CN114025826A

CN114025826A - Delivery catheter and disease treatment method

Info

Publication number: CN114025826A
Application number: CN202080046425.XA
Authority: CN
Inventors: 王立筱; J·J·陈; T·T·T·特兰
Original assignee: Neurotronic Inc
Current assignee: Neurotronic Inc
Priority date: 2019-06-25
Filing date: 2020-06-25
Publication date: 2022-02-08
Also published as: JP2022538239A; WO2020264152A1; EP3990090A1; EP3990090A4

Abstract

Embodiments of the present invention provide devices and methods for at least one disease by delivering an effective amount of energy and/or agent to tissue on or near a wall of 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 amount of agent and/or energy delivered can be effective to damage or impair tissue, nerves, and/or nerve endings to alleviate symptoms of the disease.

Description

Delivery catheter and disease treatment method

Cross Reference to Related Applications

This application claims priority rights to U.S. provisional patent application serial No. 62/866,266 filed on 25.6.2019, U.S. patent application No. 16/563,235 filed on 6.9.2019, and U.S. patent application No. 16/690,992 filed on 21.11.2019, the disclosures of which are incorporated herein by reference in their entireties.

Background

Hypertension (high blood pressure) is a major global health problem. It is estimated that 30% to 40% of adults worldwide suffer from this disease. In addition, their prevalence is expected to increase, particularly in developing countries. Diagnosis and treatment of hypertension is still not ideal and most patients are trying to properly control blood pressure.

Benign prostatic hyperplasia is a noncancerous enlargement of the prostate gland that affects more than 50% of men over the age of 60. In the early stages of life, the prostate gland is about the size of a walnut, weighing about 20 grams. Over time, prostate enlargement is considered normal. With age, the prostate gradually enlarges to at least twice its original size. Prostate growth causes increased pressure on the adjacent urethra, causing this latter organ to narrow and eventually causing obstruction of the urinary tract, making urination difficult.

Chronic Obstructive Pulmonary Disease (COPD) is associated with two major airflow obstruction disorders: chronic bronchitis and emphysema. Chronic bronchitis is caused by inflammation of the bronchial airways. The bronchial airways connect the trachea with the lungs. Emphysema is a disease caused by over-inflation of the alveoli or the air sacs of the lungs. This condition causes shortness of breath. Approximately 1600 million americans have COPD, most of which (80-90%) are lifelong smokers. COPD is a leading cause of death in the united states.

Asthma is a chronic respiratory disease characterized by excessive narrowing of the airways and is caused by airway inflammation, mucus hypersecretion, and airway hyperreactivity. This narrowing of the airway makes breathing difficult and may significantly affect the life of the patient, limiting participation in a multitude of activities. In severe cases, asthma attacks can be life threatening. To date, there is no known method of curing asthma.

Chronic Sinusitis (CS) is caused by inflammation of the membrane lining in one or more paranasal sinuses and is often associated with significant tissue damage. There are approximately 3700 ten thousand cases of CS reported to the center for disease control and prevention (CDC) each year.

Diabetes is a metabolic condition, or combination of conditions, in which an individual experiences high concentrations of blood glucose. The condition results from insufficient insulin production or an inability of cells to respond properly to insulin in the body. Glycated hemoglobin (HbA1c) is a marker of plasma glucose concentration and is used clinically for the diagnosis of diabetes. In humans, normal HbA1c levels are typically < 6.0%, pre-diabetic (prediabetes) HbA1c levels range from 6.0-6.4%, and diabetic HbA1c levels exceed 6.5%.

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 affecting almost every part of the body. For example, it is associated with blindness, heart and vascular disease, stroke, renal failure, amputation, and nerve damage.

In the united states, diabetes affects approximately 8% of the population and results in costs approaching $ 2500 billion.

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 a type 1 patient cannot produce sufficient insulin and a type 2 patient cannot respond appropriately to insulin, a condition that develops in the late stages of a pregnant female.

Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of the total cases. It is commonly associated with aging, obesity, family history, past gestational diabetes history, and inactivity. It is also more prevalent in certain ethnicities. Type 2 diabetes is also known as insulin resistant diabetes because the pancreas typically produces sufficient amounts of insulin, but the body does not respond properly to it. 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.

The liver is vital for maintaining normal glucose homeostasis, producing glucose during fasting and storing it after a meal. However, these hepatic processes are deregulated in type 1 and type 2 diabetes, and this imbalance leads to hyperglycemia in the fasted and postprandial states. Net hepatic glucose production (net hepatic glucose production) is the sum of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. Glucose levels are sensed by neurons and glial cells expressing glucose transporters (GLUTs) in the Central Nervous System (CNS) and by peripheral tissues such as the taste bud, intestinal tract 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 glycogenesis.

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

Glucagon, epinephrine, norepinephrine, cortisol, and growth hormone help maintain blood glucose levels and raise blood glucose. Diabetic patients have high concentrations of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. Glucagon is produced by the islet cells (alpha cells) in the pancreas, controlling the production of glucose and another fuel ketone in the liver. Glucagon is released during the 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 to help form new glucose and ketone units from other substances. It also promotes the breakdown of fat in adipocytes. Epinephrine and norepinephrine are very similar. Both are neurotransmitters and both increase blood pressure and blood glucose levels. Epinephrine (epinephrine) is released from nerve endings and adrenal glands and acts directly on the liver to promote the production of glucose (by glycogenolysis). Epinephrine also promotes the breakdown and release of fatty nutrients, which enter the liver and are converted to glucose and ketones. Cortisol is a steroid hormone which is also secreted from the adrenal gland. It protects adipose and muscle cells from the action of insulin and increases the glucose produced by the liver. Under normal circumstances, cortisol counteracts the action of insulin. Cortisol levels can rise and cause insulin resistance under stress or if synthetic cortisol is used as a drug (e.g. with prednisone therapy or cortisone injection). When patients suffer from type 2 diabetes, this means that they may need to take more medication or insulin to control blood glucose. Growth hormone is released from the pituitary as part of the brain. Like cortisol, growth hormone counteracts the effects of insulin on muscle and adipocytes. High levels of growth hormone cause resistance to the action of insulin.

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

Metabolic syndrome is a serious health condition affecting up to one third of the american adults and placing them at higher risk for cardiovascular disease, type 2 diabetes, stroke, and diseases associated with arterial wall fat deposition. It is a group of commonly occurring conditions. These conditions include hypertension, hyperglycemia, waist adiposity, and abnormal cholesterol or triglyceride levels. The National Institutes of Health guide defines metabolic syndrome as having three or more of The following characteristics (including The characteristics that you are controlling when taking medications): waistline (measured at least 35 inches (89 cm) waist for women and 40 inches (102 cm) waist for men), high triglyceride levels (150 milligrams/deciliter (mg/dL) or 1.7 millimoles/liter (mmol/L), or higher levels of such fats found in the blood), reduced "good" or HDL cholesterol (high density lipoprotein (HDL) cholesterol below 40mg/dL (1.04mmol/L) for men or 50mg/dL (1.3mmol/L) for women), elevated blood pressure (130/85 millitorr (mm Hg) or higher), elevated fasting glucose (100mg/dL (5.6mmol/L) or higher).

Non-alcoholic fatty liver disease is another health problem that occurs when the liver has difficulty breaking down fat, causing fat to accumulate in the liver tissue of people who have little or no alcohol consumption. It is normal for the liver to contain some fat. However, if more than 5% to 10% of the liver weight is fat, it is called fatty liver (steatosis). Nonalcoholic fatty liver disease (NAFLD) is common and does not cause signs and symptoms and complications for most people. However, in some people with nonalcoholic fatty liver disease, the accumulated fat can cause inflammation and scarring of the liver. This more severe form of nonalcoholic fatty liver disease is sometimes referred to as nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. In the most severe cases, non-alcoholic fatty liver disease progresses to liver failure. NASH is associated with dyslipidemia, low High Density Lipoprotein (HDL) (male <40mg/dL or female <50mg/dL), hypertriglyceridemia (> 150mg/dL), hypercholesterolemia (> 200mg/dL), and Triglyceride (TG)/HDL > 5.0. NASH digestion (resolution) is associated with a decrease in TG and TG/HDL ratios.

The spleen is the main filter for blood borne pathogens and is also a key organ for iron metabolism and erythrocyte 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 modulates immunity or responds to inflammatory stimuli by up-regulating sympathetic nerve transmission to the spleen, which mobilizes monocytes to tissue injury sites and releases cytokines that modulate the inflammatory response.

Disclosure of Invention

Embodiments of the present invention relate to a delivery catheter for delivering a chemical 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. The at least one disease may include hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic 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 agents to a target tissue in the body to alleviate disease symptoms, such as lowering blood pressure of hypertension, lowering blood glucose levels and AIC of diabetes, reducing body weight of obesity, reducing restenosis of coronary and peripheral diseases, reducing liver fat of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and reducing pain of cancer and arthritis. The energy may be radio frequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound energy, or combinations thereof. The target tissue may include 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, or distal end of right main renal artery branch), renal vein, gastric artery, gastric vein, hepatic artery, hepatic vein, pulmonary artery, pulmonary vein, celiac artery, celiac vein, gastroduodenal artery, gastroduodenal vein, splenic artery, splenic vein, adrenal artery, adrenal vein, diaphragmatic artery, diaphragmatic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, and urinary lumen. The delivery catheter may comprise a radio frequency 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 may include a combination of a balloon and an infusion catheter, among other delivery devices. The formulation delivered by the delivery catheter may include one or more ingredients of gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof. By delivering the formulation to a target tissue in the human body by chemical infusion from a delivery catheter, the safety and effectiveness of the treatment may be improved.

Various embodiments of the present invention provide methods of treating at least one disease comprising 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 that is a first body lumen. The treatment procedure includes inserting a delivery catheter into the body cavity. 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 (deflate) the balloon to center the distal end of the shaft in the body lumen (center). The treatment procedure includes denervating or ablating a target tissue of the body lumen with a delivery catheter, including delivering an amount of energy or agent to the target tissue effective to damage or compromise the target tissue to alleviate symptoms of the disease. The treatment procedure includes deflating the balloon (deflate). The treatment procedure also includes removing the delivery catheter from the body lumen. The method also includes performing a treatment procedure on a second body lumen different from the first body lumen.

The 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 may be a method of treating metabolic syndrome. The method may include treating first, second, third, and fourth target tissues that are all different from one another and located in first, second, third, and fourth body lumens, 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, an abdominal 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 infradiaphragmatic artery, a left infradiaphragmatic 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, an intrinsic 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 infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The third body lumen may include the splenic artery, the gastric artery, the left gastric artery, or a combination thereof. The fourth body lumen may include a gastroduodenal artery, a gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The chemical and/or energy delivered to the target tissue may reduce body weight, reduce hypertension, reduce AIC, reduce blood glucose levels, reduce body waist adipose tissue, or a combination thereof.

The 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 may be a method of treating hypertension. The method may include treating first, second, third, and fourth target tissues that are all different from one another and located in first, second, third, and fourth body lumens, respectively. The first body lumen may include a renal artery, such as 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 may include a common hepatic artery, an intrinsic 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 may include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth target tissue may include a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The chemicals and/or energy delivered to the target tissue can reduce blood pressure.

The 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 may be a method of treating diabetes. The method may include treating first, second, third, and fourth target tissues that are all different from one another and located in first, second, third, and fourth body lumens, respectively. The first body lumen may include a common hepatic artery, an intrinsic hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second 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 spleen artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen may include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth body lumen may include a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The chemical and/or energy delivered to the target tissue can reduce blood glucose levels, reduce AIC, or a combination thereof.

The 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 may be a method of treating obesity. The method may include treating first, second, third, and fourth target tissues that are all different from one another and located in first, second, third, and fourth body lumens, respectively. The first body lumen may include a common hepatic artery, an intrinsic hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second 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 spleen artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen may include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth body lumen may include a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The chemical and/or energy delivered to the target tissue may reduce body weight, reduce body mass index, or a combination thereof.

The 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 may be a method of treating non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or a combination thereof. The method may include treating first, second, third, and fourth target tissues that are all different from one another and located in first, second, third, and fourth body lumens, respectively. The first body lumen may include a common hepatic artery, an intrinsic hepatic artery, a right hepatic artery, a left hepatic artery, or a combination thereof. The second 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 spleen artery, a right gastric artery, a left gastric artery, or a combination thereof. The third body lumen may include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth body lumen may include a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right infradiaphragmatic artery, a left infradiaphragmatic artery, or a combination thereof. The chemicals and/or energy delivered to the target tissue can reduce fat in the liver.

In various embodiments, the present invention provides methods of treating diseases. The method includes inserting a delivery catheter into the body lumen, wherein the delivery catheter includes a catheter shaft, at least one jet aperture, and at least one marker band. The method includes spraying (spray) the formulation through at least one spray orifice, wherein the amount of the formulation delivered is effective to damage or impair the target tissue to alleviate symptoms of the disease. The method includes optionally removing the agent from the tissue. The method further comprises removing (withdraw) the delivery catheter from the body lumen.

In various embodiments, the present invention provides methods of treating diseases. The method includes inserting a centering balloon delivery catheter into the body lumen, wherein 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, out of, or within a wall of a body lumen. The method comprises infusing the formulation through at least one needle, wherein the amount of the formulation delivered is effective to damage or impair the target tissue to alleviate symptoms of the disease. The method optionally includes removing the agent 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.

In various embodiments, the present invention 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 portion; 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 the marker band for deploying the needle.

In various embodiments, the present invention provides a needle-based balloon delivery catheter for delivering 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 near the distal end of the shaft. The delivery catheter includes at least one needle positioned in a needle lumen, wherein the needle lumen is open to the exterior of the catheter shaft through at least one needle exit hole. The delivery catheter includes an irrigation port in fluid communication with an irrigation lumen at the proximal end of the shaft, the irrigation lumen in fluid communication with the distal end of the needle lumen, wherein the irrigation port is in fluid communication with the needle outlet aperture through the irrigation lumen. The delivery catheter includes a guidewire lumen extending through at least the distal end of the shaft. The delivery catheter includes at least one balloon adjacent 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 the interior of the balloon. The balloon is inflatable through the inflation lumen via the inflation port and substantially centers the distal end of the catheter shaft within the body lumen. The delivery catheter includes an ablation or denervation port at the proximal end of the shaft. An ablation or denervation port is in fluid communication with the at least one needle to supply ablation energy or agent thereto. 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 at least one needle into the body cavity, into a wall of the body cavity, or outside the body cavity.

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 for infusion therapy disposed near the distal end of the shaft. The delivery catheter includes an inflatable balloon disposed near the distal end of the shaft such that when the delivery catheter is placed in the lumen and the balloon is inflated, the distal end of the catheter shaft is centered within the lumen. The delivery catheter also includes a marker band located at the distal end of the shaft.

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 for infusion therapy disposed near the distal end of the shaft. The delivery catheter also includes a steering mechanism associated with the shaft such that the distal end of the shaft is steerable in a direction away from the longitudinal axis of the shaft.

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 also includes one or more needles for infusion therapy disposed near the distal end of the shaft. The delivery catheter further comprises an inflatable balloon disposed near the distal end of the shaft such that when the delivery catheter is placed in the 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 comprises 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 the longitudinal axis of the shaft; or a combination thereof.

Embodiments of the invention relate to the treatment of 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumors, pain, rheumatoid arthritis, asthma, and Chronic Obstructive Pulmonary Disease (COPD) by delivering an effective amount of the formulation to a target tissue. Such formulations include a gas, vapor, liquid, solution, emulsion, suspension, or combination thereof, of one or more ingredients. The method includes the controlled delivery of the formulation to luminal surfaces and tissues within the human body, thereby modifying these regions. Such methods can result in denervation of nerves and nerve endings within and adjacent to the body cavity. The method may further comprise beneficially severing nerves and nerve endings to interrupt neural communication. Temperature can improve the safety and effectiveness of the therapeutic formulation. The temperature of the formulation may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. In some embodiments, the formulation includes one of a binary, ternary, or quaternary component, and may 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 formulations into body tissues and the luminal nerves and nerve endings.

In one embodiment, the formulation comprises water, saline, hypertonic saline, phenols, methanol, ethanol, absolute alcohol (absolute alcohol), isopropanol, propanol (propanol), butanol (butanol), isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide (propyl iodide), isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodophor, surfactants, derivatives thereof, or combinations thereof.

In one embodiment, at least one component of the formulation is a gas. The gas comprises one of: oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, water, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, derivatives thereof, and combinations thereof.

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

In one embodiment, the formulation includes at least one of an oil, a fatty acid, and a lipid. In some embodiments, at least one of the oils, fatty acids, and lipids in the formulation is selected from butyric acid (butanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid), lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, eicosenoic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienols, butyric acid (butanoic acid), caproic acid (caproic acid), caprylic acid (caproic acid), capric acid (capric acid), lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di-or triacylglycerol, cardiolipin, phosphatidylglycerol, or phosphatidylglycerol, Phosphatidic acid, phosphatidylcholine, alpha-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobee, vesicles (niosomes) and derivatives thereof.

In another embodiment, the formulation includes a therapeutic agent or drug for denervation of nerves. The therapeutic agent includes at least one of: sodium channel blockers, tetrodotoxin (tetrodotoxin), saxitoxin (saxitoxins), decarbamoylshizotoxin (decarbamoylshixins), vanilloids (vanilloids), neosaxitoxin (neosaxitoxins), lidocaine (lidocaines), conotoxins (conotoxins), cardiac glycosides (cardiac glycosides), digoxin (digoxin), glutamates (glutamates), staurosporins (staurosporines), amlodipine (amyodies), verapamides (verapamides), magnetocannabinoids (cymarins), digitoxins (digitoxins), proscilarides (proteoliaridins), quabains (veratrididines), macrolides (macrolides), chondroitins (acetogenins), macrolides (guanethionins), and guanethionins (guanethiidines). In another embodiment, the formulation includes a contrast agent for imaging denervation of nerves. Such contrast agents include one of the following: iodine, ethyl iodide, sodium iodide, lipiodol (lipiodol), nonylphenol polyether iodide (nonoxynol iodide), iobitridol (iobitridol), iohexol (iohexol), iomeprol (iomeprol), iopamidol (iopamidol), iopentol (iopentol), iopromide (iopromide), ioversol (ioversol), ioxilan (ioxilan), iotrolan (iotrolan), iodixanol (iodixanol), iodixanoic acid (ioxaglate), derivatives thereof, and combinations thereof.

In one embodiment, the formulation comprises an azeotrope. An azeotrope is a mixture of two or more components that cannot be altered by simple distillation. This occurs because the vapor produced upon boiling has a composition that is proportional to the composition 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.

In one embodiment, the formulation is in a gas or vapor state and comprises one or more ingredients. The vapor or gas formulation may include oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, water, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl 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 may include more than four components. The vapor formulation may include an azeotrope or a contrast agent, such as iodooil or iodine, and may include a surfactant and/or a therapeutic agent. The temperature of the vapor formulation may be from 0 to 140 ℃, preferably from 15 to 100 ℃, most preferably from 20 to 85 ℃, or 0 ℃ 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 ℃ or more.

In one embodiment, the formulation is in a liquid state and includes one or more ingredients. The liquid formulation may include one of: water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodized oil, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, surfactants, and others. The liquid formulation may include an azeotrope or a contrast agent and may include a therapeutic agent. In one embodiment, the formulation may include one of a binary, ternary, or quaternary component, and may also include more than four components. In some embodiments, the liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. Liquid formulations may include solutions, suspensions, emulsions, or combinations thereof.

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 the therapeutic formulation into a tissue of the body, wherein the amount of formulation delivered is effective to beneficially damage or compromise the tissue; optionally removing the formulation; and removing the delivery catheter from the body. The damage or damage to the tissue may relieve the symptoms of the disease, for example, by lowering blood pressure, lowering blood glucose levels, reducing weight, relieving shortness of breath, relieving heart disease, relieving a vascular condition, relieving joint pain, relieving stiffness, relieving swelling, or a combination thereof. The at least one disease for which the treatment is directed includes one or more of: hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, and Chronic Obstructive Pulmonary Disease (COPD). It may be more effective to treat multiple related diseases in one procedure, for example, for patients suffering from two or more of hypertension, obesity and type 2 diabetes simultaneously. The tissue that may be treated may include renal arteries (e.g., left main renal artery, right main renal artery, renal artery branches, left renal artery branches, right renal artery branches, distal end of left main renal artery, distal end of right main renal artery, distal end of left main renal artery branches, or distal end of right main renal artery branches), renal veins, gastric arteries, gastric veins, hepatic arteries, hepatic veins, pulmonary arteries, pulmonary veins, celiac artery, celiac vein, gastroduodenal artery, gastroduodenal vein, splenic arteries, splenic veins, adrenal arteries, adrenal veins, diaphragmatic arteries, diaphragmatic veins, mesenteric arteries, airways, esophagus, stomach, duodenum, jejunum, and urinary lumen. The digestive lumen may include the esophagus, stomach, duodenum, jejunum, small and large intestines, and colon. The formulation may include a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof, of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, cooling or heat may be generated by the formulation temperature being below or above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. In one embodiment, the formulation temperature may be equal to room temperature. In one embodiment, the formulation temperature may be from-40 to-20 ℃. In another embodiment, the formulation temperature may be 15 to 80 ℃. In one embodiment, the formulation temperature may be equal to body temperature. In another embodiment, the formulation temperature may be 50 to 80 ℃. In another embodiment, the temperature of the tissue being treated can be below the temperature of the formulation and above body temperature. The temperature of the tissue being treated may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃ or-40 ℃ or lower, or less than, equal to or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 ℃ or higher. In one embodiment, the temperature of the tissue being treated may be-40 to-20 ℃. In another embodiment, the temperature of the treated tissue may be 15 to 80 ℃. In one embodiment, the temperature of the treated tissue may be equal to body temperature. In another embodiment, the temperature of the treated tissue may be 50 to 80 ℃. Delivery catheters suitable for such treatment include needles under imaging guidance or needle-based catheters. The imaging guide includes one of: ultrasound, X-ray, CT scan, MRI, OCT, or oscilloscope. The delivery catheter may also be balloon-based. Such balloon-based catheters may have both a balloon and a needle in one catheter. The delivery catheter may be jet-based. Spray-based conduits can produce very fine mist to large droplets. In some embodiments, a combination of a balloon and jet catheter may be used in a procedure (e.g., without a needle), a combination of a needle catheter and jet catheter may be used, or a combination of a needle catheter, jet catheter, and balloon catheter may 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 escaping (runaway) chemical from entering the distal portion of the untreated region; flushing from the delivery catheter; irrigation from the endoscope; removing or withdrawing the formulation from the body tissue and cavity after treatment; and the treated target area is flushed with saline. The method may further include deploying the needle, administering the formulation from the needle, and retracting the needle, if present.

In one embodiment, the delivery catheter comprises 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 substantially center the distal end of the catheter in the lumen, or to substantially center the portion of the catheter out of which the needle emerges in the lumen. The user has better control over the needle and injection depth when the distal end of the catheter is centered in the treatment cavity. 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 may be positioned at the proximal or distal end of the balloon, but in either case adjacent to the balloon to take advantage of the catheter shaft being centered in the treatment lumen. In one embodiment of the needle-catheter, there is no centering balloon.

In one embodiment, the delivery catheter comprises a jet catheter. In this embodiment, the formulation is delivered through a jet orifice at or near the distal end of the catheter, so as to be delivered in an aerosol form to the wall of the treatment lumen. This embodiment may include a sleeve positioned over the spray orifices to provide a more even distribution of the formulation to the walls of the treatment cavity. This embodiment may include a vacuum port for removing excess formulation from the treatment cavity.

Drawings

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

FIG. 1 is an exemplary embodiment of a perspective view of a dual balloon delivery catheter according to the present invention.

Fig. 2 is an embodiment showing the infusion of a formulation into the airway using a jet catheter.

Fig. 3 is an embodiment showing the infusion of a formulation into the renal artery using a three-needle balloon delivery catheter.

FIG. 4 is an embodiment of a partial cross-sectional view of a dual balloon delivery catheter in a body lumen.

Fig. 5 is an embodiment of a partial cross-sectional view of a three-needle dual balloon delivery catheter with a needle deployed in a body lumen.

Fig. 6A is an exemplary embodiment of a perspective view of an over-the-wire (otw) three-needle balloon delivery catheter of the monolithic exchange type according to the present invention.

Fig. 6B is an exemplary embodiment of a perspective view of an OTW three-needle balloon delivery catheter with a balloon and needle deployed according to the present invention.

Fig. 7A is another exemplary embodiment of a perspective view of a rapid exchange three needle balloon delivery catheter prior to needle deployment according to the present invention.

Fig. 7B is an exemplary embodiment of a perspective view of a rapid exchange three needle balloon delivery catheter with an irrigation lumen after needle deployment according to the present invention.

Fig. 7C is a cross-section at section 7C-7C of the catheter shown in fig. 7B, according to various embodiments.

Fig. 7D is a cross-section at section 7D-7D of the catheter shown in fig. 7B, according to various embodiments.

Fig. 7E is a cross-section at section 7E-7E of the catheter shown in fig. 7B, according to various embodiments.

Fig. 7F is an alternative cross-section at section 7F-7F of the catheter shown in fig. 7B, according to various embodiments.

Fig. 7G is a cross-section at section 7G-7G of the catheter shown in fig. 7B, according to various embodiments.

Fig. 8A is an exemplary embodiment of a perspective view of a steerable catheter prior to needle deployment.

Fig. 8B is an exemplary embodiment of a perspective view of a steerable catheter after needle deployment.

Fig. 9A is an exemplary embodiment of a perspective view of a steerable catheter prior to needle deployment.

Fig. 9B is an exemplary embodiment of a perspective view of a steerable catheter with needle deployment.

Fig. 9C is an embodiment of a partial cross-sectional view of a unidirectional steerable catheter with a needle deployed in a body lumen.

Figure 10 is a bar graph illustrating a reduction in Norepinephrine (NE) following renal denervation in an ethanol treated group versus a control treated group, according to various embodiments.

Fig. 11 is a histopathological image demonstrating severed renal nerve necrosis (as indicated by black arrows) following ethanol treatment, according to various embodiments.

Figure 12 is a bar graph illustrating a reduction in Norepinephrine (NE) following hepatic denervation from an ethanol treated group versus a control treated group, according to various embodiments.

FIG. 13 is an exemplary embodiment of a perspective view of a spray conduit according to the present invention.

Fig. 14 is an exemplary embodiment of a perspective view of a jet catheter having dual suction features in accordance with the present invention.

Fig. 15A is an embodiment of the infusion of formulation into the left gastric artery using a three needle balloon delivery catheter.

Fig. 15B is an embodiment of the infusion of formulation into the hepatic artery using a three needle balloon delivery catheter.

Detailed Description

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

Throughout this document, values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted as including not only about 0.1% to about 5%, but also including individual values (e.g., 1%, 2%, 3%, and 4%) and sub-ranges within the indicated 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 specified, the expression "about X, Y or about Z" has the same meaning as "about X, about Y, or about Z".

In this document, the terms "a," "an," or "the" are used to include one or more, unless the context clearly dictates otherwise. The term "or" is used to refer to a non-exclusive "or" unless otherwise indicated. 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". Also, it is to be understood that the phraseology or terminology employed herein, and not otherwise defined, is for the purpose of description only and not of limitation. Any use of section headings is intended to facilitate reading of the document and should not be construed as limiting; information related to the section title may appear within or outside of that particular section.

In the methods described herein, acts may be performed in any order, except where specific temporal or operational sequences are explicitly recited, without departing from the principles of the invention. Further, specified actions can be taken concurrently unless explicitly stated in the claim language that they are taken separately. For example, the act of performing X as claimed and the act of performing Y as claimed may occur simultaneously within a single operation, and the resulting method will fall within the literal scope of the claimed method.

The term "about" as used herein may allow for a degree of variability within a value or range, e.g., within 10%, within 5%, or within 1% of a specified limit of a specified value or range, and includes the precise specified value or range.

The term "substantially" as used herein means the majority, or predominantly, such as at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. The term "substantially free" as used herein may mean free or in a negligible amount such that the amount of material present does not affect the material properties of a composition including the material, such that about 0 wt% to about 5 wt% of the composition is the material, or 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%.

As used herein, the term "polymer" refers to a molecule having at least one repeating unit and may include copolymers.

In various embodiments, the invention provides methods 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 treating at least two different target tissues in at least two different body lumens using a delivery catheter. The method includes performing a treatment procedure on a body lumen that is a first body lumen. The treatment procedure may include inserting a delivery catheter into the body cavity. The delivery catheter may 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 may 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 damage or impair the target tissue to alleviate symptoms of the disease. The treatment procedure may include deflating the balloon. The treatment procedure may also include removing the delivery catheter from the body lumen. The method may include performing a treatment procedure on a second body lumen different from the first body lumen.

Performing a treatment procedure on the second body lumen may include using the same delivery catheter or a different delivery catheter. Performing the treatment procedure with the second body lumen may include reusing the same delivery catheter used in the treatment procedure with the second body lumen as used in the treatment procedure with the first body lumen. Performing the treatment procedure with the second body lumen may include using a different delivery catheter in the treatment procedure with the second body lumen than in the treatment procedure with 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.

Treating at least two different target tissues in at least two different body lumens refers to treating at least two types of body lumens selected from the group consisting of: renal artery, renal vein, gastric artery, gastric vein, hepatic artery, hepatic vein, pulmonary artery, pulmonary vein, celiac artery, celiac vein, gastroduodenal artery, gastroduodenal vein, splenic artery, splenic vein, adrenal artery, adrenal vein, diaphragmatic artery, diaphragmatic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, and urinary lumen. The renal arteries may include 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, and a distal end of the right main renal artery branch. The gastric arteries may include a left gastric artery, a right gastric artery, a left gastric artery branch, and a right gastric artery branch. Hepatic arteries may include hepatic artery, common hepatic artery, intrinsic hepatic artery, left hepatic artery, middle hepatic artery, and hepatic artery branches. The splenic artery may include a main splenic artery and a branch of the splenic artery. The adrenal arteries can include the right and left adrenal arteries. The phrenic arteries may include the right and left phrenic arteries. Mesenteric arteries can include superior mesenteric arteries, inferior mesenteric arteries, and branches of mesenteric arteries. The urinary lumen may include the urethra and the ureter. For example, treatment of the left gastric artery and left gastric artery branch is considered a type of treatment of body lumens. Treatment of the left gastric artery and the main splenic artery is considered as treatment of two different types of body cavities. Treating at least three different target tissues in at least three different body lumens, or treating at least four different target tissues in at least four different body lumens, respectively, is defined as treating three or four different types of body lumens, respectively.

The target tissues of the first body lumen and the second body lumen may be different and may be independently selected from the target tissues of the 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, or distal end of right main renal artery branch), renal vein, gastric artery, gastric vein, hepatic artery, hepatic vein, pulmonary artery, pulmonary vein, celiac artery, celiac vein, gastroduodenal artery, gastroduodenal vein, splenic artery, splenic vein, adrenal artery, adrenal vein, diaphragmatic artery, diaphragmatic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, and urinary lumen. The disease to be treated may be selected from hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), and combinations thereof.

Alleviation of symptoms of the disease includes alleviation of symptoms of hypertension, diabetes, obesity, coronary heart disease, peripheral disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cancer, arthritis, or a combination thereof. Alleviating the symptoms of the disease may include lowering blood pressure, lowering blood glucose levels and AIC, reducing weight, reducing restenosis, reducing liver fat, and reducing pain, or a combination thereof.

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

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

The delivery catheter may be a chemical infusion delivery catheter. The delivery catheter may be an energy delivery catheter. The delivery catheter may 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 formulation vapor into a liquid, or a combination thereof. Thus, the energy delivery catheter may be one of a radio frequency catheter, a cryoablation catheter, a microwave catheter, a laser catheter, an ultrasound catheter, a high intensity focused ultrasound catheter, an infusion catheter, or a combination thereof.

The delivery catheter may 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 may arise during the energy delivery. Examples of such complications include thrombosis, steam pops, effervescence, charring of the target tissue, restenosis, fibrosis of the media and adventitia, and others associated with catheter manipulation (i.e., perforation). Spot thermal ablation (RF ablation) is not uniform and does not reach the adventitial nerve. Partial point 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 act as an electrode (e.g., the needles can be insulated to leave only a portion for exposing the electrode, e.g., a needle non-insulated portion of 1mm to 5mm length; in other embodiments, the needles are not insulated). The needles used for radiofrequency ablation may be the same as the needles used for chemical infusion described herein, or they may be different. For example, the radiofrequency energy delivery needle can have any suitable diameter, can be solid or hollow, and can be used to deliver radiofrequency energy to the body cavity, a wall of the body cavity, or the exterior of a wall of the body cavity. For radio frequency delivery, the return electrode may be positioned on the catheter, or a device such as a pad may be used. The delivery catheter may include one or more electrodes on a wire (e.g., a wire having a spring or shape memory property to ensure good contact with the target tissue), one or more electrodes on a polymer shaft, one or more electrodes on an outer surface of the balloon, or a combination thereof. The delivery catheter may include more than one electrode to achieve a shorter treatment time. The method may include cooling the electrode, for example via passive cooling of the blood flow and/or via active fluid cooling, for example internal active cooling (closed loop) or external active fluid cooling (open loop). The size of the electrode may be reduced to increase passive cooling by blood flow. Cooling the electrode may increase energy delivery into the neural tissue of the target tissue. Cooling the needle electrode may include flowing a coolant or a liquid (e.g., a chemical or different liquid composition as described herein) that enhances RF delivery through the needle before, during, or after radiofrequency delivery. In one embodiment of external cooling (open loop) of the electrode, the chemical formulations described herein may replace the active cooling fluid. The disclosed formulations can be used not only to cool electrodes, but also for chemical ablation of target tissue. In some embodiments, the agents can uniformly diffuse and penetrate into the nerve tissue, and they can uniformly ablate nerves in the adventitia in the body lumen. Thus, the chemical ablative agent can be delivered during, before, and/or after energy ablation.

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

For any type of energy delivery, the method of using the delivery catheter may include cooling the energy source through the flush lumen to reduce the temperature of the energy source and clean the lumen (e.g., clean the artery and prevent blood blockage). In various embodiments, the needle may be used for cooling. A delivery catheter for energy delivery may include a guidewire lumen to facilitate insertion and placement of the delivery catheter.

In some embodiments, the delivery catheter is electrodeless. The delivery catheter may be devoid of any source of ablation energy, such as radiofrequency, ultrasound, and microwave energy sources.

Embodiments of the invention relate to treating at least one disease by delivering an effective amount of agent and/or energy to a target tissue. The disease may include hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), or a combination thereof. The cancer includes adrenal gland cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, renal cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, uterine cancer or their combination. The formulation may include a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof, of one or more ingredients. The methods include delivering agents and/or energy to luminal surfaces, tissues and nerves of the human body to modify these surfaces. The 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 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, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a diaphragmatic vein, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof. The digestive lumen includes the esophagus, stomach, duodenum, jejunum, small and large intestine, colon, or combinations thereof. Temperature can improve the safety and effectiveness of the therapeutic formulation. The temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the tissue being treated may be different from the formulation temperature. The temperature of the tissue being treated may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃ or-40 ℃ or lower, or less than, equal to or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 ℃ or higher. The amount of agent and energy delivered can be effective to beneficially damage, or eliminate (e.g., kill) the target tissue and thereby alleviate symptoms of the disease, for example, by lowering blood pressure, shrinking a tumor, alleviating pain, alleviating symptoms of asthma or COPD, or a combination thereof. The energy or heat may enhance the damaging/ablating effect by accelerating the rate of reaction between the agent and the tissue. The delivery method includes delivering the agent to ablate nerves around the body cavity of the human. The method may include removing or withdrawing the formulation from the tissue or cavity after treatment. Without direct observation, nerve ablation can be identified based on physiological functions corresponding to the nerve, such as glucose and Norepinephrine (NE) levels. Norepinephrine is the primary neurotransmitter used by the sympathetic nervous system, which is linked to many organs, including, for example, the heart, lungs, liver, spleen, gall bladder, stomach, intestines, kidneys, bladder, and many others. For example, in the liver, increasing the sympathetic effects of norepinephrine increases glucose production by postprandial glycogenolysis or gluconeogenesis when not recently eaten. Thus, correction of hyperactive hepatic sympathetic nerves will reduce NE content and result in lower glucose levels. In the kidney, the release of renin and retention of sodium in the bloodstream increases blood pressure. The Norepinephrine (NE) content of the tissue can be used as a biomarker to demonstrate or indicate a therapeutic effect. Various embodiments of the methods comprising treating hyperactive hepatic sympathetic nerves can result in a reduction in NE content of 20% to 99%, preferably, 50% to 98%, and most preferably, 75% to 97%, as compared to untreated (control) subjects.

In one embodiment, the formulation is a single chemical or one of a binary, ternary or quaternary component, and may also include more than four components. In one embodiment, the delivery system may be used with a less invasive percutaneous approach or a non-invasive approach. Embodiments of the present invention provide formulations comprising one or more ingredients that effect surface modification of body lumens by absorption and penetration into the tissues of the body lumens as well as nerves and nerve endings.

In one embodiment, the formulation may comprise or consist of: water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodophor, a surfactant, a derivative thereof, or a combination thereof.

In one embodiment, the ingredient of the formulation is at least one gas. The gas may be selected from the group consisting of oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, water, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

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 laurate, PEG oleate, PEG stearate, polyglycerol laurate, polyglycerol oleate, polyglycerol myristate, polyglycerol palmitate, polyglycerol-6 laurate, polyglycerol-6 oleate, polyglycerol-6 myristate, polyglycerol-6 palmitate, polyglycerol-10 laurate, polyglycerol-10 oleate, polyglycerol-10 myristate, polyglycerol-10 palmitate, polyglycerol sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, organic acids, PEG sorbitan monolaurate, and mixtures thereof, Salts of any organic acid and organic amine, polyglycidyl, glycerol, polyglycerol, galactitol, di (ethylene glycol), tri (ethylene glycol), tetra (ethylene glycol), penta (ethylene glycol), poly (ethylene glycol) oligomer, di (propylene glycol), tri (propylene glycol), tetra (propylene glycol), penta (propylene glycol), poly (propylene glycol) oligomer, block copolymers of polyethylene glycol and polypropylene glycol, Pluronic 85, derivatives thereof, and combinations thereof. In some embodiments, the surfactant may be present in the formulation in an amount of 0.1 to 80% by weight, preferably 0.5 to 50% by weight, most preferably 1 to 15% by weight.

In one embodiment, the formulation includes at least one of an oil, a fatty acid, and a lipid. The oils, fatty acids and lipids in the formulation may be selected from: butyric acid (butanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid), lauric acid, myristic acid, palmitic acid, stearic acid, octadecanoic trienic acid, arachidic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienols, butyric acid (butyric acid), caproic acid (caproic acid), caprylic acid (caproic acid), capric acid (capric acid), lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di-or triacylglyceroglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, alpha-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidic acid, palmitic acid, myristic acid, oleic acid, vaccenoic acid, linoleic acid, caproic acid, or a-fatty acids, or fatty acids, Phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobee, vesicles (niosomes), derivatives thereof, and combinations thereof.

In one embodiment, the formulation includes a therapeutic agent or drug for denervation and surface modification of nerves. The therapeutic agent is at least one of: sodium channel blockers, tetrodotoxin (tetrodotoxin), saxitoxin (saxitoxins), decarbamoylshizotoxin (decarbamoylshixins), vanilloids (vanilloids), neosaxitoxin (neosaxitoxins), lidocaine (lidocaines), conotoxins (conotoxins), cardiac glycosides (cardiac glycosides), digoxin (digoxin), glutamates (glutamates), staurosporins (staurosporines), amlodipine (amyodies), verapamides (verapamides), magnetocannabinoids (cymarins), digitoxins (digitoxins), proscilarides (proteoliaridins), quabains (veratrididines), macrolides (macrolides), chondroitins (acetogenins), macrolides (guanethionins), or guanethionins (guanethiidines). In another embodiment, the formulation includes a contrast agent for imaging denervation of nerves. Such contrast agents include iodine, ethyl iodide, sodium iodide, lipiodol (lipiodol), nonylphenol polyether iodide (nonoxynol iodide), iobitridol (iobitridol), iohexol (iohexol), iomesrol (iomeprol), iopamidol (iopamidol), iopentol (iopentol), iopromide (iopromide), ioversol (ioversol), ioxilan (ioxilan), iotrolan (iotrolan), iodixanol (iodioxanol), iodixanol (ioxaglate), derivatives thereof, and combinations thereof. The content of the contrast agent in the formulation may be 2-25% by weight, preferably 5-15% by weight.

In one embodiment, the formulation comprises an azeotrope. An azeotrope is a mixture of two or more components that cannot be altered by simple distillation. This occurs because the vapor produced upon boiling has a composition that is proportional to the composition of the original mixture. The azeotrope of the formulation may 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.

In one embodiment, the formulation is in a gaseous or vapor state and includes one or more ingredients. In one embodiment, the gas or vapor formulation comprises: oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, or combinations thereof. Vapors of organic and inorganic compounds include one of: water, phenol, methanol, ethanol, absolute ethanol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

In one embodiment, the vapor formulation includes at least one contrast agent, such as iodooil or iodine, and an azeotrope, and may further include a surfactant and/or a therapeutic agent. In one embodiment, the vapor is one of a binary, ternary, or quaternary component, and may also include more than four components. The temperature of the vapor formulation can be 0 to 140 ℃, 15 to 100 ℃, 30 to 80 ℃, or 0 ℃ 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 ℃ or more.

In one embodiment, the formulation is in a liquid state and includes one or more ingredients. The liquid formulation includes at least one of: water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodized oil, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, surfactants, and the like, and combinations thereof. In one embodiment, the liquid formulation comprises one of a contrast agent and an azeotrope, and may further comprise a therapeutic agent. In one embodiment, the liquid formulation is one of a binary, ternary, or quaternary component, and may also include more than four components. In one embodiment, the liquid formulation comprises a solution, emulsion or suspension. The temperature of the liquid formulation may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. In one embodiment, the formulation temperature may be room temperature. In one embodiment, the formulation temperature may be from-40 to-20 ℃. In another embodiment, the formulation temperature may be 15 to 80 ℃. In one embodiment, the formulation temperature may be equal to body temperature. In another embodiment, the formulation temperature may be 50 to 80 ℃.

In one embodiment, a method of treating at least one disease comprises inserting a delivery catheter into the body transdermally or orally; infusing the formulation and/or delivering energy to a target tissue or cavity within the body using a catheter; optionally removing or withdrawing the formulation from the target tissue or body cavity; and removing the delivery catheter from the body. The one or more diseases for treatment may include hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), or a combination thereof. The cancer may include 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 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 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, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a diaphragmatic vein, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof. The digestive lumen may include the esophagus, stomach, duodenum, jejunum, small and large intestines, colon, or combinations thereof. The formulation may include one or more ingredients of gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof. In embodiments where the agent comprises a vapor of one or more components, heat may be generated by condensation of the vapor into a liquid in the tissue. In embodiments where the formulation comprises a liquid or solution, cooling or heat may be generated from the formulation temperature below or above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. In one embodiment, the temperature of the tissue being treated may be different from the formulation temperature and lower or higher than the body temperature. The temperature of the tissue to be treated may be 15 to 100 ℃, more preferably 20 to 90 ℃, most preferably 36 to 80 ℃. In another embodiment, the temperature of the tissue being treated may be from-40 to-20 ℃. In some embodiments, the delivery catheter is an imaging guided needle or needle-based catheter. The imaging guide may be ultrasound, X-ray, CT scan, MRI, OCT, scope (scope), or a combination thereof. The delivery catheter may be a balloon-based needle catheter. The balloon-based needle catheter may have a single balloon or a double balloon. Balloon-based catheters may have a single needle, double needle, or triple needle. Infusion may come from a needle catheter assembly and may be defined as a needle infusion method. The infusion volume may be 0.1mL to 5mL, preferably 0.2mL to 2.5mL, most preferably 0.3mL to 1.5 mL. If the delivery catheter is a balloon and needle infusion combination device, the balloon pressure may be maintained during the infusion period in the range of 0.1 to 3atm, preferably 0.1 to 2atm, and most preferably 0.3 to 1 atm. Optionally, such low pressure balloon inflation may be operated and maintained using a syringe, and balloon size may be observed in real time by fluoroscopy. The formulation infusion temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. More detailed examples of catheters, such as single and double balloon needle delivery catheters, are shown in the following sections.

In one embodiment, the infusion lumen may be at least one needle, such as a single needle or multiple needles (fig. 3 and 5-9). The needle tip may be movable and may be positioned in the cavity wall or outside the cavity wall by piercing the cavity wall for delivery of the formulation. The needle can be very small and can have a diameter (outer diameter, OD) of about 200pm to 500pm, preferably about 300pm to 400 pm. The small size of the needle may prevent or significantly reduce leakage or bleeding after puncture and removal. The needle device can directly and accurately infuse the preparation into the adventitia layer of the cavity tissue, realizing deep treatment. The infusion time of the needle device is within 3 minutes, preferably between 5 and 150 seconds.

In one embodiment, the formulation is or includes ethanol. The formulation may be delivered to the tissue of the body cavity in vapor or liquid form. The vapour or liquid formulation temperature may be from-40 to 150 ℃, preferably from-30 to 100 ℃, most preferably from-20 to 80 ℃. The temperature of the tissue may be-40 to 90 deg.C, preferably-30 to 80 deg.C.

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

In another embodiment, the formulation is a mixture of vapors comprising water, ethanol, and oxygen. In another embodiment, the formulation is a mixture of vapors comprising water, ethanol, and air. In another embodiment, the formulation is a mixture of vapors comprising water, ethanol, oxygen, and nitrogen. Formulations containing oxygen and air are particularly useful for treating asthma and COPD.

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

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

In another embodiment, the formulation is a composition comprising ethanol and iodooil (e.g., iodine oil)

ULTRA-fluid) in a liquid, including an effective amount of iodooil to enable imaging of the mixture of vapors in the wall of the body cavity, and also beneficially damage the target nerve tissue. The iodooil content of the formulation may be from 10 to 80 wt%, preferably from 15 to 75 wt%, most preferably from 20 to 50 wt%. The formulation may be or include a mixture of liquids including water and iodophor oil, or a mixture of liquids including acetic acid and iodophor oil. The iodooil content of the formulation may be in the range 10 to 80 wt%, preferably 15 to 75 wt%, most preferably 20 to 50 wt%.

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 may be guided to the delivery site by X-ray or ultrasound imaging guidance. The needle-based balloon delivery catheter may have one or two balloons. Using a needle device, the agent infusion can be in or outside the lumen wall (e.g., intraluminal or extraluminal).

In one embodiment, the delivery catheter is a jet catheter. The application of the formulation may reach the inner wall of the body cavity. In some embodiments, the direction of the spray of the device is designed to be approximately perpendicular to the chamber wall. The spray catheter may be needle free or may include a needle for both spray-based and needle-based administration of the formulation. The jet catheter may include a centering balloon, or may be free of a balloon. The jet catheter can optionally include the ability to deliver energy to the target tissue, such as radio frequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound, or combinations thereof.

As shown in fig. 1, the delivery catheter 10 has an elongate shaft 11 having at least one lumen, a distal end 13, and a proximal end 14. At the distal end 13 are proximal 20 and distal 21 lumen-compliant (lumen-conforming) balloons. In any configuration, the tube of the catheter shaft 11 may be extruded from a plastic material such as a thermoplastic, polyimide, polyetherimide, polyethylene, polyurethane, polyester, polyamide, Pebax, nylon, fluorinated polyurethane, polyetheretherketone, or polysulfone, or the like, or combinations thereof. The catheter shaft 11 may be extruded or formed to have a variety of lumen cross-sections, including circular or elliptical lumens. Further, as shown in fig. 1, the catheter 10 may be equipped with an irrigation 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 separately. A lumen-compliant balloon is a balloon that can be inflated at a pressure less than that required to deform the lumen wall. The balloon material is selected to be flexible and usable at high temperatures so that the balloon is compliant when inflated. In one embodiment, the balloon material is one of polyamide, nylon, Pebax, polyester, polyethylene terephthalate, or copolymers thereof. The inflated diameter of the balloon may range from about 2mm to about 40mm, depending on the diameter of the treatment site. In one embodiment, each balloon is about 2 millimeters ("mm") in diameter. Alternatively, the inflated diameter of each balloon is less than, equal to, or greater than about 3mm, 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 about 40mm or more.

In one embodiment, at least one marker band 22b is located proximal to the proximal balloon 20 and at least one marker band 23a is located distal to the distal balloon 21. The balloon catheter may be an over-the-wire (rapid exchange) catheter made of any suitable biocompatible material. Marker bands may also be positioned at the other end (22a and 23b) of the balloon. Segment 25 is located between

balloons

20 and 21, has at least one infusion orifice, has a non-inflatable portion 30 and a shaft adjacent to balloon portion 24. Ports 40 and 41 for balloon inflation are for the distal and proximal balloons, respectively. The infusion port 42 is used to infuse chemicals.

The material of the

balloons

20 and 21 includes 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 the balloon 21 is equal to or smaller than the diameter of the balloon 20.

A schematic diagram of an embodiment of a jet catheter positioned within the left main bronchus for treating asthma and COPD is shown in fig. 2. The delivery catheter 198 of fig. 2 can treat the airway distal to the main bronchi 21 and 22. For example, the delivery catheter 198 may be positioned to the passage of passage 6 or even 8 to affect the distal portion of the bronchial tree 27. Delivery system 198 may be navigated through tortuous airways to perform a wide range of procedures, such as, for example, denervation of a portion of a leaf, an entire leaf, multiple leaves, or one or both lungs. In some embodiments, the lobar bronchi are treated to denervate the pulmonary lobes. For example, one or more treatment sites along the lobar bronchus may be targeted to denervate the entire leaflet attached to the lobar bronchus. The left-lobe bronchus may be treated to affect the upper left lobe and/or the lower left lobe. The right lobar bronchus may be treated to affect the right superior, right middle, and/or right inferior lobes. The leaves may be treated simultaneously or sequentially. In some embodiments, the physician can treat a leaf (lobe). Based on the effectiveness of the treatment, the physician may treat additional lobes simultaneously or sequentially. In this way, different isolated regions of the bronchial tree can be treated.

The delivery catheter 198 may also be used for segmental or sub-segmental bronchoscopy. Each segmental bronchus may be treated by delivering agents and/or energy along the segmental bronchus to a single treatment site. For example, agents and/or energy may be delivered to each segmental bronchus of the right lung. In some procedures, one or two applications of the formulation may treat most or the entire right lung. Segmented bronchi can typically be denervated using one or two applications, depending on the anatomy of the bronchial tree.

The delivery catheter 198 may affect neural tissue while maintaining the function of other tissues or anatomical features, such as mucous glands, cilia, smooth muscle, body cavities (e.g., blood vessels or other body cavities), and the like. The neural tissue may include nerve cells, nerve fibers, dendrites, and supporting tissue, such as glial cells. Nerve cells transmit electrical impulses, and nerve fibers are elongated axons that conduct impulses. The electrical impulses are converted to chemical signals to communicate with effector cells or other neural cells. For example, the delivery catheter 198 can denervate a portion of the airway of the bronchial tree 27 to attenuate one or more nervous system signals transmitted by the nervous tissue. Denervation may include (by treatment of the present invention) cutting nerve tissue of a portion of the nerve trunk to prevent signals from propagating through that particular region to more distant locations along the bronchial tree. If multiple nerve trunks extend along the airway, each nerve trunk may be severed. Thus, the nerve supply along a portion of the bronchial tree may be cut off. When the signal is switched off, the distal airway smooth muscle relaxes, causing the airway to dilate. This airway dilation reduces airflow resistance, thereby increasing gas exchange within the lungs, thereby reducing or eliminating one or more clinical manifestations such as breathlessness, wheezing, chest tightness, and the like. Tissue surrounding or near the target nerve tissue may be affected, but not permanently severed. In some embodiments, for example, similar amounts of blood may be delivered to bronchial wall tissue along bronchial vessels of the airway being treated, and similar amounts of blood may be delivered to alveolar sacs in distal regions of bronchial tree 27 along pulmonary vessels of the airway being treated before and after treatment. These vessels can continue to transport blood to maintain adequate gas exchange. In some embodiments, airway smooth muscle is largely free from beneficial damage. For example, a relatively small portion of smooth muscle in the airway wall that does not significantly affect respiratory function may be reversibly altered by this method, for example by using a formulation at a regulated temperature, to avoid irreversibly damaging neural tissue outside the airway, such as non-target smooth muscle tissue.

The delivery system 198 of fig. 2 includes a treatment controller 202 and an intraluminal elongate assembly 200 coupled to the controller 202. The elongate assembly 200 may be inserted into the trachea 20 and navigated into and through the bronchial tree 27 with or without a delivery assembly, such as a guidewire. The elongate member 200 includes a distal tip 203.

The controller 202 of fig. 2 may include one or more processors, microprocessors, Digital Signal Processors (DSPs), Field Programmable Gate Arrays (FPGAs), Application Specific Integrated Circuits (ASICs), memory devices, buses, power supplies, pumps, agent resources, vapor resources, liquid resources, contrast resources, vapor generators, desired temperature agent generators, and the like.

The distal tip 203 of fig. 2 may be targeted to various locations in the lung 10, including but not limited to neural tissue, fibrous tissue, diseased or abnormal tissue, muscle tissue, blood vessels, various anatomical features (e.g., membranes, glands, cilia, etc.), or combinations thereof.

In one embodiment, a schematic view of a single balloon needle delivery catheter (shown as a three needle balloon catheter) positioned within the renal artery is shown in fig. 3, with the needle 110 shown extended. The delivery catheter 108 of fig. 3 can treat hypertension. The formulation may be infused through a needle for denervation into the wall or outer wall of the renal artery adjacent to the renal nerve. Nerve endings and small nerve fibers are typically located in the arterial wall, while large nerve fibers and nerve bundles are usually located outside or near the arterial wall. Different degrees of denervation can thus be achieved by controlling the needle penetration depth during the procedure. Some elements of the renal vasculature are omitted from fig. 3. In fig. 3, 102 is the kidney, 105 is the guiding catheter, 106 is the main renal artery, 108 is the three-wire balloon catheter, 109 is the guidewire, 301 is the abdominal aorta, and 502 is the extra renal artery. In fig. 3-5, 6A-6B, 7A-7G, 8A-8B, and 9A-9C, the needle delivery catheter is shown and described herein with respect to delivering a chemical through a needle; however, embodiments of the needle delivery catheter may additionally or alternatively be used to deliver energy to a target tissue in the form of radiofrequency, cryoablation, microwave, laser, and/or ultrasound, for example via a needle (e.g., radiofrequency, cryoablation) and/or by other sources (e.g., microwave, laser, ultrasound).

In another embodiment, the delivery catheter 108 of fig. 3 includes a balloon that is inflated to approximately center the catheter shaft so that when the needles are deployed as shown, the needles are equally spaced from the vessel wall and can be advanced through the arterial wall at a similar depth. In some embodiments, the renal artery is treated to treat hypertension. Because the needle pierces the vessel wall or beyond, the device is able to infuse the formulation into the vessel wall or outside the outer wall. Fig. 3 shows the infusion of the formulation through needle 110 into the outer wall of the main renal artery, directly onto the renal nerves (not shown) for denervation.

In another embodiment, a three-wire balloon catheter may be positioned within the extra renal artery 502 and the formulation may be infused into or out of the wall of these vessels. Although three needles are shown, any suitable number of needles may be used, such as one, two, three, four, five or more.

In another embodiment, one denervation procedure may treat the main renal artery and the extra renal artery. The three-needle balloon catheter is positioned within the main renal artery 106 and the extra-renal artery 502 in fig. 3 and infuses the agent into or out of the walls of the multiple renal arteries. Optionally, the artery may be treated at multiple locations depending on the length of the artery.

In one embodiment, a method of treating hypertension includes inserting a delivery catheter percutaneously into a renal artery and/or additional renal arteries adjacent to nerves and nerve endings; infusing the above-described formulation and/or energy into tissue of the body cavity adjacent the nerve using a delivery catheter, wherein the amount of the delivered formulation and/or energy is effective to beneficially damage the nerve and nerve endings; and removing the delivery catheter from the body lumen. Treatment will result in a decrease in blood pressure in the treated patient.

In one embodiment, the needle delivery catheter, e.g., as shown in fig. 3 and 5-9, may be used for treatment of hypertension by renal ablation, diabetes by hepatic denervation, and/or obesity by gastric denervation. In one embodiment, the catheter 10 disclosed herein (in fig. 1) helps regulate formulation flow and therapeutic dose throughout the therapeutic window 30, as shown in fig. 4. The balloons may be inflated through their inflation lumen. The location, diameter, number and frequency of exit holes 31 results in the agent being delivered to the treatment window 30 via a needle (not shown, in a retracted position). Fig. 4 depicts a catheter positioned in a body lumen 5 having two exit orifice 31 located within a treatment window 30 for delivery of a therapeutic agent via a needle. During use, the needle projects outwardly from the needle aperture, as shown in fig. 3. As shown in fig. 4, needle outlet port 31 includes a retraction needle in fluid communication with lumen 25. A needle positioned within the exit orifice 31 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 the agent is delivered to the treatment window 30 (e.g., into the lumen, the lumen wall, or outside the lumen wall).

The agent treatment port may be located between the balloons on the shaft. The agent infusion holes may be located on the non-inflatable shaft portion between the inflatable balloon portions. During treatment, the formulation may be expelled between the balloons through the infusion orifice to a treatment window space formed by the balloons. This is an infusion embodiment where the therapeutic mechanism is the application of the agent to the interior of the vessel wall and may include allowing the agent to diffuse out through the lumen wall for therapeutic efficacy.

In one embodiment, optionally, the residue of the chemical agent/formulation may be recovered after treatment by vacuum techniques on one or more infusion ports. In this case, at least two treatment chambers are preferred: one for infusion and the other for vacuum. The agent infusion holes and vacuum holes may be located on the non-inflatable shaft portion between the inflatable balloon portions.

In addition to removing excess therapeutic agent, the remaining agent can also be diluted with saline or water to ineffective concentrations. The irrigation may be performed with saline or water using one of the catheter wire lumens, infusion lumens, or by other means. The method used depends on the site of protection or treatment. Irrigation through the lumen of the thread may be performed if the distal portion of the blood vessel needs to be protected from treatment with the agent.

In one embodiment, when deep treatment of the adventitia and/or the periadventitial space is desired, a needle-based catheter may achieve the goal in that the needle-based catheter may infuse the agent through the at least one needle into the luminal or abluminal wall. To treat the cavity evenly around its circumference, a three (or more) needle balloon catheter infuses the formulation through the needle into the target area. Fig. 5 depicts a double balloon three needle catheter positioned in a body lumen 5 with three needles 50 deployed between the two balloons. When advanced, the three needles may have a diameter greater than the balloon diameter. The needle is in fluid communication with the agent source and delivers the agent directly onto the vessel wall or into the outer wall of the body lumen. In operation, a balloon needle catheter is advanced to a target lesion or site following standard procedures, both balloons are inflated to center the intermediate non-consumable (non-expandable) shaft, a needle is then deployed from the intermediate non-expandable shaft, and depending on the depth of needle penetration, for example, the tip of the needle may be located within or outside the wall, and formulation is delivered through the needle to the wall of the lumen or vessel or to the outer wall or wall of the vessel. After treatment, the needle is retracted into the shaft and the balloon is deflated and the catheter is ready for removal.

An example of a single balloon needle catheter is shown in fig. 6A and 6B. Fig. 6A shows the three-wire balloon catheter 600 in a ready-to-use state. The needle is contained within a distal head 601 (not shown) that is the distal portion of the catheter, with a void (not shown) containing the needle and a corresponding needle exit opening 612 positioned at the distal end of the balloon, wherein the needle exit opening allows the needle to protrude from the void upon needle deployment. The distal head may serve as a marker band, or alternatively, may include a marker band 602, and may be made of any medical grade metal, such as stainless steel, and may be atraumatic (tip 608) and radiopaque (e.g., when used as a marker band). The distal head and/or marker band can be seen under X-ray (fluoroscopy), which enables the physician to accurately position the needle. The catheter has an off-center wire lumen design 603 that allows for a smaller catheter profile, e.g., better compatibility with guiding catheters. The catheter shaft 610 may be a reinforced shaft, for example, reinforced by wire braiding to increase its crush resistance and tensile strength, enabling smooth and precise needle movement for manipulation at the proximal end of the catheter. Needle movement is controlled by a handle 604 at the proximal end connected to the agent source. A catheter that can be advanced over a guidewire for delivery is shown with an over-the-wire configuration for the guidewire lumen 603. Balloon 606 may be inflated through inflation lumen 605. Fig. 6B shows catheter 600 with needle 611 in an advanced state and balloon 606 inflated. The balloon just behind the needles may center the distal end of the shaft 610 so all three needles 611 may penetrate the vessel wall at a similar depth to ensure even delivery of the formulation around the circumference of the vessel. It may be desirable to position the balloon as close as possible to the needles so that the needles are more likely to be equidistant from the vessel wall. The distance between the needle exit opening on the distal head and the balloon cone/waist transition region may be about 2mm to 12mm, preferably about 5mm to 9 mm. Smaller needle diameters can result in less pronounced needle puncture wounds, which can result in faster puncture wound healing. The needle outer diameter may be about 0.20mm to 0.50 mm; preferably about 0.28mm to 0.38 mm. The needle curvature may be designed to enable the needle 611 to align vertically with the vessel wall when delivered.

The needle may be made of any suitable material, such as stainless steel, platinum, titanium, tantalum, platinum iridium, platinum chromium, nickel titanium (nitinol); cobalt-based alloys comprising 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 needle may be made of nitinol material and may have a shape memory of the designed curvature upon exiting the receiving hole/compartment. When a nitinol needle is small and thin, it may not be sufficiently radio-opaque under X-rays during surgery. However, it is important for the surgeon to know the position of the needle during the procedure. To accomplish this, the needle may be modified with any number of suitable radiopaque metallic materials, for example, by thin film sputtering of radiopaque material onto its surface, or attachment of radiopaque material to the needle (e.g., because a marker band may be included on the shaft), or a clad metallic needle/tube that combines one or two layers of radiopaque material with a nitinol needle/tube. The coating or cladding or additional joining material may include, but is not limited to, tungsten (W), gold (Au), tantalum (Ta), platinum (Pt), and iridium (Ir), or combinations thereof, or alloys thereof, to make the nitinol needle radiopaque. The radius of curvature of the needle 611 may be about 2mm to 6mm, for example about 3mm to 4 mm. In the fully deployed state, the needle tip-to-tip span diameter (the diameter of an imaginary circle touching all needle tips) may be 5mm to 40mm, or about 5mm to 30mm, for example about 5mm to 15 mm; this may be determined by the diameter of the blood vessel being treated and the required depth of needle penetration. For example, for a 6mm blood vessel and a needle penetration depth of 2mm, the needle tip-to-tip span distance may be about 10 mm.

After treatment, the needle is first retracted into the distal head or containment compartment, then the balloon is deflated and the catheter is removed. Optionally, the distal head, needle and treated vascular region may be flushed with saline or heparinized saline through the lumen of the wire (for over-the-wire catheters) or designated lumens to dilute the residual formulation in the lumen, if any. In some procedures, the formulation cavity 604 may be flushed with saline or heparinized saline to prevent needle clogging. Although fig. 6A and 6B show three needles at the distal end of the balloon, any number of needles may be used, such as one, two, three, four, five or more, and the needles may be located at the proximal end of the balloon. The needle guide (needle guide) may optionally be flushed.

An embodiment of a rapid exchange (RX) needle balloon catheter is shown in fig. 7A, including a rapid exchange shaft. The rapid exchange configuration allows for easier and faster insertion of the catheter after wire placement during surgery. The guidewire lumen 709 has a wire inlet or outlet port 711 located near the middle or distal end of the shaft 710. Optionally, a guide groove is present on the distal head (not shown) to facilitate the feeding of the wire by the physician as the wire is fed back through the lumen distal port. The same needle and balloon procedure as described in the preceding paragraph can be applied except for the wire exchange method. Optionally, flushing and cleaning of the distal head and post needle treatment may be accomplished by direct injection of saline or heparinized saline at about 3 to 10 times the treatment volume through the formulation cavity 704.

A needle-based balloon infusion system may include a needle-based balloon catheter, a guidewire, an ablative agent, saline or heparinized saline or a therapeutic drug, and a set of reservoirs for fluid management having a volume of 1mL to 30 mL. Examples of a reservoir may include a syringe or a syringe pump.

The needle-based balloon delivery catheter may include a distal head, at least one marker band, at least one needle exit hole, at least one irrigation hole (which may be the same as the needle exit hole in some embodiments), an irrigation lumen, an irrigation port, a guidewire lumen, at least one balloon located at a substantially 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 through the inflation lumen via the inflation port; the flushing port is communicated with the flushing hole through a flushing cavity, and the guide wire cavity is connected with the groove at the head part of the far end; the needle movement controller is communicated with the needle through a needle movement shaft; the ablation port is communicated with the needle head through a needle moving shaft; the needle is connected with the needle moving shaft; and needle movement is controlled by the needle movement controller via the needle movement controller. In one embodiment, the number of needles is 1, 2, 3, 4 or 5 and the number of needle outlets is 1, 2, 3, 4 or 5. In another embodiment, the size of the catheter is 4F, 5F, 6F, 7F, 8F, 10F, 12F, 14F, 16F, 18F, 20F, 22F, 24F, or 26F. The balloon diameter may be in the range of 3mm to 40 mm. The balloon length may be in the range of 3mm to 25 mm. The needle size or needle Outer Diameter (OD) may be in the range of 0.3mm to 0.5mm and the needle Inner Diameter (ID) may be in the range of 0.2mm to 0.35 mm. When the catheter contains two or more needles, the needle span diameter may be in the range 5mm to 80mm or 5mm to 40mm, defined by the circumference of the tip end point of the needle when it is fully advanced. The catheter length may be in the range of 70cm to 260 cm. The guidewire lumen may be compatible with a 0.014 inch (0.36mm) or 0.018 inch (0.46mm) or 0.035 inch (0.89mm) guidewire. The needle span diameter can be fixed or adjustable; for example, the needle span diameter may range from 5mm to 80mm, 5mm to 30mm, or 7mm to 15 mm.

The needle may be visible under X-ray (fluoroscopy). The needle may be made of stainless steel, nitinol, cobalt chromium alloys, metal alloys and shape memory metals and their alloys. The needles may be straight or curved in shape. The radiopacity of the metal needle may be enhanced by surface modification of another or two metals (e.g., W, Au, Ta, Pt, Ir, and any combination thereof) using Physical Vapor Deposition (PVD) by sputtering another metal.

The needle-based balloon delivery catheter may include a needle movement control and an ablative agent port. The ablative agent passes directly through the port to the needle.

The needle-based balloon delivery catheter may include a wire lumen for guiding a wire. The filament cavity may be characterized as either an integrally-switched (OTW) or a rapidly-switched (RX) type. When it is an OTW shaft (catheter), the guidewire 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 a lumen through the catheter shaft. Typically, the RX wire lumens are much shorter, about 10 inches (about 25cm) in length, located at the distal portion of the catheter. RX catheters save time compared to advancing a guidewire along the full length, especially during catheter changes during surgical procedures.

The needle-based balloon delivery catheter may include at least one balloon. Short length balloons are preferred and the balloon length may range from 3mm to 20mm, preferably 5mm to 10mm long. The balloon diameter may be 3mm to 30 mm. Required balloonComplianceDepending in large part on its application, and may range from compliant to non-compliant. The balloon material may be polyethylene, polyamide and block copolymers thereof, polyurethane, polyester and block copolymers thereof, nylon 12, Pebax, and the like. The balloon may be inflated and deflated through the inflation lumen/port using a standard balloon inflation medium. The inflation device may be a syringe or balloon inflation device, howeverIf the balloon is a compliant and low pressure balloon, a syringe of appropriate volume is preferred due to the nature of the balloon.

A balloon on the catheter may be positioned behind the needle to center the distal head of the needle and prevent blood flow into the target treatment area.

The needle-based balloon delivery catheter may include markings that indicate the position of the balloon during the procedure. The marker may be a regular marker band for a balloon catheter and may be a radiopaque metal (distal) head, for example in a needle-based balloon catheter. Balloon markers may be placed at the distal, or intermediate, or proximal end of the balloon, or a combination of these locations. The radiopaque marker band may be made of platinum, platinum iridium alloys, gold metal, and polymer composites with radiopaque fillers.

The needle-based balloon delivery catheter may include an irrigation lumen in direct communication with the needle exit hole for fluid egress/passage. The flush lumen may 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 drug for internal surface treatment. The irrigation lumen may be of a coaxial construction (see fig. 7B) or have a separate conduit channel (not shown).

The needle-based balloon delivery catheter may include a balloon, three needles, a distal head of a needle compartment and radiopaque markers, a guidewire lumen, balloon inflation lumens and ports, infusion lumens and ports, and irrigation lumens and ports.

An example of a rapid exchange (RX) needle balloon delivery catheter is illustrated in fig. 7B. The catheter shaft 720 includes a separate flush lumen 715. The flush lumen 715 is connected to a needle exit hole 716 through the catheter shaft and flush port 708 so that the flush medium is expelled through the needle exit hole as indicated by the arrow. In this example, the flush lumen is coaxially disposed over the infusion lumen 714. The infusion lumen 714 is directly connected to a needle tube, which may 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, which may be a polymer tube or a reinforced polymer tube, such as a braided polymer tube, may be strong and flexible to hold the needles together and evenly separate them. Balloon 706, located behind the tip segment, serves to center the needles in the vessel to ensure that the three needles are equidistant from the vessel wall. The needle distal head 717 is the needle holding compartment and the markers for needle placement during surgery. The shape memory needle returns to the pre-formed curvature upon exiting the distal head. It has a beveled (beveled) needle distal opening 713 with the bevel facing in the direction of the inner arc (intrados) of the needle. The needle distal opening communicates with the infusion lumen 714 and the infusion port 704.

Various sections of the needle balloon delivery catheter shown in fig. 7B are shown in fig. 7C-7G, which are cross-sectional views of the sections. Fig. 7C is a cross-sectional view of section 7C-7C of the catheter of fig. 7B, including balloon body 706, guidewire lumen 709, braided outer shaft 721, three-wire tube 722 in direct communication with the distal head, and irrigation lumen 715.

Fig. 7D illustrates a cross-sectional view of section 7D-7D of the catheter of fig. 7B, including a balloon 706, a guidewire lumen 709, an inflation lumen 707, an irrigation lumen 715, a braided outer shaft 721, a needle cannula 722 with a needle bundle tube (braided tube) 712 holding the needles together and keeping the needles evenly separated. For the three needle case, the needle-to-needle spacing is 120 °.

Fig. 7E and 7F illustrate cross-sectional views of section 7E-7E and section 7F-7F, respectively, of the catheter in fig. 7B. Fig. 7E includes a guidewire lumen 709 and an inflation lumen 707, both disposed at the top of the braided outer shaft but in opposite directions. Fig. 7E also includes an irrigation lumen 715, a braided outer shaft, and an infusion lumen 714. The infusion lumen may be made of a polymer tube, or a reinforced polymer tube or a metal tube. For better pushability and dimensional stability, a Stainless Steel (SS) hypotube may 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 to a needle cannula. Alternatively, to save space or reduce the overall catheter profile, the guidewire lumen 709 and inflation lumen 707 can be co-located on the same side of the shaft, as shown in FIG. 7F. This configuration of fig. 7F is not shown in the catheter of fig. 7B.

Fig. 7G illustrates a cross-sectional view of section 7G-7G of the catheter of fig. 7B, including the braided outer shaft with inflation lumen 707 attached to the outer wall thereof, the flush lumen, and the infusion lumen of the SS hypotube. The inflation lumen 707 communicates with an inflation port 705 for balloon inflation. The infusion lumen 714 communicates with the infusion port 704 and the needle and needle distal opening 713. The flush lumen 715 communicates with the flush port 708 and the flush aperture 716.

A rapid exchange (RX) needle balloon delivery catheter may be used for ablation procedures through blood vessels. The infusion lumen and needle of the catheter may be pre-filled with an ablative agent of ethanol from its port 704; and the flush lumen may be pre-filled with a medium such as saline or heparinized saline from its port 708. The pre-filled irrigation fluid in the distal head may reduce the likelihood of needle clogging because it prevents the needle from directly contacting the blood. Less clogging may mean a longer useful life for the catheter, may be used for multiple treatments in one procedure, and may help shorten procedure time and reduce overall costs due to the fewer catheters used. The prepared catheter may then be inserted into a blood vessel within a guide catheter and advanced over a pre-positioned guidewire to a treatment site. Once the predetermined treatment site is reached, the balloon may be first inflated to the vessel diameter to center the needle segment, then the three needles may be advanced to or beyond the vessel wall, and the ablative agent may be injected through the needle infusion into the predetermined denervation region. Alternatively, therapeutic agents may be used in place of ablative agents for treatments other than ablation. After treatment, the needle may be retracted into the distal head, then irrigation media may be injected through the exit needle hole and flushed out for irrigation and cleaning, then the balloon may be deflated, and the catheter may then be ready to be withdrawn or moved to the next treatment site for another ablation. The flush medium may also be a therapeutic drug when drug delivery is desired. The liquid medication may be applied to the treatment site and its inner surface through the irrigation holes.

An irrigation lumen on the catheter may provide a safety mechanism for the patient. For example, it may dilute any excess ablative solution or any residual ablative solution within the blood vessel to a non-functional level.

The needle-based balloon delivery catheter may be a three-needle balloon delivery catheter. The needle span diameter (calculated from the circumference formed from the tip to the tip of the needle at the full advancement stage) may be 5mm to 30mm, or 7mm to 15 mm.

In one embodiment, as shown in fig. 8A and 8B, a steerable single needle catheter may be used to infuse the formulation. As shown, the catheter has bidirectional steering (steering), although one, two, three, four or more directional functions may be used. The steering mechanism may 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 a proximal direction, which causes the distal tip 801 to move away from the longitudinal axis of the catheter shaft 802. During insertion and positioning, the needle tip is retracted inside the catheter, which can be done with a guide wire. An eccentric guidewire lumen design can be used to minimize the catheter profile of 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 toward and preferably against the vessel wall. This may be visually guided using fluoroscopy. Next, the needle (803 in fig. 8B) is advanced into or through the vessel wall and the formulation is infused. If desired, the needle can be retracted and the tip can be turned to a new orientation for treatment in the new orientation. After treatment, the needle is retracted and the catheter is then removed from the patient. Optionally, the steerable catheter can be used without a guidewire since the catheter is visible under X-ray and has a steerable tip.

In another embodiment, as shown in fig. 9A, 9B and 9C, a single directional steerable catheter is used to infuse the formulation through the needle. The catheter 900 has a smaller profile than the bidirectional catheters described above and is suitable for use in smaller diameter blood vessels. As described above, the desired and controlled penetration may include a needle that achieves an approximate perpendicular orientation to the lumen wall (e.g., 90 ° or near 90 ° to the lumen wall), so that infusion direction and depth may be predicted. This may require a sharp bend at the distal end of the catheter 902 so that the tip 901 is vertically aligned with the vessel wall. This can be very difficult in small cavities, as it may be nearly impossible to push the needle through a small bend or curvature. To overcome this problem, in some embodiments, the exit orifice of the needle is placed in the side wall of the tip head instead of in the middle of the tip 903 (see fig. 9B and C). Further, the outlet hole is positioned on the side of the catheter shaft 902 in the same direction as the bending direction of the catheter tip (see fig. 9B). When the catheter is placed in the small lumen of the target area, it need only be bent a small angle (less than 90 °) to align the hole in an approximately perpendicular manner to the vessel wall 5 (see fig. 9C). Once alignment is achieved, the needle is advanced into the wall 5, as shown in fig. 9C, and the system is ready for infusion therapy. After treatment, the needle is retracted into the catheter, the catheter tip is returned to a straight position, and the catheter is ready to be removed from the patient, rotated for treatment in a different orientation, or moved to a different position for another treatment. The distal tip may be made of plastic, metal, or a combination thereof, may be radiopaque, and may contain a needle. The radiopaque tip 901 may serve as a marker band for needle positioning during surgery.

In one embodiment, the needle device can deliver a very small and accurate amount of the formulation, for example in the range of 0.01mL to 10.0mL, preferably 0.05mL to 5.0mL, most preferably 0.1mL to 1.0 mL. Due to the precise control of the microdosing and treatment volumes/doses, multiple treatments can be used at the same location/area to provide more optimal treatment results. As shown in fig. 3, a three-wire balloon catheter 108 is placed in the main renal artery 106, with a balloon and a needle 110 deployed; for example, the perivascular infusion volume of the formulation may be 0.6 mL. After needle retraction and balloon deflation, the catheter may continue to advance to the extra renal artery 502 (renal artery branch) and deploy the needle and infuse another therapeutic dose, e.g., 0.3mL, into its outer wall region (adventitia). If both additional renal arteries are accessible, both arteries may be treated with equal or different doses. To achieve similar doses per unit area during treatment, the dose of the additional renal artery treatment may be less than the dose of the main renal artery treatment, given the difference in surface area of the outer wall of the artery and the closer distance to the renal organs compared to the main renal artery. DOSE in the aorta to the kidneys (DOSE)_m) And extra renal artery (branch) (DOSE)_b) The dose relationship between may be:

DOSE_b＝DOSE_m*(D_b/D_m)

wherein D_mIs the diameter of the aorta, D_bThe diameter of the arterial branch.

For example, when the diameter of the aorta is 6mm, the diameter of the branch artery is 3mm,

DOSE_b＝DOSE_m*(D_b/D_m)＝DOSE_m(1/2) or 0.5DOSE_m

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

Sometimes, the main renal artery is long enough to allow one device to treat twice, e.g., once in the middle and another time near the bifurcation area (near the branch) of the artery. When the main renal artery was treated 2 times and 2 branch arteries were treated 1 time, the total dose for 1 renal side artery treatment was 1.8 mL.

In one embodiment, as shown in fig. 13 and 14, a jet catheter having a formulation outlet or jet orifice at its distal end can be used in a delivery catheter to achieve a wider treatment area. The catheter 1300 in fig. 13 has a shaft 1309 of coaxial design, where suction is drawn through the inner tube 1305 and spray is ejected through the space between the inner tube 1305 and the outer tube 1304. Spray holes 1301 are located on the side wall of the shaft 1309, which deliver the formulation directly to the vessel wall and provide good control of the spray direction and treatment area. The formulation is delivered to spray orifice 1301 through spray lumen 1307. If there is an excess of agent in the blood vessel after the spray treatment, it can be removed/collected by a suction function on the catheter. Removal may be accomplished by applying a vacuum to the aspiration port 1308, which may cause the formulation to be withdrawn through the aspiration site 1306. In this example, the suction opening 1306 is located distal to the ejection opening 1301. The openings for suction and ejection may be circular or any other geometric shape. There may be a single or multiple holes for both the pumping and jetting functions, and any combination of hole numbers between these two functions may be present. The number of holes and the size of the holes between suction and ejection are independent. Ideally, the spray orifice size is smaller than the suction orifice size, since for spraying, a fine mist is desired. Optionally, the suction line may be connected to a vacuum pump. The spray may include two components: a liquid formulation and a pressurized gas, such as air or oxygen. For a given volume of liquid agent, delivery is by a pressurized gas of a predetermined pressure. At this delivery pressure, the formulation is delivered in a fine mist for application to the target treatment area. The excess formulation after each spray can be collected/removed by a suction function on the catheter at the treatment portion so that the formulation can be contained in the target area.

The exact ejection location during the procedure can be visualized by a marker band under X-rays. For example, the marker band 1303 may be located at the distal end of the catheter 1309 proximal to the jet hole 1301, or a double marker band 1303 may be located at both the distal and proximal ends of the jet hole 1301. Optionally, the distal marker band is sized to occupy a space between the inside and outside of the distal shaft, which may occlude the fluid path and stop the agent at the marker band location; as a result, the priming volume in the catheter may be less, which may make the ejection volume more accurate.

In another embodiment, a dual site aspiration catheter may be used to help ensure that the formulation does not escape in either direction (distal or proximal) of the ejection orifice. This example is shown in fig. 14, where aspiration holes 1406A and 1406B are disposed on the catheter at the distal and proximal ends of the ejection site. The distal suction port and the proximal suction port may be connected by the same channel/lumen; or may be independent of each other, e.g., the distal suction aperture and the proximal suction aperture may be independently operable. Aspiration may occur at the distal location, the proximal location, or both locations simultaneously. The catheter may be operated as described above.

To accommodate the features in fig. 14, a multi-lumen shaft 1409 may be used and may be, for example, a 3-lumen shaft. Each of the

aspiration locations

1406A and 1406B has its own lumen, and thus distal aspiration and proximal aspiration can be performed independently. In one embodiment, a sleeve 1410 is placed over the spray outlet aperture 1401 to achieve a uniform circumferential spray (e.g., 360 °). Double marker bands 1403 located at the distal and proximal ends of the cannula 1410 help to accurately locate the treatment site or lesion. While fig. 14 shows a sidewall jet outlet configuration, the jet outlet may alternatively or additionally be placed at the distal tip. Through the design of the orifice size 1401, the spray pattern can be a series of delivery effects (physical form) from a fine mist to a coarse droplet to a jet.

Fig. 15A and 15B illustrate various arteries surrounding the liver and stomach and various nervous systems that innervate the liver and stomach and its surrounding organs and tissues. The liver and the peripheral arteries include the abdominal aorta 305, the celiac artery 310, the common hepatic artery 315 and the intrinsic hepatic artery 320, the gastroduodenal artery 322, the right hepatic artery 325 and the left hepatic artery 330, the splenic artery 335, and the esophageal branch 361. The various nerves that innervate the liver and stomach and its surrounding organs and tissues include the celiac plexus 340 and hepatic plexus 345 (shown only in fig. 15B). The blood supply of the liver is pumped from the heart into the aorta and then down through the abdominal aorta 305 and into the celiac artery 310. Blood passes from celiac artery 310 through common hepatic artery 315, into inherent hepatic artery 320, and then into the liver through right hepatic artery 325 and left hepatic artery 330. The common hepatic artery 315 branches from the celiac trunk and forms the gastroduodenal artery. Nerves innervating 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 intrinsic 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 anatomical structures, celiac plexus 340 and hepatic plexus 345 adhere tightly to the arterial wall, providing blood to the liver, making intravascular-to-extravascular neuromodulation particularly advantageous. In several embodiments, the average thickness of the blood vessel (e.g., hepatic artery) ranges from about 0.1cm to about 0.25 cm. In some embodiments, the agent and/or energy may be delivered to the inner wall of a target vessel or target nerve. Intravascular delivery may be used because the nerves adhere tightly to the outer wall of the artery, supplying the liver with blood (e.g., in the case of a hepatic artery branch). In some embodiments, extra-luminal/extravascular delivery is desirable and may be achieved with any of the various needle catheters disclosed herein.

The perigastric arteries include the abdominal aorta 305, the celiac artery 310, the right and left

gastric arteries

355, 360 and the esophageal branch 361. The blood supply to the stomach is pumped from the heart into the aorta and then down through the abdominal aorta 305 and into the celiac artery 310. From the celiac artery 310, blood passes through the right and left

gastric arteries

355, 360, the esophageal branch 361, and into the stomach. The left gastric artery 360 includes a left gastric artery plexus 362 (shown only in fig. 15A).

With continued reference to fig. 15B, hepatic plexus 345 is the maximum offset of the celiac plexus 340. It is believed that hepatic plexus 345 carries primarily afferent and efferent sympathetic fibers, the stimulation of which can increase blood glucose levels through a variety of mechanisms. For example, stimulation of sympathetic nerve fibers in hepatic plexus 345 may increase blood glucose levels by enhancing hepatic glucose production or by decreasing hepatic glucose uptake. Thus, disruption of sympathetic nerve signaling in hepatic plexus 345 may alter blood glucose levels.

The embodiment shown in fig. 15B may be an embodiment of a balloon needle delivery catheter positioned within the hepatic artery for the treatment of diabetes. The embodiment shown in fig. 15A may 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 of these arteries is very similar to that of the renal arteries, so the procedures described in the previous section are applicable to these embodiments.

A safe and effective amount of the formulation can be applied to satisfactorily and beneficially damage tissue, such as nerves. Generally, the dose is related to the degree of damage to the tissue. In some embodiments, the effective formulation dose range is 0.2 microliters to 200 milliliters. However, these dose limits are not defined, as other delivery parameters (e.g., delivery rate, duration, etc.) may require different doses to achieve the ultimate benefit of the lesion.

The treatment time may vary depending on the volume of the tissue mass to be treated and the desired degree of damage to the target tissue. The treatment time may vary from about 2 seconds to about 60 minutes. In some embodiments, the safe and effective treatment time ranges from about 4 seconds to about 30 minutes for inducing damage to alleviate symptoms.

The delivery rate can be set by adjusting the delivery system. Once the user determines the delivery rate, the formulation resource can determine the amount of pressure required to deliver the vapor or liquid at the desired rate.

In one embodiment, a method of treating hypertension includes inserting a delivery catheter percutaneously into a renal artery adjacent a nerve; infusing the above-described agent and/or energy into body cavity tissue adjacent the nerve using a catheter, wherein the amount of agent and/or energy delivered is effective to beneficially damage or compromise the nerve; and removing the delivery catheter from the body lumen. Damage or damage to the tissue can alleviate the symptoms of the disease, for example by lowering blood pressure. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher. The formulation infusion pressure may be from 0.1 to 14atm, preferably from 3 to 10atm, most preferably from 4 to 8 atm.

In one embodiment, a method of treating asthma comprises inserting a delivery catheter into an airway adjacent to a nerve; infusing the above-described formulation and/or energy into airway tissue adjacent the nerve using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the nerve; and removing the delivery catheter from the body lumen. Damage or damage to nerves can relieve symptoms of the disease, for example, by relieving tachypnea. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher. The formulation infusion pressure should be in the range of 0.1 to 14atm, preferably 3 to 10atm, most preferably 4 to 8 atm.

Alternatively, a jet catheter without a balloon may be used to treat asthma. In one embodiment, a method of treating asthma comprises inserting a delivery catheter into an airway adjacent to a nerve; infusing the above-described formulation and/or energy into airway tissue adjacent the nerve using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the nerve; and removing the delivery catheter from the body lumen. Damage or damage to nerves can relieve symptoms of the disease, for example, by relieving tachypnea. The advantage of this method of spraying is that it is simple, fast and capable of treating small diameter airways. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. For liquid and gaseous formulations, delivery may be preferably in a fine mist. The diameter of the formulation exiting the ejection orifice may be 0.5mm or less, more preferably 0.4mm or less. The delivery gas pressure may preferably be less than 8atm, more preferably 4atm or less.

In one embodiment, a method of treating COPD and/or asthma comprises inserting a delivery catheter into the airway adjacent to a nerve; infusing the above-described agent and/or heat into body cavity tissue adjacent the nerve using a catheter, wherein the amount of agent and/or heat delivered is effective to beneficially damage or compromise the nerve; and the delivery catheter is removed from the airway. Damage or damage to nerves can alleviate disease symptoms, for example, by alleviating COPD/asthma symptoms. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent 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 may be generated by condensation of the vapor to a liquid. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ 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 ℃ or more. The formulation infusion pressure and/or balloon inflation pressure may be 0.1 to 14atm, preferably 3 to 10atm, most preferably 4 to 8 atm.

Alternatively, COPD may also be treated with jet catheters, where the same methods described herein for asthma treatment may be used. The method also includes the combined use of a balloon catheter and a jet catheter in the same procedure, which may result in the greatest degree of denervation effect.

In one embodiment, a method of treating severe emphysema by pulmonary volume reduction includes inserting a delivery catheter into an airway adjacent a target region; spraying the above agent and/or energy using a catheter to completely destroy the target lung tissue, wherein the amount of agent and/or energy delivered is effective to beneficially damage the tissue; and the delivery catheter is removed from the airway. Damage to the tissue can relieve disease symptoms, such as emphysema symptoms. The agent and/or energy may be delivered at the distal tip leading end, or at the sidewall location, or a combination of both.

In one embodiment, a method for treating diabetes and/or non-alcoholic fatty liver disease (NAFLD) and/or non-alcoholic steatohepatitis (NASH) comprises percutaneously inserting a delivery catheter into a hepatic artery adjacent to a nerve, particularly a celiac artery, a common hepatic artery, an intrinsic hepatic artery, or left and right hepatic arteries; infusing the above-described agent and/or energy into body cavity tissue adjacent 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 damage or compromise the nerve; and removing the delivery catheter from the body lumen. The purpose of the energy/heat may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher. The formulation is delivered to the perivascular region for denervation through a needle, the formulation volume being 0.1mL to 1.0mL, preferably 0.3mL to 0.8mL, most preferably 0.4mL to 0.7 mL.

In one embodiment, a method for reducing rapid blood glucose, HbA1c, glucagon, epinephrine, norepinephrine, cortisol, or growth hormone in a diabetic patient may comprise percutaneously inserting a delivery catheter into a hepatic artery adjacent to a nerve, particularly a celiac artery, common hepatic artery, intrinsic hepatic artery, and/or left and right hepatic arteries; infusing the above-described agent and/or energy into body cavity tissue adjacent 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 damage or compromise the nerve; and removing the delivery catheter from the body lumen. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ 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 ℃ or more. The formulation is delivered to the perivascular region for denervation through a needle, the formulation volume being 0.1mL to 1.0mL, preferably 0.3mL to 0.8mL, most preferably 0.4mL to 0.7 mL.

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 adjacent to the gastric and esophageal nerves; infusing the above-described formulation and/or energy into the gastric artery tissue or outside of the artery adjacent to the nerve using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the nerve; and the delivery catheter is removed from the gastric artery. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the formulation includes a vapor of one or more components, heat may be generated by condensation of the vapor to a liquid. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher. The formulation infusion pressure and/or balloon inflation pressure should be in the range of 0.1 to 14atm, preferably 3 to 10atm, most preferably 4 to 8 atm.

In one embodiment, a method for treating obesity comprises inserting any of the delivery catheters described herein into or out of the digestive lumen adjacent to a nerve; infusing the above-described formulation and/or energy into the tissue of the digestive lumen using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the tissue; and the delivery catheter is removed from the digestive lumen. Possible digestive lumens for this embodiment include the esophagus, stomach, duodenum, jejunum, small and large intestines, and colon. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the formulation includes a vapor of one or more components, heat may be generated by condensation of the vapor to a liquid. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher.

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 adjacent to the gastric and esophageal nerves; infusing the above-described formulation and/or energy into tissue or external portions of the gastric artery adjacent the nerve using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the nerve; and the delivery catheter is removed from the gastric artery. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof, of one or more ingredients. If the formulation includes a vapor of one or more components, heat may be generated by condensation of the vapor to a liquid. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher.

In one embodiment, a method of treating a urinary system disease and/or Benign Prostatic Hyperplasia (BPH) comprises inserting a delivery catheter into a urinary system lumen; infusing the above-described formulation and/or energy into the lumen or extraluminal urinary tissues (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 damage or compromise the tissue; and the delivery catheter is removed from the urinary lumen. The purpose of the heat/energy may be to enhance the damaging/damaging effect by accelerating the rate of reaction between the agent and the nerve. The formulation includes one of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, and combinations thereof of one or more ingredients. If the formulation includes a vapor of one or more components, heat may be generated by condensation of the vapor to a liquid. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The liquid formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃, or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue adjacent the nerve may be below the formulation temperature and above body temperature. The temperature of the treated tissue adjacent to the nerve may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃, or-40 ℃ or lower, or less than, equal to, or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 ℃ or higher. The formulation infusion pressure and/or balloon inflation pressure may be 0.1 to 14atm, preferably 3 to 10atm, most preferably 4 to 8 atm.

In one embodiment, a method for treating cancer or tumor comprises inserting a needle or needle-based catheter into the cancer or tumor percutaneously, orally, or translumenally under imaging guidance; infusing the above-described formulation and/or energy into cancerous tissue of the human body using a catheter, wherein the amount of formulation and/or energy delivered is effective to beneficially damage, impair, or eliminate the cancerous tissue; and removing the delivery catheter from the body. The damage, damage or elimination of cancerous tissue may alleviate the symptoms of the disease, for example by shrinking or eliminating the tumor. Possible imaging guides include ultrasound, X-ray, CT scan, NMR imaging, and scope. The related cancers include adrenal gland 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 and uterine cancer. The purpose of the heat/energy may be to enhance the damaging/ablating effect by accelerating the rate of reaction between the agent and the cancerous tissue. The formulation includes one of a gas, a vapor, a liquid, a solution, an emulsion, a suspension, and combinations thereof of one or more ingredients. If the agent comprises a vapour of one or more components, heat may be generated by condensation of the vapour into a liquid in the tissue. If the formulation comprises a liquid or solution, heat may be transferred from the hyperthermic formulation above body temperature. The formulation temperature may be-40 to 140 ℃, -30 to 100 ℃, -30 to 80 ℃ or-40 ℃ or lower, 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 ℃ or higher. The temperature of the treated tissue may be below the temperature of the formulation and above body temperature. The temperature of the tissue being treated may be-40 to 100 ℃, -30 to 90 ℃, -20 to 80 ℃ or-40 ℃ or lower, or less than, equal to or greater than-30 ℃, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 ℃ or higher.

A method of treating myocardial infarction, atherosclerosis, Coronary Artery Disease (CAD), peripheral vascular disease (PAD), rheumatoid arthritis, or cancer due to immune response to an inflammatory condition may comprise percutaneously inserting a delivery catheter into the splenic artery adjacent to a nerve, infusing the above formulation and/or energy into body lumen tissue adjacent 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 damage or compromise the nerve; and removing the delivery catheter from the body lumen. The formulation can be delivered to the perivascular region via a needle for denervation, with a formulation volume per application ranging from 0.1mL to 1.0mL, or 0.3mL to 0.8mL, or 0.4mL to 0.7 mL.

A method 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 adjacent a nerve; infusing the above formulation into and/or applying energy to body cavity tissue adjacent to the nerve or directly to the nerve using any of the catheters described herein, wherein the amount of formulation and/or energy delivered is effective to beneficially damage or compromise the nerve; and removing the delivery catheter from the body lumen. The formulation can be delivered to the perivascular region via a needle for denervation, with a formulation volume per application ranging from 0.1mL to 1.0mL, or 0.3mL to 0.8mL, or 0.4mL to 0.7 mL.

Hypertension and hypercholesterolemia may be predisposing factors for vascular diseases such as coronary heart disease, but the two act synergistically to significantly alter risk, as their combined effect is considered multiplicative rather than additive. Thus, the risk of coronary heart disease is particularly high in people with combined risk factors. Impaired endothelium-dependent vasodilation in patients with essential hypertension may be associated with hypercholesterolemia; furthermore, increased sympathetic activity may be associated with hyperlipidemia in hypertension. For example, a positive correlation of serum triglyceride levels with blood pressure is significant, particularly for humans with a high body mass index (BMI > 24). Embodiments of the invention may not only lower blood pressure, but also lower cholesterol levels. The biological interrelationship between blood pressure and atherogenic lipid fraction, and the pathophysical factors behind these interrelationships, may influence the mechanisms associated with hypertension and increased risk of coronary heart disease. Thus, in the results of various embodiments of the methods of treatment, 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).

A method of treating a disease with a needle-based balloon infusion system (where the needle-based balloon infusion system includes 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) may include: 1) inserting a needle-based balloon delivery catheter into the body lumen, wherein the needle-based balloon delivery catheter comprises a distal head, at least one marker band, at least one needle exit hole, at least one irrigation hole, an irrigation lumen, an irrigation port, a guidewire lumen, at least one centering balloon located at a substantially 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 needle lumen is pre-filled with an ablative agent and the irrigation lumen is pre-filled with an irrigation 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, out of, or within a wall of a body lumen; 4) infusing the formulation through at least one needle, wherein the amount of the formulation delivered is effective to damage or impair the target tissue to alleviate 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 flush lumen prior to balloon deflation or prior to insertion into the next body lumen to prevent needle lumen occlusion and clot formation; 8) inserting a needle-based balloon delivery catheter into the next body cavity; 9) repeating 2) to 8) until all target body cavities are treated; and 10) removing the delivery catheter from the body lumen. The disease can be hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), or a combination thereof. The ablation agent can be one of ethanol, anhydrous ethanol, acetic acid, and diluted acetic acid. The irrigation medium may include saline or heparinized saline or a neutralizing agent for the ablative agent. The 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, 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, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a diaphragmatic vein, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary lumen, or a combination thereof.

Methods of delivering a catheter using a needle-based balloon may include: the method includes the steps of pre-filling a needle lumen with an ablative agent, pre-filling an irrigation lumen with an irrigation medium, and inserting a catheter into a guiding catheter over a guidewire. Once at the treatment site, the balloon may be inflated to the size of the vessel to center the tip segment, the needle may then be advanced to the treatment site, and the ablative agent may be infused; after infusion, the needle can be withdrawn and retracted into the distal head and an irrigation fluid can be injected to keep the needle compartment/bore and the needle tip/opening of the distal head clean and avoid direct contact with blood. The balloon may be deflated and the catheter may be withdrawn from the treatment site and/or moved to another treatment site.

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

The dose of ablative agent may be 0.1mL, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0, or 1.2mL per application/treatment of a major vessel, such as an artery. If more than one treatment is performed, the total dose (volume) for a particular major blood vessel (length) may be 0.3mL, 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 branched vessel or artery, the dose per application may be 0.1mL, 0.2, 0.3, 0.4, 0.5, or 0.6 mL. If more than one treatment is performed, the total dose for the arm may be 0.2mL, 0.4, 0.6, 0.8, 1.0, or 1.2 mL.

Various embodiments of the present invention provide needle-based balloon delivery catheters for delivering materials to a target tissue in a body lumen of a patient. The delivery catheter may include a catheter shaft having a proximal end and a distal end. The delivery catheter may include at least one marker band located near the distal end of the shaft. The delivery catheter may include at least one needle (e.g., 3 needles), with each needle being located in a needle lumen. The needle lumen may be open to the exterior of the catheter shaft through the at least one needle exit hole. The delivery catheter may include an irrigation port at the proximal end of the shaft in fluid communication with the irrigation lumen. The flush lumen is in fluid communication with the distal end of the needle lumen. The irrigation port may be in fluid communication with the needle outlet aperture through the irrigation lumen. The delivery catheter may include a guidewire lumen extending through at least the distal end of the shaft. The delivery catheter may include at least one balloon adjacent the distal end of the catheter. The delivery catheter may include an inflation lumen. The delivery catheter may include an inflation port in fluid communication with the inflation lumen and in fluid communication with the interior of the balloon. The balloon is inflatable through the inflation lumen via the inflation port, and the distal end of the catheter shaft may be substantially centered in the body lumen during inflation. The delivery catheter may include an ablation or denervation port at the proximal end of the shaft. An 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 may 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 cavity, into a wall of the body cavity, or outside the body cavity. Deploying the needle through the needle exit opening may allow the formulation to penetrate into the body cavity wall at a pressure above the body cavity pressure. The target tissue may be the 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, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a phrenic vein, an mesenteric artery, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof. The formulation pressure during infusion may be any suitable pressure, and the balloon inflation pressure may be any suitable pressure. For example, the pressure of formulation infusion may be in the range of 0.1 to 14 atm. The balloon inflation pressure may be in the range of 0.1 to 14 atm.

Examples

Various embodiments of the present invention may be better understood by reference to the following examples, which are provided by way of illustration. The present invention is not limited to the examples given herein.

Example 1 preclinical testing

Porcine animals weighing 47kg were anesthetized with isoflurane and their renal artery side was ablated with ethanol using a three-needle single balloon catheter, while the contralateral renal artery served as a control. The catheter needle span diameter is about 10 mm. The catheter balloon is a low pressure and compliant balloon with a diameter of 7mm at 1atm, which functions to center the distal shaft without over-stretching the artery. Optionally, the balloon may be inflated with a syringe without the use of an inflation device. Due to the nature of the balloon, the balloon can be used with arteries of any diameter (below or above the balloon diameter). Prior to insertion into the artery, the catheter is pre-filled with the liquid formulation until it overflows the needle (needle extension), then the needle is retracted and a syringe with a predetermined treatment volume is connected to the catheter. Using standard renal access procedures, a three-wire balloon delivery catheter is placed over the guidewire into the aorta and the target renal artery of the extra renal artery (bifurcation) in sequence. Once the target ablation site is reached, the balloon is inflated, the needle is then deployed, and absolute ethanol infusion at room temperature is injected into the adventitia and periadventitial space of the renal artery. The aortic infusion volume was 0.6mL and the branched infusion volume was 0.3mL per application using a 1mL syringe. The infusion time for both application volumes was within 5 seconds. During balloon inflation, the ratio of balloon diameter to peripheral artery diameter was monitored by fluoroscopy to be about 1:1.1 (slightly larger). By the end of the treatment time, the needle is first retracted into the catheter, the balloon is then deflated, and the catheter is ready for removal or placement to another arterial site if the next treatment is required. In this example, a total of 4 treatments were performed: aorta 2 times, and 1 time per branch, the total volume of formulation used was 1.8 mL.

Post-ablation renal angiography is obtained to check for the presence of any vascular debris, stenosis and other abnormalities. There was no significant renal artery spasm during and after the infusion treatment.

Animals were euthanized two weeks after treatment, gross necropsy revealed that all treatment-related organs were normal, and renal tissue samples were taken from the head (cranial) (n-3), middle (n-3), and tail (caudal) (n-3) of the renal cortex to determine the Noradrenaline (NE) content of the renal tissue using known HPLC methods. Norepinephrine is a neurotransmitter used by the sympathetic nervous system, the level of which is a standard measure of renal denervation. The NE concentration on the treated side was lower or much lower after denervation compared to the NE concentration on the untreated side (control), as shown in fig. 10. Ablation of the renal artery with ethanol resulted in a 94% reduction in renal norepinephrine concentration (mean NE content: control: 87ng/g versus treatment: 4.9 ng/g). The percentage reduction in NE for individuals calculated from similar tissue locations between the control and treatment groups ranged from 89% to 97.5%. Renal arteries and surrounding tissue were also collected for histopathological evaluation.

Not only was the NE content reduced after ethanol ablation, but histopathological evaluation also demonstrated renal nerve damage, as shown in fig. 11, nerves surrounded by mild fibrosis within the outer periphery of the adventitia (see arrows).

Example 2 preclinical testing

Two 46kg porcine animals were treated with hepatic arterial ethanol ablation using a formulation of absolute ethanol at room temperature and using a three-needle single balloon catheter of the same type as used in example 1. Prior to insertion into the artery, the catheter is pre-filled with the liquid formulation until it overflows the needle (needle extension), and then the needle is retracted and a syringe with a predetermined treatment volume is connected to the catheter. A standard hepatic artery access procedure was performed. Each hepatic artery was treated twice, evenly distributed along the length of the artery, and the infusion volume per application was 0.6mL using a 1mL syringe, with infusion times less than 5 seconds. The inflation balloon diameter to arterial inflation ratio was monitored to be less than 1:1.1 and inflated using a syringe. In both porcine animals of the present study, hepatic angiography showed no significant arterial spasm during and after infusion treatment. As a control, untreated swine animals of similar body weight were used for NE reduction calculation and comparison of histopathological evaluation.

Two animals were euthanized two weeks after treatment; gross necropsy revealed that 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 lateral lobe (n ═ 2), and caudate lobe (n ═ 2) to determine the hepatic tissue Norepinephrine (NE) content using known HPLC methods. NE reduction was calculated from data collected from tissues at similar locations between the treated and control groups. As shown in fig. 12, the mean liver NE concentration reduction was 85% and 94% for both animals. The individual calculated percentage range for one animal was 55% to 95% and for the other animal 86% to 97.5%. As with the renal ablation study, arteries and surrounding tissue were collected for histopathological assessment.

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

Example 3 clinical trial, Metabolic syndrome

In one example, human male patient a is 53 years old, has metabolic syndrome, has hypertension for 10 years and takes 2 hypotensive drugs, has type 2 diabetes for 2 years and takes 2T 2DM (type 2 diabetes) drugs, and has obesity for 8 years. His triglyceride level was 336mg/dL before surgery. The arteries targeted for his treatment were the renal, hepatic, splenic and left gastric arteries.

During surgery, mild sedation was used according to institutional standard practice and no general anesthesia was used. The arteries were joined using a 7F guiding catheter introduced through the femoral artery. The arteries are angiographically imaged prior to intervention. All four arteries were treated with the same procedure. The treatment starts from the upper body artery, in order, the spleen artery, the hepatic artery, the left gastric artery, the left renal artery and the right renal artery. After a preliminary angiographic examination of the hepatic, splenic, and left gastric arteries, a quick-change three-needle single balloon catheter is advanced through the guide catheter and over the guidewire into the artery. Prior to insertion into the artery, the catheter is pre-filled with a liquid ablative formulation (dehydrated ethanol) until it overflows the needle (needle extension), then the needle is retracted and a syringe with a predetermined treatment volume is connected to the catheter.

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

Under fluoroscopic guidance, a three-needle balloon delivery catheter was placed into the target splenic artery. Once at the target ablation site, the balloon is inflated, the needle is then deployed, and absolute ethanol infusion at room temperature is injected into the adventitia and periadventitial space of the splenic artery. The infusion volume per application was 0.6mL using a 1mL syringe. The infusion time for each application was within 10 seconds. During balloon inflation, the ratio of balloon diameter to peripheral artery diameter was monitored by fluoroscopy to be about 1:1.1 (slightly larger). At the end of the treatment time, the needle was retracted into the catheter, the balloon was then deflated, and the catheter was moved to a second treatment site within the same splenic artery approximately 15mm from the first treatment site. The treatment steps (balloon inflation, needle deployment, infusion ablation, needle retrieval, balloon deflation) are repeated for a second treatment. The total volume of alcohol used in both treatments for the splenic artery was 1.2 mL.

Common hepatic artery ablation employs the same treatment and surgical steps as splenic artery treatment. The catheter is replaced by a fresh catheter for hepatic artery ablation. For the common hepatic artery with the same ablation dose of 0.6mL, a total of two treatments were performed approximately 15mm apart from each other (between treatment sites). The total volume of alcohol used for hepatic artery ablation was 1.2 mL. After the liver treatment, the catheter is placed into the left gastric artery for the next ablation treatment. The same treatment and procedure were again used, except that an ablation treatment of 0.6mL of alcohol was applied to the left gastric artery. Angiography is performed after the three needle balloon delivery catheter is removed.

After the three arteries are ablated, angiography is performed on the renal arteries before intervention. Appropriate branches and aorta are evaluated and predetermined for treatment. After assessment, a three-wire balloon delivery catheter is advanced through the guiding catheter and over the (over) guidewire into the branch artery of the left renal artery and stopped just outside the bifurcation region. The same catheter procedure and procedural steps were used, and one ablation of the branch artery was performed with 0.3mL of alcohol. Once the branch ablation was completed, the catheter was pulled back to the site just after the bifurcation of the aorta and the site was treated with 0.6mL of alcohol. The catheter was then pulled back approximately 10mm from the first treatment site in the aorta to a second ablation site where a second ablation treatment was performed with 0.6mL of alcohol. The left renal artery was treated 3 times in total: aorta 2 times and branch artery 1 times, and total volume of alcohol used was 1.5 mL.

The same method and procedure steps are repeated for the right renal artery. After initial angiography and right renal artery assessment, a three-wire balloon delivery catheter was advanced through the guiding catheter and over the (over) guidewire into the branch artery # 1. Branch #1 was ablated twice at approximately 10mm distance between treatment sites and 0.3mL of alcohol was used for each treatment. The catheter was then placed into the branch artery #2 and treated twice with a volume of 0.3mL of alcohol per treatment. After the two-branch treatment, the catheter was pulled back into the aorta until its needle was near the aortic midpoint and the right aorta was ablated once with an alcohol volume of 0.6 mL. The total alcohol volume for the right renal artery treatment was also 1.8 mL.

Patient a was followed at time points of 2 weeks (2wks), 1 month (1mo) and 3 months (3mos) post-surgery, and his follow-up data, as well as its baseline (basal) data obtained prior to surgery, are listed below for comparison. There was no drug change during the follow-up.

Weight: basis 103kg, 2wk 96.2kg, 1 mos 95.6kg, and 3mos 96.2 kg. Since 3 weeks post-surgery (2wk time point), approximately 7% weight loss was observed in patients and weight loss was maintained in a follow-up visit of 3 months.

24-hour blood pressure, SBP/DBP: basis is 164/109mmHg, 1mo 140/87mmHg, 3mo 141/84 mmHg. The blood pressure data are the average of the 24-hour ambulatory blood pressure. Both Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were significantly reduced from baseline, about 14% and 20%, respectively; and maintained reduced blood pressure over a 3 month follow-up.

Blood glucose level, HbA1 c: basis 7.5%, 3mos 6.6%. The patient also had significantly improved glycated hemoglobin (HbA1c) levels. His HbA1c values varied by almost-1 (%) at 3 months of follow-up compared to baseline values.

Triglyceride: basis 336mg/dL, 2wks 160mg/dL, 1 mos 139mg/dL, and 3mos 167 mg/dL. Triglyceride (TG) is a fat (lipid) found in blood. High triglyceride levels may be a clue that the person suffers from fatty liver disease. An improvement in triglyceride levels was observed in patient a, with about a 50% reduction, over a two week follow-up period. The reduction and improvement in triglyceride levels was maintained over a 3 month follow-up. Patient a had TG levels within the normal range at 1 month follow-up.

High Density Lipoprotein (HDL): basis 39mg/dL, 2wks 42mg/dL, 1 mos 43mg/dL, and 3mos 40 mg/dL. The baseline High Density Lipoprotein (HDL) level of patient a was just within the normal range. Then in follow-up, his HDL appeared to be improved and all 3 numbers were 40 or higher. The TG/HDL ratio of patient a improved significantly from 8.6 at baseline (>5 abnormalities) to 4.2 at 3 months follow-up, which was within the normal range (< 5); if the patient suffers from NAFLD, the NASH condition of patient a is significantly improved.

The short-term results of patient a are of great significance and very encouraging to the treatment and technique. The data indicate that the health of the patients is improved and their disease associated with metabolic syndrome appears to be controlled in a follow-up visit of 3 months.

Example 4 clinical trial, hypertension

In another embodiment, multiple arteries/tissues are treated for hypertension. A 50 year old male patient B was blood pressure controlled after ablative surgery at a 3 month follow-up time point. Patient B had a 5 year history of hypertension. Patient B underwent the same surgical and ablative treatment as patient a in example 3. The treatment arteries and ablation dose for each treatment site for patient B are summarized in table 1.

TABLE 1 ablation dosage for patient B treated artery and for each treatment site

Kidney B: the renal branch artery; kidney M: the main renal artery; r: right; l: and (4) left.

Post-treatment data for mean 24-hour ambulatory blood pressure were: 136/79mmHg base, 107/61mmHg 1mo, 115/66mmHg 3-mo. Both Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) decreased significantly from baseline at 1 month follow-up, approximately 21% and 23%, respectively; and his blood pressure improvement was maintained over a 3 month follow-up period with both SBP and DBP decreased by about 15% from baseline.

Example 5 clinical trial, T2DM

In another embodiment, diabetes treatment is performed on a plurality of arteries/tissues. Patient B, the same as above, had a1 year history of T2DM and received diabetes treatment for all of its liver, spleen, abdominal cavity, right and left renal arteries. The results of the treatment in example 4 resulted in some improvement in fasting blood glucose and HbA1c values in patient B.

Post-treatment data for fasting glucose were: the base was 186mg/dL, 2wks 127mg/dL, 1 mos 92mg/dL, and 3mos 110 mg/dL. The test is performed in the morning before the patient eats. Fasting blood glucose levels of 100 to 125mg/dL (5.6 to 6.9mmol/L) are considered pre-diabetic. If 125mg/dl or higher, the person suffers from diabetes. The data indicate that patient B had diabetes prior to surgery. His fasting blood glucose levels were significantly improved after surgery compared to baseline, varying-32% at 2 weeks of follow-up and-50% at 1 month of follow-up. At 3 months of follow-up, his hypoglycemic levels remained at a low level of 110mg/dL, which was a-41% reduction from baseline.

Blood glucose HbA1c data: basis 8.1%, 3mos 6.0%. The patient's HbA1c improved the absolute value of-2.1 (%) over baseline, decreasing by almost 26% within 3 months after surgery.

Example 6 clinical trial, weight loss

In another embodiment, multiple arteries/tissues are treated to control body weight. Patient B, who had a history of 3 years obesity, had improved body weight after ablative surgery. The multiple arteries treated were the hepatic, splenic, celiac, right and left renal arteries. Treatment example 4 was used.

Weight: basis 83kg, 2wks 79.3kg, 1 mos 79.9kg, 3mos 79.1 kg. Initial weight loss of-4.5% was observed at a follow-up time of 2 weeks, decreasing from 83kg at baseline to 79.3 kg. Body weight after improvement was maintained at 3 months follow-up.

The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the embodiments of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by particular embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of embodiments of this invention.

Exemplary embodiments

The following exemplary embodiments are provided, the numbering of which should not be construed as specifying the importance level:

embodiment 1 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) 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 lumens (e.g., at least three different body lumens or at least four different body lumens), the method comprising:

performing a treatment procedure on a body lumen as a first body lumen, the treatment procedure comprising:

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;

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

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 damage or damage the target tissue to alleviate a symptom of the disease;

deflating the balloon; and

removing the delivery catheter from the body lumen;

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

Embodiment 2 provides the method of embodiment 1, wherein performing the treatment procedure on the second body lumen comprises reusing the same delivery catheter used in the treatment procedure on the second body lumen as used in the treatment procedure on the first body lumen.

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 a treatment procedure on the second body lumen than 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.

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

The target tissues of the first body cavity and the second body cavity are different and are independently selected from the group consisting of target tissues of renal artery, pulmonary artery, vascular cavity, celiac artery, common hepatic artery, intrinsic hepatic artery, gastroduodenal artery, right and left hepatic arteries, splenic artery, right and left gastric arteries, adrenal artery, diaphragmatic artery, mesenteric artery, non-vascular cavity, airway, sinus, esophagus, respiratory and digestive cavities, stomach, duodenum, jejunum, prostate, urethra, ureter, and urinary cavity; or

Wherein the first body cavity and the second body cavity belong to different classes of body cavities selected from the group consisting of: renal arteries (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), renal veins, gastric arteries, gastric veins, hepatic artery, hepatic vein, pulmonary artery, pulmonary vein, celiac artery, celiac vein, gastroduodenal artery, gastroduodenal vein, splenic artery, splenic vein, adrenal artery, adrenal vein, diaphragmatic artery, diaphragmatic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, and urinary lumen; or

Combinations thereof.

Embodiment 5 provides the method of any one of embodiments 1-4, wherein the disease is selected from the group consisting of hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), and combinations thereof.

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

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

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

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 position of the marker band under fluoroscopy.

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

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

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

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 formulation vapor into a liquid, or a combination thereof.

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

renal hypertension and diabetes, or

Renal hypertension and obesity, or

Diabetes and obesity, or

Combinations thereof.

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

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

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

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

Embodiment 19 provides the method of any one of embodiments 1-18, wherein the first body lumen or the 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).

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

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

Embodiment 22 provides a method of treating a disease, comprising:

inserting a delivery catheter into a body lumen, wherein the delivery catheter comprises a catheter shaft, at least one jet orifice, and at least one marker band;

spraying the formulation through the at least one spray orifice, wherein the amount of formulation delivered is effective to damage or impair the target tissue to alleviate symptoms of the disease;

optionally removing the agent from the tissue; and

removing the delivery catheter from the body lumen.

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 jetting.

Embodiment 24 provides the method of any one 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

Deploying the at least one needle into, out of, or within the body lumen wall; and

infusing the formulation through the infusion lumen and the at least one needle, wherein the amount of formulation delivered is effective to damage or impair the target tissue to alleviate symptoms of the disease; and

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

Embodiment 25 provides the method of any one 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 an irrigation 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 irrigation lumen is in fluid communication with the needle lumen, the method further comprising irrigating the needles with an irrigation fluid through the irrigation lumen.

Embodiment 26 provides the method of any one of embodiments 1-25, wherein the at least two needles comprise three needles and the three needles are arranged at uniform distances around a circumference of the catheter shaft and are located at a distal end of the balloon.

Embodiment 27 provides a method of treating a disease, comprising:

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;

inflating the centering balloon to center the delivery catheter shaft in a body lumen;

deploying the at least one needle into, out of, or within the body lumen wall;

infusing the formulation through the at least one needle, wherein the amount of the formulation delivered is effective to damage or compromise the target tissue to alleviate symptoms of the disease;

optionally removing the agent from the tissue;

retracting the needle into the delivery catheter and deflating the centering balloon; and

removing the delivery catheter from the body lumen.

Embodiment 28 provides a method according to any one of embodiments 1-27, wherein the disease is selected from hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), and combinations thereof.

Embodiment 29 provides the method according to embodiment 28, wherein the cancer is selected from the group consisting of 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, jejunal cancer, uterine cancer, and combinations thereof.

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 a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a phrenic vein, an mesenteric artery, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

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

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

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

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 to a liquid.

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.

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.

Embodiment 37 provides the method of any one of embodiments 1-36, wherein the temperature of the formulation ranges from 40 to 140 ℃.

Embodiment 38 provides the method of any one of embodiments 1-37, wherein the temperature of the formulation ranges from 0 to 140 ℃.

Embodiment 39 provides the method of any one of embodiments 1-38, wherein the temperature of the formulation ranges from-40 to 0 ℃.

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

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

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.

Embodiment 43 provides the method according to any one of embodiments 1-42, wherein the pressure range of the formulation infusion is 0.1 to 14 atm.

Embodiment 44 provides the method of any one of embodiments 1-43, wherein the temperature of the target tissue ranges from-40 to 100 ℃.

Embodiment 45 provides the method of any one of embodiments 1-44, wherein the temperature of the target tissue ranges from-40 to 0 ℃.

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.

Embodiment 47 provides the method according to any one of embodiments 1-46, wherein the pressure of the formulation ranges from about 2 to 200psi at a temperature ranging from about-40 to 150 ℃.

Embodiment 48 provides the method of any one of embodiments 1-47, wherein the amount of the formulation is 0.2 microliters to 200 milliliters.

Embodiment 49 provides the method according to any one of embodiments 1-48, wherein the method comprises inflating the delivery catheter in the body lumen for an inflation period of about 2 seconds to about 60 minutes.

Embodiment 50 provides the method according to any one of embodiments 1-49, wherein the method delivers about 2cal/g to about 150cal/g of heat or energy to the target tissue.

Embodiment 51 provides the method of any one 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 catheter, a dumbbell balloon infusion catheter, or a combination thereof.

Embodiment 52 provides the method according to any one of embodiments 1-51, wherein the balloon inflation pressure ranges from 0.1 to 14 atm.

Embodiment 53 provides the method according to any one 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, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodized oil, urea, and derivatives and combinations thereof.

Embodiment 54 provides the method of any one 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, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, or a combination thereof.

Embodiment 55 provides a method according to any one of embodiments 1-54, wherein the formulation comprises a therapeutic agent for denervation, wherein the therapeutic agent comprises a sodium channel blocker, tetrodotoxin (tetrodotoxin), saxitoxin (saxitoxins), decarbamoyl saxitoxins (decarbamoyl saxitoxins), vanilloids (vanilloids), neosaxitoxins (neosaxitoxins), lidocaine (lidocaines), conotoxins (conotoxins), cardiac glycosides (cardiac glycosides), digoxin (digoxins), glutamates (glutamates), staurosporins (staurosporins), amlodipine (amydipins), verapamil (verapamides), mangafosides (cyromosides), digitoxins (digitoxins), piceids (piceids), piceids (mangnolides), chondrosins (hypochonins), piceids (mangnolides), chondrosins (mangostines), piceids (mangnolides), and piceids (mangnolides), piceids (mangnolides), mangnolides (mangnolides) and mangnolides (mangnolides), Aflatoxins (aflatoxins), guanethidines (guanethidines), guanethidine sulfates (guanethidine sulfates), or combinations thereof.

Embodiment 56 provides the method of any one of embodiments 1-55, wherein the formulation comprises a denervation contrast agent for imaging nerves, wherein the contrast agent comprises iodine, ethyl iodide, sodium iodide, lipiodol (lipiodol), nonylphenol polyether iodide (nonoxynol iodide), iobitridol (iobitridol), iohexol (iohexol), iomeprol (iomeprol), iopamidol (iopamidol), iopentol (iopentol), iopromide (iopromide), ioversol (ioxilan), ioxilan (iotralan), iotrolan (iotrolan), iodixanol (ioxadiol), iodixanic acid (ioxaglate), derivatives thereof, or combinations thereof.

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

Embodiment 58 provides the method of embodiment 57, wherein the azeotrope comprises ethanol/water, propanol/water, isopropanol/water, butanol/water, acetic acid/water, lactic acid/water, ethyl lactate/ethanol, lactic acid/ethanol/water, ethyl lactate/water/ethanol, ethyl acetate/ethanol, ethyl nitrate/ethanol, isopropyl acetate/ethanol, or a combination thereof.

Embodiment 59 provides the method of any one of embodiments 1-58, wherein the formulation comprises ethanol, 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 a combination thereof.

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:

a proximal end portion;

a distal end portion;

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 the marker band for needle deployment.

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

Embodiment 62 provides the centering balloon catheter of any one of embodiments 60-61, wherein the needle deployment through the needle exit opening allows penetration of the formulation into the wall of the body lumen at a pressure above the pressure of the body lumen.

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

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

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

a catheter shaft having a proximal end and a distal end;

at least one marker band located near the distal end of the shaft;

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;

an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen in fluid communication with a distal end of the needle lumen, wherein the irrigation port is in fluid communication with the needle outlet aperture through the irrigation lumen;

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

at least one balloon adjacent the distal end of the catheter;

an inflation lumen;

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

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 agent to the at least one needle; and

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 cavity, into the body cavity wall, or outside the body cavity.

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

Embodiment 67 provides the delivery catheter of any one of embodiments 65-66, wherein the needle deployment through the needle exit opening allows penetration of the formulation into the wall of the body lumen at a pressure above the pressure of the body lumen.

Embodiment 68 provides the delivery catheter of any one of embodiments 65-67, wherein the target tissue is the following target tissue: 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, an celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a diaphragmatic artery, a phrenic vein, an mesenteric artery, an mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

Embodiment 69 provides the delivery catheter of any one of embodiments 65-68, wherein the formulation infusion pressure ranges from 0.1 to 14atm and the balloon inflation pressure ranges from 0.1 to 14 atm.

Embodiment 70 provides a delivery catheter comprising:

a shaft having a proximal end and a distal end;

one or more needles for infusion therapy disposed near the distal end of the shaft;

an inflatable balloon disposed near 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

a marker band at the distal end of the shaft.

Embodiment 71 provides a delivery catheter comprising:

a shaft having a proximal end and a distal end;

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

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.

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

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

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

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.

Embodiment 76 provides the delivery catheter of any one 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.

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

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

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

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

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

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

Embodiment 83 provides the delivery catheter of any of embodiments 70-82, wherein the shaft comprises a wire lumen, the wire lumen being an integrally exchanged (OTW) shaft.

Embodiment 84 provides the delivery catheter of any of embodiments 70-83, wherein the shaft comprises a wire lumen as a rapid exchange (RX) shaft.

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

Embodiment 86 provides the delivery catheter of any one of embodiments 71-85, wherein the needle exit opening is located on one side of the shaft in the direction of movement of the steering mechanism.

Embodiment 87 provides the delivery catheter of any one of embodiments 70-86, wherein the shaft comprises at least one jet hole.

Embodiment 88 provides the delivery catheter of any one of embodiments 85-87, wherein the shaft comprises an irrigation lumen connected to the needle exit opening.

Embodiment 89 provides the delivery catheter of embodiment 88, wherein the flush lumen is for carrying a flush fluid, wherein the flush fluid is saline, heparinized saline, a therapeutic drug, or a combination thereof.

Embodiment 90 provides the delivery catheter of any of embodiments 87-89, further comprising a sleeve over at least some of the jet holes.

Embodiment 91 provides the delivery catheter of any one of embodiments 70-90, wherein the shaft comprises at least one vacuum hole.

Embodiment 92 provides the delivery catheter of any one 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 at least one needle for supplying ablation energy or agent to the one or more needles.

Embodiment 64 provides a method, a centering balloon catheter, or a delivery catheter according to any one or any combination of embodiments 1-63, optionally configured such that all elements or options listed can be used or selected from.

Claims

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:

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

deflating the balloon; and

removing the delivery catheter from the body lumen;

2. The method of claim 1, wherein the first body cavity and the second body cavity belong to different classes of body cavities selected from the group consisting of: renal artery, renal vein, gastric artery, hepatic artery, pulmonary artery, celiac artery, gastroduodenal artery, splenic artery, adrenal artery, diaphragmatic artery, mesenteric artery, airway, esophagus, stomach, duodenum, jejunum, and urinary lumen.

3. The method of claim 1, wherein the at least one disease comprises:

at least two diseases; or

At least three diseases; or

At least four diseases.

4. The method of claim 1, wherein the disease is selected from the group consisting of hypertension, pulmonary 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, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urinary system disease, cancer, tumor, pain, Rheumatoid Arthritis (RA), asthma, Chronic Obstructive Pulmonary Disease (COPD), and combinations thereof.

5. The method of claim 1, wherein the at least one disease comprises at least two diseases comprising:

renal hypertension and diabetes, or

Renal hypertension and obesity, or

Diabetes and obesity, or

Combinations thereof.

6. The method of claim 1, wherein the alleviating a symptom of a disease comprises lowering blood pressure, lowering blood glucose levels and AIC, reducing body weight, reducing restenosis, reducing liver fat, and reducing pain, or a combination thereof.

7. The method of claim 1, wherein the delivery catheter comprises a chemical infusion delivery catheter.

8. The method of claim 1, wherein the delivery catheter comprises an energy delivery catheter.

9. The method of claim 1, 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 formulation vapor into a liquid, or a combination thereof.

10. The method of claim 1, wherein the formulation comprises one or more ingredients selected from the group consisting of: water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropanol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodized oil, urea, and derivatives and combinations thereof.

11. The method of claim 1, wherein the formulation comprises ethanol.

12. The method of claim 1, wherein the formulation comprises an azeotrope.

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

a catheter shaft having a proximal end and a distal end;

at least one marker band located near the distal end of the shaft;

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

at least one balloon adjacent the distal end of the catheter;

an inflation lumen;

14. An infusion catheter comprising:

a shaft having a proximal end and a distal end; and

wherein the infusion catheter comprises:

an inflatable balloon disposed near 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 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 the longitudinal axis of the shaft, or

Combinations thereof.

15. The infusion catheter of claim 14, wherein the one or more needles comprise more than one needle.

16. An infusion catheter of claim 15, wherein the needle comprises a needle tip-to-tip span diameter of 5mm to 80mm measured when the needle is fully advanced from the infusion catheter.

17. The infusion catheter of claim 14, wherein the one or more needles comprise a shape memory material.

18. The infusion catheter of claim 14, wherein the one or more needles comprise nitinol.

19. The infusion catheter of claim 14, wherein the one or more needles comprise one or more radiopaque materials.

20. The infusion catheter of claim 14, wherein the shaft comprises:

at least one injection hole, or

An irrigation lumen connected to said needle outlet opening, or

At least one vacuum hole, or

Combinations thereof.