# US 11,298,530 B1 · Synergistic therapies for intervertebral disc degeneration

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- Number: US 11,298,530 B1
- Document ID: US11298530B1
- Status: Granted
- Kind: B1
- Application number: 17/306,209
- Filed: 2021-05-03
- Granted: 2022-04-12
- Earliest claimed: 2021-05-03
- Assignees: Discure Technologies Ltd.
- Applicants: Rainbow Medical Ltd.
- Inventors: Yuval Mandelbaum; Yossi Gross; Yehuda Zadok
- Web page: https://patentgrep.com/patent/US11298530B1

## CPC

- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61N 1/0551: {Spinal or peripheral nerve electrodes}
- A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas}
- A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61K 47/02: Inorganic compounds
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61N 1/205: {for promoting a biological process}
- A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)}
- A61N 1/325: {for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body (electrodes for external use A61N1/0428)}
- A61L 2430/38: for reconstruction of the spine, vertebrae or intervertebral discs
- A61N 1/306: {Arrangements where at least part of the apparatus is introduced into the body}
- A61N 1/326: {for promoting growth of cells, e.g. bone cells}
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- 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)
- 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)

## Abstract

A method is provided for treating an intervertebral disc of a subject, the method including delivering cells to a nucleus pulposus of the intervertebral disc. At least one intra-pulposus exposed electrode surface is implanted in the nucleus pulposus. At least one extra-pulposus exposed electrode surface is implanted in a body of the subject outside the nucleus pulposus. The delivered cells are supported by activating control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive nutrient-containing fluid into the nucleus pulposus. Other embodiments are also described.

## Claims

### Claim 1

A method for treating an intervertebral disc of a subject, the method comprising:
delivering cells to a nucleus pulposus of the intervertebral disc;
implanting at least one intra-pulposus exposed electrode surface in the nucleus pulposus;
implanting at least one extra-pulposus exposed electrode surface in a body of the subject outside the nucleus pulposus; and
supporting the delivered cells by activating control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive nutrient-containing fluid containing oxygen into the nucleus pulposus.

### Claim 2 (depends on 1)

The method according to claim 1, wherein delivering the cells to the nucleus pulposus comprises injecting the cells into the nucleus pulposus through a hollow needle.

### Claim 3 (depends on 1)

The method according to claim 1, wherein delivering the cells to the nucleus pulposus comprises delivering the cells to the body of the subject outside the nucleus pulposus such that the cells migrate into the nucleus pulposus.

### Claim 4 (depends on 3)

The method according to claim 3, wherein delivering the cells to the body of the subject outside the nucleus pulposus comprises delivering the cells to a vertebral endplate such that the cells migrate into the nucleus pulposus.

### Claim 5 (depends on 3)

The method according to claim 3, wherein delivering the cells to the nucleus pulposus comprises delivering the cells to an annulus fibrosus of the intervertebral disc.

### Claim 6 (depends on 3)

The method according to claim 3, wherein delivering the cells to the nucleus pulposus comprises, while at least some of the cells are outside the nucleus pulposus, activating the control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the cells into the nucleus pulposus.

### Claim 7 (depends on 1)

The method according to claim 1, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to apply a mean voltage of less than 1.23 V between the intra-pulposus exposed electrode surface and the extra-pulposus exposed electrode surface, so as not to cause electrolysis.

### Claim 8 (depends on 1)

The method according to claim 1, wherein delivering the cells to the nucleus pulposus comprises delivering stem cells to the nucleus pulposus.

### Claim 9 (depends on 1)

The method according to claim 1, wherein delivering the cells to the nucleus pulposus comprises delivering disc cells to the nucleus pulposus.

### Claim 10 (depends on 1)

The method according to claim 1, wherein delivering the cells to the nucleus pulposus comprises delivering notochordal cells to the nucleus pulposus.

### Claim 11 (depends on 1)

The method according to claim 1, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to intermittently drive, during a plurality of sessions, the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus.

### Claim 12 (depends on 11)

The method according to claim 11, wherein an average duration of non-activation periods between sequential ones of the sessions is at least 12 hours.

### Claim 13 (depends on 11)

The method according to claim 11, wherein the plurality of sessions includes at least 10 sessions.

### Claim 14 (depends on 11)

The method according to claim 11, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to intermittently drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus during one or more of the sessions during each 24-hour period.

### Claim 15 (depends on 14)

The method according to claim 14, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to intermittently drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus during exactly one of the sessions during each 24-hour period.

### Claim 16 (depends on 11)

The method according to claim 11, wherein the plurality of sessions extends over at least one week.

### Claim 17 (depends on 1)

The method according to claim 1, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to apply direct current between the intra-pulposus and the extra-pulposus exposed electrode surfaces.

### Claim 18 (depends on 1)

The method according to claim 1, further comprising delivering an enzyme to the intervertebral disc or tissue around the intervertebral disc so as to facilitate electroosmotically driving the nutrient-containing fluid into the nucleus pulposus.

### Claim 19

A method for treating an intervertebral disc of a subject, the method comprising:
delivering cells to a nucleus pulposus of the intervertebral disc;
implanting at least one intra-pulposus exposed electrode surface in the nucleus pulposus;
implanting at least one extra-pulposus exposed electrode surface in a body of the subject outside the nucleus pulposus; and
supporting the delivered cells by activating control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive nutrient-containing fluid containing glucose into the nucleus pulposus.

### Claim 20 (depends on 19)

The method according to claim 19, wherein activating the control circuitry comprises activating the control circuitry to:
repeatedly assume an electroosmotic mode of operation in alternation with an oxygen-generating mode of operation,
in the electroosmotic mode of operation, electroosmotically drive the nutrient-containing fluid into the nucleus pulposus, by applying a mean voltage of less than 1.23 V between the intra-pulposus exposed electrode surface and the extra-pulposus exposed electrode surface, and
in the oxygen-generating mode of operation, generate oxygen within the nucleus pulposus by electrolysis, by applying a mean voltage of at least 1.23 V between the intra-pulposus exposed electrode surface and the extra-pulposus exposed electrode surface.

### Claim 21 (depends on 20)

The method according to claim 20, wherein activating the control circuitry comprises activating the control circuitry to, during a period of time, assume (a) the electroosmotic mode of operation at least 10 times for an aggregate first duration and (b) the oxygen-generating mode of operation at least 10 times for an aggregate second duration that is less than 10% of the aggregate first duration.

### Claim 22 (depends on 21)

The method according to claim 21, wherein the aggregate second duration is less than 1% of the aggregate first duration.

### Claim 23 (depends on 19)

The method according to claim 19, wherein delivering the cells to the nucleus pulposus comprises injecting the cells into the nucleus pulposus through a hollow needle.

### Claim 24 (depends on 19)

The method according to claim 19, wherein delivering the cells to the nucleus pulposus comprises delivering the cells to the body of the subject outside the nucleus pulposus such that the cells migrate into the nucleus pulposus.

### Claim 25 (depends on 19)

The method according to claim 19, wherein delivering the cells to the nucleus pulposus comprises delivering stem cells to the nucleus pulposus.

### Claim 26 (depends on 19)

The method according to claim 19, wherein supporting the delivered cells comprises supporting the delivered cells by activating the control circuitry to intermittently drive, during a plurality of sessions, the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus.

### Claim 27 (depends on 19)

The method according to claim 19, further comprising delivering an enzyme to the intervertebral disc or tissue around the intervertebral disc so as to facilitate electroosmotically driving the nutrient-containing fluid into the nucleus pulposus.
