# US 12,109,317 B2 · Electrospun fibrous matrix, its preparation method and uses thereof

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- Number: US 12,109,317 B2
- Document ID: US12109317B2
- Status: Granted
- Kind: B2
- Application number: 17/564,096
- Filed: 2021-12-28
- Published: 2023-06-29
- Granted: 2024-10-08
- Earliest claimed: 2021-12-28
- Assignees: National Cheng Kung University
- Applicants: National Cheng Kung University
- Inventors: Ping-Ching Wu; Cheng-Hsin Chuang; Po-Heng Chen; Yu-Yi Chiang
- Web page: https://patentgrep.com/patent/US12109317B2

## CPC

- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 35/33: Fibroblasts
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61L 15/26: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof {(A61L15/225 takes precedence)}
- A61L 15/44: Medicaments
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- C08G 63/06: derived from hydroxycarboxylic acids
- C08K 9/10: Encapsulated ingredients
- C08L 29/04: Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
- C08L 67/04: Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence)
- D01D 5/0007: {Electro-spinning (non-woven fabrics produced by electro-spinning D04H1/728)}
- D01D 5/0015: {characterised by the initial state of the material}
- D01D 5/003: {the material being a polymer solution or dispersion (D01D5/0053 takes precedence)}
- D01F 1/10: Other agents for modifying properties
- D01F 6/625: {derived from hydroxy-carboxylic acids, e.g. lactones}
- D01F 8/16: with at least one other macromolecular compound obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds as constituent
- A61L 2300/41: Anti-inflammatory agents, e.g. NSAIDs
- A61L 2300/62: Encapsulated active agents, e.g. emulsified droplets
- A61L 2300/64: Animal cells
- A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- C08L 2203/02: for biomedical use
- C08L 2203/12: used for fibers
- 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)
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)
- D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01F: CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are electrospun fibrous matrix and its production method. The method mainly includes the steps of, mixing a first polymer and a drug to form a first mixture, and sonicating the first mixture until a plurality of microparticles are formed with the drug encapsulated therein; and mixing the plurality of microparticles with a second polymer to form a second mixture, subjecting the second mixture to a wet electrospinning process to form the electrospun fibrous matrix. The thus-produced electrospun fibrous matrix is characterized by having a plurality of first and second fibrils woven together, in which each second fibril has a plurality of drug-encapsulated microparticles independently integrated and disposed along the longitudinal direction of the second fibril. Also disclosed herein is a method for treating a wound of a subject. The method includes applying the present electrospun fibrous matrix to the wound of the subject.

## Claims

### Claim 1

An electrospun fibrous matrix, comprising a plurality of a first and second fibrils that are woven together,
wherein,
each of the second fibrils has a plurality of microparticles independently integrated within the second fibril and disposed at intervals along the longitudinal direction of each of the second fibrils, wherein each of the microparticles is made of a first polymer and has a encapsulated therein,
each of the first fibrils is devoid of the microparticles and the drug; and
the plurality of the first and second fibrils are independently made of a second polymer that is different from the first polymer wherein the first polymer is poly(lactic-co-glycolic acid) (PLGA) and the second polymer is poly(vinyl alcohol) (PVA).

### Claim 2 (depends on 1)

The electrospun fibrous matrix of claim 1, wherein each of the first fibrils has a diameter ranging from 100 to 500 nm, and each of the microparticles is about 1 to 5 μm in diameter.

### Claim 3 (depends on 1)

The electrospun fibrous matrix of claim 1, wherein the electrospun fibrous matrix has a plurality of cavities independently being about 15-40 μm in diameter.

### Claim 4 (depends on 1)

The electrospun fibrous matrix of claim 1, wherein the drug is an analgesic agent, an anti-inflammatory agent, an anti-cancer agent, an antibiotic, or a combination thereof.

### Claim 5

A method of producing an electrospun fibrous matrix, comprising:
(a) mixing a first polymer and a drug to form a first mixture;
(b) sonicating the first mixture of the step (a) until a plurality of microparticles are formed with the drug being encapsulated therein;
(c) mixing the plurality of microparticles of the step (b) with a second polymer to form a second mixture;
(d) subjecting the second mixture of the step (c) to an electrospinning process in a solution to produce a plurality of first and second fibrils, wherein each of the second fibrils has the plurality of microparticles independently integrated and disposed along the longitudinal direction of the second fibrils, while each of the first fibrils is devoid of the microparticles; and
(e) weaving the plurality of first and second fibrils to form the electrospun fibrous matrix,
wherein the first polymer and the second polymer are different wherein the first polymer is poly(lactic-co-glycolic acid) (PLGA) and the second polymer is poly(vinyl alcohol) (PVA).

### Claim 6 (depends on 5)

The method of claim 5, wherein in the step (a), the first polymer and the drug are mixed at a mass ratio about 5:1 to 3:1.

### Claim 7 (depends on 5)

The method of claim 5, wherein the first polymer and the second polymer exist in a mass ratio of about 1:5 to 1:15.

### Claim 8 (depends on 5)

The method of claim 5, wherein the drug is an analgesic agent, an anti-inflammatory agent, an anti-cancer agent, an antibiotic, or a combination thereof.

### Claim 9 (depends on 5)

The method of claim 5, wherein in the step (d), the electrospinning process is conducted under a humidity of about 20-55% at a voltage of about 16-22 kV for about 5 hours.

### Claim 10 (depends on 5)

The method of claim 5, wherein in the step (d), the solution is a methanol solution.

### Claim 11 (depends on 1)

A method for treating a wound in a subject in need thereof, comprising applying the electrospun fibrous matrix of claim 1 to the wound of the subject.

### Claim 12 (depends on 11)

The method of claim 11, further comprising administering to the subject an effective amount of isolated stem cells, isolated somatic cells, or a combination thereof.

### Claim 13 (depends on 12)

The method of claim 12, wherein the isolated stem cells are selected from the group consisting of mesenchymal stem cells, adult stem cells, embryonic stem cells, bone marrow stem cells, neural stem cells, limbal stem cells, tissue-derived stem cells, dental pulp stem cells, and induced pluripotent stem cells.

### Claim 14 (depends on 12)

The method of claim 12, wherein the isolated somatic cells are selected from the group consisting of muscle cells, hepatocytes, neurons, fibroblasts, odontoblasts, epithelial cells, adipocytes, bone cells, leukocytes, lymphocytes, platelets, and mucosal cells.

### Claim 15 (depends on 12)

The method of claim 12, wherein the isolated stem cells or the isolated somatic cells are administered to the subject in the amount of about 1×104 to 1×106 cells per square centimeter of a wound area.