Invention for Devices and methods for delivering and injecting therapeutic and diagnostic agents into a target area within the body

Invented by Robert C. Glines, Gary B. Weller, ANGIOSENSE Inc, Boston Scientific Scimed Inc

The ANGIOSENSE Inc, Boston Scientific Scimed Inc invention works as follows

Background for Devices and methods for delivering and injecting therapeutic and diagnostic agents into a target area within the body

Despite the continuous advances in medical technology in treating heart disease, vascular diseases, cancer, pain and allergies, orthopedic repairs, and many other conditions and diseases, there is still a large number of patients who are unable to receive conventional surgical or interventional treatments or whose treatment is insufficient. Many patients are only able to receive medical treatment, such as drugs.

There have been recent advances in drug therapy, especially with regard to site-specific or cell-specific therapies (as opposed systemic therapeutics), such as pharmacologic (e.g. anesthetics, analgesics, and biologic (e.g. genetically engineered materials). The effectiveness of cell or site-specific therapies is dependent on their ability to deliver therapeutics precisely to the target site in the body.

Needle-based injection devices are most commonly used for site-specific administration. Even though needle-based injection systems and drug delivery systems have made significant advances, they still have many shortcomings. The disadvantages and shortcomings of these systems are best illustrated by gene therapy applications. This is the implantation or engineered cells or genetic material in specific human targets to create a therapeutic effect or preventative action.

Gene therapy can either be angiogenetic or anti-angiogenic, depending on the type of disease being treated. Angiogensis, a complex biological process resulting in the growth new blood vessels, is the intended outcome of angiogenic therapies. Experimentally, angiogenic therapy is used to treat cardiac ischemia, coronary heart disease (e.g. atherosclerosis) and peripheral vascular bed ischemia. Anti-angiogenic treatment involves reducing the proliferation of blood vessel, such as to stop the blood supply to a tumour or pannus-type tissue that is proliferating, and to prevent the abnormal growth in retinal vessels which leads to blindness.

A direct exposure to the genetic material at a target site over a long period of time is an important factor for achieving the desired results of gene therapy.” It is especially difficult for gene therapy that requires delivering genetic materials to the nuclei in cells. The exposure of genetic material at the targeted site can be done directly, either through an open surgical procedure or a less invasive one, or by using a catheter. There are challenges with any approach in delivering genetic material to cells in a safe, targeted and efficient manner.

For optimum ?up regulation? “For optimal?up regulation? The dispersion of the gene therapy drug and its absorption may be reduced if the drug is not sufficiently broken down into micro-particles. This can have a minimal or no effect on the patient. Needle-based needle syringes cannot achieve such atomization, and instead deliver the injectate as a bolus. This is less likely to effectively be dispersed and absorb within tissue.

In certain gene therapy applications, it is also important to reduce the exposure to the gene therapy agent systemically to prevent unwanted side effects. When using a needle to inject the targeted area, or any other penetrating device, a hole is unavoidably made in the tissue. The injectate will leak out and be released throughout the body. It also leads to increased treatment costs, and the need for more injections and agents.

Gene therapy, for instance, has been used to create angiogenesis (blood vessel growth) in hypoxic heart tissue. The angiogenic solution in cardiac surgery is usually delivered through a series of syringes that are injected, often in a grid pattern, into the epicardium, or outer surface of heart, at the ischemic part of the myocardium. A similar endocardial (i.e. through the inside of the heart) approach involves inserting a catheter with a distal needle into a ventricular cavity and injecting the solution through the endocardium. Both approaches are designed to induce the cells of the target tissue, to continuously express the desired protein growth factor for a specified time period. “Other methods of delivering cardiac angiogenic agents include injecting them into the pericardial (i.e. intrapericardial), coronary (i.e. intracoronary), or myocardium.

Although some recent studies have shown that syringe/needle based injections can result in a marginal angiogenic reaction, there are certain disadvantages to using a syringe/needle based injector or another tissue-penetrating tool. Myocardial ischaemia, for example, typically affects a surface area of 3 to 10 mm2. The size of the needle, and the limited ability to diffuse the agent through tissue, limit the solution dispersion of a single needle in ischemic tissues. Multiple needle-based injections are often required to disperse the treatment over the affected area. The procedure time increases as the number of injections increase. A larger volume of gene therapy agent will be required to treat the ischemic region. The cost of the procedure increases as more time is spent and the drug dose is increased.

Furthermore it is well known that needle penetration or injections into tissue can cause tissue cell traumatization or destruction and increase the risk of a post-operative arrhythmia in a patient. The difficulty of precisely controlling the depth of penetration during injection is a major factor. The greater the number of injections or penetrations the higher the risk of arrhythmia and cell death. Another disadvantage of multiple needle-based growth factor injections is the need for careful tracking of the injection sites to prevent accidental delivery of the growth factor to nondiseased tissues.

There are gene therapies which do not use needles for drug delivery. Indwelling catheters or drug-infused stents were used to release the therapeutic agent slowly and controlled. These methods carry a higher risk of systemic release. It is also more difficult to determine the exact dosage of the targeted area. These approaches are less effective, less safe and more expensive than injections.

Another condition where site-specific or locally delivered drug is used is the treatment of peripheral arterial disease (such as deep venous thrombosis, and embolisms). Venous lytic treatment, which involves the dissolution of blood clots in peripheral vessels (e.g. femoral, illiac, and iliac veins), is one such treatment. In order to perform a lytic therapy, thrombolytics such as urokinase (or streptokinase), reteplase (or tPA), and streptokinase are systemically infused. In other more recent procedures, the thrombolytics are delivered directly into the thrombus through indwelling catheters. The thrombolytics must be infused continuously for several hours or even a whole day to effectively dissolve the thrombus. This increases the length of the hospital stay as well as the cost.

Double lumen catheters is another type of AV accessibility means. They can be used either for temporary or long-term applications. Long-term catheters are placed surgically in a tunneling manner under the skin. Access catheters for AV are usually placed in the subclavian vein or jugular. Sometimes, they can be temporarily placed in a femoral vein. Short-term AV catheters are used when urgent dialysis treatment is required. AV catheters can develop infections or thrombosis, which may lead to the failure of the device. The veins in which they are placed are also prone to clotting.

Conventional treatment for problems (e.g. stenosis and infection) that can arise with AV grafts fistulas and catheters usually involves surgical intervention. This includes the repair or replacement AV device, physical removal of stenotic plate and chemical or physical removal blood clots. It is evident that avoiding any surgical procedure will reduce pain and morbidity. There is a still need for improved methods and means for treating and preventing the conditions associated with the use of AV devices.

The disadvantages associated with conventional drug delivery systems are also present in other medical conditions, such as neurovascular disease and cancer. There is therefore a need for devices, methods, and devices that deliver drugs and other solutions into bodily tissues in a more efficient, effective, and precise manner than traditional devices and methods. It is also desirable to have methods and devices for delivering solutions that are less invasive and safer than the current methods and devices. It is also necessary to have medical agent delivery systems that are easy and convenient for both self-application as well as institutional use. There is still a need to develop enabling technologies for more efficient and safe local drug delivery.

The present invention comprises novel methods and means for injecting or delivering a solution into a targeted site in the body to treat or diagnose the target site. The target site can be an area of tissues or a substance attached or adjacent to that tissue area or cells. The target site can be an organ or a body lumen.

The devices of the invention are injection systems and components that accurately and precisely deliver, inject and perfuse a therapeutic or a diagnostic agent in fluid form directly into the site of interest without the need for anything else to penetrate the tissue other than the agent. “None of the embodiments use a needle or any other penetrating devices to create a space into which the agent can be injected.

The injection systems of the invention are intended for use both in clinical settings (such as intraoperative or interventional settings) and in non-clinical environments where the patient administers the solution themselves. They are designed to deliver a solution out of an ampule, and then inject it into the target site in the body, or an artificial graft attached to the body, through a surgical or less-invasive opening (such a trocar port) or endovascularly.

Generally, injection systems consist at least in part of a propulsion device, an ampule (often called a syringe) reservoir for receiving and holding the agent or solution, and dispersion devices distal to the syringe for transporting or dispersing the agent or solution from the reservoir to target site.

The propulsion devices in the present invention can produce enough pressure to deliver a solution, or an agent into the target area without the use of a needle. These devices can be powered by any suitable propulsion mechanism, including a spring-loaded component or an inert gas cartridge (such as carbon dioxide, nitrogen or argon). For ejecting an agent from a reservoir. The propulsion apparatus, which is coupled to the reservoir, is used to propel an agent from the reservoir under a desired pressure. This can be in the range of 1800 psi up to 2300 psi. The present invention also includes means for selecting both the amount of agent that is to be propelled out of the reservoir and the pressure at which it will be propelled. The propulsion devices should be ergonomically designed to allow the user to hold and operate them with one hand.