U.S. patent application number 16/510930 was filed with the patent office on 2020-06-25 for device and method for the treatment of substance use disorders.
This patent application is currently assigned to Spark Biomedical, Inc. The applicant listed for this patent is Spark Biomedical, Inc. Invention is credited to Alejandro Covalin.
Application Number | 20200197707 16/510930 |
Document ID | / |
Family ID | 71099127 |
Filed Date | 2020-06-25 |
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United States Patent
Application |
20200197707 |
Kind Code |
A1 |
Covalin; Alejandro |
June 25, 2020 |
Device and Method for the Treatment of Substance Use Disorders
Abstract
A treatment system and method for inducing endogenous release of
peptides is provided including a concha apparatus including a first
electrode in contact with vagal related neural structures; an
earpiece connected to the concha apparatus by a first connector,
the earpiece including a PCB layer including a second electrode
configured to be in contact with a neural structure related to the
auriculotemporal nerve, and at least another electrode configured
to be in contact with or in proximity to neural structures related
to the great auricular nerve and/or its branches and/or the lesser
occipital nerve and/or its branches, and an adhesive configured to
secure the electrodes on the earpiece to the skin; and a pulse
generator connected to the earpiece by a second connector, the
pulse generator including circuitry in communication with the first
electrode of the concha apparatus, the second electrode and the at
least another electrode of the earpiece.
Inventors: |
Covalin; Alejandro; (Los
Angeles, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Spark Biomedical, Inc |
Friendswood |
TX |
US |
|
|
Assignee: |
Spark Biomedical, Inc
Friendswood
TX
|
Family ID: |
71099127 |
Appl. No.: |
16/510930 |
Filed: |
July 14, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62777569 |
Dec 10, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/36053 20130101;
A61H 2205/027 20130101; A61H 39/002 20130101; A61N 1/36021
20130101; A61N 1/0456 20130101; A61N 1/36089 20130101; A61K 31/485
20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61H 39/00 20060101 A61H039/00; A61N 1/04 20060101
A61N001/04 |
Claims
1. A wearable treatment system for providing transcutaneous
stimulation for inducing endogenous release of peptides, the
treatment system comprising: a concha apparatus for placement
external to an ear canal of an ear of a patient, including a first
electrode configured to be in contact with vagal related neural
structures of the ear of the patient, wherein the concha apparatus
is configured to be retained, at least in part, through frictional
engagement with a concha of the ear; a first connector; an earpiece
for placement around the ear of the patient, the earpiece being
connected to the concha apparatus by the first connector, the
earpiece including an insulated electronics layer including a
second electrode configured to be in contact with a neural
structure related to the auriculotemporal nerve, and at least
another electrode configured to be in contact with neural
structures related to at least one of the great auricular nerve
and/or branches of the great auricular nerve and/or the lesser
occipital nerve and/or branches of the lesser occipital nerve; a
second connector; and a pulse generator configured to be connected
to the earpiece by the second connector, the pulse generator
including circuitry in electrical communication with the first
electrode of the concha apparatus via the first connector, and the
second electrode and the at least another electrode of the earpiece
via the second connector, wherein the circuitry is configured to
provide a therapy that induces the endogenous release of peptides
through pulses of electrical stimulation to the ear and/or around
the ear of the patient via the first electrode, the second
electrode, and the at least another electrode; wherein the concha
apparatus and the earpiece are designed for secure placement of the
first electrode, the second electrode, and the at least another
electrode without piercing the dermal layers of skin on and
surrounding the ear.
2. The treatment system of claim 1, further comprising a peripheral
device configured to be in communication with the pulse generator
and configured to modify a stimulation parameter of the therapy
provided by the pulse generator to at least one electrode of the
first electrode, the second electrode, and the at least another
electrode.
3. The treatment system of claim 1, wherein the pulse generator
includes a low power field-programmable gate array for controlling
delivery of the therapy.
4. The treatment system of claim 2, wherein the stimulation
parameter is configured to cause the circuitry to synchronize at
least a portion of the pulses of electrical stimulation delivered
to the first electrode of the concha apparatus and the second
electrode of the earpiece to balance a ratio of activity between at
least one of a) the autonomic nervous system and the
parasympathetic nervous system, b) the autonomic nervous system and
the sympathetic nervous system, or c) the parasympathetic nervous
system and the sympathetic nervous system.
5. The treatment system of claim 1, wherein at least one of the
second electrode and the at least another electrode is comprised of
a grouping of two or more electrodes.
6. The treatment system of claim 1, further comprising a
multiplexor in communication with two or more electrodes of the
second electrode and/or the at least another electrode and
configured to direct the pulses of electrical stimulation towards
at least one of the two or more electrodes.
7. The treatment system of claim 24, wherein the adhesive comprises
a conductive adhesive coating on each electrode of the second
electrode and the at least another electrode.
8. The treatment system of claim 1, further comprising at least one
actuator disposed between the second electrode and a given
electrode of the at least another electrode.
9. The treatment system of claim 1, wherein the concha apparatus
comprises: a first member configured to fit within first natural
extrusions and notches of the ear to aid in retaining the concha
apparatus in the concha of the ear; and a second member configured
to fit within second natural extrusions and notches of the ear to
aid in retaining the concha apparatus in the concha of the ear.
10. The treatment system of claim 1, wherein the concha apparatus
includes a spring configured to stress a structure of the concha
apparatus to facilitate placement of the first electrode.
11. The treatment system of claim 1, wherein a structure of the
concha apparatus is configured to be mechanically stressed to
facilitate secure placement of the first electrode against the
skin.
12. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to provide the endogenous
release of peptides for treating substance use disorder and/or
pain.
13. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to provide therapy for
treatment of neonatal abstinence syndrome.
14. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to induce neuronal plasticity
for at least one of provoking cognitive improvements, stroke
recovery, PTSD, phobias, ADHD, ADD, dementia including treating
Alzheimer's disease.
15. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to be used to restore
autonomic balance to support treatment of at least one of cardiac
heart failure, atrial fibrillation, anxiety, stress, gastric
motility, depression, cluster headaches, and migraines.
16. A wearable treatment device for providing transcutaneous
stimulation for inducing endogenous release of peptides, the
treatment device comprising: a concha apparatus for placement
external to an ear canal of an ear of a patient, including a first
electrode configured to be in contact with vagal related neural
structures of the ear of the patient, wherein the concha apparatus
is configured to be retained, at least in part, through frictional
engagement with a concha of the ear; a first connector; and an
earpiece for placement around the ear of the patient, the earpiece
being connected to the concha apparatus by the first connector, the
earpiece including an insulated electronics layer including a
second electrode configured to be in contact with a neural
structure related to the auriculotemporal nerve, and at least
another electrode configured to be in contact with neural
structures related to at least one of the great auricular nerve
and/or branches of the great auricular nerve and/or the lesser
occipital nerve and/or branches of the lesser occipital nerve, and
an adhesive configured to secure the second electrode and the at
least another electrode to a portion of the skin surrounding the
ear of the patient; and a second connector; wherein the wearable
treatment device is configured to be connected to a pulse
generator, the pulse generator including circuitry configured to be
in electrical communication with the first electrode of the concha
apparatus via the first connector, and the second electrode and the
at least another electrode of the earpiece via the second connector
for providing the transcutaneous stimulation for inducing the
endogenous release of peptides; wherein the wearable treatment
device is designed for secure placement of the first electrode, the
second electrode, and the at least another electrode without
piercing the dermal layers of skin on and surrounding the ear.
17.-20. (canceled)
21. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to provide therapy for
treatment of inflammation.
22. The treatment system of claim 1, wherein the therapy induces
the endogenous release of endorphins.
23. The treatment system of claim 1, wherein the pulses of
electrical stimulation are configured to provide therapy for
treatment of chronic pain.
24. The treatment system of claim 1, wherein the earpiece further
comprises an adhesive configured to secure the second electrode and
the at least another electrode to a portion of the skin surrounding
the ear of the patient.
Description
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application Ser. No. 62/777,569, entitled "Device and Method for
the Treatment of Substance Use Disorders," filed Dec. 10, 2018. All
above identified applications are hereby incorporated by reference
in their entireties.
BACKGROUND
[0002] According to the National Survey on Drug Use and Health,
approximately 2.1 million Americans are addicted to opioid pain
relievers (OPRs), and 513,000 are addicted to heroin. In 2017 there
are a record 72,000 overdose deaths, a rise of approximately 10%
nationwide; largely fueled by new, synthetic opioids. The National
Institutes of Health (NIH) reported that in the United States alone
there are more than 115 deaths every day related to opioids.
Opioids produce a strong physiological dependence on its users; it
is this dependence that makes it extremely difficult, if not
impossible, for user willing to stop consuming this type of drug to
do so without the intervention of a healthcare professional.
[0003] The physiological reaction caused by stopping opioid intake
is known as Opioid Withdrawal. Opioid Withdrawal is generally
extremely unpleasant and in some unattended cases may lead to
death. The over usage of opioids in the country has reach such
levels that the government has labeled the current situation as a
national crisis. Interventions are needed to help alleviate the
Opioid Withdrawal symptoms felt by individuals who are in the
process of stopping opioid consumption.
[0004] Addressing strategies for addiction treatment and recovery
has become a major priority for government agencies given the
substantial impact on health, social, and economic welfare.
Treatment of opioid addiction includes pharmacotherapies and
psychosocial and behavioral adaptation approaches including:
residential treatment, mutual-help, and 12-Step treatment programs.
In many cases these interventions may be administered alone or in
combination with pharmacotherapy. Psychosocial opioid addiction
treatment approaches show value and are an important treatment
option. However, treatments with greater specificity, consistency,
and patient compliance is needed.
SUMMARY OF ILLUSTRATIVE EMBODIMENTS
[0005] The forgoing general description of the illustrative
implementations and the following detailed description thereof are
merely exemplary aspects of the teachings of this disclosure, and
are not restrictive.
[0006] In an exemplary embodiment, a wearable treatment system for
providing transcutaneous stimulation for inducing endogenous
release of peptides, includes a concha apparatus including a first
electrode configured to be in contact with vagal related neural
structures; an earpiece connected to the concha apparatus by a
first connector, the earpiece including an insulated electronics
layer including a second electrode configured to be in contact with
a neural structure related to the auriculotemporal nerve, and at
least another electrode configured to be in contact with or in
proximity to neural structures related to at least one of the great
auricular nerve and/or its branches and/or the lesser occipital
nerve and/or its branches, and an adhesive configured to secure at
least one of the earpiece and the electrodes on the earpiece to the
skin surrounding an ear of a patient; and a pulse generator
configured to be connected to the earpiece by a second connector,
the pulse generator including circuitry in communication with the
first electrode of the concha apparatus, the second electrode and
the at least another electrode of the earpiece.
[0007] In some implementations, the treatment system includes a
peripheral device configured to be in communication with the pulse
generator and configured to modify a stimulation parameter provided
to at least one electrode.
[0008] In some implementations, the pulse generator includes a low
power field-programmable gate array for controlling therapy
delivery.
[0009] In some implementations, the stimulation parameter is
configured to provide synchronized stimulations between the concha
apparatus and the earpiece configured to balance a ratio of
activity between at least one of the autonomic nervous system and
the parasympathetic nervous system, the autonomic nervous system
and the sympathetic nervous system, and the parasympathetic nervous
system and the sympathetic nervous system.
[0010] In some implementations, at least one of the second
electrode and the at least another electrode is comprised of a
grouping of two or more electrodes.
[0011] In some implementations, the treatment system includes a
multiplexor in communication with two or more of the electrodes on
the earpiece and configured to direct stimulation pulses towards at
least one of the two or more of the electrodes on the earpiece.
[0012] In some implementations, the treatment system includes a
conductive adhesive coating on each electrode.
[0013] In some implementations, the treatment system includes at
least one actuator disposed between electrodes on the earpiece.
[0014] In some implementations, the concha apparatus has a first
member on its distal end configured to fit within natural
extrusions and notches of the ear and a second member on its
proximal end configured to fit within natural extrusions and
notches of the ear.
[0015] In some implementations, the concha apparatus includes a
spring configured to stress a structure of the concha apparatus to
facilitate placement of the first electrode.
[0016] In some implementations, the structure of the concha
apparatus is configured to be mechanically stressed to facilitate
secure placement of the first electrode to the skin.
[0017] In some implementations, the treatment system is configured
to provide endogenous release for treating substance use disorder
and pain.
[0018] In some implementations, the treatment system is configured
to provide therapy for treatment of neonatal abstinence
syndrome.
[0019] In some implementations, the treatment system is configured
to induce neuronal plasticity for at least one of provoking
cognitive improvements, stroke recovery, PTSD, phobias, ADHD, ADD,
dementia including treating Alzheimer's disease.
[0020] In some implementations, the treatment system is configured
to be used to restore autonomic imbalance including at least one of
cardiac heart failure, atrial fibrillation, anxiety, stress,
gastric motility, depression, cluster headaches, and migraines.
[0021] In an exemplary embodiment, a wearable treatment device for
providing transcutaneous stimulation for inducing endogenous
release of peptides, includes a concha apparatus including a first
electrode configured to be in contact with vagal related neural
structures; and an earpiece connected to the concha apparatus by a
connector, the earpiece including an insulated electronics layer
including a second electrode configured to be in contact with a
neural structure related to the auriculotemporal nerve, and at
least another electrode configured to be in contact with or in
proximity to neural structures related to at least one of the great
auricular nerve and/or its branches and/or the lesser occipital
nerve and/or its branches, and an adhesive configured to secure the
electrodes on the earpiece to the skin; and wherein the treatment
device is configured to be connected to a pulse generator, the
pulse generator including circuitry configured to be in
communication with the first electrode of the concha apparatus, and
the second electrode and the at least another electrode of the
earpiece.
[0022] In an exemplary embodiment, a method for inducing endogenous
release of peptides, including adhering a therapy device to an
outer portion of a patient's skin including a concha apparatus
including a first electrode configured to be in contact with vagal
related neural structures, an earpiece connected to the concha
apparatus by a first connector, the earpiece including an insulated
electronics layer including a second electrode configured to be in
contact with a neural structure related to the auriculotemporal
nerve, and at least another electrode configured to be in contact
with or in proximity to neural structures related to at least one
of the great auricular nerve and/or its branches and/or the lesser
occipital nerve and/or its branches; connecting the therapy device
to a pulse generator including circuitry configured to be in
communication with the first electrode of the concha apparatus, and
the second electrode and the at least another electrode of the
earpiece; providing a first stimulation to the first electrode at a
first tissue location configured to stimulate a first pathway for
modulating a first release of a first endogenous peptide; and
providing a second stimulation at a second tissue location
configured to stimulate a second pathway for modulating a second
release of a second endogenous peptide.
[0023] In some implementations, the first stimulation is a high
frequency stimulation and the second stimulation is a low frequency
stimulation.
[0024] In some implementations, the first stimulation is configured
to stimulate a dynorphin pathway including at least one of the
auriculotemporal nerve, the lesser occipital nerve, and the great
auricular nerve.
[0025] In some implementations, the second stimulation is
configured to stimulate at least one of an endorphin pathway and
enkephalin pathway including at least one of the auricular branch
of the vagus nerve, the lesser occipital nerve, the great auricular
nerve, and the arcuate nucleus.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] The accompanying drawings, which are incorporated in and
constitute a part of the specification, illustrate one or more
embodiments and, together with the description, explain these
embodiments. The accompanying drawings have not necessarily been
drawn to scale. Any values dimensions illustrated in the
accompanying graphs and figures are for illustration purposes only
and may or may not represent actual or preferred values or
dimensions. Where applicable, some or all features may not be
illustrated to assist in the description of underlying features. In
the drawings:
[0027] FIG. 1A is a drawing identifying structures of an ear
according to an example;
[0028] FIG. 1B is a drawing of innervations of the ear amongst
which are vagal related neural structures, auriculotemporal nerve
structures, neural structures related to the lesser occipital
nerve, and neural structures related to the great auricular
nerve;
[0029] FIGS. 1C-1E are drawings identifying neural structures and
pathways for modulating the release of endogenous opiate receptor
agonist, which modulate pain, as well as pathways modulating
inflammatory and cognitive processes to an example;
[0030] FIG. 2A is a drawing of a treatment device including an
auricular component having an earpiece connected to a concha
apparatus by a first connector, and a pulse generator connected to
the earpiece of the auricular component by a second connector
according to an example;
[0031] FIG. 2B is a drawing of an alternative view of the treatment
device shown in FIG. 2A showing the concha apparatus including a
first electrode or cymba electrode, and the earpiece including a
second electrode and at least another electrode according to an
example;
[0032] FIG. 2C is a drawing of a treatment device including a
number of electrodes configured to be virtually grouped together to
form one or more effective electrodes according to an example;
[0033] FIG. 2D is a drawing of a side view of a portion of a
treatment device including haptic feedback actuators between a pair
of electrodes according to an example;
[0034] FIG. 3A is a drawing of an auricular component having an
earpiece and concha apparatus with shapes configured to aid in
securing the treatment device and respective electrodes to a
respective ear structure according to an example;
[0035] FIG. 3B is an illustration of the auricular component worn
on the ear of a patient according to an example;
[0036] FIGS. 4A-4C are drawings of a concha apparatus having a
shape configured to aid in securing the concha apparatus and
respective supported electrodes to a respective ear structure
according to another example;
[0037] FIGS. 5A-5B are exploded views of components of the
treatment device including a skin, a PCB layer, an adhesive layer
composed of two elements, a skin adhesive and a number of
conductive adhesive elements according to an example;
[0038] FIG. 6 is a drawing of a portion of an auricular component
made from a flexible PCB according to an example;
[0039] FIG. 7A-7C are drawings of the flexible PCB encapsulated in
a protective covering according to an example;
[0040] FIGS. 8A-8B are drawings of a structural-loaded component
configured to facilitate placement of the cymba electrode according
to an example;
[0041] FIGS. 9A-9C are drawings of a spring-loaded component
configured to facilitate placement of the cymba electrode according
to an example;
[0042] FIGS. 10A-10C are drawings of a system including the
treatment device in communication with third parties through a
computing cloud and/or a peripheral device according to an
example;
[0043] FIG. 11 is a drawing of a schematic of components of a pulse
generator in communication with components of the flexible PCB of
the auricular component according to an example;
[0044] FIG. 12 is a drawing of an electrode configuration and
equivalent circuit for providing therapy according to an
example;
[0045] FIG. 13 is a drawing of a method for triggering multiple
channels using a single clock according to an example;
[0046] FIG. 14A is a flow chart of a method for providing therapy
including providing a first stimulation at a first tissue location
configured to stimulate a first pathway for modulating a first
release of a first endogenous peptide and a second stimulation at a
second tissue location configured to stimulate a second pathway for
modulating a second release of a second endogenous peptide
according to an example;
[0047] FIG. 14B are examples of target locations for stimulation of
the first tissue location;
[0048] FIG. 14C are examples of target locations for stimulation of
the second tissue location;
[0049] FIG. 14D is a flow chart of a method for providing therapy
including providing a first stimulation at a first tissue location
such that neural activity at the arcuate nucleus of the
hypothalamus (ARC) is modulated such that it stimulates the
Periaqueductal Gray Area (PAG) for modulating a first release of
enkephalins and/or endorphins, and a second stimulation at a second
tissue location such that neural activity at the Parabranchial
Nucleus (PbN) is modulated such that it also stimulates the
Periaqueductal Grey Area (PAG) for modulating a second release of a
dynorphins, according to an example; and
[0050] FIG. 15 is a bar graph showing data collected using the
proposed system according to an example.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0051] The description set forth below in connection with the
appended drawings is intended to be a description of various,
illustrative embodiments of the disclosed subject matter. Specific
features and functionalities are described in connection with each
illustrative embodiment; however, it will be apparent to those
skilled in the art that the disclosed embodiments may be practiced
without each of those specific features and functionalities.
[0052] Reference throughout the specification to "one embodiment"
or "an embodiment" means that a particular feature, structure, or
characteristic described in connection with an embodiment is
included in at least one embodiment of the subject matter
disclosed. Thus, the appearance of the phrases "in one embodiment"
or "in an embodiment" in various places throughout the
specification is not necessarily referring to the same embodiment.
Further, the particular features, structures or characteristics may
be combined in any suitable manner in one or more embodiments.
Further, it is intended that embodiments of the disclosed subject
matter cover modifications and variations thereof.
[0053] It must be noted that, as used in the specification and the
appended claims, the singular forms "a," "an," and "the" include
plural referents unless the context expressly dictates otherwise.
That is, unless expressly specified otherwise, as used herein the
words "a," "an," "the," and the like carry the meaning of "one or
more." Additionally, it is to be understood that terms such as
"left," "right," "top," "bottom," "front," "rear," "side,"
"height," "length," "width," "upper," "lower," "interior,"
"exterior," "inner," "outer," and the like that may be used herein
merely describe points of reference and do not necessarily limit
embodiments of the present disclosure to any particular orientation
or configuration. Furthermore, terms such as "first," "second,"
"third," etc., merely identify one of a number of portions,
components, steps, operations, functions, and/or points of
reference as disclosed herein, and likewise do not necessarily
limit embodiments of the present disclosure to any particular
configuration or orientation.
[0054] Furthermore, the terms "approximately," "about,"
"proximate," "minor variation," and similar terms generally refer
to ranges that include the identified value within a margin of 20%,
10% or preferably 5% in certain embodiments, and any values
therebetween.
[0055] All of the functionalities described in connection with one
embodiment are intended to be applicable to the additional
embodiments described below except where expressly stated or where
the feature or function is incompatible with the additional
embodiments. For example, where a given feature or function is
expressly described in connection with one embodiment but not
expressly mentioned in connection with an alternative embodiment,
it should be understood that the inventors intend that that feature
or function may be deployed, utilized or implemented in connection
with the alternative embodiment unless the feature or function is
incompatible with the alternative embodiment.
[0056] Currently, the United States is experiencing an opioid
epidemic in the use of prescription and non-prescription drugs that
has continued to rise since the 1990's. The need for safe and
effective opioid withdrawal treatment is demanding and largely
unmet. According to the National Survey on Drug Use and Health
(NSDUH), approximately 2.1 million Americans are addicted to opioid
pain relievers (OPRs), and 513,000 are addicted to heroin. In 2005,
there were an estimated 10 million chronic pain patients receiving
daily, long-term treatment with OPRs. The continuing increase in
opioid consumption from 2005 to 2017 suggests that the number may
now exceed 11 million.
[0057] A primary constraint on the overall percentage of treatment
recipients is the limited availability of licensed physicians that
can prescribe pharmacotherapies. Additionally, prescription opioids
pose a variable level of risk on respiratory depression and
abnormal cardiac activity, thus can only be obtained from licensed
opioid treatment programs (OTPs). The lack of OTPs in many
communities presents a major challenge to expanding access to
methadone. In contrast, buprenorphine, a partial opioid agonist,
has demonstrated a better safety profile compared to methadone and
can be prescribed in an office-based setting. However,
buprenorphine includes federal limits on the number of patients a
physician may treat, ineligibility of nurse practitioners to
prescribe it, and inadequate integration of buprenorphine into
primary care treatment.
[0058] Pharmacotherapies for opioid withdrawal include full-agonist
treatment with methadone, partial-agonist with buprenorphine, and
full-antagonist with naltrexone. Methadone and buprenorphine are
semi-synthetic opioid derivatives that bind to opioid receptors and
allow addicted individuals to discontinue the misuse of opioids
without experiencing withdrawal symptoms. Buprenorphine can produce
typical opioid effects and side effects such as euphoria and
respiratory depression, however, its maximal effects are less than
those of full agonists like methadone or heroin. Dose response
curves specific to the agonist effects of buprenorphine increase
linearly with higher doses of the drug until it reaches a
plateau.
[0059] Buprenorphine can block the effects of full opioid agonists
(i.e. methadone and heroin) and can precipitate withdrawal symptoms
if administered to an opioid-addicted individual while a full
agonist is in the bloodstream. Buprenorphine has a higher affinity
than other opioids and as such will compete for the receptor and
occupy that receptor blocking other opioids from binding. If there
is an insufficient amount of buprenorphine to occupy and satisfy
the receptors, withdrawal symptoms can occur; in which case
additional buprenorphine is given until withdrawal symptoms
disappear.
[0060] Lastly, naltrexone is an opioid-antagonist that competes for
opioid-receptors and displaces opioid drugs from these receptors,
thus reversing the effects of opioids. Naltrexone is capable of
antagonizing all opioid receptors, but has a higher affinity to
.mu.- rather than .kappa.- and .delta.-receptors. By blocking the
.mu.-opioid receptor, naltrexone acts to decrease the dopamine
reward. The activity of naltrexone is thought to be a result of
both the parent and its 6.beta.-naltrexol metabolite. Naltrexone's
mechanism of action is similar to naloxone (opioid antagonist;
found in Suboxone) except that it is longer acting. Naltrexone can
be administered with a long-acting injection formulated in
microspheres that persists for 1 month after a single
injection.
[0061] Due to inadequate and scarce treatment options, finding an
effective non-pharmacological approach would be critical in
improving and expanding treatment for opioid withdrawal and
addiction. Abundant clinical evidence exists for the rapid and
effective reduction of signs and symptoms associated with opioid
withdrawal through various approaches of non-invasive
neurostimulation.
[0062] Anecdotal evidence exists for the rapid and effective
attenuation of signs and symptoms associated with opioid withdrawal
through neurostimulation.
[0063] FIG. 1A is a drawing identifying structures of an ear
showing amongst other the concha cymba, the tragus, the antihelix,
the helix, the external auditory meatus, and the Lobule. FIG. 1B is
a drawing of innervations of the ear amongst which are vagal
related neural structures, for example within the concha cymba,
auriculotemporal nerve structures, for example rostral to the
auricle, neural structures related to the lesser occipital nerve,
for example along the antihelix, and neural structures related to
the great auricular nerve, for example on the lobule region.
[0064] FIGS. 1C-1E are drawings identifying neural structures and
pathways for modulating the release of endogenous opioid receptor
agonist, which modulate pain, as well as pathways modulating
inflammatory and cognitive processes. The Nucleus of the solitary
tract (NTS) receives afferent connections from many areas including
the Trigemino-cervical complex (TCC), the cervical vagus nerve as
well as from the auricular branch of the vagus nerve (ABVN). The
TCC is a region in the cervical and brain stem area were trigeminal
and occipital fibers synapse, including the Auriculotemporal nerve,
the lesser occipital nerve and the greater auricular nerve. The TCC
projects to multiple areas in the brain stem including, but not
limited to the Nucleus Raphe Magnus (NRM), the Locus Coeruleus
(LC), Periaqueductal Gray (PAG), Nucleus Basalis (NBM) and
Parabranchial nucleus (PbN). The NTS also among others, also
projects to the Nucleus Raphe Magnus, the Locus Coeruleus, and the
Periaqueductal Gray as well as to high centers like the
hypothalamus, including into the Arcuate Nucleus (ARC) which
receives its majority of non-intrahypothalamic afferents from the
NTS. Additionally, many interconnections exist amongst different
brainstem nuclei (e.g., PAG, LC, NRM, NBM, PbN, PPN).
[0065] These connections make this neural circuit extremely
important for modulating pain, as production of endorphins,
enkephalins, and dynorphins are modulated by this circuit. In
addition, this neural circuits are crucial for learning and memory
as well as for arousal and wakefulness. For example, an interaction
between norepinephrine, produced by activity in the Locus
Coeruleus, Serotonin (5-HT), produced by activity in the Nucleus
Raphe Magnus, and Acetylcholine (Ach) produced by activity in the
Pedunculopontine Nucleus (PPN) or NBM is extremely important for
memory and learning. Arousal and wakefulness is modulated, amongst
others, by norepinephrine in the brain.
[0066] There are descending indirect connections going to the
heart, Lungs, Gut, and spleen. Indirect connections include
connections where there is at least one synapse elsewhere before
reaching the target. This means that modulating the activity of
these neural circuits can affect the respective organs. In
particular, heart rate can be modulated, for example, heart rate
can be decreased and heart rate variability can be increased;
oxygen absorption can be increased at the lungs by increasing the
compliance of the bronchi tissue and thus increasing the oxygen
transport availability therefore increasing the potential for more
oxygen to be absorbed into the blood; gut motility can be increased
by descending pathways originating in the dorsal motor nucleus of
the vagus nerve (DMV); since DMV activity is modulated by NTS
activity, motility in the gut can be affected by modulating the
activity in the NTS; and a decrease in circulating pro-inflammatory
cytokines can be achieved by modulating spleen activity via NTS
descending pathways.
[0067] There are at least three different opioid receptors, Mu
(.mu.), Delta (.delta.), and Kappa (.kappa.) in pain modulation.
The body produces endogenous agonist peptides for each of these
three receptors. These peptides are called endorphins, which
primarily binds to the Mu (.mu.) receptors, Enkephalin which
primarily binds to the Delta (.delta.) receptors, and Dynorphins,
which primarily binds to the Kappa (.kappa.) receptors. Pain
studies suggest that production of these endogenous peptides follow
different pathways. While production of endorphins and enkephalin
is mediated by activity in the Arcuate Nucleus (ARC) in the
hypothalamus, activity in the Parabranchial nucleus mediates
production of dyanophins. Furthermore, electrostimulation
experiment showed that dynorphin production was more efficiently
mediated by higher frequency than production of the endorphins
and/or enkephalins; this suggests that while the dynorphin pathway
is more efficiently activated by higher frequencies, the endorphins
and enkephalins pathway is more efficiently activated by lower
frequencies.
[0068] Percutaneous neurostimulation requires a percutaneous device
which uses small needles implanted into the skin to deliver
neurostimulation. Percutaneous neurostimulation systems present
numerous disadvantages and limitations, which include: the location
of the needles is critical and thus needle insertion must be
performed by a trained professional heath provider; the needles
must be sterile; needle sterility requirements equate to a minimal
device shelf-life; movement or dislodged needles requires the
attention of a trained clinic staff member; many patients have
inherent fear of needles; currently available systems cannot be
re-used, re-charged, or used beyond its immediate battery life;
currently available systems do not allow for fully customizable
stimulation settings; currently available systems are not capable
of determining and reporting if stimulation is being delivered;
currently available systems are not capable of gathering device
compliance data; and currently available systems are not designed
to be easy to use, aesthetically and cosmetically appealing which
has an effect on patient compliance.
[0069] In an aspect, the system relates to transcutaneous
stimulation of auricular nerve fibers for the reduction of
substance consumption, the reduction of symptoms associated with
substance withdrawal, and for the long-term maintenance to prevent
substance relapse. The proposed novel neuromodulation treatment
does not require piercing the dermal layers and the required
precision is such that any layman can apply the device and receive
therapy. In an aspect, the system is not required to be sterile, is
easy to apply, and a user can apply without a clinician. The
proposed treatment method along with the treatment device overcomes
all of the above mentioned disadvantages. Given the large unmet
medical need (i.e., opioid overuse), the fact that the treatment
device proposed here has not been offered in the manner here
proposed points to the non-obviousness nature of the proposed
treatment.
[0070] A therapy system and method are provided for rapidly
releasing endogenously produced opioid receptor agonists. The
therapy system includes a treatment device that allows the proposed
therapy to be easily and reliably applied by almost anyone at a
relatively low cost. Some advantages over the existing
neuromodulation treatment and related devices are: ease of use in
both the application of the device, customizing therapeutic
settings, and the actual wearing of the device, minimal risk of
infection, users have the ability to safely self-administer or
restart the treatment without the need to go back to a clinic,
significantly extended shelf life, reduced anxiety of patient due
to non-invasiveness, long-term use option, customizable therapeutic
settings, ability to notify user, caregiver, and clinician if
therapy is interrupted or halted, ability to report overall usage
to clinical staff or users for analysis, and the user does not have
go back to the clinic to extend treatment or to use it at any given
time when they feel it is needed present a major advantage over
existing neuromodulation therapies, opening the door to a long-term
maintenance treatment.
[0071] Furthermore, patient compliance is one of the primary
obstacles to clinical success, the proposed device has been
designed to alert the treating clinic staff when the device is not
being used as prescribed, including device malfunction, and
electrode misplacement. Since the device and therapy can be used
long-term and can be easily applied by the user, the novel
therapy/device combination lends itself to be used for consumption
reduction, consumption secession, and long-term use avoidance.
[0072] In some implementations, the treatment device can be used
for treating and/or managing symptoms for other indications. In
some implementations, the treatment device can be used to provide
therapy for the treatment of neonatal abstinence syndrome by
transcutaneous stimulation of auricular nerve fibers. Auricular
acupuncture has recently been studied as an adjunctive therapy for
neonatal abstinence syndrome in newborns. Non-insertive acupuncture
(NIA) using traditional needles as shown in a publication by
Filippelli, A. C. et. al. (2012). titled "Non-insertive Acupuncture
and Neonatal Abstinence Syndrome: A Case Series From an Inner-city
Safety Net Hospital. Global Advances in Health and Medicine,"
published in Global Advances in Health and Medicine, 48-52. 2012,
herein incorporated by reference.
[0073] Evidence that the treatment device can be used to provide
therapy for the treatment of neonatal abstinence syndrome was
provided in a study where a handheld laser was applied to the ear
of newborns with neonatal abstinence syndrome resulting in some of
the babies becoming more relaxed during their course of treatment,
as described in Raith, W., & Urlesberger, B. titled "Laser
Acupuncture as An Adjuvant Therapy for a Neonate with Neonatal
Abstinence Syndrome (NAS) Due to Maternal Substitution Therapy:
Additional Value of Acupuncture," published in Acupuncture in
Medicine, 2012, 32(6), 523-524 herein incorporated by reference.
While more in-depth studies are needed to evaluate Non-insertive
acupuncture as an effective adjunct therapy for neonatal abstinence
syndrome in newborns, the early results show promise of tapping
into the auricular neural pathways for treating neonatal abstinence
syndrome.
[0074] In an aspect, the therapy device is configured to provide
stimulation therapy to release a different type and quantity of
endogenous opioid peptides based on varying stimulation parameters.
Three families of endogenous opioid peptides have been
characterized in the CNS: enkephalins, endorphins, and dynorphins.
Supporting animal data was shown in a study examining effects of
different stimulation frequencies on the type and quantity of
endogenous opioid peptides released, as described in a publication
by Han, J. S., and Wang, Q. titled "Mobilization of specific
neuropeptides by peripheral stimulation of identified frequencies,"
in Physiology 1992, 7(4), 176-180, herein incorporated by
reference. Electro-acupuncture (EA) stimulation was delivered at
two specific acupoints on the hindlimb. Rats were given stimulation
at 2, 15, and 100 Hz. Spinal perfusate was collected before and
during stimulation. A clear difference in stimulation frequency and
type of opioid peptide release were shown including that 2 Hz was
effective at releasing enkephalins and beta-endorphins, and 100 Hz
most effectively released dynorphin. No increase in opioid peptides
was observed in non-responder rats that failed to show a response
to tail-flick during stimulation. Although, 15 Hz was capable of
releasing enkephalin and dynorphin opioid peptides, another study
shows that alternating stimulation at 2 Hz/100 Hz maximized
analgesic effects, the study by Han, J. S. titled "Acupuncture and
endorphins," published in Neuroscience letters, 2004, 361(1-3),
258-261 is herein incorporated by reference. The scientific
evidence that pain-relief is achieved by delivering
neurostimulation to release endogenous opioid peptides and fill
vacant opioid receptors, was later a tested hypothesis for reducing
the symptoms associated with opioid withdrawal.
[0075] In a randomized clinical trial, transcutaneous electrical
acupoint stimulation (TEAS) was delivered as an adjuvant to opioid
detoxification using buprenorphine-naloxone, the clinical trial as
reported by Meade, C. S., et al., titled "A randomized trial of
transcutaneous electric acupoint stimulation as adjunctive
treatment for opioid detoxification, Journal of Substance Abuse
Treatment, 2010, 38(1), 12-21, is herein incorporated by reference.
Based on the preclinical evidence described above, TEAS was
delivered at alternating low (2 Hz) and high (100 Hz) for 30
minutes each day for 3-4 days. In the active TEAS group, patients
were 77% less likely to have used any drugs as compared to 33% in
sham treatment at 2-weeks post-discharge. Additionally, active TEAS
improved pain perception and overall health.
[0076] In some implementations, the treatment device can be used to
induce neuronal plasticity or Neuroplasticity for provoking
cognitive improvements, stroke recovery, PTSD, phobias, ADHD, ADD,
dementia including treating Alzheimer's disease. Neuroplasticity
underlies learning; therefore, strategies that enhance
neuroplasticity during training have the potential to greatly
accelerate learning rates. Earlier studies have successfully
demonstrated that invasive or implanted vagus nerve stimulation
(VNS) can drive robust, specific neural plasticity. Brief bursts of
VNS are paired with training to engage pro-plasticity
neuromodulatory circuits and reinforce the specific neural networks
that are involved in learning. This precise control of
neuroplasticity, coupled with the flexibility to be paired with
virtually any training paradigm, establishes VNS as a potential
targeted neuroplasticity training paradigm.
[0077] The vagus nerve is a cranial nerve that is located adjacent
to the carotid artery in the neck. Direct stimulation of the vagus
nerve activates the nucleus tractus solitarius, which has
projections to nucleus basalis (NB) and locus coeruleus (LC). The
NB and LC are deep brain structures that release acetylcholine and
norepinephrine, which are pro-plasticity neurotransmitters
important for learning and memory. Stimulation of the vagus nerve
using a chronically implanted electrode cuff is safely used in
humans to treat epilepsy and depression and has shown success in
clinical trials for tinnitus and motor impairments after stroke.
The auricular branch of the vagus nerve innervates the dermatome
region of outer ear, being the region known as the cymba conchae
one of the areas innervated by it. Non-invasive stimulation of the
left auricular branch of the vagus nerve may drive activity in
similar brain regions as invasive vagus nerve stimulation. Recently
auricular neurostimulation has proven beneficial in treating a
number of human disorders.
[0078] In some implementations, the treatment device can be used to
restore autonomic imbalance such as cardiac heart failure, atrial
fibrillation (AF), anxiety, stress, gastric motility, depression,
cluster headaches, and migraines. Transcutaneous electrical
stimulation of the tragus, the anterior protuberance of the outer
ear, where the auricular branch of the Vagus nerve is located can
elicit evoked potentials in the brainstem in human subjects. Based
on these observations, it was demonstrated that atrial fibrillation
inducibility was suppressed by transcutaneous LL-VNS, which was
achieved through stimulation of the auricular branch of the vagus
nerve at the tragus in a canine. Noninvasive LL-TS increases AF
threshold (mitigates risk of AF), as well as alleviates AF burden
in both canines and humans. In healthy subjects, LL-TS can also
increase heart rate variability and reduce sympathetic outflow.
[0079] In an exemplary embodiment, a therapy system includes a
treatment device having an auricular component configured to be in
contact with a patient and a pulse generator or controller
configured to communicate with the treatment device. In some
implementations, a treatment device can be provided as an assembled
unit or as several pieces configured for connection prior to use.
In an example, the auricular component can be provided in a sealed
pouch and a pulse generator can be provided to connect the
auricular component to a connector on the pulse generator. In an
aspect, the system is configured to have a removable stimulator
without the need to remove the auricular component and vice-versa.
In an example, the earpiece can be placed around the auricle of the
patient before or after connection to the pulse generator.
[0080] To apply the earpiece around the auricle of the patient,
press against the patient's skin such that exposed skin adhesives
and adhesives/hydrogels adhere to the skin. Next, place the concha
apparatus in the ear such that a first portion of the concha
apparatus sits outside the external ear canal in the cavum.
Finally, flex a second or distal portion of the concha apparatus
supporting the cymba electrode until it goes into the cymba of the
ear. In some implementations, the earpiece includes one or more
protective liners on one or more of the skin adhesive, the cymba
electrode, and the non-cymba electrodes which are to be removed
before use.
[0081] In some implementations, the treatment device can be used to
provide therapy including a first stimulation configured to
stimulate pathways modulating dynorphins release and a second
stimulation configured to stimulate pathways modulating endorphins
release. In some implementations, the treatment device can be used
to provide therapy including a first stimulation configured to
stimulate pathways modulating dynorphins release and a second
stimulation configured to stimulate pathways modulating enkephalins
release. In other implementations, the treatment device can be used
to provide therapy including a first stimulation configured to
stimulate pathways modulating dynorphins release and a second
stimulation configured to stimulate pathways modulating enkephalins
and endorphins release.
[0082] In an example, the first stimulation can be a high frequency
stimulation and the second stimulation can be a low frequency. In
an example, the pathways modulating dynorphins release can include
at least one of the auriculotemporal nerve, the lesser occipital
nerve, and the great auricular nerve. In an example, the pathways
modulating dynorphins release can include stimulation of dynorphin
pathway via stimulation of the Parabranchial nucleus. In an
example, the pathways modulating endorphins and enkephalins release
can include at least one of the auricular branch of the vagus
nerve, the lesser occipital nerve, and the great auricular nerve.
In an example, the pathways modulating endorphins and enkephalins
release can include stimulation of endorphins and enkephalins
pathway via stimulation of the Arcuate nucleus of the
hypothalamus.
[0083] To provide the therapy, a provider may adjust therapy
parameters as needed and start the therapy using the controls on
either the pulse generator or the peripheral device. In some
implementations, the therapy includes providing two or more
simultaneous and/or synchronized stimulations. In an aspect, the
therapy can involve applying a first stimulation having a first set
of parameters at a first portion of the patient's skin and applying
a second stimulation having a second set of parameters at a second
portion of the patient's skin. When therapy is done, the user may
remove the earpiece and disconnect the earpiece from the pulse
generator. In an example, the used earpiece can be replaced with a
new earpiece for the next session.
[0084] In some embodiments, treatment can be applied unilaterally
(left or right) and yet in other embodiments a bilateral treatment
may be applied,
[0085] Turning to FIGS. 2A-2B, a treatment device 200 is shown
including an auricular component 201 having an earpiece 202
connected to a concha apparatus 204 by a first connector 206, and a
pulse generator 210 connected to the earpiece 202 of the auricular
component 201 by a second connector 214 according to an example. In
an example, the concha apparatus 204 includes a first electrode 220
configured to be in contact with vagal related neural structures,
and the earpiece 202 includes a second electrode 222 configured to
be in contact with a neural structure related to the
auriculotemporal nerve and at least another electrode 224, 226
configured to be in contact with or in proximity to neural
structures related to the great auricular nerve and/or its branches
as well as the lesser occipital nerve and/or its branches. In an
example, the pulse generator 210 can include a return electrode 230
configured to provide a return path or reference to electrodes
220-226. In another embodiment, electrodes 220-226 form pairs such
that for example electrodes 220 and 226 form a pair are used to
deliver bipolar stimulation; in this example a second pair could be
formed by electrodes 222 and 224 such that bipolar stimulation is
provided through them.
[0086] Turning to FIG. 2C, a treatment device can include a number
of electrodes configured to be virtually grouped together to form
one or more effective electrodes according to an example. In an
exemplary embodiment, a treatment device can include a number of
electrodes 208 that can be grouped together to form into one or
more effective electrodes 240a-c. In an example, a grouping of
electrodes 240a can be equivalent to electrode 222, a grouping of
electrodes 240b can be equivalent to electrode 224, and a grouping
of electrodes 240c can be equivalent to electrode 226.
[0087] Benefits of grouping smaller electrodes include having the
ability to have multiple electrodes each one with its own
independently controlled current source allows for the current to
be steer providing better spatial resolution and targeting
capabilities. Electrodes can also be made larger or combined such
that for example in one embodiment electrodes 1206 and 1208 be
combined into one large contact. In an example, the grouping of two
or more electrodes (208, 224, 226) can be done using a processor
such as a field-programmable gate array (FPGA) such as FPGA
1112.
[0088] In an exemplary embodiment, a treatment device includes an
auricular component 201 which has a number of electrodes that are
configured to be in contact with the dermis in and around the outer
ear. The auricular component 201 includes at least one of the
following electrodes: an electrode configured to be in contact with
vagal related neural structures; for example at the cymba concha
(also known as the concha of the cymba, concha cymba, and/or cymba)
204, an electrode 222 configured to be in contact with neural
structure related to the auriculotemporal nerve, an electrode
configured to be in contact with or in proximity to neural
structures related to the great auricular nerve and/or its
branches, as well as the lesser occipital nerve and/or its
branches, 224 and 226. Additionally, the treatment device includes
a pulse generator or controller having management software for
providing the user with at least one of: customizing the
therapeutic output, receiving confirmation of therapeutic delivery,
and receiving and saving overall stimulation logs, diagnostics, and
events.
[0089] In some implementations, a treatment device 250 can include
one or more haptic feedback actuators 270 between a pair of
electrodes 228 according to an example (FIG. 2D). In an aspect, the
one or more haptic feedback actuators 270 can move 272 from a first
position 270 to a second position 270' in repetitive patterns. In
an example, the repetitive patterns can aid to mask sensations felt
by stimulation of the electrodes. In an aspect, the one or more
haptic feedback actuators 270 can be configured to isolate or
electrically separate conductive shunting pathways between
electrodes 228, including between portions of conductive gel
260.
[0090] In an aspect, an auricular component can include an earpiece
and concha apparatus having shapes configured to aid in securing
the treatment device and the electrodes to a respective ear
structure. In an exemplary embodiment, an auricular component 300
can include an earpiece and concha apparatus having shapes 310,
320, 330 configured to aid in securing the treatment device and the
electrodes 220, 222, 224, 226 to a respective ear structure (See
FIGS. 3A-3B). Shaped portions 310, 320, 330, 332 of the earpiece
and the concha apparatus are configured to interface with
structures of the ear (302, 304, 306, 308, 309) to facilitate
secure placement of the electrodes for providing therapy. In
another exemplary embodiment, a concha apparatus 400 can have a
structural shape configured to aid in securing the concha apparatus
400 and allow for supported electrode(s) to maintain contact with a
respective ear structure (See FIGS. 4A-4C). The concha apparatus
400 includes a first member 402 connected at a distal elbow 406 to
an arm 404 having a second member 408 configured to fit within
extrusions and notches 410a-b of the ear.
[0091] In some implementations, an earpiece assembly 500 includes a
skin 502 for overlaying a PCB layer 504 having electrodes 503a-d
(220, 222, 224, 226, 228), an adhesive layer composed of two
elements, a skin adhesive 505 having corresponding apertures 506 to
adhesive elements 508 configured for enhancing electrical
interfacing of the electrodes 503a-d with the skin (See FIGS.
5A-5B). In some embodiments, the adhesive elements 508 can include
a conductive hydrogel in another embodiment the hydrogel is infused
with analgesic for a more comfortable stimulation. In an example,
the hydrogel is on top of one or more contact surfaces on the flex
PCB. In an example, the skin 502 can be made from a flexible piece
or material such as silicone.
[0092] In an example, a flexible PCB 602 can include electronic
components to suppress electrical spikes as well as a component to
identify and/or uniquely identify the PCB (See FIG. 6). Exposed
conductive surfaces 612, 620, 622, 624 on the PCB 602 serve as
contact point to connect the hydrogels 508 to the PCB 602. The PCB
602 extends forming a cable-like structure 604 to integrate the
cymba component 610 of the electrode 220 in contact with nerve
branches related to vagal nerve structures 204 without the need for
soldering and/or connecting the electrode 220 during assembly. In
one embodiment, the cable-like structure forms an anchoring
structure 606 which sits inside portions of the ear. In this
example, PCB 602 connects to the pulse generator 210 via a slim
keyed connector 630. In another embodiment, more than one electrode
can be located on the cymba component 610. In this case, additional
components can be added to the PCB 602 to accommodate additional
electrodes including additional traces on the PCB 602. In an
example, additional connections could extend along the cable-like
structure 604 and connector 630 can have additional contact pins.
In another embodiment, an analog multiplexor could be added to
control and/or direct or re-direct the stimulation pulses towards a
desired electrode and/or set of electrodes.
[0093] In an example, the flexible PCB can be encapsulated in a
protective covering as shown in FIGS. 7A-7C. The protective
covering can be made from a flexible material such as silicone. The
protective covering can be an encapsulation that may have different
thickness and densities in order to provide comfort to the touch
and robustness and protection to the PCB. The encapsulation is done
with at least one material. In some embodiments, the encapsulation
is done at least in using one mold and at least one molding
step.
[0094] In an aspect, a concha apparatus can include a component for
facilitating placement of the cymba electrode to portions of the
ear. In an exemplary embodiment, a concha apparatus can include a
structural-loaded component 800 which facilitates the placement of
the cymba electrode 204 to portions of the ear (See FIG. 8A-8B).
Spring loading has the added advantage that it is self-fitting
allowing a secure and comfortable fit for different ear sizes. The
presented shape (i.e., omega shape 814, 816) has the added
advantage that it can be made with metal and non-metal materials.
Other suitable shapes may be fabricated to allow a
structural-loaded action using metal and/or non-metal materials or
a combination of both metal and non-metal materials. In this
example, the cable-like structure 604 after encapsulation with, for
example, silicone 804 is routed such that the PCB 602 does not need
to incorporate the anchoring structure 606. In this case, the
cable-like structure 804 goes through a handle-like feature 810
that can be utilized by the user to handle and placed the component
800 on the user's ear.
[0095] An anchoring structure 812 is placed in the ear and the
electrode in contact with nerve branches related to vagal nerve
structures 204 is placed in the cymba. The use of an anchoring
structure outside the ear canal instead of a part going into the
ear canal for the placement serves three purposes, comfort,
functionally (it does not block sound) and, safety (minimal risk of
having a loose part going into the ear canal). Aside from the
handle 810 and anchoring structure 812, component 800 has two
omega-like structures 814, 816 having a structural-loaded effect, a
flat structure 802 connecting structural-loaded components 814 and
816 and a flat structure 818 attaching electrode 204 to component
800. Structural-loaded structure 814 helps in directing the rest of
component 800 (i.e. 802, 816, 818, 204) medially (i.e. towards the
user's head) while the structural-loaded structure 816 helps in
directing electrode 204 cranially inside the cymba crevice (i.e.
towards the upper portion of the cymba crevice).
[0096] In an exemplary embodiment, a concha apparatus can include a
spring-loaded component 900 which facilitates the placement of the
cymba electrode 204 on the user's ear. (See FIG. 9A-9B). Spring
loading has the added advantage that it is self-fitting allowing a
secure and comfortable fit for different ear sizes. The presented
shape (i.e. classic spring) is usually fabricated with metallic
materials. Other suitable shapes may be fabricated to allow a
spring-loaded action using metallic materials, and/or non-metal
materials or a combination of both metal and non-metal materials.
In this example, the cable-like structure 604 after encapsulation
with, for example, silicone 904 is routed such that the PCB 602
does not need to incorporate the anchoring structure 606. In this
case, the cable-like structure 904 goes through holder 910 which
can be utilized by the user to handle and placed the component 900
on the user's ear. An anchoring structure 912 is placed in the ear
and the electrode 204 in contact with nerve branches related to
vagal nerve structures is placed in the cymba. The use of an
anchoring structure outside the ear canal instead of a part going
into the ear canal for the placement serves three purposes,
comfort, functionally (it does not block sound) and, safety
(minimal risk of having a loose part going into the ear canal).
Aside from the handle 910 and anchoring structure 912, component
900 has two springs 914, 916, a flat structure 902 connecting the
two springs 914 and 916 and a flat structure 918 attaching
electrode 204 to component 900. Spring 914 helps in directing the
rest of component 900 (i.e., 902, 916, 918, 204) medially (i.e.,
towards the user's head) while spring 916 helps in directing
electrode 204 cranially inside the cymba crevice (i.e. towards the
upper portion of the cymba crevice). In some embodiments, a single
wire 920 is shaped such that components 910, 912, 914, 916, and 918
are formed (See FIG. 9C). In some embodiments, the wire is
encapsulated into a comfortable-to-the-touch and flexible material
(e.g., silicone). In some embodiments, holder 910 is longer, for
example it could bridge over the entire anchoring structure 912 for
a more functional and comfortable handling.
[0097] In some implementations, the pulse generator 210 includes a
battery, circuitry configured to produce therapy stimulation in
communication with the electrodes of the auricular component 201.
In some embodiments, the pulse generator includes at least one
antenna configured to receive programming instructions encoding
stimulation parameters. In an aspect, the system is rechargeable to
allow for long-term use.
[0098] In an exemplary embodiment, the auricular component 201 is
connected to an electrical pulse generator 210 which produces the
therapy stimulation going to the electrodes on the auricular
component 201. In one embodiment, the pulse generator 210 is
co-located in close proximity with the auricle of the patient.
[0099] In another embodiment, the pulse generator 210 is placed on
the body of the user, for example on the pectoral region just below
the clavicle. In another embodiment, the pulse generator 210 can be
clipped to the user's clothing or carried in the user's trousers
pocket or in a specially designed pouch. In one embodiment, the
pulse generator 210 is controlled via remote control for example
using a peripheral device such as a mobile device, a tablet, and a
personal computer. In an aspect, other system components are
configured to be controlled by an application on the peripheral
device. In one embodiment, data is exchanged via a computing cloud
with third parties for example healthcare professionals and/or
healthcare providers. (See FIGS. 10A-10C)
[0100] Turning to FIGS. 10A-10C, a treatment system can include a
treatment device 1000 in communication with third parties through a
computing cloud 1020 and/or a peripheral device 1010 according to
an example. In this example, the treatment device 1000 is shown
including an auricular component 1002 connected via a wire to a
pulse generator 1004, and the pulse generator 1004 is wirelessly
connected to the peripheral device 1010. Examples of peripheral
devices 1010 includes a personal computer, a tablet, a phone as
well as any other suitable device including a remote server via the
cloud 1020. In an example, the peripheral device 1010 is also
wirelessly connected to a remote server via the cloud 1020.
Wireless connections can be accomplished via any at least one
available wireless technology, for example, BlueTooth Classic,
BlueTooth Low Energy, ZigBee, WiFi or similar technology.
[0101] Portions of the treatment system and the treatment device
can be in direct or indirect communication with a remote server or
cloud 1020 with third parties. In this example, the pulse generator
210 is included in the auricular component 1002 that is, they are
co-located thus the need for and extension cable to connect them is
not necessary. The auricular component and pulse generator 210 are
wirelessly connected to an electronic device (for example a
personal computer, a tablet or a phone) and/or to a remote server
via the cloud 1020. In turn the electronic device is also
wirelessly connected to a remote server via the cloud 1020.
Wireless connections can be accomplished via any at least one
available wireless technology, for example, BlueTooth Classic,
BlueTooth Low Energy, ZigBee, WiFi or similar technology. As shown
in FIG. 10C, different communication components of the treatment
device 1000 can be in communication with the peripheral device 1010
and the remote server or cloud 1020. For example, an isolated port
on the treatment device 1000 can be in wired communication with the
peripheral device 1010, a wireless radio of the treatment device
1000 can be in wireless communication with the peripheral device
1010 or the remote server or cloud 1020.
[0102] Turning to FIG. 11, a schematic 1100 of components of a
pulse generator 1150 in communication with components of the
flexible PCB 1160 of the auricular component is shown according to
an example. The multichannel pulse generator circuit 1150 has at
least one microcontroller or a microprocessor 1110 with at least
one core. When multiple microcontrollers or multiple cores are
present, for example one controls the radio 1120 and other core(s)
are dedicated to control the therapy. In one embodiment, a low
power FPGA 1112 is also available such that the microcontroller
1110 goes into a low power mode as much as possible while the FPGA
1112 controls therapy delivery.
[0103] In some embodiments, an inverter circuit 1140 is used to
generate biphasic/bipolar pulses. In some embodiments, one inverter
circuit is use per channel, while in other embodiment, a single
inverter is used for multiple channels. In one embodiment, each
channel targets a different anatomical area 1148. A high voltage
compliance (e.g., >50V, in other embodiments >70V, and yet in
others >90V) is needed to ensure there is enough margin on the
electrical potential to generate current demanded by the intensity
control 1142. In order to enhance safety, in some embodiments an
over current detection circuit 1144 is present. In one embodiment
an impedance measuring circuit is present 1146, such that impedance
can be tracked over time and to identify when the electrodes are
not in contact or in good contact with the skin or if the cable is
disconnected, or if the electrodes have deteriorated or are
defective. Monitoring impedance over time provides the added
advantage that the condition of the contact electrode can be
followed; thus allowing the circuit to alert the user when the
contact electrodes are close to their end of life of no longer
viable.
[0104] In some embodiments, an isolated port 1118, such as a USB is
used to charge the battery, and to communicate with the
microcontroller(s) 1110. The communication can be both ways, such
that instructions or entire new code can be uploaded to the
microcontroller(s) 1110 and to download information stored in the
memory 1122. In some embodiments, memory 1122 can be added to the
circuit as an external CHIP, while in other embodiments, the memory
1122 can be internal to the microcontroller(s) 1110. In some
embodiments, the FPGA 1112 may also have internal memory. In some
embodiments, an external trigger circuit 1124 is included, such
that the stimulation can be started and/or stopped via an external
signal. In some embodiments, the external trigger signal can be
passed through the isolated port 1118; in yet other embodiments a
modify USB configuration (i.e., not using the standard USB pin
configuration) can be used to pass the trigger signal. Using a
modify USB configuration will force a custom USB cable to be used
thus ensuring that an external trigger cannot be done by mistake
using an off-the-shelf USB cable.
[0105] In some embodiments, a hardware user interface is used to
interact with the circuit 1126. In an example, the user interface
can comprise of buttons, LEDs, buzzers, and/or a display, or a
combination of any of them.
[0106] In some embodiments, an external master clock 1128 is used
to drive the microcontroller(s) 1110 and/or the FPGA 1112, in other
embodiments the clock(s) can be internal or integrated or
co-packaged with the microcontroller(s) 1110 and/or the FPGA 1112.
In some embodiments, one or more oscillators, including in some
cases adjustable oscillators 1114 are used to set pulse parameters
such as for example, frequency and/or pulse width.
[0107] In some embodiments, the auricular component 1160 is made
from a thin flex PCB, such that it is light weight and can be
easily bent to accommodate different anatomies. In some
embodiments, the auricular circuit 1160 has more than one channel.
In one embodiment, each channel includes a peak suppressing circuit
1147 and electrodes 1148 to contact the skin at the location of the
target tissue. In some embodiments, the auricular circuit 1160
includes a unique chip identifier or unique ID chip 1149. The
unique ID chip can be used to track usage as well as to prevent
other no authorized circuits to be connected to the multichannel
pulse generator 1150. At least one auricular circuit 1160 is
connected to the multichannel pulse generator 1150.
[0108] Turning to FIGS. 14A-14D, a method 1400 is disclosed for
providing therapy including providing a first stimulation 1410 at a
first tissue location configured to stimulate a first pathway 1420
for modulating a first release 1430 of at least one first
endogenous peptide and a second stimulation 1440 at a second tissue
location configured to stimulate a second pathway 1450 for
modulating a second release 1460 of a second endogenous peptide
according to an example. Examples of target pathways and structures
for stimulation of the first tissue location include those
modulating activity at/on the auricular branch of the vagus nerve,
the lesser occipital nerve, the great auricular nerve, and the
arcuate nucleus (FIG. 14B). Examples of target pathways and
structures for stimulation of the second tissue location include
those modulating activity at/on the auriculotemporal nerve, the
lesser occipital nerve, the great auricular nerve, and the
parabranchial nucleus (FIG. 14C).
[0109] FIG. 14D shows a flow chart of a method 1402 for providing
therapy including providing a first stimulation such that neural
activity at the arcuate nucleus of the hypothalamus (ARC) is
modulated such that it stimulates the Periaqueductal Gray Area
(PAG) for modulating a first release of enkephalins and/or
endorphins such that neural activity at the Parabranchial Nucleus
(PbN) is modulated such that it also stimulates the Periaqueductal
Grey Area (PAG) for modulating a second release of a dynorphins
according to an example.
[0110] In an aspect, the stimulation targets specific neural
targets in a local manner using bipolar stimulation. In an aspect,
the system can be programmed for optimal therapy according to the
needs of individual users including custom stimulation frequency,
custom pulse width, custom stim intensity (amplitude),
independently controlled stimulation channels. In some
implementations, the treatment is configured to abate withdrawal
symptoms including pain. In an aspect, pain control is due to
modulation of endorphin, enkephalins, and/or dynorphins output in
opioid related systems. In an example, the therapy can be provided
during surgery, and/or post-surgery to reduce dependency of pain
killer medications, including opioids, up to not needing medication
at all.
[0111] Turning to FIG. 12, an electrode configuration of an
auricular component 1200 and equivalent circuits 1210a-b for
providing therapy is shown according to an example. The auricular
component 1200 is shown having electrodes 1202 (220), 1204 (222),
1206 (224), and 1208 (226) configured to form corresponding
circuits 1210a-b according to an example. In an example, equivalent
circuit 1210a is formed by electrode 1202 and electrode 1206 which
are configured to stimulate tissue portion 1220. In this example,
tissue portion 1220 is configured to target the cymba conchae
region which is enervated by branches of the auricular branch of
the vagus nerve and the region behind the ear which is enervated by
branches of the great auricular nerve and branches of the lesser
occipital nerve. In an example, equivalent circuit 1210b is formed
by electrode 1204 and electrode 1208 which are configured to
stimulate tissue portion 1222. In this example, tissue portion 1222
is configured to target the region rostral to the ear which is
enervated by the Auriculotemporal nerve as well as the region
behind the ear which is enervated by branches of the great
auricular nerve and branches of the lesser occipital nerve.
[0112] In an example, the tissue portion 1220 can be the concha
which is stimulated at approximately 5 Hz. In an example, the
tissue portion 1220 can be the trigeminal nerve which is stimulated
at approximately 100 Hz.
[0113] In an example, equivalent circuit 1210a is stimulated by a
first channel and equivalent circuit 1210b is stimulated by a
second channel.
[0114] FIG. 13 is a drawing of a method 1300 for triggering
multiple channels 1304, 1306 using a master clock 1302 according to
an example. In an exemplary embodiment, the clock 1302 triggers
pulses 1304 at a predetermined clock frequency. In an example, a
first channel 1304 can be configured to trigger stimulation 1310a-b
of equivalent circuit 1210a and a second channel 1306 can be
configured to trigger stimulation 1312a-b of equivalent circuit
1210b. In an example, the triggering can be reversed where
equivalent circuit 1210b is triggered before equivalent circuit
1210a.
[0115] In an example, stimulation 1310a is configured to be
triggered by every pulse of the master clock; i.e., at a 1-to-1
ratio. In an example, stimulation 1310b is configured to be
triggered following a specific time interval after the pulse in
stimulation 1310a ends. In an example, stimulation 1312b is
configured to be triggered every two pulses of the master clock;
i.e., at a 2-to-1 ratio with the master clock. However, the
triggering of stimulation 1312b occurs after a specific time delay
after the master clock pulse 1314. In an example, stimulation 1312a
is configured to be triggered following a specific time interval
after the pulse in stimulation 1312b ends. In an example,
stimulation 1310a is offset by stimulation 1312a by a synchronous
delay 1314. In an example, the synchronous delay 1314 is preferably
2 ms and can be as little as zero (making both channels to trigger
simultaneously depending on the master clock ratio for each
channel) and as much as the master clock period less the combine
duration of stimulation 1312b and 1312a plus the time interval
between them. In some embodiments this delay can amount to 10
ms.
[0116] In some implementations, the equivalent circuits are
synchronized using a master clock counter and a register per
channel. By setting each register to a number of master clock
pulses to trigger the respective channel, each channel is
configured to be triggered when the channel register value equals
the master clock pulses. Subsequently, the counter for each channel
is reset after the channel is triggered. In an example, using a 6
bit counter and a 6 bit register, the trigger frequency can be as
high as the master clock frequency (1:1) and as low as 1/64 of the
clock frequency (64:1).
[0117] In one embodiment, the stimulation patterns are such that
stimulating frequencies are not the same in all electrodes. In one
embodiment, a stimulation frequency is varied between 2 Hz and 100
Hz such that different endogenously produced opioid receptor
agonist are released (e.g., Mu, Delta, Kappa, nociception opioid
receptor agonist). In yet another embodiment, the pulse width can
be adjusted from between 20 and 1000 microseconds to further allow
therapy customization.
[0118] In one embodiment, different stimulation frequencies are
used at the different electrodes. For example, a first or low
frequency of between 1 to 5, or 5 to 10, or 10 to 15, or 15 to 20,
or 20 to 25, or 25 to 30 Hz is used at cymba electrode 204, while a
second of high frequency of between 70 to 75, or 75 to 80, or 80 to
85, or 85 to 90, or 90 to 95, or 95 to 100, or 100 to 105, or 105
to 110, or 110 to 115, or 115 to 120, or 120 to 125, or 125 to 130,
or 130 to 135, or 135 to 140, or 140 to 145, or 145 to 150 Hz is
used at the auriculotemporal electrode 222. In other embodiments, a
third or midrange frequency of between 30 to 35 or 35 to 40 or 40
to 45 or 45 to 50 or 50 to 55 or 55 to 60 or 60 to 65 or 65 to 70
Hz can be used at either electrode.
[0119] In yet another embodiment, a low or midrange frequency can
be used in the cymba electrode 204 while high frequency is used at
the auriculotemporal electrode 222. In other embodiment, a high
frequency can be use at the cymba electrode 204 while a Low
frequency can be used at the auriculotemporal electrode 222. In yet
other embodiments, different combinations of high, midrange and low
frequency can be used at either the cymba electrode 204, the
auriculotemporal electrode 222, and/or the great auricular nerve
and lesser occipital nerve electrodes 224, 226.
[0120] Different combination of pulse widths can be used at each
electrode. First or short pulse widths of between 10 to 20, or 20
to 30, or 30 to 40, or 40 to 50 microseconds, second or low
Midrange pulse widths of between 50 to 70, or 70 to 90, or 90 to
110, or 110 to 130, or 130 to 150, or 150 to 170, or 170 to 190, or
190 to 210, or 210 to 230, or 230 to 250 microseconds, third or
high Midrange pulse widths of between 250 to 270, or 270 to 290, or
290 to 310, or 310 to 330, or 330 to 350, or 350 to 370, or 370 to
390, or 390 to 410, or 410 to 430, or 430 to 450, or 450 to 470, or
470 to 490, or 490 to 510, or 510 to 530, or 530 to 550
microseconds, fourth or long pulse widths of between 550 to 600, or
600 to 650, or 650 to 700, or 700 to 750, or 750 to 800, or 800 to
850, or 850 to 900, or 900 to 950, or 950 to 1000 microseconds.
Different embodiments can use different ranges of pulse widths at
one or more of the electrodes 204, 222, 224, 226, 230.
[0121] In yet another embodiment, a variable frequency (i.e.,
stimulating a non-constant frequency) can be used at one or more of
the electrodes 204, 222, 224, 226, 230. The variable frequency can
be a sweep, and/or a random/pseudo-random frequency variability
around a central frequency (e.g., 5 Hz +/-1.5 Hz, or 100 Hz +/-10
Hz).
[0122] In one embodiment, the auricular component 201, 600 is made
with a single flexible board containing electronic components to
uniquely identify it and, among other things, to counteract any
inductance produced by the connecting cable. This flexible
electronic circuit is over-molded onto a skin 502 allowing openings
in it to allow direct contact with the back part of the
skin-contacting electrodes 503. This auricular component 201, 600
is light-weight and extremely flexible allowing it to easily
conform to different shapes presented by the anatomic variability
of users. In one embodiment, the molded auricular component is not
homogenic, changing the density and elasticity/flexibility at
different places such that, for example, the part going around the
ear is more flexible than the part going on the ear.
[0123] In other embodiment, the flexible electronic circuit 600 is
covered with a flexible material such as a closed cell foam.
[0124] In one embodiment, the skin-contacting electrodes can be
made for example of 3-layers, being the first layer a medical-grade
double-sided conducting adhesive tape, the second layer a
conductive flexible metallic and/or fabric mesh for mechanical
robustness and homogenic electrical field distribution, and a third
layer of self-adhesive hydrogel. A two-layer version is also
possible in which both mechanical robustness and homogenic
electrical field distribution is achieved by the first layer,
rendering unnecessary the second layer described in the three-layer
electrode.
[0125] In another embodiment, the PCB electrodes 503 are made such
that they cover a similar surface area as the skin-contacting
hydrogel electrodes; such that homogenic electrical field
distribution is achieved at the hydrogels without the need of any
additional conductive layer.
[0126] In an aspect, the system can record overall therapeutic
delivery so the caregiver/clinician can measure compliance. In one
embodiment, the management software notifies the wearer, caregiver,
clinician if the device has stopped delivering therapy. In an
example, the management software can be configured to report data
related to use, events, logs, errors, and device health status. In
an aspect, the system can provide usage reports. In an aspect, the
system can have a uniquely identifiable auricular component 201
that can be used in identifying users and reported data. In an
example, the device health status can report on the condition of
the electrodes, the conductive hydrogel, and/or the analgesic.
[0127] In an exemplary embodiment, the system can utilize feedback
to monitor and/or modify the therapy. In some implementations, the
feedback can include one of electrodermal activity, movement
activity, glucose monitoring, neuro-monitoring, EKG, EEG, blood
pressure (systolic, diastolic and mean) imaging and any other type
of sensing related to the symptoms and therapy. In an example, the
electrodermal activity could be used to monitor and detect a speed
or timing of a symptom and/or therapeutic outcome. In an example,
the electrodermal activity could be sensed by electrodes on the
auricular component 201. In another example, the electrodermal
activity could be detected by electrodes on another portion of the
body and communicated to the system.
[0128] In some implementations, the system can further include one
or more accelerometers/gyroscopes that can be used gather
information to modulate the therapy. In an example, the one or more
accelerometers/gyroscopes is configured to detect a tremor and/or
physiologic movement. In an aspect, the tremor and/or the
physiologic movement can be indicative of at least one of the
underlying condition and the treatment to the underlying condition.
In an example, the tremor and/or physiologic movement can be
indicative of symptoms associated with substance withdrawal. In an
aspect, feedback from glucose monitoring can be used to modulate
the therapy.
[0129] In yet other implementation, EKG can be used to assess heart
rate and heart rate variability, to determine the activity of the
autonomic nervous system in general and/or the relative activity of
the sympathetic and parasympathetic branches of the autonomic
nervous system, and to modulate the therapy. Autonomic nervous
activity can be indicative of symptoms associated with substance
withdrawal. In an aspect, the treatment device can be used to
provide therapy for treating cardiac conditions such as atrial
fibrillation and heart failure. In an example, therapy can be
provided for modulation of the autonomic nervous system. In some
implementations, the treatment device can be used to provide
therapy to balance a ratio between any combinations of the
autonomic nervous system, the parasympathetic nervous system, and
the sympathetic nervous system.
[0130] In an aspect, the system can monitor impedance measurements
allowing closed-loop neurostimulation. In an example, monitoring
feedback can be used to alert patient/caregiver if therapy is not
being adequately delivered and if the treatment device is
removed.
[0131] Turning to FIG. 15, a graph is shown of data collected using
the proposed system according to an example. Clinical Opiate
Withdrawal Score (COWS) over time was collected from subjects being
treated with the proposed therapy. Therapy included using Low
frequency (5 Hz) between the cymba electrode 204 and an electrode
224, and High frequency (100 Hz) between the auriculotemporal
electrode 222 and electrode 226.
* * * * *