Noncrushable pill formulations

Patent metadata

Field	Value
Publication number	US-11541125-B2
Application number	US-201716469786-A
Country	US
Kind code	B2
Filing date	Dec 19, 2017
Priority date	Dec 19, 2016
Publication date	Jan 3, 2023
Grant date	Jan 3, 2023

Abstract

Non-crushable pill formulations and methods of using the formulations are disclosed. A non-crushable pill formulation for preventing unintended use of a drug, comprising a polymer, the polymer forming a polymer backbone of the complex; cross-linkers, the cross-linkers connecting the polymer backbone through covalently bonding to form at least one inner cavity within the complex; and the drug, the drug being trapped either covalently or non-covalently in the at least one inner cavity within the complex, wherein the drug is protected from releasing outside of the complex.

First claim

We claim:

1. A complex for preventing unintended use of a drug, the complex comprising:
an enzyme responsive peptide;
a polymer, the polymer forming a polymer backbone of the complex;
cross-linkers, the cross-linkers connecting the polymer backbone through covalently bonding to form at least one inner cavity within the complex; and
the drug, the drug being trapped either covalently or non-covalently in the at least one inner cavity within the complex,
wherein the drug is protected from releasing outside of the complex and
wherein the enzyme responsive peptide comprises an amino acid having an α-amino group, an α-carboxylic acid group and an ε-amine group covalently bonded with an enzyme substrate comprising phenylalanine, tyrosine, or tryptophan, wherein the α-amino group is covalently bonded with a second amino acid or a peptide, and the α-carboxylic acid is covalently bonded with a first group.

2. The complex of claim 1 , wherein the polymer forms an elastomer.

3. The complex of claim 1 , wherein the polymer is a polysiloxane.

4. The complex of claim 1 , wherein the drug is non-covalently encapsulated in the at least one inner cavity within the complex by a cross-linked elastomeric network.

5. The complex of claim 1 , wherein the cross-linkers further comprise a polymer dithiol or a polymer multithiol.

6. The complex of claim 5 , wherein the polymer dithiol is a polyethylene glycol (PEG) dithiol or the polymer multithiol is a PEG multithiol.

7. The complex of claim 1 , wherein the second amino acid or the peptide comprises a free thiol group.

8. The complex of claim 1 , wherein the first group comprises a free thiol group.

9. The complex of claim 1 , wherein the first group comprises the drug.

10. The complex of claim 1 , wherein the first group comprises the drug attached to the complex through a self-immolative linker.

11. The complex of claim 1 , wherein the enzyme responsive peptide requires digestion by at least one enzyme to cleave the bond between the α-carboxylic acid and the first group or the bond between the α-amino group and the second amino acid or the peptide.

12. The complex of claim 1 , wherein the enzyme responsive peptide requires digestion by two separate enzymes to cleave the bond between the α-carboxylic acid and the first group.

13. The complex of claim 1 , wherein the enzyme responsive peptide is cleavable under the digestion of two enzymes selected from the group consisting of trypsin, chymotrypsin, gastric lipase, pepsin, aminopeptidase, carboxypeptidase, deoxyribonuclease, dipeptidase, elastase, enterokinase, lactase, maltase, pancreatic amylase, pancreatic lipase, sucrase, dextrinase, nucleosidases, phosphatases, and any other enzyme found in the stomach or intestine.

14. The complex of claim 1 , wherein amino acid has the hydrophobic group and the hydrophobic group is an aromatic group.

15. The complex of claim 1 , wherein the amino acid is phenylalanine.

16. The complex of claim 1 , wherein the enzyme responsive peptide is cleavable under the digestion of an enzyme selected from the group consisting of trypsin, chymotrypsin, gastric lipase, pepsin, aminopeptidase, carboxypeptidase, chymotrypsin, trypsin, deoxyribonuclease, dipeptidase, elastase, enterokinase, lactase, maltase, pancreatic amylase, pancreatic lipase, sucrase, dextrinase, nucleosidases, phosphatases, and any other enzyme found in the stomach or intestine.

17. The complex of claim 1 , wherein the enzyme responsive peptide comprises

and the first group is attached at point *.

18. A polymeric formulation for controlled releasing of an active ingredient, the formulation comprising the complex of claim 1 .

Assignees

• Univ California

Inventors

• Maynard Heather D
• Boehnke Natalie
• Paluck Samantha J

Classifications

• A61K47/65 Primary

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• A61K9/2036

  Silicones; Polysiloxanes · CPC title

• A61K47/59 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• C12Y304/11

  Aminopeptidases (3.4.11) · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title