# US 2020/0392005 A1 · Particulate material production process

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2020/0392005 A1
- Document ID: US20200392005A1
- Status: Published application
- Kind: A1
- Application number: 16/764,267
- Filed: 2018-11-14
- Published: 2020-12-17
- Earliest claimed: 2017-11-14
- Assignees: N4 Pharma UK Limited
- Applicants: N4 Pharma UK Limited
- Inventors: Chengzhong (Michael) Yu; Hao Song; Graham Worrall; Lynn Donlon
- Web page: https://patentgrep.com/patent/US20200392005A1

## CPC

- C01B 33/18: Preparation of finely divided silica neither in sol nor in gel form; After-treatment thereof (preparation of aerogels by dehydrating gels C01B33/158; treatment to enhance the pigmenting or filling properties C09C)
- A01N 25/28: Microcapsules {or nanocapsules}
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61P 37/00: Drugs for immunological or allergic disorders
- B01J 13/04: by physical processes, e.g. drying, spraying
- B01J 13/18: In situ polymerisation with all reactants being present in the same phase
- B01J 13/203: {Exchange of core-forming material by diffusion through the capsule wall}
- B29B 9/12: characterised by structure or composition
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- 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 9/5115: {Inorganic compounds}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- B29B 2009/125: {Micropellets, microgranules, microparticles}
- B29B 2009/163: {Coating, i.e. applying a layer of liquid or solid material on the granule}
- B29B 2009/168: {Removing undesirable residual components, e.g. solvents, unreacted monomers; Degassing}
- C01P 2002/88: by thermal analysis data, e.g. TGA, DTA, DSC
- C01P 2004/03: obtained by SEM
- C01P 2004/34: hollow
- C01P 2004/64: Nanometer sized, i.e. from 1-100 nanometer
- C01B: NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; {METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C}
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B29B: PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C01P: INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS

## Abstract

The present invention relates to a process for producing a plurality of hollow inorganic nanoparticles, which process comprises: (a) contacting a first monomer and a second monomer in a solvent to produce a composition comprising the solvent and a plurality of polymer nanoparticles; (b) adding an inorganic compound precursor to the composition comprising the solvent and the plurality of polymer nanoparticles to produce a composition comprising the solvent and a plurality of inorganic compound-coated polymer nanoparticles; (c) adding an additional amount of the first and second monomers to the composition comprising the solvent and the plurality of inorganic compound-coated polymer nanoparticles to produce a composition comprising the solvent and a plurality of composite nanoparticles; and (d) heating the plurality of composite nanoparticles to produce the plurality of hollow inorganic nanoparticles, wherein in step (a) the first monomer and the second monomer are contacted in the solvent at a temperature of at least 30° C. The present invention also relates to plurality of hollow inorganic nanoparticles and uses thereof.

## Claims

### Claim 1

A process for producing a plurality of hollow inorganic nanoparticles, which process comprises:
(a) contacting a first monomer and a second monomer in a solvent to produce a composition comprising the solvent and a plurality of polymer nanoparticles;
(b) adding an inorganic compound precursor to the composition comprising the solvent and the plurality of polymer nanoparticles to produce a composition comprising the solvent and a plurality of inorganic compound-coated polymer nanoparticles;
(c) adding an additional amount of the first and second monomers to the composition comprising the solvent and the plurality of inorganic compound-coated polymer nanoparticles to produce a composition comprising the solvent and a plurality of composite nanoparticles; and
(d) heating the plurality of composite nanoparticles to produce the plurality of hollow inorganic nanoparticles,
wherein in step (a) the first monomer and the second monomer are contacted in the solvent at a temperature of at least 30° C.

### Claim 2 (depends on 1)

A process according to claim 1, wherein the first monomer and the second monomer are contacted in the solvent at a temperature of from 30° C. to 70° C.

### Claim 3 (depends on 1)

A process according to claim 1, wherein the first monomer and the second monomer are contacted in the solvent at a temperature of at least 30° C. for no more than four hours.

### Claim 4 (depends on 1)

A process according to claim 1, wherein the inorganic compound is silica and the hollow inorganic nanoparticles are hollow silica nanoparticles.

### Claim 5 (depends on 1)

A process according to claim 1, wherein step (a) comprises mixing the first monomer and the second monomer in the solvent,
which solvent preferably comprises water, an alcohol and ammonia.

### Claim at position 6

6-13. (canceled)

### Claim 14 (depends on 1)

A process according to claim 1, which process further comprises a step of cooling the composition comprising the solvent and the plurality of polymer nanoparticles in between step (a) and step (h),
wherein the composition comprising the solvent and the plurality of polymer nanoparticles is cooled at an average rate of from 0.5° C./min to 1.0° C./min for a time of from 10 minutes to 60 minutes.

### Claim 15

(canceled)

### Claim 16 (depends on 1)

A process according to claim 1, wherein following addition of an additional amount of the first and second monomers to the composition comprising the solvent and the plurality of inorganic compound-coated polymer nanoparticles, the concentration of first monomer is from 2.0 mM to 0.2 M and the concentration of the second monomer is from 2.0 mM to 0.2 M in the composition comprising the solvent, the plurality of inorganic compound-coated polymer nanoparticles and the first and second monomers.

### Claim at position 10

17-20. (canceled)

### Claim 21 (depends on 1)

A process according to claim 1, wherein each of the hollow inorganic nanoparticles comprises:
a shell comprising an inorganic compound;
a volume within the shell which does not comprise the inorganic compound; and
disposed on the exterior of the shell, a plurality of protrusions comprising the inorganic compound.

### Claim 22

(canceled)

### Claim 23 (depends on 1)

A process according to claim 1, which process further comprises:
(e) treating the plurality of hollow inorganic nanoparticles with an agent to produce a plurality of hollow inorganic nanoparticles loaded with the agent.

### Claim at position 14

24-26. (canceled)

### Claim 27 (depends on 23)

A process according to claim 23, which process comprises a step of treating the plurality of hollow inorganic nanoparticles with a phosphonate linker prior to treating the plurality of hollow inorganic nanoparti cies with the agent.

### Claim at position 16

28-31. (canceled)

### Claim 32

A plurality of hollow inorganic nanoparticles, wherein each of the hollow inorganic nanoparticles comprises:
a shell comprising an inorganic compound;
a volume within the shell which does not comprise the inorganic compound; and
disposed on the exterior of the shell, a plurality of protrusions comprising the inorganic compound; and
where the particle size of the plurality of hollow inorganic nanoparticles is from 100 to 500 nm.

### Claim 33

A plurality of hollow inorganic nanoparticles, Wherein each of the hollow inorganic nanoparticles comprises:
a shell comprising an inorganic compound;
a volume within the shell which does not comprise the inorganic compound; and
disposed on the exterior of the shell, a plurality of protrusions comprising the inorganic compound; and
wherein the hollow inorganic nanoparticles further comprise a plurality of acidic groups bound to the inorganic compound.

### Claim 34 (depends on 33)

A plurality of hollow inorganic nanoparticles according to claim 33, wherein the acidic groups are selected from phosphonate groups, phosphate groups, carboxylate groups and an alpha-keto carboxylate groups.

### Claim at position 20

35-41. (canceled)

### Claim 42 (depends on 32)

A composition comprising a plurality of hollow inorganic nanoparticles according to claim 32 and an agent.

### Claim at position 22

43-44. (canceled)

### Claim 45 (depends on 42)

A composition according to claim 42, wherein the agent is a pesticide, a herbicide, a therapeutic agent, a vaccine, a charge modifying agent, a transfection reagent, a nucleic acid, or a dye.

### Claim 46 (depends on 42)

A composition according to claim 42, wherein the agent is polyethyleneimine.

### Claim 47 (depends on 42)

A composition according to claim 42, wherein the plurality of hollow inorganic nanoparticles are functionalised with a phosphonate linker.

### Claim at position 26

48-49. (canceled)

### Claim 50 (depends on 42)

A composition as recited in claim 42, wherein the agent is an active agent, wherein the active agent is a vaccine and the composition is for use in the prevention or treatment of a disease in a subject by immunizing the subject against the disease using the vaccine.

### Claim 51 (depends on 42)

A method of transfecting a nucleic acid into a cell, the method comprising treating the cell with a composition as defined in claim 42.

### Claim at position 29

52-53. (canceled)

### Claim 54 (depends on 42)

A composition as defined in claim 42 for use in a method of transfecting a nucleic acid into a cell, wherein the agent is a nucleic acid and the method comprises treating the cell with the composition comprising the plurality of hollow inorganic nanoparticles and the nucleic acid, and thereby transfecting the cell with the nucleic acid and stimulating an immune response.

### Claim 55

(canceled)