U.S. patent application number 16/685950 was filed with the patent office on 2020-07-02 for methods for delivery of therapeutic materials to treat cancer.
This patent application is currently assigned to RenovoRx, Inc.. The applicant listed for this patent is RenovoRx, Inc.. Invention is credited to Ramtin AGAH, Shaun R. BAGAI, Kamran NAJMABADI, Imtiaz L. QURESHI.
Application Number | 20200206481 16/685950 |
Document ID | / |
Family ID | 58097373 |
Filed Date | 2020-07-02 |
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United States Patent
Application |
20200206481 |
Kind Code |
A1 |
AGAH; Ramtin ; et
al. |
July 2, 2020 |
METHODS FOR DELIVERY OF THERAPEUTIC MATERIALS TO TREAT CANCER
Abstract
Disclosed is a localized method for treatment of cancer
including the steps of providing a drug delivery catheter;
navigating the catheter to the bile duct; and delivering a
therapeutic agent into the bile duct. According to one aspect of
the method, the drug delivery catheter is a multi-occlusion balloon
catheter. The multi-occlusion balloon catheter may include at least
two balloons. The multi-occlusion balloon catheter may optionally
include a pressure transducer between the balloons to optimize
delivery technique.
Inventors: |
AGAH; Ramtin; (Menlo Park,
CA) ; QURESHI; Imtiaz L.; (Saratoga, CA) ;
NAJMABADI; Kamran; (Palo Alto, CA) ; BAGAI; Shaun
R.; (Mountain View, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
RenovoRx, Inc. |
Los Altos |
CA |
US |
|
|
Assignee: |
RenovoRx, Inc.
Los Altos
CA
|
Family ID: |
58097373 |
Appl. No.: |
16/685950 |
Filed: |
November 15, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15351922 |
Nov 15, 2016 |
10512761 |
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16685950 |
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14958415 |
Dec 3, 2015 |
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15351922 |
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14870833 |
Sep 30, 2015 |
9463304 |
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14958415 |
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14293603 |
Jun 2, 2014 |
9457171 |
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14870833 |
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12958711 |
Dec 2, 2010 |
8821476 |
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14293603 |
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61830218 |
Jun 3, 2013 |
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61265845 |
Dec 2, 2009 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2025/0037 20130101;
A61M 25/007 20130101; A61M 2025/0175 20130101; A61M 2210/1042
20130101; A61M 25/0097 20130101; A61M 2025/0004 20130101; A61M
2210/10 20130101; A61B 1/273 20130101; A61M 2210/00 20130101; A61M
2025/1015 20130101; A61M 25/1002 20130101; A61M 2230/30 20130101;
A61M 25/1011 20130101; A61B 17/12045 20130101; A61M 5/14 20130101;
A61B 17/12136 20130101; A61M 2025/1052 20130101 |
International
Class: |
A61M 25/10 20060101
A61M025/10; A61B 1/273 20060101 A61B001/273 |
Claims
1. (canceled)
2. A method of treatment, the method comprising: inserting a
catheter into a bile duct; occluding the bile duct with a first
occluder on a distal end region of the catheter and a second
occluder on the distal end region of the catheter proximal to the
first occluder, to isolate a region of the bile duct; delivering a
therapeutic agent into the isolated region of the bile duct; and
maintaining a pressure in the isolated region of the bile duct to
diffuse the therapeutic agent into a tissue around the bile
duct.
3. The method of claim 2, wherein maintaining the pressure of the
isolated region of the bile duct comprises delivering the
therapeutic agent into the isolated region of the bile duct under
pressure.
4. The method of claim 2, further comprising increasing or
decreasing the pressure in the isolated region of the bile duct to
change a penetration depth of the therapeutic agent into the tissue
around the bile duct.
5. The method of claim 2, wherein the tissue around the bile duct
comprises a tumor.
6. The method of claim 2, wherein the tissue around the bile duct
comprises one or more of: a pancreatic tumor, a liver tumor and a
cholangiocarcinoma.
7. The method of claim 2, wherein inserting the catheter comprises
advancing the catheter over a guidewire within the bile duct.
8. The method of claim 2, wherein inserting the catheter comprises
inserting the catheter into the bile duct to a region of the bile
duct that adjacent to a tumor.
9. The method of claim 2, wherein inserting the catheter comprises
inserting the catheter through an endoscopic retrograde
cholangiopancreatogram (ERCP) catheter.
10. The method of claim 2, wherein inserting the catheter comprises
inserting the catheter percutaneously.
11. The method of claim 2, wherein inserting comprises adjusting
the distance between the first occluder and the second occluder by
advancing the first occluder distally, wherein the first occluder
is on an inner catheter slidably disposed within a lumen of the
catheter.
12. The method of claim 2, wherein occluding the bile duct
comprises inflating the first occluder and the second occluder.
13. The method of claim 2, wherein the therapeutic agent is
selected from the group of: (5-fluorouracil (5-FU), Aldesleukin,
Axitinib, Bleomycin, Carboplatin, Cetuximab, Cisplatin,
Cyclophosphamide, Dacarbazine, Doxorubicin Hydrochloride,
doxorubicin liposomal non-pegylated (un-coated), doxorubicin
liposomal pegylated (PEG coated), Floxuridine, Gemcitabine
Hydrochloride, Irinotecan Hydrochloride Liposome, Lanreotide
Acetate, leucovorin (antidote to folic acid antagonist used with
5FU), Methotrexate, Mitomycin, Mitoxantrone, Nivolumab, Olaparib,
Oxaliplatin, Sorafenib Tosylate, Temsirolimus, Thiotepa, Topotecan
Hydrochloride, Vinblastine Sulfate, vincristine sulfate).
14. A method of treatment, the method comprising: inserting a
catheter into a bile duct to a region of the bile duct that
adjacent to a tumor; isolating a region of the bile duct adjacent
to the tumor by occluding the bile duct with a first occluder on a
distal end region of the catheter and a second occluder on the
distal end region of the catheter proximal to the first occluder;
introducing a therapeutic agent into the isolated region of the
bile duct from out of an opening in a side wall of the catheter
between the first occluder and the second occluder; and diffusing
the therapeutic agent into a tissue around the bile duct by
maintaining the pressure in the isolated region of the bile duct at
greater than an interstitial tissue pressure in the tissue around
the bile duct.
15. The method of claim 14, further comprising increasing or
decreasing the pressure in the isolated region of the bile duct to
change a penetration depth of the therapeutic agent into the tissue
around the bile duct.
16. The method of claim 14, wherein the tumor comprises one or more
of: a pancreatic tumor, a liver tumor and a cholangiocarcinoma.
17. The method of claim 14, wherein inserting the catheter
comprises advancing the catheter over a guidewire within the bile
duct.
18. The method of claim 14, wherein inserting the catheter
comprises inserting the catheter through an endoscopic retrograde
cholangiopancreatogram (ERCP) catheter.
19. The method of claim 14, wherein inserting comprises adjusting
the distance between the first occluder and the second occluder by
advancing the first occluder distally, wherein the first occluder
is on an inner catheter slidably disposed within a lumen of the
catheter.
20. The method of claim 14, wherein the therapeutic agent is
selected from the group of: (5-fluorouracil (5-FU), Aldesleukin,
Axitinib, Bleomycin, Carboplatin, Cetuximab, Cisplatin,
Cyclophosphamide, Dacarbazine, Doxorubicin Hydrochloride,
doxorubicin liposomal non-pegylated (un-coated), doxorubicin
liposomal pegylated (PEG coated), Floxuridine, Gemcitabine
Hydrochloride, Irinotecan Hydrochloride Liposome, Lanreotide
Acetate, leucovorin (antidote to folic acid antagonist used with
5FU), Methotrexate, Mitomycin, Mitoxantrone, Nivolumab, Olaparib,
Oxaliplatin, Sorafenib Tosylate, Temsirolimus, Thiotepa, Topotecan
Hydrochloride, Vinblastine Sulfate, vincristine sulfate).
21. A method of treatment, the method comprising: inserting a
catheter into a bile duct to a region of the bile duct that
adjacent to a tumor; isolating a region of the bile duct adjacent
to the tumor by occluding the bile duct with a first occluder on a
distal end region of the catheter and a second occluder on the
distal end region of the catheter proximal to the first occluder;
injecting a therapeutic agent into the isolated region of the bile
duct from out of an opening in a side wall of the catheter between
the first occluder and the second occluder so that the pressure in
the isolated region of the bile duct is greater than an
interstitial tissue pressure in a tissue around the bile duct,
whereby the therapeutic agent diffuses into the tissue around the
bile duct.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 15/351,922, filed Nov. 15, 2016, which is a
continuation-in-part of U.S. application Ser. No. 14/958,415, filed
Dec. 3, 2015, now abandoned, which is a continuation-in-part of
U.S. patent application Ser. No. 14/870,833, filed Sep. 30, 2015,
now U.S. Pat. No. 9,463,304, which is a continuation of U.S. patent
application Ser. No. 14/293,603, filed Jun. 2, 2014, now U.S. Pat.
No. 9,457,171, which claims priority to and the benefit U.S.
Provisional Patent Application No. 61/830,218, filed Jun. 3, 2013,
and which is also a continuation-in-part of U.S. patent application
Ser. No. 12/958,711, filed Dec. 2, 2010, now U.S. Pat. No.
8,821,476, which claims priority to and the benefit of U.S.
Provisional Patent Application No. 61/265,845, filed Dec. 2, 2009,
each of the disclosures of which is incorporated herein by
reference in its entirety.
BACKGROUND
[0002] The embodiments described herein relate generally to methods
for delivering a therapeutic material to treat pancreatic
cancer.
[0003] Pancreatic cancer is considered an almost chemoresistant
tumor. The ineffective result of systemic chemotherapy is at least
in part due to an insufficient drug concentration within the tumor
because of dose-limited toxicity in bone marrow and epithelial
tissue. Since systemic chemotherapy is limited its effectiveness,
localized therapy can be desirable for advanced pancreatic cancer
patients. For example, one such treatment can include local
intra-arterial delivery of chemotherapy. Intra-arterial infusion
allows higher drug concentration to reach the tumor, overcoming the
problem of poor blood flow to tumor mass in comparison to healthy
tissue. Furthermore, intra-arterial chemotherapy can also take
advantage of the first pass effect of chemotherapeutics, generating
higher-level drug concentrations at the tumor cell membrane and
therefore, enhancing cellular drug uptake as compared to
intravenous infusion. Lastly, local delivery can reduce systemic
side effects.
[0004] Such a chemotherapy treatment is usually administered
through catheters placed in the celiac/hepatic artery or portal
vein, however, a best mode of catheter placement has yet to be
established. The tumor response rates of pancreatic arterial
infusion chemotherapy can range widely, for example, from 7% to
65%, at least in part due to efficacy of drug delivery where
anticancer drugs were administered via the celiac artery without
assessment of drug distribution. Thus, a need exists for improved
methods for delivering a treatment such as a biologic agent and/or
drug formation to target tissue of the pancreas, as well as hepatic
tumors and cholangiocarinoma.
SUMMARY
[0005] Disclosed is a localized method for treatment of cancer,
comprising the steps of:
[0006] providing a drug delivery catheter; navigating the catheter
to the bile duct; delivering a therapeutic agent into the bile
duct.
[0007] According to one aspect of the aforementioned method,
wherein the drug delivery catheter is a multi-occlusion balloon
catheter. The multi-occlusion balloon catheter may comprise at
least two balloons. The multi-occlusion balloon catheter may
optionally include a pressure transducer between the balloons to
optimize delivery technique.
[0008] According to one aspect of the aforementioned method, the
therapeutic agent is selected from the group (5-fluorouracil
(5-FU), Aldesleukin, Axitinib, Bleomycin, Carboplatin, Cetuximab,
Cisplatin, Cyclophosphamide, Dacarbazine, Doxorubicin
Hydrochloride, doxorubicin liposomal non-pegylated (un-coated),
doxorubicin liposomal pegylated (PEG coated), Floxuridine,
Gemcitabine Hydrochloride, Irinotecan Hydrochloride Liposome,
Lanreotide Acetate, leucovorin (antidote to folic acid antagonist
used with 5FU), Methotrexate, Mitomycin, Mitoxantrone, Nivolumab,
Olaparib, Oxaliplatin, Sorafenib Tosylate, Temsirolimus, Thiotepa,
Topotecan Hydrochloride, Vinblastine Sulfate, vincristine
sulfate).
[0009] According to one aspect of the aforementioned method, the
navigating step includes navigating the catheter using ERCP.
[0010] According to one aspect of the aforementioned method, the
navigating step includes navigating the catheter to the bile duct
percutaneously.
[0011] According to one aspect of the aforementioned method, the
localized method is used to treat pancreatic cancer.
[0012] According to one aspect of the aforementioned method, the
localized method is used to treat at least one of hepatic tumors
and cholangiocarinoma.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is an illustration of a pancreas and related
structure in a human;
[0014] FIGS. 2 and 3 are schematic illustrations of a
multi-occlusion catheter insertion device according to an
embodiment, in a first configuration and a second configuration,
respectively;
[0015] FIG. 4 is a side view of a multi-occlusion catheter
insertion device according to an embodiment, shown in a dilated
configuration;
[0016] FIG. 5 is a side view of a portion of the multi-occlusion
catheter insertion device of
[0017] FIG. 4; and
[0018] FIGS. 6-11 are each a cross-sectional view of a different
portion of the multi-occlusion catheter insertion device of FIG. 4,
taken along lines 6-6, 7-7, 8-8, 9-9, 10-10, and 11-11,
respectively, in FIG. 5.
[0019] FIG. 12 is a side view of a multi-occlusion catheter
insertion device according to an embodiment.
[0020] FIG. 13 is a side view of a portion of the multi-occlusion
catheter insertion device of FIG. 12.
[0021] FIGS. 14-19 are each a cross-sectional view of a different
portion of the multi-occlusion catheter insertion device taken
along lines 14-14, 15-15, 16-16, 17-17, 18-18, and 19-19,
respectively, in FIG. 13.
[0022] FIG. 20 is a top view of a multi-occlusion catheter
insertion device according to an embodiment, in a first
configuration.
[0023] FIG. 21 is a side view of a handle included in the
multi-occlusion catheter insertion device of FIG. 20.
[0024] FIG. 22 is a top view of a handle included in the
multi-occlusion catheter insertion device of FIG. 20.
[0025] FIG. 23 is an enlarged cross-sectional view of a portion of
the handle of FIG. 21, indicated by the region X1 and taken along
the line 23-23 in FIG. 22.
[0026] FIG. 24 is a cross-sectional view of a portion of the
multi-occlusion catheter insertion device of FIG. 20, taken along
the line 24-24.
[0027] FIG. 25 is an enlarged cross-sectional view of a portion of
the handle of FIG. 21, indicated by the region X2 and taken along
the line 25-25 in FIG. 22.
[0028] FIG. 26 is a cross-sectional view of a portion of the
multi-occlusion catheter insertion device of FIG. 20, taken along
the line 26-26.
[0029] FIG. 27 is a cross-sectional view of a portion of the
multi-occlusion catheter insertion device of FIG. 20, taken along
the line 27-27.
[0030] FIG. 28 is a cross-sectional view of a portion of the
multi-occlusion catheter insertion device of FIG. 20, taken along
the line 28-28.
[0031] FIG. 29 is a top view of the multi-occlusion catheter
insertion device of FIG. 20 in a second configuration.
[0032] FIG. 30 is an illustration of a portion of the
multi-occlusion catheter insertion device of
[0033] FIG. 20 in use within a portion of a body.
[0034] FIG. 31 is a flowchart illustrating a method for treating
the pancreas, according to an embodiment.
DETAILED DESCRIPTION
[0035] Methods described herein can be used, for example, for the
insertion and manipulation of a multi-occlusion catheter device to
deliver a therapeutic agents to the bile duct for treatment of
pancreatic cancer or other localized cancer. Tumors localized
around the bile duct (cancer of the pancreatic head, primary and
secondary liver tumors, and cholangiocarcinoma) may benefit from
localized delivery through the bile duct itself. The bile duct can
be exogenously accessed through an endoscopic retrograde
cholangiopancreatogram (ERCP) catheter, one can envision delivery
of a double balloon catheter into the bile duct using established
ERCP technique. After localizing the double balloon catheter to the
area of bile duct involved/adjacent to the tumor, that area of bile
duct is isolated by inflating the two balloon elements.
Chemotherapeutic elements are then infused between the two
balloons. By increasing the pressure between two balloon elements
to exceed the interstitial tissue pressure, in a diffusion
dependent manner, the chemotherapeutic agent will then diffuse out
the wall of the bile duct and into the tissue.
[0036] By monitoring and/or adjusting the pressure between the
balloons, one can change the penetration depth of the chemotherapy
into the tissue.
[0037] According to some embodiments, a therapeutic material for
treatment of pancreatic cancer or other localized cancer is
delivered into the bile duct using the multi-occlusion catheter.
The gall bladder is connected to the pancreas via the common bile
duct.
[0038] Localized delivery to the site of the tumor has advantages
for both maximizing local drug concentration at the tumor site, and
decreasing systemic side effects/toxicity. Thus the approach
disclosed herein may avoid some of the toxicity related side
effects of delivering chemotherapy drugs directly to the pancreas
and may enable the use of more concentrated dosage of chemotherapy
drugs. It should be understood that therapeutic particles may be
substituted for or used in conjunction with chemotherapy drugs.
Moreover, it should be understood that in some cases it may be
useful to place a stent to open the bile duct prior to delivering
the chemotherapy and/or therapeutic agent.
[0039] By way of example, such a use can include navigating a
catheter such as a multi-occlusion catheter to the target anatomy
using conventional percutaneous approaches or the same approach
used for endoscopic retrograde cholangiopancreatogram (ERCP),
isolating the bile duct, and then exogenously introducing
therapeutic cells/agents/biologics into the isolated area, via an
infusion port of the catheter. In such fashion, the cells/agents
biologics can be delivered to the bile duct with high efficiency.
In some embodiment, a device with two sliding balloon catheters can
be used to isolate bile duct. The isolated area can then be
perfused with cells/therapeutic agents via an infusion port
disposed between the two balloon catheters. In some embodiments,
the devices described herein can be arranged such that a user can
manipulate a portion of the device substantially single handedly,
to allow for accurate delivery of a biological agent and/or drug
formulation to an isolated segment or portion of an organ.
[0040] This application incorporates by reference to co-pending
U.S. application Ser. No. 14/958,415 filed on December 3, 2015.
[0041] In some embodiments, an apparatus includes a handle, an
inner catheter, an outer catheter, an actuator, a first occlusion
element, and a second occlusion element. The inner catheter is
coupled to the handle and the first occlusion element is coupled to
the inner catheter. The inner catheter defines an inner catheter
lumen that is configured to receive a guidewire. The outer catheter
is coupled to the housing and the second occlusion element is
coupled to the outer catheter. The outer catheter defines a first
lumen that is in fluid communication with a distal opening and is
configured to introduce a therapeutic agent through the distal
opening into the bile duct. The outer catheter defines a second
lumen that is configured to receive at least a portion of the inner
catheter.
[0042] The actuator is coupled to the handle and is configured to
move the outer catheter relative to the handle. The second
occlusion element is disposed proximal to the first occlusion
element and a distance therebetween is adjustable when the outer
catheter is moved relative to the handle by the actuator.
[0043] In some embodiments, an apparatus includes a handle, an
inner catheter, an outer catheter, a first occlusion element, a
second occlusion element, and an actuator. The inner catheter is
coupled to the handle and the first occlusion element is coupled to
the inner catheter. The outer catheter is coupled to the housing
and the second occlusion member is coupled to the outer catheter.
The outer catheter defines a first lumen that is in fluid
communication with a distal opening and that is configured to
introduce a therapeutic agent therethrough and into the bile duct.
The outer catheter defines a second lumen that is configured to
receive at least a portion of the inner catheter. The second
occlusion element is disposed proximal of the first occlusion
element. The actuator is coupled to the handle and is configured to
move the outer catheter relative to the handle between a first
position in which the second occlusion element is at a first
distance from the first occlusion element and a second position in
which the second occlusion element is at a second distance from the
first occlusion element, with the second distance being greater
than the first distance.
[0044] In some embodiments, a system and/or device(s) is provided
for endovascular introduction of therapeutic materials selectively
to the bile duct for the treatment of pancreatic cancer. In some
embodiments, a device and/or system can include, for example, an
inner catheter having a distal retractable occlusion element and an
inner catheter lumen adapted and configured to introduce a
guidewire, and an outer catheter having a distal retractable
occlusion element, an infusion lumen adapted and configured to
introduce therapeutic materials to the bile duct, and a lumen for
slidably receiving the inner catheter. In such an embodiment, the
distal retractable occlusion element of the outer catheter can be
positioned proximal to the distal retractable occlusion element of
the inner catheter; and a sealing element can be included that is
configured to selectively isolate or seal an end of the outer
catheter to prevent therapeutic materials from entering into the
lumen of the outer catheter in which the inner catheter is slidably
disposed.
[0045] In some embodiments, a selective sealing element can
include, for example, a ring, a membrane, or any other suitable
element configured to prevent loss of therapeutic material into the
lumen of the outer catheter in which the inner catheter is
disposed. The lumen provided in the inner catheter can be
configured to perfuse a distal organ beyond the targeted isolation
region of the artery.
[0046] In some embodiments, a distance between the proximal
retractable occlusion element and the selective sealing element can
be configured for external adjustment, thus allowing a user to
customize the isolated area (between the two occlusion elements) to
better target the bile duct during delivery of biologics. The
proximal retractable occlusion element and the selective sealing
element can have a cross-sectional diameter, for example, between
2-12 mm.
[0047] In some embodiments, the devices and methods described
herein can be used for isolating the perfusion area of the gall
bladder for introduction of chemotherapy for treatment of
pancreatic cancer, hepatic tumors and cholangiocarinoma or other
therapeutic agents targeted to the pancreas.
[0048] As used in this specification, the singular forms "a," "an"
and "the" include plural referents unless the context clearly
dictates otherwise. Thus, for example, the term "a member" is
intended to mean a single member or a combination of members, "a
material" is intended to mean one or more materials, or a
combination thereof.
[0049] As used herein, the term "set" can refer to multiple
features or a singular feature with multiple parts. For example,
when referring to a set of ports, the set of ports can refer to a
single port or to multiple ports.
[0050] As used herein, the words "proximal" and "distal" refer to a
direction closer to and away from, respectively, an operator of,
for example, a medical device. Thus, for example, the end of the
medical device closest to the patient's body (e.g., contacting the
patient's body or disposed within the patient's body) would be the
distal end of the medical device, while the end opposite the distal
end and closest to, for example, the user of the medical device,
would be the proximal end of the medical device. Said another way,
the distal end portion is the end that is located furthest from a
point of reference, such as an origin or a point of attachment. For
example, the distal end portion would be the end farthest away from
a user's hand. The proximal end portion, thus, would be the
position nearer to a point of reference such as an origin, i.e.,
the user's hand.
[0051] Table 1 is a list of chemotherapy drugs which may be
delivered to the bile duct according to the method of the present
invention.
TABLE-US-00001 TABLE 1 Trade Common Solvents/ # Drug Name(s)
Indication(s) Diluents 1 5-fluorouracil 5FU, Breast, Liver, water
(5-FU) Flourouracil, Pancreatic, Adrucil Stomach 2 Aldesleukin
Proleukin Kidney water 3 Axitinib Inlyta Kidney water 4 Bleomycin
Blenoxane Cervical, water Testicular 5 Carboplatin Paraplatin
Ovarian water 6 Cetuximab Erbitux Colorectal, water Head, Neck 7
Cisplatin Platinol-AQ Bladder, Liver, water Ovarian, Pancreatic,
Testicular 8 Cyclo- Cytoxan Breast, Ovarian, water phosphamide
Pancreatic 9 Dacarbazine DTIC-Dome Pancreatic water 10 Doxorubicin
Adriamycin, Breast, Liver, water Hydrochloride Rubex, Ovarian, (pH
= 3) Caelyx Pancreatic, Stomach 11 doxorubicin Myocet Breast,
Liver, water liposomal, non- Ovarian, (pH = 3) pegylated (un-
Pancreatic, coated) Stomach 12 doxorubicin Doxil Breast, Liver,
water liposomal, Ovarian, (pH = 3) pegylated (PEG Pancreatic,
coated) Stomach 13 Floxuridine FUDR Liver, Pancreatic water 14
Gemcitabine Hospira, Breast, Ovarian, water Hydrochloride Gemcitab,
Pancreatic (pH = 3) Gemzar 15 Irinotecan Onivyde, Pancreatic water
Hydrochloride Camptosar (pH = 3) Liposome 16 Lanreotide Somatuline
Pancreatic water Acetate 17 leucovorin Depot Pancreatic water or
(antidote to folic oral acid antagonist used with 5FU) 18
Methotrexate Otrexup, Breast, water Rheumatrex, Pancreatic Trexall
19 Mitomycin Mutamycin, Liver, water MMC, Pancreatic, Mitomycin C,
Stomach Mitozytrex 20 Mitoxantrone Novantrone Pancreatic water 21
Nivolumab Opdivo Kidney water 22 Olaparib Lynparza Ovarian water 23
Oxaliplatin Elotaxin Pancreatic water 24 Sorafenib Nexavar Kidney
water Tosylate 25 Temsirolimus Torisel Kidney water 26 Thiotepa
Bladder, water Ovarian 27 Topotecan Hycamtin Cervical, water
Hydrochloride Ovarian (pH = 3) or oral 28 Vinblastine Velban,
Breast, water Sulfate Velsar Pancreatic, Testicular 29 vincristine
Alcrist, Pancreatic water sulfate Biocristin, Oncocristin- AQ,
VCR
[0052] FIG. 1 illustrates the liver 10, the gall bladder 20, and
the pancreas 30 situated within an abdominal cavity (not shown) of
a mammal (e.g., a human). The pancreas 30 is a gland organ which is
part of the digestive and endocrine system of vertebrates. The
pancreas 30 is both an endocrine gland producing hormones,
including insulin, glucagon, and somatostatin, as well as an
exocrine gland, secreting pancreatic juice containing digestive
enzymes that pass to the small intestine. These enzymes help in the
further breakdown of the carbohydrates, protein, and fat in the
chyme.
[0053] As shown, the common bile duct leads from the gall bladder
to the pancreas 30.
[0054] FIGS. 2 and 3 are schematic illustrations of a
multi-occlusion catheter insertion device 100 useful for delivering
therapeutic agents to the bile duct for treatment of pancreatic
cancer. The multi-occlusion catheter insertion device 100 (also
referred to herein as "device") can be arranged to allow for
substantially single handed use to, for example, isolate a segment
of a bodily lumen such as the buke duct, thereby allowing a
procedure to be performed within the isolated segment and/or
allowing a targeted delivery of a biological or therapeutic agent.
The device 100 includes a handle 110, an actuator 150, a first
catheter 160, and a second catheter 170. The handle 110 can be any
suitable shape, size, or configuration. For example, in some
embodiments, the handle 110 can have a shape and size that are
configured to enhance the ergonomics of the device 100. As
described in further detail herein, the handle 110 can be grasped
by a user to insert a portion of the first catheter 160 and a
portion of the second catheter 170 into a bodily lumen of a patient
and can be manipulated to move, inflate, deflate, adjust, and/or
otherwise reconfigure the portion of the first catheter 160 and the
portion of the second catheter 170 within the bodily lumen. For
example, the second catheter 170 can be moved relative to the first
catheter 160, or vice-versa, to adjust a distance between a first
occlusion element 168 coupled to a distal end portion of the first
catheter 160 and a second occlusion element 178 coupled to a distal
end portion of the second catheter 170. The device 100 can be used
to isolate a segment of the bile duct within the space defined
between the first occlusion element 168 and the second occlusion
element 178. Thus, a procedure can then be performed within the
isolated segment such as for example, delivering a therapeutic
agent to the isolated segment.
[0055] The handle 110 has a proximal end portion 111 and a distal
end portion 112. As described in further detail herein, the handle
110 can be arranged to enclose, house, and/or be disposed about a
portion of the first catheter 160 and the second catheter 170. For
example, the first catheter 160 and the second catheter 170 can
each be coupled to the handle 110. A first port 120 and a second
port 125 (collectively referred to herein as a first set of ports
128) are each disposed at the proximal end portion 111 of the
handle 110. The first port 120 and the second port 125 can each
define a lumen (not shown in FIGS. 2 and 3). In some embodiments,
the first port 120 and the second port 125 can be formed
monolithically or integrally with the first catheter 160. The first
port 120 and the second port 125 can be any suitable size, shape,
or configuration. For example, in some embodiments, the first port
120 and the second port 125 can extend from the proximal end
portion 111 of the housing 110 such that at least a portion of the
first port 120 and the second port 125 is accessible outside of the
handle 110. Although not shown in FIGS. 2 and 3, the first port 120
and the second port 125 can each be physically and fluidically
coupled to a device, mechanism, and/or the like, such as, for
example, a source of an inflation medium as described in more
detail below. For example, in some embodiments, the first port 120
and the second port 125 can each include a Luer-Lok.RTM. or the
like that can physically and fluidically couple the first port 120
and/or the second port 125 to such a device. As described in
further detail herein, the first set of ports 128 can be in fluid
communication with at least a portion of the first catheter 160 to
place at least the portion of the first catheter 160 in fluid
communication with a device (e.g., a source of an inflation medium)
coupled to the handle 110 via the first port 120 and/or the second
port 125. For example, the lumen of the first port 120 can be in
fluid communication with a first lumen defined by the first
catheter 160 and the lumen of the second port 125 can be in fluid
communication with a second lumen defined by the first catheter
160.
[0056] The distal end portion 112 of the handle 110 includes a
third port 130, a fourth port 135, and a fifth port 140
(collectively referred to herein as a second set of ports 143). The
second set of ports 143 can be any suitable arrangement such as,
for example, described above with reference to the first set of
ports 128. For example, the third port 130, the fourth port 135,
and the fifth port 140 can each define a lumen (not shown in FIGS.
2 and 3) and can each include a Luer-Lok.RTM. or the like that can
physically and fluidically couple the third port 130, the fourth
port 135, and/or the fifth port 140 to any suitable attachment,
device, mechanism, and/or the like. For example, the third port
130, the fourth port 135, and/or the fifth port 140 can each be
coupled to an external device such as a device supplying a
therapeutic agent, a device supplying an inflation medium or a
device supplying an irrigation solution as described in more detail
below with reference to, for example, device 400. In some
embodiments, the second set of ports 143 includes the fifth port
140 and only one of the third port 130 and the second port 135.
[0057] As described in further detail herein, the second set of
ports 143 can be in fluid communication with at least a portion of
the second catheter 170 to place at least the portion of the second
catheter 170 in fluid communication with such external devices
coupled to the handle 110 via the third port 130, the fourth port
135, and/or the fifth port 140. For example, the third port 130
and/or the fourth port 135 can be coupled to and in fluid
communication with a first lumen defined by the second catheter
170, and the fifth port 140 can be coupled to and in fluid
communication with a second lumen defined by the second catheter
170. In some embodiments, the third port 130, the fourth port 135,
and/or the fifth port 140 can be monolithically or integrally
formed with the second catheter 170. Moreover, the second set of
ports 143 can be coupled to or operably coupled to the actuator 150
as described in more detail herein.
[0058] The first catheter 160 (also referred to herein as "inner
catheter") and the second catheter 170 (also referred to herein as
"outer catheter") can be any suitable catheter device. For example,
in some embodiments, the first catheter 160 and the second catheter
170 are multi-lumen catheters. As shown in FIG. 2, the first
catheter 160 has a proximal end portion 161 and a distal end
portion 162. The proximal end portion 161 of the first catheter 160
is disposed within a portion of the handle 110. More specifically,
the proximal end portion 161 of the first catheter 160 can be
fixedly disposed within the portion of the handle 110 to place the
first catheter 160 in fluid communication with one or more of the
ports 120 and 125 of the first set of ports 128. In some
embodiments, the first catheter 160 can define a first lumen that
can be physically and fluidically coupled to the first port 120 and
a second lumen that can be physically and fluidically coupled to
the second port 125. In other embodiments, a first catheter can be
coupled to the handle and can be operably coupled to a first port
and a second port (e.g., ports 120, 125) via an intervening
structure such as, for example, flexible tubing or the like. In
this manner, the first port 120 can be placed in fluid
communication with a first lumen (not shown in FIGS. 2 and 3)
defined by the first catheter 160, as described in further detail
herein. Similarly, the second port 125 can be placed in fluid
communication with a second lumen (not shown in FIGS. 2 and 3)
defined by the first catheter 160. In some embodiments, the second
port 125 and the second lumen of the first catheter 160 can receive
a guidewire or the like, as described in further detail herein.
[0059] The distal end portion 162 of the first catheter 160 extends
beyond a distal end portion of the handle 110 and includes the
occlusion member 168. The occlusion member 168 can be any suitable
device or mechanism that is configured to selectively limit, block,
obstruct, or otherwise occlude a bodily lumen in which the
occlusion member 168 is disposed. For example, in some embodiments,
the occlusion member 168 can be an inflatable balloon or the like
that can be transitioned between a collapsed (e.g., deflated)
configuration and an expanded (e.g., inflated) configuration. In
some embodiments, the arrangement of the first catheter 160 and the
handle 110 can be such that the first port 120 is in fluid
communication with the occlusion member 168. Thus, in use, the
first port 120 can be fluidically coupled to a device that can
supply a pressurized fluid (e.g., air, inert gas, or liquid) to the
occlusion member 168 to transition the occlusion member 168 between
a collapsed configuration and an expanded configuration, as
described in further detail herein.
[0060] The second catheter 170 of the device 100 has a proximal end
portion 171 and a distal end portion 172. As shown in FIGS. 2 and
3, the second catheter 170 is movably disposed about a portion of
the first catheter 160. More specifically, the second catheter 170
can be, for example, a multi-lumen catheter and can be arranged
such that the first catheter 160 is movably disposed within a first
lumen (not shown in FIGS. 2 and 3) defined by the second catheter
170. The proximal end portion 171 can be movably disposed within
the handle 110 such that a portion of the second catheter 170 is in
fluid communication with the second set of ports 143. In some
embodiments, the second catheter 170 can be physically and
fluidically coupled to the third port 130 and the fourth port 135,
and/or the fifth port 140. In other embodiments, the second
catheter can be disposed within a handle and can be operably
coupled to one or more ports via an intervening structure such as,
for example, flexible tubing or the like. In this manner, the third
port 130 and/or the fourth port 135 can be placed in fluid
communication with the second lumen (not shown in FIGS. 2 and 3)
defined by the second catheter 170, as described in further detail
herein; the fifth port 140 can be placed in fluid communication
with a third lumen (not shown in FIGS. 2 and 3) defined by the
second catheter 170, as described in further detail herein.
[0061] The distal end portion 172 of the first catheter 170 extends
beyond a distal end portion of the handle 110 and includes an
occlusion member 178. The occlusion member 178 can be any suitable
device or mechanism that is configured to selectively limit, block,
obstruct, or otherwise occlude a lumen in which the occlusion
member 178 is disposed. For example, in some embodiments, the
occlusion member 178 can be substantially similar to the occlusion
member 168 of the first catheter 160. In some embodiments, the
arrangement of the second catheter 170 and the handle 110 can be
such that the third port 130 and/or the fourth port 135 is in fluid
communication with the occlusion member 178. Thus, in use, the
third port 130 and/or the fourth port 135 can be fluidically
coupled to a device that can supply a pressurized fluid (e.g., air,
inert gas, or liquid) to the occlusion member 178 to transition the
occlusion member 178 between a collapsed configuration and an
expanded configuration, as described in further detail herein. In
some embodiments, at least a portion of the occlusion member 178
can be selectively permeable to allow a biological agent to pass
therethrough. Although not shown in FIGS. 2 and 3, in some
embodiments, the distal end portion 172 of the second catheter 170
can define one or more openings. In such embodiments, the fifth
port 140 can be fluidically coupled to a device that can supply
irrigation, therapeutic material or agents, biological agents,
and/or the like to a volume or region disposed between the
occlusion member 168 of the first catheter 160 and the occlusion
member 178 of the second catheter 170.
[0062] As described above, the actuator 150 of the device 100 can
be operably coupled to the second set of ports 143. For example, in
some embodiments, the actuator 150 is included in and/or coupled to
the handle 110 and arranged relative to the second set of ports 143
to be operably coupled thereto. The actuator 150 can be any
suitable device, mechanism, assembly, etc. that is movable between
a first position relative to the handle 110, associated with the
device 100 in the first configuration (FIG. 2), and a second
position relative to the handle 110, associated with the device 100
in the second configuration (FIG. 3). Furthermore, with the
actuator 150 operably coupled to the second set of ports 143, the
actuator 150 can be operable in moving the second set of ports 143
between a first position relative to the handle 110 (e.g., the
distal position) and a second position relative to the handle 110
(e.g., the proximal position), as indicated by the arrow AA in FIG.
3. Thus, when the second catheter 170 is coupled to the second set
of ports 143, the actuator 150 can also move the second catheter
170 relative to the handle 110 and/or relative to the first
catheter 160 as described in more detail below.
[0063] In some embodiments, the actuator 150 can be a push or pull
slide that can move within a track (not shown in FIGS. 2 and 3)
defined by the handle 110. In other embodiments, the actuator 150
can be coupled to an energy storage device (e.g., a spring,
compressed gas, etc.) that is configured to move the actuator 150.
For example, the actuator 150 can include a push button that allows
a spring to transition from a compressed configuration towards an
uncompressed configuration to move the actuator 150 relative to the
handle 110. In other embodiments, a portion of the actuator 150 can
be rotated to move the actuator 150 between its first position and
its second position relative to the handle 110. With the second
catheter 170 physically and fluidically coupled to the second set
of ports 143 (as described above), the movement of the actuator 150
can move the second catheter 170 relative to the handle 110. More
specifically, the proximal end portion 171 of the second catheter
170 can be movably disposed within the handle 110 (as described
above) such that when the actuator 150 is moved from its first
position to its second position, the proximal end portion 171 of
the second catheter 170 is moved from a first position relative to
the handle 110 (e.g., FIG. 2) to a second position relative to the
handle 110 (e.g., FIG. 3).
[0064] With the second catheter 170 movably disposed about the
first catheter 160, the movement of the actuator 150 moves the
second catheter 170 relative to the first catheter 160. For
example, when the device 100 is in the first configuration, a first
distance D1 is defined between the occlusion member 168 of the
first catheter 160 and the occlusion member 178 of the second
catheter 170. Therefore, with the first catheter 160 fixedly
disposed within the handle 110, the movement of the second catheter
170 in the proximal direction (e.g., the AA direction) increases
the distance between the occlusion member 168 of the first catheter
160 and the occlusion member 178 of the second catheter 170 to a
second distance D2, as shown in FIG. 3.
[0065] In use, a guidewire (not shown) can be inserted into the
second port 125 and through a lumen defined by the first catheter
160. In this manner, the guidewire can be advanced through a bodily
lumen and the device 100 can be manipulated to advance the first
catheter 160 along the guidewire to place the distal end portion
162 of the first catheter 160 and the distal end portion 172 of the
second catheter 170 at a target location within the bodily lumen.
Once at the target location, the actuator 150 can be moved in the
AA direction (e.g., the proximal direction) to define a desired
distance between the occlusion member 168 of the first catheter 160
and the occlusion member 178 of the second catheter 170, thereby
placing the device 100 in the second configuration (FIG. 3). As
described above, an inflation source can be coupled to the second
port 125 of the first catheter 160 and the same inflation source or
a second inflation source can be coupled to the third port 130
and/or the fourth port 135 of the second catheter 170. With the
desired distance defined between the occlusion members 168 and 178,
the inflation source(s) can be used to inflate the occlusion
members 168 and 178. Thus, the occlusion members 168 and 178 can be
transitioned from the collapsed (e.g., deflated) configuration to
the expanded (e.g., inflated) configuration to substantially
isolate a segment of the bodily lumen disposed therebetween. With
the occlusion members 168 and 178 substantially occluding the
bodily lumen, a biological or therapeutic agent can be delivered to
the substantially isolated segment via the fourth port 135. For
example, the biological or therapeutic agent can be delivered
through the fourth port 135 into a lumen of the second catheter
that is in fluid communication with the opening (see, e.g., opening
479 in FIG. 20) defined by the distal end portion 172 of the second
catheter 170. In some instances, the substantially isolated segment
can be irrigated by coupling an irrigation source to the fifth port
140. Thus, the irrigation is delivered to the substantially
isolated segment via the opening (described above) defined by the
distal end portion 172 of the second catheter 170.
[0066] FIGS. 4-11 illustrate a dilation catheter 200 according to
an embodiment. FIG. 4 is a side view of the dilation catheter
device 200 (also referred to herein as "catheter device"). In this
embodiment, dilatation of two balloons is used to occlude a desired
length of an artery such as, for example, the splenic artery 40
(see, e.g., FIG. 2). Specifically, the catheter device 200 includes
a first catheter 260 (also referred to herein as "inner catheter")
and a second catheter 270 (also referred to herein as "outer
catheter"), a first Y-adaptor 228 (also referred to herein as
"first set of ports") and a second Y-adaptor 243 (also referred to
herein as "second set of ports"), a first occlusion element 268
(also referred to herein as "dilation element", "occluder," or
"distal occlusion element"), and a second occlusion element 278
(also referred to herein as "dilation element", "occluder," or
"proximal occlusion element") each configured to occlude a portion
of an artery. The first occlusion element 268 is coupled to the
first catheter 260 and the second occlusion element 278 is coupled
to the second catheter 270.
[0067] The occlusion elements 268 and 278 can each be moved between
a collapsed configuration (also referred to as "retracted
configuration") for insertion of the catheter device 200 into a
body of a patient (e.g., into an artery) and an expanded
configuration (also referred to as "dilated configuration" or
"inflated configuration") for occluding a portion of an artery. The
occlusion elements 268 and 278 when in the collapsed configuration
have a smaller outer perimeter (or diameter) than when in the
expanded configuration.
[0068] The catheter device 200 includes a distal end portion 212
and a proximal end portion 211. In this embodiment, the occlusion
elements 268 and 278 are expandable balloons coupled to an outer
surface of the first catheter 260 and an outer surface of the
second catheter 270, respectively, and are disposed at the distal
end portion 212 of the catheter device 200. The catheter device 200
is shown in a dilated configuration in FIG. 4 with the occlusion
elements 268 and 278 (i.e., balloons) in their expanded
configuration (i.e., inflated, dilated).
[0069] FIG. 5 is a side view of the distal end portion 212 of the
catheter device 200 (e.g., a distal end portion of the first
catheter 260 and the second catheter 270) and FIGS. 6-11 illustrate
cross-sections at various locations along the distal end portion
212 of the catheter device 200 to illustrate the various lumens of
the catheter device 200. As shown in FIGS. 6-11, the first catheter
260 defines a first lumen 265 and a second lumen 263 that each can
extend a length of the first catheter 260. The first lumen 265 can
be configured to receive a guidewire 280 (shown, for example, in
FIG. 4). The second lumen 263 can be used to communicate an
inflation medium to and from the first occlusion element 268 via an
aperture 264 in fluid communication with the first occlusion
element 268 (see, e.g., FIG. 10).
[0070] As shown, for example, in FIGS. 6 and 7, the second catheter
270 defines a first lumen 274, a second lumen 273, and a third
lumen 276. The first lumen 274 can be used to communicate an
inflation medium to and from the second occlusion element 278 via
an aperture 275 in fluid communication with the second occlusion
element 278 (see, e.g., FIG. 7). The second lumen 273 is configured
to slidably receive at least a portion of the first catheter 260
therethrough, as shown in FIGS. 6-9. The third lumen 276 can
terminate and be in fluid communication with an infusion aperture
279 near a distal end 272 of the second catheter 270 (see, e.g.,
FIG. 8). The infusion aperture 279 can be used to communicate a
cell/biological/therapeutic material to a desired location within a
body/artery of a patient.
[0071] The first Y-adaptor 228 is coupled to the first catheter 260
and includes two ports 220 and 225, as shown in FIG. 4. The port
220 defines a lumen (not shown) that is in fluid communication with
the first lumen 263 of the catheter 260 and can be used to
communicate an inflation medium to the first occlusion element 268
through the second lumen 263. For example, a source of an inflation
medium (not shown) can be coupled to the catheter device 200 via
the port 220 of the first Y-adaptor 228. The port 225 defines a
lumen (not shown) that is in fluid communication with the second
lumen 265 of the first catheter 260 (see, e.g., FIGS. 6-11) and can
be used for introduction of the guidewire 280 into the second lumen
265.
[0072] The second Y-adapter 243 is coupled to the second catheter
270 and includes three ports 230, 235 and 240, as shown in FIG. 4.
The port 230 defines a lumen (not shown) that is in fluid
communication with the second lumen 273 of the second catheter 270
(see, e.g., FIGS. 6-11) and can receive the first catheter 260
therethrough. The port 235 defines a lumen (not shown) that is in
fluid communication with the first lumen 274 of the second catheter
270 and can be used to communicate an inflation medium to and from
the second occlusion element 278 in a similar manner as described
above for port 225 and lumen 263. The port 240 defines a lumen (not
shown) that is in fluid communication with the third lumen 276 of
the second catheter 270 (see e.g., FIG. 6-11) and can be used to
introduce cells/biological/therapeutic materials into and through
the third lumen 276 and out through the infusion aperture 279.
[0073] The catheter device 200 can also include a seal element 285
(see, e.g., FIG. 9) (also referred to a as a "seal", "sealing
element", "selective sealing element", or "filter-ring") disposed
at or near a distal end 272 of the second catheter 270. The seal
element 285 can prevent the entry of cells and or biologics that
have been injected into an artery from flowing back into the lumen
273. By doing so, a maximum number of cells can be delivered to the
treatment area, and improve engraftment efficiency. The seal
element 285 can be for example, a ring, a membrane or other known
sealing elements used in medical devices.
[0074] The slidable coupling of the first catheter 260 within the
second lumen 273 of the second catheter 270 allows a collective
length of the first catheter 260 and the second catheter 270 to be
adjusted by slidably moving the first catheter 260 and the second
catheter 270 relative to each other. Because the first occlusion
element 268 is coupled to the first catheter 260 and the second
occlusion element 278 is coupled to the second catheter 270, the
slidable adjustment of the first catheter 260 and the second
catheter 270 can thus allow adjustment of a distance between the
second occlusion element 278 and the first occlusion element 268.
The second lumen 273 of the second catheter 270 can be sized to
receive the first catheter 260 with sufficient clearance to allow
for ease of sliding/adjustment.
[0075] In use, the catheter device 200 can be placed at a desired
location within an artery, such as for example, within a splenic
artery 40 (see e.g., FIG. 1) and used to infuse a cell/biological
material to a pancreas 30. A length of the first catheter 260 and
the second catheter 270 can be adjusted such that a selected
portion (e.g., a pancreatic portion) of the splenic artery 40 is
isolated between the first occlusion element 268 and the second
occlusion element 278. A cell/biologic material can be injected
through the catheter device 200 and into the isolated region of the
splenic artery 40.
[0076] The infusion of a cell/biological agent can occur in the
localized region surrounding the isolated region or segment of
vessel 40. In some instances, however, the presence of one or more
additional, side-branching vessels forming a flow-restricting
configuration in the isolated region of vessel 40 can allow
infusion to occur in a larger semi-localized region.
[0077] To allow the operator to accommodate the location of these
side branches to fall within the isolated region, the first
catheter 260 can be configured such that it is slidably associated
with the second catheter 270 and the space between (e.g., distance
between) occlusion elements 268 and 278 can be varied according to
the circumstances of the desired treatment. The positioning of the
distal occlusion element 268 within an artery can be individualized
based on the specific anatomy to allow an enclosed or isolated area
between the two occlusion elements 268 and 278 with a linear length
ranging, for example, from 3 cm to 22 cm.
[0078] The cells targeted to the pancreas 30 (see e.g., FIG. 1) can
be infused through infusion port 240, traverse through the third
lumen 276, and exit through the infusion aperture 279 into the area
isolated between the two occlusion elements 268 and 278. The
catheter device 200 can be configured to enable delivery of target
cells, such as insulin producing beta cells, and autologous stem
cells (mesenchymal, bone marrow, and others) to blood vessels in
communication with the pancreas in situ. The infusion pressure in
the isolated blood vessel region can be measured with pressure
monitoring through the infusion lumen of the catheter (with a
monometer (not shown) in line with infusion port 279). The pressure
in the third lumen 276 can be based on the size of the cells being
delivered, on the flow rate, the viscosity of the solution, and/or
flow resistance of the third lumen 276 of second catheter 270. The
flow resistance of the catheter device 200 can in turn be
determined based on, for example, the inner coating material, the
size and the length of the third lumen 276, the size of the third
port 240, and/or the size of the distal infusion aperture 279. The
catheter device 200 can allow for rapid infusion of cells (e.g., up
to 2 milliliter per second (ml/sec)). In some applications, the
rapid infusion of cells can enhance uptake and eventual
engraftment. Smaller aperture size (e.g., the infusion aperture
279), lumen size (e.g., the third lumen 276), and increased flow
resistance may cause "sludging" of cells, leading to poor
intra-arterial flow and diminished uptake. Lastly, the infusion
aperture 279 and luminal design of the catheter device 200 can be
configured to minimize risk of mechanical cell damage during the
infusion process.
[0079] FIG. 12 illustrates an embodiment of a catheter device 300
that uses two filter elements, instead of expandable balloons to
occlude and isolate the area of interest for infusion of cells or
chemotherapeutic agents, without inhibiting the flow of plasma
through the isolated area. The filter elements can be formed with,
for example, a medical mesh material. The size of the pores of the
filter elements can be, for example, about 2 microns (.mu.m) or
less in length, which can inhibit cells from passing through the
filter element, but not impede serum/plasma and other components
from passing through the filter element. The catheter device 300
can be used for the same or similar functions as described above
for catheter device 200. For example, the catheter device 300 can
be used for introduction of cells or other biologic or therapeutic
material into a desired location within a patient's body, such as
within a splenic artery.
[0080] The catheter device 300 includes a first catheter 360 and a
second catheter 370 that can be slidably coupled together as
described above for catheter device 200, a first Y-adaptor 328
(also referred to herein as "first set of ports") coupled to the
first catheter 360, a second Y-adaptor 343 (also referred to herein
as "second set of ports") coupled to the second catheter 370, a
first occlusion element 368 (also referred to herein as "dilation
element", "occluder", "distal occlusion element") and a second
occlusion element 378 (also referred to herein as "dilation
element", "occluder", "proximal occlusion element") to occlude a
portion of an artery. The first occlusion element 368 is coupled to
the first catheter 360 and the second occlusion element 378 is
coupled to the second catheter 370.
[0081] In this embodiment, the occlusion elements 368 and 378 are
filter elements that can be moved between a collapsed configuration
(also referred to as "retracted configuration" or "closed
configuration") for insertion of the catheter device 300 into a
body of a patient (e.g., into an artery) and an expanded
configuration (also referred to as "dilated configuration" or "open
configuration"), as shown in FIG. 12, for occluding a portion of an
artery. The occlusion elements 368 and 378 when in the collapsed
configuration have a smaller outer perimeter (or diameter) than
when in the expanded configuration.
[0082] The catheter device 300 includes a distal end portion 312
and a proximal end portion 311. FIG. 13 is a side view of the
distal end portion 312 of the catheter device 300 and FIGS. 14-19
illustrate cross-sections at various locations along the distal end
portion 312 of the catheter device 300. As shown in FIGS. 14-19,
the first catheter 360 defines a first lumen 363 and a second lumen
365 that each can extend a length of the first catheter 360. The
first lumen 363 can be configured to receive a wire deployment
device 382 that can be coupled to the filter element 368 and
configured to move the filter element 368 from its expanded or open
configuration and its collapsed or closed configuration. The second
lumen 365 can be configured to receive a guidewire 380 (shown in
FIG. 12).
[0083] The second catheter 370 defines a first lumen 373, a second
lumen 374, and a third lumen 376. The first lumen 373 is configured
to slidably receive at least a portion of the first catheter 360
therethrough. The second lumen 374 can be configured to receive a
wire deployment device 381. The wire deployment device 381 can be
coupled to the filter element 378 and used to move the filter
element 378 between its expanded or open configuration and its
collapsed or closed configuration. The third lumen 376 can
terminate and be in fluid communication with an infusion aperture
379 (see, e.g., FIG. 16) near a distal end 372 of the second
catheter 370. The infusion aperture 379 can be used to communicate,
for example, a cell or cells (or other therapeutic or biologic
material) to a desired location within a body of a patient.
[0084] The first Y-adaptor 328 includes a port 320 and a port 325
as shown in FIG. 12. The port 320 defines a lumen (not shown) that
is in fluid communication with the first lumen 363 of the catheter
360. The port 325 defines a lumen (not shown) that is in fluid
communication with the second lumen 365 of the catheter 360, and
can be used for introduction of the guidewire 380 into the second
lumen 365. The second Y-adapter 343 includes three ports 330, 335
and 340, as shown in FIG. 12. The port 330 defines a lumen (not
shown) that is in fluid communication with the first lumen 373 of
the second catheter 370 and can receive the first catheter 360
therethrough. The port 335 defines a lumen (not shown) that is in
fluid communication with the second lumen 374 of the second
catheter 370, and the port 335 defines a lumen (not shown) that is
in fluid communication with the third lumen 376 of the second
catheter 370.
[0085] The filter elements 368 and 378 can each be shaped as a cone
when in their expanded or open configurations as shown in FIGS. 12
and 13. The filter elements 368 and 378 can each be sized when in
their expanded or open configurations to meet the size of a
particular vessel diameter in which the catheter device 300 is to
be deployed. After infusion of cells or a therapeutic/biologic
material through the catheter device 300, the filter elements 368
and 378 can be collapsed to a smaller size for removal of the
catheter device 300 from the patient.
[0086] In some embodiments, a diameter of the occlusion elements
(e.g., 268, 278, 368, and 378) when expanded within an artery, such
as, for example, the splenic artery 40, can be adjustable to meet
anatomical variations including a) individual variability in the
size of the splenic artery 40 and b) end to end variation as the
artery size can taper down between the two ends of the artery. As
such, in some embodiments, to allow successful isolation of the
area for treatment, the proximal occlusion element (e.g., the
balloon 278 and/or the filter element 378) can be sized (e.g., have
an outer diameter or outer perimeter) between, for example, 3-12 mm
and the distal occlusion element (e.g., the balloon 268 and/or the
filter element 368) between, for example, 3-12 mm. The proximal
occlusion element can be larger than the distal occlusion element,
smaller than the distal occlusion element, or the same size as the
distal occlusion element.
[0087] Referring now to FIGS. 20-29, a multi-lumen catheter
insertion device 400 is illustrated according to an embodiment. The
multi-occlusion catheter insertion device 400 (also referred to
herein as "catheter device" or "device") includes a handle 410, an
actuator 450, a first catheter 460 (also referred to herein as
"inner catheter"), and a second catheter 470 (also referred to
herein as "outer catheter") and can be movable between a first
configuration and a second configuration. As described in further
detail herein, the device 400 can be grasped by a user (e.g., a
doctor, physician, surgeon, technician, etc.) and manipulated
substantially single handedly to insert a portion of the first
catheter 460 and a portion of the second catheter 470 into a bodily
lumen of a patient and to move, inflate, deflate, adjust, and/or
otherwise reconfigure the portion of the first catheter 460 and the
portion of the second catheter 470 within the bodily lumen. For
example, the second catheter 470 can be moved relative to the first
catheter 460, and vice-versa, to adjust a distance between a first
occlusion element 468 coupled to a distal end portion of the first
catheter 460 and a second occlusion element 478 coupled to a distal
end portion of the second catheter 470. The device 400 can be used
to isolate a segment of a bodily lumen within the space or region
defined between the first occlusion element 468 and the second
occlusion element 478. Thus, a procedure can then be performed
within the isolated segment such as, for example, delivering a cell
or a therapeutic/biological agent to the isolated segment.
[0088] The handle 410 of the device 400 can be any suitable shape,
size, or configuration. For example, in some embodiments, the
handle 410 can have a shape and size that can enhance the
ergonomics of the device 400. More specifically, the handle 410 has
a proximal end portion 411, a distal end portion 412, and a medial
portion 413 that can be shaped in such a manner as to be easily
gripped by a user (e.g., a doctor, physician, surgeon, technician,
etc.). In some embodiments, the handle 410 can include a grip
section 417 (see, e.g., FIG. 21) or the like that can have, for
example, a rough surface finish, detents, protrusions, or the like
that can enhance the ergonomics of the handle 410. In other
embodiments, the grip section can be, for example, an insert, an
over-mold, or the like that is formed from a relatively deformable
material and that can have a relatively high coefficient of
friction, thereby enhancing the ergonomics of the handle 410.
[0089] The proximal end portion 411 of the handle 410 includes a
first port 420 and a second port 425 collectively referred to
herein as a first set of ports 428). The first port 420 and the
second port 425 can be any suitable size, shape, or configuration.
In some embodiments, the first port 420 and the second port 425 can
be coupled together via any suitable method (e.g., an adhesive,
ultrasonic welding, mechanical fastener, and/or the like). In other
embodiments, the first port 420 and the second port 425 can be
monolithically formed.
[0090] The first port 420 and the second port 425 can extend from
the proximal end portion 411 of the handle 410 such that at least a
portion of the first port 420 and the second port 425 is
accessible, as shown in FIGS. 20 and 21. In some embodiments, the
first set of ports 428 can be, for example, a first Y-adapter,
substantially similar to the Y-adapter 228 and/or 328. In other
embodiments, a first port and a second port can be, for example,
substantially parallel in a stacked configuration. In yet other
embodiments, a handle can include a first port and a second port
that are substantially coaxial and arranged in a substantially
concentric configuration such that at least a portion of the first
port is disposed within the second port, or vice versa.
[0091] Although not shown in FIGS. 14-29, the first port 420 and
the second port 425 can be physically and fluidically coupled to an
exterior device, mechanism, and/or the like as described above, for
example, with reference to insertion device 100. For example, the
first port 420 and the second port 425 can each define a lumen
(described in more detail below) in fluid communication with such a
device. The first port 420 and the second port 425 can each include
a Luer-Lok.RTM. and/or any other attachment mechanism that can
physically and fluidically couple the first port 420 and/or the
second port 425 to any suitable device either directly or
indirectly (e.g., by an intervening structure such as a flexible
tubing to the like). The first set of ports 428 can be physically
and fluidically coupled to the first catheter 460 such that when an
external device is coupled to the handle 410 via the first port 420
and/or the second port 425, at least the portion of the first
catheter 460 is placed in fluid communication with that external
device via the first port 420 and/or the second port 425. For
example, the first port 420 can be coupled to a device that can,
for example, supply a pressurized fluid (e.g., an inert gas, air,
saline, water, and/or any other suitable fluid in gaseous or liquid
form) that can flow through the first port 420 to be delivered to a
portion of the first catheter 460, as described in further detail
herein. Furthermore, the second port 425 can be coupled to a device
that can advance a guidewire or the like through the second port
425 and into a portion of the first catheter 460, as described in
further detail herein. In some embodiments, a guidewire or the like
can be manually inserted through the second port 425 without the
use of an external device.
[0092] The distal end portion 412 of the handle 410 includes a
third port 430, a fourth port 435, and a fifth port 440
(collectively referred to as a second set of ports 443). In some
embodiments, the second set of ports 443 includes the fifth port
440 and only one of the third port 430 and the second port 435. The
second set of ports 443 can be any suitable size, shape, or
configuration as described above with reference to the first set of
ports 428. For example, the second set of ports 443 can be, for
example, monolithically and/or unitarily formed. In some
embodiments, the second set of ports 443 can be monolithically
formed with the catheter 470. In some embodiments, the second set
of ports 443 can be formed with and/or coupled to any suitable
structure or component of the handle 410 such that the second set
of ports 443 can be moved relative to the handle 410 as described
in more detail below.
[0093] The third port 430, the fourth port 435, and the fifth port
440 can each include a Luer-Lok.RTM. and/or any other attachment
mechanism that can physically and fluidically couple the third port
430, the fourth port 435, and/or the fifth port 440 to any suitable
attachment, device, mechanism, and/or the like. The second set of
ports 443 can be physically and fluidically coupled to the second
catheter 470 such that when an external device is coupled to the
handle 410 via the third port 430, the fourth port 435, and/or the
fifth port 440, at least a portion of the second catheter 470 is
placed in fluid communication with that external device. For
example, in some embodiments, the third port 430 and/or the fourth
port 435 can be coupled to a device that can supply a pressurized
fluid (as described above) that can flow through the third port 430
and/or the fourth port 435, respectively, to be delivered to a
portion of the second catheter 470, as described in further detail
herein. In some embodiments, the fifth port 440 is coupled to, for
example, an infusion device that is configured to deliver a
biological or therapeutic agent and/or other suitable drug
formulation to a target tissue via the fifth port 440 and a portion
of the second catheter 470. In some embodiments, the fifth port 440
can be coupled to, for example, an irrigation device that can
deliver an irrigation fluid to, for example, an isolated segment of
a bodily lumen via the fifth port 440 and a portion of the second
catheter 470. In some embodiments, the fifth port 440 can be
coupled to, for example, the infusion device configured to deliver
the biological agent and/or other suitable drug formulation, as
described in further detail herein.
[0094] As shown in FIGS. 20-22, the handle 410 defines a first
track 414 and a second track 416. The first track 414 slidably
receives a portion of the actuator 450. More specifically, at least
a portion of the actuator 450 can extend through the track 414,
thereby allowing a user to engage the actuator 450. As such, the
track 414 can define a path along which the actuator 450 can be
moved between a first position relative to the handle 410 and a
second position relative to the handle 410, as described in further
detail herein. In a similar manner, the second track 416 slidably
receives a portion of the fifth port 440. In this manner, the fifth
port 440 can extend through the second track 416 to be accessed by
a user. Moreover, the second track 416 can define a path along
which the fifth port 440 can be moved, as described in further
detail herein.
[0095] Although the device 400 is particularly shown in FIGS.
20-29, the arrangement of the first set of ports 428, the second
set of ports 443, the first track 414 and the second track 416 can
be arranged along a surface of the handle 410 in various
orientations. For example, although the first track 414 is shown as
being defined by a top surface of the handle 410 (see, e.g., FIG.
20) and the second track 416 as being defined by a side surface of
the handle 410 (see, e.g., FIG. 21), in other embodiments, a first
track configured to receive an actuator can be defined by a side
surface of a handle and a second track configured to receive a
fifth port can be defined by a top surface of the handle.
Similarly, while the first set of ports 428 and the second set of
ports 443 are shown extending from the handle 410 in a specific
orientation, the first set of ports 428 and/or the second set of
ports 443 can be oriented in any suitable manner relative to a
surface of the handle 410.
[0096] The actuator 450 of the device 400 is operably coupled to
the second set of ports 443.
[0097] For example, in some embodiments, the actuator 450 is
included in and/or coupled to the handle 410 and arranged relative
to the second set of ports 443 to be operably coupled thereto. In
other embodiments, a handle can be arranged such that at least a
portion of an actuator is monolithically formed with at least a
portion of a second set of ports. In some embodiments, an actuator
is operably coupled to a second set of ports via an intervening
structure or the like. For example, in some embodiments, the second
set of ports 443 can be coupled to a shuttle or the like, which in
turn, is coupled to an actuator. The actuator 450 can be any
suitable device, mechanism, assembly, etc. that is movable between
the first position relative to the handle 410, associated with the
device 400 in the first configuration (FIGS. 20-22), and a second
position relative to the handle 410, associated with the device 400
in the second configuration (FIG. 29).
[0098] In some embodiments, the actuator 450 can be a mechanism
that can be pushed or pulled to slide within the first track 414
defined by the handle 410 between its first position and its second
position. In some embodiments, the actuator 450 can be arranged to
slide relatively smoothly within the track 414 when moved between
its first position and its second position. In other embodiments,
the handle 410 and/or the actuator 450 can include a set of ribs,
teeth, detents, protrusions, etc. that are sequentially engaged as
the actuator 450 is moved between its first position relative to
the handle 410 and its second position relative to the handle 410.
In this manner, a user can move the actuator 450 a desired distance
that can be quantified by the actuator 450 and/or the handle 410
engaging a particular surface (e.g., a particular rib, tooth,
detent, protrusion, etc.). In some embodiments, the handle 410
and/or the actuator 450 can be arranged at a predetermined setting
that can correspond to a predetermined distance (e.g., 2 cm, 3 cm,
etc.) between an end portion of the first catheter 460 and an end
portion of the second catheter 470. In some embodiments, the set of
ribs, teeth, detents, protrusions, etc. included in the handle 410
and/or the actuator 450 can be associated with pre-defined settings
and/or adjustments.
[0099] Although not shown in FIGS. 20-29, in some embodiments, a
handle 410 can include a visual indicator such as a measuring scale
or the like. For example, in some embodiments, the handle 410 can
include indicia (e.g., lines, markings, tic marks, etc.) that
represents a gradation of a length of travel associated with moving
the actuator 450 between its first position relative to the handle
410 and its second position relative to the handle 410. In some
embodiments, the markings can represent distances of, for example,
a centimeter, half a centimeter, a millimeter, and/or the like. In
this manner, a user can view the indicia to determine a desired
distance to move that actuator 450 that would otherwise be
challenging or indeterminate. In some embodiments, the visual
indicator can substantially correspond with the ribs, teeth,
detents, protrusions, etc. of the handle 410 and/or actuator
450.
[0100] In some embodiments, the actuator 450 can be operably
coupled to one or more energy storage device (e.g., a spring or the
like) that can facilitate the movement of the actuator 450. For
example, the actuator 450 can include a push button that can
rearrange or reconfigure at least a portion of the actuator 450 to
allow a spring to transition from a compressed configuration
towards an uncompressed configuration to move the actuator 450
relative to the handle 410.
[0101] With the actuator 450 coupled to or monolithically formed
with a portion of the second set of ports 443, the actuator 450 can
be operable in moving the second set of ports 443 between a first
position relative to the handle 410 (e.g., a distal position) and a
second position relative to the handle 410 (e.g., a proximal
position). Moreover, with the second catheter 470 physically and
fluidically coupled to the second set of ports 443 (as described
above), the movement of the actuator 450 and the second set of
ports 443 can move the second catheter 470 between a first position
relative to the handle 410 and a second position relative to the
handle 410, as described in further detail herein.
[0102] The first catheter 460 and the second catheter 470 can be
any suitable catheter device. For example, in some embodiments, the
first catheter 460 and the second catheter 470 are multi-lumen
catheters. The first catheter 460 has a proximal end portion 461
(see, e.g., FIGS. 21, 23 and 29) and a distal end portion 462 (see,
e.g., FIGS. 20 and 29), and defines a first lumen 463 and a second
lumen 465 (see, e.g., FIGS. 24-28). The proximal end portion 461 of
the first catheter 460 is disposed within a portion of the handle
410. More specifically, the proximal end portion 461 of the first
catheter 460 can be fixedly disposed within the portion of the
handle 410 to place the first catheter 460 in fluid communication
with the first set of ports 428. In some embodiments, the first
catheter 460 can be physically and fluidically coupled to the first
set of ports 428. In other embodiments, a device can include a
first catheter that is monolithically formed with a first set of
ports. In this manner, the proximal end portion 461 of the first
catheter 460 is arranged such that the first lumen 463 of the first
catheter 460 is in fluid communication with a lumen 421 defined by
the first port 420 and the second lumen 465 of the first catheter
460 is in fluid communication with a lumen 426 of the second port
425, as shown in FIG. 23. Therefore, an external device (e.g., a
device that can supply a pressurized fluid, as described above) can
be physically and fluidically coupled to the first port 420 to
place the external device in fluid communication with the first
lumen 463 of the first catheter 460. Similarly, an external device
including at least a guidewire (not shown) can be coupled to the
second port 425 and can be manipulated to advance the guidewire
through the second port 425 and into the second lumen 465, as
described in further detail herein.
[0103] Referring back to FIG. 20, the distal end portion 462 of the
first catheter 460 extends beyond a distal end portion of the
handle 410 and includes an occlusion member 468. The occlusion
member 468 can be any suitable device or mechanism that is
configured to selectively limit, block, obstruct, or otherwise
occlude a body lumen (e.g., artery) in which the occlusion member
468 is disposed. For example, in some embodiments, the occlusion
member 468 can be an inflatable balloon or the like that can be
transitioned between a collapsed (e.g., deflated) configuration and
an expanded (e.g., inflated) configuration.
[0104] The arrangement of the first catheter 460 can be such that
the first lumen 463 is in fluid communication with the occlusion
member 468. For example, as shown in FIG. 24, the distal end
portion 462 of the first catheter 460 can define a channel 464 that
places the first lumen 463 in fluid communication with the
occlusion member 468. Thus, when the first port 420 is fluidically
coupled to a device that supplies a pressurized fluid (e.g., air,
inert gas, or liquid), the pressurized fluid can be delivered to
the occlusion member 468 via the lumen 421 of the first port 420,
the first lumen 463 of the first catheter 460, and the channel 464
of the first catheter 460. In this manner, the pressurized fluid
can transition the occlusion member 468 between a collapsed
configuration (not shown) and an expanded configuration (see e.g.,
FIG. 20), as described in further detail herein.
[0105] The second catheter 470 of the device 400 has a proximal end
portion 471 (see, e.g., FIGS. 20-22) and a distal end portion 472
(see, e.g., FIGS. 20 and 29), and defines a first lumen 473, a
second lumen 474, a third lumen 476 and an opening 479 (also
referred to herein as "infusion aperture") (as shown, for example,
in FIGS. 25-28). The second catheter 470 is movably disposed about
a portion of the first catheter 460 (see, e.g., FIGS. 21-23). More
specifically, the second catheter 470 can be arranged such that the
first catheter 460 is movably disposed within the first lumen 473
defined by the second catheter 470, as shown, for example, in FIGS.
26-28.
[0106] The proximal end portion 471 of the second catheter 470 is
movably disposed within the handle 410 to place the second catheter
470 in fluid communication with the second set of ports 443. In
some embodiments, the second catheter 470 can be physically and
fluidically coupled to the third port 430 and the fourth port 435,
and/or the fifth port 440. In other embodiments, a catheter
insertion device can include a second catheter that can be movably
disposed within a handle and can be operably coupled to one or more
ports via an intervening structure such as, for example, flexible
tubing or the like. In yet other embodiments, a catheter insertion
device can include a second catheter that is monolithically formed
with a third port, a fourth port, and/or a fifth port. In this
manner, the second catheter 470 is arranged such that the first
lumen 473 of the second catheter 470 movably receives the first
catheter 460, the second lumen 474 of the second catheter 470 is in
fluid communication with a lumen 431 defined by the third port 430
and a lumen 436 defined by the fourth port 435, and the third lumen
476 of the second catheter 470 is in fluid communication with a
lumen 441 defined by the fifth port 440, as shown in FIG. 25.
[0107] Referring back to FIG. 20, the distal end portion 472 of the
first catheter 470 extends beyond a distal end portion of the
handle 410 such that an occlusion member 478 of the second catheter
470 is disposed in a proximal position relative to the occlusion
member 468 of the first catheter 478. Expanding further, the first
catheter 460 extends within the proximal end portion 471 and the
distal end portion 472 when disposed in the first lumen 473. Thus,
the occlusion member 468 of the first catheter 460 can be disposed
in a distal position relative to the occlusion member 478 of the
second catheter 470. The occlusion member 478 can be any suitable
device or mechanism that is configured to selectively limit, block,
obstruct, or otherwise occlude a body lumen (e.g., artery) in which
the occlusion member 478 is disposed. For example, in some
embodiments, the occlusion member 478 can be substantially similar
to the occlusion member 468 of the first catheter 468.
[0108] The arrangement of the second catheter 470 can be such that
the second lumen 474 is in fluid communication with the occlusion
member 468. For example, as shown in FIG. 27, the distal end
portion 472 of the second catheter 470 defines a channel 475 that
places the second lumen 474 in fluid communication with the
occlusion member 478. Thus, when the third port 430 (and/or the
fourth port 435) is fluidically coupled to a device that supplies a
pressurized fluid, the pressurized fluid can be delivered to the
occlusion member 478 via the lumen 431 of the third port 430
(and/or the lumen 436 of the fourth port 435), the second lumen 474
of the second catheter 470, and the channel 475 of the second
catheter 470. In this manner, the pressurized fluid can transition
the occlusion member 478 between a collapsed configuration (not
shown) and an expanded configuration (as shown in FIGS. 20 and 29).
In a similar manner, the arrangement of the second catheter 470 can
be such that the third lumen 476 is in fluid communication with the
opening 479 (see, e.g., FIG. 28). For example, the distal end
portion 472 of the second catheter 470 defines a channel 477 that
places the third lumen 476 in fluid communication with the opening
479, as shown in FIG. 28. Thus, when the fifth port 440 is
fluidically coupled to an external device that supplies irrigation
or to a device that supplies a therapeutic agent, the irrigation
fluid or therapeutic agent can be delivered to an isolated segment
of a bodily lumen via the lumen 441 defined by the fifth port 440
and the third lumen 476, the channel 477, and the opening 479
defined by the second catheter 470.
[0109] The device 400 can be moved from the first configuration to
the second configuration by moving the actuator 450 from its first
position (e.g., a distal position) relative to the handle 410 to
its second position (e.g., a proximal position) relative to the
handle 410, as indicated by the arrow BB in FIG. 29. Expanding
further, with the second catheter 470 movably disposed about the
first catheter 460 and with the proximal end portion 471 of the
second catheter 470 operably coupled to the actuator 450, the
movement of the actuator 450 from its first position to its second
position moves the second catheter 470 relative to the first
catheter 460, as indicated by the arrow CC in FIG. 29. For example,
when the device 400 is in the first configuration, a first distance
D7 (FIG. 20) can be defined between the occlusion member 468 of the
first catheter 460 and the occlusion member 478 of the second
catheter 470. With the first catheter 460 fixedly disposed within
the handle 410, the movement of the second catheter 470 in the CC
direction (e.g., the proximal direction) increases the distance
between the occlusion member 468 of the first catheter 460 and the
occlusion member 478 of the second catheter 470 to a second
distance D8, as shown in FIG. 29. Thus, a segment or volume having
a desired length can be defined between the occlusion member 468 of
the first catheter 460 and the occlusion member 478 of the second
catheter 470.
[0110] In use, a guidewire can be inserted into the lumen 426 of
the second port 425 and through the second lumen 465 defined by the
first catheter 460. In this manner, the guidewire can be advanced
through a bodily lumen and the device 400 can be manipulated to
advance the first catheter 460 and the second catheter 470 along
the guidewire. Thus, the distal end portion 462 of the first
catheter 460 and the distal end portion 472 of the second catheter
470 can be placed at a target location within the bodily lumen such
as, for example, the haptic or splenic artery of the pancreas, as
shown in FIG. 30. At the target location, the actuator 450 can be
moved between its first position and its second position relative
to the handle 410 (e.g., the BB direction in FIG. 29) to define a
desired distance (e.g., the distance D8 in FIG. 29) between the
occlusion member 468 of the first catheter 460 and the occlusion
member 478 of the second catheter 470. With the desired distance
defined between the occlusion members 468 and 478, and with an
inflation source coupled to the first port 420 and the same or a
different inflation source coupled to the third port 430 (and/or
the fourth port 435), the occlusion member 468 of the first
catheter 460 and the occlusion member 478 of the second catheter
470, respectively, can be transitioned from a collapsed or deflated
configuration to an expanded or inflated configuration to
substantially isolate a segment of the bodily lumen disposed
therebetween (e.g., the pancreatic segment or portion of the
splenic artery 40 associated with, for example, the dorsal
pancreatic artery 42 and/or the pancreatic magnum artery 44), as
shown in FIG. 30. FIG. 30 is an illustration of the catheter device
400 disposed in situ within the splenic branch of the celiac
artery. As shown in FIG. 30, the occlusion elements 468 and 478
define or isolate an area of interest in between the occlusion
elements 468 and 478. Specifically, in this example, the region or
area of interest with blood supply to the pancreas is isolated via
the occlusion elements 468 and 478, spaced according to the
location of the dorsal pancreatic artery 42 and the pancreatic
magnum artery 44.
[0111] With the occlusion members 468 and 478 substantially
occluding the body lumen, a biological/therapeutic agent can be
delivered to the substantially isolated segment via the fifth port
440, the third lumen 476, and the opening 479 (i.e., the infusion
aperture), into the area substantially isolated between the
occlusion elements 468 and 478. In some instances, the
substantially isolated segment can be irrigated by coupling an
irrigation source to the fifth port 440. Thus, the irrigation can
be delivered to the substantially isolated segment via the lumen
441 of the fifth port 440 and the third lumen 476, the channel 477,
and the opening 479 of the second catheter 470. In some instances,
such irrigation can be delivered prior to the delivery of the
biological/therapeutic agent, after the delivery of the
biological/therapeutic agent, or substantially concurrently with
the biological/therapeutic agent.
[0112] FIG. 31 is a flowchart illustrating a method of accessing
and treating a pancreas. The method can be used, for example, to
occlude a portion of the splenic branch of the celiac artery
supplying the pancreatic tail. The method includes introducing a
catheter (e.g., the catheter device 100, 200, 300, and/or 400) into
a mammalian body over a guidewire (211, 311) into a celiac artery,
at 501. The catheter device can include an inner catheter (e.g.,
the first catheter 160, 260, 360, and/or 460) slidably coupled to
an outer catheter (e.g., the second catheter 170, 270, 370, and/or
470). In some embodiments, a guide catheter can be exchanged over
the guidewire into the celiac artery for support and introduction
of the catheter device. After the guidewire is in place, the
catheter device can be positioned over the guidewire, at 502, and
positioned to allow placement of a distal occlusion element (e.g.,
the distal occlusion element 168, 268, 368, and/or 468) of the
inner catheter at a distal edge of the pancreatic portion of the
splenic artery (see, e.g., FIG. 30). The distal occlusion element
and a proximal occlusion element (e.g., the proximal occlusion
element 178, 278, 378, and/or 478) of the outer catheter are
positioned to isolate a target portion of the pancreatic artery and
moved to an expanded configuration, at 503. After the occlusion
elements are deployed, contrast dye is injected through an
injection port of the outer catheter and the isolated area of the
splenic artery is visualized to identify the pancreatic branches,
at 504. Visualization enables the clinician to confirm isolation of
the pancreatic magnum artery and dorsal pancreatic artery or any
other large artery supplying the pancreatic body or tail in the
area, at 505. If desired, the catheter device can be moved back and
the procedure repeated until the clinician can confirm that the
catheter is correctly positioned. Some example isolation regions
include: (a) the pancreatic magnum artery 44 (and its branches),
(b) the dorsal pancreatic artery 42 if the origin is within the
splenic artery 40, and (c) both pancreatic magnum artery 44 and
dorsal pancreatic artery 42 arteries are isolated in one contiguous
area (if other extra-pancreatic arteries do not arise between the
origin of the two within the splenic artery 40).
[0113] After the first takeoff of the pancreatic magnum artery 44
is identified (or the dorsal pancreatic artery), the placement of
the outer catheter of the catheter device can allow the edge of the
distal occlusion element to be placed beyond this artery. At this
point, the inner catheter can be secured in place, and the outer
catheter can be moved relative to the inner catheter to allow the
maximum perfusion area to the body and tail of the pancreas.
Frequent injection of contrast through the infusion port can be
made to ensure no extra-pancreatic vessels are included in the
isolated area.
[0114] After the desired area is isolated and the occlusion
elements are positioned at a desired location, the therapeutic
cells/biologics/agent is introduced to the isolated area of the
splenic artery through the infusion port of the outer catheter, at
506. The infusion port design can allow rapid and atraumatic
infusion of cells/biologics/agent into the isolated area. This
allows the clinician to adjust rate of infusion of therapeutic
cells/biologics/agents into the isolated area based on specific
pharmacodynamics and or engraftment efficiency requirements. The
infusion of the therapeutic material can be followed by heparinized
blood to exclude any residual cells left behind in the dead space
of the catheter device. During isolation of the artery described
above, perfusion to the end organ to the artery spleen can be
disrupted, but the redundancy in the arterial perfusion system to
the spleen, and limited time during which the arterial supply is
interrupted, should prevent any long-term sequela, or abnormal
condition of the splenic cells. If needed and/or desired, the
guidewire port can be used to perform perfusion of the splenic
artery beyond the isolated area. For example, the guidewire can be
removed from its port after the catheter device is in place, and
the guidewire port can be connected to a source of arterial blood
with suitable pressure (i.e. the side port of an arterial sheath or
guide sheath). At the end of the infusion, both occlusion elements
are moved to a collapsed configuration and the catheter device is
removed from the body over the guidewire as one unit, followed by
the guidewire and the guide catheter.
[0115] In a variation of the method described above using balloons
as the occlusion elements, the same catheter can be used to isolate
arterial branches supplying the head of the pancreas via the
hepatic artery or superior mesenteric artery. One such clinical
possibility is treatment of pancreatic cancer with the tumor
located in the head of the pancreas. After placement of the
catheter device in the respective artery, the infusion of contrast
through the infusion port can identify the branches most proximate
to the tumor, and then after occluding the distal and proximal
portion of the artery around the branch(es), the chemotherapeutic
agent can be delivered selectively to the area of interest in the
pancreas.
[0116] In some embodiments, a method can include introducing a
catheter device into a splenic artery. The catheter device can
include an inner catheter, a first expandable occlusion element
coupled to the inner catheter, an outer catheter defining a first
lumen configured to introduce a therapeutic biologic/agent to one
or more target pancreatic vessels, a second lumen configured to
slidably receive at least a portion of the inner catheter, and a
second expandable occlusion element coupled to the outer catheter
and disposed proximally to the first occlusion element. The
catheter is advanced to a target pancreatic portion of the splenic
artery. A region of the target pancreatic portion of the splenic
artery is selectively isolated and the therapeutic biologic/agent
is injected into the isolated region. In some embodiments, the
therapeutic biologic/agent includes stem cells. In some
embodiments, the method further includes advancing at least a
portion of the catheter device to an ostium of a celiac artery, its
hepatic branch, or if necessary, the superior mesenteric artery
(based on individual anatomy). In some embodiments, a contrast dye
is injected into the isolated region and isolation of a pancreatic
magnum artery and/or a dorsal pancreatic artery can be confirmed.
In some embodiments, a guidewire can be disposed through the
infusion lumen to focally perforate the vascular lumen in the
isolated area to increase exogenous cell penetration into the
pancreatic tissue. In some embodiments, the therapeutic biologic
can be introduced into the isolated segment or region to enhance
cellular transmigration across the endothelial cells prior to
introduction of the therapeutic biologic.
[0117] In some embodiments, a method can include introducing a
catheter device into a bile duct. In use, the catheter device 200
can be placed at a desired location within the bile duct and used
to infuse a therapeutic agents into the bile duct which will
diffuse through the bile duct into the pancreas. A length of the
first catheter 260 and the second catheter 270 can be adjusted such
that a selected portion of the bile duct is isolated between the
first occlusion element 268 and the second occlusion element 278. A
therapeutic agent can be injected through the catheter device 200
and into the isolated region of the bile duct.
[0118] The infusion pressure in the isolated blood vessel region
can be measured with pressure monitoring through the infusion lumen
of the catheter (with a monometer (not shown) in line with infusion
port 279). The pressure in the third lumen 276 can be based on the
size of the agents being delivered, on the flow rate, the viscosity
of the solution, and/or flow resistance of the third lumen 276 of
second catheter 270. The flow resistance of the catheter device 200
can in turn be determined based on, for example, the inner coating
material, the size and the length of the third lumen 276, the size
of the third port 240, and/or the size of the distal infusion
aperture 279. The catheter device 200 can allow for rapid infusion
of agents (e.g., up to 2 milliliter per second (ml/sec)). In some
applications, the rapid infusion can enhance uptake and eventual
engraftment.
[0119] Any catheter device described herein and/or any combination
of the catheter devices described herein can allow the above goals
to be achieved. For example, a catheter device can include two
catheters slidably coupled where an inner catheter defines a
guidewire housing port and a distal occlusion element, and an outer
catheter forms an infusion port and a proximal occlusion element,
along with an inner lumen allowing the insertion of the inner
catheter. The two catheters can be assembled outside the body with
a distance between the two occlusion elements set to a desired
length. For example, in some embodiments, the minimum distance
between the two occlusion elements can be 3 cm, and the length can
be adjusted up to a distance between the two occlusion elements of
25 cm as needed.
[0120] The devices described herein can also be provided in a kit.
In some embodiments, a kit for use in the delivery of a biological
agent to an area proximal to the pancreas can include, for example,
one or more catheter devices (e.g., the catheter devices 100, 200,
300, and/or 400) as described herein and one or more
biologic/therapeutic agent for delivery to the pancreas. The
catheter devices can include, for example, a proximal end portion,
a distal end portion and one or more expandable devices, such as a
balloon or a filter, associated therewith. In some embodiments, the
catheter device can include a first catheter configured to be
slidably received within a lumen of a second catheter, a first
occlusion element coupled to the first catheter and a second
occlusion element coupled to the second catheter. In such an
embodiment, a distance between the first and second occlusion
elements can be varied or adjusted. The occlusion elements can be
expandable to engage a wall of a blood vessel thereby substantially
isolating an interior region of the vessel between the first and
second occlusion elements. Moreover, the first and second catheters
can be configured such that at least one of the first and second
catheters has a lumen configured to deliver a
biological/therapeutic agent to the isolated interior region via an
infusion port. The infusion port can allow for rapid and atraumatic
delivery of cells/biologics into the isolated area. In some
embodiments, a pressure regulator can be provided that is
configured to regulate the fluid pressure of the agent or the
materials used to dilate the occlusion element(s) (e.g., in a
balloon embodiment).
[0121] In some embodiments, a kit can further include one or more
biologic/therapeutic agents for delivery to the pancreas, a
stylet(s); one or more catheters adapted and configured for
accessing the pancreatic vessels; a dilator; a guidewire; a guide
catheter; capsules for direct connection of biological
materials/cells to the infusion port of the delivery catheter; a
manometer to monitor the pressure in the isolated area; and/or a
pump to regulate the infusion rate of cells/biologics.
[0122] In some embodiments, any of the components of a kit can be
packaged together and collectively sold as a catheter device or can
be packaged independently or in subgroups and sold together or
separately. For example, in some embodiments, the handle 410 can be
packaged independently from the first catheter 460 and the second
catheter 470. Moreover, the first catheter 460 and the second
catheter 470 can be packaged independent from one another or
packaged together. As such, the handle 410 can be sold independent
of the first catheter 460 and the second catheter 470. The first
catheter 460 and the second catheter 470 can be sold independent of
one another or together. Thus, in some embodiments, the handle 410
can be packaged independent of the first catheter 460 and the
second catheter 470 and, prior to use, can be coupled to the first
catheter 460 and the second catheter 470 such that the first set of
ports 428 are in fluid communication with the corresponding lumen
of the first catheter 460 and the second set of ports 443 are in
fluid communication with the corresponding lumen of the second
catheter 470. In some embodiments, the handle 410 can be, for
example, reusable, while the first catheter 460 and the second
catheter 470 are disposable. In other embodiments, the handle 410
can be coupled to the first catheter 460 and the second catheter
470 during, for example, a manufacturing process and packaged
together to be sold as a complete catheter device.
[0123] In some embodiments, placement of the occlusion elements
(e.g., the distal occlusion elements 168, 268, 368, and/or 468 and
the proximal occlusion elements 178, 278, 378, and/or 478) and the
lengths of each region therebetween can be varied based on the
needs of the individual application. The catheter devices 100, 200,
300 and/or 400 can retain sufficient trackability to allow
advancement into the target region of the patient. In some
embodiments, the catheter material can be flexible enough to
traverse local anatomy yet have enough tensile strength to be able
to be placed in position in place over a guidewire (e.g., the
guidewire 280 and/or 380). Furthermore, for the first catheters
160, 260, 360, and 460 and the second catheters 170, 270, 370, and
470, respectively, to be slidable relative to each other in situ,
various radial and tensile strengths can be incorporated in
each.
[0124] The first catheters 160, 260, 360, and/or 460 (i.e., the
inner catheters) and the second catheters 170, 270, 370, and/or 470
(i.e., the outer catheters) can be fabricated of any material
suitable for catheters, such as linear low density or high density
polyethylene, nylon, polyurethane, polypropylene, silicone rubber,
or other non-thrombogenic materials. In some embodiments, an outer
catheter can be formed from a linear low-density polyethylene,
while an inner catheter can be formed from a nylon. In some
embodiments, the outer catheters described herein can be fabricated
to include a structure for reinforcement (not shown), such as a
metal braid or the like located between an inner and outer layer.
The reinforcement structure can extend along any desired length of
such outer catheters. In some embodiments, a reinforcement
structure can extend along the entire length of an outer
catheter.
[0125] In some embodiments, regions of a first catheter (i.e., an
inner catheter) such as those described herein can also be
fabricated in any manner that allows the relative stiffness of each
region to vary. In some embodiments, an outer layer in each region
of an outer catheter and/or an inner catheter can include a
material with a different durometer measurement of hardness. For
example, the material used in an intermediate region can be
relatively harder than that used in a distal region, and the
material used in a proximal region can be relatively harder than
that used in the intermediate region. Other manners of varying the
stiffness of an inner catheter and/or an outer catheter (i.e., a
first catheter and a second catheter, respectively, such as those
described herein) can include varying the length of a reinforcement
structure, varying the degree of reinforcement provided by the
reinforcement structure along the length of the inner catheter
and/or the outer catheter, changing a cross-sectional size and/or
shape of the inner catheter and/or the outer catheter, introducing
and/or forming one or more discontinuities along a length of the
inner catheter and/or the outer catheter (e.g., one or more ribs,
notches, grooves, protrusions, etc.), and/or any other suitable
means for varying stiffness.
[0126] In some embodiments, the catheter devices described herein
can include one or more sensors that can provide relative
information such as, for example, position of the occlusion
members, movement of the actuator, flow rate of the biological
agent, and/or any other suitable information. For example, in some
embodiments, a sensor can be operably coupled to the actuator 450
of the device 400 and can be configured to provide information
associated with a distance that the actuator 450 has been moved. In
such embodiments, a user and/or an electronic device can determine
a distance between the occlusion member 468 of the first catheter
460 and the occlusion member 478 of the second catheter 470 based
on the information from the sensor. In some embodiments, a sensor
can be disposed within the third lumen 476 of the second catheter
470 that can be configured to determine a flow rate of irrigation
and/or a biological/therapeutic agent therethrough.
[0127] In some embodiments, radiopaque markers of gold or tantalum,
for example, can also be provided on or in an inner catheter
positioned, within or on an occlusion element(s) (e.g., the
occlusion elements 168, 178, 268, 278, 368, 378, 468, and/or 478),
and/or on an outer catheter to aid in visualization and to assist
in monitoring the position of at least a portion of a catheter
device (e.g., the catheter devices 100, 200, 300, and/or 400) on an
imaging device (e.g., a fluoroscope, an X-Ray, a Magnetic Resonance
Imaging (MRI) scan, a computerized tomography (CT) scan, and/or the
like) during a procedure. In some embodiments, an inner catheter
can optionally be coated with a lubricous material, such as
silicone, acrylamide, or a hydrophilic polyurethane coating, to
ease retraction. Similarly, the outer catheter and the occlusion
elements can be coated with the lubricous material to ease
advancement through a guiding catheter and/or a tortuous
vessel.
[0128] In some embodiments, an outer diameter of an outer catheter
(e.g., the second catheters 100, 200, 300 and/or 400) and
non-deployed occlusion elements (e.g., the occlusion elements 168
and 178, 268 and 278, 368 and 378, and/or 468 and 478) can be, for
example, between about 6 French and about 8 French and thus, can be
used with, for example, a 7-9 French guiding catheter (if need
be).
[0129] In some embodiments, after a guidewire (e.g., the guidewire
280 and/or 380) is removed, a corresponding lumen (e.g., the second
lumen 165, 265, 365, and/or 465 of the first catheter 160, 260,
360, and/or 460, respectively) can be used to establish arterial
blood flow distal to the occlusion end (e.g., the distal end
portion) of a catheter device or infusion of other therapeutic
agents if desired.
[0130] In some embodiments, any suitable configuration of the
catheter devices can be used to achieve the objectives described
herein including, for example, employing one or more catheter
devices 100, 200, 300, and/or 400, employing a contiguous
inflation/occluding section having differing stiffness along its
length to achieve the two occluding elements, and/or the like.
[0131] In some embodiments, to allow endovascular isolation of the
pancreatic portion of the splenic artery 40 (see e.g., FIG. 1) as a
mechanism to achieve substantially exclusive delivery of a
therapeutic agent/cells to the pancreatic parenchyma, a catheter
device such as those described herein can include anatomical and
mechanical features such as, for example, isolation of the two ends
of the pancreatic portion of the artery using two occlusion
elements; adjustment of the diameter of the occlusion elements to
meet the specific anatomical needs; adjustment of the distance
between the two occlusion elements (based on individual variation
to selectively isolate for instance the portion of the splenic
artery 40 to the pancreas 30 on one hand and maximize the perfusion
area on the other hand); an infusion port where injection of
contrast can be used to visualize the area of the artery isolated;
an infusion port, shaft, and/or aperture design to allow atraumatic
and rapid delivery of cells/therapeutic agents; and/or recovery of
the occlusion element along with the catheter at the end of the
procedure, prior to which flushes through the infusion port can
assure clearance of the cells from the isolated space.
[0132] In some instances, any portion of the catheter devices 100,
200, 300, and/or 400 can be rotated to allow for a more targeted
delivery of the biological/therapeutic agent to a selected tissue.
For example, while the infusion apertures 279, 379 and 479 are
shown as being disposed at a specific position relative to the
pancreas 30, in some instances, the catheter device 100, 200, 300,
and/or 400 can be rotated to rotate the second catheter 470
relative to the pancreas 30. Thus, the infusion aperture 279, 379,
and/or 479 is rotated about a longitudinal axis (not shown) defined
by the second catheter 270, 370, and/or 470. As such, the infusion
aperture 279, 379, and/or 479 can be positioned adjacent to a
target tissue for a more accurate delivery of the biological agent
than would otherwise be possible. In some embodiments, any portion
of the catheter device 200, 300, and/or 400 can include indicia
and/or markings that can be associated with the relative position
of the infusion aperture 279, 379, and/or 479. In this manner, a
user can visualize the radial position of, for example, an actuator
(e.g., the actuator 450) to determine the radial position of the
infusion aperture 279, 379, and/or 479.
[0133] Any catheter device described herein and/or any combination
of the catheter devices described herein can allow the above goals
to be achieved. For example, a catheter device can include two
catheters slidably coupled where an inner catheter defines a
guidewire housing port and a distal occlusion element, and an outer
catheter forms an infusion port and a proximal occlusion element,
along with an inner lumen allowing the insertion of the inner
catheter. The two catheters can be assembled outside the body with
a distance between the two occlusion elements set to a desired
length. For example, in some embodiments, the minimum distance
between the two occlusion elements can be 3 cm, and the length can
be adjusted up to a distance between the two occlusion elements of
25 cm as needed.
[0134] In some embodiments, a catheter device such as those
described herein, which is suitable for accessing the pancreas 30
(see e.g., FIG. 1) can include features and/or functions, such as,
for example, selective isolation of the targeted portion of the
pancreatic portion of the splenic artery 40 for targeted delivery
of the therapeutic agent to the pancreas 30; an adjustable distance
between the two ends of the perfusion/infusion area (e.g., an
isolated region) to accommodate individual anatomy to allow
isolation of the largest portion of the splenic artery 40 with
branches only supplying the pancreatic tail 32 and body 34 (see
e.g., FIG. 1) and if clinically indicated, the same catheter can be
used to isolate portions of the hepatic artery 54 and/or superior
mesenteric artery 52 supplying the head of the pancreas 38; an
infusion port allowing first, injection of contrast into the
isolated segment to allow direct visualization of the origin of the
branches of the splenic artery 40 supplying the pancreatic tissue,
and second, introduction of therapeutic drugs/cells, the dimensions
and design of the infusion port and catheter shaft allowing rapid
and atraumatic delivery of cells; adjustable diameter of the
proximal and/or distal occluders to allow both intravariable and
intervariable sizes of the splenic artery 40; and/or a
self-contained assembly unit with easy retrieval after completion
of the procedure.
[0135] While various embodiments have been described above, it
should be understood that they have been presented by way of
example only, and not limitation. Where schematics and/or
embodiments described above indicate certain components arranged in
certain orientations or positions, the arrangement of components
may be modified. While the embodiments have been particularly shown
and described, it will be understood that various changes in form
and details may be made. Although various embodiments have been
described as having particular features and/or combinations of
components, other embodiments are possible having a combination of
any features and/or components from any of embodiments as discussed
above. For example, the size and specific shape of the various
components can be different from the embodiments shown, while still
providing the functions as described herein. Furthermore, each
feature disclosed herein may be replaced by alternative features
serving the same, equivalent or similar purpose, unless expressly
stated otherwise. Thus, unless expressly stated otherwise, each
feature disclosed is one example only of a generic series of
equivalent or similar features.
[0136] For example, although the outer catheters 170, 270, 370,
and/or 470 of the catheter devices 100, 200, 300, and/or 400
include an infusion lumen (i.e., a third lumen) and infusion port
and/or aperture to deliver a cell/biologic/therapeutic material to
a desired blood vessel, in other embodiments, the inner catheter
160, 260, 360, and/or 460, respectively, can include the infusion
lumen. Similarly, although the guidewire lumen (i.e., a second
lumen) is described as being defined by the inner catheter 160,
260, 360, and/or 460, a guidewire lumen can be alternatively, or in
addition to, included in and/or defined by the outer catheter 170,
270, 370, and/or 470. Thus, any of the lumens of the catheter
devices 100, 200, 300, and/or 400 can be defined by either the
first catheter 160, 260, 360, and/or 460 (i.e., an inner catheter)
or the second catheter 170, 270, 370, and/or 470 (i.e., an outer
catheter). In another example, although shown coupled to the second
catheter 270 and/or 370, the sealing element 285 and/or 385 can
alternatively be coupled to the first catheter 260 and/or 360.
[0137] Although the catheter devices 100, 200, 300, and/or 400 have
been shown and described as having either two balloon occlusion
elements or two filter elements, in alternative embodiments, a
catheter device can include a combination of occlusion elements.
For example, a catheter device such as those described herein can
include one or more balloon occlusion elements (e.g., the balloon
elements 268 and/or 278) and one or more filter element occlusion
elements (e.g., the filter elements 368 and/or 378).
[0138] While various embodiments have been described above, it
should be understood that they have been presented by way of
example only, and not limitation. Where schematics and/or
embodiments described above indicate certain components arranged in
certain orientations or positions, the arrangement of components
may be modified. While the embodiments have been particularly shown
and described, it will be understood that various changes in form
and details may be made. Although various embodiments have been
described as having particular features and/or combinations of
components, other embodiments are possible having a combination of
any features and/or components from any of embodiments as discussed
above. For example, the size and specific shape of the various
components can be different from the embodiments shown, while still
providing the functions as described herein. Furthermore, each
feature disclosed herein may be replaced by alternative features
serving the same, equivalent or similar purpose, unless expressly
stated otherwise. Thus, unless expressly stated otherwise, each
feature disclosed is one example only of a generic series of
equivalent or similar features.
[0139] Where methods and/or events described above indicate certain
events and/or procedures occurring in certain order, the ordering
of certain events and/or procedures may be modified. Additionally,
certain events and/or procedures may be performed concurrently in a
parallel process when possible, as well as performed sequentially
as described above.
* * * * *