Controllably degradable compositions and methods

Patent metadata

Field	Value
Publication number	US-10780195-B2
Application number	US-201615739217-A
Country	US
Kind code	B2
Filing date	Jun 23, 2016
Priority date	Jun 24, 2015
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

Abstract

Methods, compositions, kits, and drug delivery devices are provided for treating, adhering, or sealing biological tissues. The methods include combining a first solution that includes an oligomer/polymer component and a second solution that includes a dendrimer component, and at least one of the oligomer/polymer component and dendrimer component includes at least one substituent that is capable of photoreversible dimerization. The reversible dimerization of the substituent may allow for the reversible dimerization and/or polymerization of one or more components. The substituent that is capable of photoreversible dimerization may be active by the application of light, such as UV light.

First claim

We claim:

1. A method for treating, adhering, or sealing biological tissue, the method comprising:
providing a first solution comprising a polymer component having three or more aldehyde groups, wherein the polymer component comprises two or more oligomer units substituted with one or more first substituents capable of photoreversible dimerization, wherein the one or more first substituents capable of photoreversible dimerization are dimerized to convert the two or more oligomer units to the polymer component;
providing a second solution comprising a dendrimer component, wherein the dendrimer component comprises a dendrimer having at least 2 branches with one or more surface groups;
combining the first and second solutions together to produce an adhesive formulation and contacting one or more biological tissues with the adhesive formulation; and
allowing the adhesive formulation to cure in contact with the one or more biological tissues.

2. The method of claim 1 , wherein the dendrimer is substituted with one or more second substituents capable of photoreversible dimerization.

3. The method of claim 2 , wherein the one or more first substituents capable of photoreversible dimerization and the one or more second substituents capable of photoreversible dimerization are the same.

4. The method of claim 2 , further comprising contacting the adhesive formulation with light having a wavelength sufficient to dimerize the one or more second substituents capable of photoreversible dimerization.

5. The method of claim 4 , wherein allowing the adhesive formulation to cure and contacting the adhesive formulation with light are performed simultaneously.

6. The method of claim 4 , further and subsequently comprising contacting the adhesive formulation with light having a wavelength sufficient to reverse the dimerization of the one or more first substituents capable of photoreversible dimerization and/or the one or more second substituents capable of photoreversible dimerization.

7. The method of claim 1 , wherein at least one of the two or more oligomer units comprises an oligosaccharide.

8. The method of claim 1 , wherein the method further comprises contacting the adhesive formulation with an enzyme effective to degrade the polymer component.

9. The method of claim 1 , wherein the method further comprises contacting the adhesive formulation with an amine effective to alter an equilibrium of imine bond formation between the polymer component and the dendrimer.

10. The method of claim 1 , wherein the method further and subsequently comprises altering the pH of the adhesive formulation in an amount effective to facilitate degradation of the polymer component.

11. A method for treating, adhering, or sealing biological tissue, the method comprising:
providing a first solution comprising an oligomer component having three or more aldehyde groups, wherein the oligomer component comprises two or more oligomer units substituted with one or more first substituents capable of photoreversible dimerization, and wherein the one or more first substituents capable of photoreversible dimerization are not dimerized;
providing a second solution comprising a dendrimer component, wherein the dendrimer component comprises a dendrimer having at least 2 branches with one or more surface groups;
combining the first and second solutions together to produce an adhesive formulation and contacting one or more biological tissues with the adhesive formulation;
allowing the adhesive formulation to cure in contact with the one or more biological tissues; and
contacting the adhesive formulation with light having a wavelength sufficient to dimerize the one or more first substituents capable of photoreversible dimerization to convert at least a portion of the oligomer component to a polymer component.

12. The method of claim 11 , wherein the dendrimer is substituted with one or more second substituents capable of photoreversible dimerization.

13. The method of claim 12 , wherein the one or more first substituents capable of photoreversible dimerization and the one or more second substituents capable of photoreversible dimerization are the same.

14. The method of claim 11 , wherein allowing the adhesive formulation to cure and contacting the adhesive formulation with light are performed simultaneously.

15. The method of claim 11 , further and subsequently comprising contacting the adhesive formulation with light having a wavelength sufficient to reverse the dimerization of the one or more first substituents capable of photoreversible dimerization to convert at least a portion of the polymer component to the oligomer component.

16. A kit for making an adhesive comprising:
a first part which includes a first solution comprising (i) an oligomer component having three or more aldehyde functional groups, or (ii) a polymer component having three or more aldehyde functional groups, wherein the oligomer component and the polymer component comprise two or more oligomer units substituted with one or more first substituents capable of photoreversible dimerization, wherein the one or more first substituents capable of photoreversible dimerization are not dimerized in the oligomer component, and dimerized in the polymer component; and
a second part which includes a second solution comprising a dendrimer component, wherein the dendrimer component comprises a dendrimer having at least 2 branches with one or more surface groups.

17. The kit of claim 16 , wherein the one or more first substituents capable of photoreversible dimerization of the first part are dimerized, and the first part comprises the polymer component.

18. The kit of claim 16 , wherein at least one of the two or more oligomer units comprises an oligosaccharide.

19. The kit of claim 16 , wherein the dendrimer is substituted with one or more second substituents capable of photoreversible dimerization.

20. The kit of claim 19 , wherein the one or more first substituents capable of photoreversible dimerization and the one or more second substituents capable of photoreversible dimerization are the same.

21. The kit of claim 16 , further comprising a UV light source to activate or deactivate the one or more first substituents capable of photoreversible dimerization.

22. A therapeutic or prophylactic composition comprising:
an oligomer component or a polymer component, wherein the oligomer component and the polymer component (i) have three or more aldehyde functional groups, and (ii) comprise two or more oligomer units substituted with one or more first substituents capable of photoreversible dimerization, wherein the one or more first substituents capable of photoreversible dimerization are not dimerized in the oligomer component, and dimerized in the polymer component;
a dendrimer component, wherein the dendrimer component comprises a dendrimer having at least 2 branches with one or more surface groups; and
at least one drug or cell combined with (i) the oligomer component or the polymer component, (ii) the dendrimer component, or (iii) both the dendrimer component and one of the oligomer component or the polymer component.

23. The composition of claim 22 , wherein the one or more first substituents, capable of photoreversible dimerization are dimerized, and the composition comprises the polymer component.

24. The composition of claim 22 , wherein the dendrimer is substituted with one or more second substituents capable of photorevers

Assignees

• Massachusetts Inst Technology
• Massachusetts Instiitute Of Tech

Inventors

• Artzi Natalie
• Edelman Elazer R
• Kelmansky Regina
• Cervantes Marc Mier
• Zhang Yi

Classifications

• A61L26/0066

  Medicaments; Biocides · CPC title

• A61L24/043 Primary

  Mixtures of macromolecular materials · CPC title

• A61L26/0052

  Mixtures of macromolecular compounds · CPC title

• A61L24/0015

  Medicaments; Biocides · CPC title

• C08L5/02

  Dextran; Derivatives thereof · CPC title