Intravitreal medicine delivery

Surgery – Devices transferring fluids from within one area of body to... – With flow control means

Reexamination Certificate

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C604S294000

Reexamination Certificate

active

06251090

ABSTRACT:

FIELD OF THE INVENTION
This invention pertains to intravitreal medicine delivery and more particularly to an implant device for delivering medicine to the vitreal cavity of the eye, and to a method for introducing medicines into the vitreal cavity using the device.
BACKGROUND
Within the past several decades, great advances have been made in the diagnosis and treatment of vitreoretinal diseases. Advances in laser technology, and vitreoretinal surgical techniques, have significantly improved the prognosis of numerous retinal conditions including diabetic retinopathy, macular degeneration, and retinal detachment. As the pathophysiology of these and many other vitreoretinal diseases is also becoming more clearly understood, a host of potential pharmacological agents is currently under investigation.
In addition to the numerous antibiotic, antiviral, and antifungal agents currently used to treat infections of the retina and vitreous, many antiinflammatory and anticancer drugs have been shown to be useful in treating diseases such as proliferative vitreoretinopathy. As the role of growth factors involved in diabetic retinopathy, macular degeneration, and other retinal degenerations is elucidated, new classes of agents have been found to be of possible benefit, including growth factors themselves, blocking antibodies to growth factors, antisense oligonucleotides, and even gene therapy with growth factor inserts.
Unfortunately, the delivery of drugs to the retina is often problematic. Most agents given topically to the eye (in the form of eye drops) do not penetrate through the anterior segment of the eye well enough to reach the vitreous or retina in therapeutic concentrations. Medications can be given orally or intravenously, but the blood vessels within the retina (and other parts of the central nervous system) are relatively impermeable to many agents. Furthermore, these drugs may have significant systemic side effects on other organs of the body. Drugs can be directly injected into the vitreous cavity, via a needle passed through the pars plana, and this technique is currently employed to combat certain severe, sight-threatening infections. However, this procedure itself entails certain risks, such as infection, bleeding, cataract formation, and retinal detachment. Furthermore, the majority of the injected drug is often cleared from the vitreous cavity within several days, necessitating multiple injections for prolonged treatment.
Accordingly, devices have been developed for improving the introduction of drugs to the vitreal cavity. One such device is a biodegradable polymer designed to be injected into the vitreous cavity where it slowly releases drug as it dissolves. A similar drug-containing polymer has been developed which is made in the shape of a tack or plug to be surgically inserted into the eyewall at the pars plana so that it projects into the vitreous cavity. Liposomes containing pharmacological agents have been developed to slowly release the agent after injection into the vitreous cavity. Another device is a plastic pellet which contains a retinal drug (ganoclovir) and is sutured inside of the vitreous cavity where the drug slowly dissolves into the cavity.
Although such devices as those briefly referred to above are apparently effective in delivering drugs into the vitreous cavity, they have significant disadvantages. First, all of these devices contain a certain amount of drug which when expended cannot be replenished without repeating the surgical implantation or intravitreal injection. Although these different devices can release drugs for weeks to months (or in the case of the plastic pellet, almost one year), certain indications for intravitreal drug administration require extended or lifetime therapy. Therefore, multiple procedures are often required and are highly undesirable.
Secondly, the device with the longest release rate, the plastic pellet of ganiclovir, requires a very large eyewall incision (5 mm) to implant due to its large size. Although the other devices can be implanted or injected through a smaller incision (1 mm or less), those that are injected freely into the vitreous cavity instead of anchored to the eyewall can migrate within the eye and come in direct contact with the retina where they can block vision or release high local concentrations of drug which could potentially prove toxic to delicate retinal tissue.
Third, many pharmacological agents cannot easily and effectively be incorporated into biodegradable polymers. Furthermore, many potential pharmacological agents would not remain stable for extended periods of time in the vitreous cavity. Therefore, there is a significant limitation to what pharmacological agents can be administered via the slow release devices currently available.
Fourth, since the plug or pellet is in essence the drug itself, treatment is limited to this drug, so that another surgery or procedure is required to change it if administration of a different drug is desired.
SUMMARY
The present invention is directed to intravitreal medicine delivery involving an implant device and method wherein a wide variety of beneficial drugs or other pharmacological agents or medicines can be introduced into the vitreous cavity over an extended period of time, as much as the life of the patient, with only a single initial surgery to implant the device; wherein the surgical incision needed for implantation is minimized; wherein additional amounts of drugs over an initial supply can be introduced without further invasive surgery; wherein the type of medicine can be varied or changed depending on such factors as the disease being treated or drug availability; wherein the dosage of agent being administered is controllable; and wherein damage or interference by the implant to various parts of the eye is avoided.
It is an object of the present invention to provide for improved delivery of drugs and other pharmacological agents to the vitreous cavity of the eye, especially for treating vitreoretinal diseases.
It is another object to enable medicinal agents to be delivered to the vitreous cavity with a single initial surgery and without the need for repeated invasive surgeries or procedures.
It is yet another object of this invention to allow replenishment of the drug or other medicinal agent within an implant attached to the eyewall by injection into the implant through the conjunctivae and not through the eye wall.
It is further object to be able to change the pharmacological agent being dispensed from an eye implant device into the vitreal cavity, without surgery or other invasive procedure.
It is also an object to control the dosage of drugs or other pharmacological agents delivered to the vitreous cavity from an implant device.
It is still another object of the present invention to enable the patient to control delivery of dosages of medicines to the vitreous cavity with a delivery device implanted on the patient's eyeball.
It is a still further object to implant an intravitreal medicine delivery device which dispenses medicine into the vitreous cavity without interference with or damage to various parts of the eye.
It is yet another object of the present invention to prevent inadvertent puncture of the eyeball by an injection needle used to replenish the supply of drugs or other agents in an eye implant device.
It is also an object of the subject invention to prevent an uncontrolled movement of medicines into the vitreous cavity from an intravitreal delivery implant when the supply of medicines in the implant is being replenished in situ.
It is another object of this invention to filter medicines being dispensed from an implant device before being admitted to the vitreous cavity thereby to prevent unwanted particulate matter, such as undissolved biodegradable polymer, from moving into the cavity, while allowing medicines to pass into the cavity.
It is a feature of the present invention to have a relatively large drug or other medicine-containing reservoir which is located outside the eyewall in the sub-conjunctival space and whic

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