lumen. The method includes deploying at least one needle into, outside, or within a wall of the body lumen. The method includes infusing a formulation through the at least one needle, where the amount of formulation delivered is effective to injure or impair a target tissue to relieve a symptom of the disease. The method optionally includes removing the formulation from the tissue. The method includes retracting the needle into the delivery catheter and deflating the centering balloon. The method includes removing the delivery catheter from the body lumen.

[0031] In various embodiments, the present application provides a centering balloon catheter for delivering a material to a target location in a body lumen of a patient. The centering balloon catheter includes a proximal end; a distal end; a wire lumen; a balloon inflation lumen; a formulation infusion lumen and / or a vacuum lumen; an inflatable balloon portion; at least one injection needle; at least one marker band adjacent to the centering balloon; and at least one needle exit opening adjacent to the marker band for deploying the needle.

[0032] In various embodiments, the present application provides a needle-based balloon delivery catheter for delivering a material to a target tissue in a body lumen of a patient. The delivery catheter includes a catheter shaft having a proximal end and a distal end. The delivery catheter includes at least one marker band located proximate the distal end of the shaft. The delivery catheter includes at least one needle located in a needle lumen, where the needle lumen is open to the exterior of the catheter shaft through at least one needle exit hole. The delivery catheter includes a flushing port at the proximal end of the shaft in fluid communication with a flushing lumen, the flushing lumen being in fluid communication with a distal end of the needle lumen, where the flushing port is in fluid communication with the needle exit hole through the flushing lumen. The delivery catheter includes a guide wire lumen extending at least through the distal end of the shaft. The delivery catheter includes at least one balloon adjacent to the distal end of the catheter. The delivery catheter includes an inflation lumen. The delivery catheter includes an inflation port in fluid communication with the inflation lumen and in fluid communication with an interior of the balloon. The balloon is inflatable via the inflation port through the inflation lumen and to generally center the distal end of the catheter shaft within a body lumen. The delivery catheter includes an ablation or denervation port at the proximal end of the shaft. The ablation or denervation port is in fluid communication with the at least one needle to supply ablation energy or a formulation to the at least one needle. The delivery catheter further includes a needle movement controller in electrical or mechanical communication with the at least one needle. The needle movement controller deploys the at least one needle into, into a wall of, or outside of a body lumen.

[0033] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter includes one or more needles disposed proximate the distal end of the shaft for infusion of a therapy. The delivery catheter includes an inflatable balloon disposed proximate the distal end of the shaft such that when the delivery catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered within the lumen. The delivery catheter further includes a marker band at the distal end of the shaft.

[0034] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter includes one or more needles disposed proximate the distal end of the shaft for infusion of a therapy. The delivery catheter further includes a steering mechanism associated with the shaft such that the distal end of the shaft is steerable in a direction away from a longitudinal axis of the shaft.

[0035] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter further includes one or more needles disposed proximate the distal end of the shaft for infusion of a therapy. The delivery catheter further includes an inflatable balloon disposed proximate the distal end of the shaft such that when the delivery catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered within the lumen, wherein the distal end of the shaft includes a marker band; or a steering mechanism associated with the shaft such that the distal end of the shaft is steerable in a direction away from a longitudinal axis of the shaft; or a combination thereof.

[0036] Embodiments of the present invention relate to treating hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, digestive tract disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, rheumatoid arthritis, asthma, and chronic obstructive pulmonary disease (COPD) by delivering an effective amount of a formulation to a target tissue. Such formulations include one or more components in a gas, vapor, liquid, solution, emulsion, suspension, or combinations thereof. Methods include controlled delivery of the formulation to luminal surfaces and tissues within the human body, thereby modifying these areas. Such methods can result in denervation of nerves and nerve endings within and adjacent to body lumens. The methods can also include beneficially severing nerves and nerve endings to interrupt nerve communication. Temperature can enhance the safety and effectiveness of the therapeutic formulation. The temperature of the formulation can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. In some embodiments, the formulation includes one of a binary, ternary, or quaternary component, and can include more than four components. Delivery methods include less invasive percutaneous methods and non-invasive methods. Embodiments of the present invention provide formulations and delivery catheters that enhance the absorption and penetration of the formulation into body tissues and luminal nerves and nerve endings.

[0037] In one embodiment, the formulation includes water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropyl alcohol, propanol, butanol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodine oil, a surfactant, derivatives thereof, or combinations thereof.

[0038] In one embodiment, at least one component of the formulation is a gas. The gas includes one of oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, a vapor of an organic and inorganic compound, water, phenol, methanol, ethanol, absolute alcohol, isopropyl alcohol, propanol, butanol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, derivatives thereof, and combinations thereof.

[0039] In one embodiment, at least one component of the formulation is a surfactant. The surfactant includes PEG laurate, Tween 20, Tween 40, Tween 60, Tween 80, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, organic acids, salts of any organic acid and organic amine, polyglycidol, glycerol, polyglycerol, galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomers, di(propylene glycol), tri(propylene glycol), tetra(propylene glycol), penta(propylene glycol), poly(propylene glycol) oligomers, block copolymers of polyethylene glycol and polypropylene glycol, Pluronic, Pluronic 85, derivatives thereof, or combinations thereof.

[0040] In one embodiment, the formulation includes at least one of an oil, a fatty acid, and a lipid. In some embodiments, the at least one of an oil, a fatty acid, and a lipid in the formulation is selected from butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienol, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, a-linolenic acid, g-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di-, or triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, a-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, Neobee, niosomes, and derivatives thereof.

[0041] In another embodiment, the formulation includes a therapeutic agent or drug for denervation of a nerve. The therapeutic agent includes at least one of a sodium channel blocker, a tetrodotoxin, a saxitoxin, a decarbamoyl saxitoxin, a vanilloid, a neosaxitoxin, a lidocaine, a conotoxin, a cardiac glycoside, a digoxin, a glutamate, a staurosporine, an amlodipine, a verapamil, a cymarin, a digitoxin, a proscillaridin, a quabain, a veratridine, a domoic acid, an ethanol, an oleandrin, a carbamazepine, an aflatoxin, a guanethidine, and a guanethidine sulfate. In another embodiment, the formulation includes a contrast agent for imaging denervation of a nerve. Such a contrast agent includes one of iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof, and combinations thereof.

[0042] In one embodiment, the formulation comprises azeotrope. An azeotrope is a mixture of two or more components that cannot be changed by simple distillation. It occurs because the vapor produced upon boiling has components in proportion to those of the original mixture. Possible formulation azeotropes include ethanol / water, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropanol / water, butanol / water, acetic acid / water, or combinations thereof.

[0043] In one embodiment, the formulation is in a gaseous or vapor state and includes one or more components. The vapor or gaseous formulation can include oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, water, phenol, methanol, ethanol, spirits, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, or combinations thereof. In one embodiment, the vapor formulation includes one of a binary, ternary, or quaternary component, and can include more than four components. The vapor formulation can include azeotropes or contrast agents, such as iodine oil or iodine, and can include surfactants and / or therapeutic agents. The temperature of the vapor formulation can be from 0 to 140 °C, preferably from 15 to 100 °C, most preferably from 20 to 85 °C, or 0 °C or less, or less than, equal to, or greater than 10 °C, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more.

[0044] In one embodiment, the formulation is in a liquid state and includes one or more components. The liquid formulation can include one of water, saline, hypertonic saline, phenol, methanol, ethanol, spirits, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodine oil, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, surfactants, and others. The liquid formulation can include azeotropes or contrast agents and can include therapeutic agents. In one embodiment, the formulation can include one of a binary, ternary, or quaternary component, and can also include more than four components. In some embodiments, the temperature of the liquid formulation can be from -40 to 140 °C, from -30 to 100 °C, from -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The liquid formulation can include a solution, a suspension, an emulsion, or combinations thereof.

[0045] In one embodiment, a method for treating at least one disease comprises inserting a delivery catheter percutaneously and / or orally into a target tissue in a human body; using the catheter to infuse a therapeutic agent into the tissue of the body, wherein the amount of agent delivered is effective to beneficially injure or impair the tissue; optionally removing the agent; and removing the delivery catheter from the body. The injury or impairment of the tissue can alleviate a symptom of the disease, such as by reducing blood pressure, reducing blood glucose levels, reducing body weight, alleviating shortness of breath, alleviating heart disease, alleviating a blood vessel condition, alleviating joint pain, alleviating stiffness, alleviating swelling, or a combination thereof. The at least one disease targeted by the treatment comprises one or more of the following: hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral artery disease (PAD), end-stage renal disease, a digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), a urinary system disease, cancer, a tumor, pain, rheumatoid arthritis (RA), asthma, and chronic obstructive pulmonary disease (COPD). It can be more effective to treat multiple related diseases in one procedure, such as for a patient who has two or more of hypertension, obesity, and type 2 diabetes. The tissue that can be treated can include a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, or a distal end of a right main renal artery branch), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a urinary lumen. The digestive lumen can include an esophagus, a stomach, a duodenum, a jejunum, a small intestine, a large intestine, and a colon. The agent can include one or more components of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, or a combination thereof. If the agent includes one or more components of a vapor, heat can be generated by condensation of the vapor into a liquid in the tissue. If the agent includes a liquid or a solution, cooling or heat can be generated by an agent temperature that is below or exceeds body temperature. The liquid agent temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. In one embodiment, the agent temperature can be equal to room temperature. In one embodiment, the agent temperature can be -40 to -20 °C. In another embodiment, the agent temperature can be 15 to 80 °C. In one embodiment, the agent temperature can be equal to body temperature.In another embodiment, the formulation temperature can be 50 to 80 °C. In another embodiment, the temperature of the treated tissue can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or lower, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or higher. In one embodiment, the temperature of the treated tissue can be -40 to -20 °C. In another embodiment, the temperature of the treated tissue can be 15 to 80 °C. In one embodiment, the temperature of the treated tissue can be equal to body temperature. In another embodiment, the temperature of the treated tissue can be 50 to 80 °C. Delivery catheters suitable for such treatment include a needle or needle-based catheter under imaging guidance. Imaging guidance includes one of the following: ultrasound, X-ray, CT scan, MRI, OCT, or oscilloscope. The delivery catheter can also be balloon-based. Such balloon-based catheters can have both a balloon and a needle in one catheter. The delivery catheter can be jet-based. Jet-based catheters are capable of producing very fine mist to large droplets. In some embodiments, a combination of a balloon and a jet catheter can be used in the procedure (e.g., without a needle), a combination of a needle catheter and a jet catheter can be used, or a combination of a needle catheter, a jet catheter, and a balloon catheter can be used (e.g., including jet and needle-based formulation administration). In one embodiment, the method includes flushing from the distal tip of the catheter to protect and dilute the migrating chemical and prevent runaway chemical from entering the distal portion of the untreated area; flushing from the delivery catheter; flushing from the endoscope; removing or taking out the formulation from the body tissue and cavity after treatment; and flushing the target area after treatment with saline. If a needle is present, the method can also include deploying the needle, administering the formulation from the needle, and retracting the needle.

[0046] In one embodiment, the delivery catheter includes at least one needle for delivering the formulation into the vessel wall, outside the vessel, or a combination thereof. In some needle-catheter embodiments, at least one balloon is used to center the distal end of the catheter in the cavity, or to center the portion of the catheter from which the needle emerges in the cavity. When the distal end of the catheter is centered in the treatment cavity, the user has better control of the needle and injection depth. In some needle-catheter embodiments, there are two centering balloons and at least one needle is positioned between the two balloons. In some needle-catheter embodiments, there is only one balloon and at least one needle can be positioned proximal or distal to the balloon, but in either case adjacent to the balloon to take advantage of the catheter shaft's centering in the treatment cavity. In one embodiment of the needle-catheter, there is no centering balloon.

[0047] In one embodiment, the delivery catheter comprises a jet catheter. In this embodiment, the formulation is delivered through a jet hole at or near the distal end of the catheter, thereby delivering in a mist to the walls of the treatment lumen. This embodiment can include a sleeve positioned over the jet hole to provide more even distribution of the formulation onto the walls of the treatment lumen. This embodiment can include a vacuum port for removing excess formulation from the treatment lumen. BRIEF DESCRIPTION OF DRAWINGS

[0048] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various embodiments of the application.

[0049] Figure 1 is an exemplary embodiment of a perspective view of a dual balloon delivery catheter according to the present application.

[0050] Figure 2 is an embodiment showing infusion of a formulation into an airway using a jet catheter.

[0051] Figure 3 is an embodiment showing infusion of a formulation into a renal artery using a triple needle balloon delivery catheter.

[0052] Figure 4 is an embodiment of a partial cutaway view of a dual balloon delivery catheter in a body lumen.

[0053] Figure 5 is an embodiment of a partial cutaway view of a triple needle dual balloon delivery catheter with a needle deployed in a body lumen.

[0054] Figure 6A is an exemplary embodiment of a perspective view of an over-the-wire (OTW) triple needle balloon delivery catheter according to the present application.

[0055] Figure 6B is an exemplary embodiment of a perspective view of an OTW triple needle balloon delivery catheter with a balloon and needle deployed according to the present application.

[0056] Figure 7A is another exemplary embodiment of a perspective view of a rapid exchange triple needle balloon delivery catheter according to the present application prior to needle deployment.

[0057] Figure 7B is an exemplary embodiment of a perspective view of a rapid exchange triple needle balloon delivery catheter according to the present application with a flushing lumen after needle deployment.

[0058] Figure 7C is a cross-section of a catheter according to various embodiments as shown in Figure 7B

[0059] Figure 7D is a cross-section of a catheter according to various embodiments as shown in​Figure 7B a cross-section of the catheter at section 7D-7D as shown.

[0060] Figure 7E is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments. Figure 7B a cross-section of the catheter at section 7E-7E as shown.

[0061] Figure 7F is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments. Figure 7B an alternative cross-section of the catheter at section 7F-7F as shown.

[0062] Figure 7G is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments. Figure 7B a cross-section of the catheter at section 7G-7G as shown.

[0063] Figure 8A is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments.

[0064] Figure 8B is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments.

[0065] Figure 9A is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments.

[0066] Figure 9B is an exemplary embodiment of a perspective view of a steerable catheter according to various embodiments.

[0067] Figure 9C is an embodiment of a partial cutaway view of a one-way steerable catheter with a needle deployed in a body lumen.

[0068] Figure 10 is a bar graph showing norepinephrine (NE) reduction after renal denervation in ethanol treated groups versus control treated groups according to various embodiments.

[0069] Figure 11 is a histopathology image showing necrosis of transected renal nerves (as indicated by black arrows) after ethanol treatment according to various embodiments.

[0070] Figure 12 is a bar graph showing norepinephrine (NE) reduction after hepatic denervation from ethanol treated groups versus control treated groups according to various embodiments.

[0071] Figure 13 is an exemplary embodiment of a perspective view of a jet catheter according to the present invention.

[0072] Figure 14 is an exemplary embodiment of a perspective view of a jet catheter with dual suction features according to the present invention.

[0073] Figure 15A Embodiment in which the formulation is infused into the left gastric artery using a three needle balloon delivery catheter.

[0074] Figure 15B Embodiment in which the formulation is infused into the hepatic artery using a three needle balloon delivery catheter. DETAILED DESCRIPTION

[0075] Reference will now be made in detail to certain embodiments of the subject disclosure. While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the subject matter exemplified is not intended to limit the claims to the disclosed subject matter.

[0076] Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the straight- listed range end values, but also an implicit set of intervening values as well as the individual values expressly stated. For example, a range of "about 0.1 % to about 5%" or "about 0.1 % to 5%" should be interpreted to include not only the straight-listed values but also the implied values of about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1 %, about 2%, about 3%, about 4%, and about 4.5%, as well as single values such as 1 %, 2%, 3%, and 4%, and sub-ranges within the specified range, e.g., 0.1 % to 0.5%, 1.1 % to 2.2%, 3.3% to 4.4%. Unless otherwise indicated, the expression "about X to Y" has the same meaning as "about X to about Y". Likewise, unless otherwise indicated, the expression "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z".

[0077] In this document, the terms "a," "an," or "the" are used to include one or more than one unless the context clearly dictates otherwise. The term "or" is used in the inclusive sense, unless the context clearly dictates otherwise. The expression "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B." Furthermore, it is to be understood that the use of certain terms or expressions in this document, and in the claims that follow, are used herein as descriptors for clarity and are not intended to limit the subject matter described herein. Any use of section headings is intended to aid reading the document and should not be interpreted as limiting; information that is relevant to a section heading can occur within or outside of that particular section.

[0078] In the methods described herein, unless a temporal or operational sequence is explicitly recited, acts can be performed in any order without departing from the principles of the application. Moreover, specified acts can be conducted simultaneously, unless the explicit claim language recites that they are conducted separately. For example, a recited claim to an act of performing X and an act of performing Y can be conducted simultaneously within a single operation, and the resulting method would fall within the literal scope of the recited claim.

[0079] As used herein, the term "about" can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a given value or the given limits of a range and includes the exact given value or range.

[0080] As used herein, the term "substantially" refers to a majority of, or predominantly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. As used herein, the term "substantially free of can mean having none or an insubstantial amount such that the amount of material present does not affect the material properties of a composition including the material, such that from about 0 wt% to about 5 wt% of the composition is the material, or from about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%.

[0081] As used herein, the term "polymer" refers to a molecule having at least one repeating unit and can include a copolymer.

[0082] In various embodiments, the present disclosure provides a method of treating at least one disease (e.g., one disease, two diseases, at least two diseases, three diseases, at least three diseases, four diseases, or at least four diseases). The method includes using a delivery catheter in a body lumen, e.g., treating at least two different target tissues in at least two different body lumens. The method includes performing a treatment procedure on a body lumen as a first body lumen. The treatment procedure can include inserting a delivery catheter into the body lumen. The delivery catheter can include a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon. The treatment procedure can include inflating the balloon to center the distal end of the shaft in the body lumen. The treatment procedure can include denervating or ablating a target tissue of the body lumen with the delivery catheter, including delivering an amount of energy or agent to the target tissue effective to injure or impair the target tissue to relieve symptoms of the disease. The treatment procedure can include deflating the balloon. The treatment procedure can also include removing the delivery catheter from the body lumen. The method can include performing the treatment procedure on a second body lumen different from the first body lumen.

[0083] Performing the treatment procedure on the second body lumen can include using the same delivery catheter or a different delivery catheter. Performing the treatment procedure on the second body lumen can include reusing the same delivery catheter in the treatment procedure on the second body lumen as was used in the treatment procedure on the first body lumen. Performing the treatment procedure on the second body lumen can include using a different delivery catheter in the treatment procedure on the second body lumen than was used in the treatment procedure on the first body lumen, the different delivery catheter including a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon.

[0084] Treating at least two different target tissues in at least two different body lumens refers to treating at least two different classes of body lumens selected from the group consisting of: renal arteries, renal veins, gastroduodenal arteries, gastroduodenal veins, hepatic arteries, hepatic veins, pulmonary arteries, pulmonary veins, celiac arteries, celiac veins, gastroduodenal arteries, gastroduodenal veins, splenic arteries, splenic veins, adrenal arteries, adrenal veins, phrenic arteries, phrenic veins, mesenteric arteries, mesenteric veins, airways, esophagus, stomach, duodenum, jejunum, and urinary lumens. The renal arteries can include left main renal arteries, right main renal arteries, renal artery branches, left renal artery branches, right renal artery branches, distal ends of left main renal arteries, distal ends of right main renal arteries, distal ends of left main renal artery branches, and distal ends of right main renal artery branches. The gastroduodenal arteries can include left gastroduodenal arteries, right gastroduodenal arteries, left gastroduodenal artery branches, and right gastroduodenal artery branches. The hepatic arteries can include hepatic arteries, common hepatic arteries, proper hepatic arteries, left hepatic arteries, middle hepatic arteries, and hepatic artery branches. The splenic arteries can include main splenic arteries and splenic artery branches. The adrenal arteries can include right adrenal arteries and left adrenal arteries. The phrenic arteries can include right phrenic arteries and left phrenic arteries. The mesenteric arteries can include superior mesenteric arteries, inferior mesenteric arteries, and mesenteric artery branches. The urinary lumens can include urethra and ureter. For example, treatment of left gastroduodenal arteries and left gastroduodenal artery branches is considered treatment of one class of body lumens. Treatment of left gastroduodenal arteries and main splenic arteries is considered treatment of two different classes of body lumens. Treatment of at least three different target tissues in at least three different body lumens, or treatment of at least four different target tissues in at least four different body lumens, respectively define treatment of three or four different classes of body lumens.

[0085] The target tissue of the first and second body lumens can be different and can be independently selected from the group consisting of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, or a distal end of a right main renal artery branch), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a target tissue of a urinary lumen. The disease treated can be selected from the group consisting of hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, a digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), a urinary system disease, cancer, a tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), and combinations thereof.

[0086] The alleviation of a symptom of a disease includes alleviating a symptom of hypertension, diabetes, obesity, coronary heart disease, peripheral disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cancer, arthritis, or combinations thereof. Alleviating a symptom of a disease can include reducing blood pressure, reducing blood glucose levels and AIC, reducing body weight, reducing restenosis, reducing liver fat, and reducing pain, or combinations thereof.

[0087] The at least one disease treated by the method of treating different target tissues in the first and second body lumens can include at least two diseases, such as both renal hypertension and diabetes (e.g., treating both the renal artery and the hepatic artery); or both renal hypertension and obesity (e.g., treating both the hepatic artery and the splenic artery); or both diabetes and obesity (e.g., treating the splenic artery, the hepatic artery, and the left gastric artery); or combinations thereof. The first or second body lumen can include the splenic artery. The first or second body lumen can include the renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of the left main renal artery branch, a distal end of the right main renal artery branch, or combinations thereof). The first or second body lumen can include the splenic artery. The first or second body lumen can include a main renal artery branch, an extra-renal artery branch, or combinations thereof. The first or second body lumen can include the hepatic artery, a hepatic artery branch, the right hepatic artery, the left hepatic artery, the common hepatic artery, the proper hepatic artery, the celiac artery, or combinations thereof. The first or second body lumen can include the renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of the left main renal artery branch, a distal end of the right main renal artery branch, or combinations thereof), and the method can result in at least a 40% reduction in renal norepinephrine, or at least a 10%, 15, 20, 25, 30, 35, 40, 45, or at least a 50% reduction.

[0088] The delivery catheter can further include a guidewire lumen extending at least through the distal end of the shaft, wherein the method can further include advancing the delivery catheter over a guidewire. The delivery catheter can further include a marker band on or adjacent to the balloon, wherein the method can further include monitoring the position of the marker band under fluoroscopy.

[0089] The delivery catheter can be a chemical infusion delivery catheter. The delivery catheter can be an energy delivery catheter. The delivery catheter can be a combination of a chemical infusion delivery catheter and an energy delivery catheter. For an energy delivery catheter, denervating or ablating a target tissue of a body lumen with the delivery catheter can include delivering an amount of energy (e.g., thermal energy) from the delivery catheter or to the target tissue using radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound, condensation of at least some of the agent vapor into a liquid, or combinations thereof. Thus, the energy delivery catheter can be one of a radiofrequency catheter, a cryoablation catheter, a microwave catheter, a laser catheter, an ultrasound catheter, a high intensity focused ultrasound catheter, an infusion catheter, or combinations thereof.

[0090] The delivery catheter can be a radiofrequency energy delivery catheter, or a combination of a radiofrequency energy delivery catheter and a chemical infusion catheter. In some embodiments, the safety and effectiveness of radiofrequency energy delivery is improved by increasing the size of the ablation caused by the energy delivery, while minimizing the risk of complications that can arise during energy delivery. Examples of such complications include thrombosis, steam pops, bubbling, target tissue charring, restenosis, media and adventitial fibrosis, and others related to catheter manipulation (i.e. perforation). Spot thermal ablation (RF ablation) is non-uniform and does not reach the adventitial nerves. Partial spot RF ablation results in low effectiveness (low blood pressure drop). The radiofrequency energy delivery catheter can include one or more electrodes. In various embodiments, the delivery catheter includes one or more needles, and the tip of the one or more needles can function as an electrode (e.g., the needle can be insulated to leave only a portion for the exposed electrode, e.g., 1 mm to 5 mm length of the needle non-insulated portion; in other embodiments, the needle is not insulated). The needles for radiofrequency ablation can be the same as the needles described herein for chemical infusion, or they can be different. For example, the radiofrequency energy delivery needles can have any suitable diameter, can be solid or hollow, and can be used to deliver radiofrequency energy to the body lumen, the body lumen wall, or outside of the body lumen wall. For radiofrequency delivery, a return electrode can be positioned on the catheter, or a device such as a pad can be used. The delivery catheter can include one or more electrodes on a wire (e.g., a wire with spring or shape memory properties to ensure good contact with the target tissue), one or more electrodes on a polymer shaft, one or more electrodes on the outer surface of a balloon, or a combination thereof. The delivery catheter can include more than one electrode to achieve shorter treatment times. The method can include cooling the electrode, e.g., via passive cooling via blood flow and / or via active fluid cooling, e.g., internal active cooling (closed loop) or external active fluid cooling (open loop). The size of the electrode can be reduced to increase passive cooling by blood flow. Cooling the electrode can increase the delivery of energy into the neural tissue of the target tissue. Cooling the needle electrode can include flowing a coolant or a liquid that enhances RF delivery through the needle (e.g., a chemical agent or a different liquid composition as described herein) before, during, or after radiofrequency delivery. In one embodiment of external cooling of the electrode (open loop), the chemical agents described herein can replace the active cooling fluid. The disclosed agents can be used not only to cool the electrode, but also for chemical ablation of the target tissue. In some embodiments, the agents can diffuse and penetrate uniformly into the neural tissue, and they can uniformly ablate the nerves in the adventitia in the body lumen. Thus, the chemical ablation agents can be delivered during, before, and / or after energy ablation.

[0091] For delivery catheters that deliver microwave or ultrasound, the delivery catheter can include a centering mechanism (e.g., a centering balloon) and a cooling system for the energy source. The microwave or ultrasound energy source can be located inside the balloon, cooled on the surface of the balloon or inside the balloon. The microwave or ultrasound energy source can be focused to treat only a subset of the circumference of the body lumen, or the energy source can deliver energy around the entire circumference of the body lumen. For delivery catheters that deliver laser energy, the delivery catheter can be configured such that the laser energy is emitted from the walls of the shaft. For delivery catheters that can perform cryoablation (i.e., deliver negative energy), a needle or jet hole can be used to deliver the cryoablation medium. During cryoablation, the cryoablation medium can be delivered to the target tissue, for example, through the needle. Once the substance exits the delivery catheter, the pressure drop, evaporation, or phase change of the cryoablation medium can provide the cryoablation treatment. If a liquid is used for cryoablation, the needle or jet hole can be sealed to prevent delivery until the delivery catheter is positioned, and the delivery catheter can include a gas return channel to expel the vapor from the cryoablation medium to outside the body. To perform cryoablation through a jet hole, multiple balloons can be used to create a treatment window that contains the cryoablation fluid during treatment and prevents cryoablation of the body lumen tissue outside the treatment window.

[0092] For any type of energy delivery, methods of using the delivery catheter can include cooling the energy source through the irrigation lumen to reduce the temperature of the energy source and to clean the lumen (e.g., clean the artery and prevent blood from clogging). In various embodiments, a needle can be used for cooling. Delivery catheters for energy delivery can include a guide wire lumen to facilitate insertion and placement of the delivery catheter.

[0093] In some embodiments, the delivery catheter is electrodeless. The delivery catheter can be devoid of any ablation energy source, for example, devoid of radiofrequency, ultrasound, and microwave energy sources.

[0094] Embodiments of the invention relate to treating at least one disease by delivering an effective amount of a formulation and / or energy to a target tissue. The disease can include hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), or a combination thereof. Cancer includes adrenal cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, uterine cancer, or a combination thereof. The formulation can include one or more components in a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof. The method includes delivering the formulation and / or energy to a luminal surface, tissue, and nerve of a human body to modify the surfaces, tissues, and nerves. The tissue includes a renal artery (e.g., left main renal artery, right main renal artery, renal artery branch, left renal artery branch, right renal artery branch, distal end of left main renal artery, distal end of right main renal artery, distal end of left main renal artery branch, distal end of right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof. The digestive lumen includes an esophagus, a stomach, a duodenum, a jejunum, a small and large intestine, a colon, or a combination thereof. The temperature can increase the safety and effectiveness of the therapeutic formulation. The temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the tissue being treated can be different from the formulation temperature. The temperature of the tissue being treated can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more. The amount of formulation and energy delivered can be effective to beneficially injure, damage, or eliminate (e.g., kill) the target tissue and thereby alleviate disease symptoms, for example, by lowering blood pressure, shrinking a tumor, relieving pain, relieving symptoms of asthma or COPD, or a combination thereof. The energy or heat can enhance the injure / damage / elimination effect by accelerating the reaction rate between the formulation and the tissue.The delivery method includes delivering a formulation to ablate nerves surrounding a body cavity. The method can include removing or taking the formulation from the tissue or cavity after treatment. Without direct observation, the nerve ablation can be identified based on physiological functions corresponding to the nerves, such as glucose and norepinephrine (NE) levels. Norepinephrine is the primary neurotransmitter used by the sympathetic nervous system, which is connected to many organs, including, for example, the heart, lungs, liver, spleen, gallbladder, stomach, intestines, kidneys, bladder, and many others. For example, in the liver, increased sympathetic nerve action of norepinephrine increases glucose production, which occurs through glycogenolysis after a meal or through gluconeogenesis when not recently fed. Thus, correction of overactive hepatic sympathetic nerves will decrease NE content and result in lower glucose levels. In the kidneys, release of renin and retention of sodium in the bloodstream increases blood pressure. Norepinephrine (NE) content in the tissue can be used as a biomarker to demonstrate or indicate treatment effectiveness. Various embodiments of the method including treatment of overactive hepatic sympathetic nerves can result in a decrease in NE content of 20% to 99%, preferably, 50% to 98%, and most preferably, 75% to 97% compared to untreated (control) subjects.

[0095] In one embodiment, the formulation is one of a single chemical or a binary, ternary, or quaternary component, and can also include more than four components. In one embodiment, the delivery system can be used with a less invasive percutaneous method or a non-invasive method. Embodiments of the present invention provide a formulation including one or more ingredients that perform surface modification of a body cavity by absorption and penetration into the tissue and nerves and nerve endings of the body cavity.

[0096] In one embodiment, the formulation can include or consist of water, saline, hypertonic saline, phenol, methanol, ethanol, ethyl alcohol, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodine oil, a surfactant, a derivative thereof, or a combination thereof.

[0097] In one embodiment, the ingredients of the formulation are at least one gas. The gas can be selected from the group consisting of oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, a vapor of an organic and inorganic compound, water, phenol, methanol, ethanol, ethyl alcohol, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

[0098] In one embodiment, the ingredient in the formulation is at least one surfactant. In some embodiments, the surfactant is selected from the group consisting of PEG laurate, Tween 20, Tween 40, Tween 60, Tween 80, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, organic acids, salts of any organic acid and organic amine, polyglycidol, glycerol, polyglycerol, galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomers, di(propylene glycol), tri(propylene glycol), tetra(propylene glycol), penta(propylene glycol), poly(propylene glycol) oligomers, block copolymers of polyethylene glycol and polypropylene glycol, Pluronic, Pluronic 85, derivatives thereof, and combinations thereof. In some embodiments, the content of surfactant in the formulation can be 0.1-80% by weight, preferably 0.5-50% by weight, most preferably 1-15% by weight.

[0099] In one embodiment, the formulation includes at least one of an oil, a fatty acid, and a lipid. The oil, fatty acid, and lipid in the formulation can be selected from the group consisting of butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienol, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, a-linolenic acid, g-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di- or triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, a-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobee, niosomes, derivatives thereof, and combinations thereof.

[0100] In one embodiment, the formulation includes a therapeutic agent or drug for denervation and surface modification of a nerve. The therapeutic agent is at least one of a sodium channel blocker, a tetrodotoxin, a saxitoxin, a decarbamoyl saxitoxin, a vanilloid, a neosaxitoxin, a lidocaine, a conotoxin, a cardiac glycoside, a digoxin, a glutamate, a staurosporine, an amlodipine, a verapamil, a cymarin, a digitoxin, a proscillaridin, a quabain, a veratridine, a domoic acid, an ethanol, an oleandrin, a carbamazepine, an aflatoxin, a guanethidine, or a guanethidine sulfate. In another embodiment, the formulation includes a contrast agent for imaging denervation of a nerve. Such a contrast agent includes iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof, and combinations thereof. The contrast agent can be present in the formulation in an amount of 2-25% by weight, preferably 5-15% by weight.

[0101] In one embodiment, the formulation comprises azeotrope. An azeotrope is a mixture of two or more components that cannot be changed by simple distillation. It occurs because the vapor produced upon boiling has components in proportion to those of the original mixture. The azeotrope of the formulation can be selected from the group consisting of ethanol / water, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropanol / water, butanol / water, and acetic acid / water.

[0102] In one embodiment, the formulation is in a gaseous or vapor state, comprising one or more components. In one embodiment, the gaseous or vapor formulation comprises: oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, a vapor of an organic and inorganic compound, or a combination thereof. The vapor of an organic and inorganic compound comprises one of the following: water, phenol, methanol, ethanol, anhydrous alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

[0103] In one embodiment, the vapor formulation comprises at least one contrast agent, such as iodine oil or iodine, and an azeotrope, and can further comprise a surfactant and / or a therapeutic agent. In one embodiment, the vapor is one of a binary, ternary, or quaternary component, and can further comprise more than four components. The temperature of the vapor formulation can be from 0 to 140 °C, from 15 to 100 °C, from 30 to 80 °C, or 0 °C or less, or less than, equal to, or greater than 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more.

[0104] In one embodiment, the formulation is in a liquid state, including one or more components. The liquid formulation includes at least one of the following: water, saline, hypertonic saline, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodine oil, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, a surfactant, and the like, and combinations thereof. In one embodiment, the liquid formulation includes one of a contrast agent and azeotrope, and can further include a therapeutic agent. In one embodiment, the liquid formulation is one of binary, ternary, or quaternary components, and can further include more than four components. In one embodiment, the liquid formulation includes a solution, emulsion, or suspension. The temperature of the liquid formulation can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. In one embodiment, the formulation temperature can be room temperature. In one embodiment, the formulation temperature can be -40 to -20 °C. In another embodiment, the formulation temperature can be 15 to 80 °C. In one embodiment, the formulation temperature can be equal to body temperature. In another embodiment, the formulation temperature can be 50 to 80 °C.

[0105] In one embodiment, the method of treating at least one disease comprises inserting a delivery catheter into the body percutaneously or orally; infusing a formulation and / or delivering energy to a target tissue or lumen in the body using the catheter; optionally removing or withdrawing the formulation from the target tissue or body lumen; and withdrawing the delivery catheter from the body. The one or more diseases treated can include hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, a digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), a urinary system disease, a cancer, a tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), or a combination thereof. The cancer can include an adrenal cancer, a bladder cancer, a cervical cancer, a colon cancer, an esophageal cancer, a gallbladder cancer, a kidney cancer, a liver cancer, a lung cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a rectal cancer, a stomach cancer, a uterine cancer, or a combination thereof. The body tissue includes a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of the left main renal artery branch, a distal end of the right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof. The digestive lumen can include an esophagus, a stomach, a duodenum, a jejunum, a small and large intestine, a colon, or a combination thereof. The formulation can include a gas, a vapor, a liquid, a solution, an emulsion, a suspension, and a combination thereof of one or more ingredients. In embodiments where the formulation includes a vapor of one or more ingredients, heat can be generated by condensation of the vapor into a liquid in the tissue. In embodiments where the formulation includes a liquid or a solution, cooling or heat can be generated from a formulation temperature that is below or exceeds body temperature. The liquid formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. In one embodiment, the temperature of the treated tissue can be different from the formulation temperature and lower or higher than body temperature. The temperature of the treated tissue can be 15 to 100 °C, more preferably 20 to 90 °C, and most preferably 36 to 80 °C. In another embodiment, the temperature of the treated tissue can be -40 to -20 °C. In some embodiments, the delivery catheter is an imaging-guided needle or needle-based catheter. The imaging guidance can be ultrasound, X-ray, CT scan, MRI, OCT, scope, or a combination thereof.The delivery catheter can be a balloon-based needle catheter. The balloon-based needle catheter can have a single balloon or a dual balloon. The balloon-based catheter can have a single needle, a dual needle, or a triple needle. The infusion can be from the needle catheter assembly and can be defined as a needle infusion method. The infusion volume can be 0.1 mL to 5 mL, preferably 0.2 mL to 2.5 mL, and most preferably 0.3 mL to 1.5 mL. If the delivery catheter is a balloon and needle infusion combination device, the balloon pressure can be maintained in the range of 0.1 to 3 atm, preferably 0.1 to 2 atm, and most preferably 0.3 to 1 atm during the infusion time period. Optionally, a syringe operation can be used to operate and maintain such low pressure balloon inflation, and the balloon size can be observed in real time by fluoroscopy. The formulation infusion temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or lower, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or higher. More detailed examples of catheters, such as single balloon needle and dual balloon needle delivery catheters, are shown in the following sections.

[0106] In one embodiment, the infusion lumen can be at least one needle, such as a single needle or a multi-needle (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or more needles). Figure 3 and 5 -9). The needle tip can be movable and, for delivery of the formulation, can be positioned in the lumen wall or positioned outside the lumen wall by piercing the lumen wall. The needle can be very small and can have a diameter (outer diameter, OD) of about 200 pm to 500 pm, preferably about 300 pm to 400 pm. The small size of the needle can prevent or significantly reduce leakage or bleeding after puncture and removal. The needle device can infuse the formulation directly and accurately into the adventitial layer of the lumen tissue, achieving a deep treatment. The infusion time of the needle device is within 3 minutes, preferably between 5 seconds to 150 seconds.

[0107] In one embodiment, the formulation is or includes ethanol. The formulation can be delivered in vapor or liquid form to the tissue of the body lumen. The vapor or liquid formulation temperature can be -40 to 150 °C, preferably -30 to 100 °C, and most preferably -20 to 80 °C. The temperature of the tissue can be -40 to 90 °C, preferably -30 to 80 °C.

[0108] In one embodiment, the formulation is or includes a mixture of ethanol and water. The ethanol content can be in the range of 10 to 100% by weight. The formulation can be delivered to the tissue of the body cavity in vapor or liquid form. The vapor or liquid formulation temperature can be -40 to 150°C, preferably -30 to 100°C, most preferably -20 to 80°C. The temperature of the tissue can be -40 to 90°C, preferably -30 to 80°C. The ethanol / water formulation can be a positive azeotrope. The azeotrope can be 95.63% ethanol and 4.37% water by weight. Ethanol boils at 78.4°C, water boils at 100°C, and the azeotrope boils at 78.2°C, lower than either of its components. 78.2°C is the lowest temperature at which any ethanol / water solution can boil at atmospheric pressure.

[0109] In another embodiment, the formulation is a mixture of vapor including water, ethanol, and oxygen. In another embodiment, the formulation is a mixture of vapor including water, ethanol, and air. In another embodiment, the formulation is a mixture of vapor including water, ethanol, oxygen, and nitrogen. Formulations containing oxygen and air are particularly useful for treating asthma and COPD.

[0110] In another embodiment, the formulation is a mixture of vapor including water, ethanol, and iodine, wherein an effective amount of iodine vapor is included to image the mixture of vapor in the wall of the body cavity. In another embodiment, the formulation is a mixture of liquid including water and ethanol and further including a surfactant. In another embodiment, the formulation is a mixture of liquid including water and ethanol and further including a contrast agent, wherein an effective amount of contrast agent can be included to enable tracking of the mixture in the wall of the body cavity by X-ray. The contrast agent can include iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof, and combinations thereof. The content of the contrast agent in the formulation can be 2 to 20% by weight, preferably 5 to 15% by weight.

[0111] In one embodiment, the formulation is a mixture of acetic acid and water. The acetic acid content of the formulation can be 1 to 100% by weight, preferably 10 to 75% by weight, most preferably 20 to 50% by weight. The formulation can be delivered to the tissue of the body cavity in vapor or liquid form. The vapor or liquid formulation temperature can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The temperature of the tissue can be -30 to 80°C, preferably 60 to 80°C, or -30 to -20°C. The temperature of the tissue can be -40 to 0°C, preferably -30 to -20°C. The acetic acid content of the formulation can be 2 to 75% by weight, preferably 10 to 60% by weight.

[0112] In another embodiment, the formulation is a mixture of a liquid comprising ethanol and iodized oil (e.g., ULTRA-FLUIDE) wherein an effective amount of iodized oil is included so as to enable imaging of the mixture of vapor in the wall of the body cavity and also beneficially damage the target neural tissue. The iodized oil content of the formulation can be 10 to 80% by weight, preferably 15 to 75% by weight, most preferably 20 to 50% by weight. The formulation can be or include a mixture of a liquid comprising water and iodized oil, or a mixture of a liquid comprising acetic acid and iodized oil. The iodized oil content of the formulation can be in the range of 10 to 80% by weight, preferably 15 to 75% by weight, most preferably 20 to 50% by weight.

[0113] In one embodiment, the formulation is infused into the tissue of the human body using a delivery catheter. The delivery catheter is a needle or needle-based balloon catheter and can be guided to the delivery site by X-ray or ultrasound imaging guidance. The needle-based balloon delivery catheter can have one or two balloons. Using a needle device, the formulation infusion can be in the wall of the cavity or outside the wall of the cavity (e.g., intracavitary or extravascular).

[0114] In one embodiment, the delivery catheter is a jet catheter. The application of the formulation can reach the inner wall of the body cavity. In some embodiments, the jet direction of the device is designed to be approximately perpendicular to the wall of the cavity. The jet catheter can be needleless, or can include a needle for the administration of the formulation based on both jet and needle. The jet catheter can include a centering balloon, or can be without a balloon. The jet catheter can optionally include the ability to deliver energy to the target tissue, such as radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound, or combinations thereof.

[0115] As in Figure 1As shown, the delivery catheter 10 has an elongated shaft 11 having at least one lumen, a distal end 13, and a proximal end 14. At the distal end 13 are proximal and distal 21 lumen-conforming balloons. In any configuration, the tubing of the catheter shaft 11 can be extruded from a plastic material, such as thermoplastics, polyimide, polyetherimide, polyethylene, polyurethane, polyester, polyamide, Pebax, nylon, fluorinated polyurethane, polyetheretherketone, or polysulfone, or combinations thereof. The catheter shaft 11 can be extruded or formed to have various lumen cross-sections, including circular or elliptical lumens. Furthermore, as in... Figure 1 As shown, catheter 10 may be equipped with a flushing port 43, a distal balloon inflation port 40 for inflating the distal balloon 21, and a proximal balloon inflation port 41 for inflating the proximal balloon 20, such that the proximal balloon 20 and the distal balloon 21 are inflated individually. A cavity-compliant balloon is a balloon that can be inflated at a pressure less than that required to deform the cavity wall. The balloon material is selected to be flexible and usable at high temperatures, such that the balloon is compliant during inflation. In one embodiment, the balloon material is one of polyamide, nylon, Pebax, polyester, polyethylene terephthalate, or copolymers thereof. Depending on the diameter of the treatment site, the inflation diameter of the balloon can range from about 2 mm to about 40 mm. In one embodiment, the diameter of each balloon is about 2 mm. Alternatively, the inflation diameter of each balloon may be less than, equal to or greater than approximately 3 mm, 4, 5, 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 approximately 40 mm or more.

[0116] In one embodiment, at least one marker band 22b is located at the proximal end of the proximal balloon 20, and at least one marker band 23a is located at the distal end of the distal balloon 21. The balloon catheter can be a rapid exchange or over-the-wire catheter made of any suitable biocompatible material. The marker bands can also be positioned at the other end of the balloon (22a and 23b). A segment 25 is located between balloons 20 and 21, having at least one infusion port, a non-inflatable portion 30, and an axis adjacent to the balloon portion 24. Ports 40 and 41 for balloon inflation are for the distal and proximal balloons, respectively. Infusion port 42 is for infusing chemical agents.

[0117] The materials of balloons 20 and 21 include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, Pebax, polyurethane, block copolymers of polyether and polyester, or combinations thereof. The diameter of balloon 21 is equal to or smaller than the diameter of balloon 20.

[0118] Figure 2 FIG. 6 shows a schematic view of an embodiment of a jet catheter positioned within the left main bronchus for treatment of asthma and COPD. Figure 2 Delivery catheter 198 can treat airways distal to main bronchi 21 and 22. For example, delivery catheter 198 can be positioned to the 6th generation or even the 8th generation airways to affect distal portions of bronchial tree 27. Delivery system 198 can be navigated through tortuous airways to perform a wide range of procedures, such as, for example, partial lobe, entire lobe, multiple lobes, or denervation of one or both lungs. In some embodiments, a lobar bronchus is treated to lobar denervation. For example, one or more treatment sites along a lobar bronchus can be targeted to denervate the entire lobe connected to the lobar bronchus. The left lobar bronchus can be treated to affect the left upper lobe and / or the left lower lobe. The right lobar bronchus can be treated to affect the right upper lobe, the right middle lobe, and / or the right lower lobe. Lobes can be treated simultaneously or sequentially. In some embodiments, a physician can treat a lobe. Based on the effectiveness of the treatment, the physician can treat additional lobes simultaneously or sequentially. In this manner, different isolated regions of the bronchial tree can be treated.

[0119] Delivery catheter 198 can also be used to treat segmental or subsegmental bronchi. Each segmental bronchus can be treated by delivering a formulation and / or energy along the segmental bronchus to a single treatment site. For example, a formulation and / or energy can be delivered to each segmental bronchus of the right lung. In some procedures, one or two applications of the formulation can treat most or the entire right lung. Depending on the anatomy of the bronchial tree, segmental bronchi can generally be denervated using one or two applications of a procedure.

[0120] Delivery catheter 198 can affect the neural tissue while preserving the functionality of other tissues or anatomical features, such as mucous glands, cilia, smooth muscle, body lumens (e.g., blood vessels or other body lumens), etc. Neural tissue can include nerve cells, nerve fibers, dendrites, and supporting tissue such as glial cells. Nerve cells transmit electrical impulses, while nerve fibers are elongated axons that conduct the impulses. The electrical impulses are converted into chemical signals to communicate with effector cells or other nerve cells. For example, delivery catheter 198 can denervate a portion of the airway of bronchial tree 27 to attenuate one or more nervous system signals transmitted by the neural tissue. Denervation can include severing the neural tissue of a portion of a nerve trunk to prevent signals from propagating along the bronchial tree to more distal locations past that particular region (by the treatment of the present disclosure). If multiple nerve trunks extend along the airway, each nerve trunk can be severed. Thus, the neural supply along a portion of the bronchial tree can be severed. When the signals are severed, the distal airway smooth muscle relaxes, causing the airway to dilate. This airway dilation reduces air flow resistance, thereby increasing gas exchange within the lungs, which thereby reduces or eliminates one or more clinical manifestations, such as shortness of breath, wheezing, chest tightness, etc. The tissue surrounding or near the target neural tissue can be affected, but not permanently severed. In some embodiments, for example, bronchial blood vessels along the treated airway can deliver similar amounts of blood to the bronchial wall tissue before and after treatment, and pulmonary blood vessels along the treated airway can deliver similar amounts of blood to alveolar sacs in distal regions of bronchial tree 27 before and after treatment. These blood vessels can continue to transport blood to maintain adequate gas exchange. In some embodiments, the airway smooth muscle is not substantially damaged in a way that is beneficial. For example, a relatively small portion of the smooth muscle in the airway wall that does not significantly affect respiratory function can be reversibly altered by the method, for example, by using the formulation at a modulated temperature, to avoid irreversibly damaging neural tissue outside the airway, such as non-target smooth muscle tissue.

[0121] Figure 2 Delivery system 198 of FIG. 1 includes a treatment controller 202 and an intraluminal elongate assembly 200 connected to controller 202. Elongate assembly 200 can be inserted into trachea 20 and navigated into and through bronchial tree 27 with or without the use of a delivery assembly such as a guidewire. Elongate assembly 200 includes a distal tip 203.

[0122] Figure 2 Controller 202 of FIG. 1 can include one or more processors, microprocessors, digital signal processors (DSPs), field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs), storage devices, buses, power sources, pumps, formulation resources, vapor resources, liquid resources, contrast resources, vapor generators, temperature- required formulation generators, etc.

[0123] Figure 2The distal tip 203 can target various sites in the lung 10, including but not limited to nerve tissue, fibrous tissue, diseased or abnormal tissue, muscle tissue, blood, blood vessels, various anatomical features (such as membranes, glands, cilia, etc.) or combinations thereof.

[0124] In one implementation, a schematic diagram of a single balloon needle delivery catheter (shown as a three-needle balloon catheter) positioned within the renal artery is illustrated. Figure 3 In the middle, needle 110 is shown as protruding. Figure 3 The delivery catheter 108 can treat hypertension. The preparation can be injected into the wall or outer wall of the renal artery adjacent to the renal nerve via a needle used for denervation. Nerve endings and small nerve fibers are typically located within the arterial wall, while large nerve fibers and nerve bundles are usually located outside or near the arterial wall. Therefore, different degrees of denervation can be achieved by controlling the depth of needle insertion during the procedure. Figure 3 Some elements of the renal vascular system are omitted. Figure 3 In the diagram, 102 represents the kidney, 105 the guiding catheter, 106 the main renal artery, 108 the three-needle balloon catheter, 109 the guidewire, 301 the abdominal aorta, and 502 the additional renal artery. Figures 3-5 Of the needle delivery catheters shown and described herein with respect to the delivery of chemical agents via needles, 6A-6B, 7A-7G, 8A-8B, and 9A-9C, implementations of the needle delivery catheters may additionally or alternatively be used to deliver energy to target tissue in the form of radiofrequency, cryoablation, microwave, laser, and / or ultrasound, for example via needles (e.g., radiofrequency, cryoablation) and / or via other sources (e.g., microwave, laser, ultrasound).

[0125] In another implementation scheme, Figure 3 The delivery catheter 108 includes a balloon that inflates to substantially center the catheter axis, so that when the needle is deployed as shown, the needle is equidistant from the vessel wall and can advance through the arterial wall at a similar depth. In some embodiments, the renal artery is treated to treat hypertension. Because the needle pierces or extends beyond the vessel wall, the device is able to deliver the preparation into or outside the vessel wall. Figure 3 The image shows the infusion of the preparation into the outer wall of the main renal artery via needle 110, directly into the renal nerve (not shown) for denervation.

[0126] In another embodiment, the three-needle balloon catheter can be positioned within the additional renal artery 502 and the preparation can be infused into or outside the wall of these vessels. Although three needles are shown, any suitable number of needles can be used, such as one, two, three, four, five or more.

[0127] In another implementation, a single denervation procedure can treat both the main renal artery and the lateral renal artery. A three-needle balloon catheter is positioned at...Figure 3 The main renal artery 106 and the additional renal arteries 502 within and outside the walls of the additional renal arteries 502. Optionally, the arteries can be treated at multiple locations depending on the length of the artery.

[0128] In one embodiment, a method of treating hypertension includes percutaneously inserting a delivery catheter into a renal artery and / or an additional renal artery proximate to nerves and nerve endings; infusing the above-described agent and / or energy into tissue of the body lumen proximate to the nerves using the delivery catheter, wherein the amount of agent and / or energy delivered is effective to beneficially injure the nerves and nerve endings; and removing the delivery catheter from the body lumen. The treatment will result in a reduction in blood pressure of the patient receiving the treatment.

[0129] In one embodiment, a needle delivery catheter, such as the one shown in Figure 3 and 5 -9 can be used to treat hypertension by renal ablation, to treat diabetes by hepatic denervation, and / or to treat obesity by gastric denervation. In one embodiment, the catheter 10 disclosed herein (in Figure 1 helps regulate agent flow and treatment dose throughout the treatment window 30, as shown in Figure 4 The balloons can be inflated by their inflation lumens. The location, diameter, number, and frequency of the needle exit holes 31 result in the delivery of agent to the treatment window 30 via the needles (not shown, in retracted position). Figure 4 A catheter positioned in a body lumen 5 is depicted with two needle exit holes 31 located within the treatment window 30 for delivery of a therapeutic agent via needles. During use, the needles extend outwardly from the needle exit holes, as shown in Figure 3 The needle exit holes 31 include a retracted needle in fluid communication with the inner lumen 25, as shown in Figure 4 The needles within the needle exit holes 31 located within the treatment window 30 can be in communication with the outer lumen 24 or the inner lumen 25 (not shown in the figures) such that agent is delivered to the treatment window 30 (e.g., into the lumen, to the lumen wall, or outside the lumen wall).

[0130] An agent treatment port can be located on the shaft between the balloons. An agent infusion hole can be located on a non-inflatable shaft portion between inflatable balloon portions. During treatment, agent can be expelled between the balloons through the infusion hole to the treatment window space created by the balloons. This is an infusion embodiment where the mechanism of treatment is to apply a medicament to the inside of the vessel wall and can include allowing the medicament to diffuse out through the lumen wall to achieve a therapeutic effect.

[0131] In one embodiment, optionally, the residue of the chemical agent / agent can be recovered after treatment by vacuum technology over the infusion hole(s). In this case, at least two treatment lumens are preferred: one for infusion, and the other for vacuum. The agent infusion hole and the vacuum hole can be located on a non-inflatable shaft portion between inflatable balloon portions.

[0132] In addition to removing excess therapeutic agent, the remaining agent can be diluted to an ineffective concentration with saline or water. The flushing can be performed through one of the catheter wire lumens, infusion lumens, or by other means using saline or water. The method used depends on the site of protection or treatment. If the distal portion of the vessel needs to be protected from the agent, the flushing can be performed through the wire lumen.

[0133] In one embodiment, when deep treatment of the adventitia and / or the per-adventitial space is desired, a needle-based catheter can achieve the goal as the needle-based catheter can infuse the agent through at least one needle into the lumen wall or outside the lumen wall. To treat the lumen uniformly around its circumference, a three (or more) needle balloon catheter infuses the agent through the needles into the target area. Figure 5 A double balloon three needle catheter is depicted positioned in a body lumen 5 with three needles 50 deployed between the two balloons. The three needles can have a larger diameter than the balloon diameter when advanced. The needles are in fluid communication with an agent source and deliver the agent directly onto the vessel wall or into the outer wall of the body lumen. In the procedure, the balloon needle catheter is advanced to the target lesion or location as per standard procedure, both balloons are inflated to center the intermediate non-expendable shaft, then the needles are deployed from the intermediate non-expendable shaft and depending on the needle penetration depth, for example, the needle tip can be inside or outside the wall, the agent is delivered through the needles to the wall or outer wall or outside the wall of the lumen or vessel. After treatment, the needles are retracted into the shaft and the balloons are deflated and the catheter is ready for removal.

[0134] Examples of a single balloon needle catheter are shown in Figure 6A and 6B Figure 6A ​A three needle balloon catheter 600 is shown in ready to use state. The needles are contained within the interior of a distal tip 601 (not shown in figure) which is a distal end portion of the catheter, with a void (not shown) containing the needles and a corresponding needle exit opening 612 positioned at the distal end of the balloon, where the needle exit opening allows the needles to protrude from the void when the needles are deployed. The distal tip can serve as a marker band, or alternatively, can include a marker band 602, and can be made of any medical grade metal, such as stainless steel, and can be atraumatic (tip 608) and radiopaque (such as when used as a marker band). The distal tip and / or marker band can be seen under X-ray (fluoroscopy), which allows the physician to accurately position the needles. The catheter has an eccentric lumen design 603 which allows for a smaller catheter profile, such as better compatibility with guide catheters. The catheter shaft 610 can be a reinforced shaft, such as by wire braid reinforcement to enhance its crush resistance and tensile strength, so that needle movement at the proximal end of the catheter is smooth and precise. Needle movement is controlled by a handle 604 at the proximal end connected to a source of the agent. The catheter that can be advanced over a guidewire for delivery is shown with an over-the-wire configuration for the guidewire lumen 603. The balloon 606 can be inflated by inflation lumen 605. Figure 6B A catheter 600 is shown with needles 611 in an advanced state, with balloon 606 inflated. The balloon just behind the needles can center the distal end of the shaft 610, so that all three needles 611 can penetrate the vessel wall at a similar depth, to ensure uniform delivery of the agent around the circumference of the vessel. It can be desirable to position the balloon as close to the needles as possible, so that the needles are more likely to be equidistant from the vessel wall. The distance between the needle exit opening on the distal tip and the balloon cone / waist transition area can be about 2 mm to 12 mm, preferably about 5 mm to 9 mm. Smaller needle diameters can result in less noticeable needle puncture wounds, which can result in faster healing of the puncture wounds. The needle outer diameter can be about 0.20 mm to 0.50 mm; preferably about 0.28 mm to 0.38 mm. The needle curvature can be designed so that the needles 611 are able to align perpendicularly to the vessel wall when delivered.

[0135] The needles can be made of any suitable material, such as stainless steel, platinum, titanium, tantalum, platinum-iridium alloy, platinum-chromium alloy, nickel-titanium alloy (nitinol); cobalt-based alloys including platinum (Pt), or gold (Au), or iridium (Ir), or osmium (Os), or rhenium (Re), or tungsten (W), or palladium (Pd), or tantalum (Ta) and combinations thereof, and / or chromium (Cr), and / or molybdenum (Mo) and / or nickel (Ni). The needles can be made of nitinol material and can have shape memory to the designed curvature when exiting the containment hole / compartments. When the nitinol needle is small and thin, it can not have enough radiopacity under X-ray during the procedure. However, it is important for the physician to know the location of the needle during the procedure. To achieve this, the needle can be modified with many suitable radiopaque metal materials, such as by thin film sputtering method of radiopaque material on its surface, or connection of radiopaque material with the needle (e.g., since the marker band can be included on the shaft), or cladded metal needle / tube with one or two layers of radiopaque material combined with the nitinol needle / tube. The coating or cladding or additional connection material can include, but is not limited to, tungsten (W), gold (Au), tantalum (Ta), platinum (Pt), and iridium (Ir) or combinations thereof, or their alloys, to make the nitinol needle radiopaque. The radius of curvature of the needle 611 can be about 2 mm to 6 mm, such as about 3 mm to 4 mm. In the fully deployed state, the needle tip-to-tip span diameter (diameter of an imaginary circle that touches all the needle tips) can be 5 mm to 40 mm, or about 5 mm to 30 mm, such as about 5 mm to 15 mm; this can be determined by the treated vessel diameter and the desired needle penetration depth. For example, for a 6 mm vessel and a 2 mm needle penetration depth, the needle tip-to-tip span distance can be about 10 mm.

[0136] After treatment, the needles are first retracted back into the distal head or containment compartments, then the balloon is deflated, and the catheter is removed. Optionally, the distal head, needles, and treated vessel region can be flushed with saline or heparinized saline through the wire lumen (for over-the-wire catheters) or designated lumen to dilute any residual agent in the lumen, if any. In some procedures, the agent lumen 604 can be flushed with saline or heparinized saline to prevent needle clogging. While Figure 6A and 6B Three needles are shown located distal to the balloon, but any number of needles can be used, such as one, two, three, four, five, or more, and the needles can also be located proximal to the balloon. The needle guide can optionally be flushed.

[0137] An embodiment of a rapid exchange (RX) needle balloon catheter is shown in Figure 7AIn this embodiment, a rapid exchange shaft is included. The rapid exchange configuration allows for easier and faster catheter insertion after wire placement during a procedure. The guidewire lumen 709 has a wire entry port or exit port 711 located near the middle or distal end of the shaft 710. Optionally, a guide groove is present on the distal tip (not shown) to facilitate wire feeding when the physician feeds the wire back through the lumen distal port. In addition to the wire exchange method, the same needle and balloon operation procedure described in the above paragraph can be applied. Optionally, flushing and cleaning after distal tip and needle treatment can be accomplished by direct injection of saline or heparinized saline through the formulation lumen 704 at about 3 to 10 times the treatment volume.

[0138] The needle-based balloon infusion system can include a needle-based balloon catheter, a guidewire, an ablation agent, saline or heparinized saline or a therapeutic drug, and a set of reservoirs for fluid management with a volume of 1 mL to 30 mL. Examples of the reservoirs can include a syringe or a syringe pump.

[0139] A needle-based balloon delivery catheter can include a distal tip, at least one marker band, at least one needle, at least one needle exit hole, at least one flush hole (which in some embodiments can be the same as the needle exit hole), a flush lumen, a flush port, a guidewire lumen, at least one balloon located at the distal end of the catheter, an inflation lumen, an inflation port, an ablation port, a needle movement shaft, and a needle movement controller; wherein the balloon is inflated via the inflation lumen through the inflation port; the flush port is in communication with the flush hole through the flush lumen; the guidewire lumen is in communication with a channel in the distal tip; the needle movement controller is in communication with the needle through the needle movement shaft; the ablation port is in communication with the needle through the needle movement shaft; the needle is in communication with the needle movement shaft; and needle movement is controlled by the needle movement controller through the needle movement controller. In one embodiment, the number of needles is 1, 2, 3, 4, or 5, and the number of needle exit holes is 1, 2, 3, 4, or 5. In another embodiment, the catheter size is 4F, 5F, 6F, 7F, 8F, 10F, 12F, 14F, 16F, 18F, 20F, 22F, 24F, or 26F. The balloon diameter can range from 3 mm to 40 mm. The balloon length can range from 3 mm to 25 mm. The needle size or needle outer diameter (OD) can range from 0.3 mm to 0.5 mm, and the needle inner diameter (ID) can range from 0.2 mm to 0.35 mm. When the catheter contains two or more needles, the needle span diameter can range from 5 mm to 80 mm or 5 mm to 40 mm, defined by the circumference of the needle tip point when the needle is fully advanced. The catheter length can range from 70 cm to 260 cm. The guidewire lumen can be compatible with a 0.014 inch (0.36 mm) or 0.018 inch (0.46 mm) or 0.035 inch (0.89 mm) guidewire. The needle span diameter can be fixed or adjustable; for example, the needle span diameter can range from 5 mm to 80 mm, 5 mm to 30 mm, or 7 mm to 15 mm.

[0140] The needle can be visible under X-ray (fluoroscopy). The needle can be made of stainless steel, nitinol, cobalt-chrome alloy, metal alloys, and shape memory metals and alloys thereof. The needle can be straight or curved in shape. The radiopacity of the metal needle can be enhanced by surface modification with another metal or metals (e.g., W, Au, Ta, Pt, Ir, and any combination thereof) using physical vapor deposition (PVD) by sputtering another metal.

[0141] The needle-based balloon delivery catheter can include needle movement control and an ablation agent port. The ablation agent reaches the needle directly through the port.

[0142] Needle-based balloon delivery catheters can include a wire lumen for a guide wire. The wire lumen can feature either an over-the-wire (OTW) or rapid exchange (RX) type. When it is an OTW shaft (catheter), the guide wire passes through the entire length of the catheter shaft. As a counterpart, when it is an RX shaft (catheter), the guide wire does not use the lumen through the catheter shaft. Typically, the RX wire lumen is much shorter, about 10 inches (about 25 cm) in length, located in the distal portion of the catheter. The RX catheter saves time compared to advancing the guide wire along the full length, especially during the procedure when the catheter is changed.

[0143] Needle-based balloon delivery catheters can include at least one balloon. A short length balloon is preferred, and the balloon length can range from 3 mm to 20 mm, preferably 5 mm to 10 mm long. The balloon diameter can be from 3 mm to 30 mm. The required balloon compliance depends largely on its application, and can range from compliant to non-compliant. The balloon material can be polyethylene, polyamides and block copolymers thereof, polyurethanes, polyesters and block copolymers thereof, Nylon 12, Pebax, etc. The balloon can be inflated and deflated by an inflation lumen / port using a standard balloon inflation media. The inflation device can be a syringe or a balloon inflation device, but if the balloon is a compliant and low pressure balloon, a syringe of appropriate volume is preferred due to the nature of the balloon.

[0144] The balloon on the catheter can be located behind the needle, serving to center the distal tip of the needle and to stop blood flow into the target treatment area.

[0145] Needle-based balloon delivery catheters can include markers to indicate the position of the balloon during the procedure. The markers can be a regular marker band for the balloon catheter, and can be a radiopaque metal (distal) tip, for example in needle-based balloon catheters. The balloon markers can be placed at the distal end of the balloon, or in the middle, or proximal, or a combination of these locations. The radiopaque marker band can be made of platinum, platinum-iridium alloy, gold metal, and polymer composites with radiopaque fillers.

[0146] Needle-based balloon delivery catheters can include a flush lumen in direct communication with the needle exit hole for fluid evacuation / passage. The flush lumen can be connected through a flush lumen port to a source of saline or heparinized saline for flushing and cleaning purposes, or to a source of therapeutic drugs for endovascular therapy. The flush lumen can be coaxial in construction (see Figure 7B ) or have a separate duct channel (not shown).

[0147] Needle-based balloon delivery catheters can include a balloon, three needles, a distal tip of the needle compartment and a radiopaque marker, a guide wire lumen, a balloon inflation lumen and port, an infusion lumen and port, and a flush lumen and port.

[0148] An example of a rapid exchange (RX) needle balloon delivery catheter is shown inFigure 7B The catheter shaft 720 comprises a separate flushing lumen 715. The flushing lumen 715 is connected to the out needle hole 716 and the flushing port 708, which are through the catheter shaft, so flushing media is expelled through the out needle hole as indicated by the arrow. In this example, the flushing lumen is arranged coaxially above the infusion lumen 714. The infusion lumen 714 is directly connected to the needle tube, which can be made of a polymer tube or a metal tube, preferably a stainless steel hypotube. The three needles are bundled together with a needle bundle tube 712. The needle bundle tube can be strong and flexible to hold the needles together and keep them evenly spaced apart, which can be a polymer tube or a reinforced polymer tube, such as a braided polymer tube. The balloon 706 located behind the needle tips acts to center the needles in the blood vessel to ensure equal distance of the three needles from the vessel wall. The needle distal tip 717 is the needle holding compartment and a marker for needle placement during the procedure. The shape memory needle returns to the pre-shaped curvature when leaving the distal tip. It has a beveled needle distal opening 713 with the bevel facing in the direction of the intrados of the needle. The needle distal opening is in communication with the infusion lumen 714 and the infusion port 704.

[0149] Figure 7B Various cross sections of the needle balloon delivery catheter shown in Figures 7C to 7G are cross-sectional views of the cross sections. Figure 7C are Figure 7B are cross-sectional views of the cross sections.

[0150] Figure 7D are cross-sectional views of the cross sections. Figure 7B are cross-sectional views of the cross sections.

[0151] Figure 7E are cross-sectional views of the cross sections. 7F are cross-sectional views of the cross sections. Figure 7B are cross-sectional views of the cross sections. Figure 7E are cross-sectional views of the cross sections. Figure 7EAlso included are flush lumen 715, braided outer shaft, and infusion lumen 714. The infusion lumen can be made of a polymeric tube, or a reinforced polymeric tube, or a metallic tube. For better pushability and dimensional stability, a stainless steel (SS) hypotube can be used as the infusion lumen 714. This infusion lumen 714 of the catheter is connected at the proximal end to the infusion port 704 and at the distal end of the catheter shaft to the needle tube. Alternatively, to save space or reduce the overall catheter profile, the guidewire lumen 709 and the inflation lumen 707 can be co-located on the same side of the shaft, as shown in Figure 7F . Figure 7F This configuration is not shown in the catheter of Figure 7B .

[0152] Figure 7G Illustrated is a cross-sectional view of the catheter of Figure 7B , including a braided outer shaft with an inflation lumen 707 attached to its outer wall, a flush lumen, and a SS hypotube infusion lumen. The inflation lumen 707 is in communication with the inflation port 705 for balloon inflation. The infusion lumen 714 is in communication with the infusion port 704 and the needle and needle distal end opening 713. The flush lumen 715 is in communication with the flush port 708 and the flush hole 716.

[0153] A rapid exchange (RX) needle balloon delivery catheter can be used for ablation procedures through blood vessels. The infusion lumen and needle of the catheter can be pre-filled with an ablation agent, such as ethanol, from its port 704; and the flush lumen can be pre-filled with a medium, such as saline or heparinized saline, from its port 708. The pre-filled flush fluid within the distal tip can reduce the likelihood of needle clogging as it prevents the needle from directly contacting blood. Less clogging can mean a longer useful life of the catheter, which can be used for multiple treatments in one procedure, and can help reduce procedure time and overall cost due to fewer catheters used. The prepared catheter can then be inserted into a blood vessel within a guide catheter and advanced along a pre-positioned guidewire to the treatment site. Once at the intended treatment site, the balloon can first be inflated to the vessel diameter to center the needle tip, and then the three needles can be advanced to the vessel wall or beyond the vessel wall, and the ablation agent can be infused through the needles into the intended denervation area. Alternatively, a therapeutic agent can be used instead of an ablation agent for treatments other than ablation. After treatment, the needles can be retracted into the distal tip, and then the flush medium can be injected through the needle exit hole and flushed out for flushing and cleaning, and then the balloon can be deflated, and the catheter can be subsequently ready to be withdrawn or moved to another treatment site for another ablation. The flush medium can also be a therapeutic drug when drug delivery is desired. Liquid drugs can be applied to the treatment site and its inner surface through the flush hole.

[0154] The flush lumen on the catheter can provide a safety mechanism for the patient. For example, it can dilute any excess ablation solution or any residual ablation solution within the blood vessel to a non-functional level.

[0155] The needle-based balloon delivery catheter can be a triple needle balloon delivery catheter. The span diameter of the needles (calculated from the circumference formed by the needle tip ends in the fully advanced stage) can be 5 mm to 30 mm, or 7 mm to 15 mm.

[0156] In one embodiment, as shown in Figure 8A and 8B A steerable single needle catheter can be used to infuse the agent. As shown, the catheter has bi-directional steering, although one, two, three, four, or more directional functions can be used. The steering mechanism can be, for example, a wire (not shown) attached to the distal tip 801 of the catheter shaft 802, with a handle (not shown) at the proximal end of the catheter. To steer the catheter, the user moves the handle in the proximal direction, which causes the distal tip 801 to move off the longitudinal axis of the catheter shaft 802. During insertion and positioning, the needle tip is retracted inside the catheter, which can be achieved with a guidewire. An eccentric guidewire lumen design can be used to minimize the catheter profile for small vessel access. The overall catheter profile is from 3F to 10F, preferably from 5F to 7F. Once at the treatment site, the radiopaque catheter head 801 is steered towards and preferably against the vessel wall. This can be visualized with fluoroscopy. Next, the needle (803 in Figure 8B ) is advanced into or through the vessel wall and the agent is infused. If desired, the needle can be retracted, and the tip can be steered in a new direction for treatment in the new direction. After treatment, the needle is retracted, and then the catheter is removed from the patient. Since the catheter is visible under X-ray and has a steerable tip, optionally, the steerable catheter can be used without a guidewire.

[0157] In another embodiment, as shown in Figure 9A , 9B and 9C, a single directional steerable catheter is used to infuse the agent through the needle. This catheter 900 has a smaller profile than the bi-directional catheter described above and is suitable for use in smaller diameter vessels. As described above, the desired and controlled penetration can include achieving a needle orientation that is approximately perpendicular to the lumen wall (e.g., 90° or close to 90° to the lumen wall), so the infusion direction and depth can be predicted. This can require a sharp bend at the distal end of the catheter 902 so that the tip 901 is aligned perpendicularly to the vessel wall. This can be very difficult in small lumens, as it can be nearly impossible to push the needle through a small bend or curvature. To overcome this problem, in some embodiments, the exit hole of the needle is placed in the side wall of the tip head instead of the middle of the tip 903 (see Figure 9B and C). In addition, the exit hole is positioned on the same side of the catheter shaft 902 as the direction of the catheter tip bend (see Figure 9B). When the catheter is placed in a small lumen of the target region, it only needs to bend a small angle (less than 90°) to align the hole in an approximately perpendicular way to the vessel wall 5 (see Figure 9C ) Once the alignment is achieved, as shown in Figure 9C , the needle is advanced into the wall 5 and the system is ready for infusion therapy. After the therapy, the needle is retracted into the catheter, the catheter tip resumes the straight position, and the catheter is ready to be taken out of the patient, rotated for a different orientation of therapy, or moved to a different location for another therapy. The distal tip can be made of plastic, metal, or a combination thereof, which can be radiopaque and can contain a needle. The radiopaque tip 901 can act as a marker band for needle positioning during the procedure.

[0158] In one embodiment, the needle device can deliver very small and accurate amounts of the agent, for example in the range of 0.01 mL to 10.0 mL, preferably 0.05 mL to 5.0 mL, most preferably 0.1 mL to 1.0 mL. Due to the microdose and precise control of the therapeutic volume / dose, multiple therapies can be used at the same location / region to provide a more optimized therapeutic result. As shown in Figure 3 , a three-needle balloon catheter 108 is placed in the main renal artery 106 with a balloon and needles 110 deployed; for example, the volume of the perivascular infusion of the agent can be 0.6 mL. After the needle is retracted and the balloon is deflated, the catheter can continue to advance to an additional renal artery 502 (a renal artery branch) and deploy the needle and infuse another therapeutic dose, for example 0.3 mL, to the outer wall region (adventitia) of the additional renal artery. If both additional renal arteries are accessible, both arteries can be treated with equal doses or different doses. To achieve a similar dose per unit area in the treatment, considering the difference in the surface area of the arterial outer wall and the closer distance to the kidney organ of the additional renal artery compared to the main renal artery, the dose for the additional renal artery treatment can be less than the dose for the main renal artery treatment. The dose relationship between the dose for the main renal artery (DOSE m ) and the dose for the additional renal artery (DOSE b ) can be:

[0159] DOSE b = DOSE m *(D b / D m )

[0160] where D m is the diameter of the main artery and D b is the diameter of the artery branch.

[0161] For example, when the main artery diameter is 6 mm and the branch artery diameter is 3 mm,

[0162] DOSE b= DOSE m *(D b / D m ) = DOSE m *(1 / 2) or = 0.5 DOSE m

[0163] If all three regions (one main and two branches) are treated, the total dose for arterial treatment can be 1.2 mL for one kidney.

[0164] Sometimes, the main renal artery length is long enough to allow one device to treat twice, for example once in the middle and another near the bifurcation region of the artery (close to the branches). When the main renal artery is treated 2 times and 2 branches are treated 1 time, the total dose for 1 kidney side artery treatment is 1.8 mL.

[0165] In one embodiment, as shown in FIGS. 1 1 A and 1 1 B, a jet catheter with a formulation outlet or jet hole at its distal end can be used to deliver the catheter to achieve a wider treatment area. Figure 13 and 14 As shown in FIGS. 1 1 A and 1 1 B, a jet catheter with a formulation outlet or jet hole at its distal end can be used to deliver the catheter to achieve a wider treatment area. Figure 13 Catheter 1300 in FIG. 13 has a coaxial design shaft 1309, where aspiration is through inner tube 1305, and jetting is through the space between inner tube 1305 and outer tube 1304. Jet holes 1301 are located on the sidewall of shaft 1309, which can deliver the formulation directly to the vessel wall and can well control the jet direction and treatment area. The formulation is delivered to jet holes 1301 through jetting lumen 1307. If there is excess formulation in the vessel after jet treatment, it can be removed / collected by the aspiration function on the catheter. The removal can be done by applying vacuum to aspiration port 1308, which can make the formulation be taken out through aspiration site 1306. In this example, aspiration opening 1306 is located distal to jet opening 1301. The openings for aspiration and jetting can be circular or any other geometric shape. There can be single or multiple holes for aspiration function and jetting function, and there can be any combination of the number of holes between the two functions. The number of holes and the size of the holes between aspiration and jetting are independent. Ideally, the jet hole size is smaller than the aspiration hole size, because for jetting, a fine mist is desired. Optionally, the aspiration line can be connected to a vacuum pump. The jetting can include two components: liquid formulation and pressurized gas, such as air or oxygen. For a specified volume of liquid agent, it is delivered by a pressure gas with a predetermined pressure. At this delivery gas pressure, the delivered formulation is in the form of a fine mist, which is applied to the target treatment area. The excess formulation after each jet can be collected / removed by the aspiration function on the catheter at the treatment part, so that the formulation can be contained in the target area.

[0166] The exact jetting location during a procedure can be visualized by a marker band under X-ray. For example, a marker band 1303 can be located at the distal end of the catheter 1309 proximal to the jetting hole 1301, or double marker bands 1303 can be located both distal and proximal to the jetting hole 1301. Optionally, the distal marker band is sized to occupy the space between the inside and outside of the distal shaft, which can block the fluid path and stop the formulation at the marker band location; thus, the priming volume in the catheter can be less, which can make the jetting volume more accurate.

[0167] In another embodiment, a dual site suction catheter can be used to help ensure that the formulation does not escape in either direction (distal or proximal) from the jetting hole. This example is shown in FIG. 14, where suction holes 1406A and 1406B are placed distal and proximal to the jetting site on the catheter. The distal suction hole and the proximal suction hole can be connected by the same channel / lumen; or can be independent of each other, for example, the distal suction hole and the proximal suction hole can be operated independently. Suction can occur at the distal location, the proximal location, or both locations simultaneously. The catheter can be operated as described above. Figure 14

[0168] To accommodate the features in FIG. 14, a multi-lumen shaft 1409 can be used and can be, for example, a 3-lumen shaft. Each of the suction locations 1406A and 1406B has its own lumen, thus distal suction and proximal suction can be performed independently. In one embodiment, a sleeve 1410 is placed over the jetting exit hole 1401 to achieve uniform circumferential jetting (e.g., 360°). Double marker bands 1403 located at the distal and proximal ends of the sleeve 1410 help with accurate positioning at the treatment site or lesion. While the example shown in FIG. 14 is a side wall jetting exit configuration, the jetting exit can alternatively or additionally be placed at the distal tip. Through the design of the hole size 1401, the jetting mode can be a range of delivery effects (physical form) from fine mist to coarse droplets to jet. Figure 14 Figure 14

[0169] Figure 15A and 15B Various arteries surrounding the liver and stomach and various nervous systems that innervate the liver and stomach and their surrounding organs and tissues are illustrated. The arteries surrounding the liver and stomach include the abdominal aorta 305, celiac artery 310, common hepatic artery 315, and proper hepatic artery 320, gastroduodenal artery 322, right hepatic artery 325, and left hepatic artery 330, splenic artery 335, and esophageal branches 361. The various nerves that innervate the liver and stomach and their surrounding organs and tissues include the celiac plexus 340 and the hepatic plexus 345 (only shown in the liver). Figure 15B ​​​The blood supply to the liver is pumped from the heart into the aorta, then down through the abdominal aorta 305 and into the celiac artery 310. From the celiac artery 310, blood passes through the common hepatic artery 315, into the proper hepatic artery 320, then through the right hepatic artery 325 and the left hepatic artery 330 into the liver. The common hepatic artery 315 branches from the celiac trunk and forms the gastroduodenal artery. The nerves that innervate the liver include the celiac plexus 340 and the hepatic plexus 345. The celiac plexus 340 encircles the celiac artery 310 and continues into the hepatic plexus 345, which encircles the proper hepatic artery 320 and the common hepatic artery 315, and / or continues to the right hepatic artery 325 and the left hepatic artery 330. In some anatomies, the celiac plexus 340 and the hepatic plexus 345 are intimately adhered to the arterial wall, providing blood to the liver such that intravascular to extravascular neuromodulation is particularly advantageous. In several embodiments, the average thickness of the blood vessels (e.g., hepatic arteries) ranges from about 0.1 cm to about 0.25 cm. In some embodiments, the formulation and / or energy can be delivered to the inner wall of the target blood vessel or target nerve. Intravascular delivery can be employed because the nerves are intimately adhered to the outer wall of the artery, thereby supplying blood to the liver (e.g., in the case of hepatic artery branches). In some embodiments, extravascular / endovascular delivery is desirable and can be achieved with any of the various needle catheters disclosed herein.

[0170] The arteries surrounding the stomach include the abdominal aorta 305, the celiac artery 310, the right gastric artery 355 and the left gastric artery 360, and the esophageal branches 361. The blood supply to the stomach is pumped from the heart into the aorta, then down through the abdominal aorta 305 and into the celiac artery 310. From the celiac artery 310, blood passes through the right gastric artery 355 and the left gastric artery 360, the esophageal branches 361, and into the stomach. The left gastric artery 360 includes the left gastric artery plexus 362 (shown in Figure 15A

[0171] Continuing with Figure 15B , the hepatic plexus 345 is the largest offset of the celiac plexus 340. It is believed that the hepatic plexus 345 carries primarily afferent and efferent sympathetic nerve fibers, the stimulation of which can increase blood glucose levels through a variety of mechanisms. For example, stimulation of sympathetic nerve fibers in the hepatic plexus 345 can increase blood glucose levels by enhancing hepatic glucose production or by decreasing hepatic glucose uptake. Thus, interruption of sympathetic signaling in the hepatic plexus 345 can alter blood glucose levels.

[0172] Figure 15B The embodiment shown in Figure 15A The embodiment shown inmay be an embodiment of a three-needle balloon delivery catheter positioned within the left gastric artery for the treatment of obesity and / or diabetes. The access to these arteries is very similar to the access to the renal arteries, so the procedures described in the previous subsections are applicable to these embodiments.

[0173] A safe and effective amount of the formulation can be applied to satisfactorily and beneficially injure tissue, such as a nerve. Generally, the dosage is related to the degree of injury to the tissue. In some embodiments, the effective formulation dosage ranges from 0.2 microliters to 200 milliliters. However, these dosage limits are not defined, as other delivery parameters (e.g., delivery rate, duration, etc.) can require different dosages to achieve the ultimate injury benefit.

[0174] The treatment time can vary depending on the volume of the tissue mass to be treated and the degree of injury to the target tissue desired. The treatment time can vary from about 2 seconds to about 60 minutes. In some embodiments, a safe and effective treatment time ranges from about 4 seconds to about 30 minutes in order to induce injury to relieve symptoms.

[0175] The delivery rate can be set by adjusting the delivery system. Once the user has determined the delivery rate, the formulation resource can determine the amount of pressure needed to deliver the vapor or liquid at the desired rate.

[0176] In one embodiment, a method of treating hypertension includes percutaneously inserting a delivery catheter into a renal artery proximate a nerve; infusing the above-described formulation and / or energy into the body lumen tissue proximate the nerve using the catheter, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The injury or impairment to the tissue can relieve symptoms of the disease, such as by lowering blood pressure. The purpose of the heat / energy can be to enhance the injury / impairment effect by accelerating the rate of reaction between the formulation and the nerve. Possible formulations include a gas, vapor, liquid, solution, emulsion, suspension, and combinations thereof of one or more components. If the formulation includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate the nerve can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more. The formulation infusion pressure can be 0.1 to 14 atm, preferably 3 to 10 atm, most preferably 4 to 8 atm.

[0177] In one embodiment, a method of treating asthma includes inserting a delivery catheter into the airway proximate to the nerve; infusing the above-described formulation and / or energy into the airway tissue proximate to the nerve using the catheter, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The injury or impairment to the nerve can alleviate the symptoms of the disease, for example, by alleviating shortness of breath. The purpose of the heat / energy can be to enhance the injurious / impairing effect by accelerating the rate of reaction between the formulation and the nerve. Possible formulations include gas, vapor, liquid, solution, emulsion, suspension, combinations of one or more of these, and the like. If the formulation includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The liquid formulation temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the treated tissue proximate to the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate to the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure should be in the range of 0.1 to 14 atm, preferably 3 to 10 atm, most preferably 4 to 8 atm.

[0178] Alternatively, a jet catheter without a balloon can be used to treat asthma. In one embodiment, a method of treating asthma includes inserting a delivery catheter into the airway proximate to the nerve; infusing the above-described formulation and / or energy into the airway tissue proximate to the nerve using the catheter, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The injury or impairment to the nerve can alleviate the symptoms of the disease, for example, by alleviating shortness of breath. The advantage of this jet method is that it is simple, fast, and capable of treating small diameter airways. Possible formulations include gas, vapor, liquid, solution, emulsion, suspension, combinations of one or more of these, and the like. For liquid and gas formulations, a fine mist can be preferred for delivery. The diameter of the formulation exiting the jet hole can be 0.5 mm or less, more preferably 0.4 mm or less. The delivery gas pressure can be preferably less than 8 atm, more preferably 4 atm or less.

[0179] In one embodiment, a method of treating COPD and / or asthma includes inserting a delivery catheter into an airway proximate a nerve; infusing a formulation and / or heat proximate the nerve to the body lumen tissue using the catheter, where the amount of formulation and / or heat delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the airway. The injury or impairment to the nerve can alleviate disease symptoms, such as by alleviating COPD / asthma symptoms. The purpose of the heat / energy can be to enhance the injury / impairment effect by accelerating the rate of reaction between the formulation and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, and suspensions of one or more formulations. If the formulation includes a vapor of one or more components, heat can be generated by condensing the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The formulation temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the treated tissue proximate the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate the nerve can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The formulation infusion pressure and / or balloon inflation pressure can be 0.1 to 14 atm, preferably 3 to 10 atm, most preferably 4 to 8 atm.

[0180] Alternatively, COPD can also be treated with a jet catheter, where the same methods described herein for asthma treatment can be used. The method can also include the combined use of a balloon catheter and a jet catheter in the same procedure, which can result in the maximum denervation effect.

[0181] In one embodiment, a method of treating severe emphysema by lung volume reduction includes inserting a delivery catheter into an airway proximate a target region; jetting a formulation and / or energy proximate the target lung tissue using the catheter to completely destroy the target lung tissue, where the amount of formulation and / or energy delivered is effective to beneficially injure the tissue; and removing the delivery catheter from the airway. The injury to the tissue can alleviate disease symptoms, such as emphysema symptoms. The formulation and / or energy can be delivered at the distal tip front end, or at a sidewall location, or a combination of both.

[0182] In one embodiment, a method for treating diabetes and / or nonalcoholic fatty liver disease (NAFLD) and / or nonalcoholic steatohepatitis (NASH) comprises percutaneously inserting a delivery catheter into a hepatic artery proximate to a nerve, in particular the hepatic celiac artery, the common hepatic artery, the proper hepatic artery, or the left and right hepatic arteries; infusing the above-described formulation and / or energy into the body lumen tissue proximate to the nerve or directly into the nerve using any of the catheters described herein, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The purpose of the energy / heat can be to enhance the injure / impairment effect by accelerating the rate of reaction between the formulation and the nerve. Possible formulations include gas, vapor, liquid, solution, emulsion, suspension, combinations thereof, of one or more ingredients. If the formulation includes a vapor of one or more ingredients, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate to the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate to the nerve can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more. The formulation is delivered through a needle to the perivascular region for denervation, the formulation volume is 0.1 mL to 1.0 mL, preferably 0.3 mL to 0.8 mL, most preferably 0.4 mL to 0.7 mL.

[0183] In one embodiment, a method for reducing fast blood glucose, HbAlc, glucagon, epinephrine, norepinephrine, cortisol, or growth hormone in a diabetic patient can include percutaneously inserting a delivery catheter into a hepatic artery proximate to a nerve, in particular, the hepatic celiac artery, the common hepatic artery, the proper hepatic artery, and / or the left and right hepatic arteries; infusing the above-mentioned agent and / or energy into the body lumen tissue proximate to the nerve or directly into the nerve using any of the catheters described herein, wherein the amount of agent and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The purpose of the heat / energy can be to enhance the injure / impairment effect by accelerating the rate of reaction between the agent and the nerve. Possible agents include gas, vapor, liquid, solution, emulsion, suspension, combinations thereof, of one or more ingredients. If the agent includes a vapor of one or more ingredients, heat can be generated by condensation of the vapor into a liquid in the tissue. If the agent includes a liquid or solution, heat can be transferred from the high temperature agent that exceeds body temperature. The agent temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate to the nerve can be lower than the agent temperature and higher than body temperature. The temperature of the treated tissue proximate to the nerve can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The agent is delivered through a needle to the perivascular region for denervation, the agent volume is 0.1 mL to 1.0 mL, preferably 0.3 mL to 0.8 mL, most preferably 0.4 mL to 0.7 mL.

[0184] In one embodiment, a method for treating obesity and / or diabetes comprises inserting any of the delivery catheters described herein into the left and / or right gastric artery proximate to the nerves of the stomach and esophagus; infusing the above-described formulation and / or energy into the gastric arterial tissue or extra-arterially proximate to the nerves using the catheter, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerves; and removing the delivery catheter from the gastric artery. Possible formulations include gas, vapor, liquid, solution, emulsion, suspension, combinations thereof, and one or more components. If the formulation includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The liquid formulation temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the treated tissue proximate to the nerves can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate to the nerves can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure and / or balloon inflation pressure should be in the range of 0.1 to 14 atm, preferably 3 to 10 atm, most preferably 4 to 8 atm.

[0185] In one embodiment, a method for treating obesity includes inserting any of the delivery catheters described herein into or outside of a digestive lumen proximate a nerve; infusing the above-described formulation and / or energy into the tissue of the digestive lumen using the catheter, where the amount of formulation and / or energy delivered is effective to beneficially injure or impair the tissue; and removing the delivery catheter from the digestive lumen. Possible digestive lumens for this embodiment include the esophagus, stomach, duodenum, jejunum, small intestine, and large intestine, and colon. The purpose of the heat / energy can be to enhance the injure / impair effect by accelerating the rate of reaction between the formulation and the nerve. Possible formulations include gas, vapor, liquid, solution, emulsion, suspension, and combinations thereof of one or more components. If the formulation includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The liquid formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate the nerve can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more.

[0186] In one embodiment, a method for treating obesity and diabetes comprises inserting any of the delivery catheters described herein into the left and / or right gastric artery proximate to the nerves of the stomach and esophagus; using the catheter to infuse the above-described agents and / or energy to the tissue of the gastric artery proximate to the nerves, or externally, where the amount of agent and / or energy delivered is effective to beneficially injure or impair the nerves; and removing the delivery catheter from the gastric artery. Possible agents include gas, vapor, liquid, solution, emulsion, suspension, combinations thereof, of one or more components. If the agent includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid. If the agent includes a liquid or solution, heat can be transferred from the high temperature agent, which is above body temperature. The temperature of the liquid agent can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate to the nerves can be lower than the temperature of the agent and higher than body temperature. The temperature of the treated tissue proximate to the nerves can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more.

[0187] In one embodiment, a method of treating a urinary system disease and / or benign prostatic hyperplasia (BPH) includes inserting a delivery catheter into a urinary system lumen; infusing the above-described formulation and / or energy into a lumen or extraluminal of a urinary tissue (e.g., prostate, urethra, and ureter) using any of the catheters described herein, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the tissue; and removing the delivery catheter from the urinary lumen. The purpose of the heat / energy can be to enhance the injure / impairment effect by accelerating the rate of reaction between the formulation and the nerve. The formulation includes one of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, combinations thereof, and one or more ingredients. If the formulation includes a vapor of one or more ingredients, heat can be generated by condensing the vapor into a liquid. If the formulation includes a liquid or a solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The liquid formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue proximate to the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue proximate to the nerve can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more. The formulation infusion pressure and / or balloon inflation pressure can be 0.1 to 14 atm, preferably 3 to 10 atm, most preferably 4 to 8 atm.

[0188] In one embodiment, a method for treating a cancer or tumor includes percutaneously, orally, or transluminally inserting a needle or needle-based catheter into the cancer or tumor under imaging guidance; infusing the above-described formulation and / or energy into the cancer tissue of the human using the catheter, where the amount of formulation and / or energy delivered is effective to beneficially injure, impair, or eliminate the cancer tissue; and removing the delivery catheter from the body. The injury, impairment, or elimination of the cancer tissue can alleviate disease symptoms, for example, by shrinking or eliminating the tumor. Possible imaging guidance includes ultrasound, X-ray, CT scan, NMR imaging, and a scope. Related cancers include adrenal cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gall bladder cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, and uterine cancer. The purpose of the heat / energy can be to enhance the injure / impair / eliminate effect by accelerating the rate of reaction between the formulation and the cancer tissue. The formulation includes one of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, combinations thereof, or one or more components thereof. If the formulation includes a vapor of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or a solution, heat can be transferred from the formulation at an elevated temperature above body temperature. The formulation temperature can be -40 to 140 °C, -30 to 100 °C, -30 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 °C or more. The temperature of the treated tissue can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue can be -40 to 100 °C, -30 to 90 °C, -20 to 80 °C, or -40 °C or less, or less than, equal to, or greater than -30 °C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 °C or more.

[0189] A method of treating myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), rheumatoid arthritis, or a cancer due to an immune response to an inflammatory condition can include percutaneously inserting a delivery catheter into a splenic artery adjacent to a nerve, infusing the above-described formulation and / or energy into the body lumen tissue adjacent to the nerve or directly into the nerve using any one of the catheters described herein, where the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body lumen. The formulation can be delivered through a needle to the perivascular region for denervation, with a volume of formulation per application ranging from 0.1 mL to 1.0 mL, or 0.3 mL to 0.8 mL, or 0.4 mL to 0.7 mL.

[0190] Methods of treating myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD) caused by hypercholesterolemia can include percutaneously inserting a delivery catheter into a splenic artery proximate to a nerve; infusing the above formulation and / or applying energy to body cavity tissue proximate to a nerve or directly to the nerve using any one of the catheters described herein, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or impair the nerve; and removing the delivery catheter from the body cavity. The formulation can be delivered through a needle to the perivascular region for denervation, with a volume of formulation per application ranging from 0.1 mL to 1.0 mL, or 0.3 mL to 0.8 mL, or 0.4 mL to 0.7 mL.

[0191] Hypertension and hypercholesterolemia can be predisposing factors for vascular disease such as coronary heart disease, but the two act synergistically to significantly alter risk because their combination is thought to be multiplicative rather than additive. Thus, people with combined risk factors are at particularly high risk for coronary heart disease. Impaired endothelium-dependent vasodilation in patients with essential hypertension can be related to hypercholesterolemia; in addition, enhanced sympathetic nervous activity can be related to hyperlipidemia in hypertension. For example, the positive correlation of serum triglyceride levels with blood pressure is significant, particularly for people with a high body mass index (BMI > 24). Embodiments of the present invention can not only reduce blood pressure, but also reduce cholesterol levels. The biological interrelationships between blood pressure and atherogenic blood lipids scores, and the pathophysiological factors behind these interrelationships, can influence the mechanisms by which hypertension is associated with increased risk of coronary heart disease. Thus, in the results of various embodiments of the treatment methods, a reduction in blood pressure or cholesterol levels, or a reduction in both blood pressure and cholesterol levels, can be beneficial in reducing the risk of coronary artery disease (CAD) and peripheral vascular disease (PAD).

[0192] A method of treating a disease with a needle-based balloon infusion system (where the needle-based balloon infusion system comprises a needle-based balloon delivery catheter, a guidewire, an ablative agent, saline or heparinized saline or a therapeutic drug, and a set of fluid reservoirs) can comprise: 1) inserting the needle-based balloon delivery catheter into a body lumen, where the needle-based balloon delivery catheter comprises a distal tip, at least one marker band, at least one needle, at least one needle exit hole, at least one flushing hole, a flushing lumen, a flushing port, a guidewire lumen, at least one centering balloon at the approximate distal end of the catheter, one inflation lumen, one inflation port, one ablation port, a needle movement axis, and a needle movement controller; where the needle lumen is pre-filled with an ablative agent and the flushing lumen is pre-filled with a flushing medium prior to insertion; 2) inflating the centering balloon to center the delivery catheter shaft within the body lumen; 3) deploying at least one needle into, outside, or within the wall of the body lumen; 4) infusing the agent through the at least one needle, where the amount of agent delivered is effective to damage or impair the target tissue to relieve symptoms of the disease; 5) optionally removing the agent from the tissue; 6) retracting the needle into the delivery catheter and deflating the centering balloon; 7) flushing the flushing lumen prior to deflating the balloon or prior to inserting into the next body lumen to prevent needle lumen blockage and blood clot formation; 8) inserting the needle-based balloon delivery catheter into the next body lumen; 9) repeating 2) through 8) until all target body lumens are treated; and 10) removing the delivery catheter from the body lumens. The disease can be hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, a digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), a urinary system disease, cancer, a tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), or a combination thereof. The ablative agent can be one of ethanol, anhydrous ethanol, acetic acid, dilute acetic acid. The flushing medium can comprise saline or heparinized saline or a neutralizing agent for the ablative agent. The body lumens can comprise a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof.

[0193] Methods using a needle-based balloon delivery catheter can include pre-filling the needle lumen with an ablative agent, pre-filling the flush lumen with a flushing medium, and inserting the catheter into an over-the-wire guide catheter. Once at the treatment site, the balloon can be inflated to the size of the vessel to center the needle head, then the needle can be advanced to the treatment location and the ablative agent can be infused; after infusion, the needle can be withdrawn and retracted into the distal head, flushing fluid can be infused to keep the needle compartment / hole of the distal head and the needle tip / opening clean and to avoid direct contact with blood. The balloon can be deflated and the catheter can be withdrawn from the treatment site and / or moved to another treatment site.

[0194] In some embodiments, when the target vessel is long and needs to be treated more than once, the distance between treatment sites can be used to separate the infused ablative agent. The separation distance between treatment sites can be 5 mm to 30 mm, for example 5 mm to 15 mm.

[0195] The dose of ablative agent can be 0.1 mL, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0, or 1.2 mL for each application / treatment of a main vessel, for example an artery. If more than one treatment is performed, the total dose (volume) for a particular main vessel (length) can be 0.3 mL, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, or 2.4, or up to 3.6 mL. For a branch vessel or artery, the dose for each application can be 0.1 mL, 0.2, 0.3, 0.4, 0.5, or 0.6 mL. If more than one treatment is performed, the total dose for that branch can be 0.2 mL, 0.4, 0.6, 0.8, 1.0, or 1.2 mL.

[0196] Various embodiments of the present invention provide a needle-based balloon delivery catheter for delivering a material to a target tissue in a patient body lumen. The delivery catheter can include a catheter shaft having a proximal end and a distal end. The delivery catheter can include at least one marker band located proximate the shaft distal end. The delivery catheter can include at least one needle (e.g., 3 needles), wherein each needle is located in a needle lumen. The needle lumens can be open to the exterior of the catheter shaft through at least one needle exit hole. The delivery catheter can include an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen. The irrigation lumen is in fluid communication with the distal end of the needle lumens. The irrigation port can be in fluid communication with the needle exit holes through the irrigation lumen. The delivery catheter can include a guide wire lumen extending through at least the shaft distal end. The delivery catheter can include at least one balloon proximate the distal end of the catheter. The delivery catheter can include an inflation lumen. The delivery catheter can include an inflation port in fluid communication with the inflation lumen and in fluid communication with the interior of the balloon. The balloon can be inflated via the inflation port through the inflation lumen, and the distal end of the catheter shaft can be substantially centered in the body lumen during inflation. The delivery catheter can include an ablation or denervation port at the proximal end of the shaft. The ablation or denervation port is in fluid communication with the at least one needle to supply ablation energy or agent to the at least one needle. The delivery catheter can also include a needle movement controller in electrical or mechanical communication with the at least one needle. The needle movement controller can deploy the at least one needle into the body lumen, into the body lumen wall, or outside the body lumen. Deploying the needle through the needle exit opening can allow the agent to penetrate into the body lumen wall at a pressure higher than the body lumen pressure. The target tissue can be a target tissue of the following arteries or veins: a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof. The agent pressure during infusion can be any suitable pressure, and the balloon inflation pressure can be any suitable pressure. For example, the agent infusion pressure can be in the range of 0.1 to 14 atm. The balloon inflation pressure can be in the range of 0.1 to 14 atm.

[0197] EMBODIMENT

[0198] The various embodiments of the present invention can be better understood by reference to the following examples, which are offered by way of illustration. The present invention is not limited to the examples given herein.

[0199] Example 1. Preclinical trials

[0200] A pig animal weighing 47 kg was anesthetized with isoflurane and its renal artery on one side was ablated with ethanol using a triple needle single balloon catheter while the opposite renal artery served as a control. The catheter needle spanned a diameter of about 10 mm. The catheter balloon was a low pressure and compliant balloon with a 7 mm diameter at 1 atm, which functioned to center the distal shaft without overstretching the artery. Optionally, the balloon can be inflated with a syringe without the use of an inflation device. Due to the nature of the balloon, the balloon can be used in arteries of any diameter (lower or higher than the balloon diameter). Prior to insertion into the artery, the catheter was pre-filled with the liquid formulation until it overflowed from the needle (needle protrusion), then the needle was retracted and a syringe with a predetermined treatment volume was attached to the catheter. Using standard renal access procedures, the triple needle balloon delivery catheter was placed into the target renal artery of the aorta and extra-renal artery (branch) in sequence through a guide wire. Once the target ablation site was reached, the balloon was inflated, then the needle was deployed, and anhydrous ethanol at room temperature was infused into the adventitia and per-adventitial space of the renal artery. The infusion volume per application was 0.6 mL for the aorta and 0.3 mL for the branch using a 1 mL syringe. The infusion time was within 5 seconds for both application volumes. During the balloon inflation, the ratio of the balloon diameter to the surrounding artery diameter was monitored by fluoroscopy to be about 1 : 1.1 (slightly larger). By the end of the treatment time, the needle was first retracted into the catheter, then the balloon was deflated, and the catheter was ready for removal or placement to another arterial site if a next treatment was needed. In this example, a total of 4 treatments were performed: 2 for the aorta, and 1 for each branch, with a total volume of formulation used of 1.8 mL.

[0201] A post-ablation renal angiogram was obtained to check for any vascular debris, stenosis, and other abnormalities. There was no apparent renal artery spasm during and after the infusion treatment.

[0202] The animal was euthanized two weeks post-treatment, and a gross necropsy showed all treatment-related organs to be normal, and renal tissue samples were collected from the cranial (n=3), middle (n=3), and caudal (n=3) portions of the kidney cortex to determine the norepinephrine (NE) content of the kidney tissue using a known HPLC method. Norepinephrine is a neurotransmitter used by the sympathetic nervous system, and its level is a standard measure of renal denervation. The NE concentration was lower or much lower on the denervated side compared to the untreated side (control) as shown in Figure 10 The ethanol ablation of the renal artery resulted in a 94% decrease in the norepinephrine concentration of the kidney (average NE content: control: 87 ng / g vs. treatment: 4.9 ng / g). The percent individual NE reduction calculated from similar tissue locations between the control and treatment groups ranged from 89% to 97.5%. The renal artery and surrounding tissue were also collected for histopathology evaluation.

[0203] Not only was the NE content reduced after ethanol ablation, but histopathological evaluation also demonstrated renal nerve injury, as Figure 11 As shown, the nerves (see arrows) were surrounded by mild fibrosis in the adventitia.

[0204] Example 2. Preclinical trials

[0205] Two 46 kg swine animals were treated with ethanol ablation of the hepatic artery using a formulation of absolute ethanol at room temperature and a three needle single balloon catheter of the same type used in Example 1. Prior to arterial insertion, the catheter was pre-filled with the liquid formulation until it overflowed from the needles (needle protrusion), then the needle tips were retracted and a syringe with a predetermined treatment volume was attached to the catheter. A standard hepatic artery access procedure was performed. Each hepatic artery was treated twice, evenly distributed along the artery length, and the infusion volume applied was 0.6 mL per application using a 1 mL syringe with an infusion time of less than 5 seconds. The inflated balloon diameter to artery inflation ratio was monitored to be less than 1 : 1.1 and inflation was performed using the syringe. In both swine animals of this study, hepatic angiography showed no significant arterial spasm during and after infusion treatment. As a control, a similar weight swine animal was treated without treatment and compared to the NE reduction calculation and histopathological evaluation.

[0206] Both animals were euthanized two weeks after treatment; gross necropsy showed all treatment related organs were normal and liver tissue samples were obtained from the right lateral lobe (n=2), right medial lobe (n=2), left medial lobe (n=2), left lateral lobe (n=2) and caudate lobe (n=2) to determine the hepatic tissue norepinephrine (NE) content using a known HPLC method. The NE reduction was calculated from the data collected from similar locations between the treatment and control groups. As shown in Figure 12 the average liver NE concentration was reduced by 85% and 94% for the two animals, respectively. The individual calculated percentage range for one animal was 55% to 95% and for the other animal was 86% to 97.5%. As with the renal ablation study, arterial and surrounding tissue was collected for histopathological evaluation.

[0207] The results of the above preclinical studies indicate that ethanol treatment is effective and safe.

[0208] Example 3. Clinical trials, metabolic syndrome

[0209] In one embodiment, a human male patient A is 53 years old with metabolic syndrome, has had hypertension for 10 years and is on 2 antihypertensive medications, has had type 2 diabetes for 2 years and is on 2 T2DM (type 2 diabetes mellitus) medications, and has had obesity for 8 years. His triglyceride level was 336 mg / dL prior to surgery. The target arteries for his treatment were the renal arteries, the hepatic artery, the splenic artery, and the left gastric artery.

[0210] During the procedure, moderate sedation was used in accordance with institutional standard practice and no general anesthesia was used. The artery was engaged using a 7F guide catheter introduced through the femoral artery. The artery was angiographically visualized prior to the intervention. All four arteries were treated in the same procedure. Treatment started with the superior mesenteric artery, followed by the splenic artery, the hepatic artery, the left gastric artery, the left renal artery, and the right renal artery. After initial angiographic visualization of the hepatic artery, the splenic artery, and the left gastric artery, a rapid exchange triple needle single balloon catheter was advanced through the guide catheter and over the guide wire into the artery. Prior to insertion into the artery, the catheter was pre-filled with the liquid ablation agent (dehydrated ethanol) until it overflowed from the needles (needle protrusion), then the needles were retracted and a syringe with the pre-determined treatment volume was attached to the catheter.

[0211] The maximum catheter needle span diameter was about 12 mm and the span diameter could be adjusted according to the artery diameter. The catheter balloon was a low pressure and compliant balloon with a diameter of 7 mm and a pressure of about 1 atm. The function of this balloon was to center the distal tip / shaft without overstretching the artery. The balloon was inflated with a 30 cc syringe with a stopcock (no inflation device was used) to gently control the balloon diameter.

[0212] Under fluoroscopic guidance, the triple needle balloon delivery catheter was placed into the target splenic artery. Once the target ablation site was reached, the balloon was inflated, then the needles were deployed and room temperature anhydrous ethanol was infused into the adventitia and per-adventitial space of the splenic artery. The infusion volume per application was 0.6 mL using a 1 mL syringe. The infusion time per application was within 10 seconds. During the balloon inflation, the ratio of the balloon diameter to the surrounding artery diameter was about 1 : 1.1 (slightly larger) as monitored by fluoroscopy. At the end of the treatment time, the needles were retracted into the catheter, then the balloon was deflated and the catheter was moved to a second treatment site in the same splenic artery about 15 mm from the first treatment site. The treatment steps were repeated for the second treatment (balloon inflation, needle deployment, infusion ablation, needle retrieval, balloon deflation). The total volume of alcohol used for the two treatments of the splenic artery was 1.2 mL.

[0213] The common hepatic artery ablation employed the same treatment method and procedural steps as the splenic artery treatment. The catheter was changed to a fresh catheter for the common hepatic artery ablation. For the common hepatic artery with the same ablation dose of 0.6 mL, a total of two treatments were performed about 15 mm apart from each other (between treatment sites). The total volume of alcohol used for the hepatic artery ablation was 1.2 mL. After the liver treatment, the catheter was placed into the left gastric artery for the next ablation treatment. The same treatment method and procedure were used again with the exception that one 0.6 mL alcohol ablation treatment was applied to the left gastric artery. Angiography was performed after the triple needle balloon delivery catheter was removed.

[0214] The above three arterial ablation treatments were followed by angiography of the renal arteries prior to intervention. Appropriate branches and main aorta were assessed and predetermined for treatment. Following assessment, the triple needle balloon catheter was advanced through the guide catheter and over the guide wire into the branch arteries of the left renal artery and stopped just outside the bifurcation area. The same catheter manipulation method and procedure steps were used and a 0.3 mL volume of alcohol was used for a single ablation of the branch arteries. Once the branch ablation was complete, the catheter was pulled back into the main aorta just past the bifurcation and a 0.6 mL volume of alcohol was used to treat this area. The catheter was then pulled back about 10 mm from the first treatment site in the main aorta to the second ablation site where a second ablation treatment was performed using a 0.6 mL volume of alcohol. A total of 3 treatments were performed on the left renal artery: 2 in the main aorta and 1 in the branch artery, and the total volume of alcohol used was 1.5 mL.

[0215] The same method and procedure steps were repeated for the right renal artery. Following initial angiography and assessment of the right renal artery, the triple needle balloon catheter was advanced through the guide catheter and over the guide wire into branch artery #1. Branch #1 was ablated twice between treatment sites, approximately 10 mm apart, and a 0.3 mL volume of alcohol was used for each treatment. The catheter was then placed into branch artery #2, which was treated twice with a 0.3 mL volume of alcohol for each treatment. Following the two branch treatments, the catheter was pulled back into the main aorta until its needles were near the midpoint of the main aorta and a 0.6 mL volume of alcohol was used to ablate the right main aorta once. The total volume of alcohol used for the right renal artery treatment was also 1.8 mL.

[0216] Patient A was followed up at 2 weeks (2wks), 1 month (1mo), and 3 months (3mos) post-surgery, and his follow-up data is listed below along with his baseline data obtained prior to surgery for comparison. There were no changes in medications during the follow-up period.

[0217] Weight: Baseline = 103 kg, 2wks = 96.2 kg, 1mo = 95.6 kg, 3mos = 96.2 kg. Since the 3rd week post-surgery (2wk time point), a weight loss of approximately 7% was observed and the weight loss was maintained over the 3-month follow-up period.

[0218] 24-hour blood pressure, SBP / DBP: Baseline = 164 / 109 mmHg, 1mo = 140 / 87 mmHg, 3mo = 141 / 84 mmHg. Blood pressure data is the average of 24-hour ambulatory blood pressure. Both systolic (SBP) and diastolic (DBP) blood pressures were significantly decreased from baseline by approximately 14% and 20%, respectively; and the decreased blood pressure was maintained over the 3-month follow-up period.

[0219] Blood glucose levels, HbAlc: Baseline = 7.5%, 3 mos = 6.6%. The patient also had a significant improvement in his glycosylated hemoglobin (HbAlc) levels. His HbAlc value changed by almost -1 (%) in the 3-month follow-up compared to the baseline value.

[0220] Triglycerides: Baseline = 336 mg / dL, 2 weeks = 160 mg / dL, 1 month = 139 mg / dL, 3 months = 167 mg / dL. Triglycerides (TG) are a type of fat (lipid) found in the blood. High triglyceride levels can be a clue that this person has fatty liver disease. Patient A’s triglyceride levels were observed to improve by about 50% in the two-week follow-up period. The decrease and improvement in triglyceride levels were maintained in the 3-month follow-up. In the 1-month follow-up, patient A’s TG levels were within the normal range.

[0221] High-density lipoprotein (HDL): Baseline = 39 mg / dL, 2 weeks = 42 mg / dL, 1 month = 43 mg / dL, 3 months = 40 mg / dL. Patient A’s baseline high-density lipoprotein (HDL) level was just within the normal range. Then in follow-up, his HDL appeared to improve, and all 3 numbers were at 40 or higher. Patient A’s TG / HDL ratio improved significantly from 8.6 (>5 abnormal) at baseline to 4.2 at the 3-month follow-up, which is within the normal range (<5); if the patient had NAFLD, patient A’s NASH condition was significantly improved.

[0222] Patient A’s short-term results are significant and very encouraging for the treatment and technology. The data show that the patient’s health improved, and his disease related to metabolic syndrome appeared to be controlled in the 3-month follow-up.

[0223] Example 4. Clinical trials, hypertension

[0224] In another embodiment, multiple arteries / tissues are treated for hypertension. A 50-year-old male patient B had his blood pressure controlled after the ablation procedure at the 3-month follow-up time point. Patient B had a 5-year history of hypertension. Patient B underwent the same surgical and ablation treatment method as patient A in embodiment 3. Patient B’s treatment arteries and ablation dose per treatment site are summarized in Table 1.

[0225] Table 1. Patient B’s treatment arteries and ablation dose per treatment site Kidney B: renal branch artery; Kidney M: main renal artery; R: right; L: left.

[0226]

[0227] The post-treatment data for average 24-hour ambulatory blood pressure was: baseline = 136 / 79 mmHg, 1 mo = 107 / 61 mmHg, 3-mo = 115 / 66 mmHg. At the 1-month follow-up, both systolic (SBP) and diastolic (DBP) blood pressures were significantly decreased from baseline, by approximately 21% and 23%, respectively; and his blood pressure improvement was maintained at the 3-month follow-up, with both SBP and DBP decreased by approximately 15% from baseline levels.

[0228] Example 5. Clinical trials, T2DM

[0229] In another embodiment, multiple arteries / tissues are treated for diabetes. The same patient B, who has a 1-year history of T2DM, has all of his hepatic, splenic, celiac, right renal, and left renal arteries treated for diabetes. The treatment results in Example 4 produce some improvement in patient B's fasting glucose and HbAlc values.

[0230] The post-treatment data for fasting glucose was: baseline = 186 mg / dL, 2wks = 127 mg / dL, 1 mo = 92 mg / dL, 3 mos = 110 mg / dL. This test was performed in the morning before the patient had eaten. Fasting glucose levels of 100 to 125 mg / dL (5.6 to 6.9 mmol / L) are considered pre-diabetic. If it is 125 mg / dl or higher, the person has diabetes. The data show that patient B had diabetes prior to the procedure. His fasting glucose levels improved significantly from baseline, with a -32% change at the 2-week follow-up, and a -50% change at the 1-month follow-up. At the 3-month follow-up, his low glucose levels were still maintained at a lower level of 110 mg / dL, which was -41% lower than baseline.

[0231] Blood glucose HbAlc data: baseline = 8.1%, 3 mos = 6.0%. The patient's HbAlc improved by an absolute value of -2.1(%) from baseline, a decrease of almost 26% over the 3 months after the procedure.

[0232] Example 6. Clinical trials, weight loss

[0233] In another embodiment, multiple arteries / tissues are treated to control weight. Patient B, who has a 3-year history of obesity, has improved weight after the ablation procedure. The multiple arteries treated are the hepatic, splenic, celiac, right renal, and left renal arteries. The treatment can be seen in Example 4.

[0234] Weight: baseline = 83 kg, 2wks = 79.3 kg, 1 mo = 79.9 kg, 3 mos = 79.1 kg. An initial weight loss of -4.5% was observed at the 2-week follow-up, from a baseline of 83 kg to 79.3 kg. The improved weight was maintained at the 3-month follow-up.

[0235] The terms and expressions used are descriptive rather than restrictive, and their use is not intended to exclude any equivalents of the features shown and described or portions thereof, but it should be recognized that various modifications are possible within the scope of embodiments of the invention. Therefore, it should be understood that while the invention has been specifically disclosed through particular embodiments and optional features, modifications and variations of the concepts disclosed herein can be made by those skilled in the art, and such modifications and variations are considered to be within the scope of embodiments of the invention.

[0236] Exemplary embodiments

[0237] The following exemplary implementations are provided, and their numbers should not be interpreted as specifying an importance level:

[0238] Implementation Scheme 1 provides a method for treating at least one disease (e.g., one disease, two diseases, at least two diseases, three diseases, at least three diseases, four diseases, or at least four diseases), comprising treating at least two different target tissues (e.g., at least three different target tissues or at least four different target tissues) in at least two different body cavities (e.g., at least three different body cavities or at least four different body cavities), said method comprising:

[0239] Performing a treatment procedure on a body cavity that serves as a first body cavity, the treatment procedure comprising:

[0240] A delivery catheter is inserted into the body cavity, wherein the delivery catheter includes a catheter shaft, a balloon at the distal end of the shaft, and an inflatable cavity in fluid communication with the interior of the balloon;

[0241] Inflate the balloon to center the distal end of the shaft within the body cavity;

[0242] Denervation or ablation of target tissue in the body cavity using the delivery catheter includes delivering a certain amount of energy or agent to the target tissue to effectively damage or harm the target tissue to alleviate disease symptoms;

[0243] To cause the balloon to contract; and

[0244] Remove the delivery catheter from the body cavity;

[0245] The treatment procedure is performed in a second body cavity, which is different from the first body cavity.

[0246] Implementation 2 provides the method of Implementation 1, wherein performing the treatment procedure on the second body cavity includes reusing the same delivery catheter used in the treatment procedure on the second body cavity as used in the treatment procedure on the first body cavity.

[0247] Embodiment 3 provides the method of any one of embodiments 1-2, wherein performing the treatment procedure on the second body lumen comprises using a different delivery catheter in the treatment procedure on the second body lumen than used in the treatment procedure on the first body lumen, the different delivery catheter comprising a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon.

[0248] Embodiment 4 provides the method of any one of embodiments 1-3, wherein

[0249] the target tissue of the first body lumen and the second body lumen are different and independently selected from the group consisting of a renal artery, a pulmonary artery, a vascular lumen, a celiac artery, a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, right and left hepatic arteries, a splenic artery, right and left gastric arteries, an adrenal artery, a phrenic artery, a mesenteric artery, a non-vascular lumen, an airway, a sinus, an esophagus, a respiratory and digestive lumen, a stomach, a duodenum, a jejunum, a prostate, a urethra, a ureter, and a target tissue of a urinary lumen; or

[0250] wherein the first body lumen and the second body lumen belong to different classes of body lumens selected from the group consisting of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a urinary lumen; or

[0251] a combination thereof.

[0252] Embodiment 5 provides the method of any one of embodiments 1-4, wherein the disease is selected from the group consisting of hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral artery disease (PAD), end-stage renal disease, a digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), a urinary system disease, cancer, a tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), and a combination thereof.

[0253] Embodiment 6 provides the method of any one of embodiments 1-5, wherein the alleviating symptoms of the disease comprises alleviating symptoms of hypertension, diabetes, obesity, coronary heart disease, peripheral disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cancer, arthritis, or a combination thereof.

[0254] Embodiment 7 provides the method of any one of embodiments 1-6, wherein the alleviating symptoms of the disease comprises reducing blood pressure, reducing blood glucose levels and AIC, reducing body weight, reducing restenosis, reducing liver fat, and reducing pain, or a combination thereof.

[0255] Embodiment 8 provides the method of any one of embodiments 1-7, wherein the delivery catheter further comprises a guidewire lumen extending at least through the distal end of the shaft, wherein the method further comprises advancing the delivery catheter over the guidewire.

[0256] Embodiment 9 provides the method of any one of embodiments 1-8, wherein the delivery catheter further comprises a marker band on or adjacent to the balloon, wherein the method further comprises monitoring the location of the marker band under fluoroscopy.

[0257] Embodiment 10 provides the method of any one of embodiments 1-9, wherein the delivery catheter comprises a chemical infusion delivery catheter.

[0258] Embodiment 11 provides the method of any one of embodiments 1-10, wherein the delivery catheter comprises a combination of a chemical infusion delivery catheter and an energy delivery catheter.

[0259] Embodiment 12 provides the method of any one of embodiments 1-11, wherein the delivery catheter comprises an energy delivery catheter.

[0260] Embodiment 13 provides the method of any one of embodiments 1-12, wherein denervating or ablating the target tissue of the body lumen with the delivery catheter comprises delivering an amount of energy from the delivery catheter to the target tissue using radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound, condensation of at least some of the agent vapor into a liquid, or a combination thereof.

[0261] Embodiment 14 provides the method of any one of embodiments 1-13, wherein the disease comprises:

[0262] renal hypertension and diabetes, or

[0263] renal hypertension and obesity, or

[0264] diabetes and obesity, or

[0265] a combination thereof.

[0266] Embodiment 15 provides the method of any one of embodiments 1-13, wherein the disease comprises renal hypertension and diabetes.

[0267] Embodiment 16 provides the method of any one of embodiments 1-13, wherein the disease comprises renal hypertension and obesity.

[0268] Embodiment 17 provides the method of any one of embodiments 1-13, wherein the disease comprises diabetes and obesity.

[0269] Embodiment 18 provides the method of any one of embodiments 1-17, wherein the first body lumen or second body lumen comprises a splenic artery.

[0270] Embodiment 19 provides the method of any one of embodiments 1-18, wherein the first body lumen or second body lumen comprises a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof).

[0271] Embodiment 20 provides the method of any one of embodiments 1-19, wherein the first body lumen or second body lumen comprises a hepatic artery, a hepatic artery branch, a right hepatic artery, a left hepatic artery, a common hepatic artery, a proper hepatic artery, a celiac artery, or a combination thereof.

[0272] Embodiment 21 provides the method of any one of embodiments 1-20, wherein the first body lumen or second body lumen comprises a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), wherein the method results in at least a 40% reduction in renal norepinephrine.

[0273] Embodiment 22 provides a method of treating a disease, the method comprising:

[0274] inserting a delivery catheter into a body lumen, wherein the delivery catheter comprises a catheter shaft, at least one jetting aperture, and at least one marker band;

[0275] jetting a formulation through the at least one jetting aperture, wherein the amount of formulation delivered is effective to injure or damage target tissue to relieve a symptom of the disease;

[0276] optionally removing the formulation from the tissue; and

[0277] removing the delivery catheter from the body lumen.

[0278] Embodiment 23 provides the method of embodiment 22, wherein the delivery catheter comprises at least one centering balloon, wherein the method further comprises inflating the centering balloon to center the delivery catheter shaft in the body lumen; and deflating the centering balloon after injection.

[0279] Embodiment 24 provides the method of any of embodiments 22-23, wherein the delivery catheter comprises at least one injection needle and an infusion lumen in fluid communication with the at least one injection needle, wherein the method further comprises

[0280] deploying the at least one needle into, outside, or within the wall of the body lumen; and

[0281] infusing the formulation through the infusion lumen and the at least one needle, wherein the amount of formulation delivered is effective to injure or impair the target tissue to relieve the symptoms of the disease; and

[0282] retracting the at least one needle into the delivery catheter after infusion.

[0283] Embodiment 25 provides the method of any of embodiments 1-24, wherein the at least one needle comprises at least two needles and the delivery catheter further comprises a needle lumen, a needle control mechanism, and a flushing lumen, wherein the at least two needles are deployed from the needle lumen and retracted into the needle lumen by the needle control mechanism, and a distal end of the flushing lumen is in fluid communication with the needle lumen, the method further comprising flushing the needles with a flushing fluid through the flushing lumen.

[0284] Embodiment 26 provides the method of any of embodiments 1-25, wherein the at least two needles comprise three needles and the three needles are arranged at uniform distances around the circumference of the catheter shaft and distal to the balloon.

[0285] Embodiment 27 provides a method of treating a disease, the method comprising:

[0286] inserting a centering balloon delivery catheter into a body lumen, wherein the balloon delivery catheter comprises at least one centering balloon and a catheter shaft, at least one injection needle, and at least one marker band;

[0287] inflating the centering balloon to center the delivery catheter shaft in the body lumen;

[0288] deploying the at least one needle into, outside, or within the wall of the body lumen;

[0289] infusing the formulation through the at least one needle, wherein the amount of formulation delivered is effective to injure or impair the target tissue to relieve the symptoms of the disease;

[0290] optionally removing the formulation from the tissue;

[0291] retracting the needle into the delivery catheter and deflating the centering balloon; and

[0292] removing the delivery catheter from the body lumen.

[0293] Embodiment 28 provides the method of any one of embodiments 1-27, wherein the disease is selected from hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), and combinations thereof.

[0294] Embodiment 29 provides the method of embodiment 28, wherein the cancer is selected from adrenal cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, duodenal cancer, jejunum cancer, uterine cancer, and combinations thereof.

[0295] Embodiment 30 provides the method of any one of embodiments 1-29, wherein the target tissue is a tissue of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or combinations thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or combinations thereof.

[0296] Embodiment 31 provides the method of any one of embodiments 1-30, wherein the formulation comprises or consists essentially of ethanol.

[0297] Embodiment 32 provides the method of any one of embodiments 1-31, wherein the formulation consists of ethanol.

[0298] Embodiment 33 provides the method of any one of embodiments 1-32, wherein the formulation comprises a gas, a vapor, a liquid, a solution, an emulsion, a suspension, or combinations thereof of one or more ingredients.

[0299] Embodiment 34 provides the method of any one of embodiments 1-33, wherein the formulation comprises a vapor of one or more ingredients and heat is generated by condensation of the vapor into a liquid.

[0300] Embodiment 35 provides the method of any one of embodiments 1-34, wherein the formulation comprises a liquid or solution and heat is transferred from the formulation to the target tissue.

[0301] Embodiment 36 provides the method of any one of embodiments 1-35, wherein the formulation comprises an emulsion or suspension and heat is transferred from the formulation to the target tissue.

[0302] Embodiment 37 provides the method of any one of embodiments 1-36, wherein the temperature of the formulation ranges from 40 to 140 °C.

[0303] Embodiment 38 provides the method of any one of embodiments 1-37, wherein the temperature of the formulation ranges from 0 to 140 °C.

[0304] Embodiment 39 provides the method of any one of embodiments 1-38, wherein the temperature of the formulation ranges from -40 to 0 °C.

[0305] Embodiment 40 provides the method of any one of embodiments 1-39, wherein the temperature of the formulation is room temperature.

[0306] Embodiment 41 provides the method of any one of embodiments 1-40, wherein the temperature of the target tissue is lower than the temperature of the formulation.

[0307] Embodiment 42 provides the method of any one of embodiments 1-41, wherein the temperature of the target tissue is higher than the temperature of the formulation.

[0308] Embodiment 43 provides the method of any one of embodiments 1-42, wherein the pressure of the formulation infusion ranges from 0.1 to 14 atm.

[0309] Embodiment 44 provides the method of any one of embodiments 1-43, wherein the temperature of the target tissue ranges from -40 to 100 °C.

[0310] Embodiment 45 provides the method of any one of embodiments 1-44, wherein the temperature of the target tissue ranges from -40 to 0 °C.

[0311] Embodiment 46 provides the method of any one of embodiments 1-45, wherein the temperature of the target tissue is equal to the temperature of body temperature.

[0312] Embodiment 47 provides the method according to any of Embodiments 1-46, wherein the pressure of the formulation ranges from about 2 to 200 psi at a temperature ranging from about -40 to 150 °C.

[0313] Embodiment 48 provides the method according to any of Embodiments 1-47, wherein the amount of the formulation is from 0.2 microliters to 200 milliliters.

[0314] Embodiment 49 provides the method according to any of Embodiments 1-48, wherein the method comprises inflating the delivery catheter in the body lumen for an inflation period ranging from about 2 seconds to about 60 minutes.

[0315] Embodiment 50 provides the method according to any of Embodiments 1-49, wherein the method delivers heat or energy to the target tissue ranging from about 2 cal / g to about 150 cal / g.

[0316] Embodiment 51 provides the method according to any of Embodiments 1-50, wherein the delivery catheter is a needle or needle-based delivery catheter, a single balloon delivery catheter, a dual balloon delivery catheter, an energy delivery catheter, an infusion catheter, a balloon infusion catheter, a balloon catheter, a dumbbell balloon infusion catheter, or a combination thereof.

[0317] Embodiment 52 provides the method according to any of Embodiments 1-51, wherein the balloon inflation pressure ranges from 0.1 to 14 atm.

[0318] Embodiment 53 provides the method according to any of Embodiments 1-52, wherein the formulation comprises one or more ingredients selected from the group consisting of water, saline, hypertonic saline, phenol, methanol, ethanol, spirits, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodized oil, urea, derivatives and combinations thereof.

[0319] Embodiment 54 provides the method according to any of Embodiments 1-53, wherein the formulation comprises a gas or vapor of oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, water, phenol, methanol, ethanol, spirits, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, or combinations thereof.

[0320] Embodiment 55 provides the method of any one of embodiments 1-54, wherein the formulation comprises a therapeutic agent for denervation, wherein the therapeutic agent comprises a sodium channel blocker, a tetrodotoxin, a saxitoxin, a decarbamoyl saxitoxin, a vanilloid, a neosaxitoxin, a lidocaine, a conotoxin, a cardiac glycoside, a digoxin, a glutamate, a staurosporine, an amlodipine, a verapamil, a cymarin, a digitoxin, a proscillaridin, a quabain, a veratridine, a domoic acid, an oleandrin, a carbamazepine, an aflatoxin, a guanethidine, a guanethidine sulfate, or a combination thereof.

[0321] Embodiment 56 provides the method of any one of embodiments 1-55, wherein the formulation comprises a contrast agent for imaging denervation of a nerve, wherein the contrast agent comprises iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, a derivative thereof, or a combination thereof.

[0322] Embodiment 57 provides the method of any one of embodiments 1-56, wherein the formulation comprises an azeotrope.

[0323] Embodiment 58 provides the method of embodiment 57, wherein the co-solvent comprises ethanol / water, propanol / water, isopropanol / water, butanol / water, acetic acid / water, lactic acid / water, ethyl lactate / water, ethyl lactate / ethanol, lactic acid / ethanol / water, ethyl lactate / water / ethanol, ethyl acetate / ethanol, ethyl nitrate / ethanol, isopropyl acetate / ethanol, or combinations thereof.

[0324] Embodiment 59 provides the method of any one of embodiments 1-58, wherein the formulation comprises ethanol, ethanol / water, ethanol / water / oxygen, ethanol / water / air, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropanol / water, butanol / water, acetic acid / water, or combinations thereof.

[0325] Embodiment 60 provides a centering balloon catheter for delivering a material to a target location in a body lumen of a patient, the centering balloon catheter comprising:

[0326] a proximal end;

[0327] a distal end;

[0328] a wire lumen;

[0329] a balloon inflation lumen;

[0330] a formulation infusion lumen and / or a vacuum lumen;

[0331] an inflatable balloon portion;

[0332] at least one injection needle;

[0333] at least one marker band adjacent to the centering balloon; and

[0334] at least one needle exit opening adjacent to the marker band for needle deployment.

[0335] Embodiment 61 provides the centering balloon catheter of embodiment 60, comprising three injection needles.

[0336] Embodiment 62 provides the centering balloon catheter of any one of embodiments 60-61, wherein the needle deployment through the needle exit opening allows the formulation to penetrate into a wall of the body lumen at a pressure higher than a pressure of the body lumen.

[0337] Embodiment 63 provides the centering balloon catheter of any of embodiments 60-62, wherein the target tissue is a target tissue of a renal artery, a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof.

[0338] Embodiment 64 provides the centering balloon catheter of any of embodiments 60-63, wherein the formulation infusion pressure ranges from 0.1 to 14 atm, and the balloon inflation pressure ranges from 0.1 to 14 atm.

[0339] Embodiment 65 provides a needle-based balloon delivery catheter for delivering a material to a target tissue in a body lumen of a patient, the delivery catheter comprising:

[0340] a catheter shaft having a proximal end and a distal end;

[0341] at least one marker band located proximate the distal end of the shaft;

[0342] at least one needle located in a needle lumen, wherein the needle lumen is open to the exterior of the catheter shaft through at least one needle exit hole;

[0343] an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen, the irrigation lumen being in fluid communication with a distal end of the needle lumen, wherein the irrigation port is in fluid communication with the needle exit hole through the irrigation lumen;

[0344] a guidewire lumen extending through at least the distal end of the shaft;

[0345] at least one balloon proximate a distal end of the catheter;

[0346] an inflation lumen;

[0347] an inflation port in fluid communication with the inflation lumen and in fluid communication with an interior of the balloon, wherein the balloon is inflatable via the inflation port through the inflation lumen and to substantially center the distal end of the catheter shaft in the body lumen;

[0348] an ablation or denervation port at the proximal end of the shaft, wherein the ablation or denervation port is in fluid communication with the at least one needle for supplying ablation energy or a formulation to the at least one needle; and

[0349] a needle movement controller in electrical or mechanical communication with the at least one needle, wherein the needle movement controller deploys the at least one needle into the body lumen, into a wall of the body lumen, or outside of the body lumen.

[0350] Embodiment 66 provides the delivery catheter of embodiment 65, comprising three injection needles.

[0351] Embodiment 67 provides the delivery catheter of any one of embodiments 65-66, wherein the needle deployment through the needle exit opening allows the agent to penetrate into a wall of the body lumen at a pressure higher than a pressure of the body lumen.

[0352] Embodiment 68 provides the delivery catheter of any one of embodiments 65-67, wherein the target tissue is a target tissue of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of a left main renal artery, a distal end of a right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof.

[0353] Embodiment 69 provides the delivery catheter of any one of embodiments 65-68, wherein a pressure range of the agent infusion is 0.1 to 14 atm, and a balloon inflation pressure range is 0.1 to 14 atm.

[0354] Embodiment 70 provides a delivery catheter, comprising:

[0355] a shaft having a proximal end and a distal end;

[0356] one or more needles for infusion of a therapy disposed proximate the distal end of the shaft;

[0357] an inflatable balloon disposed proximate the distal end of the shaft such that when the delivery catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered in the lumen; and

[0358] a marker band at the distal end of the shaft.

[0359] Embodiment 71 provides a delivery catheter, comprising:

[0360] a shaft having a proximal end and a distal end;

[0361] one or more needles for infusion therapy disposed near the distal end of the shaft; and

[0362] a steering mechanism associated with the shaft such that the distal end of the shaft is steerable in a direction away from a longitudinal axis of the shaft.

[0363] Embodiment 72 provides the delivery catheter of any of embodiments 70-71, wherein the one or more needles comprises one needle.

[0364] Embodiment 73 provides the delivery catheter of any of embodiments 70-71, wherein the one or more needles comprises more than one needle.

[0365] Embodiment 74 provides the delivery catheter of embodiment 73, wherein the one or more needles comprises a needle tip-to-tip span diameter of 5 mm to 80 mm measured when the one or more needles are fully advanced from the delivery catheter.

[0366] Embodiment 75 provides the delivery catheter of embodiments 73-74, wherein the delivery catheter comprises a fixed needle tip-to-tip span diameter measured when the one or more needles are fully advanced from the delivery catheter.

[0367] Embodiment 76 provides the delivery catheter of any of embodiments 73-75, wherein the delivery catheter comprises an adjustable needle tip-to-tip span diameter measured when the one or more needles are fully advanced from the delivery catheter.

[0368] Embodiment 77 provides the delivery catheter of any of embodiments 70-71 and 73-76, wherein the one or more needles comprises three needles.

[0369] Embodiment 78 provides the delivery catheter of any of embodiments 70-77, wherein the one or more needles comprises a shape memory material.

[0370] Embodiment 79 provides the delivery catheter of any of embodiments 70-78, wherein the one or more needles comprises nitinol.

[0371] Embodiment 80 provides the delivery catheter of any of embodiments 70-79, wherein the one or more needles comprises one or more radiopaque materials.

[0372] Embodiment 81 provides the delivery catheter of any of embodiments 70-80, wherein the one or more needles comprises a film comprising the one or more radiopaque materials.

[0373] Embodiment 82 provides the delivery catheter of any of Embodiments 70-81, wherein the one or more needles comprise one or more radiopaque materials including tungsten (W), gold (Au), tantalum (Ta), platinum (Pt), iridium (Ir), compounds thereof, or combinations thereof.

[0374] Embodiment 83 provides the delivery catheter of any of Embodiments 70-82, wherein the shaft comprises a wire lumen that is an over-the-wire (OTW) shaft.

[0375] Embodiment 84 provides the delivery catheter of any of Embodiments 70-83, wherein the shaft comprises a wire lumen that is a rapid exchange (RX) shaft.

[0376] Embodiment 85 provides the delivery catheter of any of Embodiments 70-84, wherein the shaft comprises one or more needle exit openings at the distal end of the shaft.

[0377] Embodiment 86 provides the delivery catheter of any of Embodiments 71-85, wherein the needle exit openings are located on one side of the shaft in the direction of movement of the steering mechanism.

[0378] Embodiment 87 provides the delivery catheter of any of Embodiments 70-86, wherein the shaft comprises at least one jetting aperture.

[0379] Embodiment 88 provides the delivery catheter of any of Embodiments 85-87, wherein the shaft comprises an irrigation lumen connected to the needle exit openings.

[0380] Embodiment 89 provides the delivery catheter of Embodiment 88, wherein the irrigation lumen is for carrying an irrigation fluid, wherein the irrigation fluid is saline, heparinized saline, a therapeutic drug, or combinations thereof.

[0381] Embodiment 90 provides the delivery catheter of any of Embodiments 87-89, further comprising a sleeve over at least some of the jetting apertures.

[0382] Embodiment 91 provides the delivery catheter of any of Embodiments 70-90, wherein the shaft comprises at least one vacuum aperture.

[0383] Embodiment 92 provides the delivery catheter of any of Embodiments 70-91, wherein the delivery catheter comprises an ablation or denervation port at the proximal end of the shaft, wherein the ablation or denervation port is in fluid communication with the one or more needles for supplying ablation energy or agents to the one or more needles.

[0384] Embodiment 64 provides the method, centering balloon catheter, or delivery catheter according to any or any combination of Embodiments 1-63, optionally configured such that all elements or options recited can be used or selected from.

[0385] Further, the present application is also directed to embodiments of the following.

[0386] 1. A method of treating at least one disease, comprising treating at least two different target tissues in at least two different body lumens, the method comprising:

[0387] performing a treatment procedure on a body lumen that is a first body lumen, the treatment procedure comprising:

[0388] inserting a delivery catheter into the body lumen, wherein the delivery catheter comprises a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon;

[0389] inflating the balloon to center the distal end of the shaft in the body lumen;

[0390] denervating or ablating a target tissue of the body lumen with the delivery catheter, comprising delivering an amount of energy or agent to the target tissue effective to injure or impair the target tissue to relieve a symptom of a disease;

[0391] deflating the balloon; and

[0392] removing the delivery catheter from the body lumen;

[0393] performing the treatment procedure on a second body lumen different from the first body lumen.

[0394] 2. The method of item 1, wherein the first body lumen and the second body lumen are of different classes of body lumens selected from the group consisting of: renal artery, renal vein, gastroduodenal artery, hepatic artery, pulmonary artery, celiac artery, gastroduodenal artery, splenic artery, adrenal artery, phrenic artery, mesenteric artery, airway, esophagus, stomach, duodenum, jejunum, and urogenital lumen.

[0395] 3. The method of item 1, wherein the at least one disease comprises:

[0396] at least two diseases; or

[0397] at least three diseases; or

[0398] at least four diseases.

[0399] 4. The method of item 1, wherein the disease is selected from the group consisting of hypertension, pulmonary arterial hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, digestive system disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), and combinations thereof.

[0400] 5. The method of item 1, wherein the at least one disease comprises at least two diseases, the at least two diseases comprising:

[0401] renal hypertension and diabetes, or

[0402] renal hypertension and obesity, or

[0403] diabetes and obesity, or

[0404] combinations thereof.

[0405] 6. The method of item 1, wherein the alleviating a symptom of a disease comprises reducing blood pressure, reducing blood glucose levels and AIC, reducing body weight, reducing restenosis, reducing liver fat, and reducing pain, or combinations thereof.

[0406] 7. The method of item 1, wherein the delivery catheter comprises a chemical infusion delivery catheter.

[0407] 8. The method of item 1, wherein the delivery catheter comprises an energy delivery catheter.

[0408] 9. The method of item 1, wherein the denervating or ablating a target tissue of the body lumen with the delivery catheter comprises delivering an amount of energy from the delivery catheter to the target tissue using radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound, condensation of at least some of the formulation from a vapor to a liquid, or combinations thereof.

[0409] 10. The method of item 1, wherein the formulation comprises one or more ingredients selected from the group consisting of water, saline, hypertonic saline, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propyl alcohol, butyl alcohol, isobutyl alcohol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodized oil, urea, derivatives and combinations thereof.

[0410] 11. The method of item 1, wherein the formulation comprises ethanol.

[0411] 12. The method of item 1, wherein the formulation comprises an azeotrope.

[0412] 13. A needle-based balloon delivery catheter for delivering a material to a target tissue in a body lumen of a patient, the delivery catheter comprising:

[0413] a catheter shaft having a proximal end and a distal end;

[0414] at least one marker band located proximate the distal end of the shaft;

[0415] at least one needle located in a needle lumen, wherein the needle lumen is open to the exterior of the catheter shaft through at least one needle exit hole;

[0416] an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen, the irrigation lumen being in fluid communication with a distal end of the needle lumen, wherein the irrigation port is in fluid communication with the needle exit hole through the irrigation lumen;

[0417] a guidewire lumen extending through at least the distal end of the shaft;

[0418] at least one balloon proximate the distal end of the catheter;

[0419] an inflation lumen;

[0420] an inflation port in fluid communication with the inflation lumen and in fluid communication with an interior of the balloon, wherein the balloon is inflatable via the inflation port through the inflation lumen and substantially centers the distal end of the catheter shaft in a body lumen;

[0421] an ablation or denervation port at the proximal end of the shaft, wherein the ablation or denervation port is in fluid communication with the at least one needle for supplying ablation energy or agents to the at least one needle; and

[0422] a needle movement controller in electrical or mechanical communication with the at least one needle, wherein the needle movement controller deploys the at least one needle into the body lumen, into a wall of the body lumen, or outside of the body lumen.

[0423] 14. An infusion catheter, comprising:

[0424] a shaft having a proximal end and a distal end; and

[0425] one or more needles for infusing a therapy disposed proximate the distal end of the shaft;

[0426] wherein the infusion catheter comprises:

[0427] an inflatable balloon disposed proximate the distal end of the shaft such that when the infusion catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered in the lumen, wherein the distal end of the shaft comprises a marker band, or

[0428] a steering mechanism associated with the shaft such that the distal end of the shaft can be steered in a direction away from a longitudinal axis of the shaft, or

[0429] a combination thereof.

[0430] 15. The infusion catheter of item 14, wherein the one or more needles comprises more than one needle.

[0431] 16. The infusion catheter of item 15, wherein the needle comprises a needle tip to tip span diameter of 5 mm to 80 mm measured when the needle is fully advanced from the infusion catheter.

[0432] 17. The infusion catheter of item 14, wherein the one or more needles comprises a shape memory material.

[0433] 18. The infusion catheter of item 14, wherein the one or more needles comprises nitinol.

[0434] 19. The infusion catheter of item 14, wherein the one or more needles comprises one or more radiopaque materials.

[0435] 20. The infusion catheter of item 14, wherein the shaft comprises:

[0436] at least one jetting aperture, or

[0437] an irrigation lumen connected to the needle exit opening, or

[0438] at least one vacuum aperture, or

[0439] a combination thereof.

Claims

1. A catheter for performing a method of treating at least two diseases, the method comprising ablative treatment of at least two different target tissues in at least two different body lumens using energy, the method comprising: inserting the catheter into a first body lumen comprising a hepatic artery; inflating the balloon to center the distal end of the shaft in the first body lumen; delivering energy to a target tissue of the first body lumen to ablate neural tissue; removing the catheter from the first body lumen; inserting the catheter into a second body lumen comprising a renal artery; and delivering energy to a target tissue of the second body lumen to ablate neural tissue; the catheter comprising: a catheter shaft having a proximal end and a distal end; a balloon at the distal end of the shaft; an inflation lumen in fluid communication with an interior of the balloon; and an energy delivery element comprising a radiofrequency electrode, a cryoablation system, a microwave energy source, a laser energy source, or an ultrasound transducer, wherein the energy delivered during the method comprises ultrasound energy.

2. The catheter of claim 1, wherein the at least two diseases comprise hypertension and diabetes. the needle lumen opens to the catheter shaft through at least one needle exit hole, and wherein the method further comprises deploying the at least one needle into or through a wall of a body lumen.

3. The catheter of claim 1, further comprising at least one needle positioned within the needle lumen, wherein, 4. The catheter of claim 3, comprising three needles evenly arranged around a circumference of the catheter shaft.

5. The catheter of claim 1, further comprising a guide wire lumen extending through at least the distal end of the shaft.

6. The catheter of claim 1, further comprising a flushing lumen and a flushing port for delivering a flushing medium to the first body lumen and / or the second body lumen.

7. The catheter of claim 1, wherein the energy delivery element comprises the radiofrequency electrode, and delivering energy comprises delivering radiofrequency energy at a temperature range of -30°C to 80°C.

8. The catheter of claim 7, wherein the method comprises cooling the radiofrequency electrode during energy delivery.

9. The catheter of claim 1, wherein the energy delivery element comprises the microwave energy source, and wherein delivering energy comprises delivering focused microwave energy around a selected circumferential portion of a body lumen.

10. The catheter of claim 1, wherein the energy delivery element comprises the ultrasound transducer, and wherein delivering energy comprises delivering high intensity focused ultrasound energy to neural tissue.

11. The catheter of claim 1, wherein the energy delivery element comprises the laser energy source, and wherein delivering energy comprises emitting laser energy from a wall of the catheter shaft.

12. The catheter of claim 1, wherein the energy delivery element comprises the cryoablation system, wherein delivering energy comprises delivering a cryoablation medium through at least one needle or jetting hole, and wherein the method comprises creating a pressure drop or phase change of the cryoablation medium to provide cryoablation therapy.

13. The catheter of claim 1, wherein the hepatic artery is selected from a common hepatic artery, a proper hepatic artery, and a gastroduodenal artery, and the renal artery is selected from a left main renal artery, a right main renal artery, and a renal artery branch. ​ 14. The catheter of claim 13, wherein the hepatic artery is the common hepatic artery.

15. The catheter of claim 13, wherein, Treatment of the at least two diseases includes reducing blood pressure by hepatic and renal nerve ablation.

16. The catheter of claim 13, wherein, Treatment of the at least two diseases includes reducing blood glucose levels and HbAlc.

17. The catheter of claim 1, wherein the balloon is a low compliance balloon having a diameter of 3 mm to 40 mm when inflated, and wherein the method includes inflating the balloon at a pressure of 0.1 to 3 atmospheres.

18. The catheter of claim 1, further comprising a needle movement controller in communication with at least one needle, wherein the method includes causing the controller to deploy the needle to a penetration depth of 2 mm from within a wall of the first and / or second body lumen to outside a wall of the first and / or second body lumen.

19. The catheter of claim 1, wherein the method includes treating metabolic syndrome by treating target tissue in at least four different body lumens selected from the group consisting of a renal artery, a hepatic artery, a splenic artery, and a gastric artery, thereby reducing body weight, blood pressure, and blood glucose levels.

20. The catheter of claim 1, wherein the method further includes treating an additional body lumen selected from the group consisting of a splenic artery, a gastric artery, a pulmonary artery, a celiac artery, and a gastroduodenal artery.

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