Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-09-16
2001-08-21
Azpuru, Carlos A. (Department: 2165)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C523S113000, C523S114000, C623S014110
Reexamination Certificate
active
06277392
ABSTRACT:
TECHNICAL FIELD
This invention relates to an injectable composition of physiologically compatible and appropriately sized particles carried in a lubricative, biologically compatible fluid of gel. The composition is formulated to be delivered into a body to a tissue site through a small-bore instrument to strengthen, build-up and otherwise augment the tissue site and surrounding area.
BACKGROUND OF THE INVENTION
The percutaneous injection of substances into tissues to augment, support, or reconfigure anatomic structure has been the subject of significant research and development and is well known in the art. See, for example, U.S. Pat. Nos. 4,803,075 and 5,204,382 to Wallace et al., and U.S. Pat. No. 5,258,028 to Ersek et al. Procedures have been described in the medical literature for correction of dermatological, otolaryngological problems and for treatment of urological disorders, e.g., Smith et al., “Evaluation of Polydimethylsiloxane as an Alternative in the Endoscopic Treatment of Vesicoureteral Reflux”,
J. Urol.,
152: 1221-1224, 1994, and Walker et al., “Injectable Bioglass as a Potential Substitute for Injectable: Polytetrafluorethylene”,
J Urol.,
148:645-7 (1992) and the references cited therein.
Urinary incontinence and vesicourethral reflux are urological disorders that have responded to treatments with augmentative materials. Incontinence occurs when the resistance to urine flow has decreased to the point where the resistance can no longer resist the intra-abdominal pressure. Nearly all procedures developed to restore continence are based on restoring the lost resistance to urine outflow. U.S. Pat. Nos. 5,007,940; 5,158,573; and 5,116,387 to Berg disclose biocompatible compositions comprising discrete, polymeric and silicone rubber bodies injectable into urethral tissue for the purpose of treatment of urinary incontinence by tissue bulking. Further, U.S. Pat. No. 5,452,406 to Lawin discloses biocompatible compositions comprising carbon coated substrate particles injectable into a tissue, such as the tissues of and that overlay the urethra and bladder neck, for the purpose of treatment of urinary incontinence by tissue bulking.
The most serious adverse effects that may occur from therapies of this type relate to the migration of the solid materials from the original site of placement into repository sites in various body organs and the chronic inflammatory response of tissue to particles that are too small. These adverse effects are well documented in the urologic literature, specifically in Malizia, A. A. et al., “Migration and Granulomatous Reaction After Periurethral Injection of Polytef (Teflon)”,
JAMA
251:3277-3281 (1984) and Claes, H., Stroobants, D. et al., “Pulmonary Migration Following Periurethral Polytetrafluoroethylene Injection For Urinary Incontinence”,
J. Urol.,
142:821-822 (1989). An important factor in assuring the absence of migration is the administration of properly sized particles. If the particle is too small, it can be engulfed by the body's white cells (phogocytes) and carried to distant organs or be carried away in the microvasculature and travel until it reaches a site of greater constriction. Target organs for deposition include the lungs, liver, spleen, brain, kidney, and lymph nodes.
The use of small diameter particulate spheres, in the range of 1-20 microns, formed of materials such as cross linked collagen or synthetic polymers suspended in an aqueous medium having biocompatible lubricant has been disclosed in Wallace et al., U.S. Pat. No. 4,803,075. While these materials showed positive, short term augmentation results, this result was short lived as the material had a tendency to migrate and/or be absorbed by the host tissue. Teflon paste was used early to treat stress urinary incontinence. Politano, V. S., Small, M. P., Harper, J. M., Lynne, C. M., “Periurethral Teflon Injection for Urinary Incontinence”,
J. Urol.,
111:180-183 (1974). The Teflon paste consisted of Polytetrafluoroethylene particles in a size range of 1 to 100 microns. More than ninety percent of the particles were in the range of 1 to 40 microns. Malizia, A. A. Reiman, H. M., Myers, R. P. et al. , “Migration and Granulomatous Reaction After Periurethral Injection of Polytef (Teflon)”,
JAMA,
251:24:3277-3281 (1984). This product demonstrated foreign body granuloma formation at the injection site and local migration. Boedts, D., Roels, H., Kluyskens, P., “Laryngeal Tissue Responses to Teflon”,
Arch Otolarynqol,
86:562-567 (1967).
Proper particle size selection is important. Studies indicate that a particle size for Teflon (PTFE) in the range of between 1 and 100 microns is unacceptable for injectable material. Particles in this size range show local and distant migration, produce chronic inflammatory responses in tissue, and has been associated with clinical complications. Particles that are too large are difficult to deposit e.g. will not go down a needle small enough to have clinical application.
U.S. Pat. No. 5,792,478 to Lawin, issued Aug. 11, 1998, assigned to the assignee of the present invention, discusses pure carbon beads (either graphite or pyrolytic carbon substrate material) which is coated with pyrolytic carbon to form a pure carbon bead and a B-glucan carrier gel.
The primary focus of the present invention has been directed toward the development of improved biocompatible, nonmigratory particles that are effectively delivered to the desired tissue site in an improved lubricative, biocompatible fluid or gel carrier. The preferred carrier shall not cause any deleterious effects from the site by normal biological or biochemical processes such as excretion or metabolic breakdown.
SUMMARY OF THE INVENTION
In accordance with the present invention there is provided an injectable, biocompatible composition comprised of a plurality of discrete, physiologically compatible, isotropic pyrolytic carbon particles of a predetermined size range and a lubricative fluid or gel in which the particles are carried. The carrier is preferably a biologically compatible solution or suspension. The particles range in size from 90 to 1,000 microns in transverse, cross-sectional dimension.
The composition is designed to be delivered into the body through a small-bore needle, cannula, or catheter to a tissue site for the purpose of augmenting the tissue site and surrounding area, thereby correcting a defect, filling a void or strengthening the support structures of the tissue.
The invention is comprised of two components. The first is a plurality of low temperature isotropic (LTI) pyrolytic carbon particles ranging in size as microbeads or microparticles from a minimum of 90 microns to a maximum of 1,000 microns. The LTI particles are created, utilizing the pyrolytic process, to coat a preferred deposition material with LTI carbon. After the pyrolytic process is completed, the pyrolytic carbon is removed from the deposition material by milling, grinding, machining or otherwise to produce particles of the desired particle size. The resulting pure pyrolytic carbon particles are cleaned and sieved to provide particles of the desired size and shape.
The second component acts as the lubricative carrier for the LTI carbon particles and is comprised of a suspension, solution, or other biologically compatible fluid or a gel. The preferred embodiment is a gel of B-glucan with the addition of agarose to form a self supporting gel. Other lubricative carriers can include undiluted agarose, hyaluronic acid and derivatives thereof, polyvinyl pyrrolidone or a hydrogel derivative thereof, dextran or hydrogen derivatives thereof, glycerol, polyethylene glycol, succinylated collagen, liquid collagen, and other polysaccharide or biocompatible polymers, either singly or in combination with one or more of the above-referenced solutions. The carrier must be capable of being formulated into a viscous fluid or into a self-supporting gel. For purposes of this invention, the carrier shall be of sufficient viscosity to suspend the particles for sufficient duration to inject the composition.
Azpuru Carlos A.
Carbon Medical Technologies, Inc.
Nawrocki, Rooney & Sivertson P.A.
LandOfFree
Tissue injectable composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Tissue injectable composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Tissue injectable composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2501036