Delivery catheters and disease treatment methods

Abstract

Embodiments of the present invention provide devices and methods for treating at least one disease by delivering an effective amount of energy and / or an agent to tissue on or near a body cavity wall. The agent may include at least one of a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof of one or more components. The amount of agent and / or energy delivered is effective to damage or injure tissue, nerves, and / or nerve endings to alleviate disease symptoms.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 62 / 866,266, filed on June 25, 2019, U.S. Patent Application No. 16 / 563,235, filed on September 6, 2019, and U.S. Patent Application No. 16 / 690,992, filed on November 21, 2019, the disclosures of which are incorporated herein by reference in their entireties. Background Art

[0003] Hypertension (or high blood pressure) is a major global health problem. An estimated 30% to 40% of adults worldwide suffer from this condition. Furthermore, its prevalence is expected to increase, particularly in developing countries. Diagnosis and treatment of hypertension remain suboptimal, and most patients struggle to adequately control their blood pressure.

[0004] Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland that affects more than 50% of men over the age of 60. Early in life, the prostate is about the size of a walnut and weighs approximately 20 grams. Prostate enlargement over time is considered normal. With aging, the prostate gradually increases to at least twice its original size. Prostate growth increases pressure on the adjacent urethra, causing it to narrow and eventually lead to urinary tract obstruction, making urination difficult.

[0005] Chronic obstructive pulmonary disease (COPD) is associated with two main airflow obstruction conditions: chronic bronchitis and emphysema. Chronic bronchitis is caused by inflammation of the bronchial airways, which connect the trachea to the lungs. Emphysema is a disease caused by overinflation of the alveoli, or air sacs in the lungs. This condition causes shortness of breath. Approximately 16 million Americans have COPD, most of whom (80-90%) are lifelong smokers. COPD is the leading cause of death in the United States.

[0006] Asthma is a chronic respiratory disease characterized by excessive narrowing of the airways caused by airway inflammation, excessive mucus secretion, and airway hyperresponsiveness. This airway narrowing makes breathing difficult and can significantly impact a patient's life, limiting participation in many activities. In severe cases, asthma attacks can be life-threatening. To date, there is no known cure for asthma.

[0007] 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. Approximately 37 million cases of CS are reported annually to the Centers for Disease Control and Prevention (CDC).

[0008] Diabetes is a metabolic condition, or combination of conditions, in which an individual experiences high blood sugar levels. The condition is caused by insufficient insulin production in the body or the inability of cells to respond appropriately to insulin. Glycated hemoglobin (HbA1c) is a marker of plasma glucose concentration and is clinically used to diagnose diabetes. In humans, normal HbA1c levels are typically <6.0%, HbA1c levels in prediabetes range from 6.0-6.4%, and HbA1c levels in diabetes exceed 6.5%.

[0009] Diabetes is one of the leading causes of death and disability in the United States and other developed countries. It is associated with long-term complications that affect nearly every part of the body. For example, it is linked to blindness, heart and blood vessel disease, stroke, kidney failure, amputation, and nerve damage.

[0010] In the United States, diabetes affects approximately 8% of the population and results in a cost of nearly $250 billion.

[0011] Diabetes is typically classified as type 1 (also known as insulin-dependent diabetes or juvenile diabetes), type 2 (also known as non-insulin-dependent diabetes, adult-onset diabetes or obesity-related diabetes), in which patients with type 1 do not produce enough insulin, or type 2 patients who do not respond appropriately to insulin, or gestational diabetes, a condition that develops in women late in pregnancy.

[0012] Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of all cases. It is often associated with older age, obesity, a family history, a previous history of gestational diabetes, and inactive physical activity. It is also more prevalent in certain ethnic groups. Type 2 diabetes is also known as insulin-resistant diabetes because the pancreas normally produces sufficient amounts of insulin, but the body cannot respond appropriately 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.

[0013] The liver is of vital importance for maintaining normal glucose homeostasis, producing glucose during fasting and storing glucose after meals. However, these liver processes are imbalanced in type 1 and type 2 diabetes, and this imbalance leads to hyperglycemia in fasting and postprandial states. 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 peripheral tissues such as taste buds, intestinal tract and carotid body. In the liver, glucose levels are also sensed at the portal vein. Activation of the sympathetic efferent nerves increases the production of glucose and inhibits glycogenesis.

[0014] To measure fasting blood sugar, a blood sample can be collected after fasting overnight. A fasting blood sugar level below 100mg / dL (5.6mmol / L) is normal. A fasting blood sugar level of 100-125mg / dL (5.6-6.9mmol / L) is considered prediabetes. A measurement of 126mg / dL (7mmol / L) or higher in two separate tests is considered to indicate diabetes. The fasting blood sugar level of a diabetic patient ranges from 126mg / dL to 400mg / dL or even higher, or from 126mg / dL to 300mg / dL, or from 126mg / dL to 250mg / dL. The liver acts as a glucose (or fuel) reservoir for the body and helps maintain the stability and constancy of circulating blood sugar levels and other body fuels. The liver stores and manufactures glucose according to the needs of the body. The need to store or release glucose is primarily signaled by insulin and glucagon. During meals, the liver stores sugar, or glucose, as glycogen for later use when the body needs it. High insulin levels and suppressed glucagon levels during meals promote the storage of glucose as glycogen. When not eating—especially overnight or between meals—the body must produce its own sugar. The liver provides this supply by converting glycogen into glucose in a process called glycogenolysis. The liver can also produce the necessary sugar, or glucose, by collecting amino acids, waste products, and fat byproducts. This process is called gluconeogenesis. As the body's glycogen stores become low, the body begins to conserve sugar for organs that always need it. These organs include the brain, red blood cells, and parts of the kidneys. To supplement the limited sugar supply, the liver produces alternative fuels from fat called ketones. This process is called ketosis. The hormonal signal to initiate ketosis is low insulin levels. The ketones are burned as fuel by muscles and other organs, while the sugar remains for organs that need it.

[0015] Glucagon, epinephrine, norepinephrine, cortisol, and growth hormone help maintain blood sugar levels and increase blood sugar levels. People with diabetes have high levels of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. Glucagon is produced by islet cells (α cells) in the pancreas and controls the production of glucose and another fuel, ketones, in the liver. Glucagon is released at night and between meals and is important for maintaining the body's glucose and fuel balance. It signals the liver to break down its starch or glycogen stores and helps form new glucose units and ketone units from other substances. It also promotes the breakdown of fat in fat cells. Epinephrine and norepinephrine are very similar. Both are neurotransmitters and increase blood pressure and blood sugar levels. Epinephrine (adrenaline) is released from nerve endings and the adrenal glands and acts directly on the liver to promote glucose production (through glycogenolysis). Epinephrine also promotes the breakdown and release of nutrients from fat, which enter the liver and are converted into glucose and ketones. Cortisol is a steroid hormone also secreted by the adrenal glands. It makes fat and muscle cells resistant to the effects of insulin and increases glucose production in the liver. Under normal circumstances, cortisol counteracts the effects of insulin. However, under stress or if synthetic cortisol is used as a medication (for example, with prednisone therapy or cortisone injections), cortisol levels can rise and lead to insulin resistance. When patients have type 2 diabetes, this means they may need to take more medication or insulin to control their blood sugar. Growth hormone is released from the pituitary gland, which is part of the brain. Like cortisol, growth hormone counteracts the effects of insulin on muscle and fat cells. High levels of growth hormone cause resistance to the effects of insulin.

[0016] Obesity is another major health problem, particularly in developed countries. It is a complex, multifactorial and chronic condition characterized by excessive body fat, which is caused by an imbalance between energy expenditure and caloric intake. Although the causes of this imbalance are not yet fully understood, genetic and / or acquired physiological events and environmental factors are considered to contribute. The adverse health effects associated with obesity and particularly morbid obesity have become more established in recent years. Such adverse effects include, but are not limited to, cardiovascular disease, diabetes, hypertension, arthritis and sleep apnea. In general, as the patient's body mass index (BMI) increases, the likelihood of developing the adverse effects associated with obesity also increases.

[0017] Metabolic syndrome is a serious health condition that affects up to one-third of American adults and puts them at higher risk for cardiovascular disease, type 2 diabetes, stroke, and diseases related to the buildup of fat in artery walls. It is a group of co-occurring conditions that include high blood pressure, high blood sugar, excess fat around the waist, and abnormal cholesterol or triglyceride levels. The National Institutes of Health guidelines define metabolic syndrome as having three or more of the following characteristics (including the characteristic you're taking medication to control): a large waist (measuring at least 35 inches (89 cm) for women and 40 inches (102 cm) for men), high triglyceride levels (150 mg / dL or 1.7 mmol / L, or higher, of these fats found in the blood), low "good" or HDL cholesterol (HDL cholesterol less than 40 mg / dL (1.04 mmol / L) for men or less than 50 mg / dL (1.3 mmol / L) for women), elevated blood pressure (130 / 85 mm Hg or higher), and elevated fasting blood sugar (100 mg / dL (5.6 mmol / L) or higher).

[0018] Nonalcoholic fatty liver disease (NAFLD) is another health problem that occurs when the liver has trouble breaking down fat, causing fat to build up in liver tissue in people who drink little or no alcohol. It is normal for the liver to contain some fat. However, if more than 5% to 10% of the liver's weight is fat, it is called fatty liver disease (steatosis). Nonalcoholic fatty liver disease (NAFLD) is common and, in most people, does not cause signs, symptoms, or complications. But in some people with NAFLD, the accumulated fat can lead to inflammation and scarring of the liver. This more serious form of NAFLD is sometimes called nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. In its most severe cases, NAFLD can progress to liver failure. NASH is associated with dyslipidemia, low high-density lipoprotein (HDL) (<40 mg / dL in men or <50 mg / dL in women), hypertriglyceridemia (≥150 mg / dL), hypercholesterolemia (≥200 mg / dL), and a triglyceride (TG) / HDL ratio >5.0. NASH resolution is associated with a decrease in TG and the TG / HDL ratio.

[0019] The spleen is a major filter for blood-borne pathogens and a key organ for iron metabolism and red blood cell homeostasis. The spleen also plays an important role in the immune response to inflammatory conditions, including rheumatoid arthritis (RA), cancer, myocardial infarction, and atherosclerosis. The autonomic nervous system regulates immunity or responds to inflammatory stimuli by upregulating sympathetic nerve transmission to the spleen, which can mobilize monocytes to sites of tissue injury and release cytokines that regulate the inflammatory response. Summary of the Invention

[0020] Embodiments of the present invention relate to a delivery catheter for delivering chemical preparations and / or energy, and a method for treating at least one disease, such as by treating at least two different target tissues in a procedure.Described at least one disease can 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 its combination.Delivery catheter can deliver effective amount of energy or / and chemical preparation to target tissue in body, to alleviate disease symptoms, such as reduce the blood pressure of hypertension, reduce blood sugar level and AIC of diabetes, reduce the weight of obesity, reduce restenosis of coronary artery and peripheral disease, reduce the liver fat of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and reduce the pain of cancer and arthritis. Energy can be radiofrequency, cryoablation, microwave, laser, ultrasound, high intensity focused ultrasound energy or a combination thereof. Target tissue can 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch or the distal end of the right main renal artery branch), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum and a urinary cavity. Delivery catheters can include radiofrequency catheters, cryoablation catheters, microwave catheters, laser catheters, ultrasound catheters, high intensity focused ultrasound catheters or a combination thereof. Delivery catheters can include a combination of balloons and infusion catheters, as well as other delivery devices. The formulation delivered by the delivery catheter can include one or more components in the form of gas, vapor, liquid, solution, emulsion, suspension, or combinations thereof. By delivering the formulation to target tissues in the human body through chemical infusion from the delivery catheter, the safety and efficacy of the treatment can be improved.

[0021] Various embodiments of the present invention provide a method for treating at least one disease, comprising treating at least two different target tissues in at least two different body cavities. The method comprises performing a treatment procedure on a body cavity that is a first body cavity. The treatment procedure comprises inserting a delivery catheter into the body cavity. The delivery catheter comprises a catheter shaft, a balloon at the distal end of the shaft, and an inflation cavity in fluid communication with the interior of the balloon. The treatment procedure comprises inflating the balloon so that the distal end of the shaft is centered in the body cavity. The treatment procedure comprises denervating or ablating the target tissue of the body cavity with the delivery catheter, comprising delivering a certain amount of energy or formulation to the target tissue to effectively damage or impair the target tissue to alleviate the symptoms of the disease. The treatment procedure comprises deflation of the balloon. The treatment procedure also comprises removing the delivery catheter from the body cavity. The method also comprises performing the treatment procedure on a second body cavity that is different from the first body cavity.

[0022] The method for treating at least one disease of at least two different target tissues in at least two different body cavities using a delivery catheter can be a method for treating metabolic syndrome.The method can include treating the first, second, third and fourth target tissues that are all different from each other and are respectively positioned at the first, second, third and fourth body cavities.The first body cavity can include renal artery (for example, the distal end of left main renal artery, right main renal artery, renal artery branch, left renal artery branch, right renal artery branch, left main renal artery, the distal end of the distal end of right main renal artery, the distal end of left main renal artery branch or right main renal artery branch), renal vein, pulmonary artery, vascular cavity, celiac artery, common hepatic artery, proper hepatic artery, gastroduodenal artery, right hepatic artery, left hepatic artery, splenic artery, right gastric artery, left gastric artery, right adrenal artery, left adrenal artery, right subphrenic artery, left subphrenic artery, non-vascular cavity, esophagus, digestive cavity, stomach, duodenum, jejunum or its combination. The second body cavity may include the right main renal artery, the left main renal artery, the right renal branch artery, the left renal branch artery, the common hepatic artery, the proper hepatic artery, the gastroduodenal artery, the right hepatic artery, the left hepatic artery, the splenic artery, the right gastric artery, the left gastric artery, the right adrenal artery, the left adrenal artery, the right subphrenic artery, the left subphrenic artery, or a combination thereof. The third body cavity may include the splenic artery, the gastric artery, the left gastric artery, or a combination thereof. The fourth body cavity may include the gastroduodenal artery, the gastric artery, the left gastric artery, the right adrenal artery, the left adrenal artery, the right subphrenic artery, the left subphrenic artery, or a combination thereof. The chemical formulation and / or energy delivered to the target tissue may reduce weight, lower hypertension, lower AIC, lower blood sugar levels, reduce body waist fat tissue, or a combination thereof.

[0023] A method of treating at least one disease comprising using a delivery catheter to treat at least two different target tissues in at least two different body cavities may be a method of treating hypertension. The method may include treating first, second, third, and fourth target tissues, all of which are distinct from one another and located in first, second, third, and fourth body cavities, respectively. The first body cavity may include a renal artery, such as the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof. The second body cavity may include the common hepatic artery, the proper hepatic artery, the gastroduodenal artery, the right hepatic artery, the left hepatic artery, the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The third body cavity may include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth target tissue may include the gastroduodenal artery, the right gastric artery, the left gastric artery, the right adrenal artery, the left adrenal artery, the right inferior phrenic artery, the left inferior phrenic artery, or a combination thereof. The chemical agent and / or energy delivered to the target tissue may lower blood pressure.

[0024] A method for treating at least one disease comprising using a delivery catheter to treat at least two different target tissues in at least two different body cavities can be a method for treating diabetes. The method can include treating first, second, third, and fourth target tissues, all of which are different from each other and located in first, second, third, and fourth body cavities, respectively. The first body cavity can include the common hepatic artery, the proper hepatic artery, the right hepatic artery, the left hepatic artery, or a combination thereof. The second body cavity can include a renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch, or the distal end of the right main renal artery branch), the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The third body cavity can include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth body cavity can include the gastroduodenal artery, the right gastric artery, the left gastric artery, the right adrenal artery, the left adrenal artery, the right subphrenic artery, the left subphrenic artery, or a combination thereof. The chemical formulation and / or energy delivered to the target tissue can reduce blood glucose levels, reduce AIC, or a combination thereof.

[0025] A method for treating at least one disease comprising using a delivery catheter to treat at least two different target tissues in at least two different body cavities can be a method for treating obesity. The method can include treating first, second, third, and fourth target tissues, all of which are different from each other and located in first, second, third, and fourth body cavities, respectively. The first body cavity can include the common hepatic artery, the proper hepatic artery, the right hepatic artery, the left hepatic artery, or a combination thereof. The second body cavity can include a renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch, or the distal end of the right main renal artery branch), the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The third body cavity can include the splenic artery, the right gastric artery, the left gastric artery, or a combination thereof. The fourth body cavity can include the gastroduodenal artery, the right gastric artery, the left gastric artery, the right adrenal artery, the left adrenal artery, the right subphrenic artery, the left subphrenic artery, or a combination thereof. The chemical formulation and / or energy delivered to the target tissue can reduce weight, lower body mass index, or a combination thereof.

[0026] The method for treating at least one disease including using a delivery catheter to treat at least two different target tissues in at least two different body cavities can be a method for treating non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) or a combination thereof. The method can include treating the first, second, third and fourth target tissues that are all different from each other and are located in the first, second, third and fourth body cavities respectively. The first body cavity can include the common hepatic artery, the proper hepatic artery, the right hepatic artery, the left hepatic artery or a combination thereof. The second body cavity can include a renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch or the distal end of the right main renal artery branch), a splenic artery, a right gastric artery, a left gastric artery or a combination thereof. The third body cavity can include a splenic artery, a right gastric artery, a left gastric artery or a combination thereof. The fourth body cavity can include a gastroduodenal artery, a right gastric artery, a left gastric artery, a right adrenal artery, a left adrenal artery, a right subphrenic artery, a left subphrenic artery or a combination thereof. Chemicals and / or energy delivered to target tissues can reduce fat in the liver.

[0027] In various embodiments, the present invention provides a method for treating a disease. The method comprises inserting a delivery catheter into a body cavity, wherein the delivery catheter comprises a catheter shaft, at least one spray hole, and at least one marker band. The method comprises spraying a formulation through the at least one spray hole, wherein the amount of formulation delivered is effective to damage or impair target tissue to alleviate symptoms of the disease. The method comprises optionally removing the formulation from the tissue. The method further comprises withdrawing the delivery catheter from the body cavity.

[0028] In various embodiments, the present invention provides a method for treating a disease. The method includes inserting a centering balloon delivery catheter into a body cavity, wherein the balloon delivery catheter includes at least one centering balloon and a catheter shaft, at least one injection needle, and at least one marking band. The method includes inflating the centering balloon to center the delivery catheter shaft in the body cavity. The method includes deploying at least one needle into, outside, or inside the body cavity wall. The method includes infusing a formulation through at least one needle, wherein the amount of formulation delivered effectively damages or impairs the target tissue to alleviate the symptoms of the disease. The method optionally includes removing the formulation from the tissue. The method includes retracting the needle into the delivery catheter and deflating the centering balloon. The method includes removing the delivery catheter from the body cavity.

[0029] In various embodiments, the present invention provides a centering balloon catheter for delivering a material to a target location in a body cavity of a patient. The centering balloon catheter comprises a proximal end; a distal end; a wire lumen; a balloon inflation lumen; a formulation infusion lumen and / or a vacuum lumen; an expandable balloon portion; at least one injection needle; at least one marker band adjacent to the centering balloon; and at least one needle exit opening adjacent to the marker band for deploying the needle.

[0030] In various embodiments, the present invention provides a needle-based balloon delivery catheter for delivering a material to a target tissue in a body cavity of a patient. The delivery catheter comprises 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 comprises at least one needle located within a needle lumen, wherein the needle lumen opens to the exterior of the catheter shaft through at least one needle exit aperture. The delivery catheter includes an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen, the irrigation lumen being in fluid communication with the distal end of the needle lumen, wherein the irrigation port is in fluid communication with the needle exit 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 to the distal end of the catheter. The delivery catheter includes an inflation lumen. The delivery catheter includes an inflation port in fluid communication with the inflation lumen and with the interior of the balloon. The balloon can be inflated through the inflation lumen via the inflation port, thereby substantially centering the distal end of the catheter shaft within the body cavity. The delivery catheter includes an ablation or denervation port at the proximal end of the shaft. The ablation or denervation port is in fluid communication with the at least one needle to supply ablative energy or agent to the at least one needle. The delivery catheter also includes a needle movement controller in electrical or mechanical communication with the at least one needle. The needle movement controller deploys the at least one needle into the body cavity, into the wall of the body cavity, or outside the body cavity.

[0031] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter includes one or more needles disposed near the distal end of the shaft for infusion therapy. The delivery catheter includes 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 within the lumen. The delivery catheter also includes a marker band located at the distal end of the shaft.

[0032] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter includes one or more needles disposed near the distal end of the shaft for infusion therapy. The delivery catheter also includes a steering mechanism associated with the shaft that allows the distal end of the shaft to be steered in a direction away from the longitudinal axis of the shaft.

[0033] In various embodiments, the present invention provides a delivery catheter. The delivery catheter includes a shaft having a proximal end and a distal end. The delivery catheter also includes one or more needles disposed near the distal end of the shaft for infusion therapy. The delivery catheter also includes 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 within the lumen, wherein the distal end of the shaft includes a marker band; or a steering mechanism associated with the shaft such that the distal end of the shaft can be steered in a direction away from the longitudinal axis of the shaft; or a combination thereof.

[0034] Embodiments of the present invention relate to treating hypertension, diabetes, obesity, metabolic syndrome, heart failure, myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), end-stage renal disease, digestive tract disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urological diseases, cancer, tumors, pain, rheumatoid arthritis, asthma and chronic obstructive pulmonary disease (COPD) by delivering an effective amount of a formulation to a target tissue. Such a formulation comprises a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof of one or more components. The method comprises controlled delivery of the formulation to luminal surfaces and tissues within the human body, thereby modifying these areas. Such a method can result in denervation of nerves and nerve endings within and adjacent to the body cavity. The method can also include beneficially cutting off nerves and nerve endings to interrupt neural communication. Temperature can improve the safety and effectiveness of the therapeutic formulation. The temperature of the formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or higher. 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 absorption and penetration of the formulation into body tissues and luminal nerves and nerve endings.

[0035] In one embodiment, the formulation comprises water, saline, hypertonic saline, phenols, methanol, ethanol, absolute alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodized oil, a surfactant, a derivative thereof, or a combination thereof.

[0036] In one embodiment, at least one component of the formulation is a gas. The gas comprises one of the following: oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, water, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, derivatives thereof, and combinations thereof.

[0037] In one embodiment, at least one component of the formulation is a surfactant. The surfactants include PEG laurate, Tween 20, Tween 40, Tween 60, Tween 80, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG dehydrated sorbitan. PEG sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, an organic acid, a salt of any organic acid and an organic amine, polyglycidol, glycerol, polyglycerol, galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomers, di(propylene glycol), tri(propylene glycol), tetra(propylene glycol), penta(propylene glycol), poly(propylene glycol) oligomers, block copolymers of polyethylene glycol and polypropylene glycol, Pluronic, Pluronic 85, a derivative thereof, or a combination thereof.

[0038] In one embodiment, the formulation comprises at least one of an oil, a fatty acid, and a lipid. In some embodiments, at least one of the oil, fatty acid, and lipid in the formulation is selected from the group consisting of butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienols, butyric acid, caproic acid, caprylic acid, capric acid, and decanoic acid. acid), lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, α-linolenic acid, γ-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di- or triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, α-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobees, niosomes and their derivatives.

[0039] In another embodiment, the formulation includes a therapeutic agent or drug for denervation of a nerve. The therapeutic agent includes at least one of the following: sodium channel blockers, tetrodotoxins, saxitoxins, decarbamoyl saxitoxins, vanilloids, neosaxitoxins, lidocaine, conotoxins, cardiac glycosides, digoxins, glutamates, staurosporines, amlodipines, verapamils, cymarins, digitoxins, proscillaridins, quabains, veratridines, domoic acids, In another embodiment, the formulation includes a contrast agent for imaging denervation of a nerve. Such a contrast agent includes one of the following: iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof, and combinations thereof.

[0040] In one embodiment, the formulation comprises an azeotrope. An azeotrope is a mixture of two or more components that cannot be changed by simple distillation. This occurs because the vapor produced during boiling has components proportional to the components of the original mixture. Possible formulation azeotropes include ethanol / water, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropyl alcohol / water, butanol / water, acetic acid / water, or a combination thereof.

[0041] In one embodiment, the preparation is in a gaseous or vaporous state and comprises one or more components. Steam or gas preparations may comprise oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, water, phenol, methanol, ethanol, absolute alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate or its combination. In one embodiment, the steam preparation comprises one of binary, ternary or quaternary components, and may comprise more than four components. The steam preparation may comprise azeotropes or contrast agents, such as lipiodol or iodine, and may comprise surfactants and / or therapeutic agents. The temperature of the vapor formulation may be from 0 to 140°C, preferably from 15 to 100°C, most preferably from 20 to 85°C, or 0°C or less, or less than, equal to, or greater than 10°C, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more.

[0042] In one embodiment, the preparation is liquid and includes one or more components.Liquid preparation can include one of: water, saline, hypertonic saline, phenol, methanol, ethanol, absolute alcohol, isopropyl alcohol, propyl alcohol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodized oil, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, surfactant and other.Liquid preparation can include azeotrope or contrast agent and can include therapeutic agent. In one embodiment, preparation can include one of binary, ternary or quaternary components, and can also include more than four components. In some embodiments, the liquid formulation temperature can be -40 to 140° C., -30 to 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. The liquid formulation can include a solution, a suspension, an emulsion, or a combination thereof.

[0043] In one embodiment, the method for treating at least one disease comprises inserting a delivery catheter percutaneously and / or perorally into a target tissue in a human body; using the catheter to infuse a therapeutic formulation into the tissue of the body, wherein the amount of formulation delivered is effective to beneficially injure or damage the tissue; optionally removing the formulation; and removing the delivery catheter from the body. The injury or damage to the tissue can alleviate the symptoms of the disease, for example, by lowering blood pressure, lowering blood sugar levels, reducing weight, relieving shortness of breath, relieving heart disease, relieving vascular conditions, relieving joint pain, relieving stiffness, relieving swelling, or a combination thereof. The at least one disease targeted by the treatment includes one or more of the following: high blood pressure, 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 diseases, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urological diseases, cancer, tumors, pain, rheumatoid arthritis (RA), asthma, and chronic obstructive pulmonary disease (COPD). In a program, treat multiple related diseases and may be more effective, for example, for suffering from two or more patients in hypertension, obesity and type 2 diabetes simultaneously.The tissue that can treat can comprise renal artery (for example, the distal end of left main renal artery, right main renal artery, renal artery branch, left renal artery branch, right renal artery branch, left main renal artery, the distal end of right main renal artery, the distal end of left main renal artery branch or the 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, phrenic artery, phrenic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum and urinary cavity.Digestive cavity can comprise esophagus, stomach, duodenum, jejunum, small intestine and large intestine and colon.Preparation can comprise the gas, steam, liquid, solution, emulsion, suspension of one or more compositions, or its combination. If the preparation includes the vapor of one or more components, heat can be generated by condensing the vapor into a liquid in the tissue. If the preparation includes a liquid or solution, cooling or heat can be generated by a preparation temperature that is lower than or higher than body temperature. The liquid preparation temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C or -40°C or lower, or less than, equal to or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130 or 140°C or higher. In one embodiment, the preparation temperature can be equal to room temperature. In one embodiment, the preparation temperature can be -40 to -20°C. In another embodiment, the preparation temperature can be 15 to 80°C. In one embodiment, the preparation temperature can be equal to body temperature.In another embodiment, the temperature of the formulation can be between 50 and 80°C. In another embodiment, the temperature of the treated tissue can be below the formulation temperature and above body temperature. The temperature of the treated tissue can be between -40 and 100°C, -30 and 90°C, -20 to 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or higher. In one embodiment, the temperature of the treated tissue can be between -40 and -20°C. In another embodiment, the temperature of the treated tissue can be between 15 and 80°C. In one embodiment, the temperature of the treated tissue can be equal to body temperature. In another embodiment, the temperature of the treated tissue can be between 50 and 80°C. Delivery catheters suitable for this treatment include needles or needle-based catheters under imaging guidance. Imaging guidance includes one of the following: ultrasound, X-ray, CT scan, MRI, OCT, or oscilloscope. The delivery catheter can also be balloon-based. Such a balloon-based catheter can have both a balloon and a needle in one catheter. The delivery catheter can be jet-based. Jet-based catheters are capable of producing very fine mists to large droplets. In some embodiments, a combination of a balloon and a jet catheter can be used in the procedure (e.g., without a needle), a combination of a needle catheter and a jet catheter can be used, or a combination of a needle catheter, a jet catheter, and a balloon catheter can be used (e.g., including jet- and needle-based formulation administration). In one embodiment, the method includes flushing from the distal tip of the catheter to protect and dilute the migrating chemicals and prevent runaway chemicals from entering the distal portion of the untreated area; flushing from the delivery catheter; flushing from the endoscope; removing or taking out the formulation from body tissues and cavities after treatment; and flushing the treated target area with saline. If a needle is present, the method may also include deploying the needle, administering the formulation from the needle, and retracting the needle.

[0044] In one embodiment, the delivery catheter includes at least one needle for delivering the formulation into the vessel wall, outside the vessel, or a combination thereof. In some needle-catheter embodiments, at least one balloon is used to approximately center the distal end of the catheter in the cavity, or approximately center the portion of the catheter from which the needle emerges in the cavity. When the distal end of the catheter is centered in the treatment cavity, the user has better control over the needle and injection depth. In some needle-catheter embodiments, there are two centering balloons and the at least one needle is positioned between the two balloons. In some needle-catheter embodiments, there is only one balloon and the at least one needle can 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 in the center of the treatment cavity. In one embodiment of the needle-catheter, there is no centering balloon.

[0045] In one embodiment, the delivery catheter comprises a spray catheter. In this embodiment, the formulation is delivered through a spray orifice at or near the distal end of the catheter, thereby delivering the formulation to the walls of the treatment lumen in the form of a mist. This embodiment may include a sleeve positioned above the spray orifice to provide a more even distribution of the formulation to the walls of the treatment lumen. This embodiment may include a vacuum port for removing excess formulation from the treatment lumen. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The drawings illustrate generally and by way of example and not limitation, various embodiments of the invention.

[0047] Figure 1 is an exemplary embodiment of a perspective view of a dual balloon delivery catheter according to the present invention.

[0048] Figure 2 is an embodiment demonstrating the use of a jet catheter to infuse a formulation into the airway.

[0049] Figure 3 is an embodiment demonstrating the use of a three-needle balloon delivery catheter to infuse the formulation into the renal artery.

[0050] Figure 4 is an embodiment of a partial cross-sectional view of a double-balloon delivery catheter in a body lumen.

[0051] Figure 5 is an embodiment of a partial cross-sectional view of a triple needle dual balloon delivery catheter with needles deployed in a body lumen.

[0052] Figure 6A is an exemplary embodiment of a perspective view of an over-the-wire (OTW) three-needle balloon delivery catheter according to the present invention.

[0053] Figure 6B is an exemplary embodiment of a perspective view of an OTW triple needle balloon delivery catheter with a balloon and needle deployed in accordance with the present invention.

[0054] Figure 7A is another exemplary embodiment of a perspective view of a rapid exchange three-needle balloon delivery catheter prior to needle deployment in accordance with the present invention.

[0055] Figure 7B is an exemplary embodiment of a perspective view of a rapid exchange three-needle balloon delivery catheter with a flush lumen after needle deployment in accordance with the present invention.

[0056] Figure 7C According to various embodiments such as Figure 7B A cross section of the catheter is shown at section 7C-7C.

[0057] Figure 7D According to various embodiments such as Figure 7B A cross section of the catheter is shown at section 7D-7D.

[0058] Figure 7E According to various embodiments such as Figure 7B A cross section of the catheter is shown at section 7E-7E.

[0059] Figure 7F According to various implementation plans Figure 7B An alternative cross section of the conduit is shown at section 7F-7F.

[0060] Figure 7G According to various embodiments such as Figure 7B A cross section of the catheter is shown at section 7G-7G.

[0061] Figure 8A is an exemplary embodiment of a perspective view of a steerable catheter prior to needle deployment.

[0062] Figure 8B is an exemplary embodiment of a perspective view of a steerable catheter after needle deployment.

[0063] Figure 9A is an exemplary embodiment of a perspective view of a steerable catheter prior to needle deployment.

[0064] Figure 9B is an exemplary embodiment of a perspective view of a steerable catheter with needle deployment.

[0065] Figure 9C is an embodiment of a partial cross-sectional view of a one-way steerable catheter with a needle deployed in a body lumen.

[0066] Figure 10 is a bar graph showing the reduction in norepinephrine (NE) following renal denervation in an ethanol-treated group versus a control-treated group, according to various embodiments.

[0067] Figure 11 are histopathological images showing necrosis of severed renal nerves (indicated by black arrows) following ethanol treatment, according to various embodiments.

[0068] Figure 12 is a bar graph showing the reduction in norepinephrine (NE) following liver denervation from ethanol-treated groups versus control-treated groups, according to various embodiments.

[0069] Figure 13 is an exemplary embodiment of a perspective view of an injection conduit according to the present invention.

[0070] Figure 14 is an exemplary embodiment of a perspective view of a jet conduit having a dual suction feature according to the present invention.

[0071] Figure 15A is an embodiment in which the formulation is infused into the left gastric artery using a three-needle balloon delivery catheter.

[0072] Figure 15B is an embodiment in which the formulation is infused into the hepatic artery using a three-needle balloon delivery catheter. DETAILED DESCRIPTION

[0073] 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 illustrated subject matter is not intended to limit the claims to the disclosed subject matter.

[0074] Throughout this document, values ​​expressed in range format should be interpreted in a flexible manner to include not only the values ​​explicitly stated as range limits, but also all individual values ​​or subranges contained in the range, as if each value and subrange were explicitly stated. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only about 0.1% to about 5%, but also individual values ​​(e.g., 1%, 2%, 3%, and 4%) and subranges within the specified range (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%). Unless otherwise specified, the expression "about X to Y" has the same meaning as "about X to about Y." Similarly, unless otherwise specified, the expression "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z."

[0075] In this document, unless the context clearly dictates otherwise, the terms "a", "an" or "the" are used to include one or more. Unless otherwise specified, the term "or" is used to refer to a non-exclusive "or". The expression "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B". In addition, it should be understood that the words or terms used herein, and in the absence of any contrary qualification, are for descriptive purposes only and have no limiting effect. Any use of section headings is intended to facilitate reading of the document and should not be construed as limiting; information related to a section heading may appear within or outside that particular section.

[0076] In the methods described herein, unless a chronological or operational order is explicitly stated, the actions may be performed in any order without departing from the principles of the present invention. Furthermore, specified actions may be performed simultaneously unless explicit claim language specifies that they be performed separately. For example, performing a claimed action of X and performing a claimed action of Y may be performed simultaneously within a single operation, and the resulting method would fall within the literal scope of the claimed method.

[0077] As used herein, the term "about" can allow a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of the specified limit of a specified value or range, and includes the exact specified value or range.

[0078] As used herein, the term "substantially" means a 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%. As used herein, the term "substantially free" can mean having no or insignificant amounts of a material such that the amount of material present does not affect the material properties of the composition including the material, such that from about 0 wt % to about 5 wt % of the composition is the material, or from about 0 wt % to about 1 wt %, or about 5 wt % or less, or less than, equal to, or greater than about 4.5 wt %, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt % or less, or about 0 wt %.

[0079] As used herein, the term "polymer" refers to a molecule having at least one repeating unit and may include copolymers.

[0080] In various embodiments, the present invention provides a method for treating at least one disease (e.g., one disease, two diseases, at least two diseases, three diseases, at least three diseases, four diseases, or at least four diseases). The method comprises using a delivery catheter in a body cavity, for example, to treat at least two different target tissues in at least two different body cavities. The method comprises performing a treatment procedure on a body cavity that is a first body cavity. The treatment procedure may comprise inserting a delivery catheter into the body cavity. The delivery catheter may comprise a catheter shaft, a balloon at the distal end of the shaft, and an inflation lumen in fluid communication with the interior of the balloon. The treatment procedure may comprise inflating the balloon so that the distal end of the shaft is centered in the body cavity. The treatment procedure may comprise denervating or ablating a target tissue of the body cavity with the delivery catheter, comprising delivering an amount of energy or agent to the target tissue to effectively damage or impair the target tissue to alleviate symptoms of the disease. The treatment procedure may comprise deflation of the balloon. The treatment procedure may also comprise removing the delivery catheter from the body cavity. The method may comprise performing a treatment procedure on a second body cavity that is different from the first body cavity.

[0081] Performing the treatment procedure on the second body lumen may include using the same delivery catheter or a different delivery catheter. Performing the treatment procedure on the second body lumen may include reusing the same delivery catheter used in the treatment procedure on the first body lumen in the treatment procedure on the second body lumen. Performing the treatment procedure on the second body lumen may include using a different delivery catheter in the treatment procedure on the second body lumen than used in the treatment procedure on the first body lumen, the different delivery catheter comprising a catheter shaft, a balloon at a distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon.

[0082] Treating at least two different target tissues in at least two different body cavities refers to treating at least two body cavities selected from the following: 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, phrenic artery, phrenic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, and urinary cavity. The renal artery may include the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch, and the distal end of the right main renal artery branch. The gastric artery may include the left gastric artery, the right gastric artery, a left gastric artery branch, and a right gastric artery branch. The hepatic artery may include the hepatic artery, the common hepatic artery, the proper hepatic artery, the left hepatic artery, the middle hepatic artery, and a hepatic artery branch. The splenic artery may include the main splenic artery and a splenic artery branch. The adrenal artery may include the right adrenal artery and the left adrenal artery. The phrenic artery may include the right inferior phrenic artery and the left inferior phrenic artery. The mesenteric artery may include the superior mesenteric artery, the inferior mesenteric artery and the mesenteric artery branches. The urinary cavity may include the urethra and the ureters. For example, treatment of the left gastric artery and the left gastric artery branches is considered to be treatment of one type of body cavity. Treatment of the left gastric artery and the main splenic artery is considered to be treatment of two different types of body cavities. Treating at least three different target tissues in at least three different body cavities, or treating at least four different target tissues in at least four different body cavities, is defined as treating three or four different types of body cavities, respectively.

[0083] The target tissues of the first and second body cavities can be different and can be independently selected from 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, or the distal end of a right main renal artery branch), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a target tissue of the urinary cavity. The disease to be treated can 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 diseases, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urological diseases, cancer, tumors, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD) and combinations thereof.

[0084] Relief of disease symptoms includes relieving the 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. Relief of disease symptoms may include lowering blood pressure, lowering blood sugar levels and AIC, reducing weight, reducing restenosis, reducing liver fat and alleviating pain or a combination thereof.

[0085] The at least one disease treated by the method of treating different target tissues in the first and second body cavities may include at least two diseases, such as both renal hypertension and diabetes (e.g., treating both the renal artery and the hepatic artery); or both renal hypertension and obesity (e.g., treating both the hepatic artery and the splenic artery); or both diabetes and obesity (e.g., treating the splenic artery, the hepatic artery, and the left gastric artery); or a combination thereof. The first or second body cavity may include the splenic artery. The first or second body cavity may include a renal artery (e.g., the left main renal artery, the right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of the left main renal artery branch, the distal end of the right main renal artery branch, or a combination thereof). The first or second body cavity may include the splenic artery. The first or second body cavity may include a main renal artery branch, an extra-renal artery branch, or a combination thereof. The first or second body cavity may include the hepatic artery, a hepatic artery branch, the right hepatic artery, the left hepatic artery, the common hepatic artery, the proper hepatic artery, the celiac artery, or a combination thereof. The first or second body cavity 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof), and the method may result in a reduction in renal norepinephrine of at least 40%, or at least 10%, 15, 20, 25, 30, 35, 40, 45, or at least 50%.

[0086] The delivery catheter may further include a guidewire lumen extending through at least the distal end of the shaft, wherein the method may further include advancing the delivery catheter over the guidewire. The delivery catheter may further include a marker band on or adjacent to the balloon, wherein the method may further include monitoring the position of the marker band under fluoroscopy.

[0087] The delivery catheter can be a chemical infusion delivery catheter. The delivery catheter can be an energy delivery catheter. The delivery catheter can be a combination of a chemical infusion delivery catheter and an energy delivery catheter. For an energy delivery catheter, denervating or ablating a target tissue in a body cavity with a delivery catheter can include using radiofrequency, cryoablation, microwaves, lasers, ultrasound, high-intensity focused ultrasound, condensation of at least some of the agent vapor into a liquid, or a combination thereof to deliver a certain amount of energy (e.g., thermal energy) from the delivery catheter or to the target tissue. Thus, the energy delivery catheter can be one of a radiofrequency catheter, a cryoablation catheter, a microwave catheter, a laser catheter, an ultrasound catheter, a high-intensity focused ultrasound catheter, an infusion catheter, or a combination thereof.

[0088] The delivery catheter can be a radiofrequency energy delivery catheter, or a combination of a radiofrequency energy delivery catheter and a chemical infusion catheter. In some embodiments, the safety and effectiveness of radiofrequency energy delivery is improved by increasing the size of the ablation caused by energy delivery while minimizing the risk of complications that may arise during energy delivery. Examples of such complications include thrombosis, steam burst, bubbling, target tissue charring, restenosis, fibrosis of the media and adventitia, and others related to catheter manipulation (i.e., perforation). Point thermal ablation (RF ablation) is uneven and does not reach the adventitial nerves. Partial point RF ablation results in low effectiveness (low blood pressure drop). The radiofrequency energy delivery catheter may include one or more electrodes. In various embodiments, the delivery catheter includes one or more needles, and the tips of the one or more needles can serve as electrodes (e.g., the needles can be insulated to leave only a portion for exposing the electrode, such as a 1 mm to 5 mm length of the needle non-insulated portion; in other embodiments, the needles are not insulated). The needles used for radiofrequency ablation can be the same as the needles described herein for chemical infusion, or they can be different. For example, the RF energy delivery needle can have any suitable diameter, can be solid or hollow, and can be used to deliver RF energy to a body cavity, a body cavity wall, or the exterior of a body cavity wall. For RF delivery, the return electrode can be positioned on the catheter, or a device such as a pad can be used. The delivery catheter can include one or more electrodes on a wire (e.g., a wire with spring or shape memory properties to ensure good contact with the target tissue), one or more electrodes on a polymer shaft, one or more electrodes on the outer surface of the balloon, or a combination thereof. The delivery catheter can include more than one electrode to achieve a shorter treatment time. The method can include cooling the electrode, such as by passive cooling via blood flow and / or by active fluid cooling, such as internal active cooling (closed loop) or external active fluid cooling (open loop). The size of the electrode can be reduced to increase passive cooling by blood flow. Cooling the electrode can increase energy delivery to the neural tissue of the target tissue. Cooling the needle electrode can include flowing a coolant or a liquid that enhances RF delivery through the needle (e.g., a chemical formulation or different liquid composition as described herein) before, during, or after RF delivery. In one embodiment of external cooling (open loop) of the electrode, the chemical formulations described herein can replace active cooling fluids. The disclosed formulations can be used not only to cool the electrode, but also for chemical ablation of target tissue. In some embodiments, the formulations can diffuse and penetrate into the neural tissue uniformly, and they can uniformly ablate the nerves in the adventitia in the body cavity. Thus, the chemical ablation formulation can be delivered during, before, and / or after energy ablation.

[0089] 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 ultrasound energy source may be located inside the balloon and cooled on the balloon surface or inside the balloon. The microwave or ultrasound energy source may be focused so as to treat only a subset of the circumference of the body cavity, or the energy source may deliver energy around the entire circumference of the body cavity. For delivery catheters that deliver laser energy, the delivery catheter may be configured so that the laser energy is emitted from the wall of the shaft. For delivery catheters that can perform cryoablation (i.e., deliver negative energy), a needle or jet hole may be used to deliver a cryoablative medium. During cryoablation, the cryoablative medium may be delivered to the target tissue, for example, through a needle. Once the substance leaves the delivery catheter, the pressure drop, evaporation, or phase change of the cryoablative medium may provide cryoablative treatment. If a liquid is used for cryoablation, the needle or jet hole may be sealed to prevent delivery until the delivery catheter is positioned, and the delivery catheter may include a gas return channel to discharge vapor from the cryoablative medium to the body. To perform cryoablation through the injection orifice, multiple balloons may be used to create a treatment window that contains the cryoablative fluid during treatment and prevents cryoablation of body cavity tissue outside the treatment window.

[0090] For any type of energy delivery, methods using a delivery catheter can include cooling the energy source by flushing the lumen to reduce the temperature of the energy source and clean the lumen (e.g., to clean an artery and prevent blood from clogging it). In various embodiments, a needle can be used for cooling. A delivery catheter for energy delivery can include a guidewire lumen to facilitate insertion and placement of the delivery catheter.

[0091] In some embodiments, the delivery catheter is electrodeless.The delivery catheter may be free of any ablative energy source, such as radiofrequency, ultrasound, and microwave energy sources.

[0092] Embodiments of the present invention relate to treating at least one disease by delivering an effective amount of preparation and / or energy to 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 its combination.Cancer includes adrenal cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, gastric cancer, uterine cancer or its combination.Preparation can include the gas, steam, liquid, solution, emulsion, suspension of one or more components, or its combination.Described method includes delivering preparation and / or energy to the cavity surface of human body, tissue and nerve to modify (modify) these surfaces, tissue and nerve. Tissue includes renal artery (for example left main renal artery, right main renal artery, renal artery branch, left renal artery branch, right renal artery branch, the distal end of left main renal artery, the distal end of right main renal artery, the distal end of left main renal artery branch, the distal end of right main renal artery branch or its combination), 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, phrenic artery, phrenic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, urinary cavity or its combination.Digestive cavity includes esophagus, stomach, duodenum, jejunum, small intestine and large intestine, colon or its combination.Temperature can improve the safety and effectiveness of therapeutic preparation. The temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated can be different from the temperature of the formulation. The temperature of the tissue being treated can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The amount of agent and energy delivered can be effective to beneficially injure, damage or eliminate (e.g., kill) the target tissue and thereby alleviate disease symptoms, such as by lowering blood pressure, shrinking tumors, relieving pain, relieving symptoms of asthma or COPD, or a combination thereof. Energy or heat can enhance the injuring / damaging / eliminating effect by accelerating the reaction rate between the agent and the tissue.The delivery method includes delivering a formulation to ablate nerves surrounding a human cavity. The method may include removing or extracting the formulation from the tissue or cavity after treatment. In the absence of direct observation, nerve ablation can be identified based on physiological functions corresponding to the nerves, such as glucose and norepinephrine (NE) levels. Norepinephrine is the primary neurotransmitter used by the sympathetic nervous system, which is connected to many organs, including, for example, the heart, lungs, liver, spleen, gallbladder, stomach, intestines, kidneys, bladder, and many other organs. For example, in the liver, increasing the sympathetic effects of norepinephrine increases glucose production, which is produced through postprandial glycogenolysis or gluconeogenesis when food has not been consumed recently. Therefore, correction of overactive hepatic sympathetic nerves will reduce NE content and lead to lower glucose levels. In the kidneys, the release of renin and the retention of sodium in the bloodstream increase blood pressure. The norepinephrine (NE) content in the tissue can be used as a biomarker to demonstrate or indicate the effectiveness of treatment. Various embodiments comprising methods of treating overactive hepatic sympathetic nerves can result in a decrease in NE levels of 20% to 99%, preferably, 50% to 98%, and most preferably, 75% to 97%, compared to untreated (control) subjects.

[0093] 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 can be used with less invasive transdermal or non-invasive methods. Embodiments of the present invention provide formulations comprising one or more ingredients that modify the surface of a body cavity by absorption and penetration into the tissues, nerves, and nerve endings of the body cavity.

[0094] In one embodiment, the formulation may comprise or consist of water, saline, hypertonic saline, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, iodized oil, a surfactant, a derivative thereof, or a combination thereof.

[0095] In one embodiment, the component of the formulation is at least one gas. The gas can be selected from oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, water, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

[0096] In one embodiment, the ingredient in the formulation is at least one surfactant. In some embodiments, the surfactant is selected from PEG laurate, Tween 20, Tween 40, Tween 60, Tween 80, PEG oleate, PEG stearate, PEG glyceryl laurate, PEG glyceryl oleate, PEG glyceryl stearate, polyglyceryl laurate, polyglyceryl oleate, polyglyceryl myristate, polyglyceryl palmitate, polyglyceryl-6 laurate, polyglyceryl-6 oleate, polyglyceryl-6 myristate, polyglyceryl-6 palmitate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 palmitate, PEG Sorbitan monolaurate, PEG sorbitan monolaurate, PEG sorbitan monooleate, PEG sorbitan stearate, PEG oleyl ether, PEG lauryl ether, organic acid, salt of any organic acid and organic amine, polyglycidol, glycerol, polyglycerol, galactitol, di(ethylene glycol), tri(ethylene glycol), tetra(ethylene glycol), penta(ethylene glycol), poly(ethylene glycol) oligomers, di(propylene glycol), tri(propylene glycol), tetra(propylene glycol), penta(propylene glycol), poly(propylene glycol) oligomers, block copolymers of polyethylene glycol and polypropylene glycol, Pluronic, Pluronic 85, derivatives thereof, and combinations thereof. In some embodiments, the content of the surfactant in the formulation may be 0.1-80% by weight, preferably 0.5-50% by weight, and most preferably 1-15% by weight.

[0097] In one embodiment, the formulation comprises at least one of an oil, a fatty acid, and a lipid. The oil, fatty acid, and lipid in the formulation can be selected from the group consisting of butanoic acid, hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, octadecatrienoic acid, eicosanoic acid, eicosenoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexaenoic acid, tocotrienols, butyric acid, caproic acid, caprylic acid, capric acid, and decanoic acid.

[0014] The present invention also includes but is not limited to oleic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, α-linolenic acid, γ-linolenic acid, behenic acid, erucic acid, lignoceric acid, natural or synthetic phospholipids, mono-, di-, or triacylglycerols, cardiolipin, phosphatidylglycerol, phosphatidic acid, phosphatidylcholine, α-tocopherol, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, dimyristoylphosphatidylcholine, dioleoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids, prostaglandins, gangliosides, neobees, niosomes, derivatives thereof, and combinations thereof.

[0098] 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 the following: sodium channel blockers, tetrodotoxins, saxitoxins, decarbamoyl saxitoxins, vanilloids, neosaxitoxins, lidocaine, conotoxins, cardiac glycosides, digoxins, glutamates, staurosporines, amlodipines, verapamils, cymarins, digitoxins, proscillaridins, quabains, veratridines, domoic acid In another embodiment, the formulation includes a contrast agent for imaging denervation of a nerve. Such contrast agents include iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof, and combinations thereof. The content of the contrast agent in the preparation may be 2-25% by weight, preferably 5-15% by weight.

[0099] In one embodiment, the preparation comprises an azeotrope. An azeotrope is a mixture of two or more components that cannot be changed by simple distillation. It occurs because the vapor produced during boiling has components proportional to the components of the original mixture. The azeotrope of the preparation can be selected from ethanol / water, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropyl alcohol / water, butanol / water, and acetic acid / water.

[0100] In one embodiment, the formulation is in a gaseous or vaporous state and includes one or more components. In one embodiment, the gaseous or vaporous formulation includes: oxygen, nitrogen, helium, argon, air, carbon dioxide, nitric oxide, vapors of organic and inorganic compounds, or combinations thereof. The vapors of organic and inorganic compounds include one of the following: water, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, and mixtures thereof.

[0101] In one embodiment, the vapor formulation includes at least one contrast agent, such as lipiodol 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 may be 0 to 140°C, 15 to 100°C, 30 to 80°C, or 0°C or less, or less than, equal to, or greater than 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more.

[0102] In one embodiment, the preparation is liquid and includes one or more components. The liquid preparation includes at least one of: water, saline, hypertonic saline, phenol, methanol, ethanol, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, iodized oil, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, urea, surfactant etc. and combination thereof. In one embodiment, the liquid preparation includes one of a contrast agent and an azeotrope, and may also include a therapeutic agent. In one embodiment, the liquid preparation is one of a binary, ternary or quaternary component, and may also include more than four components. In one embodiment, the liquid preparation includes a solution, an emulsion or a suspension. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or higher. In one embodiment, the formulation temperature can be room temperature. In one embodiment, the formulation temperature can be -40 to -20°C. In another embodiment, the formulation temperature can be 15 to 80°C. In one embodiment, the formulation temperature can be equal to body temperature. In another embodiment, the formulation temperature can be 50 to 80°C.

[0103] In one embodiment, the method for treating at least one disease comprises inserting a delivery catheter into the body percutaneously or orally; using the catheter to infuse the preparation and / or deliver energy to a target tissue or cavity in the body; optionally removing or removing the preparation 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. 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. Body tissue includes renal artery (for example, left main renal artery, right main renal artery, renal artery branch, left renal artery branch, right renal artery branch, the distal end of left main renal artery, the distal end of right main renal artery, the distal end of left main renal artery branch, the distal end of right main renal artery branch or its combination), 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, phrenic artery, phrenic vein, mesenteric artery, mesenteric vein, airway, esophagus, stomach, duodenum, jejunum, urinary cavity or its combination. Digestive cavity may include esophagus, stomach, duodenum, jejunum, small intestine and large intestine, colon or its combination. Preparation may include gas, steam, liquid, solution, emulsion, suspension and combination thereof of one or more components. In the embodiment in which preparation includes the steam of one or more components, heat can be generated by condensing steam into liquid in tissue. In embodiments where the formulation comprises a liquid or solution, cooling or heat can be generated from a formulation temperature that is lower than or higher than body temperature. The liquid formulation temperature can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or higher. In one embodiment, the temperature of the treated tissue can be different from the formulation temperature and lower than or higher than body temperature. The temperature of the treated tissue can be 15 to 100°C, more preferably 20 to 90°C, and most preferably 36 to 80°C. In another embodiment, the temperature of the treated tissue can be -40 to -20°C. In some embodiments, the delivery catheter is an imaging-guided needle or a needle-based catheter. Imaging guidance can be ultrasound, X-ray, CT scan, MRI, OCT, scope, or a combination thereof.The delivery catheter can be a balloon-based needle catheter. The balloon-based needle catheter can have a single balloon or a double balloon. The balloon-based catheter can have a single needle, a double needle, or a triple needle. The infusion can be from a needle-catheter assembly and can be defined as a needle infusion method. The infusion volume can be 0.1 mL to 5 mL, preferably 0.2 mL to 2.5 mL, and most preferably 0.3 mL to 1.5 mL. If the delivery catheter is a balloon and needle infusion combination device, the balloon pressure can be maintained in the range of 0.1 to 3 atm, preferably 0.1 to 2 atm, and most preferably 0.3 to 1 atm during the infusion period. Optionally, a syringe can be used to operate and maintain the inflation of this low-pressure balloon, and the balloon size can be observed in real time by fluoroscopy. The formulation infusion temperature can be -40 to 140° C., -30 to 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. More detailed examples of catheters, such as single balloon needle and double balloon needle delivery catheters, are shown in the following sections.

[0104] In one embodiment, the infusion lumen can be at least one needle, such as a single needle or multiple needles ( Figure 3 and 5 -9). The needle tip can be removable and can be positioned within the lumen wall or positioned outside the lumen wall by puncturing the lumen wall to deliver the formulation. The needle can be very small and can have a diameter (outer diameter, OD) of approximately 200 μm to 500 μm, preferably approximately 300 μm to 400 μm. The small size of the needle can prevent or significantly reduce leakage or bleeding after puncture and removal. The needle device can directly and accurately infuse the formulation into the adventitia layer of the lumen tissue, achieving deep treatment. The infusion time of the needle device is within 3 minutes, preferably between 5 seconds and 150 seconds.

[0105] In one embodiment, the formulation is or includes ethanol. The formulation can be delivered to the tissue of the body cavity in vapor or liquid form. The vapor or liquid formulation temperature can be between -40 and 150°C, preferably between -30 and 100°C, and most preferably between -20 and 80°C. The temperature of the tissue can be between -40 and 90°C, preferably between -30 and 80°C.

[0106] In one embodiment, the formulation is or includes a mixture of ethanol and water. The ethanol content can range from 10 to 100% by weight. The formulation can be delivered to tissue in a body cavity in vapor or liquid form. The vapor or liquid formulation temperature can be between -40 and 150°C, preferably between -30 and 100°C, and most preferably between -20 and 80°C. The temperature of the tissue can be between -40 and 90°C, preferably between -30 and 80°C. The ethanol / water formulation can be a positive azeotrope. The azeotrope can be 95.63% ethanol and 4.37% water by weight. Ethanol boils at 78.4°C, water boils at 100°C, and the azeotrope boils at 78.2°C, which is lower than any of its components. 78.2°C is the lowest temperature at which any ethanol / water solution can boil at atmospheric pressure.

[0107] In another embodiment, the formulation is a mixture comprising vapors of water, ethanol, and oxygen. In another embodiment, the formulation is a mixture comprising vapors of water, ethanol, and air. In another embodiment, the formulation is a mixture comprising vapors of water, ethanol, oxygen, and nitrogen. Formulations containing oxygen and air are particularly useful for treating asthma and COPD.

[0108] In another embodiment, the preparation is a mixture comprising the vapor of water, ethanol and iodine, wherein the iodine vapor is included in an effective amount to image the mixture of vapor in the body cavity wall. In another embodiment, the preparation is a mixture comprising water and ethanol and also comprising a liquid of a surfactant. In another embodiment, the preparation is a mixture comprising water and ethanol and also comprising a liquid of a contrast agent, wherein the contrast agent can be included in an effective amount so that the mixture can be tracked in the body cavity wall by X-rays. The contrast agent can include iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, derivatives thereof and combinations thereof. The content of the contrast agent in the preparation may be 2 to 20% by weight, preferably 5 to 15% by weight.

[0109] In one embodiment, the preparation is a mixture of acetic acid and water. The acetic acid content of the preparation can be 1 to 100% by weight, preferably 10 to 75% by weight, and most preferably 20 to 50% by weight. The preparation can be delivered to the tissue of the body cavity in vapor or liquid form. The vapor or liquid preparation temperature can be -40 to 100°C, -30 to 90°C, -20 to 80°C or -40°C or lower, or less than, equal to or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100°C or higher. The temperature of the tissue can be -30 to 80°C, preferably 60 to 80°C or -30 to -20°C. The temperature of the tissue can be -40 to 0°C, preferably -30 to -20°C. The acetic acid content in the preparation can be 2 to 75% by weight, preferably 10 to 60% by weight.

[0110] In another embodiment, the formulation is a formulation comprising ethanol and lipiodol (e.g. In some embodiments, the present invention provides a mixture of a liquid containing iodized lipiodol (ULTRA-FLUIDE), wherein the iodized lipiodol comprises an effective amount so that the mixture of the steam in the body cavity wall can be imaged, and also usefully damages the target nerve tissue. The iodized lipiodol content of the preparation can be 10 to 80 % by weight, preferably 15 to 75 % by weight, most preferably 20 to 50 % by weight. The preparation can be or include a mixture comprising the liquid of water and iodized lipiodol, or a mixture comprising the liquid of acetic acid and iodized lipiodol. The iodized lipiodol content of the preparation can be 10 to 80 % by weight, preferably 15 to 75 % by weight, most preferably in the scope of 20 to 50 % by weight.

[0111] In one embodiment, a delivery catheter is used to infuse the preparation into the tissue of the human body. The delivery catheter is a needle or a needle-based balloon catheter and can be guided to the delivery site by X-ray or ultrasound imaging. The needle-based balloon delivery catheter can have one or two balloons. Using a needle device, the preparation infusion can be in the cavity wall or outside the cavity wall (e.g., inside or outside the cavity).

[0112] In one embodiment, the delivery catheter is a jet catheter. The application of the formulation can reach the inner wall of the body cavity. In some embodiments, the spray direction of the device is designed to be approximately perpendicular to the cavity wall. The jet catheter can be needle-free, or can include a needle for both jet-based and needle-based administration of the formulation. The jet catheter can include a centering balloon, or can be balloon-free. The jet catheter can optionally include the ability to deliver energy to the target tissue, such as radiofrequency, cryoablation, microwave, laser, ultrasound, high-intensity focused ultrasound, or a combination thereof.

[0113] As in Figure 1As shown in , the delivery catheter 10 has an elongated shaft 11 having at least one lumen, a distal end 13, and a proximal end 14. At the distal end 13 are proximal 20 and distal 21 lumen-conforming balloons. In any configuration, the tube of the catheter shaft 11 can be extruded from a plastic material such as a thermoplastic, polyimide, polyetherimide, polyethylene, polyurethane, polyester, polyamide, Pebax, nylon, fluorinated polyurethane, polyetheretherketone, or polysulfone, or a combination thereof. The catheter shaft 11 can be extruded or formed to have a variety of lumen cross-sections, including circular or elliptical lumens. Additionally, as shown in Figure 1 As shown in , the catheter 10 can be equipped with a flush 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, so 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. Depending on the diameter of the treatment site, the inflated diameter of the balloon can be in the range of about 2 mm to about 40 mm. In one embodiment, the diameter of each balloon is about 2 mm ("mm"). Alternatively, the inflated diameter of each balloon is less than, equal to, or greater than about 3 mm, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or about 40 mm or more.

[0114] In one embodiment, at least one marker band 22b is located at the proximal end of the proximal balloon 20, and at least one marker band 23a is located at the distal end of the distal balloon 21. The balloon catheter can be a rapid exchange or over-the-wire catheter made of any suitable biocompatible material. The marker band can also be positioned at the other end of the balloon (22a and 23b). Segment 25 is located between balloons 20 and 21, has at least one infusion port, has a non-expandable portion 30 and an axis near the balloon portion 24. Ports 40 and 41 for balloon inflation are used for the distal balloon and the proximal balloon, respectively. Infusion port 42 is used to infuse chemical preparations.

[0115] The materials of balloons 20 and 21 include polyester, polyamide, nylon 12, nylon 11, polyamide 12, block copolymers of polyether and polyamide, Pebax, polyurethane, block copolymers of polyether and polyester, or combinations thereof. The diameter of balloon 21 is equal to or smaller than the diameter of balloon 20.

[0116] Figure 2 A schematic diagram of an embodiment of a jet catheter positioned within the left mainstem bronchus for the treatment of asthma and COPD is shown in FIG. Figure 2 The delivery catheter 198 can treat airways distal to the main bronchi 21 and 22. For example, the delivery catheter 198 can be positioned to a 6th or even 8th generation airway to affect a distal portion of the bronchial tree 27. The delivery system 198 can be navigated through tortuous airways to perform a wide range of procedures, such as, for example, denervation of a portion of a lobe, an entire lobe, multiple lobes, or one or both lungs. In some embodiments, a lobar bronchi are treated to denervate a lung lobe. For example, one or more treatment sites along a lobar bronchus can be targeted to denervate the entire lobe connected to that lobar bronchus. The left lobar bronchus can be treated to affect the left upper lobe and / or the left lower lobe. The right lobar bronchus can be treated to affect the right upper lobe, right middle lobe, and / or right lower lobe. The lobes can be treated simultaneously or sequentially. In some embodiments, the physician can treat a lobe. Based on the effectiveness of the treatment, the physician can treat additional lobes simultaneously or sequentially. In this way, different isolated areas of the bronchial tree can be treated.

[0117] Delivery catheter 198 can also be used for segmental or subsegmental bronchi. Each segmental bronchus can be treated by delivering the agent and / or energy to a single treatment site along the segmental bronchus. For example, the agent and / or energy can be delivered to each segmental bronchus in the right lung. In some procedures, a single or double application of the agent can treat most or the entire right lung. Depending on the anatomy of the bronchial tree, segmental bronchi can often be denervated using a single or double application.

[0118] Delivery catheter 198 can 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), etc. Nervous tissue may include nerve cells, nerve fibers, dendrites, and supporting tissue, such as glial cells. Nerve cells transmit electrical impulses, while nerve fibers are elongated axons that conduct impulses. The electrical impulses are converted into chemical signals for communication with effector cells or other nerve cells. For example, delivery catheter 198 can denervate a portion of the airway of bronchial tree 27 to weaken one or more nervous system signals transmitted by the neural tissue. Denervation can include (through the treatment of the present invention) severing the neural tissue of a portion of a nerve trunk to prevent the signal from passing through that specific area and propagating to more distant locations along the bronchial tree. If multiple nerve trunks extend along the airway, each nerve trunk can be severed. Thus, the nerve supply along a portion of the bronchial tree can be severed. When the signal is severed, the smooth muscle of the distal airway relaxes, causing the airway to dilate. This airway dilation reduces airflow resistance, thereby increasing gas exchange within the lungs, thereby alleviating or eliminating one or more clinical manifestations, such as shortness of breath, wheezing, chest tightness, etc. Tissue surrounding or adjacent to the target neural tissue may be affected, but will not be permanently severed. In some embodiments, for example, bronchial vessels along the treated airway can deliver similar amounts of blood to bronchial wall tissue, and pulmonary vessels along the treated airway can deliver similar amounts of blood to alveolar sacs in the distal region of the bronchial tree 27 before and after treatment. These blood vessels can continue to deliver blood to maintain adequate gas exchange. In some embodiments, the airway smooth muscle is largely unharmed. For example, a relatively small portion of the smooth muscle in the airway wall that does not significantly affect respiratory function can be reversibly altered by this method, for example by using a formulation at a regulated temperature to avoid irreversible damage to neural tissue outside the airway, such as non-target smooth muscle tissue.

[0119] Figure 2 The delivery system 198 includes a treatment controller 202 and an intraluminal elongate assembly 200 connected to the controller 202. The elongate assembly 200 can be inserted into the trachea 20 and navigated into and through the bronchial tree 27 with or without the use of a delivery assembly, such as a guidewire. The elongate assembly 200 includes a distal tip 203.

[0120] Figure 2 The controller 202 may include one or more processors, microprocessors, digital signal processors (DSPs), field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs), storage devices, buses, power supplies, pumps, formulation resources, vapor resources, liquid resources, imaging resources, vapor generators, desired temperature formulation generators, and the like.

[0121] Figure 2The distal tip 203 can target various locations in the lung 10, including but not limited to neural tissue, fibrous tissue, diseased or abnormal tissue, muscle tissue, blood, blood vessels, various anatomical features (e.g., membranes, glands, cilia, etc.), or combinations thereof.

[0122] In one embodiment, a schematic diagram of a single balloon needle delivery catheter (a triple needle balloon catheter is shown) positioned within a renal artery is shown in FIG. Figure 3 , in which needle 110 is shown extended. Figure 3 Delivery catheter 108 can treat hypertension. The formulation can be infused into the wall or outer wall of the renal artery adjacent to the renal nerves via a denervation needle. Nerve endings and small nerve fibers are typically located within the arterial wall, while large nerve fibers and nerve bundles are typically located outside or near the arterial wall. Therefore, varying degrees of denervation can be achieved by controlling the depth of needle insertion during surgery. Figure 3 Some elements of the renal vascular system are omitted. Figure 3 In the diagram, 102 is the kidney, 105 is the guide catheter, 106 is the main renal artery, 108 is the three-needle balloon catheter, 109 is the guide wire, 301 is the abdominal aorta, and 502 is the extra renal artery. Figure 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 formulation through a needle; however, embodiments of the needle delivery catheter may additionally or alternatively be used to deliver energy to the target tissue in the form of radiofrequency, cryoablation, microwave, laser and / or ultrasound, for example via a needle (e.g., radiofrequency, cryoablation) and / or through other sources (e.g., microwave, laser, ultrasound).

[0123] In another embodiment, Figure 3 The delivery catheter 108 includes a balloon inflated to approximately center the catheter shaft, so that when the needle is deployed as shown, it is equidistant from the vessel wall and can be advanced through the arterial wall to a similar depth. In some embodiments, the renal artery is treated to treat hypertension. Because the needle pierces the vessel wall or extends beyond the vessel wall, the device is capable of infusing the agent into or outside the vessel wall. Figure 3 Infusion of the formulation into the outer wall of the main renal artery through needle 110 is shown, directly onto the renal nerves (not shown) for denervation.

[0124] In another embodiment, a three-needle balloon catheter can be positioned within the extra renal artery 502 and can infuse the formulation into or outside the walls of these vessels. Although three needles are shown, any suitable number of needles can be used, such as one, two, three, four, five, or more.

[0125] In another embodiment, a single denervation procedure can treat both the main and extra renal arteries. A three-needle balloon catheter is positioned in Figure 3 The formulation is infused into the main renal artery 106 and the additional renal artery 502 in the artery and into the wall or outside of the wall of multiple renal arteries. Optionally, the artery can be treated at multiple locations depending on the length of the artery.

[0126] In one embodiment, a method of treating hypertension comprises percutaneously inserting a delivery catheter into a renal artery and / or an additional renal artery adjacent to nerves and nerve endings; using the delivery catheter to infuse the above-described agent and / or energy into tissue of a body cavity adjacent to the nerve, wherein the amount of agent and / or energy delivered is effective to beneficially damage the nerves and nerve endings; and removing the delivery catheter from the body cavity. Treatment will result in a decrease in blood pressure in the patient being treated.

[0127] In one embodiment, a needle delivery catheter, e.g. Figure 3 and 5 -9, can be used to treat hypertension by renal ablation, treat diabetes by liver denervation, and / or treat obesity by gastric denervation. In one embodiment, the catheter 10 disclosed herein (in Figure 1 ) helps regulate the flow of the formulation and the therapeutic dose throughout the therapeutic window 30, such as Figure 4 The balloons can be inflated through their inflation lumens. The location, diameter, number and frequency of the needle holes 31 result in the formulation being delivered to the therapeutic window 30 via the needle (not shown, in a retracted position). Figure 4 A catheter is depicted positioned in a body cavity 5 having two needle exit holes 31 within a therapeutic window 30 for delivering a therapeutic agent via the needle. During use, the needle extends outwardly from the needle hole, as shown in FIG. Figure 3 As shown. Figure 4 As shown, needle exit aperture 31 includes a retracted needle in fluid communication with inner lumen 25. The needle within needle exit aperture 31 located within therapeutic window 30 can communicate with outer lumen 24 or inner lumen 25 (not shown) so that the agent is delivered to therapeutic window 30 (e.g., into the lumen, to the lumen wall, or to the outside of the lumen wall).

[0128] The drug treatment port can be located between the balloons on the shaft. The drug infusion port can be located on the non-expandable shaft portion between the expandable balloon portion. During treatment, the drug can be expelled through the infusion port between the balloons into the therapeutic window space formed by the balloons. This is an infusion embodiment where the treatment mechanism is to apply the drug to the interior of the vessel wall and can include allowing the drug to diffuse out through the lumen wall to achieve therapeutic efficacy.

[0129] In one embodiment, chemical / formulation residues can optionally be recovered post-treatment at one or more infusion ports using vacuum technology. In this case, at least two treatment lumens are preferred: one for infusion and one for vacuum. The formulation infusion port and vacuum port can be located on the non-expandable shaft portion between the inflatable balloon portion.

[0130] In addition to removing excess therapeutic agent, the remaining agent can be diluted with saline or water to an ineffective concentration. Flushing with saline or water can be performed using either the catheter wire lumen, the infusion lumen, or other means. The method used depends on the site of protection or treatment. If a distal portion of a vessel requires protection from the therapeutic agent, flushing can be performed through the wire lumen.

[0131] In one embodiment, when deep treatment of the adventitia and / or periadventitia space is desired, a needle-based catheter can achieve this goal because the needle-based catheter can deliver the agent into the lumen wall or the abluminal wall through at least one needle. To treat the lumen uniformly around its circumference, a three (or more) needle balloon catheter delivers the agent into the target area through the needle. Figure 5 Depicts a double-balloon three-needle catheter positioned in a body cavity 5, which has three needles 50 deployed between two balloons. When advanced, the three needles can have a diameter larger than the balloon diameter. The needle is in fluid communication with the preparation source and delivers the preparation directly to the blood vessel wall or to the outer wall of the body cavity. During surgery, the balloon needle catheter advances to the target lesion or position according to standard surgery, and both balloons are inflated to center the middle non-expendable (non-expendable) axis, then the needle is deployed from the middle non-expendable (non-expendable) axis, and according to the needle penetration depth, for example, the needle tip can be located inside or outside the wall, and the preparation is delivered to the wall or outer wall or outside the wall of the cavity or blood vessel by the needle. After treatment, the needle is retracted into the axis, and the balloon is deflated, and the catheter is ready to be removed.

[0132] Examples of single balloon needle catheters include Figure 6A and 6B shown. Figure 6AShown is a three-needle balloon catheter 600 in a ready-to-use state. The needle is contained in the interior of a distal head 601 (not shown) which is the distal end portion of the catheter, wherein a space (not shown) containing the needle and a corresponding needle exit opening 612 are positioned at the distal end of the balloon, wherein the needle exit opening allows the needle to protrude from the space when the needle is deployed. The distal head can be used as a marker band, or alternatively, a marker band 602 can be included and can be made of any medical grade metal, such as stainless steel, and can be non-traumatic (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 doctor to accurately locate the needle. The catheter has an eccentric lumen design 603, which allows for a smaller catheter profile, for example, better compatibility with a guide catheter. The catheter shaft 610 can be a reinforced shaft, for example, reinforced by wire braiding to enhance its compressive and tensile strength, so that the needle movement operated at the proximal end of the catheter can be smooth and precise. Needle movement is controlled by a handle 604 at the proximal end connected to a source of the agent. A catheter that can be advanced over a guidewire for delivery is shown with an integral over-the-wire configuration for a guidewire lumen 603. A balloon 606 can be inflated via an inflation lumen 605. Figure 6B Catheter 600 is shown with needle 611 in an advanced position and balloon 606 inflated. The balloon positioned just behind the needles can center the distal end of shaft 610 so that all three needles 611 can penetrate the vessel wall to similar depths, ensuring even delivery of the formulation around the circumference of the vessel. It may be ideal to position the balloon as close as possible to the needles, which increases the likelihood that the needles will be equidistant from the vessel wall. The distance between the needle exit opening on the distal tip and the balloon's cone / waist transition region can be approximately 2 mm to 12 mm, preferably approximately 5 mm to 9 mm. A smaller needle diameter can result in a less noticeable needle puncture wound, which can lead to faster wound healing. The needle outer diameter can be approximately 0.20 mm to 0.50 mm; preferably approximately 0.28 mm to 0.38 mm. The needle curvature can be designed to enable needle 611 to align perpendicularly with the vessel wall during delivery.

[0133] The needle can be made of any suitable material, such as stainless steel, platinum, titanium, tantalum, platinum-iridium alloy, platinum-chromium alloy, nickel-titanium alloy (nitinol); cobalt-based alloys including platinum (Pt), or gold (Au), or iridium (Ir), or osmium (Os), or rhenium (Re), or tungsten (W), or palladium (Pd), or tantalum (Ta) and combinations thereof, and / or chromium (Cr), and / or molybdenum (Mo) and / or nickel (Ni). The needle can be made of nitinol material and can have a shape memory of the designed curvature when leaving the receiving hole / compartment. When the nitinol needle is small and thin, it may not be sufficiently radiopaque under X-rays during surgery. However, it is important for the physician to know the position of the needle during surgery. To achieve this, the needle can be modified with a number of suitable radiopaque metallic materials, for example, by a thin film sputtering process employing a radiopaque material on its surface, or by attaching a radiopaque material to the needle (for example, because a marker band can be included on the shaft), or by a clad metallic needle / tube incorporating one or two layers of radiopaque material into the nitinol needle / tube. The coating or cladding or additional attaching 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 render the nitinol needle radiopaque. The radius of curvature of the needle 611 may be about 2 mm to 6 mm, for example, about 3 mm 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 5 mm to 40 mm, or about 5 mm to 30 mm, for example, about 5 mm to 15 mm; this may be determined by the diameter of the vessel being treated and the desired needle penetration depth. For example, for a 6 mm vessel and a 2 mm needle penetration depth, the needle tip to tip span distance may be approximately 10 mm.

[0134] After treatment, the needle is first retracted into the distal tip or receiving compartment, the balloon is then deflated, and the catheter is removed. Optionally, the distal tip, needle, and treated vascular area can be flushed with saline or heparinized saline through the wire lumen (for over-the-wire catheters) or a designated lumen to dilute any residual formulation in the lumen. In some procedures, the formulation lumen 604 can be flushed with saline or heparinized saline to prevent needle clogging. Although Figure 6A and 6B Three needles are shown located at the distal end of the balloon, but any number of needles may be used, such as one, two, three, four, five or more, and needles may also be located at the proximal end of the balloon. The needle guide may optionally be flushed.

[0135] An embodiment of a rapid exchange (RX) needle balloon catheter is shown in Figure 7A, including a quick exchange shaft. The quick exchange configuration allows for easier and faster insertion of the catheter after the wire is placed during surgery. The guidewire lumen 709 has a wire inlet port or outlet port 711 located near the middle or distal end of the shaft 710. Optionally, there are guide grooves on the distal head (not shown) to facilitate wire feeding when the doctor feeds the wire back at the distal port of the wire lumen. In addition to the wire changing method, the same needle and balloon operation procedure described in the above paragraph can be applied. Optionally, flushing and cleaning of the distal head and needle after treatment can be completed by directly injecting saline or heparinized saline at approximately 3 to 10 times the treatment volume through the preparation lumen 704.

[0136] The needle-based balloon infusion system may include a needle-based balloon catheter, a guidewire, an ablative agent, saline or heparinized saline or therapeutic drug, and a reservoir with a volume of 1 mL to 30 mL for drug administration. Examples of the reservoir may include a syringe or a syringe pump.

[0137] A needle-based balloon delivery catheter may include a distal head, at least one marker band, at least one needle, at least one needle exit port, at least one irrigation port (which in some embodiments may be the same as the needle exit port), 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 irrigation port is connected to the irrigation port via the irrigation lumen, the guidewire lumen is connected to the recess of the distal head; the needle movement controller is connected to the needle via the needle movement shaft; the ablation port is connected to the needle via the needle movement shaft; the needle is connected to the needle movement 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 exit ports 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 can be in the range of 3mm to 40mm. The balloon length can be in the range of 3mm to 25mm. The needle size or needle outer diameter (OD) can be in the range of 0.3mm to 0.5mm, and the needle inner diameter (ID) can be in the range of 0.2mm to 0.35mm. When the catheter comprises two or more needles, the needle span diameter can be in the range of 5mm to 80mm or 5mm to 40mm, defined by the circumference of the needle tip point when the needle is fully advanced. The catheter length can be in the range of 70cm to 260cm. The guidewire lumen can be compatible with 0.014 inch (0.36mm) or 0.018 inch (0.46mm) or 0.035 inch (0.89mm) guidewires. The needle span diameter may be fixed or adjustable; for example, the needle span diameter may be adjustable within a range of 5 mm to 80 mm, 5 mm to 30 mm, or 7 mm to 15 mm.

[0138] The needle can be visible under X-ray (fluoroscopy). The needle can be made of stainless steel, nitinol, cobalt-chromium alloys, metal alloys and shape memory metals and their alloys. The needle can be straight or curved in shape. The radiopacity of the metal needle can be enhanced by surface modification of another metal or two metals (e.g., W, Au, Ta, Pt, Ir and any combination thereof) using physical vapor deposition (PVD) by sputtering the other metal.

[0139] Needle-based balloon delivery catheters can include needle movement controls and an ablative agent port through which the ablative agent is delivered directly to the needle.

[0140] The balloon delivery catheter based on needle may include a wire lumen for guiding the wire. The wire lumen may be characterized by an overall exchange type (OTW) or a rapid exchange (RX) type. When it is an OTW shaft (catheter), the guide wire passes through the entire length of the catheter shaft. As a counterpart, when it is an RX shaft (catheter), the guide wire does not use a lumen passing through the catheter shaft. Typically, the RX wire lumen is much shorter, with a length of about 10 inches (about 25 cm), located at the distal end of the catheter. Compared with advancing the guide wire along the full length, the RX catheter saves time, especially during the replacement of the catheter during surgery.

[0141] The needle-based balloon delivery catheter may include at least one balloon. A short length balloon is preferred, and the balloon length may range from 3 mm to 20 mm, preferably 5 mm to 10 mm long. The balloon diameter may range from 3 mm to 30 mm. The desired balloon Compliance The balloon's pressure depends largely on its application and can range from compliant to non-compliant. Balloon materials can include polyethylene, polyamides and their block copolymers, polyurethanes, polyesters and their block copolymers, nylon 12, Pebax, etc. The balloon can be inflated and deflated using standard balloon inflation media through the inflation chamber / port. The inflation device can be a syringe or a balloon inflation device, but if the balloon is compliant and low-pressure, a syringe of appropriate volume is preferred due to the nature of the balloon.

[0142] A balloon on the catheter can be positioned behind the needle, serving to center the distal tip of the needle and prevent blood flow into the target treatment area.

[0143] The balloon delivery catheter based on needle can include a marker to indicate the position of the balloon during surgery. The marker can be a regular marker band for the balloon catheter, and can be a radiopaque metal (distal end) head, such as in a balloon catheter based on needle. The balloon marker can be placed at the distal end, or the middle, or the proximal end, or a combination of these positions of the balloon. The radiopaque marker band can be made of platinum, platinum-iridium alloy, gold metal, and a polymer composite material with radiopaque filler.

[0144] The needle-based balloon delivery catheter may include a flush lumen in direct communication with the needle exit port for fluid drainage / passage. The flush lumen may be connected via a flush lumen port to a source of saline or heparinized saline for flushing and cleaning purposes, or to a source of therapeutic agents for internal surface treatment. The flush lumen may be of coaxial construction (see Figure 7B ) or have separate conduit channels (not shown).

[0145] The needle-based balloon delivery catheter may include a balloon, three needles, a distal tip of the needle compartment and radiopaque marker, a guidewire lumen, a balloon inflation lumen and port, an infusion lumen and port, and an irrigation lumen and port.

[0146] Examples of rapid exchange (RX) needle balloon delivery catheters are Figure 7B Illustrated in FIG. The catheter shaft 720 includes a separate flush lumen 715. The flush lumen 715 is connected to a needle exit hole 716 and flush port 708 extending through the catheter shaft, allowing flushing medium to be discharged through the needle exit hole as indicated by the arrow. In this example, the flush lumen is coaxially arranged above the infusion lumen 714. The infusion lumen 714 is directly connected to the needle tubing, which can be made of polymer or metal tubing, preferably stainless steel hypotube. The three needles are bundled together using a needle bundle 712. The bundle can be strong yet flexible to hold the needles together and evenly spaced, and can be a polymer tube or a reinforced polymer tube, such as a braided polymer tube. A balloon 706 located behind the needle head serves to center the needles within the vessel, ensuring that all three needles are at equal distances from the vessel wall. The distal needle head 717 serves as a needle retaining compartment and a marker for needle placement during surgery. The shape-memory needles return to their pre-formed curvature upon exiting the distal head. It has a beveled needle distal opening 713 , wherein the bevel faces the intrados direction of the needle. The needle distal opening is in communication with an infusion lumen 714 and an infusion port 704 .

[0147] Figure 7B The various cross-sections of the needle balloon delivery catheter shown in FIG. Figures 7C to 7G , which is a cross-sectional view of a section. Figure 7C yes Figure 7B The cross-sectional view of the middle catheter 7C-7C shows a balloon body 706, a guidewire lumen 709, a braided outer shaft 721, a three-needle tube 722 directly connected to the distal head, and a flushing lumen 715.

[0148] Figure 7D The diagram illustrates Figure 7B Section 7D-7D of the middle catheter shows a cross-sectional view of the balloon 706, the guidewire lumen 709, the inflation lumen 707, the flush lumen 715, the braided outer shaft 721, and the needle tube 722 with the needle bundle (braided tube) 712 that holds the needles together and evenly spaced. For the three-needle configuration, the needles are spaced 120° apart.

[0149] Figure 7E and 7F The diagrams illustrate Figure 7B Cross-sectional views of the catheter at section 7E-7E and section 7F-7F. Figure 7E It includes a guidewire lumen 709 and an inflation lumen 707, both of which are arranged on top of the braided outer shaft but in opposite directions. Figure 7EAlso included is a flushing lumen 715, a braided outer shaft, and an infusion lumen 714. The infusion lumen can be made of a polymer tube, a reinforced polymer tube, or a metal tube. For better pushability and dimensional stability, a stainless steel (SS) hypotube can be used as the infusion lumen 714. The infusion lumen 714 of the catheter is connected to the infusion port 704 at the proximal end and to the needle at the distal end of the catheter. Alternatively, in order to save space or reduce the overall catheter profile, the guidewire lumen 709 and the inflation lumen 707 can be co-located on the same side of the shaft, such as Figure 7F shown. Figure 7F This configuration is not shown in Figure 7B in the catheter.

[0150] Figure 7G The diagram illustrates Figure 7B Cross-sectional view of the middle catheter, section 7G-7G, includes a braided outer shaft with an inflation lumen 707 attached to its outer wall, an irrigation lumen, and an infusion lumen of a SS hypotube. Inflation lumen 707 communicates with inflation port 705 for balloon inflation. Infusion lumen 714 communicates with infusion port 704 and the needle and distal needle opening 713. Irrigation lumen 715 communicates with irrigation port 708 and irrigation port 716.

[0151] A rapid exchange (RX) needle balloon delivery catheter can be used for ablation procedures through blood vessels. The catheter's infusion lumen and needle can be pre-filled with an alcohol-based ablative agent from its port 704; and the flush lumen can be pre-filled with a medium such as saline or heparinized saline from its port 708. The pre-filled flushing fluid within the distal tip can reduce the likelihood of needle clogging by preventing the needle from coming into direct contact with blood. Fewer clogging opportunities can mean a longer lifespan for the catheter, allowing for multiple treatments in a single procedure, and, because fewer catheters are used, can help shorten procedure times and reduce overall costs. The prepared catheter can then be inserted into the vessel within the guiding catheter and guided along a pre-positioned guidewire to the treatment site. Once at the intended treatment site, the balloon can first be inflated to the vessel diameter to center the needle tip, then the three needles can be advanced into or beyond the vessel wall, and the ablative agent can be infused through the needles into the intended denervated area. Alternatively, a therapeutic agent can be used in place of the ablative agent for treatments other than ablation. After treatment, the needle can be retracted into the distal tip, and an irrigation medium can be injected through the needle exit port and flushed out for irrigation and cleaning. The balloon can then be deflated, and the catheter can then be ready for withdrawal or movement to the next treatment site for another ablation. If drug delivery is desired, the irrigation medium can also be a therapeutic drug. Liquid medication can be applied to the treatment site and its interior surfaces through the irrigation port.

[0152] The flush lumen on the catheter provides a safety mechanism for the patient. For example, it can dilute any excess ablative solution or any residual ablative solution within the vessel to a non-functional level.

[0153] The needle-based balloon delivery catheter may be a three-needle balloon delivery catheter. The span diameter of the needle (measured from the needle tip to the circumference formed by the tip in the fully advanced stage) may be 5 mm to 30 mm, or 7 mm to 15 mm.

[0154] In one embodiment, Figure 8A and 8B As shown, a steerable single needle catheter can be used for infusion of preparations. As shown, the catheter has bidirectional steering (steering), although one, two, three, four or more directional functions can be used. The steering mechanism can be, for example, a wire (not shown) attached to the distal tip 801 of the catheter shaft 802, with a handle (not shown) at the proximal end of the catheter. To steer the catheter, the user moves the handle in the proximal direction, which causes the distal tip 801 to move away from the longitudinal axis of the catheter shaft 802. During insertion and positioning, the needle tip is retracted into the interior of the catheter, which can be achieved using a guidewire. An eccentric guidewire lumen design can be used to minimize the catheter profile for small vascular access. The entire catheter profile is from 3F to 10F, preferably from 5F to 7F. Once the treatment site is reached, the catheter head 801, which can be non-radiopaque, is steered toward and preferably against the vessel wall. This can be visualized using fluoroscopy. Next, the needle ( Figure 8B The catheter is inserted into the vessel wall or through the wall and the preparation is infused. If necessary, the needle can be retracted and the tip can be turned to a new direction to treat in the new direction. After treatment, the needle is retracted and the catheter is removed from the patient's body. Since the catheter is visible under X-rays and has a steerable tip, optionally, a steerable catheter can be used without a guide wire.

[0155] In another embodiment, Figure 9A 、 9B and 9C , a single directional steerable catheter is used to infuse the formulation through a needle. This catheter 900 has a smaller profile than the bidirectional catheters described above and is suitable for use in smaller diameter vessels. As described above, the desired and controlled puncture can include achieving a needle that is oriented approximately perpendicular to the lumen wall (e.g., at or near 90° to the lumen wall) so that the infusion direction and depth can be predicted. This may require a sharp bend in the distal end of the catheter 902 so that the tip 901 is aligned perpendicular to the vessel wall. This can be very difficult in small lumens because it can be almost impossible to push the needle through the small bend or curvature. To overcome this problem, in some embodiments, the exit hole of the needle is placed on the side wall of the tip head rather than in the middle of the tip 903 (see Figure 9B and C). In addition, the exit hole is positioned on the side of the catheter shaft 902 in the same direction as the direction of curvature of the catheter tip (see Figure 9BWhen the catheter is placed in the small lumen of the target area, it only needs to bend at a small angle (less than 90°) to align the hole in a nearly perpendicular manner to the vessel wall 5 (see Figure 9C ). Once alignment is achieved, as Figure 9C As shown, the needle is advanced into wall 5 and the system is ready for infusion therapy. After treatment, the needle is retracted into the catheter, the catheter tip returns 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 location for another treatment. The distal tip can be made of plastic, metal, or a combination thereof, can be radiopaque, and can contain the needle. The radiopaque tip 901 can serve as a marker for needle positioning during surgery.

[0156] In one embodiment, the needle device can deliver very small and accurate amounts of formulation, for example, in the range of 0.01 mL to 10.0 mL, preferably 0.05 mL to 5.0 mL, and most preferably 0.1 mL to 1.0 mL. Due to microdosing and precise control of treatment volume / dose, multiple treatments can be used at the same location / area to provide more optimized treatment results. Figure 3 As shown in FIG, a three-needle balloon catheter 108 is placed in the main renal artery 106 with a balloon and needle 110 deployed therein; for example, the perivascular infusion volume of the formulation may be 0.6 mL. After the needle is retracted and the balloon deflated, the catheter may continue to advance to the additional renal artery 502 (renal artery branch) and deploy the needle and infuse another therapeutic dose, for example 0.3 mL, into its outer wall area (adventitia). If both additional renal arteries are accessible, both arteries may be treated with equal doses or different doses. To achieve a similar dose per unit area in treatment, the dose of the additional renal artery treatment may be less than the dose of the main renal artery treatment, taking into account the difference in surface area of ​​the outer wall of the additional renal artery and the closer distance to the kidney organ compared to the main renal artery. Dose to the main renal artery (DOSE m ) and additional renal artery (branch) dose (DOSE b ) can be:

[0157] DOSE b =DOSE m *(D b / D m )

[0158] Among them D m is the aorta diameter, D b is the diameter of the arterial branch.

[0159] For example, when the diameter of the aorta is 6 mm and the diameter of the branch artery is 3 mm,

[0160] DOSE b=DOSE m *(D b / D m )=DOSE m *(1 / 2) or = 0.5 DOSE m

[0161] If all three areas (one main and two branches) are treated, the total dose to the arterial treatment can be 1.2 mL per kidney.

[0162] Sometimes, the main renal artery is long enough to allow one device to treat twice, for example, once in the middle and once near the bifurcation area (near the branches) of the artery. When the main renal artery is treated twice and both arteries are treated once, the total dose to treat one renal artery is 1.8 mL.

[0163] In one embodiment, Figure 13 and 14 As shown, 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. Figure 13 The catheter 1300 in FIG. 1 has a coaxial shaft 1309, with suction passing through an inner tube 1305 and jet passing through the space between inner tube 1305 and outer tube 1304. Jet orifices 1301 are located in the sidewall of shaft 1309, enabling direct delivery of the agent to the vessel wall and providing fine control over the jet direction and treatment area. Agent is delivered to jet orifices 1301 via jet lumen 1307. If excess agent remains in the vessel after jet treatment, it can be removed / collected using the catheter's suction function. This removal can be accomplished by applying a vacuum to suction port 1308, which allows the agent to be withdrawn through suction site 1306. In this example, suction opening 1306 is located distal to jet opening 1301. The openings for suction and jet can be circular or any other geometric shape. A single or multiple holes can be used for both suction and jet functions, and any combination of hole numbers can be used for both functions. The number and size of holes are independent of each other. Ideally, the injection orifice size is smaller than the suction orifice size because a fine mist is desired for injection. Optionally, a suction line can be connected to a vacuum pump. The injection can include two components: a liquid agent and a pressurized gas, such as air or oxygen. A specified volume of liquid agent is delivered via pressurized gas at a predetermined pressure. At this delivery pressure, the delivered agent is applied to the target treatment area in the form of a fine mist. Excess agent after each injection can be collected / removed using suction on the catheter at the treatment site, thereby ensuring that the agent is contained in the target area.

[0164] The exact injection location during surgery can be visualized by a marker band under X-ray. For example, marker band 1303 can be located at the distal end of catheter 1309 proximal to injection orifice 1301, or dual marker bands 1303 can be located at both the distal and proximal ends of injection orifice 1301. Optionally, the distal marker band is sized to occupy the space between the inner and outer portions of the distal shaft, which can block the fluid path and stop the formulation at the marker band location; thus, the priming volume in the catheter can be less, which can make the injection volume more accurate.

[0165] In another embodiment, a dual-site aspiration catheter can be used to help ensure that the formulation does not escape in either direction (distal or proximal) of the injection orifice. Figure 14 , wherein suction holes 1406A and 1406B are disposed distally and proximally of the injection site on the catheter. The distal and proximal suction holes can be connected via the same channel / lumen; or they can be independent of each other, for example, the distal and proximal suction holes can be operated independently. Suction can occur at the distal location, the proximal location, or both locations simultaneously. The catheter can be operated as described above.

[0166] To adapt Figure 14 In accordance with the features of the present invention, a multi-lumen shaft 1409 may be used and may be, for example, a 3-lumen shaft. Each of the suction locations 1406A and 1406B has its own lumen so that distal and proximal suction can be performed independently. In one embodiment, a cannula 1410 is placed over the jet outlet orifice 1401 to achieve a uniform circumferential jet (e.g., 360°). Dual marking bands 1403 at the distal and proximal ends of the cannula 1410 aid in accurate positioning at the treatment site or lesion. Although Figure 14 A sidewall spray outlet configuration is shown, but the spray outlet may alternatively or additionally be placed at the distal tip.By design of the aperture size 1401, the spray pattern may be a range of delivery effects (physical forms) from a fine mist to coarse droplets to a jet.

[0167] Figure 15A and 15B The diagram illustrates various arteries surrounding the liver and stomach and various nerve systems that control the liver and stomach and their surrounding organs and tissues. The arteries surrounding the liver and stomach include the abdominal aorta 305, the celiac artery 310, the common hepatic artery 315 and the proper 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 branches 361. The various nerves that control the liver and stomach and their surrounding organs and tissues include the celiac plexus 340 and the hepatic plexus 345 (only in Figure 15B305 and enter the celiac artery 310. From the celiac artery 310, blood passes through the common hepatic artery 315, enters the proper hepatic artery 320, and then enters the liver through the right hepatic artery 325 and the left hepatic artery 330. The common hepatic artery 315 branches from the celiac trunk and forms the gastroduodenal artery. The nerves that innervate the liver include the celiac plexus 340 and the hepatic plexus 345. The celiac plexus 340 surrounds the celiac artery 310 and continues into the hepatic plexus 345, which surrounds the proper hepatic artery 320 and the common hepatic artery 315, and / or continues to the right hepatic artery 325 and the left hepatic artery 330. In some anatomical structures, the celiac plexus 340 and the hepatic plexus 345 are tightly adhered to the arterial wall, supplying blood to the liver, making neuromodulation from inside to outside the blood vessels particularly advantageous. In several embodiments, the average thickness of the blood vessels (e.g., the hepatic artery) ranges from about 0.1 cm to about 0.25 cm. In some embodiments, the formulation and / or energy can be delivered to the inner wall of a target vessel or target nerve. Intravascular delivery can be used because nerves adhere tightly to the outer wall of arteries that supply blood to the liver (e.g., in the case of bifurcations of the hepatic artery). In some embodiments, extraluminal / extravascular delivery is desired and can be achieved using any of the various needle catheters disclosed herein.

[0168] The arteries surrounding the stomach include the abdominal aorta 305, the celiac artery 310, the right and left gastric arteries 355 and 360, and the esophageal branches 361. The blood supply to the stomach is pumped from the heart into the aorta, then down through the abdominal aorta 305 and into the celiac artery 310. From the celiac artery 310, blood passes through the right and left gastric arteries 355 and 360, the esophageal branches 361, and into the stomach. The left gastric artery 360 includes the left gastric arterial plexus 362 (only in Figure 15A shown in ).

[0169] Continue to refer Figure 15B The hepatic plexus 345 is the largest offset from the celiac plexus 340. The hepatic plexus 345 is believed to primarily carry afferent and efferent sympathetic nerve fibers, whose stimulation can increase blood glucose levels through various mechanisms. For example, stimulation of sympathetic nerve fibers in the hepatic plexus 345 can increase blood glucose levels by enhancing hepatic glucose production or by reducing hepatic glucose uptake. Thus, disruption of sympathetic nerve signaling in the hepatic plexus 345 can alter blood glucose levels.

[0170] Figure 15B The embodiment shown in may be an embodiment of a balloon needle delivery catheter positioned within the hepatic artery for treating diabetes. Figure 15A The embodiment shown in can be an embodiment of a three-needle balloon delivery catheter positioned in the left gastric artery for the treatment of obesity and / or diabetes. The access to these arteries is very similar to that of the renal arteries, so the procedures described in the previous section are applicable to these embodiments.

[0171] Can use safe and effective amount of preparation, to damage tissue, such as nerve satisfactorily and beneficially.Usually, dosage is relevant to the degree of damage to tissue.In some embodiments, effective preparation dosage range is 0.2 microliters to 200 milliliters.However, these dosage limits are not defined, because other delivery parameters (such as delivery rate, duration, etc.) may need different dosages to achieve the final damage benefit.

[0172] The treatment time can vary depending on the volume of tissue to be treated and the desired degree of damage to the target tissue. The treatment time can vary from about 2 seconds to about 60 minutes. In some embodiments, to induce damage to relieve symptoms, a safe and effective treatment time range is from about 4 seconds to about 30 minutes.

[0173] 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.

[0174] In one embodiment, the method for treating hypertension comprises percutaneously inserting a delivery catheter into a renal artery adjacent to a nerve; using the catheter to infuse the above-mentioned formulation and / or energy into body cavity tissue adjacent to the nerve, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the body cavity. Damage or damage to the tissue can alleviate symptoms of the disease, for example by lowering blood pressure. The purpose of heat / energy can be to enhance the damage / damage effect by accelerating the reaction rate between the formulation and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the formulation can be between -40 and 140°C, -30 and 100°C, -30 and 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be between -40 and 100°C, -30 and 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure may be 0.1 to 14 atm, preferably 3 to 10 atm, and most preferably 4 to 8 atm.

[0175] In one embodiment, a method for treating asthma comprises inserting a delivery catheter into an airway adjacent to a nerve; using the catheter to infuse the above-described formulation and / or energy into airway tissue adjacent to the nerve, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the body cavity. Injury or damage to the nerve can alleviate symptoms of the disease, for example, by relieving shortness of breath. The purpose of the heat / energy can be to enhance the effect of the injury / damage by accelerating the reaction rate between the formulation and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure should be in the range of 0.1 to 14 atm, preferably 3 to 10 atm, and most preferably 4 to 8 atm.

[0176] Alternatively, a jet catheter without a balloon can be used to treat asthma. In one embodiment, the method for treating asthma comprises inserting a delivery catheter into an airway adjacent to a nerve; using the catheter to infuse the above-mentioned formulation and / or energy into the airway tissue adjacent to the nerve, wherein the amount of formulation and / or energy delivered is effective to beneficially damage or impair the nerve; and removing the delivery catheter from the body cavity. Damage or damage to the nerve can alleviate the symptoms of the disease, for example, by relieving shortness of breath. The advantage of this jet method is that it is simple, fast and can treat small diameter airways. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. For liquid and gas formulations, a fine mist may be preferably delivered. The diameter of the formulation leaving the jet hole may be 0.5 mm or less, more preferably 0.4 mm or less. The delivery gas pressure may preferably be less than 8 atm, more preferably 4 atm or less.

[0177] In one embodiment, a method for treating COPD and / or asthma comprises inserting a delivery catheter into an airway adjacent to a nerve; using the catheter to infuse the above-described formulation and / or heat into body cavity tissue adjacent to the nerve, wherein the amount of formulation and / or heat delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the airway. Injury or damage to the nerve can alleviate symptoms of the disease, for example, by alleviating COPD / asthma symptoms. The purpose of the heat / energy can be to enhance the damaging / damaging effect by accelerating the reaction rate between the formulation and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, and suspensions of one or more formulations. If the formulation includes vapors of one or more ingredients, heat can be generated by condensing the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the formulation can be between -40 and 140° C., -30 and 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. The temperature of the tissue being treated adjacent to the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue adjacent to the nerve can be -40 to 140° C., -30 to 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. The formulation infusion pressure and / or balloon inflation pressure can be 0.1 to 14 atm, preferably 3 to 10 atm, and most preferably 4 to 8 atm.

[0178] Alternatively, COPD can also be treated with a jet catheter, where the same methods described herein for asthma treatment can be used. This approach also includes combining the use of a balloon catheter and a jet catheter in the same procedure, which may result in a maximal denervation effect.

[0179] In one embodiment, a method for treating severe emphysema by lung volume reduction comprises inserting a delivery catheter into an airway adjacent to a target area; using the catheter to spray the formulation and / or energy described above to completely destroy the target lung tissue, wherein the amount of formulation and / or energy delivered is effective to beneficially damage the tissue; and removing the delivery catheter from the airway. The damage to the tissue can alleviate symptoms of the disease, such as emphysema symptoms. The formulation and / or energy can be delivered at the distal tip, at the sidewall, or a combination of both.

[0180] In one embodiment, the 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 the celiac artery, the common hepatic artery, the proper hepatic artery, or the left and right hepatic arteries; using any catheter described herein to infuse the above-mentioned formulation and / or energy into body cavity tissue adjacent to the nerve or directly into the nerve, wherein the amount of formulation and / or energy delivered is effective for beneficially injuring or damaging the nerve; and removing the delivery catheter from the body cavity. The purpose of the energy / heat can be to enhance the injury / damage effect by accelerating the reaction rate between the formulation and the nerve. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensing the vapor into a liquid in the tissue. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the formulation can be between -40 and 140°C, -30 and 100°C, -30 and 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be between -40 and 100°C, -30 and 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation is delivered through a needle to the perivascular area for denervation in a volume of 0.1 mL to 1.0 mL, preferably 0.3 mL to 0.8 mL, and most preferably 0.4 mL to 0.7 mL.

[0181] In one embodiment, a method for lowering 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 the celiac artery, the common hepatic artery, the proper hepatic artery, and / or the left and right hepatic arteries; infusing the above-described agent and / or energy into body cavity tissue adjacent to the nerve or directly into the nerve using any of the catheters described herein, wherein the amount of agent and / or energy delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the body cavity. The purpose of the heat / energy may be to enhance the injuring / damaging effect by accelerating the reaction rate between the agent and the nerve. Possible agents include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the agent comprises vapors of one or more components, heat may be generated by condensation of the vapor into a liquid in the tissue. If the agent comprises a liquid or solution, heat may be delivered from an elevated temperature above body temperature. The temperature of the formulation can be between -40 and 140° C., -30 and 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. The temperature of the tissue being treated adjacent to the nerve can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue adjacent to the nerve can be -40 to 140° C., -30 to 100° C., -30 to 80° C., or -40° C. or less, or less than, equal to, or greater than -30° C., -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140° C. or more. The formulation is delivered to the perivascular area for denervation via a needle in a volume of 0.1 mL to 1.0 mL, preferably 0.3 mL to 0.8 mL, and most preferably 0.4 mL to 0.7 mL.

[0182] In one embodiment, the method for treating obesity and / or diabetes comprises inserting any delivery catheter described herein into the left and / or right gastric artery adjacent to the stomach and esophageal nerves; using the catheter to infuse the above-mentioned formulation and / or energy into the gastric artery tissue or the artery adjacent to the nerves, wherein the amount of formulation and / or energy delivered is effective to beneficially damage or injure the nerves; and removing the delivery catheter from the gastric artery. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensing the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure and / or balloon inflation pressure should be in the range of 0.1 to 14 atm, preferably 3 to 10 atm, and most preferably 4 to 8 atm.

[0183] In one embodiment, a method for treating obesity comprises inserting any of the delivery catheters described herein into or outside a digestive cavity adjacent to a nerve; using the catheter to infuse the above-described formulation and / or energy into tissue of the digestive cavity, wherein the amount of formulation and / or energy delivered is effective to beneficially injure or damage the tissue; and removing the delivery catheter from the digestive cavity. Possible digestive cavities 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 reaction rate between the formulation and the nerves. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensing the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more.

[0184] In one embodiment, the method for treating obesity and diabetes comprises inserting any delivery catheter described herein into the left and / or right gastric artery adjacent to the gastric and esophageal nerves; using the catheter to infuse the above-mentioned formulation and / or energy into the tissue or exterior of the gastric artery adjacent to the nerves, wherein the amount of formulation and / or energy delivered is effective to beneficially damage or impair the nerves; and removing the delivery catheter from the gastric artery. Possible formulations include gases, vapors, liquids, solutions, emulsions, suspensions, and combinations thereof of one or more components. If the formulation includes vapors of one or more components, heat can be generated by condensation of the vapor into a liquid. If the formulation includes a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more.

[0185] In one embodiment, the method for treating urological diseases and / or benign prostatic hyperplasia (BPH) comprises inserting a delivery catheter into the urinary system cavity; using any catheter described herein to infuse the above-mentioned preparation and / or energy into the cavity or outside the cavity of urinary tissue (e.g., prostate, urethra, and ureter), wherein the amount of the preparation and / or energy delivered is effective for beneficially damaging or impairing the tissue; and removing the delivery catheter from the urinary cavity. The purpose of heat / energy can be to enhance the damage / damage effect by accelerating the reaction rate between the preparation and the nerves. The preparation includes one of a gas, vapor, liquid, solution, emulsion, suspension, and a combination thereof of one or more ingredients. If the preparation includes vapor of one or more ingredients, heat can be generated by condensing the vapor into a liquid. If the preparation includes a liquid or solution, heat can be transferred from a high-temperature preparation that exceeds body temperature. The temperature of the liquid formulation can be -40 to 140°C, -30 to 100°C, -30 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or more. The temperature of the tissue being treated near the nerve can be lower than the temperature of the formulation and higher than body temperature. The temperature of the tissue being treated near the nerve can be -40 to 100°C, -30 to 90°C, -20 to 80°C, or -40°C or less, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or more. The formulation infusion pressure and / or balloon inflation pressure may be 0.1 to 14 atm, preferably 3 to 10 atm, and most preferably 4 to 8 atm.

[0186] In one embodiment, a method for treating a cancer or tumor comprises inserting a needle or needle-based catheter percutaneously, orally, or intracavitary into the cancer or tumor under imaging guidance; using the catheter to deliver the aforementioned agent and / or energy into the cancerous tissue of the human body, wherein the amount of agent and / or energy delivered is effective to beneficially injure, damage, or eliminate the cancerous tissue; and removing the delivery catheter from the body. Injury, damage, or elimination of the cancerous tissue can alleviate disease symptoms, for example, by shrinking or eliminating the tumor. Possible imaging guidance methods include ultrasound, X-rays, CT scans, NMR imaging, and endoscopy. Relevant cancers 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, and uterine cancer. The purpose of the heat / energy can be to enhance the injurious / damaging / eliminating effect by accelerating the reaction rate between the agent and the cancerous tissue. The agent comprises one or more components selected from the group consisting of a gas, vapor, liquid, solution, emulsion, suspension, and combinations thereof. If the agent comprises vapor of one or more components, heat can be generated by condensation of the vapor into a liquid in the tissue. If the formulation comprises a liquid or solution, heat can be transferred from a high-temperature formulation that exceeds body temperature. The formulation temperature can be between -40 and 140°C, -30 and 100°C, -30 and 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140°C or higher. The temperature of the treated tissue can be lower than the formulation temperature and higher than body temperature. The temperature of the treated tissue can be between -40 and 100°C, -30 and 90°C, -20 to 80°C, or -40°C or lower, or less than, equal to, or greater than -30°C, -20, -10, -5, 0, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100°C or higher.

[0187] A method for treating myocardial infarction, atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), rheumatoid arthritis, or cancer caused by an immune response to an inflammatory condition can include percutaneously inserting a delivery catheter into a splenic artery adjacent to a nerve, using any of the catheters described herein to infuse the above-mentioned formulation and / or energy into body cavity tissue adjacent to the nerve or directly into the nerve, wherein the amount of the formulation and / or energy delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the body cavity. The formulation can be delivered to the perivascular area for denervation via a needle, with the formulation volume of each application ranging from 0.1 mL to 1.0 mL, or from 0.3 mL to 0.8 mL, or from 0.4 mL to 0.7 mL.

[0188] A method for treating myocardial infarction, atherosclerosis, coronary artery disease (CAD), or peripheral vascular disease (PAD) caused by hypercholesterolemia may include percutaneously inserting a delivery catheter into a splenic artery adjacent to a nerve; using any of the catheters described herein to infuse the above-mentioned formulation into and / or apply energy to body cavity tissue adjacent to the nerve or directly to the nerve, wherein the amount of the formulation and / or energy delivered is effective to beneficially injure or damage the nerve; and removing the delivery catheter from the body cavity. The formulation can be delivered to the perivascular area through a needle for denervation, with the formulation volume for each application ranging from 0.1 mL to 1.0 mL, or from 0.3 mL to 0.8 mL, or from 0.4 mL to 0.7 mL.

[0189] Hypertension and hypercholesterolemia may be predisposing factors for vascular diseases such as coronary artery disease (CAD), but the two act synergistically to significantly alter risk, as their combined effects are thought to be multiplicative rather than additive. Therefore, individuals with combined risk factors are at particularly high risk for CAD. Impaired endothelium-dependent vasodilation in patients with essential hypertension may be associated with hypercholesterolemia; furthermore, increased sympathetic nerve activity may be associated with hyperlipidemia in hypertension. For example, the positive correlation between serum triglyceride levels and blood pressure is significant, particularly in individuals with a high body mass index (BMI>24). Embodiments of the present invention can lower not only blood pressure but also cholesterol levels. The biological interrelationship between blood pressure and atherogenic lipid fractions, as well as the pathophysiological factors underlying these interrelationships, may influence the mechanisms by which hypertension is associated with an increased risk of CAD. Therefore, in various embodiments of the treatment methods, reductions in blood pressure or cholesterol levels, or both, may be beneficial in reducing the risk of coronary artery disease (CAD) and peripheral vascular disease (PAD).

[0190] A method for treating a disease with a needle-based balloon infusion system (wherein 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 the needle-based balloon delivery catheter into a body cavity, wherein the needle-based balloon delivery catheter includes a distal head, at least one marker band, at least one needle, at least one needle exit hole, at least one flushing hole, a flushing cavity, a flushing port, a guidewire cavity, at least one centering balloon located at a substantially distal end of the catheter, an inflation cavity, an inflation port, an ablation port, a needle movement shaft, and a needle movement controller; wherein the needle cavity is pre-filled with an ablative agent, the flushing cavity is pre-filled with an ablative agent, and the flushing cavity is pre-filled with an ablative agent. The cavity is pre-filled with a flushing medium before insertion; 2) inflating the centering balloon to center the delivery catheter shaft within the body cavity; 3) deploying at least one needle into, outside, or within the wall of the body cavity; 4) infusing a formulation through the at least one needle, wherein the amount of formulation delivered is effective to damage or injure the target tissue to alleviate disease symptoms; 5) optionally removing the formulation from the tissue; 6) retracting the needle into the delivery catheter and defl ying the centering balloon; 7) flushing the flushing cavity before defl ying the balloon or before inserting into the next body cavity to prevent needle cavity obstruction and blood clot formation; 8) inserting the needle-based balloon delivery catheter into the next body cavity; 9) repeating 2) to 8) until all target body cavities have been treated; and 10) removing the delivery catheter from the body cavity. 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 ablative agent can be one of ethanol, anhydrous ethanol, acetic acid, and dilute acetic acid. The flushing medium can include saline or heparinized saline or a neutralizer for the ablative agent. The body cavity 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

[0191] A method for using a needle-based balloon delivery catheter may include pre-filling the needle lumen with an ablative agent, pre-filling the irrigation lumen with an irrigation medium, and inserting the catheter into a guide catheter over a guidewire. Once at the treatment site, the balloon may be inflated to the size of the vessel to center the needle head, the needle may then be advanced to the treatment location, and the ablative agent may be infused; following infusion, the needle may be removed and retracted to the distal head, and an irrigation fluid may be injected to keep the needle compartment / aperture and needle tip / opening of the distal head clean and avoid direct contact with blood. The balloon may be deflated and the catheter may be removed from the treatment site and / or moved to another treatment site.

[0192] In some embodiments, when the target vessel is long and needs to be treated more than once, the distance between treatment sites can be used to separate the infused ablative agent. The separation distance between treatment sites can be 5 mm to 30 mm, for example 5 mm to 15 mm.

[0193] For each application / treatment of a main vessel, such as an artery, the dose of ablative agent may be 0.1 mL, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, 1.0, or 1.2 mL. If more than one treatment is performed, the total dose (volume) for a particular main vessel (length) may be 0.3 mL, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, or 2.4, or up to 3.6 mL. For a branch vessel or artery, the dose per application may be 0.1 mL, 0.2, 0.3, 0.4, 0.5, or 0.6 mL. If more than one treatment is performed, the total dose for that branch may be 0.2 mL, 0.4, 0.6, 0.8, 1.0, or 1.2 mL.

[0194] Various embodiments of the present invention provide a needle-based balloon delivery catheter for delivering a material to a target tissue in a patient's body cavity. 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., three needles), each needle located in a needle lumen. The needle lumen may be open to the exterior of the catheter shaft through at least one needle exit aperture. The delivery catheter may include a flush port at the proximal end of the shaft in fluid communication with a flush lumen. The flush lumen is in fluid communication with the distal end of the needle lumen. The flush port may be in fluid communication with the needle exit aperture through the flush 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 located adjacent to 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 may be inflated through the inflation lumen via the inflation port, and the distal end of the catheter shaft may be substantially centered within the body cavity during inflation. The delivery catheter may include an ablation or denervation port at the proximal end of the shaft. The ablation or denervation port is in fluid communication with the at least one needle to supply ablative energy or agent to the at least one needle. The delivery catheter may also include a needle movement controller electrically or mechanically connected to the at least one needle. The needle movement controller can deploy the at least one needle into a body cavity, into a body cavity wall, or outside the body cavity. Deploying the needle through the needle exit opening can allow the agent to penetrate the body cavity wall at a pressure higher than the body cavity pressure. The target tissue can be a target tissue of the following arteries or veins: a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof. The formulation pressure during infusion can be any suitable pressure, and the balloon inflation pressure can be any suitable pressure. For example, the pressure of the formulation infusion can be in the range of 0.1 to 14 atm. The balloon inflation pressure can be in the range of 0.1 to 14 atm.

[0195] Example

[0196] 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.

[0197] Example 1. Preclinical trials

[0198] Pig animals weighing 47 kg were anesthetized with isoflurane and one side of their renal artery was ablated with ethanol using a three-needle single-balloon catheter, while the contralateral renal artery was used as a control. The catheter needle span diameter was approximately 10 mm. The catheter balloon is a low-pressure and compliant balloon with a diameter of 7 mm at 1 atm, the function of which is to center the distal axis without overstretching the artery. Optionally, the balloon can be inflated with a syringe without using an inflation device. Due to the characteristics of the balloon, the balloon can be used for arteries of any diameter (lower or higher than the balloon diameter). Before being inserted into the artery, the catheter is pre-filled with a liquid formulation until it overflows from the needle (the needle extends out), the needle is then retracted, and the syringe with a predetermined treatment volume is connected to the catheter. Using standard renal access procedures, the three-needle balloon delivery catheter is placed sequentially in the target renal artery of the aorta and the extra renal artery (branch) via a guidewire. Once the target ablation site is reached, the balloon is inflated, the needle is then deployed, and anhydrous ethanol at room temperature is infused into the adventitia and periadventitia space of the renal artery. The infusion volume of the aorta used at each application using a 1mL syringe is 0.6mL, and the infusion volume of the branch is 0.3mL. The infusion time of both application volumes is all within 5 seconds. During the balloon inflation process, the ratio of the balloon diameter to the surrounding artery diameter is about 1:1.1 (slightly larger) monitored by fluoroscopy. By the end of the treatment time, the needle is first retracted into the catheter, the balloon is then deflated, and if necessary, the catheter is ready to be removed or placed in another artery position. In the present embodiment, a total of 4 treatments were carried out: 2 times for the aorta and 1 time for each branch, and the total volume of the preparation used was 1.8mL.

[0199] Post-ablation renal angiography was obtained to examine for any vascular debris, stenosis, and other abnormalities. There was no significant renal artery spasm during and after the infusion therapy.

[0200] Two weeks after treatment, the animals were euthanized, and gross necropsy revealed that all treatment-related organs were normal. Renal tissue samples were collected from the cranial (n=3), middle (n=3), and caudal (n=3) renal cortex to measure renal tissue norepinephrine (NE) content using a known HPLC method. Norepinephrine is a neurotransmitter used by the sympathetic nervous system, and its level is used as a standard measure of renal denervation. Compared to the NE concentration in the untreated side (control), the NE concentration in the treated side after denervation was lower or much lower, as shown in Figure 2. Figure 10 As shown. Ethanol ablation of the renal artery resulted in a 94% reduction in renal norepinephrine concentration (mean NE content: control: 87 ng / g vs. treatment: 4.9 ng / g). The percentage of individual NE reductions calculated from similar tissue locations between the control and treatment groups ranged from 89% to 97.5%. Renal artery and surrounding tissue were also collected for histopathological evaluation.

[0201] Not only was NE content reduced after ethanol ablation, but histopathological evaluation also demonstrated renal nerve damage, e.g. Figure 11 Shown is a nerve surrounded by mild fibrosis within the outer edge of the adventitia (see arrow).

[0202] Example 2. Preclinical trials

[0203] Two 46 kg porcine animals were treated with hepatic artery ethanol ablation using a formulation that was anhydrous ethanol at room temperature and a three-needle single balloon catheter of the same type as used in Example 1. Prior to insertion into the artery, the catheter was pre-filled with the liquid formulation until overflow from the needle (needle extended), then the needle was retracted and a syringe with a predetermined treatment volume was connected to the catheter. Standard hepatic artery access procedures were performed. Each hepatic artery was treated twice, evenly distributed along the length of the artery, and the infusion volume for each application was 0.6 mL using a 1 mL syringe and the infusion time was less than 5 seconds. The inflated balloon diameter to artery expansion ratio was monitored to be less than 1:1.1, and the syringe was used for inflation. In both porcine animals in this study, hepatic angiography showed no significant arterial spasm during and after the infusion treatment. As a control, untreated porcine animals of similar weight were used for NE reduction calculation and histopathological evaluation for comparison.

[0204] Two weeks after treatment, two animals were euthanized; gross necropsy showed 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 medial lobe (n=2), left lateral lobe (n=2), and caudate lobe (n=2) to measure liver tissue norepinephrine (NE) content using a known HPLC method. NE reduction was calculated based on data collected from tissues at similar locations between the treatment and control groups. Figure 12 As shown, the mean hepatic NE concentration reduction in the two animals was 85% and 94%, respectively. Individual calculated percentages ranged from 55% to 95% in one animal and from 86% to 97.5% in the other. As with the renal ablation studies, arterial and surrounding tissues were harvested for histopathological evaluation.

[0205] The above preclinical study results show that ethanol treatment is effective and safe.

[0206] Example 3. Clinical trial, metabolic syndrome

[0207] In one embodiment, human male patient A is 53 years old and has metabolic syndrome. He has had hypertension for 10 years and has taken two antihypertensive drugs, has had type 2 diabetes for 2 years and has taken two T2DM (type 2 diabetes) drugs, and has been obese for 8 years. His triglyceride level was 336 mg / dL before surgery. The target arteries for his treatment are the renal arteries, hepatic arteries, splenic arteries, and left gastric artery.

[0208] During the procedure, moderate sedation was used in accordance with institutional standard practice, and no general anesthesia was used. The arteries were ligated using a 7F guiding catheter introduced through the femoral artery. Angiography of the arteries was performed before intervention. All four arteries were treated with the same procedure. Treatment began with the upper body arteries, in the order of the splenic artery, hepatic artery, left gastric artery, left renal artery, and right renal artery. After preliminary angiography of the hepatic artery, splenic artery, and left gastric artery, a rapid-change three-needle single-balloon catheter was advanced through the guiding catheter and into the artery over the guidewire. Prior to insertion into the artery, the catheter was pre-filled with liquid ablation agent (dehydrated ethanol) until it overflowed from the needle (needle extended), the needle was then retracted, and a syringe with a predetermined treatment volume was connected to the catheter.

[0209] The maximum catheter needle span diameter is approximately 12 mm, and the span diameter can be adjusted based on arterial diameter. The catheter balloon is a low-pressure, compliant balloon with a diameter of 7 mm and a pressure of approximately 1 atm. The function of this balloon is to center the distal tip / shaft without excessively stretching the artery. The balloon is inflated using a 30cc syringe with a stopcock (without an inflation device) to gently control the balloon diameter.

[0210] Under fluoroscopic guidance, a three-needle balloon delivery catheter was placed into the target splenic artery. Once the target ablation site was reached, the balloon was inflated, the needle was deployed, and absolute ethanol at room temperature was infused into the adventitia and peritumoral space of the splenic artery. The infusion volume for each application was 0.6 mL using a 1 mL syringe. The infusion time for each application was within 10 seconds. During the balloon inflation process, the ratio of the balloon diameter to the surrounding artery diameter was monitored by fluoroscopic examination and was approximately 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 in the same splenic artery approximately 15 mm away from the first treatment site. The treatment steps (balloon inflation, needle deployment, ablation infusion, needle retrieval, balloon deflation) were repeated for the second treatment. The total volume of ethanol used in the two treatments for the splenic artery was 1.2 mL.

[0211] Common hepatic artery ablation followed the same treatment and surgical procedures as the splenic artery treatment. The catheter was replaced with a fresh one for common hepatic artery ablation. Two treatments were performed with the same ablation dose of 0.6 mL, approximately 15 mm apart (between treatment sites), to the common hepatic artery. The total volume of alcohol used for hepatic artery ablation was 1.2 mL. Following liver treatment, a catheter was placed into the left gastric artery for the next ablation. The same treatment and procedure were used again, except that a single ablation with 0.6 mL of alcohol was applied to the left gastric artery. Angiography was performed after removal of the three-needle balloon delivery catheter.

[0212] After the above three arterial ablation treatments, angiography of the renal arteries was performed before intervention. The appropriate branches and aorta were evaluated and pre-determined for treatment. After evaluation, a three-needle balloon delivery catheter was advanced through the guide catheter and over the guidewire into the branch artery of the left renal artery, and stopped just outside the bifurcation area. The same catheter operation method and procedural steps were used, and the branch artery was ablated once with 0.3 mL 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 0.6 mL of alcohol. The catheter was then pulled back approximately 10 mm from the first treatment site in the aorta to the second ablation site, where a second ablation treatment was performed with 0.6 mL of alcohol. A total of 3 treatments were performed on the left renal artery: 2 times on the aorta and 1 time on the branch artery, and the total volume of alcohol used was 1.5 mL.

[0213] The same method and procedural steps were repeated for the right renal artery. After initial angiography and assessment of the right renal artery, a three-needle balloon delivery catheter was advanced through the guiding catheter and over the guidewire into branch artery #1. Branch #1 was ablated twice with a distance of approximately 10 mm between treatment sites, and 0.3 mL of alcohol was used for each treatment. The catheter was then placed into branch artery #2, and treated twice with a volume of 0.3 mL of alcohol per treatment. After both branches were treated, the catheter was pulled back into the aorta until its needle approached the midpoint of the aorta, and the right aorta was ablated once with a volume of 0.6 mL of alcohol. The total alcohol volume used for the right renal artery treatment was also 1.8 mL.

[0214] Patient A was followed up at 2 weeks (2 weeks), 1 month (1 month), and 3 months (3 months) after surgery, and his follow-up data are listed below along with his baseline data obtained before surgery for comparison. No medication changes were made during the follow-up period.

[0215] Body weight: Baseline = 103 kg, 2 wk = 96.2 kg, 1 mo = 95.6 kg, 3 mos = 96.2 kg. Since week 3 post-surgery (2 wk time point), the patient was observed to have lost approximately 7% of body weight and maintained the weight loss at the 3-month follow-up.

[0216] 24-hour blood pressure (SBP / DBP): Baseline = 164 / 109 mmHg, 1 month = 140 / 87 mmHg, 3 months = 141 / 84 mmHg. Blood pressure data are the average of 24-hour ambulatory blood pressure measurements. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly compared to baseline, by approximately 14% and 20%, respectively; these reductions were maintained during the 3-month follow-up.

[0217] Blood sugar levels, HbA1c: baseline = 7.5%, 3mos = 6.6%. The patient also had significant improvement in his glycated hemoglobin (HbA1c) level. Compared to his baseline value, his HbA1c value changed by almost -1% at the 3-month follow-up.

[0218] Triglycerides: Baseline = 336 mg / dL, 2 weeks = 160 mg / dL, 1 month = 139 mg / dL, 3 months = 167 mg / dL. Triglycerides (TG) are a type of fat (lipid) found in the blood. High triglyceride levels may be a clue that a person has fatty liver disease. Patient A's triglyceride levels improved over the two-week follow-up, decreasing by approximately 50%. The reduction and improvement in triglyceride levels were maintained at the three-month follow-up. At the one-month follow-up, Patient A's TG levels were within the normal range.

[0219] High-density lipoprotein (HDL): Baseline = 39 mg / dL, 2 weeks = 42 mg / dL, 1 month = 43 mg / dL, 3 months = 40 mg / dL. Patient A's baseline high-density lipoprotein (HDL) level was just within the normal range. Then at follow-up, his HDL seemed to improve, and all 3 numbers were 40 or higher. Patient A's TG / HDL ratio improved significantly from 8.6 (>5 abnormal) at baseline to 4.2 at 3 months of follow-up, which is within the normal range (<5); if the patient had NAFLD, Patient A's NASH condition improved significantly.

[0220] The short-term results for Patient A are significant and very encouraging for the treatment and technology. The data show that the patient's health status has improved, and his metabolic syndrome-related diseases appear to be under control at 3 months of follow-up.

[0221] Example 4. Clinical trial, hypertension

[0222] In another example, hypertension was treated in multiple arteries / tissues. A 50-year-old male, Patient B, had blood pressure controlled after an ablation procedure at a 3-month follow-up timepoint. Patient B had a 5-year history of hypertension. Patient B underwent the same surgical and ablation treatment as Patient A in Example 3. Patient B's treated arteries and the ablation dose at each treatment site are summarized in Table 1.

[0223] Table 1. The treated artery and the ablation dose at each treatment site in patient B.

[0224] Kidney B: renal branch artery; Kidney M: main renal artery; R: right; L: left.

[0225]

[0226] Post-treatment average 24-hour ambulatory blood pressure data were: baseline = 136 / 79 mmHg, 1 month = 107 / 61 mmHg, 3 months = 115 / 66 mmHg. At 1-month follow-up, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly from baseline by approximately 21% and 23%, respectively. These improvements were maintained at 3 months of follow-up, with both SBP and DBP decreasing by approximately 15% from baseline.

[0227] Example 5. Clinical trial, T2DM

[0228] In another example, multiple arteries / tissues are treated for diabetes. The same patient, Patient B, had a one-year history of T2DM and received treatment for diabetes in their liver, spleen, abdominal cavity, right kidney, and left renal arteries. The treatment results in Example 4 resulted in some improvement in Patient B's fasting blood glucose and HbA1c levels.

[0229] The post-treatment data for fasting blood glucose were: Basal = 186 mg / dL, 2wks = 127 mg / dL, 1mo = 92 mg / dL, 3mos = 110 mg / dL. The test was performed in the morning before the patient ate. A fasting blood glucose level of 100 to 125 mg / dL (5.6 to 6.9 mmol / L) is considered prediabetes. If it is 125 mg / dl or higher, the person has diabetes. The data indicate that Patient B had diabetes before surgery. His fasting blood glucose level improved significantly after surgery compared to baseline, with a change of -32% at the 2-week follow-up and a change of -50% at the 1-month follow-up. At the 3-month follow-up, his hypoglycemic level remained at a low level of 110 mg / dL, which was a decrease of -41% from baseline.

[0230] Blood glucose HbA1c data: Baseline = 8.1%, 3mos = 6.0%. The patient's HbA1c improved by an absolute value of -2.1 (%) compared to the baseline, and decreased by almost 26% within 3 months after the operation.

[0231] Example 6. Clinical trial, weight loss

[0232] In another example, multiple arteries / tissues were treated to manage weight. Patient B, who had a three-year history of obesity, experienced weight loss after ablation. The multiple arteries treated were the hepatic, splenic, celiac, right, and left renal arteries. See Example 4 for more information on this treatment.

[0233] Weight: Baseline = 83 kg, 2 weeks = 79.3 kg, 1 month = 79.9 kg, 3 months = 79.1 kg. A -4.5% decrease in initial weight was observed at the 2-week follow-up, from 83 kg at baseline to 79.3 kg. The improved weight was maintained at the 3-month follow-up.

[0234] The terms and expressions used are used as descriptive rather than limiting terms, and when such terms and expressions are used, it is not intended to exclude any equivalents of the features shown and described or portions thereof, but it should be recognized that various modifications are possible within the scope of the embodiments of the present invention. Therefore, it should be understood that although the present invention has been specifically disclosed through specific embodiments and optional features, those of ordinary skill in the art may make modifications and variations to the concepts disclosed herein, and such modifications and variations are considered to be within the scope of the embodiments of the present invention.

[0235] Exemplary embodiments

[0236] The following exemplary embodiments are provided, the numbering of which should not be construed as designating a level of importance:

[0237] 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 cavities (e.g., at least three different body cavities or at least four different body cavities), the method comprising:

[0238] A treatment procedure is performed on a body cavity as a first body cavity, the treatment procedure comprising:

[0239] inserting a delivery catheter into the body cavity, 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;

[0240] inflating the balloon to center the distal end of the shaft within the body lumen;

[0241] denervating or ablating a target tissue in the body cavity using the delivery catheter, including delivering an amount of energy or agent to the target tissue to effectively injure or damage the target tissue to alleviate disease symptoms;

[0242] deflation of the balloon; and

[0243] removing the delivery catheter from the body cavity;

[0244] The treatment procedure is performed on a second body lumen different from the first body lumen.

[0245] Embodiment 2 provides the method of embodiment 1, wherein performing the treatment procedure on the second body cavity comprises reusing the same delivery catheter for the treatment procedure on the second body cavity as used in the treatment procedure on the first body cavity.

[0246] Embodiment 3 provides the method of any of embodiments 1-2, wherein performing the treatment procedure on the second body cavity includes using a different delivery catheter in the treatment procedure on the second body cavity than used in the treatment procedure on the first body cavity, the different delivery catheter comprising a catheter shaft, a balloon at the distal end of the shaft, and an inflation lumen in fluid communication with an interior of the balloon.

[0247] Embodiment 4 provides the method of any one of embodiments 1-3, wherein

[0248] The target tissues of the first and second body cavities are different and are independently selected from the group consisting of a renal artery, a pulmonary artery, a vascular cavity, a celiac artery, a common hepatic artery, a proper hepatic artery, a gastroduodenal artery, a right and left hepatic artery, a splenic artery, a right and left gastric artery, an adrenal artery, a phrenic artery, a mesenteric artery, a non-vascular cavity, an airway, a sinus, an esophagus, a respiratory and digestive cavity, a stomach, a duodenum, a jejunum, a prostate, a urethra, a ureter, and a urinary cavity; or

[0249] wherein the first body cavity and the second body cavity belong to different types of body cavities selected from the group consisting of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, a distal end of the left main renal artery, a distal end of the right main renal artery, a distal end of a left main renal artery branch, a distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, and a urinary cavity; or

[0250] Its combination.

[0251] Embodiment 5 provides the method of any one of embodiments 1-4, 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 diseases, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urological system diseases, cancer, tumors, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD), and combinations thereof.

[0252] Embodiment 6 provides the method of any one of embodiments 1-5, wherein the alleviating disease symptoms comprises alleviating 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.

[0253] Embodiment 7 provides the method of any one of embodiments 1-6, wherein the alleviating disease symptoms comprises lowering blood pressure, lowering blood glucose levels and AIC, reducing weight, reducing restenosis, reducing liver fat, and reducing pain, or a combination thereof.

[0254] Embodiment 8 provides the method of any 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.

[0255] 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.

[0256] Embodiment 10 provides the method of any one of embodiments 1-9, wherein the delivery catheter comprises a chemical infusion delivery catheter.

[0257] 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.

[0258] Embodiment 12 provides the method of any one of embodiments 1-11, wherein the delivery catheter comprises an energy delivery catheter.

[0259] Embodiment 13 provides a method according to any one of embodiments 1-12, wherein denervating or ablating the target tissue of the body cavity with the delivery catheter comprises delivering an amount of energy from the delivery catheter to the target tissue using radiofrequency, cryoablation, microwaves, laser, ultrasound, high-intensity focused ultrasound, condensation of at least some of the agent vapor into a liquid, or a combination thereof.

[0260] Embodiment 14 provides the method of any one of embodiments 1-13, wherein the disease comprises:

[0261] renal hypertension and diabetes, or

[0262] Renal hypertension and obesity, or

[0263] diabetes and obesity, or

[0264] Its combination.

[0265] Embodiment 15 provides the method of any one of embodiments 1-13, wherein the disease comprises renal hypertension and diabetes.

[0266] Embodiment 16 provides the method of any one of embodiments 1-13, wherein the disease comprises renal hypertension and obesity.

[0267] Embodiment 17 provides the method of any one of embodiments 1-13, wherein the disease comprises diabetes and obesity.

[0268] Embodiment 18 provides the method of any one of embodiments 1-17, wherein the first or second body lumen comprises the splenic artery.

[0269] Embodiment 19 provides a method of any of embodiments 1-18, wherein the first body cavity or the second body cavity 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof).

[0270] Embodiment 20 provides the method of any one of embodiments 1-19, wherein the first or second body lumen comprises the hepatic artery, a hepatic artery branch, the right hepatic artery, the left hepatic artery, the common hepatic artery, the proper hepatic artery, the hepatic celiac artery, or a combination thereof.

[0271] Embodiment 21 provides a method of any of embodiments 1-20, wherein the first or second body lumen comprises a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof), wherein the method results in a reduction in renal norepinephrine of at least 40%.

[0272] Embodiment 22 provides a method for treating a disease, the method comprising:

[0273] inserting a delivery catheter into a body cavity, wherein the delivery catheter comprises a catheter shaft, at least one injection orifice, and at least one marker band;

[0274] ejecting the formulation through the at least one ejection orifice, wherein the amount of the formulation delivered is effective to injure or damage the target tissue to alleviate symptoms of the disease;

[0275] optionally removing the preparation from the tissue; and

[0276] The delivery catheter is removed from the body cavity.

[0277] 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 cavity; and defl ucing the centering balloon after injection.

[0278] 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

[0279] deploying the at least one needle into, outside, or inside a wall of the body cavity; and

[0280] infusing a formulation through the infusion lumen and the at least one needle, wherein the amount of formulation delivered is effective to injure or damage target tissue to alleviate symptoms of the disease; and

[0281] The at least one needle is retracted into the delivery catheter after infusion.

[0282] Embodiment 25 provides a method according to 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 cavity, a needle control mechanism, and a flushing cavity, wherein the at least two needles are deployed from the needle cavity and retracted into the needle cavity by the needle control mechanism, and the distal end of the flushing cavity is in fluid communication with the needle cavity, the method further comprising flushing the needle with a flushing fluid through the flushing cavity.

[0283] Embodiment 26 provides the method of any one of embodiments 1-25, wherein the at least two needles include three needles and the three needles are arranged at uniform distances around the circumference of the catheter shaft and are located distal to the balloon.

[0284] Embodiment 27 provides a method for treating a disease, the method comprising:

[0285] inserting a centering balloon delivery catheter into a body cavity, 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;

[0286] inflating the centering balloon to center the delivery catheter shaft within the body lumen;

[0287] deploying the at least one needle into, outside, or inside a wall of the body cavity;

[0288] infusing a formulation through the at least one needle, wherein the amount of formulation delivered is effective to injure or damage the target tissue to alleviate symptoms of the disease;

[0289] optionally removing the preparation from the tissue;

[0290] retracting the needle into the delivery catheter and defusing the centering balloon; and

[0291] The delivery catheter is removed from the body cavity.

[0292] 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 diseases, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), urological system diseases, cancer, tumors, pain, rheumatoid arthritis (RA), asthma, chronic obstructive pulmonary disease (COPD) and combinations thereof.

[0293] Embodiment 29 provides a method according to embodiment 28, wherein the cancer is selected from adrenal cancer, bladder cancer, cervical cancer, colon cancer, esophageal cancer, gallbladder cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, gastric cancer, duodenal cancer, jejunal cancer, uterine cancer and combinations thereof.

[0294] Embodiment 30 provides a method according to any one of embodiments 1-29, wherein the target tissue is 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, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

[0295] Embodiment 31 provides the method of any one of embodiments 1-30, wherein the formulation comprises or consists essentially of ethanol.

[0296] Embodiment 32 provides a method according to any one of embodiments 1-31, wherein the formulation consists of ethanol.

[0297] Embodiment 33 provides a method according to any one of embodiments 1-32, wherein the formulation comprises a gas, vapor, liquid, solution, emulsion, suspension, or a combination thereof of one or more components.

[0298] Embodiment 34 provides a method according to any one of embodiments 1-33, wherein the formulation comprises vapor of one or more ingredients and heat is generated by condensation of the vapor into a liquid.

[0299] Embodiment 35 provides a method according to 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.

[0300] Embodiment 36 provides a method according to any one of embodiments 1-35, wherein the formulation comprises an emulsion or a suspension and heat is transferred from the formulation to the target tissue.

[0301] Embodiment 37 provides the method of any one of embodiments 1-36, wherein the temperature of the formulation ranges from 40 to 140°C.

[0302] Embodiment 38 provides the method of any one of embodiments 1-37, wherein the temperature of the formulation ranges from 0 to 140°C.

[0303] Embodiment 39 provides the method of any one of embodiments 1-38, wherein the temperature of the formulation ranges from -40 to 0°C.

[0304] Embodiment 40 provides the method of any one of embodiments 1-39, wherein the temperature of the formulation is room temperature.

[0305] Embodiment 41 provides a method according to any one of embodiments 1-40, wherein the temperature of the target tissue is lower than the temperature of the formulation.

[0306] Embodiment 42 provides a method according to any one of embodiments 1-41, wherein the temperature of the target tissue is higher than the temperature of the formulation.

[0307] Embodiment 43 provides a method according to any one of embodiments 1-42, wherein the formulation is infused at a pressure ranging from 0.1 to 14 atm.

[0308] Embodiment 44 provides a method according to any one of embodiments 1-43, wherein the temperature of the target tissue ranges from -40 to 100°C.

[0309] Embodiment 45 provides a method according to any one of embodiments 1-44, wherein the temperature of the target tissue ranges from -40 to 0°C.

[0310] Embodiment 46 provides a method according to any one of embodiments 1-45, wherein the temperature of the target tissue is equal to body temperature.

[0311] Embodiment 47 provides a method according to any one of embodiments 1-46, wherein the pressure of the formulation is in the range of about 2 to 200 psi at a temperature in the range of about -40 to 150°C.

[0312] 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.

[0313] Embodiment 49 provides a 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.

[0314] Embodiment 50 provides a method according to any one of embodiments 1-49, wherein the method delivers about 2 cal / g to about 150 cal / g of heat or energy to the target tissue.

[0315] Embodiment 51 provides a method according to any one of embodiments 1-50, wherein the delivery catheter is a needle or needle-based delivery catheter, a single balloon delivery catheter, a double balloon delivery catheter, an energy delivery catheter, an infusion catheter, a balloon infusion catheter, a balloon catheter, a dumbbell balloon infusion catheter, or a combination thereof.

[0316] Embodiment 52 provides a method according to any one of embodiments 1-51, wherein the balloon inflation pressure ranges from 0.1 to 14 atm.

[0317] Embodiment 53 provides a 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, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, iodized oil, urea, and derivatives and combinations thereof.

[0318] Embodiment 54 provides a method according to 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, anhydrous alcohol, isopropyl alcohol, propanol, butanol, isobutanol, ethylene glycol, glycerol, acetic acid, lactic acid, propyl iodide, isopropyl iodide, ethyl iodide, methyl acetate, ethyl acetate, ethyl nitrate, isopropyl acetate, ethyl lactate, or a combination thereof.

[0319] 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 sodium channel blockers, tetrodotoxins, saxitoxins, decarbamoyl saxitoxins, vanilloids, neosaxitoxins, lidocaine, conotoxins, cardiac glycosides, glycosides, digoxins, glutamates, staurosporines, amlodipines, verapamils, cymarins, digitoxins, proscillaridins, quabains, veratridines, domoic acids, oleandrins, carbamazepines, aflatoxins, guanethidines, guanethidine sulfates, or a combination thereof.

[0320] Embodiment 56 provides a method according to any one of embodiments 1-55, wherein the formulation comprises a contrast agent for imaging denervation of a nerve, wherein the contrast agent comprises iodine, ethyl iodide, sodium iodide, lipiodol, nonoxynol iodine, iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iotrolan, iodixanol, ioxaglate, a derivative thereof, or a combination thereof.

[0321] Embodiment 57 provides the method of any one of embodiments 1-56, wherein the formulation comprises an azeotrope.

[0322] Embodiment 58 provides a method according to embodiment 57, wherein the azeotrope comprises ethanol / water, propanol / water, isopropanol / water, butanol / water, acetic acid / water, lactic acid / water, ethyl lactate / water, ethyl lactate / ethanol, lactic acid / ethanol / water, ethyl lactate / water / ethanol, ethyl acetate / ethanol, ethyl nitrate / ethanol, isopropyl acetate / ethanol, or a combination thereof.

[0323] Embodiment 59 provides a method according to any one of embodiments 1-58, wherein the formulation comprises ethanol, ethanol / water, ethanol / water / oxygen, ethanol / water / air, ethanol / water / contrast agent, ethanol / water / surfactant, ethanol / water / contrast agent / surfactant, propanol / water, isopropanol / water, butanol / water, acetic acid / water, or a combination thereof.

[0324] Embodiment 60 provides a centering balloon catheter for delivering a material to a target location in a body cavity of a patient, the centering balloon catheter comprising:

[0325] proximal end;

[0326] distal end;

[0327] Line cavity;

[0328] balloon inflation chamber;

[0329] Preparation infusion chamber and / or vacuum chamber;

[0330] an expandable balloon portion;

[0331] At least one injection needle;

[0332] at least one marker band adjacent to the centering balloon; and

[0333] At least one needle exit opening is adjacent to the marker band for needle deployment.

[0334] Embodiment 61 provides the centering balloon catheter of embodiment 60, comprising three injection needles.

[0335] Embodiment 62 provides the centering balloon catheter of any of embodiments 60-61, wherein deployment of the needle through the needle exit opening allows the formulation to penetrate into the wall of the body lumen at a pressure higher than the pressure of the body lumen.

[0336] Embodiment 63 provides the centering balloon catheter of any one of embodiments 60-62, wherein the target tissue is a target tissue of a renal artery, a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

[0337] Embodiment 64 provides the centering balloon catheter of any one of embodiments 60-63, wherein the formulation is infused at a pressure ranging from 0.1 to 14 atm, and the balloon inflation pressure is in a range of 0.1 to 14 atm.

[0338] Embodiment 65 provides a needle-based balloon delivery catheter for delivering a material to a target tissue in a body cavity of a patient, the delivery catheter comprising:

[0339] a catheter shaft having a proximal end and a distal end;

[0340] at least one marker band located adjacent said distal end of said shaft;

[0341] 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 aperture;

[0342] an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen, 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 exit aperture through the irrigation lumen;

[0343] a guidewire lumen extending through at least the distal end of the shaft;

[0344] at least one balloon adjacent the distal end of the catheter;

[0345] inflation cavity;

[0346] an inflation port in fluid communication with the inflation lumen and with the interior of the balloon, wherein 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;

[0347] 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 ablative energy or agent to the at least one needle; and

[0348] A needle movement controller is 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 a wall of the body cavity, or outside of the body cavity.

[0349] Embodiment 66 provides the delivery catheter of embodiment 65, comprising three injection needles.

[0350] Embodiment 67 provides the delivery catheter of any of embodiments 65-66, wherein deployment of the needle through the needle exit opening allows the formulation to penetrate into the wall of the body lumen at a pressure higher than the pressure of the body lumen.

[0351] Embodiment 68 provides the delivery catheter of any one of embodiments 65-67, wherein the target tissue is a target tissue of a renal artery (e.g., a left main renal artery, a right main renal artery, a renal artery branch, a left renal artery branch, a right renal artery branch, the distal end of the left main renal artery, the distal end of the right main renal artery, the distal end of a left main renal artery branch, the distal end of a right main renal artery branch, or a combination thereof), a renal vein, a gastric artery, a gastric vein, a hepatic artery, a hepatic vein, a pulmonary artery, a pulmonary vein, a celiac artery, a celiac vein, a gastroduodenal artery, a gastroduodenal vein, a splenic artery, a splenic vein, an adrenal artery, an adrenal vein, a phrenic artery, a phrenic vein, a mesenteric artery, a mesenteric vein, an airway, an esophagus, a stomach, a duodenum, a jejunum, a urinary cavity, or a combination thereof.

[0352] Embodiment 69 provides the delivery catheter of any one of embodiments 65-68, wherein the formulation is infused at a pressure ranging from 0.1 to 14 atm, and the balloon inflation pressure ranges from 0.1 to 14 atm.

[0353] Embodiment 70 provides a delivery catheter comprising:

[0354] a shaft having a proximal end and a distal end;

[0355] one or more needles disposed near the distal end of the shaft for infusion therapy;

[0356] an inflatable balloon disposed adjacent the distal end of the shaft such that when the delivery catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered within the lumen; and

[0357] A marker band is provided at the distal end of the shaft.

[0358] Embodiment 71 provides a delivery catheter comprising:

[0359] a shaft having a proximal end and a distal end;

[0360] one or more needles disposed near the distal end of the shaft for infusion therapy; and

[0361] A steering mechanism is 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.

[0362] Embodiment 72 provides the delivery catheter of any of embodiments 70-71, wherein the one or more needles comprises a needle.

[0363] Embodiment 73 provides the delivery catheter of any of embodiments 70-71, wherein the one or more needles comprises more than one needle.

[0364] Embodiment 74 provides the delivery catheter of embodiment 73, wherein the one or more needles comprise a needle tip to tip span diameter of 5 mm to 80 mm measured when the one or more needles are fully advanced from the delivery catheter.

[0365] 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.

[0366] 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.

[0367] Embodiment 77 provides the delivery catheter of any one of embodiments 70-71 and 73-76, wherein the one or more needles comprises three needles.

[0368] Embodiment 78 provides the delivery catheter of any of embodiments 70-77, wherein the one or more needles comprise a shape memory material.

[0369] Embodiment 79 provides the delivery catheter of any of embodiments 70-78, wherein the one or more needles comprise nitinol.

[0370] Embodiment 80 provides the delivery catheter of any of Embodiments 70-79, wherein the one or more needles comprise one or more radiopaque materials.

[0371] Embodiment 81 provides the delivery catheter of any of Embodiments 70-80, wherein the one or more needles comprise a film comprising the one or more radiopaque materials.

[0372] Embodiment 82 provides the delivery catheter of any 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.

[0373] Embodiment 83 provides a delivery catheter according to any one of embodiments 70-82, wherein the shaft comprises a lumen that is an exchange-over-all (OTW) shaft.

[0374] Embodiment 84 provides a delivery catheter according to any one of embodiments 70-83, wherein the shaft comprises a wire lumen that is a rapid exchange (RX) shaft.

[0375] Embodiment 85 provides a delivery catheter according to any one of Embodiments 70-84, wherein the shaft includes one or more needle exit openings at the distal end of the shaft.

[0376] Embodiment 86 provides a delivery catheter according to any one of embodiments 71-85, wherein the needle exit opening is located on a side of the shaft in the direction of movement of the steering mechanism.

[0377] Embodiment 87 provides a delivery catheter according to any one of embodiments 70-86, wherein the shaft comprises at least one injection hole.

[0378] Embodiment 88 provides a delivery catheter according to any one of embodiments 85-87, wherein the shaft includes a flush lumen connected to the needle exit opening.

[0379] Embodiment 89 provides a delivery catheter according to 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.

[0380] Embodiment 90 provides a delivery catheter according to any one of embodiments 87-89, further comprising a sleeve over at least some of the injection holes.

[0381] Embodiment 91 provides a delivery catheter according to any one of embodiments 70-90, wherein the shaft includes at least one vacuum hole.

[0382] Embodiment 92 provides a delivery catheter according to any of embodiments 70-91, wherein the delivery catheter includes 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.

[0383] Embodiment 64 provides a method, centering balloon catheter, or delivery catheter according to any one or any combination of embodiments 1-63, optionally configured such that all of the listed elements or options may be used or selected therefrom.

Claims

1. A needle-based balloon delivery catheter for delivering a material to a target tissue in a body cavity of a patient, the delivery catheter comprising: a catheter shaft having a proximal end and a distal end; at least one marker band located adjacent said distal end of said shaft; at least one needle, the at least one needle being 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; an irrigation port at the proximal end of the shaft in fluid communication with an irrigation lumen, 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 exit aperture through the irrigation lumen; a guidewire lumen extending through at least the distal end of the shaft; at least one balloon adjacent said distal end of said catheter; inflation cavity; an inflation port in fluid communication with the inflation lumen and with the interior of the balloon, wherein 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; 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 ablative 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 wall of the body cavity, or outside the body cavity, The needle exit hole is located at the distal end of the balloon or on a non-expandable catheter shaft between the balloons, wherein the curvature of the needle enables the needle to be oriented approximately perpendicular to the body cavity wall when the needle is deployed.

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

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

4. The delivery catheter of claim 1 , wherein the delivery catheter is used to denervate or ablate target tissue in the body cavity, wherein the denervation or ablation of target tissue in the body cavity comprises delivering an amount of energy from the delivery catheter to the target tissue using radiofrequency, cryoablation, microwaves, lasers, ultrasound, high-intensity focused ultrasound, condensation of at least some of the vapor of the agent into a liquid, or a combination thereof.

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

7. The delivery catheter of claim 1, wherein the formulation comprises an azeotrope.

8. Infusion catheter, including: a shaft having a proximal end and a distal end; and one or more needles disposed near the distal end of the shaft for infusion therapy; The infusion catheter comprises: an inflatable balloon disposed proximate the distal end of the shaft such that when the infusion catheter is placed in a lumen and the balloon is inflated, the distal end of the catheter shaft is centered within the lumen, wherein the distal end of the shaft includes a marker band, or a steering mechanism associated with the shaft such that the distal end of the shaft is steerable in a direction away from the longitudinal axis of the shaft, or Its combination, The needle exit hole is located at the distal end of the balloon or on the non-expandable shaft between the balloons, wherein the curvature of the needle enables the needle to be oriented approximately perpendicular to the body cavity wall when the needle is deployed.

9. The infusion catheter of claim 8, wherein the one or more needles comprise more than one needle.

10. The infusion catheter of claim 9, wherein the needle comprises a needle tip-to-tip span diameter of 5 mm to 80 mm measured when the needle is fully advanced from the infusion catheter.

11. The infusion catheter of claim 8, wherein the one or more needles comprise a shape memory material.

12. The infusion catheter of claim 8, wherein the one or more needles comprise nitinol.

13. The infusion catheter of claim 8, wherein the one or more needles comprise one or more radiopaque materials.

14. The infusion catheter of claim 8, wherein the shaft comprises: At least one injection hole, or an irrigation lumen connected to the needle exit port, or At least one vacuum hole, or Its combination.

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