# US 12,109,410 B2 · Bioelectric stimulator

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- Number: US 12,109,410 B2
- Document ID: US12109410B2
- Status: Granted
- Kind: B2
- Application number: 17/216,423
- Filed: 2021-03-29
- Published: 2021-08-05
- Granted: 2024-10-08
- Earliest claimed: 2016-03-15
- Assignees: Leonhardt Ventures LLC
- Applicants: Leonhardt Ventures LLC
- Inventors: Howard J. Leonhardt; Jorge Genovese
- Web page: https://patentgrep.com/patent/US12109410B2

## CPC

- A61N 1/326: {for promoting growth of cells, e.g. bone cells}
- A61M 39/0208: {Subcutaneous access sites (implantable infusion devices A61M5/14276; transcutaneous access sites A61M39/0247)}
- A61N 1/37205: {Microstimulators, e.g. implantable through a cannula}
- A61N 1/375: Constructional arrangements, e.g. casings
- A61B 5/243: specially adapted for magnetocardiographic [MCG] signals
- A61M 5/14276: {specially adapted for implantation}
- 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 1/36007: {of urogenital or gastrointestinal organs, e.g. for incontinence control}
- A61N 1/36071: {Pain}
- A61N 1/36114: {Cardiac control, e.g. by vagal stimulation (stimulating the heart A61N1/362)}
- A61N 1/3629: {in combination with non-electric therapy}
- 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)
- 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)}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Described is a low voltage, pulsed electrical stimulation device for controlling expression of, for example, follistatin, a muscle formation promotion protein, by tissues. Epicardial stimulation is especially useful for heart treatment. Follistatin controlled release is also useful for treating other ailments, such as erectile dysfunction, aortic aneurysm, and failing heart valves.

## Claims

### Claim 1

A method of using a bioelectric stimulator to stimulate target tissue of a subject to control stem cell homing, proliferation, or differentiation and/or upregulate expression of at least one protein by the target tissue, wherein the protein is selected from the group consisting of activin, epidermal growth factor (EGF), follistatin, hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1), platelet-derived growth factor (PDGF), receptor activator of nuclear factor kappa-B ligand (RANKL), stromal cell-derived factor 1 (SDF1), tropoelastin, vascular endothelial growth factor (VEGF) and any combination thereof, the method comprising:
delivering at least one bioelectric signal to the target tissue so as to control stem cell homing, proliferation, or differentiation and/or to upregulate expression of at least one protein in the target tissue, wherein the bioelectric signal(s) comprise(s) at least one bioelectric signal(s) selected from the group consisting of
(a) 2 Hz, square biphasic wave, pulse width 1,000 μs so as to upregulate expression of RANKL by the target tissue;
(b) within 15%, 30 Hz, square biphasic wave, pulse width 100 μs so as to upregulate expression of SDF1 to the target tissue and stimulate stem cell homing to the target tissue;
(c) within 15%, 100 Hz, square biphasic wave, pulse width 100 μs so as to upregulate expression of PDGF and stimulate stem cell homing to the target tissue;
(d) 20 Hz, square wave, pulse width 200 to 700 μs so as to stimulate stem cell proliferation;
(e) 10 Hz, square biphasic wave, pulse width 200 μs so as to upregulate expression of PDGF by the target tissue and stem cell homing to the target tissue;
(f) within 15%, 150 Hz, monophasic square wave, pulse width 100 μs so as to upregulate expression of activin by the target tissue;
(g) within 15%, 500 Hz, square biphasic wave, pulse-width 180 μs so as to upregulate expression of EGF by the target tissue;
(h) within 15%, 22 Hz, square monophasic wave, pulse width 50% duty cycle so as to upregulate expression of IGF-1 by the target tissue;
(i) 70 Hz, square wave, pulse width 10%-50% duty cycle,
(j) 200 picoamps with a pulse having an amplitude of 5 V and a width of 0.5 milliseconds so as to stimulate stem cell proliferation;
(k) 50 Hz, square wave so as to upregulate expression of follistatin, tropoelastin, VEGF and HGF by the target tissue, and
(l) any combination(s) thereof.

### Claim 2 (depends on 1)

The method according to claim 1, further comprising:
separately delivering to the subject an admixture 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 3 (depends on 1)

The method according to claim 1, wherein the target tissue is selected from the group consisting of brain, scalp, eye, ear, skin, tooth, dental gum, tooth root, sub-mucosa, breast, aorta, limb, artery, heart, heart valve, kidney, pancreas, bladder, liver, joint, bone, and any combination thereof.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s): a signal of 2 Hz, square biphasic wave, pulse width 1,000 μs so as to upregulate expression of RANKL.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s), within 15%, 30 Hz, square biphasic wave, pulse width 100 μs so as to upregulate expression of SDF-1.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s): a signal of 100 Hz, square biphasic wave, pulse width 100 μs so as to upregulate expression of PDGF.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s): a signal of 20 Hz, square wave, pulse width 200 to 700 μs so as to increase stem cell proliferation.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s): a signal of 10 Hz, square biphasic wave, pulse width 200 μs so as to upregulate expression of PDGF.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s), within 15%, 150 Hz, monophasic square wave, pulse width 100 μs so as to upregulate expression of activin.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s), within 15%, 500 Hz, square biphasic wave, pulse-width 180 μs so as to upregulate expression of EGF.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s), within 15%, 22 Hz, square monophasic wave, pulse width 50% duty cycle so as to upregulate expression of IGF-1.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s) a signal of 70 Hz, square wave, pulse width 10%-50% duty cycle so as to increase stem cell proliferation.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s) a signal of 200 picoamps with a pulse having an amplitude of 5 V and a width of 0.5 milliseconds so as to induce stem cell differentiation.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s), within 15%, 50 Hz, square wave so as to upregulate expression of follistatin, tropoelastin, and/or VEGF.

### Claim 15 (depends on 1)

The method according to claim 1, wherein the bioelectric signal(s) comprise(s): a signal of within 15%, 50 Hz, square biphasic wave, pulse width 100 μs, with surge delivery of 10 seconds on and 30 seconds off so as to upregulate expression of HGF.