# US 11,285,308 B2 · Microstructure for transdermal absorption and method for manufacturing same

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

- Number: US 11,285,308 B2
- Document ID: US11285308B2
- Status: Granted
- Kind: B2
- Application number: 16/064,302
- Filed: 2016-12-22
- Published: 2019-01-03
- Granted: 2022-03-29
- Earliest claimed: 2015-12-28
- Assignees: Endoderma Co., Ltd.
- Applicants: Endoderma Co., Ltd.
- Inventors: Jae Soo Kim; Soon Chang Kwon; Sang Jin Park
- Web page: https://patentgrep.com/patent/US11285308B2

## CPC

- A61M 37/0015: {by using microneedles}
- A61K 9/0021: {Intradermal administration, e.g. through microneedle arrays or needleless injectors}
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- B29C 39/02: for making articles of definite length, i.e. discrete articles
- B81B 1/008: {Microtips}
- B81C 1/00: Manufacture or treatment of devices or systems in or on a substrate (B81C3/00 takes precedence)
- B81C 1/00111: {Tips, pillars, i.e. raised structures (microneedles A61M37/0015)}
- B81C 99/0085: {using moulds and master templates, e.g. for hot-embossing}
- C08B 15/04: Carboxycellulose, e.g. prepared by oxidation with nitrogen dioxide
- C08B 37/0072: {Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates}
- C08L 101/16: the macromolecular compounds being biodegradable
- C09J 101/28: Alkyl ethers
- C09J 105/00: Adhesives based on polysaccharides or on their derivatives, not provided for in groups C09J101/00 or C09J103/00
- C09J 201/00: Adhesives based on unspecified macromolecular compounds
- A61M 2037/0023: {Drug applicators using microneedles}
- A61M 2037/0046: {Solid microneedles}
- A61M 2037/0053: {Methods for producing microneedles}
- A61M 2207/10: Device therefor
- B29C 39/026: {characterised by the shape of the surface}
- B29K 2005/00: Use of polysaccharides or derivatives as moulding material
- B29K 2883/00: Use of polymers having silicon, with or without sulfur, nitrogen, oxygen, or carbon only, in the main chain, as mould material
- B29K 2995/0056: Biocompatible, e.g. biopolymers or bioelastomers
- B29K 2995/006: Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
- B29L 2031/7544: {Injection needles, syringes}
- B29L 2031/756: {Microarticles, nanoarticles}
- B81B 2201/055: Microneedles
- 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)}
- 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)
- 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)
- B81B: MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES (piezoelectric, electrostrictive or magnetostrictive elements per se H10N30/00, H10N35/00)
- B81C: PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS (making microcapsules or microballoons B01J13/02; processes or apparatus specially adapted for the manufacture or treatment of piezoelectric, electrostrictive or magnetostrictive elements per se H10N30/01)
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- C09J: ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES (preparation of glue or gelatine C09H)
- 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
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

The present invention relates to a microstructure including a biocompatible polymer or an adhesive and to a method for manufacturing the same. The present inventors optimized the aspect ratio according to the type of each microstructure, thereby ensuring the optimal tip angle and the diameter range for skin penetration. Especially, the B-type to D-type microstructures of the present invention minimize the penetration resistance due to skin elasticity at the time of skin attachment, thereby increasing the penetration rate of the structures (60% or higher) and the absorption rate of useful ingredients into the skin. In addition, the D-type microstructure of the present invention maximizes the mechanical strength of the structure by applying a triple structure, and thus can easily penetrate the skin. When the plurality of microstructures are arranged in a hexagonal arrangement type, a uniform pressure can be transmitted to the whole microstructures on the skin.

## Claims

### Claim 1

A method for manufacturing a microstructure, the method comprising:
(a) supplying a biodegradable and biocompatible polymer or an adhesive into a micro-mold, wherein the biodegradable and biocompatible polymer or the adhesive comprise hyaluronic acid;
(b) injecting the biodegradable and biocompatible polymer or adhesive into a hole of the micro-mold;
(c) drying the biodegradable and biocompatible polymer or adhesive; and
(d) separating the dried biocompatible polymer and biocompatible or adhesive from the micro-mold to form a microstructure,
wherein the aspect ratio (w:h), configured of the diameter (w) of the bottom surface of the microstructure and the height (h) of the microstructure, is 1:5 to 1:1.5, and the angle of a distal tip (α) is 10°-40°,
wherein injecting is carried out by (i) applying a centrifugal force of 800-1000 g to the micro-mold or (ii) applying a pressure of not less than 500 and less than 760 mmHg inside the micro-mold.

### Claim 2 (depends on 1)

The method of claim 1, wherein step (c) is carried out (i) at room temperature for 36 to 60 hours, (ii) at 40 to 60° C. for 5 to 16 hours, or (iii) at 60 to 80° C. for 2 to 4 hours.

### Claim 3 (depends on 1)

The method of claim 1, wherein the biodegradable and biocompatible polymer further comprises at least one polymer selected from the group consisting of carboxymethyl cellulose (CMC), alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan polylactide, polyglycolide (PGA), polylactide-glycolide copolymer (PLGA), pullulan polyanhydride, polyorthoester, polyetherester, polycaprolactones, polyesteramide, poly(butyric acid), poly(valeric acid), polyurethane, polyacrylate, ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chlorosulphonate polyolefin, polyethylene oxide, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), hydroxypropyl cellulose (HPC), cyclodextrin, copolymers of monomers forming these polymers, and cellulose.

### Claim 4 (depends on 1)

The method of claim 1, wherein the hyaluronic acid has a molecular weight of 240 to 490 kDa.

### Claim 5 (depends on 1)

The method of claim 1, wherein, in step (a), the solid content of the biodegradable and biocompatible polymer is 1 to 30% (w/v) on the basis of the entire composition of the microstructure.

### Claim 6 (depends on 1)

The method of claim 1, wherein the adhesive further comprises at least one material selected from the group consisting of silicone, polyurethane, a physical adhesive, a polyacrylic material, ethylcellulose, hydroxymethyl cellulose, ethylene vinyl acetate, and polyisobutylene.

### Claim 7 (depends on 1)

The method of claim 1, wherein a plurality of microstructures are arranged in a square or hexagonal shape.

### Claim 8 (depends on 7)

The method of claim 7, wherein the plurality of microstructures are arranged at intervals (p) of 250 to 1500 μm.

### Claim 9 (depends on 1)

The method of claim 1, wherein the microstructure has i) a cone shape; ii) a double structure of a cylinder and a cone; iii) a double structure of a truncated cone and a cone; or iv) a triple structure of two truncated cones and a cone.