Fast-acting insulin composition comprising a citric acid salt

Patent metadata

Field	Value
Publication number	US-2018236080-A1
Application number	US-201715625684-A
Country	US
Kind code	A1
Filing date	Jun 16, 2017
Priority date	Feb 22, 2017
Publication date	Aug 23, 2018
Grant date	—

Abstract

In embodiments, the present disclosure provides an aqueous pharmaceutical composition that includes insulin in hexameric form, and citric acid or a salt thereof at a concentration from 6 to 30 mM, wherein the composition is suitable for injecting into a diabetic patient to treat diabetes.

First claim

1 . An aqueous pharmaceutical composition comprising:
insulin in hexameric form, and citric acid or a salt thereof at a concentration from 6 to 30 mM,
wherein the composition is suitable for injecting into a diabetic patient to treat diabetes,
wherein the composition does not contain any one of
EDTA,
anionic compounds whose chemical structure includes at least one carboxyl functional group to which is covalently bonded an amino-acid residue,
saccharides whose chemical structure includes at least one carboxyl functional group to which is covalently bonded an amino-acid residue, and
oligosaccharides whose chemical structure includes at least one carboxyl functional group to which is covalently bonded an amino-acid residue.

2 . An aqueous pharmaceutical composition comprising:
insulin in hexameric form, and citric acid or a salt thereof at a concentration from 6 to 30 mM,
wherein the composition is suitable for injecting into a diabetic patient to treat diabetes, and
wherein the composition does not contain more than 80 μg/ml of an insulin accelerant either alone or in combination with citrate.

3 . The aqueous pharmaceutical composition according to claim 1 , wherein the onset of action is at least 10% more rapid than that of a reference composition at the same insulin concentration in absence of citric acid or a salt thereof when measured according to the protocol for the measurement of pharmacodynamics and pharmacokinetics of insulin solutions.

4 . The aqueous pharmaceutical composition according to claim 1 , wherein the onset of appearance is at least 10% more rapid than that of a reference composition at the same insulin concentration in absence of citric acid or a salt thereof when measured according to the protocol for the measurement of pharmacodynamics and pharmacokinetics of insulin solutions.

5 . The aqueous pharmaceutical composition according to claim 1 , wherein the fast uptake of insulin is at least 10% more than that of a reference composition at the same insulin concentration in absence of citric acid or a salt thereof when measured according to the protocol for the measurement of pharmacodynamics and pharmacokinetics of insulin solutions.

6 . The aqueous pharmaceutical composition according to claim 1 , wherein the insulin is insulin lispro or insulin aspart.

7 . The aqueous pharmaceutical composition according to claim 1 , wherein the insulin is insulin lispro.

8 . The aqueous pharmaceutical composition according to claim 1 , wherein the insulin concentration in the composition is between 600 to 1800 μM (100 to 300 U/ml).

9 . The aqueous pharmaceutical composition according to claim 1 , wherein the composition further comprises a surfactant.

10 . The aqueous pharmaceutical composition according to claim 1 , wherein the pH of the composition is from 6.0 to 8.0.

11 . An injection device which contains the aqueous pharmaceutical composition according to claim 1 .

12 . A vial which contains the aqueous pharmaceutical composition according to claim 1 .

13 . A cartridge adapted for being inserted into an injection device and comprising the aqueous pharmaceutical composition according to claim 1 .

14 . A unit dose which contains the aqueous pharmaceutical composition according to claim 1 .

15 . A method of treating diabetes comprising administering to a human patient in need thereof an effective dose of the aqueous pharmaceutical composition according to claim 1 .

16 . A method according to claim 14 , wherein the administering produces an uptake of insulin or an onset of appearance in the patient's blood that is at least 10% more rapid than that for a reference composition with the same concentration of insulin that does not contain the citric acid or salt thereof.

Assignees

• Adocia

Inventors

• Soula Gerard

Classifications

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K38/28

  Insulins · CPC title

• A61K47/12 Primary

  Carboxylic acids; Salts or anhydrides thereof · CPC title