Biodegradable and biocompatible medical products, namely adhesives, sealants, and hemostats

Patent metadata

Field	Value
Publication number	US-12209206-B2
Application number	US-202418814146-A
Country	US
Kind code	B2
Filing date	Aug 23, 2024
Priority date	Apr 13, 2023
Publication date	Jan 28, 2025
Grant date	Jan 28, 2025

Abstract

Adhesive compositions for medical and non-medical uses are provided. The adhesive compositions can include cyclic disulfide monomers, oligomers of reactions between the cyclic disulfides, polymers of the cyclic disulfides, solid articles formed formed from the polymers, and any combination thereof. Methods of making, using, and recycling the adhesive compositions are provided, including use of the adhesive compositions on a variety of substrates that include biological tissue; biomaterials, including synthetics and natural such as bone, wood, and cellulosics; metals and alloys; polymers, plastics, and rubbers; ceramics; composites; and, any combination of these materials. The adhesives can adhere to substrates in a variety of environmental conditions that include ambient atmospheric conditions, wet conditions that include adhering materials underwater, and in a wide variety of temperatures and pressures, such as those temperatures and pressures found in medical environments, including in living tissue, as well as many residential, commercial, industrial, and manufacturing environments.

First claim

We claim:

1. A medical product, comprising:
a liquid composition including
a plurality of substituted 1,2-dithiolane monomers, the substituted 1,2-dithiolane monomers functional to polymerize through a ring-opening reaction to form a polydisulfide polymer having
a first active thiol end and a second active thiol end; and,
a plurality of repeating units having a substituted dithioalkyl structure from the ring opening reaction as follows

wherein,
n is 3;
each R i and R k is independently selected from the group consisting of H; alkyl, cycloalkyl, alkenyl, alkynyl, and aryl groups, each of the groups having from 1-8 carbons; hydroxylated alkyl, cycloalkyl, alkenyl, alkynyl, and aryl groups, each of the groups having from 1-8 carbons; and, carboxylated alkyl, cycloalkyl, alkenyl, alkynyl, and aryl groups, each of the groups having from 1-8 carbons; wherein, i and k are integers, and at least one R i or R k in each repeating unit includes a carbonyl functionality;
and,
m is an integer selected to match a desired molecular weight of the polymer;

and,
a plurality of stabilizer molecules configured to stabilize the first active thiol end of the polymer, the plurality of stabilizer molecules being the substituted cyclic disulfide molecules derivatized to include a functional group that forms a first labile bond with the first active thiol end, the first labile bond selected from the group consisting of a thioester bond, a thiocarbamate bond, and a thioether bond;

the polydisulfide polymer formed by reacting the plurality of monomers and the plurality of stabilizers in the liquid; or,
a combination of the liquid and the polydisulfide polymer;
wherein,
the repeating units and the stabilizer molecules are the same, or substantially the same, chemical moieties following a depolymerization of the polymer; and,
the polymer is biocompatible and biodegradable for a medical use.

2. The medical product of claim 1 , the liquid further including a plurality of terminator molecules for forming a labile bond with the second active thiol group, the plurality of terminator molecules selected from the group consisting of R′OH, R′CO 2 H, and R′SH, and R′ is selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, and aryl groups, each of the groups having from 1-8 carbons; and, the second labile bond is selected from the group consisting of thioethers, thioesters, and disulfides.

3. The medical product of claim 1 , the liquid further including a plurality of terminator molecules for forming a labile bond with the second active thiol group, the plurality of terminator molecules selected from the group consisting of alkanols having from 1-8 carbons, alkanoic acids having from 1-8 carbons, and alkylthiols having from 1-8 carbons, and the second labile bond is selected from the group consisting of thioethers, thioesters, and disulfides.

4. The medical product of claim 1 , the liquid further including a plurality of terminator molecules for forming a labile bond with the second active thiol group, the plurality of terminator molecules selected from the group consisting of ethanol, and a substituted 1,2-dithiolane with a hydroxyl functionality.

5. The medical product of claim 1 , wherein:
the repeating unit is a substituted 1,3-dithiopropyl structure as follows

wherein,
m is an integer;
R i includes R 1 , R 2 , and R 3 ; and,
each R k is H;

and,
each stabilizer molecule includes the substituted 1,3-dithiopropyl structure.

6. The medical product of claim 5 , wherein:
the repeating unit is a substituted 1,3-dithiopropyl structure as follows

wherein,
m is an integer;
R 1 is a pentanoic acid group, and R 2 and R 5 are each H;

and,
each stabilizer molecule includes the substituted 1,3-dithiopropyl structure, wherein R 1 is a pentanoic acid group, and R 2 and R 3 are each H.

7. The medical product of claim 1 , wherein the product is a self-healing product.

8. A method of adhering a first biological tissue to a substrate, the method comprising:
applying the medical product of claim 1 to the first biological tissue; and,
creating a joint between the first tissue and the substrate to adhere the first biological tissue to the substrate.

9. The method of claim 8 , wherein the substrate is a second biological tissue.

10. The method of claim 8 , wherein the substrate is a medical device.

11. The method of claim 8 , wherein the product is a topical adhesive, sealant, and/or hemostat, and the method is a topical tissue closure treatment of a subject.

12. The method of claim 8 , wherein the product is a topical adhesive, sealant, and/or hemostat, and the method is a topical tissue closure treatment of a traumatic injury of a subject.

13. The method of claim 8 , wherein the product is a topical adhesive, sealant, and/or hemostat, and the method is a skin graft treatment of a subject.

14. The method of claim 8 , wherein the product is a topical adhesive, sealant, and/or hemostat, and the method is a wound dressing attachment in a treatment of a subject.

15. The method of claim 8 , wherein the product is a topical adhesive, sealant, and/or hemostat, and the method is a medical device attachment in a treatment of a subject.

16. The method of claim 8 , wherein the product is an internal adhesive, sealant, and/or hemostat, and the method is an internal tissue closure treatment of a subject.

17. The method of claim 8 , wherein the product is an internal adhesive, sealant, and/or hemostat, and the method is an internal tissue closure treatment of a traumatic injury of a subject.

18. The method of claim 8 , wherein the product is an internal adhesive, sealant, and/or hemostat, and the method is an internal tissue closure treatment of a subject, and the internal closure treats an organ puncture.

19. The method of claim 8 , wherein the product is an internal adhesive, sealant, and/or hemostat, and the method is an internal cartilage repair treatment of a subject.

20. The method of claim 8 , wherein the product is an internal adhesive, sealant, and/or hemostat, and the method is an internal anastomosis treatment of a subject.

Assignees

• Univ California

Inventors

• Messersmith Phillip B
• Pal Subhajit
• Defrates Kelsey G
• Shin Jisoo

Classifications

• C08G75/14

  Polysulfides · CPC title

• C08G75/26

  Polythioesters · CPC title

• A61L24/046 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence) · CPC title

• C08G75/06

  from cyclic thioethers · CPC title

• C09D181/02

  Polythioethers; Polythioether-ethers · CPC title