U.S. patent application number 12/143698 was filed with the patent office on 2008-12-25 for devices and methods for delivering therapeutic substances for the treatment of sinusitis and other disorders.
This patent application is currently assigned to Acclarent, Inc.. Invention is credited to John Y. Chang, William M. Facteau, Hung V. Ha, Joshua Makower, John H. Morriss, Ketan P. Muni, Amrish Jayprakash Walke.
Application Number | 20080319424 12/143698 |
Document ID | / |
Family ID | 38541560 |
Filed Date | 2008-12-25 |
United States Patent
Application |
20080319424 |
Kind Code |
A1 |
Muni; Ketan P. ; et
al. |
December 25, 2008 |
Devices and Methods for Delivering Therapeutic Substances for the
Treatment of Sinusitis and Other Disorders
Abstract
Devices and methods for delivering drugs and other therapeutic
or diagnostic substances to desired locations within the bodies of
human or non-human animal subjects. An implantable delivery device
comprising a reservoir is initially attached to a deliver catheter
or delivery tool and is introduced into the body and positioned at
a desired site. A therapeutic or diagnostic substance is then
introduced into the reservoir and the delivery catheter or deliver
tool is then removed, leaving the implantable delivery device
implanted within the body. The substance is then delivered from the
reservoir at a rate that causes the desire diagnostic or
therapeutic effect. Also provided are substance eluting stents that
elute substance from a selected surface of the stent (e.g., the
outer surface) but not from another surface of the stent (e.g., the
inner surface).
Inventors: |
Muni; Ketan P.; (San Jose,
CA) ; Ha; Hung V.; (San Jose, CA) ; Makower;
Joshua; (Los Altos, CA) ; Morriss; John H.;
(Portola Valley, CA) ; Chang; John Y.; (Mountain
View, CA) ; Facteau; William M.; (Mountain View,
CA) ; Walke; Amrish Jayprakash; (Santa Clara,
CA) |
Correspondence
Address: |
Robert D. Buyan, Stout, Uxa, Buyan & Mullins,;LLP/Acclarent, Inc.
4 Venture, Suite 300
Irvine
CA
92618
US
|
Assignee: |
Acclarent, Inc.
Menlo Park
CA
|
Family ID: |
38541560 |
Appl. No.: |
12/143698 |
Filed: |
June 20, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11234395 |
Sep 23, 2005 |
7410480 |
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12143698 |
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10829917 |
Apr 21, 2004 |
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11234395 |
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10912578 |
Aug 4, 2004 |
7361168 |
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10829917 |
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Current U.S.
Class: |
604/890.1 ;
604/103.01; 604/257 |
Current CPC
Class: |
A61B 34/20 20160201;
A61F 2250/0039 20130101; A61M 25/007 20130101; A61M 31/00 20130101;
A61B 17/320758 20130101; A61B 2034/107 20160201; A61F 2/92
20130101; A61M 25/10 20130101; A61F 2220/0075 20130101; A61B
2017/22061 20130101; A61B 17/3478 20130101; A61F 2/82 20130101;
A61M 2025/004 20130101; A61B 17/320783 20130101; A61B 5/416
20130101; A61F 2/18 20130101; A61B 17/24 20130101; A61F 2220/005
20130101; A61B 17/320725 20130101; A61B 90/361 20160201; A61B 5/411
20130101; A61B 2090/365 20160201; A61F 2220/0058 20130101; A61M
31/002 20130101; A61F 2210/0076 20130101; A61M 2025/1052 20130101;
A61B 2034/2051 20160201; A61B 5/064 20130101; A61B 2034/105
20160201; A61B 2034/2048 20160201 |
Class at
Publication: |
604/890.1 ;
604/257; 604/103.01 |
International
Class: |
A61K 9/22 20060101
A61K009/22; A61M 31/00 20060101 A61M031/00; A61M 29/02 20060101
A61M029/02 |
Claims
1-83. (canceled)
84. An implantable substance delivery device comprising: a
removable portion comprising an elongate shaft having a lumen and a
distal end; and an implantable portion detachably attached to the
removable portion; said implantable portion comprising a substance
delivery reservoir that is in communication with the lumen of the
removable portion such that a therapeutic or diagnostic substance,
or a component thereof, may be introduced through the lumen into
the reservoir; said reservoir being initially disposed in a first
configuration and transitionable to a second configuration by
introduction of the substance, or component thereof, into the
reservoir; said implantable portion being detachable from the
removable portion such that the removable portion may be removed
from the subject's body leaving the implantable portion within the
subject's body.
85. A device according to claim 84 sized and configured for
transnasal insertion and implantation of the implantable portion
within the ear, nose or throat of a human or animal subject.
86. A device according to claim 84 wherein at least a part of the
implantable portion is implantable within a paranasal sinus.
87. A device according to claim 86 wherein the reservoir, while in
the first configuration, is advanceable through an opening of a
paranasal sinus and into that paranasal sinus and, after being
transitioned to its second configuration, is retained within that
paranasal sinus.
88-100. (canceled)
101. A device according to claim 84 further comprising an apparatus
for preventing backflow of substance out of the reservoir after the
removable portion has been removed.
102-104. (canceled)
105. A device according to claim 101 wherein the apparatus for
preventing backflow of substance out of the reservoir comprises a
valve.
106. A device according to claim 105 wherein the implantable
portion further comprises a tube having a substance introducing
lumen and wherein the valve comprises a check valve that allows
fluid to be infused in a first direction through the substance
introducing lumen but prevents fluid from flowing in a second
direction through the reservoir filling lumen.
107. A device according to claim 105 wherein the valve is located
with the reservoir.
108. A device according to claim 106 wherein the valve is located
within the reservoir filling lumen.
109-110. (canceled)
111. A device according to claim 84 further comprising at least one
imagable marker.
112. A device according to claim 111 wherein the at least one
imagable marker marks the location of the reservoir.
113. (canceled)
114. A device according to claim 84 further comprising an anchor
for anchoring the implantable portion.
115. A device according to claim 114 wherein the anchor comprises a
suture receiving member to which a suture may be attached.
116. (canceled)
117. A device according to claim 114 wherein the anchor comprises
at least one deployable member that abuts against or engages an
adjacent anatomical structure.
118-120. (canceled)
121. A device according to claim 84 wherein the reservoir has at
least one substance release location through which substance
escapes from the reservoir.
122. A device according to claim 121 wherein the at least one
substance release location comprises at least one aperture formed
in the reservoir such that substance introduced into the reservoir
will pass out of the reservoir through said at least one
aperture.
123. A device according to claim 121 wherein the reservoir
comprises a balloon and said at least one aperture is formed in the
balloon.
124. A device according to claim 122 wherein said at least one
aperture is between about 0.2 microns to about 200 microns in its
largest cross dimension.
125. A device according to claim 121 wherein the at least one
substance release location comprises at least one barrier that
allows a substance having a certain property to pass out of the
reservoir through the barrier at a known rate.
126. A device according to claim 125 wherein the certain property
is selected from the group consisting of viscosity, molecular
weight, electrical charge, osmolarity, osmolality, hydrophobicity,
hydrophilicity and presence of a certain chemical group.
127-132. (canceled)
133. A device according to claim 125 wherein the barrier comprises
a semipermeable barrier.
134-135. (canceled)
136. A device according to claim 84 wherein the implantable portion
is at least partially biodegradable.
137. A device according to claim 84 wherein the implantable portion
is not biodegradable.
138. A device according to claim 137 further comprising a graspable
member that extends from the implantable portion and is useable to
facilitate removal of the implantable portion.
139-144. (canceled)
145. A device according to claim 84 further comprising a quantity
of a substance for introduction into the reservoir, said substance
selected from the group consisting of: an imagable contrast agent;
a diagnostic indicator agent; an antibiotic; an antifungal; an
antiparasitic; an antimicrobial; a steroid; a vasoconstrictor; a
leukotriene inhibitor; an IgE inhibitor; an anti-inflammatory; a
mast cell stabilizer; an antihistamine; an immunomodulator; an SYK
kinase Inhibitor a chemotherapeutic agent; an antineoplastic agent;
a mucolytic agent; an agent that thins or otherwise changes the
viscosity of mucous; and a substance that facilitates remodeling of
soft tissue and/or bone and/or cartilage.
146. A device according to claim 145 wherein the implantable
portion is configured to be implanted within the nose, paranasal
sinus, Eustachian tube or naso-lacrimal duct and wherein the
substance comprises a steroid or non-steroidal anti-inflammatory
agent that causes reduction of the inflammation.
147. A device according to claim 146 wherein the substance
comprises a steroid that is selected from the group of steroids
consisting of beclomethasone, flunisolide, fluticasone,
triamcinolone, mometasone, aclometasone, desonide, hydrocortisone,
betamethasone, clocortolone, desoximetasone, fluocinolone,
flurandrenolide, mometasone, prednicarbate; amcinonide,
desoximetasone, diflorasone, fluocinolone, fluocinonide,
halcinonide, clobetasol, augmented betamethasone, diflorasone,
halobetasol, prednisone, dexamethasone and methylprednisolone.
148. A device according to claim 145 wherein the implantable
portion is configured to be implanted within or near a microbially
infected anatomical structure and wherein the substance comprises
an antimicrobial.
149. A device according to claim 148 wherein the antimicrobial is
selected from the group consisting of: acyclovir, amantadine,
rimantadine, oseltamivir, zanamivir, aminoglycosides, amikacin,
gentamicin, tobramycin, amoxicillin, amoxicillin/clavulanate,
amphotericin B, ampicillin, ampicillin/sulbactam, atovaquone,
azithromycin, cefazolin, cefepime, cefotaxime, cefotetan,
cefpodoxime, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime,
cefuroxime axetil, cephalexin, chloramphenicol, clotrimazole,
ciprofloxacin, clarithromycin, clindamycin, dapsone, dicloxacillin,
doxycycline, erythromycin, fluconazole, foscamet, ganciclovir,
atifloxacin, imipenem/cilastatin, isoniazid, itraconazole,
ketoconazole, metronidazole, nafcillin, nafcillin, nystatin,
penicillins including penicillin G, pentamidine,
piperacillin/tazobactam, rifampin, quinupristin-dalfopristin,
ticarcillin/clavulanate, trimethoprim/sulfamethoxazole,
valacyclovir, vancomycin, mafenide, silver sulfadiazine, mupirocin,
nystatin, triamcinolone/nystatin, clotrimazole/betamethasone,
clotrimazole, ketoconazole, butoconazole, miconazole, tioconazole,
detergent-like chemicals that disrupt or disable microbes,
nonoxynol-9, octoxynol-9, benzalkonium chloride, menfegol, and
N-docasanol, chemicals that block microbial attachment to target
cells, chemical that inhibits entry of infectious pathogens into
cells, sulphated polymers, sulphonated polymers, carrageenan,
antiretroviral agents, PMPA gel, antibodies, genetically engineered
or naturally occurring antibodies that combat pathogens,
plantibodies, agents which change the condition of the tissue to
make it hostile to the microbes, agents which alter mucosal pH,
buffer gel, acidform non-pathogenic microbes that kill or inhibit
the growth of pathogenic microbes and antimicrobial metals.
150. A device according to claim 84 wherein the reservoir contains
a first component of the substance while in its first configuration
and wherein a second component of the substance is subsequently
introduceable into the reservoir such that it combines with the
first component, thereby forming said substance within the
reservoir and thereby causing the reservoir to transition to its
second configuration.
151. A device according to claim 150 wherein the first component
comprises a reconstitutable form of a therapeutic or diagnostic
substance and the second component comprises a reconstituting agent
which combines with the reconstitutable form of a therapeutic or
diagnostic substance to cause the reservoir to contain a
reconstituted therapeutic or diagnostic substance that is
deliverable from the substance delivery reservoir.
152. A device according to claim 151 wherein the reconstitutable
form of a therapeutic or diagnostic substance comprises a dried or
lyophilized form of the therapeutic or diagnostic substance and the
reconstituting agent comprises a liquid in which the dried or
lyophilized form of the therapeutic or diagnostic substance becomes
dissolved or suspended in a form that is deliverable from the
substance delivery reservoir.
153. A device according to claim 151 wherein the first component
comprises an inactive form or component of a therapeutic or
diagnostic substance and the second component comprises an
activating agent which combines with the inactive form or component
to cause the reservoir to contain an active therapeutic or
diagnostic substance that is deliverable from the substance
delivery reservoir.
154. A device according to claim 84 further comprising a refill
port through which additional substance, or an additional component
of the substance, may be introduced into the reservoir after the
implantable portion has been implanted within a subject's body and
detached from the removable portion.
155. A device according to claim 84 wherein the implantable portion
further comprises a tubular member having an substance introducing
lumen, the substance introducing lumen of said tubular member being
initially connected to the lumen of the elongate shaft such that,
in Step E, the substance or component thereof may be introduced
through the lumen of the elongate shaft, through the substance
lumen of the implantable portion and into the reservoir.
156-158. (canceled)
159. A device according to claim 84 wherein the implantable portion
is configured such that, when the reservoir is in its second
configuration, a body fluid may flow through or around the
implantable portion.
160. A device according to claim 159 wherein the reservoir, when in
its second configuration, has at least one body contacting area
that contacts an adjacent body surface and at least one non-body
contacting area that remains a spaced distance away from the
adjacent body surface such that mucous or other fluid may pass
between the at least one non-body contacting area and the adjacent
body surface.
161. A device according to claim 160 wherein the reservoir is
positionable such that the at least one body contacting area is in
contact with the opening of a paranasal sinus and the at least one
non-body contacting area remains spaced away from the opening of
the paranasal sinus such that mucous or other fluid may flow past
the at least one non-body contacting area and out of the opening of
the paranasal sinus.
162-165. (canceled)
166. A device according to claim 84 wherein the removable portion
further comprises a detachment tool for detaching the implantable
portion from the removable portion.
167-169. (canceled)
170. A device according to claim 84 wherein the implantable portion
comprises a reservoir and a tube that extends through the
reservoir, said tube having a proximal lumen through which
substance may be introduced into the reservoir and a distal lumen
through which substance will pass out of the reservoir.
171. A device according to claim 170 wherein the tube further
comprises a through lumen that extends from a proximal opening
proximal to the reservoir to a distal opening distal to the
reservoir.
172. (canceled)
173. A sinusitis treating system comprising an implantable
substance delivery device according to claim 84 in combination with
a dilation device, the dilation device being useable to dilate the
opening of a paranasal sinus and the implantable substance delivery
device being thereafter implantable within that paranasal sinus or
within the dilated opening of that paranasal sinus.
174. A system according to claim 173 wherein the dilation device
comprises a balloon sized to dilate the opening of the paranasal
sinus.
175. A system according to claim 174 wherein the balloon comprises
a non-compliant balloon.
176-177. (canceled)
178. A device according to claim 84 wherein the device has a length
of between about 15 cm and about 135 cm.
179. A device according to claim 84 wherein the implantable portion
has a length of between about 20 mm and about 80 mm.
180-189. (canceled)
Description
RELATED APPLICATIONS
[0001] This application is a division of U.S. patent application
Ser. No. 11/234,395 filed Sep. 23, 2005 which is a
continuation-in-part of copending U.S. patent application Ser. No.
10/829,917 entitled Devices, Systems and Methods for Diagnosing and
Treating Sinusitis and Other Disorders of the Ears, Nose and/or
Throat filed on Apr. 21, 2004 and 10/912,578 entitled Implantable
Device and Methods for Delivering Drugs and Other Substances to
Treat Sinusitis and Other Disorders filed on Aug. 4, 2004, each of
which is expressly incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to medical devices
and methods and more particularly to substance delivering implants
and methods for treating a broad range of disorders including but
not limited to sinusitis and other ear, nose and throat
disorders.
BACKGROUND
[0003] The paranasal sinuses are cavities formed within the bones
of the face. The paranasal sinuses include frontal sinuses, ethmoid
sinuses, sphenoid sinuses and maxillary sinuses. The paranasal
sinuses are lined with mucous-producing epithelial tissue.
Normally, mucous produced by the linings of the paranasal sinuses
slowly drains out of each sinus through an opening known as an
ostium, and into the nasopharynx. Disorders that interfere with
drainage of mucous (e.g., occlusion of the sinus ostia) can result
in a reduced ability of the paranasal sinuses to function normally.
This results in mucosal congestion within the paranasal sinuses.
Such mucosal congestion of the sinuses can cause damage to the
epithelium that lines the sinus with subsequent decreased oxygen
tension and microbial growth (e.g., a sinus infection).
[0004] The nasal turbinates are three (or sometimes four) bony
processes that extend inwardly from the lateral walls of the nasal
cavity and are covered with mucosal tissue. These turbinates serve
to increase the interior surface area of the nose and to impart
warmth and moisture to air that is inhaled through the nose. The
mucosal tissue that covers the turbinates is capable of becoming
engorged with blood and swelling or becoming substantially devoid
of blood and shrinking, in response to changes in physiologic or
environmental conditions. The curved edge of each turbinate defines
a passageway known as a meatus. For example, the inferior meatus is
a passageway that passes beneath the inferior turbinate. Ducts,
known as the nasolacrimal ducts, drain tears from the eyes into the
nose through openings located within the inferior meatus. The
middle meatus is a passageway that extends inferior to the middle
turbinate. The middle meatus contains the semilunar hiatus, with
openings or ostia leading into the maxillary, frontal, and anterior
ethmoid sinuses. The superior meatus is located between the
superior and medial turbinates.
[0005] Nasal polyps are benign masses that grow from the lining of
the nose or paranasal sinuses. Nasal polyps often result from
chronic allergic rhinitis or other chronic inflammation of the
nasal mucosa. Nasal polyps are also common in children who suffer
from cystic fibrosis. In cases where nasal polyps develop to a
point where they obstruct normal drainage from the paranasal
sinuses, they can cause sinusitis.
[0006] The term "sinusitis" refers generally to any inflammation or
infection of the paranasal sinuses. Sinusitis can be caused by
bacteria, viruses, fungi (molds), allergies or combinations
thereof.
[0007] Various drugs have been used to treat sinusitis, including
systemic antibiotics. Intranasal corticosteroid sprays and
intranasal decongestant sprays and drops have also been used.
However, the use of intranasal sprays and drops by most patients
does not result in the drug actually entering the affected
intranasal sinuses. Rather, such sprays and drops typically contact
only tissues located within the nasal cavity. The introduction of
drugs directly into the sinuses has been proposed by others, but
has not become a widely used treatment technique. For example,
United States Patent Application Publication 2004/0116958A1
(Gopferich et al.) describes a tubular sheath or "spacer" formed of
biodegradable or non-biodegradable polymer that, prior to insertion
in the patient's body, is loaded with a controlled amount of an
active substance, such as a corticosteroid or anti-proliferative
agent. Surgery is performed to create a fenestration in a frontal
sinus and the sheath is inserted into such fenestration.
Thereafter, the sheath which has been preloaded with the active
substance is inserted into the surgically created fenestration
where it a) deters closure of the surgically created fenestration,
b) serves as a conduit to facilitate drainage from the sinus and d)
delivers the active substance. The sheath of United States Patent
Application Publication 2004/0116958A1 (Gopferich et al.) remains
substantially in a single configuration (i.e., it does not
transition between a collapsed configuration and an expanded
configuration) although it may be coated with a material that
swells when in contact with mucous or body fluid. In some
embodiments, the sheath is formed of multiple layers of polymeric
material, one or more of which is/are loaded with the active
substance and one or more of which is/are free of the active
substance. In other embodiments, the sheath has a "hollow body"
which forms a reservoir system wherein the active substance is
contained and a membrane which controls the release of the active
substance from the reservoir. In some embodiments, the sheath may
be anchored by causing the end of the sheath that extends into the
sinus to swell or otherwise enlarge.
[0008] Also, Min, Yang-Gi, et al., Mucociliary Activity and
Histopathology of Sinus Mucosa in Experimental Maxillary Sinusitis:
A Comparison of Systemic Administration of Antibiotic and
Antibiotic Delivery by Polylactic Acid Polymer, Laryngoscope,
105:835-842 (August 1995) describes experiments wherein
experimental sinusitis was induced in three groups of rabbits by
"pasting" the natural sinus ostia, forming an incision and small
bore hole made in the anterior wall of the sinus, introducing
pathogenic microbes through the bore hole and then closing the
incision. Five days after introduction of the pathogenic microbes,
the natural sinus ostia were reopened and the rabbits were divided
into three (3) groups. Group 1 (control) received no treatment.
Group 2 received repeated intramuscular injections of ampicillin.
In the animals of Group 3, 1.5 cm.times.1.5 cm sheets of polylactic
acid polymer (PLA) film containing ampicillin (0.326 mg/sheet) were
rolled up and inserted through the natural ostia into the infected
sinuses. Thereafter, measurements of mucocilliary transport speed
were made and the tissues lining the affected sinuses were examined
histopathologically. The authors concluded that the therapeutic
effect observed in the animals that had received intrasinus
implants of PLA/Ampicillin film (Group 3) was significantly better
that that observed in the untreated control animals (Group1) or
those that has received repeated intramuscular doses of ampicillin
(Group 2).
[0009] U.S. Pat. No. 3,948,254 (Zaffaroni) describes implantable
drug delivery devices comprising a drug reservoir surrounded by a
microporous wall. The reservoir may be formed of a solid drug
carrier that is permeable to passage of the drug. The rate of
passage of the drug through the wall may be slower than the rate at
which the drug passes through the solid drug carrier that forms the
reservoir. U.S. Pat. No. 3,948,254 (Zaffaroni) describes a number
of applications for the implantable drug delivery devices including
placement in a nasal passage. Specifically, U.S. Pat. No. 3,948,254
(Zaffaroni) claimed a nasal delivery device for dispensing a drug
within a nasal passage at a controlled rate wherein the nasal
device is comprised of (a) a wall defining the device dimensioned
for insertion and placement within a nasal passage, with the wall
formed of a nasal acceptable microporous material, (b) a reservoir
surrounded by the wall and comprised of a solid carrier permeable
to drug and containing drug in an amount sufficient for the device
to meter it at a continuous and controlled rate for a prolonged
period of time from the device, (c) a liquid medium permeable to
the passage of drug by diffusion charged in the micropores, and (d)
wherein the device releases drug when in a nasal environment by
passage of drug from the carrier and through the liquid to the
exterior of the device to produce a useful result. The entire
disclosure of U.S. Pat. No. 3,948,254 (Zaffaroni) is expressly
incorporated herein by reference.
[0010] Other publications have also reported that introduction of
drugs directly into the paranasal sinuses is effective in the
treatment of sinusitis. See, Tarasov, D. I., et al., Application of
Drugs Based on Polymers in the Treatment of Acute and Chronic
Maxillary Sinusitis, Vestn Otorinolaringol. Vol. 6, Pages 45-7
(1978). Also, R. Deutschmann, et al., A Contribution to the Topical
Treatment of [Maxillary] Sinusitis Preliminary Communication,
Stomat. DDR 26 (1976), 585-592 describes the placement of a
resorbable drug delivery depot within the maxillary sinus for the
purposes of eluting drugs, specifically Chloramphenicol. In this
clinical series a water soluble gelatin was used as carrier and was
mixed with the drug prior to application and introduced as a mass
into the sinus. Since the substance had little mechanical integrity
and dissolved in a relatively short timeframe, to achieve a
therapeutic effect, the author suggested that it must be instilled
every 2 to 3 days. An alternative to gelatin could be a sponge
loaded with the therapeutic substance as suggested in U.S. Pat. No.
6,398,758 (Jacobsen, et al.). In this patent directed at delivering
a sustained release device against the wall of a blood vessel, a
hollow cylindrical sponge is loaded with drug and pressed against
the wall. This allows the drug to contact the wall while sustaining
blood flow within the center of the lumen. Further, a skin is
provided to direct the drug into the walls of the blood vessel and
prevent drug from flowing into the lumen. While sponges loaded with
drug at the time of their application do permit some degree of
sustained release, the time required to load them also correlates
closely the time over which they will elute substance. Thus, if
delivery is required for a longer period of time additional
mechanisms must be employed to regulate their release.
[0011] There are also several examples in the patent literature
where various sustained release mechanisms have generally been
proposed using systems with pre-incorporated drugs into matrices or
polymers. These include U.S. Pat. No. 3,948,254 (Zafferoni), US
2003/0185872A2 (Kochinke), WO 92/15286 (Shikani), and U.S. Pat. No.
5,512,055 (Domb, et al.). In general, these references discuss
various materials and structures that may be used to construct
sustained drug delivery vehicles and provide a good overview of the
state of sustained drug delivery art. While helpful in laying out
certain materials and schemes for creating sustained release
systems for drugs, each of these references, however, do not
describe specific methods, means or structures which would permit
them to be easily adapted for intended uses in the targeted in this
application.
[0012] Another common ear, nose and throat disorder is otitis media
or inflammation of the middle ear. Most cases of otitis media are
associated with some degree of Eustachian tube disfunction. Because
air cannot adequately pass through the Eustachian tube into the
middle ear, negative pressure can be created within the middle ear.
This negative pressure may essentially pull or draw fluid out of
the lining of the middle ear/mastoid, thereby resulting in an
accumulation of fluid in the middle ear behind the eardrum. In some
cases, fluid that accumulates within the middle ear can become
infected. Several types of otitis have been identified. Serous
otitis typically results from a fairly sudden obstruction of the
Eustachian tube and is characterized by the collection of generally
thin, clear fluid in the middle ear and mastoid. If this fluid does
not clear within a few weeks, it is considered chronic serous
otitis. Secretory otitis typically occurs in small children and is
characterized by the collection of a thick fluid in the middle ear
and mastoid. This thick fluid contains muccoid material that has
been secreted by the mucous glands of the middle ear and also
contains enzymes that can damage the small bones and other tissues
of the middle ear. If left untreated, these enzymes can erode the
bones enough to cause permanent hearing loss. Acute otitis media is
characterized by the accumulation of pus in the middle ear and
typically occurs in patients who have active respiratory infections
which result in an abrupt obstruction of the Eustachian tube at the
same time as infectious bacteria are present. Without antibiotic
treatment, acute otitis of bacterial origin can cause perforation
of the eardrum, with drainage of pus from the ear. Although the
eardrum may heal after the infection has resolved, permanent damage
to the middle ear and/or the inner ear can sometimes result from
infections of this severity. Chronic otitis media is typically
caused by a form of chronic mastoiditis and results in a chronic
infection of the middle ear and mastoid cavity. Because the mastoid
bone is involved, treatment with antibiotics administered by
traditional routes of administration (i.v., i.m., oral, etc.)
sometimes does not remove the infection from the bone and surgical
removal of the infected mastoid bone may be necessary. A common
complication associated with chronic otitis and mastoiditis is
cholesteatoma. A cholesteatoma is a soft tissue sac that emanates
from the eardrum and grows back into the middle ear or mastoid,
thereby creating a mass of progressively increasing size which can
destroy or damage the bones of the middle ear, the inner ear, the
facial nerve and/or portions of the brain. Thus, the various forms
of otits can be very serious if left untreated.
[0013] There remains a need in the art for the development of new
devices and methods for delivering drugs and other therapeutic or
diagnostic substances into paranasal sinuses, Eustachian tubes,
middle ear and/or other locations within the body for the treatment
of sinusitis, otitis or other diseases and disorders.
SUMMARY OF THE INVENTION
[0014] In accordance with the present invention there is provided a
substance delivery device that generally comprises i) a removable
portion comprising an elongate shaft having a lumen and a distal
end and ii) an implantable portion comprising a substance delivery
reservoir having a first configuration and a second configuration,
said reservoir being in communication with the lumen of the
removable portion such that a therapeutic or diagnostic substance,
or a component thereof, may be introduced through the lumen and
into the reservoir, said implantable portion being detachable from
the removable portion such that the removable portion may be
removed from the subject's body leaving the implantable portion
within the subject's body. The reservoir may comprise a balloon or
other vessel that expands or otherwise changes configuration when
filled with the diagnostic or therapeutic substance. The removable
portion may include a lumen, advanceable needle, injector or other
substance introducing apparatus that is useable to introduce the
desired substance, or a component thereof, into the reservoir after
the reservoir has been introduced into the body. In addition to
delivering the substance, all or part of the implantable portion of
the device may function as a stent and/or scaffold and/or drain
and/or vent.
[0015] Further in accordance with the present invention, there is
provided a method for using a substance delivery device of the
above-summarized character, such method generally comprising the
steps of; i) introducing the substance delivery device into the
subject's body while the reservoir is in a first configuration; ii)
positioning the implantable portion at a desired location within
the subject's body; iii) providing a therapeutic or diagnostic
substance; iv) introducing the substance, or a component thereof,
through the lumen and into the reservoir thereby causing the
reservoir to assume the second configuration; v) detaching the
removable portion from the implantable portion; and vi) removing
the removable portion from the subject's body. In some embodiments
of the method the substance delivery device is implanted within the
ear, nose, throat or paranasal sinus of the subject, but such
methods also have applicability in many other areas of the
body.
[0016] Still further in accordance with the invention, there is
provided a substance eluting implant (e.g., a stent) that generally
comprises core that contains the substance, a layer on one side of
the core through which the substance elutes and a layer on another
side of the core through which substance does not elute. Thus, one
surface (e.g., an outer tissue-contacting surface) of the
implantable device may elute the substance while another surface
(e.g., an inner or non-tissue contacting surface) does not elute
the substance.
[0017] Still further in accordance with the present invention,
there is provided a method for using a substance eluting implant of
the above-summarized character, such method generally comprising
the step of implanting the implant within the body of a human or
non-human animal subject such that a substance eluting surface of
the implant will elute the substance and a non-substance eluting
surface of the implant will not elute any substantial amount of the
substance.
[0018] Still further aspects and details of the present invention
will be understood upon reading of the detailed description and
examples set forth herebelow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 shows a side view of an embodiment of a implantable
sinus substance delivery device disposed on a removable delivery
catheter
[0020] FIG. 1A shows a perspective view of the sinus substance
delivery device of FIG. 1.
[0021] FIGS. 1B and 1B' show side views of the deployment mechanism
of the sinus substance delivery device of FIG. 1 in the un-deployed
and deployed states respectively.
[0022] FIG. 1C shows a cross section through the plane 1C-1C of the
delivery catheter of FIG. 1.
[0023] FIG. 1D-1F show various steps of introducing and deploying
the substance delivery device of FIG. 1 into a paranasal sinus
through the ostium of the paranasal sinus.
[0024] FIG. 2A shows a side view of an embodiment of a substance
delivery device comprising a filling tube having a valve in the
lumen of the filling tube.
[0025] FIGS. 2B, 2C and 2D show cross sections of the device shown
in FIG. 2A through the planes 2B-2B, 2C-2C and 2D-2D
respectively.
[0026] FIGS. 2E and 2F show longitudinal cross sections of an
embodiment of a substance delivery device comprising a coaxial
filling lumen and an elastomeric sleeve valve.
[0027] FIGS. 2G and 2H show cross sections through a portion of a
substance delivery device comprising an elastomeric sleeve valve
located in a region of an elongate shaft enclosed by a substance
reservoir.
[0028] FIGS. 2I and 2J show a partial view of a region of a
substance delivery device comprising a duck-bill valve.
[0029] FIGS. 2K and 2L show a partial view of a region of a
substance delivery device comprising a dome valve.
[0030] FIGS. 2M and 2N show longitudinal sections through the
filling mechanism of an embodiment of a substance delivery device
comprising a self-sealing membrane.
[0031] FIGS. 2O and 2P show longitudinal sectional views of a
region of an embodiment of a substance delivery device comprising a
plugging mechanism.
[0032] FIGS. 3A and 3B show a longitudinal section through a
proximal region of a substance delivery device deployed by a
sliding tube.
[0033] FIGS. 4A through 4E show a coronal view of a human head
showing the various steps of a method of delivering an implantable
substance delivery device to one of the paranasal sinuses of a
patient.
[0034] FIGS. 4A' through 4E' show a coronal view of a human head
showing the various steps of an embodiment of a method of
delivering an implantable substance delivery device to a Eustachian
tube or middle ear of a patient.
[0035] FIG. 4F shows a region of a substance delivery device
comprising an inflatable balloon comprising two or more lobes.
[0036] FIG. 4G shows a cross section of the balloon shown in FIG.
4F through the plane 4G-4G.
[0037] FIG. 4H shows a perspective view of an embodiment of an
inflatable substance reservoir comprising a spiral inflatable
balloon.
[0038] FIG. 4I shows a perspective view of a region of a substance
delivery device comprising an inflatable balloon having one or more
radial protrusions.
[0039] FIG. 4J shows a perspective view of a region of a substance
delivery device comprising an inflatable balloon oriented
transversely to the axis of the substance delivery device.
[0040] FIG. 4K shows a substance delivery device comprising an
inflatable balloon that acts as a substance reservoir.
[0041] FIG. 4L shows a section through a substance delivery device
comprising an inflatable substance delivery reservoir shaped to
produce an atraumatic distal end.
[0042] FIG. 4M shows a cross section through a substance delivery
device comprising two substance reservoirs that also act as
anchors.
[0043] FIG. 4N shows a partial view of an embodiment of a substance
delivery device comprising a substance reservoir made of foam.
[0044] FIG. 5A shows a sectional view of an embodiment of a drug
delivery device comprising a pressure exerting mechanism.
[0045] FIG. 5A' shows a sectional view of the substance delivery
device shown in FIG. 5A showing the pressure exerting mechanism
exerting a pressure on a substance reservoir.
[0046] FIG. 5B shows a cross sectional view of an embodiment of a
substance delivery device comprising a controlled substance release
element in the form of a wick.
[0047] FIG. 5C shows the side view of an embodiment of an elongate
porous tube that may be used to control the rate of delivery of a
substance to the anatomy from a substance delivery device.
[0048] FIG. 5D shows a cross sectional view of an embodiment of a
substance delivery device comprising the porous tube of FIG.
5C.
[0049] FIG. 5E shows a cross sectional view of an embodiment of a
substance delivery device comprising a porous shaft region for
controlled delivery of a substance to the anatomy.
[0050] FIG. 5F shows a cross section of the substance delivery
device of FIG. 5E through the plane 5F-5F.
[0051] FIG. 6A shows an embodiment of a substance delivery device
comprising an anchoring or retention element comprising deployable
arms.
[0052] FIG. 6A' shows the substance delivery device of FIG. 6A
deployed in a sphenoid sinus.
[0053] FIG. 6B shows a perspective view of an embodiment of a
substance delivery device comprising a bent or angled shaft.
[0054] FIG. 6B' shows substance delivery device 610 of FIG. 6B
deployed in a sphenoid sinus.
[0055] FIG. 6C shows a perspective view of an embodiment of a
substance delivery device comprising a shaft comprising a curved or
coiled region.
[0056] FIG. 6C' shows the substance delivery device of FIG. 6C
deployed in a sphenoid sinus.
[0057] FIG. 6D shows a perspective view of an embodiment of a
substance delivery device comprising an elongate shaft comprising
flexible, projections.
[0058] FIG. 6D' shows the substance delivery device of FIG. 6D
deployed in a sphenoid sinus.
[0059] FIG. 6E shows a perspective view of an embodiment of a
substance delivery device comprising a substance reservoir having
one or more radial projections.
[0060] FIG. 6E' shows substance delivery device 352 of FIG. 6E
deployed in a sphenoid sinus.
[0061] FIGS. 6F-6H show embodiment of substance delivery devices
comprising suturing arrangement to suture the substance delivery
devices to anatomical structures.
[0062] FIG. 7A shows a perspective view of an embodiment of a
substance delivery device comprising an elastic, super-elastic or
shape-memory material.
[0063] FIG. 7B shows a cross section through shaft 652 of substance
delivery device 650 of FIG. 7A through the plane 7B-7B.
[0064] FIG. 7C shows the substance delivery device of FIG. 7A
loaded on a delivery device.
[0065] FIG. 7D shows a cross section through the plane 7D-7D of
FIG. 7B
[0066] FIG. 7E shows the substance delivery device of FIG. 7A
loaded on the delivery device of FIG. 7C being introduced through
an elongate introducing device.
[0067] FIG. 8A shows an embodiment of an elongate substance
delivery device comprising an elongate filament being introduced in
a sphenoid sinus.
[0068] FIG. 8B shows a cross sectional view through a region of the
substance delivery device of FIG. 8A through plane 8B-8B.
[0069] FIG. 9A shows a method of delivering a substance to the
lateral wall of a maxillary sinus by the substance delivery device
of FIG. 5B.
[0070] FIG. 9B shows a method of delivering a substance to the
medial wall of a frontal sinus by a device similar to the substance
delivery device of FIG. 4L.
[0071] FIGS. 10A through 10C show the various steps of a method of
implanting a substance delivering stent in an anatomical
region.
[0072] FIG. 10D shows a cross section through a region 10D of an
embodiment of the device of FIG. 10C.
[0073] FIGS. 11A through 11C show a sequence of steps to deliver a
substance delivery device through a sinus ostium that prevents
post-surgical adhesions and also allows the natural flow of mucous
through the sinus ostium.
DETAILED DESCRIPTION
[0074] The following detailed description and the accompanying
drawings are intended to describe some, but not necessarily all,
examples or embodiments of the invention only. This detailed
description and the accompanying drawings do not limit the scope of
the invention in any way.
[0075] The present invention provides devices that may be
positioned within naturally occurring or man-made anatomical
cavities such as a nostrils, nasal cavities, nasal meatus, ostia or
interior of paranasal sinuses, etc.; or naturally occurring or
man-made passageways such as Eustachian tubes, naso-lachrymal
ducts, etc. to deliver a diagnostic or therapeutic substance to
tissues located adjacent to or near the implanted device. Certain
non-limiting examples of the present invention are shown in FIGS.
1-11C and described in detail herebelow. Although certain examples
shown in these drawings are targeted to the paranasal sinuses,
regions of the middle ear, Eustachian tubes, etc., the devices and
methods of the present invention are useable in a wide range of
applications in various area of the body, including but not limited
to natural or man made orifices and passageways such as
naso-lachrymal ducts, subcutaneous locations, intravascular or
intracardiac locations and locations within the gastrointestinal
tract.
[0076] More specifically, one or more of the substance delivery
devices disclosed herein may be positioned within natural or
man-made openings to the frontal, maxillary, sphenoid, anterior or
posterior Ethmoid sinuses; other cells or cavities; anatomical
regions such as nostrils, nasal cavities, nasal meatus, etc.; and
other passageways such as Eustachian tubes, naso-lachrymal ducts,
etc. The step of placement of the substance delivery devices
disclosed herein may be combined with a step of artificially
creating an opening to an anatomical region. In one embodiment, the
substance delivery devices disclosed herein are placed through
natural or dilated anterior or posterior ethmoid sinus ostia or
artificially created openings to the ethmoid sinuses. The
artificially created openings may be created by punching a wall of
the ethmoid sinuses. The sinus ostia or artificially created
openings may be accessed through one or more artificially created
holes in the ethmoid bulla. Such artificially created holes in the
ethmoid bulla may be created by punching through the ethmoid bulla.
In another embodiment, the substance delivery devices disclosed
herein are placed through artificially created openings to the
maxillary sinuses.
[0077] The term substance as used herein is to be broadly construed
to include any feasible drugs, prodrugs, proteins, gene therapy
preparations, cells, diagnostic agents, contrast or imaging agents,
biologicals, etc. Such substances may be in bound or free form,
liquid or solid, colloid or other suspension, solution or may be in
the form of a gas or other fluid or non-fluid. For example, in some
applications where it is desired to treat or prevent a microbial
infection, the substance delivered may comprise a pharmaceutically
acceptable salt or dosage form of an antimicrobial agent (e.g.,
antibiotic, antiviral, antiparasitic, antifungal, etc.), a
corticosteroid or other anti-inflammatory (e.g., an NSAID), a
decongestant (e.g., vasoconstrictor), a mucous thinning agent
(e.g., an expectorant or mucolytic), an agent that prevents of
modifies an allergic response (e.g., an antihistamine, cytokine
inhibitor, leucotriene inhibitor, IgE inhibitor, immunomodulator),
an anesthetic agent with or without a vasoconstriction agents (e.g.
Xylocaine with or without Epinephrine), an analgesic agent, an
allergen or another substance that causes secretion of mucous by
tissues, hemostatic agents to stop bleeding, anti-proliferative
agents, cytotoxic agents e.g. alcohol, biological agents such as
protein molecules, stem cells, genes or gene therapy preparations,
viral vectors carrying proteins or nucleic acids such as DNA or
mRNA coding for important therapeutic functions or substances,
cauterizing agents e.g. silver nitrate, etc.
[0078] Some nonlimiting examples of antimicrobial agents that may
be used in this invention include acyclovir, amantadine,
rimantadine, oseltamivir, zanamivir, aminoglycosides (e.g.,
amikacin, gentamicin and tobramycin), amoxicillin,
amoxicillin/clavulanate, amphotericin B, ampicillin,
ampicillin/sulbactam, atovaquone, azithromycin, cefazolin,
cefepime, cefotaxime, cefotetan, cefpodoxime, ceftazidime,
ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil,
cephalexin, chloramphenicol, clotrimazole, ciprofloxacin,
clarithromycin, clindamycin, dapsone, dicloxacillin, doxycycline,
erythromycin, fluconazole, foscarnet, ganciclovir, atifloxacin,
imipenem/cilastatin, isoniazid, itraconazole, ketoconazole,
metronidazole, nafcillin, nafcillin, nystatin, penicillins
including penicillin G, pentamidine, piperacillin/tazobactam,
rifampin, quinupristin-dalfopristin, ticarcillin/clavulanate,
trimethoprim/sulfamethoxazole, valacyclovir, vancomycin, mafenide,
silver sulfadiazine, mupirocin, nystatin, triamcinolone/nystatin,
clotrimazole/betamethasone, clotrimazole, ketoconazole,
butoconazole, miconazole, tioconazole, detergent-like chemicals
that disrupt or disable microbes (e.g., nonoxynol-9, octoxynol-9,
benzalkonium chloride, menfegol, and N-docasanol); chemicals that
block microbial attachment to target cells and/or inhibits entry of
infectious pathogens (e.g., sulphated and sulphonated polymers such
as PC-515 (carrageenan), Pro-2000, and Dextrin 2 Sulphate);
antiretroviral agents (e.g., PMPA gel) that prevent retroviruses
from replicating in the cells; genetically engineered or naturally
occurring antibodies that combat pathogens such as anti-viral
antibodies genetically engineered from plants known as
"plantibodies;" agents which change the condition of the tissue to
make it hostile to the pathogen (such as substances which alter
mucosal pH (e.g., Buffer Gel and Acidform); non-pathogenic or
"friendly" microbes that cause the production of hydrogen peroxide
or other substances that kill or inhibit the growth of pathogenic
microbes (e.g., lactobacillus); antimicrobial proteins or peptides
such as those described in U.S. Pat. No. 6,716,813 (Lin et al.)
which is expressly incorporated herein by reference or
antimicrobial metals (e.g., colloidal silver).
[0079] Additionally or alternatively, in some applications where it
is desired to treat or prevent inflammation the substances
delivered in this invention may include various steroids or other
anti-inflammatory agents (e.g., nonsteroidal anti-inflammatory
agents or NSAIDs), analgesic agents or antipyretic agents. For
example, corticosteroids that have previously administered by
intranasal administration may be used, such as beclomethasone
(Vancenase.RTM. or Beconase.RTM.), flunisolide (Nasalide.RTM.),
fluticasone proprionate (Flonase.RTM.), triamcinolone acetonide
(Nasacort.RTM.), budesonide (Rhinocort Aqua.RTM.), loterednol
etabonate (Locort) and mometasone (Nasonex.RTM.). Other salt forms
of the aforementioned corticosteroids may also be used. Also, other
non-limiting examples of steroids that may be useable in the
present invention include but are not limited to aclometasone,
desonide, hydrocortisone, betamethasone, clocortolone,
desoximetasone, fluocinolone, flurandrenolide, mometasone,
prednicarbate; amcinonide, desoximetasone, diflorasone,
fluocinolone, fluocinonide, halcinonide, clobetasol, augmented
betamethasone, diflorasone, halobetasol, prednisone, dexamethasone
and methylprednisolone. Other anti-inflammatory, analgesic or
antipyretic agents that may be used include the nonselective COX
inhibitors (e.g., salicylic acid derivatives, aspirin, sodium
salicylate, choline magnesium trisalicylate, salsalate, diflunisal,
sulfasalazine and olsalazine; para-aminophenol derivatives such as
acetaminophen; indole and indene acetic acids such as indomethacin
and sulindac; heteroaryl acetic acids such as tolmetin, dicofenac
and ketorolac; arylpropionic acids such as ibuprofen, naproxen,
flurbiprofen, ketoprofen, fenoprofen and oxaprozin; anthranilic
acids (fenamates) such as mefenamic acid and meloxicam; enolic
acids such as the oxicams (piroxicam, meloxicam) and alkanones such
as nabumetone) and Selective COX-2 Inhibitors (e.g.,
diaryl-substituted furanones such as rofecoxib; diaryl-substituted
pyrazoles such as celecoxib; indole acetic acids such as etodolac
and sulfonanilides such as nimesulide).
[0080] Additionally or alternatively, in some applications, such as
those where it is desired to treat or prevent an allergic or immune
response and/or cellular proliferation, the substances delivered in
this invention may include a) various cytokine inhibitors such as
humanized anti-cytokine antibodies, anti-cytokine receptor
antibodies, recombinant (new cell resulting from genetic
recombination) antagonists, or soluble receptors; b) various
leucotriene modifiers such as zafirlukast, montelukast and
zileuton; c) immunoglobulin E (IgE) inhibitors such as Omalizumab
(an anti-IgE monoclonal antibody formerly called rhu Mab-E25) and
secretory leukocyte protease inhibitor).
[0081] Additionally or alternatively, in some applications, such as
those where it is desired to shrink mucosal tissue, cause
decongestion or effect hemostasis, the substances delivered in this
invention may include various vasoconstrictors for decongestant and
or hemostatic purposes including but not limited to
pseudoephedrine, xylometazoline, oxymetazoline, phenylephrine,
epinephrine, etc.
[0082] Additionally or alternatively, in some applications, such as
those where it is desired to facilitate the flow of mucous, the
substances delivered in this invention may include various
mucolytics or other agents that modify the viscosity or consistency
of mucous or mucoid secretions, including but not limited to
acetylcysteine (Mucomyst.TM., Mucosil.TM.) and guaifenesin.
[0083] Additionally or alternatively, in some applications such as
those where it is desired to prevent or deter histamine release,
the substances delivered in this invention may include various mast
cell stabilizers or drugs which prevent the release of histamine
such as cromolyn (e.g., Nasal Chrom.RTM.) and nedocromil.
[0084] Additionally or alternatively, in some applications such as
those where it is desired to prevent or inhibit the effect of
histamine, the substances delivered in this invention may include
various antihistamines such as azelastine (e.g., Astylin.RTM.),
diphenhydramine, loratidine, etc.
[0085] Additionally or alternatively, in some embodiments such as
those where it is desired to dissolve, degrade, cut, break or
remodel bone or cartilage, the substances delivered in this
invention may include substances that weaken or modify bone and/or
cartilage to facilitate other procedures of this invention wherein
bone or cartilage is remodeled, reshaped, broken or removed. One
example of such an agent would be a calcium chelator such as EDTA
that could be injected or delivered in a substance delivery implant
next to a region of bone that is to be remodeled or modified.
Another example would be a preparation consisting of or containing
bone degrading cells such as osteoclasts. Other examples would
include various enzymes of material that may soften or break down
components of bone or cartilage such as collagenase (CGN), trypsin,
trypsin/EDTA, hyaluronidase, and tosyllysylchloromethane
(TLCM).
[0086] Additionally or alternatively, in some applications, the
substances delivered in this invention may include other classes of
substances that are used to treat rhinitis, nasal polyps, nasal
inflammation, and other disorders of the ear, nose and throat
including but not limited to anti-cholinergic agents that tend to
dry up nasal secretions such as ipratropium (Atrovent Nasal.RTM.),
as well as other agents not listed here.
[0087] Additionally or alternatively, in some applications such as
those where it is desired to draw fluid from polyps or edematous
tissue, the substances delivered in this invention may include
locally or topically acting diuretics such as furosemide and/or
hyperosmolar agents such as sodium chloride gel or other salt
preparations that draw water from tissue or substances that
directly or indirectly change the osmolar content of the mucous to
cause more water to exit the tissue to shrink the polyps directly
at their site.
[0088] Additionally or alternatively, in some applications such as
those wherein it is desired to treat a tumor or cancerous lesion,
the substances delivered in this invention may include antitumor
agents (e.g., cancer chemotherapeutic agents, biological response
modifiers, vascularization inhibitors, hormone receptor blockers,
cryotherapeutic agents or other agents that destroy or inhibit
neoplasia or tumorigenesis) such as; alkylating agents or other
agents which directly kill cancer cells by attacking their DNA
(e.g., cyclophosphamide, isophosphamide), nitrosoureas or other
agents which kill cancer cells by inhibiting changes necessary for
cellular DNA repair (e.g., carmustine (BCNU) and lomustine (CCNU)),
antimetabolites and other agents that block cancer cell growth by
interfering with certain cell functions, usually DNA synthesis
(e.g., 6 mercaptopurine and 5-fluorouracil (5FU), antitumor
antibiotics and other compounds that act by binding or
intercalating DNA and preventing RNA synthesis (e.g., doxorubicin,
daunorubicin, epirubicin, idarubicin, mitomycin-C and bleomycin)
plant (vinca) alkaloids and other anti-tumor agents derived from
plants (e.g., vincristine and vinblastine), steroid hormones,
hormone inhibitors, hormone receptor antagonists and other agents
which affect the growth of hormone-responsive cancers (e.g.,
tamoxifen, herceptin, aromatase inhibitors such as
aminoglutethimide and formestane, triazole inhibitors such as
letrozole and anastrozole, steroidal inhibitors such as
exemestane), anti-angiogenic proteins, small molecules, gene
therapies and/or other agents that inhibit angiogenesis or
vascularization of tumors (e.g., meth-1, meth-2, thalidomide),
bevacizumab (Avastin), squalamine, endostatin, angiostatin,
Angiozyme, AE-941 (Neovastat), CC-5013 (Revimid), medi-522
(Vitaxin), 2-methoxyestradiol (2ME2, Panzem), carboxyamidotriazole
(CAI), combretastatin A4 prodrug (CA4P), SU6668, SU11248,
BMS-275291, COL-3, EMD 121974, IMC-1C11, IM862, TNP-470, celecoxib
(Celebrex), rofecoxib (Vioxx), interferon alpha, interleukin-12
(IL-12) or any of the compounds identified in Science Vol. 289,
Pages 1197-1201 (Aug. 17, 2000) which is expressly incorporated
herein by reference, biological response modifiers (e.g.,
interferon, bacillus calmette-guerin (BCG), monoclonal antibodies,
interluken 2, granulocyte colony stimulating factor (GCSF), etc.),
PGDF receptor antagonists, herceptin, asparaginase, busulphan,
carboplatin, cisplatin, carmustine, chlorambucil, cytarabine,
dacarbazine, etoposide, flucarbazine, fluorouracil, gemcitabine
hydroxyurea, ifosphamide, irinotecan, lomustine, melphalan,
mercaptopurine, methotrexate, thioguanine, thiotepa, tomudex,
topotecan, treosulfan, vinblastine, vincristine, mitoazitrone,
oxaliplatin, procarbazine, streptocin, taxol, taxotere,
analogs/congeners and derivatives of such compounds as well as
other antitumor agents not listed here.
[0089] Additionally or alternatively, in some applications such as
those where it is desired to grow new cells or to modify existing
cells, the substances delivered in this invention may include cells
(mucosal cells, fibroblasts, stem cells or genetically engineered
cells) as well as genes and gene delivery vehicles like plasmids,
adenoviral vectors or naked DNA, mRNA, etc. injected with genes
that code for anti-inflammatory substances, etc., and, as mentioned
above, osteoclasts that modify or soften bone when so desired.
[0090] Additionally or alternatively to being combined with a
device and/or a substance releasing modality, it may be ideal to
position the device in a specific location upstream in the mucous
flow path (i.e. frontal sinus or ethmoid cells). This could allow
the deposition of fewer drug releasing devices, and permit the
"bathing" of all the downstream tissues with the desired drug. This
utilization of mucous as a carrier for the drug may be ideal,
especially since the concentrations for the drug may be highest in
regions where the mucous is retained; whereas non-diseased regions
with good mucous flow will be less affected by the drug. This could
be particularly useful in chronic sinusitis, or tumors where
bringing the concentration of drug higher at those specific sites
may have greater therapeutic benefit. In all such cases, local
delivery will permit these drugs to have much less systemic impact.
Further, it may be ideal to configure the composition of the drug
or delivery system such that it maintains a loose affinity to the
mucous permitting it to distribute evenly in the flow. For example,
one or more substance eluting regions of a substance delivery
device may be in physical contact with the mucous. Also, in some
applications, rather than a drug, a solute such as a salt or other
mucous soluble material may be positioned at a location whereby
mucous will contact the substance and a quantity of the substance
will become dissolved in the mucous thereby changing some property
(e.g., pH, osmolarity, etc) of the mucous. In some cases, this
technique may be used to render the mucous hyperosmolar so that the
flowing mucous will draw water and/or other fluid from polyps,
edematous mucosal tissue, etc., thereby providing a drying or
desiccating therapeutic effect.
[0091] Additionally or alternatively to substances directed towards
local delivery to affect changes within the sinus cavity, the nasal
cavities provide unique access to the olfactory system and thus the
brain. Any of the devices and methods described herein may also be
used to deliver substances to the brain or alter the functioning of
the olfactory system. Such examples include, the delivery of energy
or the deposition of devices and/or substances and/or substance
delivering implant(s) to occlude or alter olfactory perception, to
suppress appetite or otherwise treat obesity, epilepsy (e.g.,
barbiturates such as phenobarbital or mephobarbital; iminostilbenes
such as carbamazepine and oxcarbazepine; succinimides such as
ethylsuximide; valproic acid; benzodiazepines such as clonazepam,
clorazepate, diazepam and lorazepam, gabapentin, lamotrigine,
acetazolamide, felbamate, levetiraceam, tiagabine, topiramate,
zonisamide, etc.), personality or mental disorders (e.g.,
antidepressants, antianxiety agents, antipsychotics, etc.), chronic
pain, Parkinson's disease (e.g., dopamine receptor agonists such as
bromocriptine, pergolide, ropinitrol and pramipexole; dopamine
precursors such as levodopa; COMT inhibitors such as tolcapone and
entacapone; selegiline; muscarinic receptor antagonists such as
trihexyphenidyl, benztropine and diphenhydramine) and Alzheimer's
disease, Huntington's disease or other dementias, disorders of
cognition or chronic degenerative diseases (e.g. tacrine,
donepezil, rivastigmine, galantamine, fluoxetine, carbamazepine,
clozapine, clonazepam and proteins or genetic therapies that
inhibit the formation of beta-amyloid plaques), etc.
[0092] The devices and methods disclosed herein may be used to
deliver several combinations of two or more substances disclosed
herein to a suitable target anatomical region. In one particular
embodiment, the devices and methods disclosed herein are used to
deliver a combination of an anti-inflammatory agent (e.g. a steroid
or an NSAID) and a mucolytic agent.
[0093] The inner surface of some anatomical regions such as
paranasal sinuses is lined by mucous. This mucous is continuously
generated within the paranasal sinuses. Simultaneously, this mucous
continuously flows out of paranasal sinuses through an ostium of
the paranasal sinuses. Thus, a substance delivered to a paranasal
sinus tends to be lost from the paranasal sinus along with the
mucous flow. This reduces the net amount of the substance remaining
in the paranasal sinus. Hence, there exists a need to replenish the
substance delivered to the paranasal sinus to maintain an effective
amount of the substance in the paranasal sinus. In order to address
this need, one or more of the substance delivery devices disclosed
herein may comprise one or more substance reservoirs to allow an
effective amount of a substance to be delivered to target
anatomical regions over an effective period of time.
[0094] Turning now to FIGS. 1-11C, it is to be understood that such
figures show specific examples of the devices and methods of the
present invention. Any elements, attributes, components,
accessories or features of one embodiment or example shown in these
figures may be eliminated from that embodiment or example, or may
be included in any other embodiment or example, unless to do so
would render the resultant embodiment or example unusable for its
intended purpose.
[0095] FIG. 1 shows a side view of an embodiment of a device of the
present invention comprising an implantable sinus substance
delivery device 100 (e.g., an implantable portion) and a removable
delivery catheter 102 (e.g, a removable portion). The implantable
substance delivery device 100 is disposed on and is delivered by
the removable delivery catheter 102. The implantable portion or
substance delivery device 100 of this example comprises a tube or
elongate shaft 104 and a substance reservoir 106 from which a
desired substance is eluted or otherwise delivered. Elongate shaft
104 may be made of suitable biocompatible materials including, but
not limited to Pebax, PEEK, Nylon, polyethylene, etc. This tube or
elongate shaft may function and a stent and/or drain and/or vent
when implanted. In this regard, the elongate shaft 104 may
incorporate one or more lumens that are designed to allow drainage
of secretions or other fluid substances and/or ventilation of air
into desired anatomical regions (e.g., paranasal sinuses, the
middle ear, etc. Additionally or alternatively, the elongate shaft
104 of the implantable portion 102 may incorporate a substance
introducing lumenthat may be used to fill a reservoir 106 with
fluid substances. As described in more detail below, the
implantable drug delivery device 100 may also incorporate apparatus
for preventing backflow of substance out of the reservoir 106 after
the removable delivery catheter 102 has been removed. For example,
the implantable substance delivery device 100 may have a substance
introducing lumen through which a substance, or a component of the
substance, may be introduced into the reservoir 106 and a check
valve may be positioned within that substance introducing lumen
and/or within the reservoir to prevent backflow out of that
substance introducing lumen. In this regard, the substance
introducing lumen may have a collapsible or elastomeric region that
is biased to a closed or collapsed configuration so as to thereby
act as a valve. This collapsible or elastomeric region will then
expand when a user is filling reservoir 106 with a fluid substance
under pressure, thus allowing the fluid substance to flow into the
reservoir 106. The substance introducing lumen may be detachably
connected to reservoir 106. In some embodiments, the reservoir 106
may be inflatable or expandable. In such inflatable or expandable
embodiments, the reservoir 106 may be inflated or expanded in situ,
after it has been implanted or otherwise positioned in a desired
anatomical location. Thus the profile of substance delivery device
100 is reduced during the step of introducing reservoir 106 in the
desired anatomical location. The lumen of elongate shaft 104 may be
fitted with a one way valve to prevent unwanted drainage of a
substance used to fill reservoir 106. In the embodiment shown in
FIG. 1, reservoir 106 comprises a balloon that may be made from
suitable biocompatible materials such as polyurethane,
polyethylene, Nylon, etc. The balloon may comprise one or more
pores or openings to allow delivery of the substance in reservoir
106 to the surrounding anatomy. Those pores or openings may be
sized to allow the substance to be delivered from the reservoir 106
at a desired rate.
[0096] In some embodiments, a navigational marker 108 such as a
radiopaque marker band may be present on elongate shaft 104 in the
region enclosed by drug reservoir 106 or elsewhere on the device.
The substance delivery device 100 is introduced into and advanced
to a desired implantation site or target anatomy by the removable
delivery catheter 102. The delivery catheter 102 provides support
to substance delivery device 100 while substance delivery device
100 is introduced into and is delivered to the target anatomy.
Delivery catheter 102 is also used to fill substance delivery
device 100 with a suitable substance to be delivered to the
anatomy. Delivery catheter 102 comprises an elongate shaft 110 that
can be made of suitable biocompatible materials including, but not
limited to metals e.g. stainless steel, titanium, Nickel-titanium
alloy (e.g., Nitinol), etc.; polymers e.g. Pebax, PEEK, Nylon,
polyethylene, etc. In one embodiment, the proximal end of elongate
shaft 110 comprises a hub 112 such as a female luer hub. Hub 112 is
in fluid communication with a lumen of elongate shaft 110. The
lumen of elongate shaft 110 is in fluid communication with the
lumen of elongate shaft 104 used to fill reservoir 106. The distal
end of elongate shaft 110 is detachably connected to the proximal
end of elongate shaft 104. Delivery catheter 102 may further
comprise a deployment mechanism for deploying substance delivery
device 100 in a desired location in the anatomy. In the embodiment
shown in FIG. 1, the deployment mechanism comprises a pushing tube
114 that can be made of suitable biocompatible materials including,
but not limited to Pebax, PEEK, Nylon, polyethylene, etc. Pushing
tube 114 encloses and slides on elongate tube 110. To deploy
substance delivery device 100 in the anatomy, a user pushes pushing
tube 114 in the distal direction. The distal end of pushing tube
114 then pushes a proximal region of elongate shaft 104 that is
detachably attached to elongate shaft 110. This causes substance
delivery device 100 to detach from delivery catheter 102 thereby
implant substance delivery device 100 in the anatomy. After
implanting substance delivery device 100 in the anatomy, delivery
catheter 102 is removed from the anatomy.
[0097] FIG. 1A shows a perspective view of sinus substance delivery
device 100 showing elongate shaft 104 and reservoir 106 and
navigational marker 108 located on elongate shaft 104.
[0098] FIGS. 1B and 1B' show side views of the deployment mechanism
of the sinus substance delivery device of FIG. 1 in the un-deployed
and deployed states respectively. In FIG. 1B, the proximal end of
elongate shaft 104 of substance delivery device 100 is detachably
attached to the distal end of elongate shaft 110 of delivery
catheter 102. In FIG. 1B', a user pushes pushing tube 114 in the
distal direction over elongate shaft 110. The distal end of pushing
tube 114 pushes elongate shaft 104. This causes the proximal end of
elongate shaft 104 to detach from the distal end of elongate shaft
110. This in turn causes substance delivery device 100 to detach
from delivery catheter 102, thereby deploying substance delivery
device 100 in the anatomy.
[0099] FIG. 1C shows a cross section through the plane 1C-1C of
removable delivery catheter 102 of FIG. 1. FIG. 1C shows pushing
tube 114 over the outer surface of elongate shaft 110. Elongate
shaft 110 encloses guidewire GW.
[0100] FIG. 1D-1F show various steps of introducing and deploying
implantable substance delivery device 100 of FIG. 1 into a
paranasal sinus through the ostium of the paranasal sinus by a
removable delivery catheter 102.
[0101] Substance delivery device 100 may be advanced into the
anatomy by a suitable introducing device. In one embodiment,
substance delivery device 100 is advanced into the anatomy by a
suitable guidewire GW as shown in FIGS. 1D-1F. In this embodiment,
substance delivery device 100 may comprise one or more arrangements
to allow a user to introduce substance delivery device 100 over the
guidewire. For example, elongate shaft 104 may comprise an
end-to-end guidewire lumen, a rapid exchange guidewire lumen, etc.
In another embodiment, substance delivery device 100 is advanced
into the anatomy through a suitable guide catheter.
[0102] Substance delivery device 100 may be inserted into an
anatomical region such as a paranasal sinus of a patient through
natural ostia as shown in FIGS. 1D-1F or artificially created
openings of the paranasal sinus. Substance delivery device 100 may
be inserted into the paranasal sinus before or after sinus
procedures such as FESS or Balloon Sinuplasty.TM.. Substance
delivery device 100 may be used to prevent or reduce post
procedural scarring or adhesions and/or to provide ventilation or
drainage of the paranasal sinus. Substance delivery device 100 may
comprise one or more anchors or other retaining mechanisms to
maintain the position of substance delivery device 100 inside the
paranasal sinus for a desired treatment duration. In one
embodiment, inflated reservoir 106 acts as an anchor. Substance
delivery device 100 may be designed to allow its removal from the
anatomy without the use of ionizing radiation such as X-rays.
[0103] The length of the implantable substance delivery device 100
may range from about 20 mm to about 80 mm. The combined length of
the implantable substance delivery device 100 and the removable
delivery catheter 102 may range from about 15 cm to about 135
cm.
[0104] In two preferred embodiments, the length of substance
delivery device 100 is around 5 cm. Hub 112 is a luer lock. This
enables a user to fill a suitable substance into reservoir 106
using a standard syringe. The length of the delivery system from
the proximal end of the female luer hub to the distal end of
elongate shaft 110 is around 25 cm. Elongate shaft 104 comprises a
monorail guidewire lumen. The inner diameter of the monorail
guidewire lumen is 0.037''. This enables a user to introduce
substance delivery device 100 into an anatomical region over a
suitable 0.035'' guidewire. Substance delivery device 100 and the
suitable 0.035'' guidewire may be delivered through a guide
catheter of inner diameter 0.100''. The filling lumen of elongate
shaft 104 comprises a one way micro-valve. The micro-valve is
located 4 cm proximal to the distal tip of elongate shaft 104. In
an alternate embodiment, the micro-valve is located 1 cm from the
distal tip of elongate shaft 104. Reservoir 106 comprises an
elastomeric balloon of an inflated diameter ranging from 7-10 mm.
The elastomeric balloon may be made from suitable biocompatible
materials such as polyurethane, polyethylene, Nylon, etc. The
length of the elastomeric balloon is about 10 mm. The inflated
elastomeric balloon acts as an anchor to retain the position of
substance delivery device 100 in the anatomy. A user may remove
substance delivery device 100 from the anatomy by gently pulling
substance delivery device 100. The elastomeric balloon is designed
to touch at least one mucosal region in the anatomy after substance
delivery device 100 is introduced in the anatomy. The substance
stored in reservoir 106 may be delivered to the surrounding anatomy
through one or more pores located on the elastomeric balloon or on
a distal region of elongate shaft 104. In the first preferred
embodiment, the elastomeric balloon comprises two micropores of
diameter 80 microns. The two micropores are located on diagonally
opposite regions on the proximal tapered region of the elastomeric
balloon. This first embodiment was filled with 0.15 ml of distilled
water at 37 degrees Celsius. The rate of delivery of the distilled
water was measured in a shaker bath. This embodiment of substance
delivery device 100 delivered 0.006-0.017 ml of distilled water in
15 hours. In the second preferred embodiment, a single micropore is
located on elongate shaft 104. The micropore is located 10 mm from
distal tip of elongate shaft 104. The micropore has a pore size of
60 microns. The elastomeric balloon was then inflated with 0.2 ml
of a Kenalog solution and the rate of release of the Kenalog
solution was measured in a shaker bath at a temperature of 37
degrees Celsius. This embodiment of substance delivery device 100
delivered 0.12-0.18 ml of the Kenalog solution in 24 hours.
[0105] The various substance delivery devices disclosed herein may
comprise one or more substance reservoirs that are introduced in
the anatomy in a first configuration. Thereafter, the reservoirs
are filled with a suitable substance. This causes the reservoirs to
assume a second configuration. Such a reservoir design having two
or more configurations is especially useful to reduce the profile
of the substance delivery devices while introducing the substance
delivery devices in the anatomy. Such a reservoir design is also
useful when the reservoir acts as an anchor. For example, substance
delivery device 100 comprises an inflatable reservoir 106.
Reservoir 106 is introduced in the anatomy in the un-inflated first
configuration to reduce the profile of reservoir 106. Thereafter,
reservoir 106 is filled with a suitable substance to cause
reservoir 106 to assume a inflated second configuration.
[0106] The various substance delivery devices disclosed herein may
comprise one or more rate limiting barriers to regulate the
delivery of the substance stored in the substance delivery device
to the surrounding anatomy. For example, in the two preferred
embodiments described in the previous paragraph, the rate limiting
barrier comprises micropores or apertures located on an elastomeric
balloon or on a region of the elongate shaft. The rate limiting
barrier may be designed to regulate the delivery of the substance
to the surrounding anatomy based on one or more chemical or
physical properties of the substance. In one embodiment, the rate
limiting barrier is designed to regulate the delivery of the
substance to the surrounding anatomy based on the viscosity of the
substance. In another embodiment, the rate limiting barrier is
designed to regulate the delivery of the substance to the
surrounding anatomy based on the molecular weight of the substance.
In another embodiment, the rate limiting barrier is designed to
regulate the delivery of the substance to the surrounding anatomy
based on the electric charge of the molecules of the substance. In
another embodiment, the rate limiting barrier is designed to
regulate the delivery of the substance to the surrounding anatomy
based on the osmolarity or osmolality of the substance. In another
embodiment, the rate limiting barrier is designed to regulate the
delivery of the substance to the surrounding anatomy based on the
hydrophobic or hydrophilic nature of the molecules of the
substance. In another embodiment, the rate limiting barrier is
designed to regulate the delivery of the substance to the
surrounding anatomy based on the presence of a certain chemical
group or atom in the molecules of the substance. In another
embodiment, the rate limiting barrier is a semipermeable barrier.
The semipermeable barrier may be designed to contain pores of a
known size or a distribution of sizes to regulate the delivery of
the substance to the surrounding anatomy.
[0107] The reservoirs of the substance delivery devices disclosed
herein may be filled with a suitable substance through a substance
introducing lumen located in a substance filling tube. Such a
filling tube may be provided with one or more closure apparatus or
mechanisms to prevent unwanted leakage of the suitable substance
through the lumen of the substance filling tube. Examples of such
closure apparatus or mechanisms include, but are not limited to
valves such as check valves, clipping mechanisms, plugging
mechanisms, etc. The valves may be located on the region of a
substance delivery device enclosed by a substance reservoir. FIG.
2A shows a side view of an embodiment of a substance delivery
device comprising a filling tube having a valve in the lumen of the
filling tube. Substance delivery device 118 comprises a substance
reservoir 106. Substance reservoir 106 comprises a means for
delivering a stored substance to the surrounding anatomy over a
period of time. In the example shown in FIG. 2A, substance
reservoir 106 is an inflatable balloon. The length of the
inflatable balloon may range from 10-20 mm. The inflated diameter
of the inflatable balloon ranges preferably from 7-10 mm. The
inflatable balloon is preferably made from suitable elastomeric
materials including, but not limited to low density polyethylene,
low durometer Pebax, polyurethane, etc. The inflatable balloon may
also act as an anchor to secure the position of substance reservoir
106 in the anatomy. In one method embodiment, substance reservoir
106 is inserted into a paranasal sinus through the ostium of the
paranasal sinus. Thereafter, the inflatable balloon is inflated
with a suitable substance such that the size of the inflatable
balloon is greater than the size of the ostium of the paranasal
sinus. The inflatable balloon then acts as an anchor to secure the
position of substance reservoir 106 in the paranasal sinus.
Substance reservoir 106 can be filled with a suitable substance by
an elongate shaft 104 that acts as a filling tube. Elongate shaft
104 comprises a lumen. A valve 120 is present in elongate shaft
104. In the example shown in FIG. 2A, valve 120 is a duck-bill
valve. Other examples of valves include, but are not limited to
flutter valves, slit valves, relief valves comprising springs,
poppet valves, valves comprising one or more leaflets, etc. Valve
120 allows a user to fill substance reservoir 106. Valve 120 also
prevents leakage of the substance from the proximal end of elongate
shaft 104. In the example shown in FIG. 2A, valve 120 is located
about 3-5 cm from the proximal end of substance reservoir 106.
Alternatively, valve 120 may be located in the region of elongate
shaft 104 enclosed by substance reservoir 106. In one embodiment,
the outer diameter of the region of substance delivery device 118
enclosing valve 120 ranges from 2-3 mm. The proximal region of
elongate shaft 104 may comprise a suitable hub such as a luer lock.
Alternatively, the proximal region of elongate shaft 104 may be
attached to the distal region of a second tube 122. The proximal
region of second tube 122 may comprise a suitable hub such as a
luer lock 112. Second tube 122 is made preferably from materials
such as low density polyethylene, Pebax, polyurethane, etc. The
attachment between the proximal region of elongate shaft 104 and
the distal region of a second tube 122 may be non-detachable or
detachable. In one embodiment the outer diameter of second tube 122
is around 0.05 inches and the inner diameter is around 0.03 inches.
Substance delivery device 118 may comprise one or more mechanisms
to allow substance delivery device 118 to be introduced in the
anatomy along introducing devices. For example, substance delivery
device 118 may be introduced over suitable guidewires, through
suitable guide catheters, etc. In the example shown in FIG. 2A,
substance delivery device 118 comprises a rapid exchange lumen
located in a parallel tube 124 that is parallel to elongate shaft
104. In one embodiment, the outer diameter of parallel tube 124 is
0.048 inches and the inner diameter of parallel tube 124 is 0.038
inches. The distal region of the inflatable balloon is fixed to a
region of parallel tube 124 to form a distal balloon joint. In one
embodiment, the length of the distal balloon joint ranges from 2-3
mm. The proximal region of the inflatable balloon is fixed to a
region of parallel tube 124 and elongate shaft 104 to form a
proximal balloon joint. In one embodiment, the length of the
proximal balloon joint ranges from 2-4 mm. The length from the
proximal end of the proximal balloon joint till the proximal end of
parallel tube 124 may range from 2-3 cm. The length from the distal
end of the distal balloon joint till the distal end of parallel
tube 124 may range from 1-2 mm. Substance delivery device 118 may
comprise a marker 126 to allow the position of substance delivery
device 118 to be tracked in the anatomy. In the example shown in
FIG. 2A, marker 126 is a radiopaque marker. In one embodiment, the
length of substance delivery device 118 measured from the distal
end of hub 112 till the distal end of parallel tube 124 is around
30 cm.
[0108] FIGS. 2B, 2C and 2D show cross sections of the device shown
in FIG. 2A through the planes 2B-2B, 2C-2C and 2D-2D respectively.
FIG. 2B shows a cross section of parallel tube 124. FIG. 2C shows a
cross section of elongate shaft 104 and parallel tube 124. FIG. 2D
shows a cross section of second tube 122.
[0109] Various novel elastomeric sleeve valves may be used to
design the various embodiments of the substance delivery devices
disclosed herein. Such elastomeric sleeve valves comprise a sleeve
or tubular piece of an elastomeric substance that is located near
an opening of a reservoir filling lumen. For example, FIGS. 2E and
2F show longitudinal cross sections of an embodiment of a substance
delivery device comprising a coaxial filling lumen and an
elastomeric sleeve valve. Substance delivery device 127 of FIG. 2E
comprises a substance reservoir 106. Substance reservoir 202
comprises a means for delivering a stored substance to the
surrounding anatomy over a period of time. In the example shown in
FIG. 2E, substance reservoir 106 is an inflatable balloon. The
length of the inflatable balloon may range from 10-20 mm. The
inflated diameter of the inflatable balloon ranges preferably from
7-10 mm. The inflatable balloon is preferably made from suitable
elastomeric materials including, but not limited to low density
polyethylene, low durometer Pebax, polyurethane, etc. Substance
delivery device 126 further comprises a coaxial tube comprising an
outer tube 128 and an inner tube 130. Inner tube 130 comprises a
first lumen 132. The region between outer tube 128 and inner tube
130 encloses a coaxial second lumen 134. In one embodiment, second
lumen 134 is a substance introducing lumen used to fill substance
reservoir 106. Substance delivery device 126 further comprises a
second tube 136. The region between the inner surface of second
tube 136 and the outer surface of the coaxial tube encloses a third
lumen 138. In the example shown in FIG. 2E, the proximal end of the
inflatable balloon is attached to a distal region of second tube.
The distal end of the inflatable balloon is attached to the distal
region of inner tube 130. Substance delivery device 126 further
comprises a one way elastomeric sleeve valve 140. In the example
shown in FIG. 2E, valve 140 comprises an elongate tube enclosing a
lumen. Valve 140 can be made of suitable biocompatible materials
including, but not limited to C-flex.TM., Kraton.TM., polyurethane,
LDPE, silicone, EVA, other thermoplastic elastomers, etc. The one
end of valve 140 is attached to a region of outer tube 128 by a
fluid tight seal. The other end of valve is unattached. The
unattached region of valve 140 compresses on the outer surface of
inner tube 130 to seal second lumen 134 from third lumen 138. In
FIG. 2E, a user introduces a substance in second lumen 134 under
pressure. The pressure from second lumen 134 causes the unattached
region of valve 140 to expand as shown. This causes the substance
to travel from second lumen 134 to third lumen 138 and fills
substance reservoir 106. In FIG. 2F, the introduction of the
substance into second lumen 134 is stopped. This releases the
pressure on valve 140 from second lumen 134. Thus the unattached
region of valve 140 compresses on the outer surface of inner tube
130. This seals second lumen 134 from third lumen 138 thereby
preventing the emptying of substance reservoir 106 through second
lumen 134. First lumen 132 may be used to introduce substance
delivery device 126 into the anatomy over an introducing device
such as a guidewire.
[0110] The shafts of the substance delivery devices disclosed
herein may comprise one or more valves present in the region
enclosed by a substance reservoir. For example, FIGS. 2G and 2H
show cross sections through a portion of a substance delivery
device comprising an elastomeric sleeve valve located in a region
of an elongate shaft enclosed by a substance reservoir. FIG. 2G
shows a cross sectional view of a drug delivery device 144
comprising an elongate shaft 104. Elongate shaft 104 may be made of
suitable biocompatible materials including, but not limited to
Pebax, PEEK, Nylon, polyethylene, etc. Elongate shaft 104 encloses
a substance introducing lumen 146. A distal region of lumen 146 is
blocked by a plug 148. A substance reservoir 106 is located on a
distal region of elongate shaft 104. In the example shown in FIG.
2G, substance delivery reservoir comprises an inflatable balloon.
The inflatable balloon is preferably made from suitable elastomeric
materials including, but not limited to low density polyethylene,
low durometer Pebax, polyurethane, etc. Lumen 146 is in fluid
communication with substance reservoir 106 through one or more
first openings or pores 150. Lumen 146 may thus be used to fill
substance reservoir 106 with a suitable substance. An elastomeric
sleeve valve 152 is located near first openings or pores 150. Valve
152 allows the substance to flow from lumen 146 to substance
reservoir 106. Also, valve 152 prevents or substantially reduces
the flow of the substance from substance reservoir 106 to lumen
146. In the example shown in FIG. 2G, valve 152 comprises an
elongate tube enclosing a lumen. Valve 152 can be made of suitable
biocompatible materials including, including, but not limited to
C-flex.TM., Kraton.TM., polyurethane, LDPE, silicone, EVA, other
thermoplastic elastomers, etc. One end of valve 152 is attached to
a region of elongate tube 104 by a fluid tight seal. The other end
of valve 152 is unattached. The unattached region of valve 152
compresses on the outer surface of elongate tube 104 to seal
substance reservoir 106 from lumen 146. In FIG. 2G, a user
introduces a substance in lumen 146 under pressure. The pressure
from lumen 146 causes the unattached region of valve 152 to expand
as shown. This causes the substance to flow from lumen 146 to
substance reservoir 106. In FIG. 2H, the introduction of the
substance into lumen 146 is stopped. This releases the pressure on
valve 152 from lumen 146. Thus the unattached region of valve 152
compresses on the outer surface of elongate tube 104. This seals
lumen 146 from substance reservoir 106 thereby preventing or
substantially reducing the flow of the substance from substance
reservoir 106 to lumen 146. The substance stored in substance
reservoir 106 is controllably released into the surrounding anatomy
through a substance delivery mechanism. In the example shown in
FIGS. 2G and 2H, the substance delivery mechanism comprises one or
more second openings or pores 154 that create a fluid communication
between substance reservoir 106 and lumen 146. The distal end of
lumen 146 opens into the surrounding anatomy such that the
substance flows from substance reservoir 106 to the surrounding
anatomy.
[0111] Valve 140 and valve 152 are made from elastomeric materials
including, but not limited to C-flex.TM., Kraton.TM., polyurethane,
LDPE, silicone, etc. The preferred thickness of the wall of the
material of valve 140 and valve 152 ranges from 0.001 inches to
0.008 inches. The preferred longitudinal length of valve 140 and
valve 152 ranges from 4-10 mm. Valve 140 and valve 152 may attached
to an outer surface of elongate shafts by a variety of attachment
mechanisms. In one embodiment of an attachment mechanism, valve 140
and valve 152 are attached by suitable biocompatible adhesives. For
example, an adhesive such as Loctite.RTM. 4011 may be used with or
without primers such as Loctite.RTM. 7701. In another embodiment of
an attachment mechanism, valve 140 and valve 152 are attached to
the elongate shafts by the mechanical compressive force of the
elastomeric material of the valves. In another embodiment of an
attachment mechanism, a cylindrical piece of heat-shrink tubing is
clamped around a region of valve 140 and valve 152. In another
embodiment of an attachment mechanism, valve 140 and valve 152 are
laser welded or thermally welded to the elongate shafts.
[0112] The substance delivery devices disclosed herein may comprise
various types of one-way valves. Such one-way valves enable a user
to fill a substance reservoir with a suitable substance, but
prevent the backflow of the substance after the substance reservoir
is filled. For example, FIGS. 2I and 2J show a partial view of a
region of a substance delivery device comprising a duck-bill valve.
FIG. 2I shows a region of a substance delivery device 158
comprising a hollow shaft 160. Hollow shaft 160 encloses a
reservoir filling lumen. A duck-bill valve 162 is provided in the
substance introducing lumen of hollow shaft 160. Duck-bill valve
162 comprises a hollow body 164 enclosing a lumen. The distal
region of duck-bill valve 162 comprises two or more leaflets 166.
In one embodiment, duck-bill valve 162 is attached to the inner
surface of hollow shaft 160 by a suitable adhesive. In the
embodiment shown in FIG. 2I, the inner surface of hollow shaft 160
comprises a notch 168. An outer region of hollow body 164 of
duck-bill valve 162 is locked in notch 168 as shown to attach
duck-bill valve 162 to hollow shaft 160. Duck-bill valve 162 allows
the flow of a fluid in the distal direction along hollow shaft 160.
This enables a user to fill a substance reservoir located distal to
duck-bill valve 162. Duck-bill valve 162 prevents the flow of fluid
in the proximal direction along hollow shaft 160. This prevents
unwanted drainage of the fluid substance from the substance
reservoir through hollows shaft 160. FIG. 2J shows the step of
filling the substance reservoir of substance delivery device 158 by
inserting a fluid substance through the proximal region of hollow
shaft 160. The pressure of the fluid substance spreads apart two or
more leaflets 166 to open duck-bill valve 162. This allows the flow
of the fluid substance in the distal direction along hollow shaft
160. Duck-bill valve 162 may be made from suitable biocompatible
materials including, but not limited to elastomeric materials such
as silicone, fluorosilicone, etc. In one embodiment, duck-bill
valve 162 is made from a single piece of a suitable material.
[0113] FIGS. 2K and 2L show a partial view of a region of a
substance delivery device comprising a dome valve. FIG. 2K shows a
region of a substance delivery device 170 comprising a hollow shaft
172. Hollow shaft 172 encloses a reservoir filling lumen. A dome
valve 174 is provided in the lumen of hollow shaft 172. Dome valve
174 comprises a hollow body 176 enclosing a lumen. The distal
region of dome valve 174 comprises a dome 178. One or more slits
180 are located in the distal most region of dome 178. To introduce
a fluid substance in the lumen of hollow shaft 172 distal to dome
valve 174, a user inserts an injecting device through slits 180 as
shown in FIG. 2L. In the embodiment shown in FIGS. 2K and 2L, the
injecting device comprises a hollow shaft 182 enclosing a lumen.
Hollow shaft 182 comprises an atraumatic distal end. Hollow shaft
182 further comprises an opening or pore 184 that creates a fluid
communication between the lumen of hollow shaft 182 and the
exterior of hollow shaft 182. Slits 180 allow the passage of the
injecting device through them while maintaining a substantial fluid
seal around the injecting device. The user can then introduce the
fluid substance through the lumen of the injecting device to fill a
substance reservoir located distal to dome valve 174. After the
injecting device is withdrawn, dome valve 174 prevents the flow of
fluid in the proximal direction along hollow shaft 172. This
prevents unwanted drainage of the fluid substance from the
substance reservoir through hollows shaft 172. In one embodiment,
dome valve 174 is attached to the inner surface of hollow shaft 172
by a suitable adhesive. In the embodiment shown in FIGS. 2K and 2L,
the inner surface of hollow shaft 172 comprises a notch 186. An
outer region of hollow body 176 of dome valve 174 is locked in
notch 186 as shown to attach dome valve 174 to hollow shaft 172.
Dome valve 174 may be made from suitable biocompatible materials
including, but not limited to elastomeric materials such as
silicone, fluorosilicone, etc. In one embodiment, dome valve 174 is
made from a single piece of a suitable material.
[0114] Similarly, substance delivery devices disclosed herein may
comprise a variety of valves to allow a user to fill a substance
reservoir located distal to the valves while preventing unwanted
drainage of the fluid substance from the substance reservoir.
Examples of such valves include, but are not limited to cross slit
valves, umbrella valves, combinations of umbrella valve and
duck-bill valve, valve balls, etc.
[0115] The shafts of the substance delivery devices disclosed
herein may comprise various filling mechanisms to fill one or more
substance reservoirs located distal to the filling mechanisms
without leakage of the substance from the shafts. Such filling
mechanisms may comprise a self-sealing membrane located proximal to
the substance reservoirs. For example, FIGS. 2M and 2N show
longitudinal sections through the filling mechanism of an
embodiment of a substance delivery device comprising a self-sealing
membrane. Substance delivery device 190 of FIGS. 2M and 2N
comprises a hollow shaft 104. Hollow shaft 104 encloses a reservoir
filling lumen. A proximal region of the lumen of hollow shaft 104
is plugged by a self sealing membrane 192. Self-sealing membrane
192 may be made of suitable biocompatible materials including, but
not limited to silicone elastomers. Substance delivery device 190
further comprises a substance reservoir located distal to self
sealing membrane 192. In FIG. 2M, substance delivery device 190 is
introduced into the anatomy. In the embodiment shown in FIGS. 2M
and 2N, substance delivery device 190 is introduced into the
anatomy by a proximal shaft 110 that pushes hollow shaft 104 in the
distal direction. Proximal shaft 110 comprises a lumen. An
injecting device 194 is introduced through the lumen of proximal
shaft 110. The distal tip of injecting device 194 punctures
self-sealing membrane 192 and enters the region distal to
self-sealing membrane 192. Self-sealing membrane 192 allows the
passage of injecting device 194 while maintaining a substantial
fluid seal around injecting device 194. Injecting device 194 may
thereafter be used to introduce a fluid substance in the region
distal to self-sealing membrane 192. Thus, injecting device 194 may
be used to fill a substance reservoir located distal to
self-sealing membrane 192. In FIG. 2N, injecting device 194 is
pulled in the proximal direction and removed from self-sealing
membrane 192. The area where injecting device 194 had punctured
self-sealing membrane 192 seals itself due to the self-sealing
property of self-sealing membrane 192. This prevents unwanted
drainage of the fluid substance through the proximal end of hollow
shaft 104.
[0116] The substance delivery devices disclosed herein may comprise
various plugging mechanisms to plug a lumen of a filling lumen
after filling a substance reservoir through the filling lumen. For
example, FIGS. 2O and 2P show longitudinal sectional views of a
region of an embodiment of a substance delivery device comprising a
plugging mechanism. Substance delivery device 196 of FIGS. 2O and
2P comprises an elongate shaft 104 enclosing a reservoir filling
lumen. The filling lumen may be used to fill one or more substance
reservoirs located in the distal region of elongate shaft 104. A
proximal region of elongate shaft 104 comprises a port 198
enclosing a lumen. In one embodiment, port 198 is made by locally
reducing the diameter of elongate shaft 104. In another embodiment,
port 198 is made of suitable biocompatible materials including, but
not limited to silicone rubber, thermoplastic elastomers, etc. An
injecting tube 200 is inserted through port 198. The outer diameter
of injecting tube 200 is approximately equal to the inner diameter
of the lumen enclosed by port 198. This creates a substantial fluid
seal between the outer surface of injecting tube 200 and the inner
surface of the lumen enclosed by port 198. Injecting tube 200
encloses a lumen that is in fluid communication with the exterior
of injecting tube 200 through an opening or pore 202. The distal
end of the lumen of injecting tube 200 is plugged by a suitable
plug 204. Plug 204 is frictionally attached to a surface of
injecting tube 200. The outer diameter of plug 204 is greater than
the inner diameter of the lumen enclosed by port 198. Plug 204 may
be made of suitable biocompatible materials including, but not
limited to silicone rubber, thermoplastic elastomers, etc. In FIG.
2O, substance delivery device 196 is introduced into the anatomy.
In the embodiment shown in FIGS. 2O and 2P, substance delivery
device 196 is introduced into the anatomy by a proximal shaft 110
that pushes elongate shaft 104 in the distal direction. In FIG. 2O,
a user injects a fluid substance through injecting device 200 in
the region distal to port 198. This step may be used to fill a
substance reservoir located distal to port 198. In FIG. 2P, the
user pulls injecting device 200 in the proximal direction. This
causes plug 204 to plug the lumen enclosed by port 198 as shown in
FIG. 2P. When injecting device 200 is pulled further in the
proximal direction, plug 204 detaches from injecting device 200.
Thus the proximal end of the filling lumen is plugged by plug 204.
This prevents or reduces leakage of the fluid substance through the
proximal end of the filling lumen. Similarly, various other
embodiments of plugging mechanisms may be used to prevent or reduce
leakage of the fluid substance through the proximal end of the
filling lumen.
[0117] In an alternate embodiment, plug 204 is located on the inner
surface of the filling lumen of elongate shaft 104. Plug 204
comprises a swellable material that swells and increase in volume
on coming into contact with the fluid substance. Plug 204 then
occludes the filling lumen of elongate shaft 104 thereby preventing
the leakage of the fluid substance from the proximal end of
elongate shaft 104.
[0118] The substance delivery devices disclosed herein may be
introduced into the anatomy by a variety of introducing devices
comprising means for controllably deploying the substance delivery
devices from the introducing devices. For example, FIGS. 3A and 3B
show a longitudinal section through a proximal region of a
substance delivery device deployed by a pushing tube similar to
pushing tube 114 of FIG. 1. FIG. 3A shows the proximal region of a
substance delivery device 100. In the embodiment substance delivery
device comprises an elongate shaft 104 comprising a reservoir
filling lumen. Elongate shaft 104 may be constructed from suitable
biocompatible materials including, but not limited to metals,
polymers, etc. The proximal region of elongate shaft 104 slides
over the distal region of an elongate shaft 110 of an introducing
device 102. The inner surface of elongate shaft 104 frictionally
attaches to the outer surface of elongate shaft 110. This
frictional attachment is strong enough to prevent detachment of
substance delivery device 100 from introducing device 102 while
inserting and navigating substance delivery device 100 through the
anatomy. A pushing tube 114 slides on the outer surface of elongate
shaft 110 proximal to the proximal end of elongate shaft 104.
Pushing tube 114 can be moved over the outer surface of elongate
shaft 110 by a user. In the step of deploying substance delivery
device 100 from introducing device 102, the user pushes pushing
tube 114 over the outer surface of elongate shaft 110 in the distal
direction as shown in FIG. 3B. The distal end of pushing tube 114
pushes the proximal end of elongate shaft 104 to overcome the
frictional attachment between the inner surface of elongate shaft
104 and the outer surface of elongate shaft 110. This causes
elongate shaft 104 to be released from elongate shaft 110. Thereby,
substance delivery device 100 is deployed from introducing device
102.
[0119] In an alternate means for controllably deploying the
substance delivery devices, a substance delivery device is deployed
by withdrawing a filling device from the substance delivery device.
Three embodiments of this mechanism are illustrated in FIGS. 2K-2L,
2M-2N and 2O-2P.
[0120] In an alternate means for controllably deploying the
substance delivery devices, the substance delivery devices are
deployed by cutting or severing a region of the substance delivery
devices. This causes the portion of the substance delivery device
distal to the severed region to be deployed in the anatomy.
[0121] The various methods and devices disclosed herein may be used
to delivery one or more substances to various regions in the head
and neck as shown in FIGS. 4A-4E and 4A'-4E'. Examples of such
regions include, but are not limited to paranasal sinuses,
Eustachian tubes, middle ear regions, etc. FIGS. 4A through 4E show
a coronal view of a human head showing the various steps of a
method of delivering an implantable substance delivery device to
one of the paranasal sinuses of a patient. In this example, a
frontal sinus FS is used as an example of a paranasal sinus.
Methods similar to those shown in FIGS. 4A through 4E may be used
to deliver a substance delivery device in other paranasal sinuses
or other spaces or cavities in the head. The substance delivery
devices may be introduced along introducing devices such as
guidewires, guide catheters, etc. For example, in FIG. 4A, a
guidewire GW is introduced through a nostril of the patient. The
distal end of the guidewire is navigated through the anatomy such
that the distal end of the guidewire enters a paranasal sinus. This
may be done by one or more methods disclosed in U.S. patent
application Ser. Nos. 10/829,917; 10/912,578; 11/037,548 and
i0/944,270, the entire disclosures of which are expressly
incorporated herein by reference. Thereafter, in FIG. 4B, a
substance delivery device 100 is introduced over the guidewire GW
into the frontal sinus. In the embodiment shown in FIG. 4B,
substance delivery device 100 comprises an elongate shaft 104 and a
substance reservoir 106. In the example shown, substance delivery
device 100 comprises a rapid exchange lumen which allows substance
delivery device 100 to be introduced over guidewire GW.
Alternatively substance delivery device 100 may comprise an
end-to-end guidewire lumen. In FIG. 4B, the proximal end of
substance delivery device 100 is connected to the distal end of a
removable delivery catheter 102. In the embodiment shown, delivery
and inflation device 114 comprises an elongate tube 114 comprising
a lumen. The distal end of the lumen of elongate tube 114 is in
fluid communication with the proximal end of a substance
introducing lumen in elongate shaft 104. The proximal end of the
lumen of elongate tube 114 is in fluid communication with a hub
112. A suitable syringe can be connected to hub 112 to inject a
substance into reservoir 106 of substance delivery device 100. In
the step shown in FIG. 4C, the guidewire GW is removed from the
anatomy. In the step shown in FIG. 4D, reservoir 106 is filled with
a substance through a syringe connected to hub 112. In the step
shown in FIG. 4E, the proximal end of substance delivery device 100
is detached from the distal end of delivery catheter 102 thereby
implanting substance delivery device 100 in the anatomy.
Thereafter, delivery catheter 102 is removed from the anatomy.
Substance delivery device 100 may be placed in the anatomy for a
period ranging from 0.5 hours to 60 days after which it may be
removed.
[0122] In another example, FIGS. 4A' through 4E' show a coronal
view of a human head showing the various steps of an embodiment of
a method of delivering an implantable substance delivery device to
a Eustachian tube or middle ear of a patient. The method is
performed by inserting a substance delivery device through the
pharyngeal ostium of the Eustachian tube. Methods similar to those
shown in FIGS. 4A' through 4E' may be used to deliver one or more
substances to the Eustachian tubes or various regions of the middle
or inner ear of patients. Examples of such inner ear regions
include, but are not limited to cochlea, vestibule, etc. The
substance delivery devices may be introduced along introducing
devices such as guidewires, guide catheters, etc. For example, in
FIG. 4A', a guidewire GW is introduced through a nostril of the
patient. The distal end of the guidewire is navigated through the
anatomy such that the distal end of the guidewire enters a
Eustachian tube through the pharyngeal ostium of the Eustachian
tube. This may be done by one or more methods disclosed in U.S.
patent application Ser. Nos. 10/829,917; 10/912,578; 11/037,548 and
i0/944,270, the entire disclosures of which are expressly
incorporated herein by reference. In a particular embodiment, the
guidewire GW is introduced through a guide catheter. Thereafter, in
FIG. 4B', a substance delivery device 100 is introduced over the
guidewire GW into the Eustachian tube. In the embodiment shown in
FIG. 4B', substance delivery device 100 comprises an elongate shaft
104 and a reservoir 106. In the example shown, substance delivery
device 100 comprises a rapid exchange lumen which allows substance
delivery device 100 to be introduced over guidewire GW.
Alternatively substance delivery device 100 may comprise an
end-to-end guidewire lumen. In FIG. 4B', the proximal end of
substance delivery device 100 is connected to the distal end of a
removable delivery catheter 102. In the embodiment shown, delivery
catheter 102 comprises an elongate tube 114 comprising a lumen. The
distal end of the lumen of elongate tube 114 is in fluid
communication with the proximal end of a substance introducing
lumenin elongate shaft 104. The proximal end of the lumen of
elongate tube 114 is in fluid communication with a hub 112. A
suitable syringe can be connected to hub 112 to inject a substance
into reservoir 106 of substance delivery device 100. In the step
shown in FIG. 4C', the guidewire GW is removed from the anatomy. In
the step shown in FIG. 4D', reservoir 106 is filled with a
substance through a syringe connected to hub 112. In the step shown
in FIG. 4E, the proximal end of substance delivery device 100 is
detached from the distal end of delivery catheter 102 thereby
implanting substance delivery device 100 in the anatomy.
Thereafter, delivery catheter 102 is removed from the anatomy.
Substance delivery device 100 may be placed in the anatomy for a
period ranging from 0.5 hours to 60 days after which it may be
removed.
[0123] Similar methods may be used to deliver a substance delivery
device to a naso-lachrymal duct of a human or animal subject to
deliver a substance to the naso-lachrymal duct.
[0124] The guidewires disclosed herein may comprise one or more
anchors to temporarily anchor the guidewires to an anatomical
region. Examples of such anchors include, but are not limited to
anchoring balloons, notches on the guidewires, bent regions on the
guidewires, self expanding elements, hooks, coiled elements, etc.
The guidewires disclosed herein may comprise one or more sensors
located on the distal region of the guidewires. The sensors enable
the guidewires to be used in conjunction with suitable surgical
navigation systems. In one embodiment, the sensor is an
electromagnetic sensor used in conjunction with an electromagnetic
surgical navigation system such as GE InstaTrak.TM. 3500 plus
system etc. One or more sensors or other types of surgical
navigation sensors or transmitters may also be located on other
diagnostic or therapeutic devices disclosed herein.
[0125] The various substance reservoirs disclosed herein may be
inflatable or non-inflatable. Inflatable substance reservoirs may
be made of suitable balloons. The balloons may be made of various
shapes including, but not limited to the balloon shapes disclosed
herein and in the patent documents incorporated herein by
reference. The balloons may be designed to also function as
anchoring mechanisms to anchor the substance reservoir to the
anatomy. Such anchoring is especially useful when the substance
reservoirs are inserted into hollow regions such as paranasal
sinuses. FIGS. 4F through 4L show various embodiments of substance
reservoirs that can be used to design the various substance
delivery devices disclosed herein. FIG. 4F shows a perspective view
of an embodiment of an inflatable substance reservoir comprising an
inflatable balloon comprising two or more lobes. FIG. 4F shows a
region of a substance delivery device 210 comprising an inflatable
balloon 212 comprising two or more lobes 214. Such a balloon shape
comprising two or more lobes is useful to allow drainage of
secretions when the balloon is placed in an anatomical region. For
example, when inflatable balloon 212 is placed in a paranasal sinus
through an ostium of the paranasal sinus, lobes 214 allows sinus
secretions to flow between the lobes of the balloon and out of the
ostium of the paranasal sinus. Inflatable balloon 212 may be made
of suitable compliant, non-compliant or semi-compliant
biocompatible materials. Examples of such materials include, but
are not limited to polyurethane, silicone, Nylon, PET,
polyethylene, PVC, etc. Inflatable balloon 212 is inflated by a
substance introducing lumen in elongate shaft 104. FIG. 4G shows a
cross section of inflatable balloon 212 shown in FIG. 4F through
the plane 4G-4G. FIG. 4G shows inflatable balloon 212 comprising
multiple lobes 214. In the example shown in FIGS. 4F and 4G, the
substance reservoir comprised a balloon having 10 lobes. Similarly
other substance reservoirs may be designed comprising a balloon
having two or more lobes.
[0126] FIG. 4H shows a perspective view of an embodiment of an
inflatable substance reservoir comprising a spiral inflatable
balloon. FIG. 4F shows a region of a substance delivery device 218
comprising a spiral inflatable balloon 220. Such a spiral balloon
is useful to allow drainage of secretions when the balloon is
placed in an anatomical region. For example, when the balloon is
placed in a paranasal sinus through an ostium of the paranasal
sinus, a spiral balloon allows sinus secretions to flow between
adjacent turns of the spiral balloon and out of the ostium of the
paranasal sinus. Inflatable balloon 220 may be made of suitable
compliant, non-compliant or semi-compliant biocompatible materials.
Examples of such materials include, but are not limited to
polyurethane, silicone, Nylon, PET, polyethylene, PVC, etc.
Inflatable balloon 220 is inflated by an elongate shaft 104.
[0127] The inflatable substance reservoirs disclosed herein may
comprise one or more radial protrusions. For example, FIG. 4I shows
a perspective view of a region of a substance delivery device
comprising an inflatable balloon having one or more radial
protrusions. Substance delivery device 222 comprises an inflatable
balloon 224. The inflatable balloon 224 comprises one or more
radial protrusions 226. Radial protrusions 226 are oriented
radially to the axis of inflatable balloon 224. Radial protrusions
226 may be inflatable or non-inflatable. This increases the profile
of inflatable balloon 224 when inflatable balloon 224 is inflated.
Such a balloon comprising one or more radial protrusions is useful
to allow drainage of secretions when the balloon is placed in an
anatomical region. For example, when balloon 224 is placed in a
paranasal sinus through an ostium of the paranasal sinus, balloon
224 allows sinus secretions to flow between adjacent protrusions
226 and out of the ostium of the paranasal sinus. Protrusions 226
also help to anchor balloon 224 to the surrounding anatomy.
Inflatable balloon 224 may be made of suitable compliant,
non-compliant or semi-compliant biocompatible materials. Examples
of such materials include, but are not limited to polyurethane,
silicone, Nylon, PET, polyethylene, PVC, etc. Inflatable balloon
224 is inflated by a substance introducing lumenin elongate shaft
104.
[0128] The inflatable substance reservoirs disclosed herein may
comprise a balloon oriented transversely to the axis of an
inflating shaft. For example, FIG. 4J shows a perspective view of a
region of a substance delivery device comprising an inflatable
balloon oriented transversely to the axis of the substance delivery
device. In FIG. 4J, a substance delivery device 228 is inserted
through a paranasal sinus ostium into a paranasal sinus. Substance
delivery device 228 comprises an elongate inflatable balloon 230.
The axis of inflatable balloon is substantially perpendicular to
the axis of substance delivery device 228. This increases the
profile of inflatable balloon 230 when inflatable balloon 230 is
inflated. This helps to anchor balloon 242 to the surrounding
anatomy while still allowing secretions to flow around balloon 230.
Inflatable balloon 230 may be made of suitable compliant,
non-compliant or semi-compliant biocompatible materials. Examples
of such materials include, but are not limited to polyurethane,
silicone, Nylon, PET, polyethylene, PVC, etc. Inflatable balloon
230 is inflated by a substance introducing lumen in elongate shaft
231.
[0129] The inflatable substance reservoirs disclosed herein may
comprise a balloon having one or more vents to prevent vacuum
formation inside a substance reservoir. For example, FIG. 4K shows
a side view of a region of an inflatable substance reservoir
comprising a balloon with one or more pores and a vent. FIG. 4K
shows a substance delivery device 232 comprising an inflatable
balloon 234 that acts as a substance reservoir. Inflatable balloon
234 may be made of suitable non-compliant or semi-compliant
biocompatible materials. Examples of such materials include, but
are not limited to polyurethane, Nylon, PET, polyethylene, PVC,
etc. Inflatable balloon 234 is inflated by an elongate shaft 104
comprising a reservoir filling lumen. The lumen of elongate shaft
104 is in fluid communication with inflatable balloon 234.
Inflatable balloon 234 comprises one or more pores 236. The
substance stored in inflatable balloon 234 is delivered through
pores 236 into the surrounding anatomy. Thus, the volume of the
substance stored in inflatable balloon 234 gradually reduces. This
process gradually creates a vacuum inside inflatable balloon 234.
The vacuum prevents or reduces the delivery of the substance stored
in inflatable balloon 234 through pores 236. In order to prevent or
reduce the formation of the vacuum, substance delivery device 232
further comprises a vent 238. Vent 238 allows air to enter
inflatable balloon 234. This air replaces the amount of substance
lost through pores 236 and thus prevents the formation of a vacuum
in inflatable balloon 234. This in turn maintains the rate of
delivery of the substance stored in inflatable balloon 234 through
pores 236.
[0130] The distal end of one or more substance delivery devices
disclosed herein may be designed to prevent or reduce trauma to the
surrounding anatomy. In the embodiments of substance delivery
devices comprising an inflatable substance reservoir, a portion of
the inflatable reservoir may be designed to generate an atraumatic
distal region. For example, FIG. 4L shows a section through a
substance delivery device comprising an inflatable substance
delivery reservoir shaped to produce an atraumatic distal end. In
FIG. 4L, substance delivery device 240 comprises an inflatable
balloon 242 that acts as a substance reservoir. Inflatable balloon
242 may be made of suitable compliant, non-compliant or
semi-compliant biocompatible materials. Examples of such materials
include, but are not limited to polyurethane, silicone, Nylon, PET,
polyethylene, PVC, etc. Inflatable balloon 242 is inflated through
an elongate shaft 104 comprising a reservoir filling lumen. The
lumen of elongate shaft 104 is in fluid communication with balloon
242 through a shaft opening 244. A distal region of elongate shaft
104 is plugged or blocked by a plug 246. Inflatable balloon 242 may
further comprise one or more pores 248 that are in fluid
communication with the exterior of inflatable balloon 242.
Substance delivery device 240 may deliver a substance to the
surrounding anatomy through pores 248. Inflatable balloon 242 is
connected to elongate shaft 104 at a proximal region and at a
distal region of inflatable balloon 242. The distal region of
inflatable balloon 242 is everted and connected to elongate shaft
104 as shown in FIG. 4L. Thus, when inflatable balloon 242 is
inflated, a distal region of inflatable balloon 104 protrudes
distal to the distal end of elongate shaft 104 as shown in FIG. 4L.
This creates an atraumatic distal end of substance delivery device
240.
[0131] The one or more pores on the inflatable substance reservoirs
such as the inflatable substance reservoirs disclosed in FIGS. 4K
and 4L may be created by laser drilling the surface of the
materials of the inflatable substance reservoirs. In one example of
a method of creating the one or more pores, an Excimer laser is
used to create pores. The Excimer laser may be used to create pores
of a pore size ranging from about 20 microns to about 200 microns.
Inflatable balloon 234 and inflatable balloon 242 of FIGS. 4K and
4L respectively may have a balloon diameter ranging from around
7-10 mm and balloon length ranging from around 10-20 mm. The
balloon wall thickness may range from around 0.001-0.003 inches.
The number and pore size of the one or more pores and the balloon
wall thickness may be designed to avoid jetting of the substance
stored in the inflatable substance reservoirs through the one or
more pores.
[0132] One or more substance delivery devices disclosed herein may
comprise more than one substance reservoirs that are inflated
through one or more reservoir filling lumens. Also, one or more
substance reservoirs disclosed herein may act as anchors to prevent
or reduce relative motion between the substance delivery devices
and regions of the anatomy. For example, FIG. 4M shows a cross
section through a substance delivery device comprising two
substance reservoirs that also act as anchors. Substance delivery
device 250 of FIG. 4M comprises an outer tube 252 and an inner tube
254 enclosed by outer tube 252. Outer tube 252 and inner tube 254
may be made of suitable biocompatible materials including, but not
limited to Pebax, PEEK, Nylon, polyethylene, polyurethane,
polyethylene terephthalate, etc. Inner tube 254 encloses an inner
lumen 256. The annular region between the outer surface of inner
tube 254 and the inner surface of outer tube 252 forms an outer
lumen 258. The distal end of outer lumen 258 is plugged by an
annular plug 260. Inner tube 254 comprises a first opening or pore
262 located distal to the distal end of outer tube 252. First
opening or pore 262 creates a fluid communication between inner
lumen 256 and a distal balloon 264. Thus, inner lumen 256 may be
used to inflate distal balloon 264 with a suitable fluid substance.
A distal region of distal balloon 264 is attached to the outer
surface of inner tube 254 and a proximal region of distal balloon
264 is attached to the outer surface of outer tube 252 as shown. A
region of outer tube 252 proximal to annular plug 260 comprises a
second opening or pore 266. Second opening or pore 266 creates a
fluid communication between outer lumen 258 and a proximal balloon
268. Thus, outer lumen 258 may be used to inflate proximal balloon
268 with a suitable fluid substance. Outer lumen 258 and inner
lumen 256 may be provided with valves, plugging mechanisms, etc.
disclosed elsewhere in this patent application to prevent the
leakage of the fluid substance from the proximal ends of outer
lumen 258 and inner lumen 256. In one method embodiment, substance
delivery device 250 is introduced through an anatomical opening
such as a paranasal sinus ostium. Substance delivery device 250 is
positioned such that distal balloon 264 lies distal to the
anatomical opening and proximal balloon 268 lies proximal to the
anatomical opening. Thereafter, both distal balloon 264 and
proximal balloon 268 are inflated. Both distal balloon 264 and
proximal balloon 268 acts as anchors and prevent or reduce the
motion of substance delivery device 250 relative to the anatomical
opening. In the embodiment shown in FIG. 4M, distal balloon 262 and
proximal balloon 268 are inflated by two separate lumens. In an
alternate embodiment, distal balloon 262 and proximal balloon 268
are inflated by a single lumen.
[0133] Although the substance reservoirs disclosed herein are
mostly illustrated as inflatable balloons, the substance delivery
devices disclosed herein may comprise several other embodiments of
substance reservoirs. For example, the substance reservoirs
disclosed herein may comprise an absorbent element. Examples of
such absorbent elements include, but are not limited to foams,
fibrous elements, etc. FIG. 4N shows a partial view of an
embodiment of a substance delivery device comprising a substance
reservoir made of foam. Substance delivery device 270 of FIG. 4N
comprises an elongate shaft 104. Elongate shaft 104 comprises a
reservoir filling lumen. The filling lumen is in fluid
communication with a substance reservoir 272 located on the distal
region of elongate shaft 104. The filling lumen may be used to
introduce a suitable substance into substance reservoir 272 before
or after insertion of substance delivery device 270 into the
anatomy. Substance reservoir 272 may be made from suitable
biocompatible foam materials including, but not limited to
polyvinyl acetate, polyurethane, polylactides, carboxymethylated
cellulose, polyethylene, silicone, biodegradable materials such as
gelatin, fibers such as cotton, etc. Substance reservoir 272 may be
connected to a controlled delivery element. The controlled delivery
element may be used to deliver the substance in substance reservoir
272 to the surrounding anatomy at a controlled rate over a desired
period of time. In one embodiment, the controlled delivery element
comprises a membrane located on the outer surface of substance
reservoir 272. The membrane regulates the delivery of the substance
from substance reservoir 272 to the surrounding anatomy. Substance
reservoir 272 may be enclosed in a series of struts that contain
substance reservoir 272. In one embodiment, the struts are
substantially parallel to elongate shaft 104.
[0134] One or more of the drug delivery devices disclosed herein
may comprise a controlled substance release mechanism to
controllably release a substance from a substance reservoir into
the surrounding anatomy over a period of time. In one embodiment,
the controlled substance release mechanism comprises a pressuring
mechanism that exerts a pressure on the substance reservoir to
squeeze the substance out of the substance reservoir into the
surrounding anatomy. The pressuring mechanism may be designed to
exert a fairly constant pressure over the treatment duration.
[0135] One example of a pressuring mechanism is shown in FIG. 5A.
FIG. 5A shows a sectional view of an embodiment of a substance
delivery device comprising a pressure exerting mechanism. The
design of substance delivery device 276 of FIG. 5A is similar to
the design of substance delivery substance 240 of FIGS. 2G and 2H.
Drug delivery device 276 comprises an elongate shaft 278. Elongate
shaft 278 may be made of suitable biocompatible materials
including, but not limited to Pebax, PEEK, Nylon, polyethylene,
etc. Elongate shaft 278 encloses a substance introducing lumen 280.
A distal region of lumen 280 is blocked by a plug 232. A substance
reservoir 282 is located on a distal region of elongate shaft 278.
In the example shown in FIG. 5A, substance delivery reservoir 282
comprises an inflatable balloon. The inflatable balloon is
preferably made from suitable non-compliant, compliant or
semi-compliant materials including, but not limited to
polyurethane, silicone, Nylon, PET, polyethylene, PVC, C-flex.TM.,
etc. The material of the inflatable balloon is substantially
impermeable to water. Lumen 280 is in fluid communication with
substance reservoir 282 through one or more first openings or pores
284. Lumen 280 may thus be used to fill substance reservoir 282
with a suitable substance. A valve 286 is located near first
openings or pores 284. Valve 286 allows the substance to flow from
lumen 280 to substance reservoir 282. Also, valve 286 prevents or
substantially reduces the flow of the substance from substance
reservoir 282 to lumen 280. The design of valve 286 in FIG. 5A is
similar to the design of valve 252 in FIGS. 2G and 2H. The
substance stored in substance reservoir 282 is released into the
surrounding anatomy through one or more second openings or pores
288 that create a fluid communication between substance reservoir
282 and lumen 280. In the example shown in FIG. 5A, one or more
second openings or pores 288 are present on the region of elongate
shaft 278 enclosed by substance reservoir 282. In this example, the
distal end of lumen 280 opens into the surrounding anatomy such
that the substance flows from substance reservoir 282 to the
surrounding anatomy. Substance delivery device 276 further
comprises a pressure exerting mechanism comprising a water
permeable membrane 290 and a water-swellable material 292 enclosed
within water permeable membrane 290. Water-swellable material 292
is sandwiched between water permeable membrane 290 and the outer
surface of substance delivery reservoir 282 as shown in FIG. 5A.
After substance delivery device 276 is implanted in a target
anatomical region such as a paranasal sinus, water molecules from
the surrounding fluids e.g. sinus mucous gradually permeate through
water permeable membrane 290. These water molecules then come into
contact with water-swellable material 292. This in turn causes
water-swellable material 292 to gradually swell over a period of
time. FIG. 5A' shows a sectional view of the embodiment of the
substance delivery device shown in FIG. 5A showing the pressure
exerting mechanism exerting a pressure on a substance reservoir.
Swelling of water-swellable material 292 exerts a gradually
increasing pressure on substance delivery reservoir 282 as shown in
FIG. 5A'. This gradually squeezes substance reservoir 282 and
causes the substance stored in substance reservoir 282 to be
gradually released through one or more second openings or pores 288
into the surrounding anatomy. Water permeable membrane 290 may be
made of suitable materials that allow water molecules to pass
through but filter out dissolved or un-dissolved solids including
the substance stored in substance reservoir 282 as shown in FIG.
5A'. Examples of such membranes include, but not limited to reverse
osmosis membranes, nanofiltration membranes, etc. Water permeable
membrane 290 may be made of a wide variety of natural and synthetic
polymers, including, but not limited to polydimethylsiloxanes
(silicone rubbers), ethylene-vinylacetate copolymers,
polyurethanes, polyurethane-polyether copolymers, polyethylenes,
polyamides, polyvinylchlorides (PVC), polypropylenes,
polycarbonates, polytetrafluoroethylenes (PTFE),
polyacrylonitriles, polysulfones, cellulosic materials (e.g.,
cellulose monoacetate, cellulose diacetate, cellulose triacetate,
cellulose nitrate, etc.), hydrogels (e.g.,
2-hydroxymethylmethacrylate), etc. In one embodiment,
water-swellable material 292 is made of suitable super-absorbent
polymers including, but not limited to sodium salts of crosslinked
polyacrylic acid, potassium salts of crosslinked polyacrylic
acid/polyacrylamide copolymer, synthetic polyacrylamide with a
potassium salt base, graft copolymers of cross-linked polyacrylic
acid and starch, SNAPs (Safe and Natural Absorbent Polymers),
etc.
[0136] FIG. 5B shows a cross sectional view of an embodiment of a
substance delivery device comprising a controlled substance release
element in the form of a wick. The basic design of substance
delivery device 296 of FIG. 5B is similar to the design of
substance delivery device 240 of FIG. 4L. Substance delivery device
296 comprises a substance reservoir. In the embodiment shown in
FIG. 5B, the substance reservoir is an inflatable balloon 106.
Inflatable balloon 106 may be made of suitable compliant or
semi-compliant biocompatible materials. Examples of such materials
include, but are not limited to polyurethane, silicone, Nylon, PET,
polyethylene, PVC, etc. Inflatable balloon 106 is inflated through
an elongate shaft 104 comprising a reservoir filling lumen.
Inflatable balloon 106 is connected to elongate shaft 104 at a
proximal region and at a distal region of inflatable balloon 106.
The distal region of inflatable balloon 106 is everted and
connected to elongate shaft 104 as shown in FIG. 5B. Thus, when
inflatable balloon 106 is inflated, a distal region of inflatable
balloon 106 protrudes distal to the distal end of elongate shaft
104 as shown in FIG. 5B. This creates an atraumatic distal end of
substance delivery device 296. The lumen of elongate shaft 104 is
in fluid communication with inflatable balloon 106 through a shaft
opening 298. The lumen of elongate shaft 104 further comprises a
plugging mechanism e.g. a one way valve. The plugging mechanism is
located proximal to shaft opening 298. The plugging mechanism
prevents the backflow of fluid along the proximal direction after a
user fills inflatable balloon 106 with a suitable fluid substance
through the lumen of elongate shaft 104. Substance delivery device
296 further comprises a controlled delivery mechanism for
controlled delivery of a substance from substance delivery device
296. In the embodiment shown in FIG. 5B, the controlled delivery
mechanism is an elongate wick 300 attached to the distal end of
elongate shaft 104. Wick 300 is in fluid communication with the
lumen of elongate shaft 104. Wick 300 comprises a plurality of
pores or channels such that a fluid in contact with the proximal
region of wick 300 is transported in the distal direction along
wick 300 by capillary action. Wick 300 may be made of suitable
biocompatible polymers including, but not limited to cellulose,
collagen, polyvinyl acetate, etc. Wick 300 may comprise a variety
of two-dimensional or three dimensional shapes. For example, wick
300 may comprise one or more turns, coils, bends, curves or angled
regions, etc. to increase the area of contact surface between wick
300 and a region of the anatomy. Wick 300 regulates the delivery of
the substance from the substance reservoir to the surrounding
anatomy and thus allows for extended delivery of the substance to
the surrounding anatomy. In one embodiment of a method of using
substance delivery device 296, a user introduces substance delivery
device 296 into a target anatomical region such that one or more
regions of wick 300 are in contact with the anatomical region.
Thereafter, the user introduces a suitable substance in inflatable
balloon 106. Thereafter, the substance in inflatable balloon 106
comes into contact with the proximal region of wick 300. The
substance is then transported along wick 300 by capillary action.
The substance is then delivered to the anatomical region at a
controlled rate through wick 300.
[0137] In an alternate embodiment, the controlled delivery
mechanism is a thin elongate delivery tube comprising a delivery
lumen. The proximal end of the delivery lumen is in fluid
communication with the substance stored in substance delivery
device 296. The substance is delivered to the surrounding anatomy
from the distal tip of the delivery lumen. The delivery tube may
comprise one or more turns, coils, bends, curves or angled regions,
etc. The delivery tube regulates the delivery of the substance from
the substance reservoir to the surrounding anatomy and thus allows
for extended delivery of the substance to the surrounding
anatomy.
[0138] One or more embodiments of substance delivery devices
disclosed herein may comprise various embodiments of porous
elements for controlling the rate of delivery of a substance to the
anatomy. Such porous elements may comprise one or more pores. The
pore size of such pores may range from 0.2 microns to 200 microns.
For example, FIG. 5C shows the side view of an embodiment of an
elongate porous tube 302 that may be used to control the rate of
delivery of a substance to the anatomy from a substance delivery
device. Porous tube 302 comprises an elongate tube comprising a
lumen. The elongate tube may be made of suitable biocompatible
materials including, but not limited to silicone, Pebax, PEEK,
Nylon, polyethylene, polyurethane, etc. The elongate tube comprises
one or more pores that create a fluid communication between the
exterior of porous tube 302 and the lumen of porous tube 302. The
one or more pores may have a pore size ranging from 0.2 microns to
200 microns. The proximal end of porous tube 302 is plugged by a
plug 304. An atraumatic tip 306 may be attached to the distal end
of porous tube 302 to prevent or reduce damage to the anatomy by
the distal end of porous tube 302.
[0139] FIG. 5D shows a cross sectional view of an embodiment of a
substance delivery device comprising the porous tube 302 of FIG.
5C. Substance delivery device 308 comprises a substance reservoir.
In the embodiment shown in FIG. 5D, the substance reservoir is an
inflatable balloon 106. Inflatable balloon 106 may be made of
suitable compliant or semi-compliant biocompatible materials.
Examples of such materials include, but are not limited to
polyurethane, silicone, Nylon, polyethylene, PVC, etc. Inflatable
balloon 106 is inflated through an elongate shaft 310 comprising a
reservoir filling lumen. Elongate shaft 310 comprises a proximal
opening 312 that creates a fluid communication between the lumen of
elongate shaft 310 and inflatable balloon 106. The lumen of
elongate shaft 310 further comprises a plugging mechanism e.g. a
one way valve. The plugging mechanism is located proximal to
proximal opening 312. The plugging mechanism prevents the backflow
of fluid along the proximal direction after a user fills inflatable
balloon 106 with a suitable fluid substance through the lumen of
elongate shaft 310. Elongate shaft 310 further comprises a distal
opening 314 that creates another fluid communication between the
lumen of elongate shaft 310 and inflatable balloon 106. Distal
opening 314 is located distal to proximal opening 312 as shown in
FIG. 5D. The inner diameter of the lumen of elongate shaft 310 is
slightly larger than the outer diameter of porous tube 302. This
allows porous tube 302 to be inserted into elongate shaft 310
through the distal end of elongate shaft 310 as shown in FIG. 5D.
Porous tube 302 is positioned relative to elongate shaft 310 such
that plug 304 is located between distal opening 314 and proximal
opening 312. Thereafter, porous tube 302 is attached to elongate
shaft 310. A fluid substance present in inflatable balloon 106 can
flow through distal opening 314 and thereafter through the walls of
porous tube 302 and thereafter through the distal end of porous
tube 302. Thus, substance delivery device 308 can be used to
deliver a fluid substance to the surrounding anatomy at a
controlled rate that is controlled by the design of porous tube
302. Substance delivery device 308 may adapted to be inserted into
an anatomical region such as a paranasal sinus along an introducing
device. Examples of such introducing devices include, but are not
limited to guidewires, guide catheters, etc. In the example shown
in FIG. 5D, substance delivery device 308 further comprises a
second elongate shaft 316 comprising a lumen. Second elongate shaft
316 is attached to elongate shaft 310 such that second elongate
shaft 316 is substantially parallel to elongate shaft 310. The
lumen of second elongate shaft 316 acts as a rapid-exchange lumen
to allow a user to advance substance delivery device 316 into the
anatomy over a suitable guidewire.
[0140] FIG. 5E shows a cross sectional view of an embodiment of a
substance delivery device comprising a porous shaft region for
controlled delivery of a substance to the anatomy. Substance
delivery device 318 comprises a substance reservoir. In the
embodiment shown in FIG. 5E, the substance reservoir is an
inflatable balloon 106. Inflatable balloon 106 may be made of
suitable compliant or semi-compliant biocompatible materials.
Examples of such materials include, but are not limited to
polyurethane, silicone, Nylon, polyethylene, PVC, etc. Inflatable
balloon 106 is inflated through an elongate shaft 104 comprising a
substance introducing lumen 320. The distal end of elongate shaft
104 terminates within inflatable balloon 106 to create a fluid
communication between the lumen 320 and inflatable balloon 106.
Lumen 320 may be used to introduce a fluid substance into
inflatable balloon 106. Lumen 320 further comprises a plugging
mechanism e.g. a one way valve. The plugging mechanism prevents the
backflow of fluid along the proximal direction after a user fills
inflatable balloon 106 with a suitable fluid substance through
lumen 320. Substance delivery device 318 may adapted to be inserted
into an anatomical region such as a paranasal sinus along an
introducing device. Examples of such introducing devices include,
but are not limited to guidewires, guide catheters, etc. In the
example shown in FIG. 5E, substance delivery device 318 further
comprises a second elongate shaft 124 comprising a lumen 322. A
region of second elongate shaft 124 is attached to elongate shaft
104 such that second elongate shaft 124 is substantially parallel
to elongate shaft 104. Thus, lumen 322 can be used as a
rapid-exchange lumen to allow a user to advance substance delivery
device 318 into the anatomy over a suitable guidewire. Substance
delivery device 318 further comprises a third elongate shaft 324.
Third elongate shaft 324 is coaxial to second elongate shaft 124 as
shown in FIG. 5E. Third elongate shaft 324 may be made of suitable
biocompatible materials including, but not limited to silicone,
Pebax, PEEK, Nylon, polyethylene, polyurethane, etc. Third elongate
shaft 324 and second elongate shaft 124 enclose a lumen 328. The
proximal end of lumen 328 is plugged with an annular plug 326 as
shown in FIG. 5E. Third elongate shaft 324 comprises one or more
pores that create a fluid communication between inflatable balloon
106 and lumen 328. The one or more pores may have a pore size
ranging from 0.2 microns to 200 microns. A fluid substance present
in inflatable balloon 106 can flow through the porous walls of
third elongate shaft 324 and thereafter through the distal end of
lumen 328. Thus, substance delivery device 318 can be used to
deliver a fluid substance to the surrounding anatomy at a
controlled rate that is controlled by the porous walls of third
elongate shaft 324.
[0141] FIG. 5F shows a cross section of the substance delivery
device of FIG. 5E through the plane 5F-5F. FIG. 5F shows second
elongate shaft 124 enclosing lumen 322. Also shown is third
elongate shaft 324 coaxial to second elongate shaft 124. Third
elongate shaft 324 and second elongate shaft 124 enclose lumen
328.
[0142] In an alternate embodiment, the controlled substance release
mechanism comprises a diffusion barrier. The diffusion barrier is
in fluid communication with a substance stored in a substance
reservoir. The substance diffuses through the diffusion barrier and
into the surrounding over a period of time.
[0143] The substance delivery devices disclosed herein may comprise
one or more anchoring or retention elements to secure the position
of the substance delivery devices relative to the anatomy. In some
embodiments, the one or more substance reservoirs may act as the
anchoring or retention elements. For example, in one embodiment of
a substance delivery device comprising an inflatable substance
reservoir, the inflatable substance reservoir is located within a
paranasal sinus. The size of the inflated inflatable substance
reservoir is greater than the size of the ostium of the paranasal
sinus. This prevents or minimizes the risk of the inflatable
substance reservoir sliding out of the paranasal sinus. The
inflatable substance reservoir may comprise a shape specially
designed to prevent or minimize the risk of the inflatable
substance reservoir sliding out of the paranasal sinus. Examples of
such shapes include, but are not limited to the inflatable
reservoir shapes shown in FIGS. 4F-4J.
[0144] The one or more anchoring or retention elements may be
present on the shafts of the substance delivery devices disclosed
herein. Examples of such anchoring or retention elements are shown
in FIGS. 6A-6E'. FIG. 6A shows an embodiment of a substance
delivery device comprising an anchoring or retention element
comprising deployable arms. Substance delivery device 334 of FIG.
6A comprises an elongate shaft 104 connected to a substance
reservoir 106. Substance delivery device 334 further comprises an
outer sheath 336 that slides over elongate shaft 104. One or more
deployable arms 338 are connected to outer sheath 336 and elongate
shaft 104. In the embodiment shown in FIG. 6A, substance delivery
device 334 comprises two deployable arms 338. Each deployable arm
338 comprises a bent, curved or angled region. The distal end of
each deployable arm 338 is connected to elongate shaft 104. The
proximal end of each deployable arm 338 is connected to a distal
region of outer sheath 336. Deployable arms 338 may be made of
suitable elastic materials including, but not limited to metals
such as Nitinol, stainless steel, etc.; polymers such as Nylon,
PET, Pebax, PEEK, etc. Deployable arms 338 assume a bent
configuration in the relaxed state. In this configuration, a bent
region of deployable arms 338 extends in a radially outward
direction as shown in FIG. 6A'. This increases the profile of
substance delivery device 334, thereby preventing substance
delivery device 334 from slipping out of an anatomical region such
as a paranasal sinus. A user can temporarily reduce the profile of
substance delivery device 334 by pulling outer sheath 336 in the
proximal direction relative to elongate shaft 104. This causes
deployable arms 338 to get stretched along the axis of substance
delivery device 334, thereby reducing the profile of substance
delivery device 334. Substance delivery device 334 can be inserted
into or removed from an anatomical region in this configuration.
FIG. 6A' shows substance delivery device 334 of FIG. 6A deployed in
a sphenoid sinus.
[0145] FIG. 6B shows a perspective view of an embodiment of a
substance delivery device comprising a bent or angled shaft.
Substance delivery device 340 of FIG. 6B comprises an elongate
shaft 342 connected to a substance reservoir 106. Elongate shaft
342 may be made of suitable elastic materials including, but not
limited to Pebax, Nylon, polyethylene, etc. A region of elongate
shaft 342 comprises a bent or angled region as shown in FIG. 6B.
The bent or angled region increases the profile of substance
delivery device 340, thereby preventing substance delivery device
340 from slipping out of an anatomical region such as a paranasal
sinus. A user may temporarily reduce the profile of substance
delivery device 340 by using a suitable device such as a stylet,
guidewire, guide catheter, etc. to temporarily straighten elongate
shaft 342. The user may then introduce substance delivery device
340 into a region of the anatomy. The user may remove substance
delivery device 340 from the anatomy by pulling elongate shaft 342
in the proximal direction with a force sufficient to cause elongate
shaft 342 to temporarily straighten. FIG. 6B' shows substance
delivery device 340 of FIG. 6B deployed in a sphenoid sinus.
[0146] FIG. 6C shows a perspective view of an embodiment of a
substance delivery device comprising a shaft comprising a curved or
coiled region. Substance delivery device 344 of FIG. 6C comprises
an elongate shaft 346 connected to a substance reservoir 624.
Elongate shaft 346 may be made of suitable elastic materials
including, but not limited to Pebax, Nylon, polyethylene, etc. A
region of elongate shaft 346 comprises a curved or coiled region as
shown in FIG. 6C. The curved or coiled region increases the profile
of substance delivery device 344, thereby preventing substance
delivery device 344 from slipping out of an anatomical region such
as a paranasal sinus. A user may temporarily reduce the profile of
substance delivery device 344 by using a suitable device such as a
stylet, guidewire, guide catheter, etc. to temporarily straighten
elongate shaft 342. The user may then introduce substance delivery
device 344 into a region of the anatomy. The user may remove
substance delivery device 344 from the anatomy by pulling elongate
shaft 346 in the proximal direction with a force sufficient to
cause elongate shaft 346 to temporarily straighten. FIG. 6C' shows
substance delivery device 344 of FIG. 6C deployed in a sphenoid
sinus.
[0147] FIG. 6D shows a perspective view of an embodiment of a
substance delivery device comprising an elongate shaft comprising
flexible, projections. Substance delivery device 348 of FIG. 6D
comprises an elongate shaft 104 connected to a substance reservoir
106. Elongate shaft 104 may be made of suitable materials
including, but not limited to metals such as Nitinol, stainless
steel, etc.; polymers such as Nylon, PET, Pebax, PEEK,
polyethylene, silicone, etc. A region of elongate shaft 104
comprises one or more projections or arms 350. The one or more
projections or arms 350 may be made of suitable flexible,
biocompatible materials including, but not limited to metals such
as Nitinol, stainless steel, etc.; polymers such as Nylon, PET,
Pebax, PEEK, polyethylene, silicone, etc. The one or more
projections or arms 350 extend in a radially outward direction from
elongate shaft 104. This increases the profile of substance
delivery device 348. Substance delivery device 348 may be inserted
through an anatomical opening by pushing substance delivery device
348 with a sufficient force in the distal direction. This force
bends the one or more projections or arms 350 and thus reduces the
profile of substance delivery device 348. After substance delivery
device 348 is inserted through the anatomical opening, the one or
more projections or arms 350 extend in a radially outward direction
and prevent slipping of substance delivery device 348 out of the
anatomical opening. Substance delivery device 348 may be removed
through the anatomical opening by pulling substance delivery device
348 with a sufficient force in the proximal direction. FIG. 6D'
shows substance delivery device 348 of FIG. 6D deployed in a
sphenoid sinus.
[0148] The substance delivery devices disclosed herein may comprise
one or more anchoring or retention elements located on the
substance reservoirs. Such anchoring or retention elements help to
secure the position of the substance delivery devices relative to
the anatomy. Such anchoring or retention elements may also help to
maintain a particular position of the substance reservoir relative
to an anatomical region to allow the natural flow of anatomical
fluids around the substance reservoirs. For example, FIG. 6E shows
a perspective view of an embodiment of a substance delivery device
comprising a substance reservoir having one or more radial
projections. Substance delivery device 352 of FIG. 6E comprises an
elongate shaft 104 connected to a substance reservoir 106. Elongate
shaft 104 may be made of suitable materials including, but not
limited to metals such as Nitinol, stainless steel, etc.; polymers
such as Nylon, PET, Pebax, PEEK, polyethylene, silicone, etc.
Substance reservoir 106 comprises one or more radial projections or
arms 354. The one or more projections or arms 354 may be made of
suitable flexible, biocompatible materials including, but not
limited to polymers such as Nylon, PET, Pebax, PEEK, polyethylene,
silicone, etc. The one or more projections or arms 354 extend in a
radially outward direction substance reservoir 106. This increases
the profile of substance reservoir 106 after substance reservoir
106 is filled with a suitable substance. Substance delivery device
352 may be inserted through an anatomical opening by pushing
substance delivery device 352 with a sufficient force in the distal
direction. Thereafter, substance reservoir 106 is filled with a
suitable substance. One or more projections or arms 354 extend in a
radially outward direction and prevent slipping of substance
delivery device 352 out of the anatomical opening. FIG. 6E' shows
substance delivery device 352 of FIG. 6E deployed in a sphenoid
sinus. In FIG. 6E', projections or arms 354 cause substance
reservoir 352 to be positioned at a particular distance away from
the sphenoid sinus ostium SSO. This prevents substance reservoir
354 from blocking the natural flow of mucous through the sphenoid
sinus ostium.
[0149] The substance delivery devices disclosed herein may be
sutured to an anatomical region to secure the position of the
substance delivery devices relative to the anatomical region. This
may be achieved by passing a suture through one or more suturing
arrangements present on the substance delivery devices. Examples of
such suturing arrangements are shown in FIGS. 6F-6H.
[0150] FIG. 6F shows a perspective view of an embodiment of a
substance delivery device comprising a suturing arrangement
comprising a loop. Substance delivery device 358 of FIG. 6F
comprises an elongate shaft 104 and a substance reservoir 106
located on the distal region of shaft 104. Shaft 104 further
comprises a loop 360. A user can pass a suitable suture 362 through
loop 360 and secure substance delivery device 358 to an anatomical
region. Suture 362 may be biodegradable or non-biodegradable.
[0151] FIG. 6G shows a perspective view of an embodiment of a
substance delivery device comprising a suturing arrangement
comprising an aperture. Substance delivery device 358 of FIG. 6G
comprises an elongate shaft 104 and a substance reservoir 106
located on the distal region of shaft 104. Shaft 104 further
comprises one or more apertures 364. In the embodiment shown in
FIG. 6G, the one or more apertures 364 are located on a rectangular
tab 365 attached to a region of shaft 104. A user can pass a
suitable suture 362 through one or more apertures 364 and secure
substance delivery device 363 to an anatomical region. In an
alternate embodiment, one or more apertures 364 are located on a
region of shaft 104. Suture 362 may be biodegradable or
non-biodegradable.
[0152] FIG. 6H shows a perspective view of an embodiment of a
substance delivery device comprising a suturing arrangement
comprising a coiled, twisted or bent region. Substance delivery
device 366 of FIG. 6H comprises an elongate shaft 104 and a
substance reservoir 106 located on the distal region of shaft 104.
Shaft 104 further comprises a coiled, twisted or bent region 368.
In the embodiment shown in FIG. 6H, coiled, twisted or bent region
368 is a spring attached to a proximal region of shaft 104. A user
can pass a suitable suture 362 around coiled, twisted or bent
region 368 and secure substance delivery device 366 to an
anatomical region. Suture 362 may be biodegradable or
non-biodegradable.
[0153] One or more of the substance delivery devices disclosed
herein may comprise an elastic, super-elastic or shape-memory
material. Such an elastic, super-elastic or shape-memory material
may be used to temporarily reduce the profile of the substance
delivery devices while they are being inserted or removed through
the anatomy. For example, FIG. 7A shows a perspective view of an
embodiment of a substance delivery device comprising an elastic,
super-elastic or shape-memory material. Substance delivery device
370 of FIG. 7A comprises an elongate shaft 372. Shaft 372 has a
sufficient strength to allow a user to pull substance delivery
device 370 out of an anatomical region after substance delivery
device 370 has been placed in that anatomical region. Shaft 372 may
be made of suitable biocompatible materials including, but not
limited to polymers such as polyethylene, Pebax, PEEK, etc.; metals
or metals alloys such as stainless steel, nickel-titanium alloys,
titanium, etc. Substance delivery device 370 further comprises a
loop 374 located on the distal region of shaft 372. Loop 374 can be
made from suitable elastic, super-elastic or shape-memory materials
including, but not limited to polymers; metals or metals alloys
such as stainless steel, nickel-titanium alloys, titanium, etc. A
region of loop 374 is attached to a distal region of shaft 372 as
shown in FIG. 7A. During the insertion of substance delivery device
370 into the anatomical region or removal of substance delivery
device 370 from the anatomical region, loop 374 may temporarily
deform or bend to reduce the profile of substance delivery device
370. After insertion of substance delivery device 370 into the
anatomical region or removal of substance delivery device 370 from
the anatomical region, loop 374 substantially regains its original
shape and orientation. Substance delivery device 370 further
comprises a cup shaped membrane 376. Membrane 376 may be coated or
impregnated with one or more substances to be delivered to the
surrounding anatomy. Membrane 376 is attached to substance delivery
device 370 such that loop 374 is attached to the rim of the cup
shaped membrane 376. The concave surface of membrane 376 faces the
proximal direction and the convex surface of membrane 376 faces the
distal direction. Membrane 376 may be made of suitable
biocompatible materials including, but not limited to polyurethane,
Nylon, polyethylene, silicon, etc. FIG. 7B shows a cross section
through shaft 372 of substance delivery device 370 of FIG. 7A
through the plane 7B-7B.
[0154] FIG. 7C shows a perspective view of the substance delivery
device of FIG. 7A loaded on a delivery device. Delivery device 378
comprises a distal hollow tube 380. The inner diameter of distal
hollow tube 380 is larger than the outer diameter of shaft 372.
This allows a proximal region of shaft 372 to be introduced into
hollow tube 380 as shown in FIG. 7C. Delivery device 378 further
comprises an elongate pusher 382 attached to the proximal region of
distal hollow tube 380. During a method of deploying substance
delivery device 370 into an anatomical region, a user pushes pusher
382 in the distal direction. This in turn causes the distal end of
distal hollow tube 380 to push substance delivery device 370 into
the anatomical region. FIG. 7D shows a cross section through the
plane 7D-7D of FIG. 7C showing shaft 372 of substance delivery
device 370 of FIG. 7A enclosed by distal hollow tube 380 of
delivery device 378.
[0155] Substance delivery device 370 and delivery device 378 may be
introduced into the anatomy through one or more introducing
devices. For example, FIG. 7E shows substance delivery device 370
of FIG. 7A loaded on delivery device 378 of FIG. 70 being
introduced through a guide catheter 384. Guide catheter 384
comprises an elongate hollow introducing shaft 386. The diameter of
the lumen of introducing shaft 386 is larger than the outer
diameter of delivery device 378. This allows a user to introduce
delivery device 378 through the lumen of introducing shaft 386.
Substance delivery device 370 may be present in a collapsed or
folded state within introducing shaft 386 and thereafter expand or
unfold after being placed in a desired anatomical region. The
proximal end of introducing shaft 386 may comprises a suitable hub
such as a female luer lock 388. Guide catheter 384 may in turn be
introduced over a guidewire into an anatomical region. In the
embodiment shown in FIG. 7E, guide catheter 384 further comprises a
rapid exchange lumen located on a short tube 390 attached to a
distal region of introducing shaft 386. The distal end of tube 390
and/or introducing shaft 386 may comprise a radio-opaque marker 392
such as a radio-opaque marker band to enable the user to track
guide catheter 384 using X-rays. The distal end of tube 390 and/or
introducing shaft 386 may comprise an atraumatic tip to reduce or
prevent damage to anatomical structures by the distal end of guide
catheter 384.
[0156] One or more of the substance delivery devices disclosed
herein may comprise an elongate filament, coil or wire. Such
substance delivery devices may be introduced in an anatomical
region through a suitable introducing device. Such substance
delivery devices may be fully or partially biodegradable or
non-biodegradable. Such substance delivery devices may comprise an
elastic, super-elastic or shape-memory material to enable the
substance delivery devices to assume a two or three dimensional
shape after being deployed in an anatomical region. For example,
FIG. 8A shows an embodiment of an elongate substance delivery
device comprising an elongate filament being introduced in a
sphenoid sinus. Substance delivery device 394 comprises an elongate
filament can be introduced into a suitable anatomical region such
as a paranasal sinus to deliver one or more substances. The
diameter of substance delivery device 394 may range from 0.01 to 1
mm. This size allows mucous or other anatomical fluids to flow
around substance delivery device 394 and out of a paranasal sinus
when substance delivery device 394 is inserted into the paranasal
sinus. Substance delivery device 394 can be delivered by a user
into an anatomical region through a hollow introducing device 396.
In the embodiment shown in FIG. 8A, introducing device 396
comprises a hollow, elongate shaft 398 and a suitable hub 400
connected to the proximal end of elongate shaft 398. FIG. 8B shows
a cross sectional view through a region of substance delivery
device 394 of FIG. 8A through plane 8B-8B. In the embodiment shown,
substance delivery device 394 comprises an inner filament 402.
Filament 402 may be made of suitable biocompatible materials such
as various biodegradable or non-biodegradable suture materials.
Examples of such materials include, but are not limited to
poly-glycolic acid poly-L-lactic acid, polydioxanone,
polyglyconate, Nylon, polyester, polypropylene, etc. Filament 402
may be manufactured by extrusion or drawing. Filament 402 is coated
with a basecoat. The basecoat in turn is dip coated or spray coated
with a matrix layer 404 comprising a substance to be delivered to
the surrounding anatomy. Matrix layer 404 in turn may be coated
with a topcoat 406 to control diffusion and release rate of the
substance in matrix layer 404. In one embodiment, topcoat 406 is
made of PBMA or phosphatidylcholine and the substance in matrix
layer 404 is a steroid, antibiotic or an antifungal agent. In this
embodiment, substance delivery device 394 is delivered through an
opening of a paranasal sinus such that at least one region of
substance delivery device 394 touches a region of the mucosa of the
paranasal sinus.
[0157] Several anatomical regions are lined by a layer of mucous
that flows in a particular flow path. The devices and methods
described herein may be used to selectively deliver a substance to
an upstream region on the mucous flow path. This upstream region
may be chosen such that the mucous flow delivers the substance
throughout the anatomical region. For example, FIG. 9A shows a
method of delivering a substance to the lateral wall of a maxillary
sinus by the substance delivery device 296 of FIG. 5B. Wick 300 of
substance delivery device 296 touches the mucous layer on the
lateral wall of the maxillary sinus. Thereafter, the substance in
inflatable balloon 106 is delivered by wick 300 to the mucous on
the lateral wall of the maxillary sinus at a controlled rate. The
substance is then transported along with the mucous flow to cover
the entire inner wall of the maxillary sinus as shown in FIG.
9A.
[0158] In another example, FIG. 9B shows a method of delivering a
substance to the medial wall of a frontal sinus by a device similar
to the substance delivery device of FIG. 4L. Substance delivery
device 408 of FIG. 9B is similar to substance delivery device 240
of FIG. 4L. Substance delivery device 408 comprises an inflatable
balloon 242 that acts as a substance reservoir. Inflatable balloon
242 further comprises one or more pores 248. One or more pores 248
are located only on one side of inflatable balloon 242. One or more
pores 248 are oriented so that they deliver the substance stored in
inflatable balloon 242 at a controlled rate to the mucous layer on
the medial wall of a frontal sinus as shown in FIG. 9B. The
substance is then transported along with the mucous flow to cover
the entire inner wall of the frontal sinus as shown in FIG. 9B.
Substance delivery device 408 further comprises an orientation
marker to ensure that one or more pores 248 face the medial wall of
the frontal sinus. In the embodiment shown in FIG. 9B, the
orientation marker comprises a radiopaque marker 409 located on
elongate shaft 104. Radiopaque marker 409 and one or more pores 248
are located in the same radial direction from the axis of elongate
shaft 104. This enables a user to orient one or more pores 248 to
face the medial wall of the frontal sinus under radiographic
visualization.
[0159] One or more of the elongate devices disclosed herein may be
used as stents. The stents may be positioned within natural or
man-made openings to the frontal, maxillary, sphenoid, anterior or
posterior Ethmoid sinuses; other cells or cavities; anatomical
regions such as nostrils, nasal cavities, nasal meatus, etc.; and
other passageways such as Eustachian tubes, naso-lachrymal ducts,
etc.
[0160] For example, one or more of the elongate devices disclosed
herein may be used as sinus stents. Sinus stents are used to
prevent adhesions between mucosal surfaces that have been cut
during surgical procedures such as FESS. Current sinus stents are
bulky. They are difficult to insert and remove. Also, they are
difficult to insert through small openings. Therefore low profile
stents are needed to minimize invasiveness during insertion,
removal and during the period they are implanted. One or more of
the elongate devices disclosed herein including, but not limited to
the devices illustrated in FIGS. 1, 2A, 4E, 4E' and 4M may be used
as sinus stents. Such sinus stents may comprise one or more anchors
or other mechanisms to secure the position of the sinus stents in
the anatomy. Such sinus stents may for example be placed in
anterior or posterior Ethmoid ostia or artificial openings leading
to Ethmoid sinuses, natural or surgically created openings to other
paranasal sinuses, etc. The step of placement of such sinus stents
may be preceded by a step of surgically modifying an anatomical
region. For example, a user may surgically create an artificial
opening to the Ethmoid sinuses and thereafter place a sinus stent
through the artificial opening.
[0161] FIGS. 10A through 10C show the various steps of a method of
implanting a substance delivering stent in an anatomical region.
The stent may be biodegradable or non-biodegradable. In one
embodiment of a biodegradable stent, the stent is made of a
combination of PLLA and PGA. In another embodiment of a
biodegradable stent, the stent is made of a combination of
mometasone furoate and poly(ester urethane) multi-block copolymers.
The poly(ester urethane) multi-block copolymers may be made by
combining different combinations of DL-lactide, glycolide,
.epsilon.-caprolactone and polyethylene glycol. The stent may be
made of a rolled sheet of a material or a tube. In the example
shown in FIG. 10A, stent 410 comprises a rolled sheet of a
biocompatible material. The rolled sheet comprises one or more
substances to be delivered to an anatomical region where stent 410
is delivered. Stent 410 may comprise one or more windows or slots
412 that allow a fluid to pass through the wall of stent 410. Such
a stent 410 does not substantially disrupt the normal drainage of
anatomical fluids in the anatomical region. Stent 410 may be used
to deliver steroids or other substances to anatomical regions
including, but not limited to sinus ostia and/or passageways over a
desired period of time. In one embodiment, stent 410 is a
self-expanding stent. Such as self-expanding stent 410 may be
introduced through a hollow guide or sheath into an anatomical
region. Stent 410 may be pushed out of the hollow sheath or guide
by a pusher. In the method embodiment shown in FIGS. 10A through
10C, stent 410 is a balloon-expandable stent inserted in an
anatomical region by a balloon catheter 414. Balloon catheter 414
comprises an elongate shaft 416 and an inflatable balloon 418 on
the distal end of elongate shaft 416. Inflatable balloon 418 may be
made of suitable compliant, non-compliant or semi-compliant
materials. Stent 410 is tightly rolled on the surface of inflatable
balloon 418. This reduces the profile of stent 410. Balloon
catheter 414 and stent 410 are inserted into an anatomical region.
In FIG. 1A, an ostium of a paranasal sinus is used as an example of
the anatomical region. In FIG. 10B, inflatable balloon 418 is
inflated by a user. This causes stent 410 to expand as shown in
FIG. 10B. In one embodiment, inflatable balloon 418 is also used as
a dilating balloon to dilate the anatomical region. Thereafter,
inflatable balloon 418 is deflated. This causes stent 410 to
separate from balloon catheter 414. Thereafter, as shown in FIG.
10C, balloon catheter 414 is removed from the anatomical region.
Stent 410 remains in the anatomical region. Stent 410 encloses a
hollow region that allows a user to pass a range of devices through
the hollow region. Examples of such devices include, but are not
limited to guidewires, catheters, flexible scopes and cutters.
[0162] In one embodiment, the material of stent 410 comprises a
polymer, one or more substances to be delivered and a stabilizer.
Stent 410 may be designed to delivery a substance through only one
surface of the rolled sheet. FIG. 10D shows a cross section through
a region 10D of an embodiment of the device of FIG. 10C. In the
embodiment of stent 410 shown in FIG. 10D, the wall of stent 410
comprises three layers. Inner layer 420 is thick and provides
mechanical strength to stent 410. In one example, inner layer 420
is made of ethylene vinyl acetate (EVA). Middle layer 422 comprises
a suitable substance to be delivered to the surrounding anatomy. In
one example, middle layer 422 comprises a mixture of EVA and
dexamethasone and polyvinyl pyrrolidone. The substance to be
delivered to the surrounding anatomy cannot diffuse through inner
layer 420, but can diffuse through an outer layer 424. Outer layer
424 thus controls the rate of release of the substance to the
surrounding anatomy. In one example, outer layer is made of EVA.
Stent 410 is designed to be easily removable after a desired period
of time. Stent 410 may be removed for example by forceps or other
grasping devices. In one embodiment, stent 410 comprises a removal
element that enables a user to easily remove stent 410 from the
anatomy. In one embodiment, the removal element of an elongate
string or filament attached to stent 410. A user pulls the elongate
string or filament in the proximal direction to remove stent 410
from the anatomical region.
[0163] The various substance delivery devices disclosed herein may
comprise a hollow tubular region through which anatomical fluids
can flow. Such embodiments of substance delivery devices cause
minimal or zero disruption to the natural flow of anatomical fluids
such as mucous. Such embodiments of substance delivery devices may
also be used to prevent adhesions between mucosal surfaces that
have been cut during surgical procedures such as FESS. For example,
FIGS. 11A through 11C show a sequence of steps to deliver a
substance delivery device through a sinus ostium that prevents
post-surgical adhesions and also allows the natural flow of mucous
through the sinus ostium. FIG. 11A shows a cross section of a sinus
ostium OS of a patient with sinusitis. In FIG. 11B, the sinus
ostium OS is surgically dilated. This dilation may be performed by
a variety of methods including, but not limited to the Balloon
Sinuplasty.TM. procedure, FESS, etc. Thereafter, in FIG. 11C, a
substance delivery device 428 is inserted through the sinus ostium
OS. Substance delivery device 428 comprises an elongate shaft 104
and a substance reservoir 106. The outer diameter D.sub.1 of
elongate shaft 104 is slightly smaller than the inner diameter
D.sub.2 of the dilated sinus ostium OS. This enables a user to
introduce substance delivery device 248 through the dilated sinus
ostium OS. Elongate shaft comprise an end-to-end lumen. This
end-to-end lumen allows the natural flow of mucous generated within
the sinus thereby preventing unwanted accumulation of the mucous
within the sinus. Elongate shaft 104 also prevents prevent
adhesions between mucosal surfaces of the sinus ostium OS that have
been dilated thereby acting as a sinus stent.
[0164] The stent devices disclosed herein may be retained in the
anatomy for a desired time period ranging from approximately 3 days
to approximately 4 weeks. Such stents may be implanted in suitable
anatomical regions such as surgically enlarged or dilated
opening(s) of a paranasal sinus. They may be sized to maintain a
desired diameter of said surgically enlarged or dilated opening
between about 2 mm and about 10 mm.
[0165] The devices and methods disclosed herein may be used to
deliver substances to anatomical regions such as paranasal sinuses
by dripping and evaporation of the substances. In one method
embodiment, dexamethasone is delivered to paranasal sinuses. In
this embodiment, dexamethasone is dissolved in a volatile solvent
such as ethanol to achieve a solution with a desired dexamethasone
concentration (e.g. 10 mg/ml). A substance delivery device such as
substance delivery device 240 of FIG. 4L is then inserted into a
paranasal sinus. A suitable volume of the solution (e.g. approx.
0.2 ml) is then delivered to inflatable balloon 242 of drug
delivery device 240. The solution is then allowed to drip and
evaporate slowly through one or more pores 248 located on
inflatable balloon 242. The size of one or more pores 248 may range
from 20 to 100 microns. Dripping and evaporation of the solution
through one or more pores 248 of substance delivery device 240
causes the dexamethasone to be delivered to the inner walls of the
paranasal sinuses. Similarly, other devices disclosed herein such
as substance delivery device 296 of FIG. 5B may be used to deliver
substances to anatomical regions such as paranasal sinuses by
dripping and evaporation of the substances.
[0166] The devices and methods disclosed herein may be used to
deliver gels or viscous liquids comprising one or more substances
to anatomical regions such as paranasal sinuses. Such gels or
viscous liquids may coat and adhere to a mucous membrane and thus
provide sustained delivery of one or more substances to the mucous
membrane. In one embodiment, a plasticized hydrocarbon gel
comprising gelatin, pectin and sodium carboxymethylcellulose and a
suitable substance may be delivered to a mucous membrane such as
the mucous membrane of a paranasal sinus. Such gels can be used for
sustained delivery of the suitable substance to the mucous
membrane.
[0167] One or more of the substance reservoirs disclosed herein may
comprise multiple compartments such that each compartment stores a
particular substance formulation. The multiple compartments prevent
mixing of multiple substance formulations before substance
formulations are delivered to the anatomy.
[0168] One or more of the substance reservoirs comprising pores may
be filled with a suitable substance at a sufficiently high pressure
to cause a portion of the substance to squirt out of the pores.
This process may be used to deliver an initial bolus of the
substance to the surrounding anatomy.
[0169] One or more of the substance reservoirs disclosed herein may
be filled with a suitable substance after the substance reservoir
is introduced in an anatomical region. Alternatively, one or more
of the substance reservoirs disclosed herein may be filled with a
suitable substance before the substance reservoir is introduced in
an anatomical region. Alternatively, one or more of the substance
reservoirs disclosed herein may be pre-filled with a solid,
lyophilized or concentrated substance. The solid, lyophilized or
concentrated substance is converted to an active form by
introducing a solvent into the substance reservoir. This may be
done just before or after the substance reservoir is introduced in
an anatomical region. Alternatively, one or more of the substance
reservoirs disclosed herein may be pre-filled with an inactive form
of a substance. The inactive form of the substance is converted to
an active form by introducing an activating agent into the
substance reservoir. This may be done just before or after the
substance reservoir is introduced in an anatomical region.
[0170] The devices and methods disclosed herein may be used to
treat middle ear or inner ear pathologies. This may be done by
accessing the middle ear through the Eustachian tube or through the
tympanum. For example, the devices and methods disclosed herein may
be used to treat Meniere's disease by delivering gentamicin to the
inner ear through the round window membrane. The devices and
methods disclosed herein may be used to treat a variety of diseases
or disorders by a variety of substances including, but not limited
to the substances and diseases or disorders disclosed in Table
1.
TABLE-US-00001 TABLE 1 ANATOMICAL LOCATION OF DISEASE/ EXAMPLES OF
THE DISEASE/ DISORDER TO SUBSTANCES THAT MAY BE DISORDER BE TREATED
DELIVERED Inner ear Meniere's Gentamicin, Vestibular disease,
suppressants (e.g. Vertigo anticholinergics, antihistamines, and
benzodiazepines), antiemetic drugs, diuretics, etc. Inner ear
Autoimmune Corticosteroids, etc. inner ear disease Inner ear Free
radical Glutamate antagonists(e.g. induced damage memantine,
caroverine and magnesium), Calpain inhibitor (e.g. Leupeptin),
Antioxidants (e.g. glutathione, Methionine), etc. Inner ear Hearing
loss Neurotrophic factors (e.g. and tinnitus NeuroTrophin-3), Genes
for Neurotrophic factors such as BDNF (brain-derived neurotropic
factor), etc. Middle ear Otitis media Amoxicillin, ampicillin,
azithromycin, cefaclor, cefdinir, ceftibuten, ceftriaxone,
erythomycin, clarithromycin, combination of
trimethoprim/sulfamethoxazole, ofloxacin, etc. Inner ear
Degeneration of Grafted neural stem cells, inner ear cells,
embryonic stem cells, dorsal especially sensory ganglion cells and
cell lines hair cells and derived from fetal inner ear associated
cells, autologous bone marrow neurons, stromal cells, etc.
[0171] It is to be further appreciated that, as described herein,
the implantable portion of a substance delivery device 100 may
include a through lumen that may function as a vent and/or drain
when such implantable portion device is in the Eustachian tube or
through an opening formed in the tympanum.
[0172] The devices and methods disclosed herein may be used to mark
an anatomical region with a suitable imagable marker. For example,
the devices and methods disclosed herein may be used to deliver a
radio opaque marker such as a radio opaque contrast agent to an
ostium of a paranasal sinus. This enables a user to image the
ostium of the paranasal sinus using X-rays or fluoroscopy.
[0173] One or more of the substance delivery devices disclosed
herein may comprise a curved, bent or angled region to enable the
drug delivery devices to navigate through the anatomy.
[0174] The distal-most regions of one or more substance delivery
devices disclosed herein may comprise an atraumatic tip. The
atraumatic tip is used to prevent or reduce damage to the anatomy
by the distal-most regions of the one or more substance delivery
devices.
[0175] The outer surface of one of more substance delivery devices
disclosed herein may comprise a coating that reduces or eliminates
the risk of encrusting of the outer surface by a biological
material. In one embodiment, the coating comprises a material that
absorbs water to form a gel. Examples of such materials include,
but are not limited to hyaluronic acid, etc.
[0176] One or more of the substance delivery devices disclosed
herein may be designed to be easily removable from the anatomy
after completion of a treatment.
[0177] One or more of the substance delivery devices disclosed
herein may be refilled after a significant volume of substance
filled in a substance reservoir has been delivered to the
anatomy.
[0178] One or more of the substance delivery devices disclosed
herein may comprise one or more markers to enable a user to locate
and/or navigate the substance delivery devices through the anatomy.
For example, the substance delivery devices may comprise visual
markers to enable the user to determine the depth of insertion of
the substance delivery devices into the anatomy. In another
example, the substance delivery devices may comprise imaging
markers to enable the user to locate and/or navigate the substance
delivery devices using imaging modalities such as X-rays, MRI,
etc.
[0179] As used herein, the term "opening or a paranasal sinus"
shall include any transnasally accessible opening in a paranasal
sinus or air cell such as natural ostia, surgically altered natural
ostia, surgically created openings, antrostomy openings, osteotomy
openings, burr holes, drilled holes, ethmoidectomy openings,
natural or man made passageways, etc.
[0180] As used herein, the term "implantable" shall include any
device that is maintained in the body of a human or animal for a
period ranging from 30 minutes to 60 days.
[0181] As used herein, the term "porous" shall include any element
that comprises one or more pores or apertures.
[0182] It is to be appreciated that the invention has been
described hereabove with reference to certain examples or
embodiments of the invention but that various additions, deletions,
alterations and modifications may be made to those examples and
embodiments without departing from the intended spirit and scope of
the invention. For example, any element or attribute of one
embodiment or example may be incorporated into or used with another
embodiment or example, unless to do so would render the embodiment
or example unsuitable for its intended use. All reasonable
additions, deletions, modifications and alterations are to be
considered equivalents of the described examples and embodiments
and are to be included within the scope of the following
claims.
* * * * *