U.S. patent application number 14/689605 was filed with the patent office on 2015-10-22 for devices and methods for therapeutic heat treatment.
This patent application is currently assigned to BOSTON SCIENTIFIC SCIMED, INC.. The applicant listed for this patent is Boston Scientific Scimed, Inc.. Invention is credited to JAMES M. ANDERSON, CASS ALEXANDER HANSON, PATRICK A. HAVERKOST, JOSEPH ALAN KRONSTEDT, TIMOTHY A. OSTROOT, BRIAN R. REYNOLDS, DEREK C. SUTERMEISTER, JAN WEBER, MARTIN R. WILLARD.
Application Number | 20150297763 14/689605 |
Document ID | / |
Family ID | 53008934 |
Filed Date | 2015-10-22 |
United States Patent
Application |
20150297763 |
Kind Code |
A1 |
SUTERMEISTER; DEREK C. ; et
al. |
October 22, 2015 |
DEVICES AND METHODS FOR THERAPEUTIC HEAT TREATMENT
Abstract
A microparticle includes a plurality of magnetic nanoparticles
having a Curie temperature between 40.degree. and 100.degree. C.
The microparticle further includes a biocompatible polymer and/or
biocompatible ceramic and a plurality of radiopaque
nanoparticles.
Inventors: |
SUTERMEISTER; DEREK C.; (HAM
LAKE, MN) ; REYNOLDS; BRIAN R.; (RAMSEY, MN) ;
OSTROOT; TIMOTHY A.; (COKATO, MN) ; ANDERSON; JAMES
M.; (CORCORAN, MN) ; HANSON; CASS ALEXANDER;
(ST. PAUL, MN) ; WEBER; JAN; (MAASTRICHT, NL)
; KRONSTEDT; JOSEPH ALAN; (NEW HOPE, MN) ;
HAVERKOST; PATRICK A.; (BROOKLYN CENTER, MN) ;
WILLARD; MARTIN R.; (BURNSVILLE, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Boston Scientific Scimed, Inc. |
Maple Grove |
MN |
US |
|
|
Assignee: |
BOSTON SCIENTIFIC SCIMED,
INC.
Maple Grove
MN
|
Family ID: |
53008934 |
Appl. No.: |
14/689605 |
Filed: |
April 17, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61980952 |
Apr 17, 2014 |
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61981003 |
Apr 17, 2014 |
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61980936 |
Apr 17, 2014 |
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61980995 |
Apr 17, 2014 |
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Current U.S.
Class: |
424/1.61 ;
604/187 |
Current CPC
Class: |
A61B 2018/00125
20130101; A61B 2018/00714 20130101; A61B 2018/087 20130101; A61M
37/00 20130101; A61B 2018/00577 20130101; A61M 2025/105 20130101;
A61K 47/6957 20170801; A61M 2025/1081 20130101; A61N 1/406
20130101; A61B 2018/00595 20130101; A61M 2025/1086 20130101; A61B
2018/00148 20130101; A61B 2018/00511 20130101; A61B 2018/00404
20130101; A61B 18/04 20130101; A61B 2018/00214 20130101; A61B
2018/00267 20130101; A61B 2018/00815 20130101; A61M 25/0082
20130101; A61B 2018/00011 20130101; A61B 18/1492 20130101; A61B
2018/0022 20130101; A61P 35/00 20180101; A61B 2018/00178 20130101;
A61M 25/0043 20130101; A61B 2018/00601 20130101; A61M 2025/0042
20130101; A61B 2017/22061 20130101; A61B 2018/00136 20130101; A61B
2018/00154 20130101; A61B 2017/00088 20130101; A61B 2018/00642
20130101; A61B 2018/1465 20130101; A61K 41/0052 20130101; A61B
2018/00434 20130101; A61B 18/082 20130101; A61B 17/320725 20130101;
A61B 18/14 20130101; A61B 2018/0016 20130101 |
International
Class: |
A61K 51/12 20060101
A61K051/12; A61M 25/00 20060101 A61M025/00 |
Claims
1. A microparticle comprising: a plurality of magnetic
nanoparticles, the magnetic nanoparticles having a Curie
temperature between 40.degree. and 100.degree. C.; a plurality of
radiopaque nanoparticles; and a biocompatible polymer and/or
biocompatible ceramic.
2. The microparticle of claim 1, wherein the Curie temperature of
the magnetic nanoparticles is greater than 45.degree. C.
3. The microparticle of claim 1, wherein the Curie temperature of
the magnetic nanoparticles is in the range of 42.degree. to
48.degree. C.
4. The microparticle of claim 1, wherein the radiopaque
nanoparticles comprise gold.
5. The microparticle of claim 1, wherein the microparticle has a
diameter in the range of 1-30 microns.
6. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic is biodegradable.
7. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic further comprises a therapeutic
drug.
8. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic is a biocompatible polymer having a
melting point less than the Curie temperature of the magnetic
nanoparticles.
9. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic is a biocompatible polymer comprising
a polyamide.
10. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic is a biocompatible polymer comprising
polylactic acid, poly(lactic-co-glycolic acid), or combinations
thereof.
11. The microparticle of claim 1, wherein the biocompatible polymer
and/or biocompatible ceramic is a biocompatible ceramic comprising
tri-calcium phosphate.
12. A catheter comprising: a catheter shaft defining a lumen and
having a distal end portion, the distal end portion comprising an
elastic orifice having a closed configuration and an open
configuration; a handle portion defining a reservoir, the reservoir
in communication with the lumen, the reservoir having therein a
liquid composition; and a plurality of microparticles comprising a
metallic component having a Curie temperature between 35.degree.
and 100.degree. C., the microparticles configured to travel through
the lumen, wherein the microparticles have a cross-section larger
than the cross-section of the elastic orifice when the elastic
orifice is in the closed configuration.
13. The catheter of claim 12, wherein the handle portion comprises
a syringe, the syringe defining the reservoir.
14. The catheter of claim 13, wherein the microparticles are
disposed within the reservoir.
15. The catheter of claim 12, wherein at least some of the
microparticles contain a therapeutic drug.
16. The catheter of claim 12, wherein at least some of the
microparticles include a polymeric portion.
17. A method of treating a medical condition inside a body cavity
or lumen comprising: inserting a first plurality of microseeds into
the body cavity or lumen, wherein the microseeds of the first
plurality of microseeds have a diameter of 1-30 microns and a Curie
temperature between 30.degree. and 440.degree. C.; and inserting a
second plurality of microseeds into the body cavity or lumen
subsequent to the first plurality of microseeds, wherein the
microseeds of the second plurality of microseeds have a diameter of
30 microns to 1000 microns and a Curie temperature between
30.degree. and 440.degree. C.; the first plurality of microseeds
being configured to perform a different function within the body
cavity or lumen than the second plurality of microseeds.
18. The method of claim 17, wherein the function of the microseeds
of the first plurality of microseeds is a first function, the first
function is: releasing a drug thereform, thermally treating tissue,
cauterizing tissue, or occluding the body cavity or lumen and the
function of the microseeds of the second plurality of microseeds is
a second function, the second function is: releasing a drug
thereform, thermally treating tissue, cauterizing tissue, or
occluding the body cavity or lumen, wherein the first function is
different from the second function.
19. The method of claim 17, wherein the function of the microseeds
of the first plurality of microseeds is a first function, the first
function is raising the first plurality of microseeds to a first
Curie temperature and the function of the microseeds of the second
plurality of microseeds is a second function, the second function
is raising the second plurality of microseeds to a second Curie
temperature different from the first Curie temperature.
20. The method of claim 17, wherein the function of the microseeds
of the first plurality of microseeds is a first function, the first
function is releasing a first drug from the microseeds of the first
plurality of microseeds and the function of the microseeds of the
second plurality of microseeds is a second function, the second
function is releasing a second drug from the microseeds of the
second plurality of microseeds, wherein the first drug is different
from the second drug.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The following commonly assigned patent applications are
incorporated herein by reference, each in its entirety:
[0002] U.S. Pat. App. Ser. No. 61/980,995 (Sutermeister et al.),
entitled DEVICES AND METHODS FOR THERAPEUTIC HEAT TREATMENT, filed
on Apr. 17, 2104.
[0003] U.S. Pat. App. Ser. No. 61/980,952 (Sutermeister et al.),
entitled MEDICAL DEVICES FOR THERAPEUTIC HEAT TREATMENTS, filed on
Apr. 17, 2014; and
[0004] U.S. Pat. App. Ser. No. 61/981,003 (Sutermeister et al.),
entitled COMPOSITIONS FOR THERAPEUTIC HEAT DELIVERY, filed on Apr.
17, 2014 and
[0005] U.S. Pat. App. Ser. No. 61/980,936 (Sutermeister et al.),
entitled DEVICES AND METHODS FOR THERAPEUTIC HEAT TREATMENT, filed
on Apr. 17, 2104.
TECHNICAL FIELD
[0006] The present disclosure pertains to medical devices, systems,
and methods for therapeutic treatment using heat. More
particularly, the present disclosure pertains to heat treatment of
tumors and other undesirable tissues.
BACKGROUND
[0007] Body tissues may undesirably grow or swell due to
unregulated cell division, resulting in the formation of benign,
pre-malignant, or malignant tumors. Such tumors are generally
treated by a variety of therapeutic approaches such as excision,
chemotherapy, radiotherapy, or a combination of these approaches.
Each approach has limitations affecting its clinical utility. For
example, excision may not be appropriate where the tumor presents
as a diffuse mass or is in a surgically inoperable location.
Chemotherapeutic agents are generally non-specific, thus resulting
in the death of both normal and diseased cells. Radiotherapy is
also non-specific and results in the death of normal tissues
exposed to ionizing radiation. In addition, the core of a tumor
mass may be relatively resistant to ionizing radiation or
chemotherapeutic agents.
[0008] Typically, hyperthermia is used for treating tumors
alongside the above therapeutic approaches or as a standalone
therapy. Known hyperthermia treatments suffer from a number of
potential risks. For example, in addition to heating cancer cells,
known hyperthermia treatments tend to heat the surrounding healthy
cells. Depending upon the hyperthermia treatment, the damage to
healthy cells can be at least somewhat widespread.
[0009] Consequently, there remains a need for devices and methods
for effective heat treatment of tumors and undesirable tissues with
robust and precise temperature control with localized focus.
SUMMARY
[0010] In some embodiments a catheter includes a catheter shaft, a
handle portion, and a plurality of microparticles. The catheter
shaft defines a lumen and has a distal end portion, which includes
an elastic orifice. The elastic orifice has a closed configuration
and an open configuration. The handle portion defines a reservoir
that is in communication with the lumen and stores a liquid
composition. In some embodiments, the liquid composition is a
saline solution. The microparticles include a metallic component
having a Curie temperature between 35.degree. and 100.degree. C.
The microparticles are configured to travel through the lumen and
have a cross-section larger than the cross-section of the elastic
orifice when the elastic orifice is in the closed
configuration.
[0011] In some embodiments, an implantable therapeutic device has a
metallic portion, a first thermoplastic polymer portion, and a
therapeutic drug. The metallic portion has a Curie temperature. The
first thermoplastic polymer portion at least partially encases the
therapeutic drug and has a melting temperature less than the Curie
temperature of the metallic portion, wherein heating of the
metallic portion to the Curie temperature melts the first
thermoplastic polymer portion and releases the drug.
[0012] In some embodiments a microparticle includes an inner
portion and an outer portion surrounding the inner portion. The
inner portion includes a biocompatible polymer and/or biocompatible
ceramic and a plurality of magnetic nanoparticles having a Curie
temperature between 40.degree. and 100.degree. C. The outer portion
includes a biocompatible polymer and/or biocompatible ceramic and a
plurality of radiopaque nanoparticles.
[0013] In some embodiments, a method of treating a medical
condition inside a body cavity or lumen includes inserting a first
plurality of microseeds into the body cavity or lumen. The
microseeds of the first plurality of microseeds have a diameter of
1-30 microns and a Curie temperature between 30.degree. and
440.degree. C. The method further includes inserting a second
plurality of microseeds into the body cavity or lumen subsequent to
the first plurality of microseeds. The microseeds of the second
plurality of microseeds have a diameter of 30 microns to 1000
microns and a Curie temperature between 30.degree. and 440.degree.
C. The first plurality of microseeds is configured to perform a
different function within the body cavity or lumen than the second
plurality of microseeds.
[0014] The above summary of some embodiments is not intended to
describe each disclosed embodiment or every implementation of the
present disclosure. The Figures, and Detailed Description, which
follow, more particularly exemplify these embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] A detailed description of the invention is hereafter
described with specific reference being made to the drawings.
[0016] FIG. 1 is a cross-sectional view of an embodiment of a
microparticle;
[0017] FIGS. 2A and 2B are cross-sectional views of an embodiment
of an implantable therapeutic device in a closed configuration and
an open configuration, respectively;
[0018] FIGS. 3A and 3B are cross-sectional views of an embodiment
of an implantable therapeutic device in a closed configuration and
an open configuration, respectively;
[0019] FIG. 4 illustrates an embodiment of an implantable
therapeutic device;
[0020] FIG. 5 illustrates an embodiment of an implantable
therapeutic device;
[0021] FIGS. 6-8 are schematic illustrations of catheters for
delivering implantable therapeutic devices;
[0022] FIG. 9 shows a schematic illustration of the catheter of
FIG. 6 within a body lumen;
[0023] FIG. 10 shows a schematic illustration of the catheter of
FIG. 7 within a body lumen;
[0024] FIG. 11 shows a detailed schematic view of a portion of the
catheter of FIG. 6;
[0025] FIG. 12 shows a detailed schematic view of a tissue
site;
[0026] FIGS. 13A and 13B illustrate radiofrequency (RF) pulses, as
applied over time, to the implantable therapeutic devices;
[0027] FIG. 14 illustrates implantable therapeutic devices in body
tissue; and
[0028] FIG. 15 illustrates a distributed antenna array for
delivering signals to the implantable therapeutic devices of FIG.
14.
[0029] While the disclosure is amenable to various modifications
and alternative forms, specifics have been shown by way of example
in the drawings and will be described in detail. It should be
understood, however, that the intention is not to limit the
invention to the particular embodiments described. On the contrary,
the intention is to cover all modifications, equivalents, and
alternatives falling within the spirit and scope of the
disclosure.
DETAILED DESCRIPTION
[0030] Hyperthermia provides localized thermal treatment of tumor
cells and lacks any cumulative toxicity in contrast to chemotherapy
and radiotherapy. A variety of hyperthermia therapeutic approaches
are used for treatment of tumors. One such approach involves
deployment of magnetic nanoparticles to a tumor site. These
magnetic nanoparticles have a selected Curie temperature and
generate heat when subjected to an applied alternating field. While
the present disclosure is discussed relative to the thermal
treatment of tumor cells, it is contemplated that the devices and
methods described herein can be applied to other parts of the
anatomy where hyperthermia treatments or the controlled application
of heat is desired. For example, the devices and methods may be
applied to other parts of the anatomy, such as, but not limited to,
the vasculature, the nervous system, gastrointestinal, urological,
gynecological, etc.
[0031] Although the magnetic nanoparticles provide non-invasive
localized heating of the tumor, random and unknown distribution of
magnetic nanoparticles over the volume of the tumor disrupts
homogeneous heating of the tumor for treatment. Moreover, heating
of such magnetic nanoparticles usually raises their temperature
over a small, fixed range, as defined by the Curie temperature of
the magnetic nanoparticles. Such limited and fixed temperature
range may not be sufficient to induce the requisite therapeutic
effect for treatment.
[0032] The recitation or disclosure of numerical ranges by
endpoints includes all numbers within that range (e.g., 1 to 5
includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).
[0033] As used in this specification and the appended claims, the
singular forms "a", "an", and "the" include plural referents unless
the content clearly dictates otherwise. As used in this
specification and the appended claims, the term "or" is generally
employed in its sense including "and/or" unless the content clearly
dictates otherwise.
[0034] References in the specification to "an embodiment", "some
embodiments", "other embodiments", etc., indicate that an
embodiment includes a particular feature, structure, or
characteristic, but every embodiment may not necessarily include
the particular feature, structure, or characteristic. Moreover,
such phrases do not necessarily refer to the same embodiment.
Further, when a particular feature, structure, or characteristic is
described in connection with an embodiment, it should be understood
that such feature, structure, or characteristic may also be used in
connection with other embodiments, whether or not explicitly
described unless clearly evidenced or stated to the contrary.
[0035] "Curie temperature" is defined as the temperature at which
permanent magnetic properties of a material convert into induced
magnetic properties, or vice versa.
[0036] "Curie materials" refer to those metals or metal alloys that
exhibit magnetic properties based on selected Curie temperatures.
The Curie temperature of a Curie material may be altered by using
composite materials, which may or may not be ferromagnetic. Changes
in doping, additives, composites, alloying, and density of Curie
materials can alter the structure and behavior of the Curie
material and the Curie temperature.
[0037] As used herein, a "thermoset" polymer (e.g., a thermoset)
refers to a polymer that, once having been cured (or hardened) by a
chemical reaction (e.g., covalent bond forming, crosslinking,
etc.), will not soften or melt when subsequently heated.
[0038] As used herein, a "thermoplastic" polymer (e.g., a
thermoplast) refers to a polymeric material that softens when
heated and hardens upon cooling, processes that are reversible and
repeatable.
[0039] As used herein, "particle size" of a particle refers to the
largest dimension (chosen from length, width, and height) of the
particle. For example, for a spherical particle, the largest
dimension is the diameter. As used herein, the "particle size" of a
plurality of particles refers to the average (i.e., mean) of the
particle sizes of the particles, based on the population of
particles. As used herein, a "range of particle size" of a
plurality of particles refers to a range in which at least ninety
percent of the population of particles has a particle size within
that range, allowing for a combined up to ten percent of the
population of particles to be above the recited range and below the
recited range. For example, a range of particle size of a plurality
of particles of from 1 nanometer to 100 nanometers refers to a
plurality of particles wherein at least ninety percent of the
population of particles has a particle size from 1 nanometer to 100
nanometers (meaning that the sum of the populations of particles
less than 1 nanometer and particles greater than 100 nanometers
does not exceed 10% of the total population), with 0-10% of the
population being less than 1 nanometer and 0-10% of the population
being greater than 100 nanometers.
[0040] The following detailed description should be read with
reference to the drawings in which similar elements in different
drawings are numbered the same. The drawings, which are not
necessarily to scale, depict illustrative embodiments and are not
intended to limit the scope of the disclosure.
[0041] FIG. 1 is a cross-sectional view of an embodiment of an
implantable therapeutic device 100. In some embodiments, the
implantable therapeutic device 100 comprises a microparticle. In
some embodiments, the implantable therapeutic device 100 includes
an outer portion 102 and an inner portion 104. The outer portion
102 may envelop or surround the inner portion 104. The inner
portion 104 comprises magnetic nanoparticles 106 that are made of
Curie materials. The term "magnetic nanoparticles" includes
anti-ferromagnetic, ferromagnetic, and ferrimagnetic materials. In
some embodiments, the magnetic nanoparticles 106 are formed from
one or more materials such that they have a selected Curie
temperature (T.sub.c) between 35.degree. Celsius (.degree. C.) and
100.degree. C. In some embodiments, the magnetic nanoparticles have
a Curie temperature of approximately 80.degree. C. When these
magnetic nanoparticles 106 are subjected to an alternating magnetic
field, the magnetic nanoparticles 106 undergo power dissipation in
the form of heat caused by relaxation phenomena of the particles'
magnetic moments following the electromagnetic field and the
mechanical rotation of particles themselves within the dispersant
medium. At temperatures less than the Curie temperature
(T<T.sub.c), the magnetic nanoparticles 106 are ferro- (or
ferri-) magnetic, whereas the nanoparticles 106 transition into a
paramagnetic phase to stabilize the nanoparticle 106 temperature at
the predetermined Curie temperature.
[0042] In some embodiments, the magnetic nanoparticles 106 are made
of one or more Curie materials having a predetermined composition
that has a Curie temperature greater than 45.degree. C. Such Curie
materials may be used to heat undesirable tissues up to the pain
threshold of a patient, or beyond if pain mitigation drugs and/or
anesthetic is used, for example. Examples of such compositions of
Curie materials include Fe 70% Ni 30%, having a Curie temperature
of 82.degree. C.; Fe 75% Ni 25% with 1 wt. % Mn, having a Curie
temperature of 78.degree. C. In some embodiments, the magnetic
nanoparticles 106 comprise Curie materials of a predetermined
composition having a Curie temperature from 42.degree. C. to
48.degree. C., for example Manganese Arsenide having a Curie
Temperature of 45.degree. C. Other suitable Curie materials are
disclosed in the concurrently filed application titled, "MEDICAL
DEVICES FOR THERAPEUTIC HEAT TREATMENTS", U.S. Pat. App. Ser. No.
61/980,952 (Sutermeister et al.), filed on Apr. 17, 2014, which is
herein incorporated by reference. Additionally, the contents of the
co-filed Application entitled, "COMPOSITIONS FOR THERAPEUTIC HEAT
DELIVERY", U.S. Pat. App. Ser. No. 61/981,003 (Sutermeister et
al.), also filed on Apr. 17, 2014, are herein incorporated by
reference.
[0043] In one or more embodiments, the Curie temperature material
includes a zinc oxide mixed (e.g., combined, doped, etc.) with a
rare earth element (e.g., a Lanthanum metal, etc.). In some
embodiments, the rare earth element is present in a non-zero
quantity. For example, the Curie temperature material including
zinc oxide may include at least five (e.g., at least 6, at least 7,
at least 8, at least 9, at least 10, at least 15) weight percent of
a rare earth element, based on the sum of the weight of the rare
earth element and the weight of the zinc oxide. In one or more
embodiments in which the Curie temperature material includes zinc
oxide and more than one rare earth element, then the sum of the
rare earth element weight percentage may be at least five (e.g., at
least 6, at least 7, at least 8, at least 9, at least 10, at least
15) weight percent, based on the sum of the weight of the more than
one rare earth elements and the weight of the zinc oxide.
[0044] In one or more embodiments, the Curie temperature material
includes gallium, manganese, and nitrogen (e.g., gallium manganese
nitride, etc.). In one or more embodiments, the Curie temperature
material includes gallium, manganese, and oxygen (e.g., gallium
manganese oxide). In one or more embodiments, the Curie temperature
material includes gadolinium, manganese, and nitrogen (e.g.,
gadolinium manganese nitride). In one or more embodiments, the
Curie temperature material includes one or more of gallium
arsenide, dysprosium, cobalt, magnetite, and neodymium.
[0045] In one or more embodiments, the Curie temperature material
may include a magnetic nanoparticle of the composition disclosed by
Kim et al. (European Pat. Publ. No. EP 2 671 570 A2, entitled
"Magnetic Nanoparticle, Having A Curie Temperature Which Is Within
Biocompatible Temperature Range, And Method For Preparing Same").
The magnetic nanoparticle disclosed by Kim et al. includes a rare
earth metal, a divalent metal and a transition metal oxide and has
a Curie temperature in the range of -80.degree. C. to about
41.degree. C. In the present disclosure, a composition may include
any of the Curie materials disclosed by Kim et al. (European Pat.
Publ. No. EP 2 671 570 A2) with a polymeric binder and a thermal
interface material wherein the Curie temperature of the composition
is in the range of about 17 degrees Celsius to about 400 degrees
Celsius. Such magnetic nanoparticles may be formed by the methods
disclosed in Kim et al. (European Pat. Publ. No. EP 2 671 570
A2).
[0046] In one or more embodiments, the Curie temperature material
includes at least one element selected from iron (Tc=770.degree.
C.), nickel (Tc=354.degree. C.), zinc (Tc=415.degree. C.), cobalt
(Tc=1115.degree. C.), gadolinium (Tc=20.degree. C.), chromium,
manganese, copper, gallium, yttrium, aluminum, silver, and/or their
alloys. In one or more embodiments, a Curie temperature material
may include boron (B), bismuth (Bi), antimony (Sb), arsenic (As),
carbon (C), silicon (Si), sulfur (S), selenium (Se), tellurium
(Te), germanium (Ge), cerium (Ce), neodymium (Nd), erbium (Er),
holmium (Ho), strontium (Sr), titanium (Ti), calcium (Ca),
lanthanum (La), and/or oxygen (O).
[0047] In one or more embodiments, the Curie material includes an
iron-cobalt-chromium compound such as, for example,
(Fe.sub.65Co.sub.35).sub.71Cr.sub.18Zr.sub.7B.sub.4, (having a
Curie temperature of 74.5.degree. C.), which may be suitable in
heat delivery applications including ablation of biological tissue.
Methods of forming
(Fe.sub.65Co.sub.35).sub.71Cr.sub.18Zr.sub.7B.sub.4, and
ferrofluids thereof, and heat testing such materials are described
by Miller et al. (See Miller et al., "Fe--Co--Cr nanocomposites for
application in self-regulated rf heating," J. Applied Phys., 2010,
107, 09A313-1 to 09A313-3.) For example: "Ferrofluids of varying
[magnetic nanoparticle] concentration were rf heated by applying a
27.2 mT ac magnetic field at 267 kHz. Temperature change was
measured as a function of exposure time in the cryomilled
Fe--Co--Cr ferrofluids using a Luxtron optical fiber temperature
probe. Using a 1.24 vol % concentration of
(Fe.sub.65Co.sub.35).sub.71Cr.sub.18Zr.sub.7B.sub.4 [magnetic
nanoparticles] in 10 ml of 0.150 M Pluronic F127 ferrofluid, the
solution was effectively heated to reach temperatures
>50.degree. C. in .about.70 [seconds], while demonstrating
Curie-limiting self-regulating behavior was demonstrated
.about.74.5.degree. C."
[0048] In one or more embodiments, the Curie material includes a
material having the formula
Fe.sub.73.5-xCr.sub.xSi.sub.13.5Cu.sub.1B.sub.9Nb.sub.3 (x=0 to
10), which may be amorphous or crystalline, or may be a combination
of amorphous and crystalline phases. For example, Gomez-Polo has
reported preparing
Fe.sub.73.5-xCr.sub.xSi.sub.13.5Cu.sub.1B.sub.9Nb.sub.3 (x=3, 7,
and 10) with and without crystallization and magnetic
characterization thereof (See Gomez-Polo et al., "Analysis of
heating effects (magnetic hyperthermia) in FeCrSiBCuNb amorphous
and nanocrystalline wires," J. Applied Phys., 2012, 111, 07A314-1
to 07A314-3.)
[0049] In one or more embodiments, a Curie temperature material
includes an antiperovskite compound. For example, antiperovskite
compounds having the formula Ga.sub.1-xCMn.sub.3+x, wherein x=0,
0.06, 0.07, and 0.08 are described by Wang et al., "Reversible
room-temperature magnetocaloric effect with large temperature span
in antiperovskite compounds Ga.sub.1-xCMn.sub.3+x (x=0, 0.06, 0.07,
and 0.08)," J. Appl. Phys., 2009, 105, 083907-1 to 083907-5. At
page 083904-2, Wang et al. reported an experimental procedure for
making the compounds and reported that the Curie temperatures of
such compounds, determined from the derivative of magnetism as a
function of temperature curves, were found to be 250, 281.5, 296.5,
and 323.5 K for x=0, 0.06, 0.07, and 0.08, respectively. In the
present disclosure, in one or more embodiments in which the Curie
material has the formula Ga.sub.1-xCMn.sub.3+x, the value for x may
be any value from 0 to 0.08, or even greater than 0.08.
[0050] In one or more embodiments, a suitable Curie temperature
material includes one or more of YMn.sub.5 (having a Curie
temperature of 216.degree. C.), Ni (having a Curie temperature of
357.degree. C.), Gd (having a Curie temperature of 19.degree. C.),
MnBi (having a Curie temperature of 358.degree. C.), MnSb (having a
Curie temperature of 314.degree. C.), CrO.sub.2 (having a Curie
temperature of 112.degree. C.), MnAs (having a Curie temperature of
45.degree. C.), MnOFe.sub.2O.sub.3 (having a Curie temperature of
300.degree. C.), Y.sub.3Fe.sub.5O.sub.12 (having a Curie
temperature of 287.degree. C.), chromium (having a Curie
temperature of 113.degree. C.), lanthanum strontium manganite (LSM)
(having a Curie temperature of 75.degree. C.), as well as
combinations of these.
[0051] Suitable Curie temperature materials are also disclosed by
Haik et al. (U.S. Pat. No. 7,842,281; "Magnetic Particle
Composition for Therapeutic Hyperthermia") such as essentially any
composition that has a desired Curie temperature and that can be
effectively heated by application of a magnetic field, such as
iron, nickel, zinc, cobalt, gadolinium, chromium, manganese, and/or
their alloys, an alloy of copper and nickel, an alloy of 71 to 71.4
wt % nickel with the balance consisting essentially of copper, an
alloy of 71 wt % nickel and 29 wt % copper, a Mn--Zn ferrite having
the formula Zn.sub.xMn.sub.(1-x)Fe.sub.2O.sub.4 where x is between
0.6 and 0.8, a Gd-substituted Mn--Zn ferrite, a ferrite having the
formula Mn.sub.0.5Zn.sub.0.5Gd.sub.xFe.sub.(2-x)O.sub.4 where x is
between 0 and 1.5, an iron compound having a composition of
Fe.sub.(1-x)Zn.sub.xFe.sub.2O.sub.4 where x is between 0.7 and 0.9,
ZnFe.sub.2O.sub.4, and ZnGd.sub.xFe.sub.(2-x)O.sub.4 where x is
between 0.01 and 0.8. See Haik et al. (U.S. Pat. No. 7,842,281) at
column 5, lines 10-33. Methods of making such materials are also
disclosed by Haik et al. (U.S. Pat. No. 7,842,281) at column 6,
line 53 to column 9, line 11 and in the Examples at column 10, line
45 to column 17, line 14.
[0052] In one or more embodiments, the Curie material includes an
iron-nickel compound (e.g., Fe.sub.70Ni.sub.30) that may or may not
include chromium. In one or more embodiments, a Curie temperature
material includes an iron-nickel alloy having the formula
Fe.sub.xNi.sub.1-x, wherein x is from 0.10 to 0.40 (e.g., x may be
0.12, 0.14, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, etc.). In one or
more embodiments, Fe.sub.xNi.sub.1-x may have manganese added
thereto (e.g., 1 wt % Mn added to Fe.sub.xNi.sub.1-x, such as when
x=0.25). McNerny et al. describe chemical synthesis of monodisperse
Fe--Ni magnetic nanoparticles with tunable Curie temperatures. (See
McNerny et al., "Chemical synthesis of monodisperse .gamma.-Fe--Ni
magnetic nanoparticles with tunable Curie temperatures for
self-regulated hyperthermia," J. Applied Phys., 2010, 107, 09A312-1
to 09A312-3.) For example, McNerny reported that
Fe.sub.0.70Ni.sub.0.30 magnetic nanoparticles have a Curie
temperature of about 82.degree. C., a temperature that may be
useful for heat delivery (e.g., medical applications involving
ablation, etc.). In another example, McNerny reported that 1 weight
percent of manganese added to Fe.sub.0.75Ni.sub.0.25 has a Curie
temperature of about 78.degree. C.
[0053] In the present disclosure, a Curie temperature material may
have a Curie temperature in the range of 40.degree. C. to
80.degree. C. For example, Martirosyan has reported a number of
Curie temperature materials having a Curie temperature in the range
of about 45.degree. C. to about 50.degree. C. (See Martirosyan,
"Thermosensitive Magnetic Nanoparticles for Self-Controlled
Hyperthermia Cancer Treatment," J. Nanomed. Nanotechnol., 2012,
3(6): 1000e112 (1-2).) For example, Martirosyan has disclosed
ultrafine alumina coated particles of substituted ferrite
Co.sub.1-xZn.sub.xFe.sub.2O.sub.4 and yttrium-iron garnet
Y.sub.3Fe.sub.5-xAl.sub.xO.sub.12 having a Curie temperature of
about 50.degree. C. (citing Giri et al., "Investigation on Tc tuned
nano particles of magnetic oxides for hyperthermia applications,"
Biomed. Mater. Eng., 2003, 13: 387-399); copper nickel (CuNi) alloy
nanoparticles with varying Curie temperature from 40 to 60.degree.
C., synthesized by several techniques (citing Kuznetsov et al.,
"Local radiofrequency-induced hyperthermia using CuNi nanoparticles
with therapeutically suitable Curie temperature," J. Magn. Magn.
Mater., 2007, 311: 197-203); Nickel-Chromium (Ni.sub.1-xCr.sub.x)
particles having a Curie temperature in range of 43-44.degree. C.,
the Curie temperatures of the alloys decreasing almost linearly
with increasing chromium concentration from 4.54 to 5.9 wt %
(citing Akin et al., "Ni.sub.1-xCr.sub.x alloy for self controlled
magnetic hyperthermia," Crystal Research and Technology, 2009, 44:
386-390); Gd.sub.5(Si.sub.1-xGe.sub.x).sub.4 and
(Gd.sub.1-xR.sub.x).sub.5Si.sub.4 series, with R=Ce, Nd, Er, and
Ho, have been studied (citing Ahmad et al., "Optimization of
(Gd).sub.5Si.sub.4 based materials: A step toward self-controlled
hyperthermia applications," J. Appl. Phys., 2009, 106: 064701);
ferromagnetic La.sub.0.73Sr.sub.0.27MnO.sub.3 nanoparticles
(particle size of 20-100 nm) having a Curie temperature of about
45.degree. C. (citing Prasad et al., "TC-Tuned biocompatible
suspension of La.sub.0.73Sr.sub.0.27MnO.sub.3 for magnetic
hyperthermia," J. Biomed. Mater. Res. B Appl. Biomater., 2008, 85:
409-416); unaggregated La.sub.0.82Sr.sub.0.18MnO.sub.3+.delta.
perovskite nanoparticles with a mean crystallite size of 22 nm
having a Curie temperature of about 43.degree. C.; complex ferrite
nanoparticles with formula Mg.sub.1+xFe.sub.2-2xTi.sub.xO.sub.4,
(where 0<x<0.5) having a Curie temperatures in the range of
about 45-50.degree. C. (citing Shimizu et al., "Ferromagnetic
exchange interaction and Curie temperature of Mg1+xFe2-2xTixO4
(x=0-0.5) system," J. Magn. Magn. Mater., 2007, 310:1835-1837 and
Martirosyan, "Thermosensitive nanostructured media for imaging and
hyperthermia cancer treatment," Bulletin of the American Physical
Society, 2001, 56:1); Zn-doped Mn-ferrite, Mn.sub.1-xZn.sub.xO and
the Gd-doped Zn-ferrite, ZnGd.sub.xFe.sub.2-xO.sub.4 nanoparticles
having Curie temperatures tuned to about 43.degree. C.; and
magnetic nanocomposite
Ni.sub.0.2Ca.sub.0.8Gd.sub.0.08Fe.sub.1.92O.sub.4 encapsulated by
poly vinyl alcohol and synthesized by a two steps chemical reaction
including solgel combustion and solvent casting technique also can
be applicable for self controlled hyperthermia (citing Prasad et
al. "Gd substituted NiCa ferrite/poly vinyl alcohol nanocomposite,"
J. Magn. Magn. Mater., 2012, 324: 869-872).
[0054] In one or more embodiments, a Curie temperature material may
include a rare-earth manganite material. In one or more
embodiments, the Curie material includes a lanthanum oxide compound
(e.g., La.sub.0.8Ag.sub.0.15MnO.sub.2.95, La0.75Sr0.25MnO3,
La.sub.0.8Sr.sub.0.2MnO.sub.3, etc.). For example,
La.sub.1-xSr.sub.xMnO.sub.3-.delta. (LSMO) and
La.sub.1-xAg.sub.yMnO.sub.3-.delta. (LAMO) may be useful. In one or
more embodiments wherein a Curie temperature material includes
La.sub.1-xAg.sub.yMnO.sub.3-.delta. (LSMO), x may be 0.01 to 0.30
(e.g., 0.20), y may be 0.01 to 0.30 (e.g., 0.15), and .delta. may
be 0.00 to 0.10 (e.g., 0.05) (e.g.,
La.sub.0.8Ag.sub.0.15MnO.sub.2.95, which has been reported as
having a Curie temperature in the range of about 42-44.degree. C.).
(See Atsarkin et al., "Solution to the bioheat equation for
hyperthermia with La.sub.1-xAg.sub.yMnO.sub.3-d nanoparticles: The
effect of temperature autostabilization," Int. J. Hyperthermia,
2009 May; 25(3):240-247.) In one or more embodiments wherein a
Curie temperature material includes
La.sub.1-xSr.sub.xMnO.sub.3-.delta. (LSMO), x may be 0.01 to 0.30
(e.g., 0.05, 0.10, 0.15, 0.20, 0.25) and .delta. may be 0.00 to
0.10 (e.g., 0.00) (e.g., La.sub.0.75Sr.sub.0.5MnO.sub.3 (having a
Curie temperature of about 56.degree. C.),
La.sub.0.8Sr.sub.0.2MnO.sub.3 (having a Curie temperature of about
48.degree. C.), La.sub.0.85Sr.sub.0.15MnO.sub.3, etc.). In one or
more embodiments, a composition having a Curie temperature of about
42.degree. C. may be useful in one or more heat delivery
applications (e.g., hyperthermia treatment of biological tissue
wherein heat is to be delivered while reducing or avoiding undue
thermal damage to the surrounding tissue).
[0055] In one or more embodiments, a Curie temperature material
includes a chromium arsenic alloy, such as CrAs,
CrAs.sub.50S.sub.50, CrAs.sub.50Sb.sub.50, CrAs.sub.50Se.sub.50,
CrAs.sub.50Te.sub.50.
[0056] In one or more embodiments, the composition includes a Curie
temperature material and a secondary material. In one or more
embodiments, the secondary material may include a metal (e.g., an
elemental metal, a metal oxide, a metal salt, an alloy, etc.) that
is different from the Curie temperature material. In some
embodiments, the secondary material may be one metal or may be an
alloy of two or more metals. In one or more embodiments, the
secondary material may include a small amount of one or more
non-metals (e.g., less than five percent by weight based on the
combined weight of the Curie temperature material and the one or
more non-metals). In the present disclosure, a secondary material
may include an alloy such as, for example, an iron-nickel alloy, a
nickel-copper alloy, an iron-nickel-chromium alloy, or the like. In
the present disclosure, the secondary material includes, but is not
limited to, iron, cobalt, nickel, gadolinium, dysprosium, MnBi,
MnSb, CrO.sub.2, MnAs, EuO, Fe.sub.2O.sub.3, FeOFe.sub.2O.sub.3,
NiOFe.sub.2O.sub.3, CuOFe.sub.2O.sub.3, MgOFe.sub.2O.sub.3,
MnOFe.sub.2O.sub.3, Y.sub.3Fe.sub.6O.sub.12, chromium, lanthanum
strontium manganite, YMn.sub.5, silicon, aluminum, manganese, ZnO,
and GaMnN.
[0057] In one or more embodiments, the Curie temperature material
and the secondary material may form a homogenous mixture.
Alternatively, the Curie temperature material and the secondary
material may be mixed (e.g., combined, doped, etc.) to form a
heterogeneous mixture.
[0058] In one or more embodiments, the composition includes a
mixture that includes first Curie temperature material and a second
Curie temperature material that is different from the first Curie
temperature material. In some embodiments, a third Curie
temperature material may be included in the composition with the
first and second Curie temperature materials. Suitable materials
for each of the first, second, and third Curie temperature
materials include any Curie temperature material including, but not
limited to, the Curie temperature materials disclosed herein. In
one or more embodiments, a mixture of one or more Curie temperature
materials exhibits a Curie temperature in a range of about 38
degrees Celsius to about 45 degrees Celsius or in a range of about
55 degrees Celsius to about 95 degrees Celsius. In some
embodiments, a mixture of first and second Curie temperature
materials includes an alloy of the first and second Curie
temperature materials (e.g., first and second metallic Curie
temperature materials, etc.). In some embodiments, a mixture of
first and second Curie temperature materials includes a first Curie
temperature material doped with a second Curie temperature
material. In one or more embodiments, a mixture of first and second
Curie temperature materials includes a nanocomposite (e.g., a
composite of two materials in the form of a nanoparticle, etc.) of
the first and second Curie temperature materials.
[0059] In one or more applications of heat delivery (e.g.,
therapeutic heat delivery), a particular Curie temperature or a
range of Curie temperatures may be desired. In the present
disclosure, it is contemplated that a composition may be selected
(e.g., formulated, etc.) with a target Curie temperature (or range
of Curie temperatures) to provide a desired temperature treatment
to a subject (e.g., the object to be heat treated, tissue to be
heat treated, etc.). It should be recognized that one of skill in
the art may select a Curie temperature material having a Curie
temperature and may tune that Curie temperature by, for example,
modifying chemical composition (e.g., mixing, doping, etc.),
modifying shape (e.g., providing spherical particles, providing
non-spherical particles), modifying particle size, and/or modifying
domain control of the composition to reach a desired temperature of
heat delivery.
[0060] For example, particle size in a crystal lattice changes
Curie temperature. Although not wishing to be bound by theory, as
particle size decreases, the fluctuations in electron spins becomes
more significant, causing disorder in magnetic moments and lowering
Curie temperature. For example, in superparamagnetism, magnetic
moments change randomly, creating disorder in small ferromagnetic
particles. For example, in some instances, by reducing the particle
size to the nanometer scale, the specific absorption rate, or
magnetic absorbance, may be increased by a factor of around 10.
[0061] Although not wishing to be bound by theory, Curie
temperature of nanoparticles are also affected by the crystal
lattice structure, body-centered cubic (bcc), face-centered cubic
(fcc) and a hexagonal structure (hcp) all have different Curie
Temperatures due to magnetic moments reacting to their neighboring
electron spins. For example, tighter lattice structures (e.g., fcc
and hcp) have higher Curie temperatures than other lattice
structures (e.g., bcc) as the magnetic moments have stronger
effects when closer together. In smaller systems, the coordination
number for the surface may be more significant and the magnetic
moments may have a stronger effect on the system.
[0062] In some embodiments, a composition that includes a secondary
material (e.g., a second Curie temperature material different from
a first Curie temperature material) may have a Curie temperature
that is reduced as compared to the composition without (e.g., in
the absence of) that secondary material. In one or more
embodiments, in some combinations of two or more Curie materials
(e.g., each having greater than 10% by weight), the combined
material has a Curie temperature that is reduced as compared to
either individual material. For example, each of iron and nickel
has a higher Curie temperature than that of at least some
iron-nickel alloy compositions. For example, although the Curie
temperature of iron is about 770.degree. C. and the Curie
temperature of nickel is about 354.degree. C., an alloy of
Fe.sub.60Ni.sub.40 has a Curie temperature of about 300.degree. C.
In one or more embodiments, alloying a given Curie temperature
material with an element such as silicon (Si), Aluminum (Al), or
manganese (Mn) may result in a mixture having a Curie temperature
that is reduced as compared to the given Curie temperature
material.
[0063] In one or more embodiments, the composition may include a
secondary material that is a non-Curie temperature material (e.g.,
not having a Curie temperature). In one or more embodiments,
inclusion of a secondary material that is a non-Curie temperature
material in a sufficient quantity may affect (e.g., reduce or
increase) the Curie temperature of the overall composition.
[0064] In one or more embodiments, the shape of a Curie temperature
material may be selected to tune the Curie temperature of a
material. For example, Iorga et al. ("Low Curie Temperature in
Fe--Cr--No--Mn Alloys," U.P.B. Sci. Bull. Series B, 2011, 73(4):
195-202) disclose in Table 3 that Curie temperatures of four
chemical compositions in spherical and toroidal form can vary from
about 1 to about 5.degree. C. Iorga et al. found the following
Curie temperatures for spherical and toroidal samples:
Cr.sub.4Ni.sub.32Fe.sub.62Mn.sub.1.5Si.sub.0.5 (328 K vs. 330 K);
Cr.sub.4Ni.sub.33Fe.sub.62.5Si.sub.0.5 (393 K vs. 398 K);
Cr.sub.10Ni.sub.33Fe.sub.53.5Mn.sub.3Si.sub.0.5 (283 K vs. 285 K);
Cr.sub.11Ni.sub.35Fe.sub.53.5Si.sub.0.5 (339 K vs. 340 K). The
results of Iorga et al. also exemplify the effect of increasing
manganese content in lowering a Curie temperature. It can also be
seen that in these samples, the effect of increasing manganese
content had a greater effect than increasing chromium content.
[0065] In one or more embodiments, a Curie temperature material may
include non-zero quantities of both chromium and manganese. In at
least one embodiment, the sum of chromium and manganese may be from
about 4 percent to about 13 percent (e.g., 4-6%), based on the
weight of the Curie temperature material. In some embodiments, the
inclusion of both manganese and chromium may result in a cost
savings for a given amount of Curie temperature reduction.
[0066] The impact of lattice structure and elemental spacing on
Curie temperature is disclosed by Bose et al. ("Exchange
interactions and Curie temperatures in Cr-based alloys in Zinc
Blende structure: volume- and composition-dependence,"
arXiv:0912.1760 [cond-mat.mtrl-sci], 5 Feb. 2010; 16 pgs.) at FIGS.
17-19 for Cr-based pnictides and chalcogenides of the form CrX with
X=As, Sb, S, Se and Te, and the mixed alloys CrAs.sub.50X.sub.50
with X=Sb, S, Se, and Te. Although not wishing to be bound by
theory, the lattice spacings are generally governed by formulation,
underscoring the impact of formulation (i.e., composition) on Curie
temperature.
[0067] Although not wishing to be bound by theory, generally,
alignment of magnetic moments and material density affect the bulk
and surface Curie temperatures of a given composition. The
inclusion of additives impacts the lattice structure of a
composition, which is important due to the impact of additives on
both of these features (i.e., alignment of magnetic moments and
density of the composition). For example, a decrease in alignment
of magnetic moments decreases the overall magnetism of the bulk
material, thus generally lowering the Curie temperature. In another
example, a decrease in the density of Curie temperature materials
within a composition serves to separate magnetic moments, thus
generally lowering Curie temperature.
[0068] In the present disclosure, altering the alignment of
magnetic moments may be accomplished with any of a wide variety of
different binders (e.g., a polymeric binder, a non-polymeric binder
that includes a metal or a ceramic, etc.). Although not wishing to
be bound by theory, within a small Curie temperature element (e.g.,
having a dimension in the nano and/or micro scale), the shift in
alignment is primarily a function of lattice structure, however
grain boundaries may play a role (much more common in larger bulk
structures). In some embodiments, a nanocomposite material may
include high and low bulk Curie temperatures, but will exhibit only
one mean-field Curie temperature. Generally, a higher proportion of
lower bulk temperatures results in a lower mean-field Curie
temperature. In the present disclosure, by forming a composition
including a Curie temperature material and a binder (e.g., polymer,
non-polymer, ceramic, non-Curie temperature metallic material,
etc.) a Curie temperature material's magnetism is reduced, lowering
the Curie temperature.
[0069] In some embodiments, the outer portion 102 comprises
radiopaque particles 108 residing outside the inner portion 104. As
shown, the outer portion 102 may enclose radiopaque particles 108
which, in some embodiments, are made of gold. Other examples of
materials for such radiopaque particles 108 include, but not
limited to, titanium dioxide, bismuth subcarbonate, platinum and
barium sulfate, platinum iridium, platinum tungsten, or any other
suitable alloy of platinum, palladium, or gold. The radiopaque
particles may allow for the detection of the exact distribution
(and, as such, density) of magnetic nanoparticles 106 in or
adjacent to undesirable tissue or tumor, using a variety of
techniques. For example, a computerized tomography (CT) scan of a
portion of the patient's body may be used to view where the
magnetic nanoparticles 106 are released or injected. In some
embodiments, the radiopaque particles 108 are nanoparticles.
[0070] In some embodiments, the outer portion 102 includes a
therapeutic drug in lieu of or in addition to the radiopaque
particles 108. The terms "therapeutic agents," "drugs," "bioactive
agents," "pharmaceuticals," "pharmaceutically active agents", and
other related terms may be used interchangeably herein and include
genetic therapeutic agents, non-genetic therapeutic agents, and
cells. Therapeutic agents may be used singly or in combination. A
wide range of therapeutic agent loadings can be used in conjunction
with the devices of the present invention, with the
pharmaceutically effective amount being readily determined by those
of ordinary skill in the art and ultimately depending, for example,
upon the condition to be treated, the nature of the therapeutic
agent itself, the tissue into which the dosage form is introduced,
and so forth.
[0071] Some specific beneficial agents include chemotherapeutic
agents, anti-thrombotic agents, anti-proliferative agents,
anti-inflammatory agents, anti-migratory agents, agents affecting
extracellular matrix production and organization, antineoplastic
agents, anti-mitotic agents, anesthetic agents, anti-coagulants,
vascular cell growth promoters, vascular cell growth inhibitors,
cholesterol-lowering agents, vasodilating agents, and agents that
interfere with endogenous vasoactive mechanisms.
[0072] The therapeutic drug may be a chemotherapeutic agent
including, but not limited to, Everolimus, platins, such as
carboplatin and cisplatin, taxanes such as docetaxel and
paclitaxel; gemcitabine, VP16, mitomycin, idoxuridine,
topoisomerase 1 inhibitors such as irinotecan, topotecan and
camptothecins; nitrosoureas such as BCNU, ACNU or MCNU,
methotrexate, bleomycin, adriamycin, cytoxan and vincristine;
immunomodulating cytokines such as IL2, IL6, IL12 and IL13, and
interferons. Certain chemotherapeutic agents are known to be
potentiated by heating the tissue and/or the chemotherapeutic
agent. Examples of possible heat-activated or heat-enhanced
chemotherapeutic agents include bleomycin, BCNU, cisplatin,
cyclophosphamide, melphalan, mitoxantrone, mitomycin C, thiotepa,
misonidazole, 5-thi-D-glucose, amphotericin B, cysteine,
cysteamine, and AET.
[0073] Numerous additional therapeutic agents useful for the
practice of the present invention may be selected from those
described in paragraphs [0040] to [0046] of commonly assigned U.S.
Patent Application Pub. No. 2003/0236514, the entire disclosure of
which is hereby incorporated by reference.
[0074] In some embodiments, one or both of the outer portion 102
and the inner portion 104 is made of a variety of biocompatible
thermoplastic polymers or ceramics, or any combination thereof.
Examples of these biocompatible thermoplastic polymers include, but
not limited to, polyglycolide (PGA), copolymers of glycolide such
as glycolide/L-lactide copolymers (PGA/PLLA),
glycolide/trimethylene carbonate copolymers (PGA/TMC); polylactides
(PLA), stereocopolymers of PLA such as poly-L-lactide (PLLA),
Poly-DL-lactide (PDLLA), L-lactide/DL-lactide copolymers;
copolymers of PLA such as lactide/tetramethylglycolide copolymers,
lactide/trimethylene carbonate copolymers,
lactide/.delta.-valerolactone copolymers, lactide
.epsilon.-caprolactone copolymers, polydepsipeptides,
PLA/polyethylene oxide copolymers, unsymmetrically 3,6-substituted
poly-1,4-dioxane-2,5-diones; poly-.beta.-hydroxybutyrate (PHBA),
PHBA/.beta.-hydroxyvalerate copolymers (PHBA/HVA),
poly-.beta.-hydroxypropionate (PHPA), poly-p-dioxanone (PDS),
poly-.delta.-valerolatone, poly-.epsilon.-caprolactone,
methylmethacrylate-N-vinyl pyrrolidone copolymers, polyesteramides,
polyesters of oxalic acid, polydihydropyrans,
polyalkyl-2-cyanoacrylates, polyurethanes (PU), polyvinyl alcohol
(PVA), polypeptides, poly-.beta.-maleic acid (PMLA),
poly-.beta.-alkanoic acids, or any combination thereof. Examples of
biocompatible ceramics include, but not limited to, calcium
phosphate-based ceramics such as hydroxyapatite (HAP), tricalcium
phosphate .beta. (.beta. TCP), and a mixture of HAP and .beta.
TCP.
[0075] In some embodiments, the inner portion 104 is made of a
biocompatible polymer including a polyamide. In some embodiments,
the inner portion 104 is made of a biocompatible polymer including
polylactic acid, poly(lactic-co-glycolic) acid (PLGA), or
combinations thereof. In some embodiments, the inner portion 104 is
made of a biocompatible ceramic including tri-calcium phosphate.
These biocompatible polymers and ceramics may be made biodegradable
for use in vivo.
[0076] In some embodiments, the inner portion 104 is coated with a
biodegradable phase change material, used in conjunction with a
therapeutic drug and Curie nanoparticles 106, in order to trigger
drug release at a specified temperature. In some embodiments, the
Curie nanoparticles 106 have a Curie temperature that is the same
as or slightly above the phase change temperature of the
biodegradable material. For example, in the presence of an applied
electric and/or magnetic field, the Curie nanoparticles 106 may
heat to their Curie temperature. Once the phase change temperature
of the biodegradable material has been reached, it may soften and
the drug within the biodegradable material released. In some
embodiments, the biodegradable phase change material, such as
1-tetradecanol, has a melting or phase change temperature of
39.degree. C., although other suitable biodegradable phase change
materials, such as lauric acid, are also contemplated. In some
embodiments, the inner portion 104 is made of porous PLGA
particles. In some embodiments, a solution of 1-tetradecanol is
prepared in di-ethyl ether and added with 10% by weight of
Lanthanum Strontium Manganese Nickel Oxide (LSMNO) nanoparticles
using an ultrasonic spray system. The LSMNO nanoparticles may be
coated with gold for increased radiopacity of the final solution.
In some embodiments, the PLGA, in the inner portion 104, is coated
with gold-coated LSMNO nanoparticles, including a layer of
1-tetradecanol, using a fluidized bed system.
[0077] The implantable therapeutic device 100 can range in size
from 1 micron (.mu.m) to 30 microns, based on the intended purpose
for treatment of the tissue. The implantable therapeutic device 100
can also be smaller than 1 micron and larger than 30 microns. For
example, the implantable therapeutic device 100 may be sized
according the location in which it is to be implanted. In some
embodiments, the implantable therapeutic device 100 may be
injected, or otherwise implanted, into the body to occlude the
vascular bed of the undesirable tissue due to its predetermined
size in the given size range. Such implantable therapeutic devices
100 may function to block the oxygen supply, in addition to
delivering heat and/or a therapeutic drug, to the tissue for
treatment. In other embodiments, the implantable therapeutic device
100 may be injected, or otherwise implanted, into the body or bulk
of the tumor or undesirable tissue.
[0078] Once implanted, the therapeutic device 100 may be subjected
to an alternating electric or magnetic field. The electric or
magnetic field may be applied from a location external to the body
and directed at the location of the therapeutic device(s) 100. When
subjected to a field of sufficient intensity, the metallic
nanoparticles 106 heat up to a characteristic temperature at which
their magnetic properties switch to paramagnetic properties and at
which the temperature of the Curie temperature material stops
increasing. The heat generated by the metallic nanoparticles 106
may trigger a release of a therapeutic drug and/or heat the
surrounding tissue to provide hyperthermic treatment. It is further
contemplated that the implantable therapeutic device 100 could act
as a temperature catalyst for another reaction in which a reaction
or an activity is dormant until heat activated. The device 100
heats only in the presence of a specified electric or magnetic
field and frequency and only to the Curie temperature of the
nanoparticles 106. When the Curie temperature is reached, the
material goes from magnetic to non-magnetic, discontinuing the
heating. This is a cyclic process that permanently and rapidly
maintains the therapeutic device 100 temperature at the set Curie
point of the material, as long as the electric or magnetic field is
applied.
[0079] FIGS. 2A and 2B are cross-sectional views of an embodiment
of an implantable therapeutic device 200 in a closed configuration
and an open configuration, respectively. In some embodiments, the
implantable therapeutic device 200 includes a metallic or metal
composite shell 202 made up of one or more Curie materials having a
predefined Curie temperature. The size of the implantable
therapeutic device 200 may range from 1 micron to 3000 microns. In
some embodiments, however, the implantable therapeutic device 200
comprises a microparticle, ranging in size from 1 micron to 1000
microns. For example, the implantable therapeutic device 200 may be
sized according the location in which it is to be implanted.
[0080] As shown in FIG. 2A, the metallic shell 202 includes a
cavity 205 having a first portion 204 and a second portion 206, the
second portion 206 extending from the first portion 204 to the
outer surface 207 of the metallic shell 202. In some embodiments,
the first portion 204 is substantially larger than the second
portion 206, which is relatively small, although this is not
required. Further, in some embodiments, the first portion 204 is
located at or near the center of the metallic shell 202. Further
still, in some embodiments, one or both of the first and the second
portions 204, 206 comprise a biocompatible thermoplastic polymer
and/or biocompatible ceramic 208, having a drug 210 or radiopaque
material, or both. Alternatively, the first and the second portions
204, 206 may include suitable different and/or separate
biocompatible thermoplastic polymers and/or biocompatible ceramics.
In some embodiments, the second portion 206 is sealed by the
thermoplastic polymer or ceramic 208 prior to release of the
biocompatible thermoplastic polymer and/or biocompatible ceramic
and drug 210. For example an electric or magnetic field may be
applied to the implantable therapeutic device 200 causing the
metallic shell 202 to heat to its Curie temperature. The heat from
the metallic shell 202 may be passed to the thermoplastic polymer
or ceramic 208, causing the thermoplastic polymer or ceramic 208 to
soften and/or melt and release the drug 210. In order to release
the drug 210, the thermoplastic polymer/ceramic 208 may have a
melting temperature below the Curie temperature of the metallic
shell 202.
[0081] In some embodiments, the implantable therapeutic device 200
is formed using a porous metallic microparticle (e.g., formed by
sintering nanoparticles or smaller micro-particles together). The
porous metallic microparticle is dipped into a solution of the drug
and a dissolvable wax. In some embodiments, the porous metallic
microparticles are formed by mixing 2 micrometer iron particles
into a polymer solution (e.g., 50% polymer by weight), and
spraying, out of the solution, microparticles being approximately
100 micrometers in size. Then, the resulting microparticles (at
this stage containing iron particles and polymer) are sintered to
burn off the polymer, leaving behind porous metallic
microparticles, to which the drug and wax can be added.
[0082] As shown in FIG. 2B, the metallic shell 202 is heated (shown
at reference number 209) to a temperature T1 under the influence of
an applied alternating magnetic or electric field. At temperature
T1, the thermoplastic polymer/ceramic 208 weakens, loosens, softens
and/or melts to open a path 211 for the drug 210 and/or radiopaque
particles to flow out from the metallic shell 202 into the body
lumen or body tissue. The thermoplastic polymer/ceramic 208 may
weaken, loosen, soften and/or melt at a temperature T1 below the
Curie temperature of the metallic sheet 202, although this is not
required. In some embodiments, or in some methods of treatment,
once the drug 210 is released, the intensity of the applied
magnetic field or electric field may be increased to further raise
the temperature of the metallic shell 202 near or to its Curie
temperature. As a result, localized thermal therapy or
cauterization of undesirable tissue can be undertaken in addition
to the drug therapy from the released drug 210. However, the
metallic shell 202 does not heat above its Curie temperature.
[0083] FIGS. 3A and 3B are cross-sectional views of an embodiment
of an implantable therapeutic device 300 which, in some
embodiments, comprises a microparticle. FIG. 3A shows the
implantable therapeutic device 300 in a closed configuration, while
FIG. 3B shows the implantable therapeutic device in an open
configuration. In some embodiments, the implantable therapeutic
device 300 includes a metallic or metal composite core 302
comprising a Curie material having a predefined Curie temperature.
The size of the implantable therapeutic device 300 may range from 1
micron to 3000 microns; where the implantable therapeutic device is
a microparticle, it may range in size from 1 micron to 1000
microns. For example, the implantable therapeutic device 200 may be
sized according the location in which it is to be implanted.
[0084] As shown in FIG. 3A, the outer surface 303 of the metallic
core 302 is covered with a therapeutic drug 304, examples of which
are discussed above, and/or radiopaque particles. The metallic core
302 and the therapeutic drug 304 are enclosed within or surrounded
by a suitable biocompatible thermoplastic polymer and/or
biocompatible ceramic 306. The melting temperature of the
thermoplastic polymer or biocompatible ceramic 306 may be less than
or approximately equal to the Curie temperature of the metallic
core 302. When the implantable therapeutic device 300 is subjected
to an appropriate alternating magnetic or electric field, the
metallic core 302 begins to heat. The temperature of the metallic
core 302 may be limited, however, upon reaching the Curie
temperature, as the metallic core 302 becomes paramagnetic.
[0085] In some embodiments, the melting temperature of the
biocompatible thermoplastic polymer and/or biocompatible ceramic
306 is at or slightly below the Curie temperature of the metallic
core 302. In some embodiments, however, the melting temperature of
the biocompatible thermoplastic polymer and/or biocompatible
ceramic 306 is significantly below the Curie temperature of the
metallic core 302. An electric or magnetic field may be applied to
the implantable therapeutic device 300 causing the metallic shell
302 to heat to or towards its Curie temperature. The heat from the
metallic shell 302 may be passed to the thermoplastic polymer or
ceramic 308, causing the thermoplastic polymer or ceramic 308 to
soften and/or melt and release the drug 304. In this way, once the
drug 304 is released, intensity of the applied magnetic or electric
field may be increased to further raise the temperature of the
metallic core 302 near or to its Curie temperature. As a result,
the metallic core 302 can further be used for localized thermal
therapy or cauterization of undesirable tissue after deployment of
a therapeutic drug 304. Heating ceases once the temperature of the
metallic core 302 reaches its Curie temperature.
[0086] In some embodiments, a first portion of the metallic core
302 is surrounded by a first thermoplastic polymer and/or ceramic,
and a second portion of the metallic core 302, along with the drug
304, is surrounded by a second thermoplastic polymer and/or
ceramic. The melting temperature of the second thermoplastic
polymer/ceramic may be greater than the melting temperature of the
first thermoplastic polymer/ceramic but less than the Curie
temperature of the metallic core 302. As a result, when subjected
to an alternating magnetic or electric field, the heat dissipated
by the metallic core 302 breaks the first thermoplastic polymer
first followed by breaking of the second thermoplastic polymer,
thereby releasing the drug 304 in parts. It is contemplated that
the drug 304 may be disposed under one or both the first and second
thermoplastic polymer and/or ceramic. It is further contemplated
that the implantable therapeutic device 300 may include any number
of thermoplastic polymers and/or ceramics desired, such as, but not
limited to, one, two, three, four, or more.
[0087] FIG. 4 illustrates a schematic of an embodiment of an
implantable therapeutic device 400 which, in some embodiments,
comprises a microparticle. The implantable therapeutic device 400
includes a base 402 having a sharp edge 404 protruding outwards
from the outer surface 403 of the base 402. The sharp edge 404 may
be configured to cauterize or cut undesirable tissue. The base 402
may be a metal or metal composite made up of one or more Curie
materials having a predefined Curie temperature. In some
embodiments, the base 402 may be substantially spherical. The base
402 can also take on any other desirable form, such as, but not
limited to a ring. In some embodiments, the base 402 and the sharp
edge 404 may be made from one or more suitable Curie materials
having the same or different Curie temperatures. Under the
influence of an alternating magnetic or electric field, the base
402 and/or the sharp edge 404 can be raised to the Curie
temperature, as previously discussed, in order to cauterize the
surrounding tissue. In some embodiments, the base 402 and/or sharp
edge 404 have a Curie temperature between 100 and 400 degrees
Celsius.
[0088] With regard to FIG. 5, in some embodiments, an implantable
therapeutic device 500 comprises a portion 502 made up of one or
more Curie materials having a predetermined Curie temperature. In
some embodiments, the implantable therapeutic device comprises a
microparticle. In some embodiments, the portion 502 has a through
hole 504 extending through the device 500 to receive a guidewire
for delivery. The hole 504 may be located at about the center of
the portion 502, but may also be located at any suitable location
on the portion 502. Under the influence of an alternating magnetic
or electric field, the metallic portion 502 dissipates heat to the
surrounding tissue. The implantable therapeutic devices 400 and 500
may have variable sizes ranging from 1 micron to 3000 microns based
on the intended purpose for treatment of the undesirable tissue, as
discussed above.
[0089] FIGS. 6, 7, and 8 are schematic illustrations of catheters
for delivering the implantable therapeutic devices. As illustrated,
the catheters 600, 700, 800 are configured to navigate through a
patient's vasculature to a desired treatment site. Each of the
catheters 600, 700, 800 comprises a catheter shaft 601. The
catheter shaft 601 has a distal end portion 602. The proximal end
of each of the catheters 600, 700, 800 may include a hub (not
shown) attached thereto for connecting other diagnostic and/or
treatment devices and/or a port for facilitating interventions. In
addition, the catheters 600, 700, 800 have a cross-sectional shape
or configuration adapted to be received in a desired body lumen.
For instance, the catheters 600, 700, 800 may be specially sized
and configured to accommodate passage through the intravascular
path, which leads from a percutaneous access site in, for example,
the femoral, brachial, or radial artery, to a targeted treatment
site, for example, within the stomach or other organ of a
patient.
[0090] The stiffness of the catheters 600, 700, 800 may be set for
use in various body lumen diameters. To this end, the material used
for manufacturing the catheters 600, 700, 800 may include any
suitable biocompatible material such as, but are not limited to,
polymers, or alloys, either in combination or alone. In general,
suitable polymeric materials include, but are not limited to,
silicone, polyamide, polyether block amides, polyurethane,
polyethylene, nylon, and polyethylene terephthalate. In some
embodiments, the material employed has enough stiffness for use in
various body lumen diameters, and sufficient flexibility to
maneuver through tortuous and/or stenotic lumens, avoiding any
undesirable tissue injuries. It will be appreciated that delivery
devices can include cutting, cauterizing, and/or piercing
capabilities for the purpose of deploying the implantable
therapeutic devices in non-luminal target locations, as well.
[0091] FIG. 6 illustrates a catheter 600 for delivering one or more
implantable therapeutic devices to body tissue using a fluid, which
can be pressurized to deliver the implantable therapeutic devices.
The catheter 600 may include a lumen 603 extending from the distal
end portion 602 towards the proximal end portion. The distal end
portion 602 of the catheter shaft 601 comprises an elastic orifice
604 that is capable of transitioning between a closed configuration
and an open configuration. The orifice 604 may be biased towards
the closed configuration. An applied force may cause the orifice
604 to move between the closed configuration and the open
configuration.
[0092] In some embodiments, the catheter 600 comprises a handle
portion 607. The handle portion 607 has a reservoir 608 which is in
fluid communication with the lumen 603. Within the reservoir 608 is
a fluid 609. In some embodiments, the reservoir 608 comprises a
syringe in fluid communication with the lumen 603 and elastic
orifice 604. The cross-sectional diameter of the lumen 603 is sized
to receive one or more implantable therapeutic devices, for example
microparticles such as, but not limited to the therapeutic device
100 discussed above. While the catheter 600 is described with
respect to the implantable therapeutic device 100 described with
respect to FIG. 1, it is contemplated that any of the implantable
therapeutic devices 100, 200, 300, 400, 500 described herein can be
delivered with the catheter 100. The elastic orifice 604 may be
biased towards the closed configuration when the implantable
therapeutic device 100 is within the lumen of the catheter 600.
[0093] In some embodiments, the catheter 600 comprises a precision
volume pump 606 and a reservoir 608 that stores the fluid 609, for
example, saline or any other suitable biocompatible fluid. In some
embodiments, the reservoir 608 is coupled to the lumen such that
when the pump 606 is activated, the fluid 609 flows into the lumen,
pushing the implantable therapeutic device 100, distally. The
pressure from the fluid 609 and the distally advancing therapeutic
device may apply a force to the orifice 604 causing the orifice to
open. The pushed implantable therapeutic device 100 may flow out
from the elastic orifice 604, which transitions from the closed
configuration to the open configuration to release the implantable
therapeutic device 100 into a body lumen or tissue. In some
embodiments, the stored potential energy of the elastic orifice 604
in the closed configuration converts into kinetic energy in the
open configuration to additionally apply a distal force on the
microparticle 100. In some embodiments, the applied force drives
the implantable therapeutic device 100 into the body lumen or
tissue.
[0094] FIG. 7 illustrates a catheter 700 configured to deliver an
implantable therapeutic device over a guidewire 610 to body tissue.
The catheter 700 is configured to receive one or more implantable
therapeutic devices such as, but not limited to, the implantable
therapeutic device 500 described with respect to FIG. 5, which can
be mounted over the guidewire 610. The catheter 700 includes a
first lumen 611 extending between a proximal opening at the
proximal end 620 and a distal opening 622 at the distal end 624.
The cross-sectional diameter of the first lumen 611 is sufficient
to receive the implantable therapeutic device 500 mounted over the
guidewire 610. At the proximal end, the catheter 700 has a push
shaft 612 surrounding the guidewire 610. The push shaft 612 may be
extended or advanced distally over the guidewire 610 to
mechanically push the implantable therapeutic devices 500 distally
off of the guidewire and into a body lumen or tissue.
[0095] FIG. 8 illustrates a catheter 800 for fusible release of
implantable therapeutic devices, such as, but not limited to, the
implantable therapeutic device 500 described with respect to FIG. 5
mounted over a fusible link 614 using electrical discharge or
releasable mechanical interlock. As shown, the catheter 800 is
configured to receive a plurality of implantable therapeutic
devices 500, such as a microparticle, mounted over and/or to the
fusible link 614. The catheter 800 includes a lumen 626 extending
between a proximal opening at the proximal end 628 and a distal
opening 630 at the distal end 632. The catheter 800 further
includes a cathode wire 616 and an anode wire 618, each attached to
the distal end of the catheter 800 and extending proximally for
coupling to a power supply (not shown) at the proximal end 628 of
the catheter 800. In some embodiments, the wires 616, 618 are
insulated from each other except at the distal end of the catheter
602. An electrical discharge is produced between the cathode and
the anode wires 616, 618 at the distal end of the catheter 800. The
electrical discharge may be sufficient to disconnect the fusible
link 614, breaking free the implantable therapeutic device 500 from
the remaining implantable therapeutic devices 500. Such a
configuration can be referred to as bipolar. Moreover, the skilled
artisan will appreciate that a monopolar configuration can also be
employed, using a ground pad on the patient's body and the fusible
link comprises the anode.
[0096] In some embodiments, the catheters 600, 700, 800 deploy
multiple implantable therapeutic devices (e.g., microparticles) in
batches. For example, a first batch (i.e., plurality) of
implantable therapeutic devices may be delivered substantially
simultaneously, and subsequently, a second batch (i.e., plurality)
of implantable therapeutic devices may be delivered substantially
simultaneously. In this context, it is understood that
substantially simultaneously includes a single or continuous
activation of the deployment mechanism such as the pump 606, push
shaft 612, or electrical activation of cathode wire 616 and anode
wire 618, for delivering the implantable therapeutic device,
although not all of the implantable therapeutic devices may exit
from the catheters 600, 700, 800 at the exact same time. Any number
of batches useful to achieve the desired therapeutic effect may be
deployed via the catheters 600, 700, 800. Additionally, it is
understood that the batches, e.g., the first and second batches of
implantable therapeutic devices, may be sized differently and/or
include implantable therapeutic devices of different shapes, sizes
and/or configurations within each batch. In some embodiments, the
first batch of implantable therapeutic devices may have a first
dimension (e.g., diameter) whereas the second batch of implantable
therapeutic devices may have a second dimension (e.g., diameter),
which may be relatively larger than the first dimension. The
dimensions of these batches of implantable therapeutic devices may
be selected such that upon deployment in the body lumen surrounding
the undesirable tissue, the implantable therapeutic devices block
or occlude the body lumen, or are capable of delivering a
predetermined amount of heat to the undesirable tissue.
[0097] FIGS. 9 and 10 illustrate methods of delivering implantable
therapeutic devices to a tissue location. During operation, the
catheters 600, 700, 800 may be advanced into a body lumen 750 or
cavity through a natural opening or an incision in a body. The
distal portion 602 is positioned adjacent to an undesirable tissue
using, for example, an endoscope, for treatment. Once positioned,
one or more implantable therapeutic devices (e.g., microparticles,
which may alternatively be referred to as microseeds) (such as the
microparticles 100, 500), having Curie temperatures ranging between
40.degree. C. and 440.degree. C., are injected into the body lumen
towards the undesirable tissue by applying pressurized fluid,
mechanical push, or electrical discharge, as discussed above.
[0098] Any of the implantable therapeutic devices disclosed herein
can be implanted via any suitable method or device. For example,
the implantable therapeutic devices can be implanted by way of
percutaneous orthoscopic, fluoroscopic, or MR (magnetic resonance)
guided delivery; the implantable therapeutic devices can also be
delivered surgically.
[0099] With regard to FIG. 11, in some embodiments, the elastic
orifice 604 is configured to expand upon deployment of the
implantable therapeutic device 100 and retract once the implantable
therapeutic device has exited the elastic orifice 604. Further, in
some embodiments, the elastic orifice 604 has sufficient elastic
recoil to handle a variety of sizes of implantable therapeutic
devices 100.
[0100] With regard to FIG. 12, in some embodiments, at least some
of the first set of implantable therapeutic devices is injected
into cavities in the vascular bed of the tissue 702 where the first
set holds their position due to comparable sizes of the implantable
therapeutic devices and the cavities (e.g., the implantable
therapeutic devices are lodged in tissue or a body lumen). In some
embodiments, such implantable therapeutic devices block the supply
of oxygen, which can assist in treating tissue 702.
[0101] In some embodiments, the implantable therapeutic devices
100, 500 that are injected into the body lumen have different
sizes, for example, a first set of implantable therapeutic devices
having a first size and a second set of implantable therapeutic
devices having a second size, which is larger or smaller than the
first size. In some embodiments, the first set of implantable
therapeutic devices may have a first Curie temperature and is
configured for distal-most placement in the body lumen 750,
adjacent to or in communication with the undesirable tissue.
Further, the second set of implantable therapeutic devices may have
a second Curie temperature and is configured for placement proximal
to the first set, within the body lumen 750. In some embodiments,
the first set has a first size of the microparticles ranging from 1
micron to 30 microns and the second set has a second size of
microparticles ranging from 30 microns to 1000 microns. This is
just an example. In some embodiments, the first set includes a
first drug and the second set of microparticles includes a second
drug different from the first drug.
[0102] In some embodiments, the implantable therapeutic devices are
configured to release a drug into the tissue 702, as discussed
above. In some embodiments, at least a portion of the implantable
therapeutic devices are configured to degrade over time. In
particular, the biodegradable polymer of some embodiments of the
implantable therapeutic device 100 breaks down, with the
biodegradable polymer being absorbed by surrounding tissue.
Consequently, the magnetic nanoparticles, along with radiopaque
particles, if present, can be consumed by macrophages within the
body and removed via normal body function.
[0103] In some embodiments, the delivered implantable therapeutic
devices are wirelessly heated through induction with radiofrequency
(RF) signals that are high frequency alternating current (AC)
signals. Referring to FIGS. 13A and 13B, an AC signal is pulsed to
raise the temperature of the implantable therapeutic devices. The
amount of energy delivered is based on frequency and pulse duration
of the AC signal. For example, FIG. 13A illustrates an AC signal
802 having durations of active pulses and inactive pulses as `a1`
and `b1`, respectively, and an AC signal 804 having durations of
active pulses and inactive pulses as `a2` and `b2`, respectively.
The ratio of durations of each active pulse and inactive pulse of
the AC signal 802 is less than that of the AC signal 804, as shown
in Equation 1. Stated differently, the on/off ratio of time in FIG.
13A is less than the on/off ratio of time for that of FIG. 13B.
Therefore, the energy delivered by the signal 804 is greater than
the energy delivered by the signal 802.
a 1 b 1 < a 2 b 2 ( 1 ) ##EQU00001##
[0104] The pulsed AC signals may be wirelessly applied to the
injected implantable therapeutic devices, such as the implantable
therapeutic devices 100, 500, so that the implantable therapeutic
devices are subjected to an alternating field. The alternating
field can be an electric field or, in some embodiments, a magnetic
field can be applied. As a result of the applied field, Curie
portions of the implantable therapeutic devices begin to rise in
temperature. Consequently, when the injected implantable
therapeutic devices contain a drug and/or radiopaque particles
secured by a biocompatible thermoplastic polymer or ceramic layer,
the rise in temperature of the Curie portions breaks open or
otherwise melts the thermoplastic polymer or ceramic layer to
release the drug and/or the radiopaque particles. It will be
appreciated that, in some embodiments, release of the drug (e.g.,
drug 210) will not occur until the thermoplastic polymer or ceramic
208 has been sufficiently heated. In this way, it is possible to
avoid releasing drugs into parts of the body where the drug is not
desired, for example in the case of an errant implantable
therapeutic device having a drug, by focusing the AC signal on only
the desired region of treatment.
[0105] The exact distribution or density of the injected
implantable therapeutic devices adjacent to or in the tissue 702
may be detected using a variety of techniques such as a CT scan,
for example, based on the presence of the radiopaque particles.
Such detection may be performed after the implantable therapeutic
devices are injected into the body lumen but prior to heating the
implantable therapeutic devices.
[0106] Based on the detected density of the implantable therapeutic
devices and a priori knowledge about the amount of energy that may
be transferred to each implantable therapeutic device by each
active pulse of the AC signal, rise in temperature of each segment
in the entire volume of the tissue 702 may be calculated. This
calculated rise in temperature for each segment of the tissue 702
allows for a predetermined amount of energy to be delivered to the
segments where the microparticle density is less, and vice versa,
(as shown in FIG. 14), thereby achieving a homogeneous temperature
rise over the entire volume of the tissue 702. Such homogeneous
temperature rise facilitates safe thermal treatment of the tissue
702. In order to provide a homogeneous temperature rise over the
volume of tissue 702, having regions of higher/lower density of
implantable therapeutic devices, some embodiments employ a
distributed antenna array 900, as shown in FIG. 15. The distributed
antenna array 900 can be used to direct greater amounts of energy
to areas having a lower density of microparticles, for example, in
order to achieve a uniform temperature rise over the area of
treatment. In some embodiments and methods, however, the
distributed antenna array 900 is used to provide an intentionally
heterogeneous temperature rise. In this way, it is possible to
increase the temperature more at desired locations.
[0107] In some embodiments, the distributed antenna array includes
multiple spatially distributed antennas 902, 904, 906 (e.g.,
dipoles) as shown in FIG. 15. These antennas 902 are placed around
the tissue 702 outside the body. Based on the microparticle density
in the volume of the tissue 702, each antenna is tuned in pulse
frequency of the AC signal for delivering a predetermined amount of
power to the microparticles, thereby achieving the desired power
distribution over the tissue 702. In some embodiments, for example,
more power is applied to regions of cancerous tissue having a lower
density of microparticles by providing such regions with more AC
pulses.
[0108] Further, the inner magnetic kernel, such as the metallic
shell 202 and the metallic core 302 discussed above, or magnetic
nanoparticles 106 in the microparticles may be made of Curie
materials with Curie temperatures higher than 45.degree. C. to
raise the microparticle temperature beyond 45.degree. C. In some
embodiments, the surrounding thermoplastic polymer and/or ceramic
layer moderate the release of energy over time and can act as
thermal mass. Moreover, since each microparticle has a known
loading of magnetic nanoparticles 106 or other Curie material, a
temperature to which the microparticle is heated by a single active
pulse of the AC signal can be determined. Consequently, a desired
amount of energy can be transmitted to the tissue and homogeneous
temperature can be maintained, as desired.
[0109] After each active pulse of the AC signal, the heat from the
microparticles dissipates through the surrounding tissue and heats
the volume of the tissue 702 to a desired temperature. Repeating
such active pulses may raise the overall temperature of the tissue
702 to a further desired temperature level. Varying ON and OFF
ratio between the pulses, allows the operator to precisely control
the target temperature or temperature profile across the tissue 702
for treatment, while staying just below the pain threshold of the
patient. The amount of energy supplied per implantable therapeutic
device, microparticle, nanoparticle, etc., can be regulated by
pulse frequency or pulse duration, or both. Nonetheless, the upper
temperature limit is determined by the Curie temperature.
[0110] In some embodiments, various medical devices such as
balloons or stents may be coupled with Curie temperature-controlled
elements such as implantable therapeutic devices 100 and 500 for
treatment of various medical conditions. When subjected to an
electromagnetic field, Curie portions of the implantable
therapeutic devices begin to generate heat up until they reach the
Curie temperature. The generated heat may be used to perform,
without limitation, tissue modulation, tissue propagation, and
nerve modulation for treatment. Tissue modulation may include, but
is not limited to, (1) circulatory modulation involving heat
treatment of blood vessel tissues and prostate tissues; (2) tumor
modulation involving heat treatment of pre-cancerous and cancerous
cells as well as lesions, undesirable tissue growth, and warts; (3)
sensor modulation involving treatment of carotid body using heat;
and (4) gland modulation involving heat treatment of mucocytes, for
example, in salivary glands. Tissue propagation may involve heat
treatment of endometriosis. Further, nerve modulation may involve
heat treatment of both afferent and efferent sympathetic nerves as
well as parasympathetic nerves. The implantable therapeutic
devices, or portions thereof, may also be used for providing
selectively paced or continuous heating to a target site within the
body for mitigating pain such as chronic back pain and menstrual
pain.
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equation for hyperthermia with La.sub.1-xAg.sub.yMnO.sub.3-d
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[0138] A description of some embodiments are contained in one or
more of the following numbered statements:
Statement 1. A microparticle comprising:
[0139] an inner portion and an outer portion surrounding the inner
portion, the inner portion comprising a biocompatible polymer
and/or biocompatible ceramic and a plurality of magnetic
nanoparticles, the magnetic nanoparticles having a Curie
temperature between 40.degree. and 100.degree. C., the outer
portion comprising a biocompatible polymer and/or biocompatible
ceramic and a plurality of radiopaque nanoparticles.
Statement 2. The microparticle of statement 1, wherein the Curie
temperature of the magnetic nanoparticles is greater than
45.degree. C. Statement 3 The microparticle of statement 2, wherein
the Curie temperature of the magnetic nanoparticles is 42.degree.
to 48.degree. C. Statement 4. The microparticle of any one of the
preceding statements, wherein the radiopaque nanoparticles comprise
gold. Statement 5. The microparticle of any one of the preceding
statements having a diameter of 1-30 microns. Statement 6. The
microparticle of any one of the preceding statements, wherein the
biocompatible polymer and/or biocompatible ceramic is
biodegradable. Statement 7. The microparticle of any one of the
preceding statements, wherein the outer portion further comprises a
drug. Statement 8. A catheter comprising:
[0140] a catheter shaft defining a lumen and having a distal end
portion, the distal end portion comprising an elastic orifice
having a closed configuration and an open configuration;
[0141] a handle portion defining a reservoir, the reservoir in
communication with the lumen, the reservoir having therein a liquid
composition; and
[0142] a plurality of microparticles comprising a metallic
component having a Curie temperature between 35.degree. and
100.degree. C., the microparticles configured to travel through the
lumen, wherein the microparticles have a cross-section larger than
the cross-section of the elastic orifice when the elastic orifice
is in the closed configuration. Statement 9. The catheter of
statement 8, wherein the handle portion comprises a syringe, the
syringe defining the reservoir.
Statement 10. The catheter of statement 9, wherein the reservoir
has the microparticles therein. Statement 11. The catheter of any
one of statements 8, 9, and 10, wherein at least some of the
microparticles contain a drug. Statement 12. The catheter of any
one of statements 8, 9, 10, and 11, wherein at least some of the
microparticles include a polymeric portion. Statement 13. The
catheter of any one of statements 8-12, wherein at least some of
the microparticles are radiopaque. Statement 14. The catheter of
any one of statements 8-12, wherein at least some of the
microparticles have a metallic shell defining a cavity. Statement
15. The catheter of statement 14, wherein the metallic shell
comprises the metallic component. Statement 16. The catheter of any
one of statements 8-15, wherein the liquid composition is a
solution or suspension of liquid and semi-liquid, the semi-liquid
having a viscosity between 0.8 cP and 20,000 cP. Statement 16. A
catheter comprising:
[0143] a catheter shaft defining a lumen and having a distal end
portion, the distal end portion comprising an elastic orifice
having a closed configuration and an open configuration;
[0144] a handle portion defining a reservoir, the reservoir in
communication with the lumen, the reservoir having therein a liquid
composition; and
[0145] a plurality of microparticles comprising a metallic
component having a Curie temperature between 35.degree. and
100.degree. C., the microparticles configured to travel through the
lumen, wherein the microparticles have a cross-section larger than
the cross-section of the elastic orifice when the elastic orifice
is in the closed configuration.
Statement 17. The catheter of statement 16, wherein the handle
portion comprises a syringe, the syringe defining the reservoir.
Statement 18. The catheter of statement 16, wherein the reservoir
has the microparticles therein. Statement 19. The catheter of
statement 16, wherein at least some of the microparticles contain a
drug. Statement 20. The catheter of statement 16, wherein at least
some of the microparticles are radiopaque. Statement 21. The
catheter of statement 16, wherein at least some of the
microparticles include a polymeric portion. Statement 22. A
microparticle comprising:
[0146] an inner portion and an outer portion surrounding the inner
portion, the inner portion comprising a biocompatible polymer
and/or biocompatible ceramic and a plurality of magnetic
nanoparticles, the magnetic nanoparticles having a Curie
temperature between 40.degree. and 100.degree. C., the outer
portion comprising a biocompatible polymer and/or biocompatible
ceramic and a plurality of radiopaque nanoparticles.
Statement 23. The microparticle of statement 22, wherein the Curie
temperature of the magnetic nanoparticles is greater than
45.degree. C. Statement 24. The microparticle of statement 22,
wherein the Curie temperature of the magnetic nanoparticles is
42.degree. to 48.degree. C. Statement 25. The microparticle of
statement 22 wherein the radiopaque nanoparticles comprise gold.
Statement 26. The microparticle of statement 22 having a diameter
of 1-30 microns. Statement 27. The microparticle of statement 22,
wherein the biocompatible polymer and/or biocompatible ceramic is
biodegradable. Statement 28. The microparticle of statement 22,
wherein the outer portion further comprises a drug. Statement 29.
The microparticle of statement 22, wherein the biocompatible
polymer and/or biocompatible ceramic of the inner portion is a
biocompatible polymer and consists of a polyamide. Statement 30.
The microparticle of statement 22, wherein the biocompatible
polymer and/or biocompatible ceramic of the inner portion is a
biocompatible polymer and consists of polylactic acid,
poly(lactic-co-glycolic acid), or combinations thereof. Statement
31. The microparticle of statement 22, wherein the biocompatible
polymer and/or biocompatible ceramic of the inner portion is a
biocompatible ceramic and consists of tri-calcium phosphate.
Statement 32. A method of treating a medical condition inside a
body cavity or lumen comprising:
[0147] inserting a first plurality of microseeds into the body
cavity or lumen, wherein the microseeds of the first plurality of
microseeds have a diameter of 1-30 microns and a Curie temperature
between 30.degree. and 440.degree. C.; and
[0148] inserting a second plurality of microseeds into the body
cavity or lumen subsequent to the first plurality of microseeds,
wherein the microseeds of the second plurality of microseeds have a
diameter of 30 microns to 1000 microns and a Curie temperature
between 30.degree. and 440.degree. C.;
[0149] the first plurality of microseeds being configured to
perform a different function within the body cavity or lumen than
the second plurality of microseeds.
Statement 33. The method of statement 32, wherein the function of
the microseeds of the first plurality of microseeds is a first
function, the first function is: releasing a drug therefrom,
thermally treating tissue, cauterizing tissue, or occluding the
body cavity or lumen and the function of the microseeds of the
second plurality of microseeds is a second function, the second
function is: releasing a drug therefrom, thermally treating tissue,
cauterizing tissue, or occluding the body cavity or lumen, wherein
the first function is different from the second function. Statement
34. The method of statement 32, wherein the function of the
microseeds of the first plurality of microseeds is a first
function, the first function is raising the first plurality of
microseeds to a first Curie temperature and the function of the
microseeds of the second plurality of microseeds is a second
function, the second function is raising the second plurality of
microseeds to a second Curie temperature different from the first
Curie temperature. Statement 35. The method of statement 32,
wherein the function of the microseeds of the first plurality of
microseeds is a first function, the first function is releasing a
first drug from the microseeds of the first plurality of microseeds
and the function of the microseeds of the second plurality of
microseeds is a second function, the second function is releasing a
second drug from the microseeds of the second plurality of
microseeds, wherein the first drug is different from the second
drug.
[0150] The above disclosure is intended to be illustrative and not
exhaustive. This description will suggest many variations and
alternatives to one of ordinary skill in this field of art. All
these alternatives and variations are intended to be included
within the scope of the claims where the term "comprising" means
"including, but not limited to." Those familiar with the art may
recognize other equivalents to the specific embodiments described
herein which equivalents are also intended to be encompassed by the
claims.
[0151] Further, the particular features presented in the dependent
claims can be combined with each other in other manners within the
scope of the invention such that the invention should be recognized
as also specifically directed to other embodiments having any other
possible combination of the features of the dependent claims. For
instance, for purposes of claim publication, any dependent claim
which follows should be taken as alternatively written in a
multiple dependent form from all prior claims which possess all
antecedents referenced in such dependent claim if such multiple
dependent format is an accepted format within the jurisdiction
(e.g. each claim depending directly from claim 1 should be
alternatively taken as depending from all previous claims). In
jurisdictions where multiple dependent claim formats are
restricted, the following dependent claims should each be also
taken as alternatively written in each singly dependent claim
format which creates a dependency from a prior
antecedent-possessing claim other than the specific claim listed in
such dependent claim below.
[0152] This completes the description of the preferred and
alternate embodiments of the invention. Those skilled in the art
may recognize other equivalents to the specific embodiment
described herein which equivalents are intended to be encompassed
by the claims attached hereto.
* * * * *
References