Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-04-09
2001-04-10
Azpuru, Carlos A. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S423000, C424S424000, C424S426000, C514S772300, C604S890100
Reexamination Certificate
active
06214370
ABSTRACT:
TECHNICAL FIELD
This invention relates to a device and method for administering analgesics to the neuraxis of an organism. More specifically, this invention relates to the long term release of an analgesic from a biocompatible polymeric matrix device implanted into the central nervous system of a human patient or other warm blooded animal.
BACKGROUND OF THE INVENTION
Constant or chronic pain is a significant medical problem, for example in terminal cancer patients. Many of the drugs, such as the opioid class of analgesics, used to treat severe chronic pain act on receptors found in the neuraxis. By “neuraxis” as used herein is meant any region of tissue that comprises the spinal cord, brain or central nervous system.
The current regimen for treatment of these patients is systemic administration of relatively high doses of analgesics by for example oral, subcutaneous, intramuscular, intravenous and related routes on a daily or continuous basis. Oral administration of an analgesic is problematic because the patient experiences high systemic concentration of drug at the time of ingestion followed by a gradual decrease in systemic concentration of the drug until the next dose is ingested. Other methods of systemic administration are problematic because they may be invasive, for example placement of an intravenous catheter for continuous administration of the analgesic. In either case, however, the analgesic is distributed equally throughout the body after being administered systemically and diffuses across the blood brain barrier into the neuraxis to its central site of action, blocking pain messages to the brain. The cost for treating these patients is high from a hospital care as well as from a pharmaceutical standpoint since many patients must be maintained in the hospital to continue their pain treatment regimen of high doses of the analgesic. Furthermore, side effects related to the systemic administration of high doses of, for example, opioids include sedation, respiratory depression, nausea, constipation and vomiting. These side effects are well documented in product labeling and the literature and detract greatly from the already compromised quality of life of these patients.
More recently, transdermal patches have been developed as a means for efficiently delivering analgesics to patients on a continuous basis. A patch is loaded with an analgesic such as fentanyl and is attached to the patient's skin by means of typically an adhesive. The analgesic diffuses out of the patch and crosses the patient's skin, where it is absorbed by the body. Patients may be required to wear a number of patches to obtain adequate therapeutic response, as the analgesic site of action is in the neuraxis. While less invasive than other administration techniques listed above, systemic side effects resulting from high levels of analgesic in the body are still a significant medical problem and continue to compromise patient quality of life.
Alternatively, spinal administration (intrathecal or epidural) of centrally acting analgesics via an externalized spinal catheter, a spinal catheter connected to an external infusion pump, a spinal catheter connected to a fully implanted infusion pump and other related systems has been shown to be therapeutically effective for the treatment of chronic pain. To reduce systemic side effects caused by relatively high dosage systemic delivery, direct spinal delivery of the analgesic is preferred. In this way, drug is delivered in a concentrated manner and at low doses to its specific site of action on receptors in the neuraxis, minimizing systemic side effects as outlined above. Spinal catheter placement and infusion pump use, while shown to be highly effective, represent a therapy alternative that is relatively expensive and invasive to implant. These therapies also present with risk of spinal infection such as meningitis since the blood-brain barrier has been compromised and drug is delivered to the neuraxis from an external source such as a drug pump.
Recent research has also demonstrated that living cells that produce natural analgesics can be encapsulated into a silicone sheath and implanted into the central nervous system. It has not been established whether these cells produce therapeutic quantities of analgesics while in vivo or how long the encapsulated cells will remain viable. Doses of analgesic that the cells produce in many instances can not be controlled and external stimuli, for example nicotine, may change cell viability parameters. Finally, potential for infection in the neuraxis if one of these modules were to rupture has not been characterized.
The present invention provides an alternative means for achieving continuous central nervous system administration of an analgesic into the neuraxis via intraventricular, epidural, intrathecal and related routes for those suffering chronic pain and is directed to solving one or more of the problems noted above. The invention comprises an analgesic carrying device and its method of use, including implantation, which releases the analgesic in a continuous and sustained-release manner. The device consists of a biocompatible polymer matrix body loaded with an analgesic such that a slow, preferably constant release of the analgesic is provided. The polymer matrix substrate may be constructed of any of a number of biostable or biodegradable polymers that act as the carrier matrix for the analgesic. Ideally, therapeutic levels of the analgesic will be delivered over the long term, i.e., one month to one year. Two preferred analgesics are fentanyl and sufentanil, opioids about 100 to 500 and 1000 to 5000 times, respectively, more potent than morphine. Preferably the method of the invention administers the analgesic intraventricularly, intrathecally, epidurally, or by other related routes to the neuraxis. The intrathecal route of administration is preferred.
SUMMARY OF THE INVENTION
With this invention it is recognized for the first time that increased cost-effectiveness and simplicity of the administration of analgesics directly to the central nervous system, i.e., neuraxially, may be accomplished by means of a polymer matrix body loaded with an analgesic and made available for diffusion from the matrix into the biologic neuraxial environment.
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Bergan Matthew A.
Nelson Timothy S.
Azpuru Carlos A.
Medtronic Inc.
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