# US 10,864,303 B2 · Method comprising contacting tissue with a cross-linkable polyester prepolymer

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- Number: US 10,864,303 B2
- Document ID: US10864303B2
- Status: Granted
- Kind: B2
- Application number: 16/206,937
- Filed: 2018-11-30
- Published: 2019-03-28
- Granted: 2020-12-15
- Earliest claimed: 2006-01-12
- Assignees: Massachusetts Institute of Technology
- Applicants: Massachusetts Institute of Technology
- Inventors: Christopher J. Bettinger; Joost P. Bruggeman; Lino da Silva Ferreira; Jeffrey M. Karp; Robert S. Langer; Christiaan Nijst; Andreas Zumbuehl; Jason Burdick; Sonia J. Kim
- Web page: https://patentgrep.com/patent/US10864303B2

## CPC

- A61L 27/3804: {characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells}
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/48: Reproductive organs
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 31/148: {Materials at least partially resorbable by the body}
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- C08G 63/6854: {derived from polycarboxylic acids and polyhydroxy compounds}
- C08J 3/24: Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K)
- C08J 3/246: {Intercrosslinking of at least two polymers}
- C08K 5/0025: {Crosslinking or vulcanising agents; including accelerators}
- C12N 11/087: Acrylic polymers
- C12N 11/096: Polyesters; Polyamides
- C08J 2367/00: Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J 2367/07: having terminal carbon-to-carbon unsaturated bonds
- C12N 11/082: obtained by reactions only involving carbon-to-carbon unsaturated bonds
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)
- C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present inventions in various aspects provide elastic biodegradable polymers. In various embodiments, the polymers are formed by the reaction of a multifunctional alcohol or ether and a difunctional or higher order acid to form a pre-polymer, which is cross-linked to form the elastic biodegradable polymer. In preferred embodiments, the cross-linking is performed by functionalization of one or more OR groups on the pre-polymer backbone with vinyl, followed by photopolymerization to form the elastic biodegradable polymer composition or material. Preferably, acrylate is used to add one or more vinyls to the backbone of the pre-polymer to form an acrylated pre-polymer. In various embodiments, acrylated pre-polymers are co-polymerized with one or more acrylated co-polymers.

## Claims

### Claim 1

A method for forming a biodegradable elastomeric material, comprising the steps of:
(a) reacting a first component comprising two or more functionalities of the general formula —OR, where R of each group is independently hydrogen or alkyl, with a second component comprising two or more acid ester functionalities to form a mixture of pre-polymers having a molecular weight in the range between about 300 Da and about 75,000 Da;
(b) reacting the mixture of pre-polymers with an acrylate to form a mixture of acrylated pre-polymers; and
(c) irradiating the acrylated pre-polymer mixture to cross-link at least a portion of the acrylated pre-polymers and form a biodegradable elastomeric material; wherein the pre-polymer mixture is not heated above about 45° C. during irradiation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the acrylate is a methacrylate or a vinyl methacrylate.

### Claim 3 (depends on 1)

The method of claim 1, wherein the acrylate has a structure as follows:
wherein, R1 represents methyl or hydrogen;
R2, R2′, and R2″ represent independently alkyl, aryl, heterocycles, cycloalkyl, aromatic heterocycles, multicycloalkyl, hydroxyl, ester, ether, halide, carboxylic acid, amino, alkylamino, dialkylamino, trialkylamino, amido, carbamoyl thioether, thiol, alkoxy, or ureido groups, and branched and substituted versions thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the acrylate has a structure as follows:

### Claim 5 (depends on 1)

The method of claim 1, wherein the pre-polymer mixture is not heated above about 25° C. during irradiation.

### Claim 6 (depends on 1)

The method of claim 1, wherein step (b) comprises adding to the reaction one or more of an acrylated dextran, acrylated hyaluronic acid, acrylated chitosan, and acrylated poly(ethylene glycol).

### Claim 7 (depends on 1)

The method of claim 1, wherein the second component is a substituted or unsubstituted dioic acid ester.

### Claim 8 (depends on 1)

The method of claim 1, wherein the second component comprises an amino ester functionality and the biodegradable elastomeric material comprises a poly-β-amino ester polymer.

### Claim 9 (depends on 1)

The method of claim 1, wherein, in step (c) the mixture comprises a photoinitiator.

### Claim 10 (depends on 9)

The method of claim 9, wherein the photoinitiator is selected from the group consisting of 2-dimethoxy-2-phenyl-acetophenone, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone, 1-hydroxycyclohexyl-1-phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-benzyl-2-(dimehylamino)-1-[4-morpholinyl) phenyl]-1-butanone, methylbenzoylformate, oxy-phenyl-acetic acid-2-[2-oxo-2-phenyl-acetoxy-ethoxy]-ethyl ester, 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone, diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, phosphine oxide, phenyl bis(2,4,6-trimethyl benzoyl), and combinations thereof.