Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Dissolving or eluting from solid or gel matrix
Reexamination Certificate
1999-05-13
2001-12-25
Jones, Dameron L. (Department: 1616)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Dissolving or eluting from solid or gel matrix
C424S001110, C424S001650, C600S003000, C600S004000, C604S264000, C514S944000
Reexamination Certificate
active
06333020
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is directed to methods for treating arteriovenous malformations (AVM) by use of radioactive compositions. Specifically, these methods entail the in vivo delivery of radioactive compositions which are delivered as a fluid to one or more vascular sites in the AVM. Subsequent solidification of this composition in the AVM results in vascular embolization to at least partially ablate the AVM as well as delivery of a controlled amount of radiation to further ablate the AVM and to inhibit regrowth of the AVM.
In one embodiment, the fluidic radioactive compositions employed in the methods of this invention comprise a biocompatible polymer, a biocompatible solvent and a radioactive agent which provides a sufficient dose of radiation to at least partially ablate the AVM. In another embodiment, the fluidic radioactive compositions employed in the methods of this invention comprise a biocompatible prepolymer, a radioactive agent and optionally a biocompatible solvent which provides a sufficient dose of radiation to at least partially ablate the AVM and to inhibit regrowth of the AVM.
References
The following publications, patents and patent applications are cited in this application as superscript numbers:
1
Dunn, et al., U.S. Pat. No. 4,938,763 for “Biodegradable in-Situ Forming Implants and Methods of Producing Same”, issued Jul. 3, 1990
2
Kinugasa, et al., “Direct Thrombois of Aneurysms with Cellulose Acetate Polymer”, J. Neurosurg., 727:501-507 (1992)
3
“CANCER, Principles & Practice of Oncology”, 4th Ed., Volume 1, “Cancer Treatment”, pp. 545-548 (1993)
4
Greff, et al., U.S. Pat. No. 5,667,767, for “Novel Compositions for Use in Embolizing Blood Vessels”, issued Sep. 16, 1997
5
Greff, et al., U.S. Pat. No. 5,580,568 for “Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels”, issued Dec. 3, 1996
6
Kinugasa, et al., “Early Treatment of Subarachioid Hemorrhage After Preventing Rerupture of an Aneurysm”, J. Neurosurg., 83:34-41 (1995)
7
Kinugasa, et al., “Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery”, Neurosurg., 3:661 (1995)
8
Taki, et al., “Selection and Combination of Various Endovascular Techniques in the Treatment of Giant Aneurysms”, J. Neurosurg., 77:37-24 (1992)
9
Evans, et al., U.S. patent application Ser. No. 08/802,252 for “Novel Compositions for Use in Embolizing Blood Vessels”, filed Feb. 19, 1997
10
Castaneda-Zuniga, et al., Intervenlional Radiology, in Vascular Embolotherapy, Part 1, 1:9-32, Williams & Wilkins, Publishers (1992)
11
Rabinowitz, et al., US. Pat. No. 3,527,224 for “Method of Surgically Bonding Tissue Together”, issued Sep. 8, 1970
12
Hawkins, et al., U.S. Pat. No. 3,591,676 for “Surgical Adhesive Compositions”, issued Jul. 6, 1971
13
Ondra, et al., J. Neurosurg., 73:387-391 (1990)
14
Ogilvy, Internet publication, http:/
eurosurgery.mgh.harvard.edu/v-s-93-4.1, “Combined Modality Treatment in the Management of Brain Arteriovenous Malformations (AVMs)”
15
Greff, et al., U.S. patent application Ser. No. 08/962,819, Radioactive Einbolizing Compositions, filed Nov. 3, 1997
All of the above publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual reference was specifically and individually indicated to be incorporated herein by reference in its entirety.
2. State of the Art
An arteriovenous malformation (AVM) is a congenital disorder characterized by a complex, tangled web of arteries and veins. An AVM may occur in the brain, brainstem, or spinal cord of a mammal or may be at a peripheral site such as in the pelvic areas, limbs, lungs, etc. and is caused by abnormal development of blood vessels. The most common symptoms of AVM include hemorrhaging (bleeding) and, for AVMs of the brain, brainstem or spinal cord, seizures, headaches, and neurological problems such as paralysis or loss of speech, memory, or vision. The symptoms of AVMs are often due to circulatory “steal” or insufficiencies caused by the AVM.
AVMs, particularly those located in the brain or spine of mammals (humans), are difficult or dangerous to treat. Cerebral AVMs, for example, are most commonly discovered in young human adults aged 20-40 years. These lesions are usually detected in patients as the result of a seizure or hemorrhage. AVMs hemorrhage at a rate of 4% per year.
13
Approximately half of these hemorrhages will carry significant morbidity or mortality and, accordingly, the lifetime risk of hemorrhage can be substantial.
Treatment of AVMs has employed a team approach utilizing combined modality therapy.
14
Three modalities of treatment heretofore employed include endovascular introduction of tissue glues which occlude parts or all of the AVM, microsurgical techniques to remove the AVM or radiosurgery (focused radiation) to ablate the AVM. Combined modality therapies include a first reduction of the AVM via endovascular introduction of tissue glues followed by stereotactic radiosurgery where a focused beam of radiation is used on a one-time treatment basis at a dose of from about 10 to 30 Gy with an average dose of about 20 Gy. This radiation causes changes in blood vessel walls, and over the course of 2-3 years the remainder of the AVM can be obliterated. This technique is most effective in smaller lesions (diameters less than 2.5 cm). Obliteration rates of up to 85% have been reported by two years after treatment. The risk of injury to surrounding normal tissue (e.g., brain tissue) is significant and is dependent upon the dose and focus of the radiation used which is kept to minimal levels to prevent collateral damage to healthy tissue.
Notwithstanding the benefits of a team approach of combined modalities for the treatment of AVMs, such a team approach requires at least two separate medical procedures on the patient. Accordingly, simplier procedures to effect treatment of AVMs would be particularly beneficial.
SUMMARY OF THE INVENTION
This invention is directed to methods for treating AVMs by use of radioactive embolization compositions. These compositions are delivered to one or more vascular sites of the AVM in a mammal as a fluid composition which solidifies in vivo to form a solid, coherent radioactive mass. The solidified mass embolizes the vascular site thereby ablating or obliterating at least part of the AVM and the radioactivity attendant with the composition results in further ablation or obliteration of the AVM and inhibits regrowth of the AVM. This combined approach reduces the number of steps required to effect treatment of the AVM thereby providing a one-step treatment regimen for treating AVMs while inhibiting regrowth of the AVM.
Accordingly, in one of its method aspects, this invention is directed to a method for treating an arteriovenous malformation in a mammal which method comprises:
(a) selecting a fluidic composition comprising a biocompatible polymer, a biocompatible solvent and a water insoluble radioisotope; and
(b) injecting a sufficient amount of said composition into one or more vascular sites leading to or within the AVM under conditions wherein a solid mass is formed thereby ablating at least part of the AVM
wherein the radioisotope is employed in an amount effective to further ablate the AVM and inhibit regrowth of the AVM.
Preferably the radioactive fluid composition employed in this aspect of the methods of this invention comprises:
(a) a biocompatible polymer;
(b) a biocompatible solvent; and
(c) from about 0.1 to about 35 weight percent of a water insoluble radioisotope having a radioactive content of from about 0.1 microcuries to about 35 microcuries.
The biocompatible polymer employed in these compositions and methods can be either a biodegradable polymer or a non-biodegradable polymer but is, preferably, a non-biodegradable polymer.
In another aspect of this invention, the biocompatible polymer can be replaced with a biocompatible prepolymer and, when so used, the presence of the biocompatible solvent becomes optional. In this embodi
Greff Richard J.
Wallace George
Burns Doane Swecker and Mathis LLP
Jones Dameron L.
Micro Therapeutics Inc.
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