Insulin preparations for pulmonary delivery containing menthol
AssigneeNovo Nordisk A/S
InventorSvend Havelund
Life of this patent
Estimating the term…
Abstract
A stable, aqueous insulin formulation suitable for pulmonary delivery is disclosed. The formulation has increased convenience for the patient and improved bioavailability of insulin.
Claims20
A method for enhancing the bioavailability of human insulin or an analogue or derivative upon pulmonary administration, said method comprising:
- providing an aqueous insulin formulation comprising:
- human insulin or an analogue or a derivative thereof, 2 to 5 Zn2+ ions per six molecules of insulin, 3 to 18 phenolic molecules per six molecules of insulin, and menthol, wherein:
- (i) said insulin analogue or derivative exhibits insulin bioactivity, (ii) said insulin analogue comprises (a) human insulin in which one or more amino acids have been deleted and/or replaced by other amino acids or (b) human insulin containing at least one additional amino acid, (iii) said insulin derivative comprises human insulin in which at least one organic substituent is bound to one or more of the amino acids of said insulin;
- (iv) said phenolic molecules are selected from the group consisting of phenol, m-cresol, chloro-cresol, thymol, 7-hydroxyindole, 2,6-dihydroxynaphthalene, 2,7-dihydroxynaphthalene, and mixtures of any of the foregoing phenolic molecules and (v) said menthol increases the bioavailability of said insulin, analogue, or derivative following pulmonary administration.
A formulation comprising (i) human insulin or an analogue or a derivative thereof, (ii) 2 to 5 Zn2+ ions per six molecules of insulin, (iii) 3 to 18 phenolic molecules per six molecules of insulin, (iv) menthol, and (v) between 0.001% by weight and 1% by weight of a surfactant.
A formulation comprising (i) an analogue of human insulin, (ii) 2 to 5 Zn2+ ions per six molecules of insulin, (iii) 3 to 18 phenolic molecules per six molecules of insulin, and (iv) menthol, wherein (a) said analogue comprises Asp, Lys, Leu, Val or Ala at position B28 and Lys or Pro at position B29;
- or (b) said analogue is des(B28-30), des(B27) or des(B30) human insulin.
A formulation comprising (i) a derivative of human insulin, (ii) 2 to 5 Zn2+ ions per six molecules of insulin, (iii) 3 to 18 phenolic molecules per six molecules of insulin, and (iv) menthol, wherein said derivative of human insulin has one or more lipophilic substituents.
A method of administering insulin to a patient suffering from type I or type II diabetes, said method comprising administering by inhalation to said patient an insulin formulation comprising human insulin or an analogue or a derivative thereof, 2 to 5 Zn2+ ions per six molecules of insulin, 3 to 18 phenolic molecules per six molecules of insulin, and menthol, wherein:
- (i) said insulin analogue or insulin derivative exhibits insulin bioactivity, (ii) said insulin analogue comprises (a) human insulin in which one or more amino acids have been deleted and/or replaced by other amino acids or (b) human insulin containing at least one additional amino acid, (iii) said insulin derivative comprises human insulin in which at least one organic substituent is bound to one or more of the amino acids of said insulin;
- and (iv) said phenolic molecules are selected from the group consisting of phenol, m-cresol, chloro-cresol, thymol, 7-hydroxyindole, 2,6-dihydroxynaphthalene, 2,7-dihydroxynaphthalene, and mixtures of any of the foregoing phenolic molecules, and (v), said menthol increases the bioavailability of said insulin, insulin analogue, or insulin derivative following said administration.
Dependencies are inferred from the claim text.