RU2001113283A - MENTOL-INSULIN PREPARATIONS FOR DELIVERY THROUGH EASY - Google Patents

Claims (23)

1. An aqueous preparative form of insulin, comprising: human insulin or an analogue or derivative thereof, from 2 to 5 Zn ^{2+ ions} per six insulin molecules, from 3 to 18 phenolic molecules per six insulin molecules, and menthol.  2. The preparative form of insulin according to claim 1, containing from 0.5 to 4 mm menthol.  3. The preparative form of insulin according to claim 1 or 2, containing from 4 to 9 phenolic molecules per six insulin molecules, preferably about 6 phenolic molecules per six insulin molecules.  4. The preparative form of insulin according to any one of the preceding paragraphs, in which the phenolic molecules are selected from the group consisting of phenol, m-cresol, chlorocresol, thymol, or any mixture thereof.  5. The preparative form of insulin according to any one of the preceding paragraphs, comprising from 0.3 to 20 mm, preferably from 0.6 to 15 mm, more preferably from 3 to 12 mm of human insulin or its analogue or derivative thereof.  6. A formulation of insulin according to any one of the preceding claims, comprising less than 50 mM, preferably less than 30 mM chloride, more preferably 5 to 20 mM chloride.  7. The preparative form of insulin according to any one of the preceding paragraphs, containing less than 10 mm any anion other than chloride and acetate.  8. The preparative form of insulin according to any one of the preceding paragraphs, containing up to 5 mm phosphate. 9. The preparative form of insulin according to any one of the preceding paragraphs, containing from 2 to 4 Zn ²⁺ ions, preferably from 2.2 to 3.2 Zn ²⁺ ions per six insulin molecules.  10. The preparative form of insulin according to any one of the preceding paragraphs, additionally containing from 5 to 150 mm zwitterionic amine, preferably glycylglycine or glycine.  11. The preparative form of insulin according to any one of the preceding paragraphs, optionally containing from 5 to 50 mm Trishydroxymethyl-aminomethane.  12. The preparative form of insulin according to any one of the preceding paragraphs, containing sodium ions, potassium ions, or a mixture of them as cations.  13. The preparative form of insulin according to any one of the preceding paragraphs, optionally containing a surfactant in the range between 0.001 wt. % and 1 wt. %, preferably Tween 20 or Polox 188.  14. The preparative form of insulin according to any one of the preceding paragraphs, containing human insulin.  15. The preparative form of insulin according to any one of paragraphs. 1-13, containing a human insulin analogue in which position B28 represents Asp, Lys, Leu, Val or Ala, and position B29 represents Lys or Pro; or des (B28-B30), des (B27) or des (B30) human insulin. 16. The insulin formulation of claim 15, comprising a human insulin analogue in which position B28 is Asp or Lys and position B29 is Lys or Pro, preferably Asp ^{B28 is} human insulin or Lys ^B28 Pro ^{B29 is} human insulin.  17. The preparative form of insulin according to any one of paragraphs. 1-13, containing a derivative of human insulin having one or more lipophilic substituents, preferably acylated insulin. 18. The preparative form of insulin according to claim 17, wherein the insulin derivative is selected from the group consisting of B29-N ^ε- myristoyl des (B30) human insulin, B29-N ^ε -palmitoyl des (B30) human insulin, B29- N ^{ε ε-} myristyl of human insulin, B29-N ^ε- palmitoyl of human insulin, B28-N ^ε- myristoyl Lys ^B28 Pro ^B29 human insulin, B28-N ^ε -palmito-ylus ^B28 Pro ^B29 human insulin, B30-N ^ε- myristoyl-Thr ^B29 Lys ^B30 human insulin, B30-N ^ε -palmitoyl-Thr ^B29 Lys ^B30 human insulin, B29-N ^ε - (N-palmitoyl-γ-glutamyl) des (B30) human insulin, B 29-N ^ε - (N-lithocholyl-γ-glutamyl) des (B30) of human insulin, B29-N ^ε - (ω-carboxyheptadecanoyl) -dez (B30) of human insulin and B29-N ^ε - (ω-carboxyheptadecanoyl) human insulin. 19. The preparative form of insulin according to claim 18, wherein the insulin derivative is B29-N ^ε- myristoyl des (B30) human insulin or B29-N ^ε - (N-lithocholyl-γ-glutamyl) des (B30) human insulin .  20. The preparative form of insulin according to any one of the preceding paragraphs, containing an insulin analogue or human insulin, as well as an insulin derivative.  21. The preparative form of insulin according to any one of the preceding paragraphs, having a hydrogen index in the range from 7 to 8.5, preferably from 7.4 to 7.9.  22. A method of treating type I or type II diabetes, comprising administering to a patient in need of such treatment, the insulin formulation of any one of the preceding claims.  23. The method according to p. 22, in which insulin is administered in connection with meals.