# US 10,493,160 B2 · Microstructure using cross-linked hyaluronic acid hydrogel, and method for producing same

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

- Number: US 10,493,160 B2
- Document ID: US10493160B2
- Status: Granted
- Kind: B2
- Application number: 15/550,743
- Filed: 2016-02-15
- Published: 2018-01-25
- Granted: 2019-12-03
- Earliest claimed: 2015-02-13
- Assignees: Endoderma Co., Ltd.
- Applicants: Endoderma Co., Ltd.
- Inventors: Jae Soo Kim; Soon Chang Kwon; Sang Jin Park
- Web page: https://patentgrep.com/patent/US10493160B2

## CPC

- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- A61M 37/00: Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04)
- A61M 37/0015: {by using microneedles}
- B29B 13/06: by drying (B29B13/08 takes precedence {; drying moulded articles or half products B29C37/0092})
- B29C 45/0001: {characterised by the choice of material}
- B29C 45/40: Removing or ejecting moulded articles
- A61M 2037/0046: {Solid microneedles}
- A61M 2037/0053: {Methods for producing microneedles}
- B29K 2105/0061: {Gel or sol}
- 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)}
- 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
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS

## Abstract

The present invention provides microstructures using crosslinked hyaluronic acid hydrogels and the method for preparing the same. The present invention for preparing microstructures using crosslinked hyaluronic acid hydrogels allows the preparation of microstructures with a uniform shape and minimum deformation. Furthermore, the microstructures made using crosslinked hyaluronic acid hydrogels in the present invention can improve skin aging, e.g. wrinkles, replenish moisture, easily absorb body fluids due to its outstanding swelling performance, provide a longer duration in the body due to its resistance against a hyaluronic acid hydrolyzing enzyme, enabling the safe delivery of effective components in the body.

## Claims

### Claim 1

A microstructure formed from crosslinked hyaluronic acid hydrogels and non-crosslinked hyaluronic acid,
wherein the microstructure provides mechanical properties appropriate for skin penetration and is selected from the group consisting of microneedle, microblade, microknife, microspike, microprobe, microbarb, microarray, and microelectrode, and
wherein the weight ratio of the non-crosslinked hyaluronic acid to the crosslinked hyaluronic acid hydrogels is 1:1 to 10:1 and the solid content of the crosslinked hyaluronic acid hydrogels is equal to or below 15% (w/v) in the microstructure.

### Claim 2 (depends on 1)

The microstructure of claim 1, wherein the crosslinked hyaluronic acid hydrogel has the crosslinking rate of 1-50%.

### Claim 3

A method for preparing microstructures formed from crosslinked hyaluronic acid hydrogels and non-crosslinked hyaluronic acid comprising the following steps:
(a) supplying a mixture of crosslinked hyaluronic acid hydrogel and non-crosslinked hyaluronic acid into a micro-mold;
(b) injecting the mixture into the micro-mold cavities; and
(c) separating the micro-mold and the mixture to form a microstructure,
wherein the microstructure provides mechanical properties appropriate for skin penetration and is selected from the group consisting of microneedle, microblade, microknife, microspike, microprobe, microbarb, microarray, and microelectrode, and
wherein the weight ratio of the non-crosslinked hyaluronic acid to the crosslinked hvaluronic acid hydrogels is 1:1 to 10:1 and the solid content of crosslinked hyaluronic acid hydrogels is equal to or below 15% (w/v) in the microstructure.

### Claim 4 (depends on 3)

The method of claim 3, wherein the crosslinked hyaluronic acid hydrogel has a crosslinking density of 1-50%.

### Claim 5 (depends on 3)

The method of claim 3, wherein the injection is carried out by applying an external force to the mixture.

### Claim 6 (depends on 5)

The method of claim 5, wherein the external force is a centrifugal force.

### Claim 7 (depends on 3)

The method of claim 3, wherein the injection is carried out at a pressure below atmospheric pressure.

### Claim 8 (depends on 7)

The method of claim 7, wherein the pressure below atmospheric pressure is 100-750 mmHg.

### Claim 9 (depends on 3)

The method of claim 3, wherein the method further comprises the step of drying the mixture after the step (a).

### Claim 10 (depends on 3)

The method of claim 3, wherein the method further comprises the step of drying the mixture after the step (b).

### Claim 11 (depends on 3)

The method of claim 3, wherein the method further comprises the step of drying the mixture before the step (a).

### Claim 12 (depends on 9)

The method of claim 9, wherein the drying is carried out for 10 minutes to 60 hours at 15 to 90° C.

### Claim 13 (depends on 9)

The method of claim 9, wherein the drying is carried out at a pressure below atmospheric pressure.

### Claim 14 (depends on 3)

The method of claim 3, wherein the method comprises the step of homogenizing the crosslinked hyaluronic acid hydrogel before the step (a).

### Claim 15 (depends on 3)

The method of claim 3, wherein the crosslinked hyaluronic acid hydrogel is crosslinked by an ether crosslinking agent.

### Claim 16 (depends on 3)

The method of claim 3, wherein the crosslinked hyaluronic acid hydrogel is crosslinked by a 1,4butanediol diglycidyl ether.