Tissue adhesive and method for producing same

Patent metadata

Field	Value
Publication number	US-10064973-B2
Application number	US-201314761326-A
Country	US
Kind code	B2
Filing date	Nov 22, 2013
Priority date	Jan 18, 2013
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

There is provided a tissue adhesive to be applied to a tissue by mixing an adhesive component including an aqueous solution of a fish-derived gelatin with a curative component including an aqueous solution of a water-soluble crosslinking reagent, wherein the water-soluble crosslinking reagent has an amide linkage or an ethylene glycol unit or a sugar chain in the molecular main chain thereof and has two or more of an active ester group or an acid anhydride or an aldehyde group.

First claim

The invention claimed is:

1. A tissue adhesive to be applied to a tissue consisting of:
an adhesive component consisting of a solution of a hydrophobically modified fish-derived gelatin in a phosphate buffer solution (PBS) having a pH of from 6.0 to 8.0; and
a curative component consisting of a solution of a water-soluble crosslinking reagent in a phosphate buffer solution (PBS) having a pH of from 6.0 to 8.0, the curative component being provided for mixture with the adhesive component at the time of applying to a tissue,
wherein the water-soluble crosslinking reagent is pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG).

2. The tissue adhesive according to claim 1 , wherein the hydrophobically modified fish-derived gelatin comprises, as its main chain, a fish-derived gelatin in which the number of hydroxyproline per 1000 constitutional amino acids thereof is 90 or less.

3. The tissue adhesive according to claim 1 , wherein the hydrophobically modified, fish-derived gelatin comprises Lys and a part of the amino groups of the Lys have been substituted with a hydrophobic group.

4. The tissue adhesive according to claim 1 , wherein the hydrophobic groups include one type or a combination of two or more types selected from the group consisting of an ethyl group (2 carbon atoms), a propyl (3 carbon atoms), a butyl group (4 carbon atoms), a pentyl group (5 carbon atoms), a hexanoyl group (6 carbon atoms), a heptanoyl group (7 carbon atoms), an octanoyl group (8 carbon atoms), a nonanoyl group (9 carbon atoms), a decanoyl group (10 carbon atoms), an undecanoyl group (11 carbon atoms), a dodecanoyl group (12 carbon atoms), a tridecanoyl group (13 carbon atoms), a tetradecanoyl group (14 carbon atoms), a pentadecanoyl group (15 carbon atoms), a hexadecanoyl group (16 carbon atoms), a heptadecanoyl group (17 carbon atoms), a stearoyl group (18 carbon atoms), which are saturated fatty acids; an isopropyl (3 carbon atoms), an isobutyl group (4 carbon atoms), an isopentyl group (5 carbon atoms), an isohexanoyl group (6 carbon atoms), an isoheptanoyl group (7 carbon atoms), an isooctanoyl group (8 carbon atoms), an isononanoyl group (9 carbon atoms), an isodecanoyl group (10 carbon atoms), an isoundecanoyl group (11 carbon atoms), an isododecanoyl group (12 carbon atoms), an isotridecanoyl group (13 carbon atoms), an isotetradecanoyl group (14 carbon atoms), an isopentadecanoyl group (15 carbon atoms), an isohexadecanoyl group (16 carbon atoms), an isopalmityl group (16 carbon atoms), an isoheptadecanoyl group (17 carbon atoms), an isostearoyl group (18 carbon atoms), which are branched saturated fatty acids; an oleyl group (18 carbon atoms, one unsaturated carbon atom), a linolenyl group (18 carbon atoms, two unsaturated carbon atoms), an α-linolenyl group (18 carbon atoms, three unsaturated carbon atoms), which are unsaturated fatty acids; and a cholesteryl group, which is a cell membrane component.

5. The tissue adhesive according to claim 1 , wherein the hydrophobically modified fish-derived gelatin is derived from tilapia, sea bream, or cod.

6. The tissue adhesive according to claim 1 , wherein the molecular weight of the hydrophobically modified, fish-derived gelatin is not less than 50000 and less than 100000.

7. The tissue adhesive according to claim 1 , wherein the aqueous solution of the hydrophobically modified, fish-derived gelatin is liquid at normal temperatures.

8. A method for producing the tissue adhesive according to claim 1 , comprising:
a step of synthesizing the hydrophobically modified, fish-derived gelatin by adding an organic molecule having a hydrophobic group to a solution comprising the fish-derived gelatin in the presence of amine to substitute a part of the amino groups on a side chain of the fish-derived gelatin, wherein the number of hydroxyproline per 1000 constitutional amino acids thereof is 90 or less,
a step of preparing the adhesive component by dispersing the hydrophobically modified fish-derived gelatin in a phosphate buffer solution (PBS) having a pH of from 6.0 to 8.0, and
a step of preparing the curative component by dispersing a water-soluble crosslinking reagent in a phosphate buffer solution (PBS) having a pH of from 6.0 to 8.0, wherein the water-soluble crosslinking reagent is 4S-PEG.

9. A method for using the tissue adhesive according to claim 1 , comprising:
a step of mixing the adhesive component with the curative component.

Assignees

• Nat Inst Materials Science

Inventors

• Taguchi Tetsushi

Classifications

• A61L24/104 Primary

  Gelatin · CPC title