Microneedle device having a peptide therapeutic agent and an amino acid and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-10154957-B2
Application number	US-201715480813-A
Country	US
Kind code	B2
Filing date	Apr 6, 2017
Priority date	Nov 30, 2011
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

A medical device including an array of microneedles and a coating disposed on or within the microneedles and a method of making such a device are disclosed. The coating includes a peptide therapeutic agent and an amino acid. A method of stabilizing a peptide therapeutic agent with an amino acid on an array of microneedles is also disclosed. In some cases, the peptide therapeutic agent and the amino acid either both have a net positive charge or both have a net negative charge. In some cases, the peptide therapeutic agent is histidine.

First claim

What is claimed is:

1. A medical device comprising:
an array of microneedles; and
a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,

wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 2:1, wherein the histidine stabilizes the peptide therapeutic agent in the coating, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .

2. The medical device of claim 1 , wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 1.5:1.

3. A method of making a medical device comprising an array of microneedles and a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,
wherein the molar ratio of the histidine to the peptide therapeutic agent is less than 2:1, the method comprising:
providing an aqueous composition comprising the peptide therapeutic agent and histidine, wherein the molar ratio of the histidine to the peptide therapeutic agent in the aqueous composition is less than 2:1;
contacting the microneedles with the aqueous composition; and
volatilizing a portion of the aqueous composition to provide a coating on at least a portion of the microneedles, wherein the coating comprises at least the peptide therapeutic agent and the histidine, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .

4. The method of claim 3 , wherein the aqueous composition has a pH in a range from 3 to 11.

5. The method of claim 3 , wherein the molar ratio of histidine to the peptide therapeutic agent is less than 1.5:1.

6. The method of claim 3 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.

7. The method of claim 3 , wherein the aqueous composition further comprises a buffer, wherein the buffer comprises phosphate, acetate, citrate, or tris(hydroxymethyl)aminomethane.

8. The method of claim 3 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.

9. The method of claim 3 , wherein the aqueous composition is substantially free of sorbitol.

10. The medical device of claim 1 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.

11. The medical device of claim 1 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.

12. The medical device of claim 1 , wherein the coating is substantially free of sorbitol.

13. A medical device comprising:
an array of microneedles; and
a coating on or within at least a portion of the microneedles, wherein the coating comprises:
a peptide therapeutic agent; and
histidine,

wherein the molar ratio of the histidine to the peptide therapeutic agent is in a range from 0.25:1 to 55:1, and wherein the peptide therapeutic agent is a parathyroid hormone-related protein (PTHrP) analogue represented by formula [Glu 22,25 ,Leu 23,28,31 ,Aib 29 ,Lys 26,30 ]hPTHrP(1-34)NH 2 .

14. The medical device of claim 13 , wherein the histidine stabilizes the peptide therapeutic agent in the coating.

15. The medical device of claim 13 , wherein histidine is present in the coating in a range from 0.1 to 15 percent by weight, based on the total weight of the coating.

16. The medical device of claim 13 , wherein the coating is present on the microneedles in an average amount of 0.01 to 2 micrograms per microneedle.

17. The medical device of claim 13 , wherein the coating is substantially free of sorbitol.

18. The medical device of claim 13 , wherein the array of microneedles comprises a dissolvable matrix material.

19. The medical device of claim 13 , wherein at least some of the microneedles are hollow.

Assignees

• 3M Innovative Properties Co

Inventors

• Zhang Ying
• Fenn Percy T
• Johnson Peter R

Classifications

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K38/28

  Insulins · CPC title

• A61K9/0021 Primary

  Intradermal administration, e.g. through microneedle arrays or needleless injectors · CPC title

• A61K38/23

  Calcitonins · CPC title

• A61K31/4172

  Imidazole-alkanecarboxylic acids, e.g. histidine · CPC title