# US 12,766,217 B2 · Embolic microspheres

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- Number: US 12,766,217 B2
- Document ID: US12766217B2
- Status: Granted
- Kind: B2
- Application number: 17/557,175
- Filed: 2021-12-21
- Published: 2022-04-14
- Granted: 2026-10-20
- Earliest claimed: 2017-07-13
- Assignees: Varian Medical Systems, Inc.
- Applicants: Varian Medical Systems, Inc.
- Inventors: Hongxia Zeng; Bruce R. Forsyth; Hong Cao; Matthew R. DeWitt; Heidi Schwanz
- Web page: https://patentgrep.com/patent/US12766217B2

## CPC

- A61L 24/02: containing inorganic materials
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/1617: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61L 24/0015: {Medicaments; Biocides}
- A61L 24/0031: {Hydrogels or hydrocolloids}
- A61L 24/0042: {Materials resorbable by the body}
- A61L 24/043: {Mixtures of macromolecular materials}
- A61L 24/046: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence)}
- A61L 24/06: obtained by reactions only involving carbon-to-carbon unsaturated bonds {(A61L24/043, A61L24/046 take precedence)}
- A61L 2300/604: Biodegradation
- A61L 2300/608: having two or more layers
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2420/06: Coatings containing a mixture of two or more compounds
- A61L 2420/08: Coatings comprising two or more layers
- A61L 2430/36: for embolization or occlusion, e.g. vaso-occlusive compositions or devices
- A61M 25/0097: {characterised by the hub (tube connectors or tube couplings A61M39/10)}
- 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)
- 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

In some aspects, the disclosure pertains to injectable particles that contain at least one pH-altering agent that is configured to be released from the injectable particles in vivo, upon embolization of an intratumoral artery of a tumor with the injectable particles. In certain instances, the pH altering agent may be a basic agent having a pH value of 7.5, a buffering agent having a pKa value of 7.6 or more, or both. Other aspects of the disclosure pertain to preloaded containers containing such injectable particles and methods of using such injectable particles.

## Claims

### Claim 1

Injectable particles comprising:
a biostable core; and
a coating comprising at least one pH-altering agent that is configured to be released from the injectable particles in vivo upon embolization of an intratumoral artery of a tumor with the injectable particles,
wherein the at least one pH-altering agent includes a basic agent having a pH of 7.5 or more and a buffering agent having a pKa value of 7.6 or more, and
the pH-altering agent includes at least one of a carbonate, a bicarbonate, and a phosphate,
wherein the pH-altering agent is configured to be released from the injectable particle by a mechanism selected from (a) diffusion from all or a portion of the injectable particles, (b) biodisintegration of a portion of the injectable particles wherein the injectable particles further comprise a biodisintegrable polymer, or (c) or a combination of (a) and (b).

### Claim 2 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles are configured such that, upon embolization of the intratumoral artery of the tumor with the injectable particles, the injectable particles release the pH-altering agent such that a microenvironment is created in a vascular bed of the tumor downstream of the injectable particles that has a pH that is higher than a pH that would otherwise exist in the absence of the pH-altering agent.

### Claim 3 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles are spherical particles.

### Claim 4 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles range from 20 to 1500 microns in diameter.

### Claim 5 (depends on 1)

The injectable particles of claim 1, wherein the pKa value is in a range of 7.6 to 35.

### Claim 6 (depends on 1)

The injectable particles of claim 1, wherein the pH-altering agent further comprises an organic compound.

### Claim 7 (depends on 1)

The injectable particles of claim 1, wherein the pH-altering agent is present in the injectable particles in an amount ranging from 10% to 50% by weight, based on a total weight of the injectable particles.

### Claim 8 (depends on 1)

The injectable particles of claim 1, wherein the biostable core is a hydrogel core.

### Claim 9 (depends on 1)

The injectable particles of claim 1, wherein the biostable core comprises a polymer that comprises one or more of methyl methacrylate monomer and vinyl alcohol monomer.

### Claim 10 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles further comprise an additional coating that comprises poly [bis (trifluroethoxy) phosphazene].

### Claim 11 (depends on 1)

The injectable particles of claim 1, wherein the coating further comprises a binder material or a matrix material.

### Claim 12 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles further comprise at least one therapeutic agent.

### Claim 13 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles further comprise at least one osmotic agent in an amount ranging from 5% to 40%, based on a total weight of the injectable particles.

### Claim 14 (depends on 2)

The injectable particles of claim 2, wherein the microenvironment is created in a vascular bed of the tumor downstream of the injectable particles that has a pH that is 0.2 pH units higher than a pH that would otherwise exist in the absence of the pH-altering agent.

### Claim 15 (depends on 2)

The injectable particles of claim 2, wherein the microenvironment is created in a vascular bed of the tumor downstream of the injectable particles that has a pH that is 0.5 pH units higher than a pH that would otherwise exist in the absence of the pH-altering agent.

### Claim 16 (depends on 1)

The injectable particles of claim 1, wherein the injectable particles further comprise an agent that increases radiopacity of the injectable particles.

### Claim 17 (depends on 1)

The injectable particles of claim 1, further comprising an osmotic agent of dextrose in an amount ranging from 0.001 wt % to 5 wt %, based on a total weight of the injectable particles.