Tissue coating for preventing undesired tissue-to-tissue adhesions
View Patent ↗Disclosed herein are a kit and a method for forming a tissue coating that prevents undesired tissue-to-tissue adhesions resulting from trauma, surgery, infection, or other stimulus. The tissue coating is a hydrogel formed by reacting an aminocarboxymethyldextran containing primary amine groups with an oxidized carboxymethylcellulose containing aldehyde groups.
1. A kit suitable for forming a tissue coating that is capable of preventing undesired tissue-to-tissue adhesions comprising:
a) at least one carboxymethyldextran that has been derivatized to provide at least one aminocarboxymethyldextran that contains primary amine groups wherein each said primary amine group is directly bound to a primary, secondary or tertiary carbon atom, said at least one carboxymethyldextran having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, and a degree of carboxymethylation of about 0.1 to about 2.5, said at least one aminocarboxymethyldextran having a primary amine substitution level of about 10% to about 150%; and
b) at least one carboxymethylcellulose that has been oxidized to provide at least one oxidized carboxymethylcellulose containing aldehyde groups, said at least one oxidized carboxymethylcellulose having a weight-average molecular weight of about 5,000 to about 100,000 Daltons, and an equivalent weight per aldehyde group of about 125 to about 750 Daltons.
2. The kit according to claim 1 wherein the degree of carboxymethylation of the carboxymethyldextran is about 0.9 to about 2.1.
3. The kit according to claim 1 wherein the weight-average molecular weight of the carboxymethyldextran is about 10,000 to about 60,000 Daltons.
4. The kit according to claim 1 wherein the primary amine substitution level of the aminocarboxymethyldextran is about 10% to about 75%.
5. The kit according to claim 1 wherein the weight-average molecular weight of the oxidized carboxymethylcellulose is about 10,000 to about 30,000 Daltons.
6. The kit according to claim 1 wherein the equivalent weight per aldehyde group of the oxidized carboxymethylcellulose is about 180 to about 495 Daltons.
7. The kit according to claim 1 wherein the aminocarboxymethyldextran is contained in a first aqueous solution or dispersion and the oxidized carboxymethylcellulose is contained in a second aqueous solution or dispersion.
8. The kit according to claim 7 wherein the first aqueous solution or dispersion contains the aminocarboxymethyldextran at a concentration of about 5% to about 50% by weight relative to the total weight of the solution or dispersion.
9. The kit according to claim 7 wherein the second aqueous solution or dispersion contains the oxidized carboxymethylcellulose at a concentration of about 5% to about 50% by weight relative to the total weight of the solution or dispersion.
10. The kit according to claim 7 wherein at least one of the first aqueous solution or dispersion or the second aqueous solution or dispersion further comprises at least one additive selected from the group consisting of pH modifiers, viscosity modifiers, antimicrobials, colorants, healing promoters, surfactants, pharmaceutical drugs and therapeutic agents.
11. The kit according to claim 1 wherein the aminocarboxymethyldextran and the oxidized carboxymethylcellulose are in the form of finely divided powders.
12. A dried hydrogel formed by a process comprising the steps of:
a) reacting in a solvent (i) at least one carboxymethyldextran that has been derivatized to provide at least one aminocarboxymethyldextran that contains primary amine groups wherein said primary amine group is directly bound to a primary, secondary or tertiary carbon atom, said at least one carboxymethyldextran having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, and a degree of carboxymethylation of about 0.1 to about 2.5, said at least one aminocarboxymethyldextran having a primary amine substitution level of about 10% to about 150%; with (ii) at least one carboxymethylcellulose that has been oxidized to provide at least one oxidized carboxymethylcellulose containing aldehyde groups, said at least one oxidized carboxymethylcellulose having a weight-average molecular weight of about 5,000 to about 100,000 Daltons, and an equivalent weight per aldehyde group of about 125 to about 750 Daltons, to form a hydrogel; and
b) treating said hydrogel to remove at least a portion of said solvent to form the dried hydrogel.
13. The dried hydrogel according to claim 12 wherein said dried hydrogel is in the form of a film.
14. The dried hydrogel according to claim 12 wherein said dried hydrogel is in the form of finely divided particles.
15. A method for forming a tissue coating that is capable of preventing undesired tissue-to-tissue adhesions comprising:
applying to an anatomical site on tissue of a living organism:
a) at least one carboxymethyldextran that has been derivatized to provide at least one aminocarboxymethyldextran that contains primary amine groups wherein said primary amine group is directly bound to a primary, secondary or tertiary carbon atom, said at least one carboxymethyldextran having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, and a degree of carboxymethylation of about 0.1 to about 2.5, said at least one aminocarboxymethyldextran having a primary amine substitution level of about 10% to about 150%; followed by
b) at least one carboxymethylcellulose that has been oxidized to provide at least one oxidized carboxymethylcellulose containing aldehyde groups, said at least one oxidized carboxymethylcellulose having a weight-average molecular weight of about 5,000 to about 100,000 Daltons, and an equivalent weight per aldehyde group of about 125 to about 750 Daltons;
or applying (b) followed by (a) and mixing (a) and (b) on the site;
or
premixing (a) and (b) and applying the resulting mixture to the site.