# US 11,110,274 B2 · System and method for treating inflammation

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- Number: US 11,110,274 B2
- Document ID: US11110274B2
- Status: Granted
- Kind: B2
- Application number: 16/137,467
- Filed: 2018-09-20
- Published: 2019-01-24
- Granted: 2021-09-07
- Earliest claimed: 2016-03-15
- Assignees: Leonhardt Ventures LLC
- Applicants: Leonhardt Ventures LLC
- Inventors: Howard J. Leonhardt
- Web page: https://patentgrep.com/patent/US11110274B2

## CPC

- A61N 1/36031: {using physiological parameters for adjustment}
- A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes}
- A61B 5/372: Analysis of electroencephalograms
- A61B 5/6803: {Head-worn items, e.g. helmets, masks, headphones or goggles}
- A61H 39/002: {Using electric currents (electrotherapy A61N1/32)}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/195: {Chemokines, e.g. RANTES}
- A61K 38/2006: {IL-1}
- A61K 38/204: {IL-6}
- A61K 38/2066: {IL-10}
- A61M 5/14276: {specially adapted for implantation}
- A61M 39/0208: {Subcutaneous access sites (implantable infusion devices A61M5/14276; transcutaneous access sites A61M39/0247)}
- A61N 1/36139: {with automatic adjustment}
- A61N 1/3627: {for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy}
- A61N 1/3629: {in combination with non-electric therapy}
- A61N 1/37205: {Microstimulators, e.g. implantable through a cannula}
- A61B 5/026: Measuring blood flow {(A61B3/1233, A61B3/1241 take precedence)}
- A61B 5/0533: Measuring galvanic skin response
- A61B 5/14542: {for measuring blood gases (A61B5/14551 takes precedence)}
- A61B 5/4082: {Diagnosing or monitoring movement diseases, e.g. Parkinson, Huntington or Tourette}
- A61B 5/4088: {Diagnosing of monitoring cognitive diseases, e.g. Alzheimer, prion diseases or dementia}
- A61H 2201/165: Wearable interfaces
- A61M 2039/0036: {characterised by a septum having particular features, e.g. having venting channels or being made from antimicrobial or self-lubricating elastomer}
- A61M 2202/07: Proteins
- A61M 2205/05: combined with other kinds of therapy
- A61M 2205/50: with microprocessors or computers
- A61M 2205/502: User interfaces, e.g. screens or keyboards
- A61N 1/36002: {Cancer treatment, e.g. tumour}
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61H: PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY (electrotherapy, magnetotherapy, radiation therapy or ultrasound therapy A61N)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

Described is a low voltage, pulsed electrical stimulation device for reducing inflammation in a subject, which can be useful in the treatment of concussions, traumatic brain injury, cancer, and so forth.

## Claims

### Claim 1

A device that determines a subject's level of inflammation following organ and/or tissue injury in the subject and then, in response to said determination, is programmed to provide at least one bioelectric signal to tissue of the subject so as to regulate expression of selected protein(s) by the tissue, so as to balance inflammation in the subject for organ and/or tissue healing and recovery in the subject, wherein the device comprises:
sensor(s) for determining the subject's level of inflammation;
a microprocessor that, based upon the subject's level of inflammation, is programmed to provide at least one bioelectric signal in order to balance inflammation in the subject; and
electrode(s) for applying bioelectric signal(s) to tissue of the subject,
wherein the applied bioelectric signal(s) influence expression of protein(s) in the tissue of the subject to which a bioelectric signal or signals is applied.

### Claim 2 (depends on 1)

The device of claim 1, wherein the device is programmed to produce bioelectric signals comprising at least each of the following:
a bioelectric signal of, within 15%, 100 mV, 50 Hz, square wave;
a bioelectric signal of 3 V, 10 Hz, square wave, and/or 20 V, 100 Hz, square wave;
a bioelectric signal of, within 15%, alternating high-frequency and medium-frequency signals, symmetric, biphasic, trapezoid pulses, with 400-μs pulse duration and 1.5/1-s ramp-up/ramp-down duration, respectively, and
a bioelectric signal of, within 15%, 3.5 V stimulation in 10 second bursts, one (1) burst every 30 seconds at a frequency of about 50 Hz.

### Claim 3 (depends on 2)

A method of using the device of claim 2 to treat a subject with a concussion or other brain injury,
the method comprising:
applying the bioelectric signals to the subject's tissue.

### Claim 4 (depends on 1)

The device of claim 1, wherein the device is programmed to produce at least one bioelectric signal selected from the group consisting of
(a) within 15%, 3 mV with a frequency of about 22 Hz, and a current of about 1 mA, followed by 3 mA;
(b) a biphasic, continuous current of 10 μA at 50 Hz;
(c) 3 mV at 2/100 Hz, alternating frequency, with current of 3 mA, followed by 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses followed by 200 μs pulse duration at 30 Hz and with current amplitude of 140 mA;
(d) 20 V, 1 Hz with a pulse of 5 ms: and
any combination thereof.

### Claim 5 (depends on 4)

A method of using the device of claim 4 in a subject to regenerate brain cells in the subject, the method comprising:
generating bioelectric signals from the device to upregulate the expression of a protein in the subject, wherein the protein is selected from the group consisting of insulin-like growth factor 1 (“IGF1”), tumor necrosis factor alpha (“TNF-α”), C—X—C motif chemokine 5 (“CXCL5”), and any combination thereof.

### Claim 6 (depends on 5)

The method according to claim 5, further comprising:
separately delivering to the subject stem cells and/or growth factors comprising any combination of IGF1, insulin-like growth factor 1 (“IGF1”), interleukin 6 (“IL-6”), interleukin 10 (“IL-10”), interleukin-1β(“IL-1β”), transforming growth factor-β(“TGFβ”), TNF-α, CXCL5, and any combination thereof.

### Claim 7 (depends on 1)

The device of claim 1, wherein the upregulation of expression of the selected protein(s) in the subject occurs without a diminishing effect over time.

### Claim 8 (depends on 1)

A method of treating a subject suffering from a brain concussion or traumatic brain injury (“TBI”), the method comprising:
utilizing the device of claim 1 to treat the subject's brain by applying said bioelectric signal(s) to tissue of the subject.

### Claim 9 (depends on 8)

The method according to claim 8, comprising the application of bioelectric protein expression and/or release sequence(s) to the subject comprises:
from about five (5) to about forty (40) minutes, to increase IL-1β,
wherein the device then determines and adjusts the bioelectric protein expression signals to the subject's tissue for about five (5) minutes of an IL-1β inhibition shut off signal, and then from about five (5) to forty (40) minutes, a rise in TNF-α,
wherein the device then determines and adjusts the bioelectric protein expression signals to the subject's tissue for about five (5) minutes of TNF-α inhibition shut off signal, and then from about five (5) to forty (40) minutes rise in TGFβ, and
wherein the device then determines and adjusts the bioelectric protein expression signals to the subject's tissue for about five (5) minutes of a TGFβ inhibition shut off signal, and then about three (3) minutes of a rise in IL-10.

### Claim 10 (depends on 1)

A method of using the device of claim 1 to treat a subject having heart failure, the method comprising:
delivering selected bioelectric protein expression and/or release signals to the subject so as to control protein expression and/or release of a protein or proteins selected from the group consisting of tumor necrosis factor alpha (“TNF-α”), vascular endothelial growth factor (“VEGF”), endothelial NOS (“eNOS”), SDF, C—X—C motif chemokine 5 (“CXCL5”), and any combination thereof to aid in the treatment of the subject's heart.

### Claim 11 (depends on 10)

The method according to claim 10, further comprising:
separately delivering to the subject a cocktail of regenerative agents comprising any combination of the following: stem cells, endothelial progenitor cells, selected exosomes, selected alkaloids, selected anti-inflammatory agents, nutrient hydrogel, organ specific matrix, selected growth factors, amniotic fluid, placenta fluid, cord blood, and embryonic sourced growth factors and cells.

### Claim 12 (depends on 1)

A method of using the device of claim 1 in a subject's tissue to control expression and/or release of a protein, wherein the electrical signal stimulates the production of a protein selected from the group consisting of insulin-like growth factor 1 (“IGF1”), tumor necrosis factor alpha (“TNF-α”), C—X—C motif chemokine 5 (“CXCL5”), and any combination thereof.

### Claim 13 (depends on 1)

A method of using the device of claim 1 to achieve a desired result in a subject, wherein the desired result is selected from the group consisting of brain regeneration, cognitive function brain improvement, treatment of brain stroke, treatment of traumatic injury, treatment of eye injury, and ear hearing regeneration.

### Claim 14 (depends on 1)

The device of claim 1, wherein the device is programmed to produce bioelectric signals comprising at least each of the following:
a bioelectric signal of, within 15%, a frequency of 50 Hz, square wave;
a bioelectric signal of 10 a frequency of Hz, square wave, and/or a frequency of 100 Hz, square wave;
a bioelectric signal of, within 15%, alternating high-frequency and medium-frequency signals, symmetric, biphasic, trapezoid pulses, with 400-μs pulse duration and 1.5/1-s ramp-up/ramp-down duration, respectively, and
a bioelectric signal of one (1) burst every 30 seconds at a frequency of about 50 Hz.

### Claim 15 (depends on 1)

The device of claim 1, wherein the device is programmed to produce at least one bioelectric signal selected from the group consisting of
(a) within 15%, a frequency of about 22 Hz;
(b) a biphasic, continuous current at a frequency of 50 Hz;
(c) a frequency of 2/100 Hz, alternating frequency, followed by a frequency of 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses followed by a frequency of 30 Hz and 200 μs pulse duration;
(d) a frequency of 1 Hz with a pulse of 5 ms: and
(e) any combination thereof.