Sustained release formulations
View Patent ↗A composition for sustained release comprises a carrier material containing a non-polymeric, non-water soluble liquid material having a viscosity of at least 5,000 cP at 37° C. that does not crytallize neat under ambient physiological conditions, a multivalent metal cation, and growth hormone.
1. A composition for sustained release, comprising:
a carrier material comprising a non-polymeric, non-water soluble liquid material having a viscosity of at least 5,000 cP at 37° C. that does not crystallize neat under ambient physiological conditions;
growth hormone; and
a multivalent metal cation;
wherein the composition releases at most 4% of the growth hormone in vitro within the first 24 hours as determined by Release Rate Determination.
2. The composition of claim 1 , wherein the liquid material is a stearate ester, a stearate amide, a long-chain fatty acid amide, a long-chain fatty alcohol, a long-chain ester, or a disaccharide ester.
3. The composition of claim 1 , wherein the liquid material is acetylated sucrose distearate.
4. The composition of claim 1 , wherein the liquid material is disaccharide acetate butyrate.
5. The composition of claim 4 , wherein the liquid material is sucrose acetate isobutyrate.
6. The composition of claim 5 , wherein the growth hormone is human growth hormone.
7. The composition of claim 5 , wherein the multivalent metal cation has a valence of two.
8. The composition of claim 7 , wherein the multivalent metal cation is Zn 2+ .
9. The composition of claim 5 , further comprising a solvent.
10. A composition for sustained release, comprising:
sucrose acetate isobutyrate;
a solvent;
zinc; and
growth hormone;
wherein the composition releases at most 4% of the growth hormone in vitro within the first 24 hours as determined by Release Rate Determination.
11. The composition of claim 10 , wherein the composition has a viscosity less than 1000 cP at room temperature.
12. The composition of claim 10 , wherein the composition has a viscosity less than 200 cP at room temperature.
13. The composition of claim 10 , wherein the solvent is ethanol, benzyl benzoate, miglyol, propylene carbonate, benzyl alcohol, ethyl lactate, glycofurol, N-methylpyrrolidone, 2-pyrrolidone, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, triacetin, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, or 1-dodecyazacycloheptan-2-one.
14. The composition of claim 10 , wherein the solvent is ethanol, benzyl benzoate, miglyol, propylene carbonate, or benzyl alcohol.
15. The composition of claim 10 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 85:15 w/w.
16. The composition of claim 10 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 75:25 w/w.
17. The composition of claim 10 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
18. The composition of claim 10 , wherein the molar ratio of zinc to growth hormone is from 100:1 to 1:1.
19. The composition of claim 10 , wherein the molar ratio of zinc to growth hormone is from 20:1 to 1:1.
20. The composition of claim 10 , wherein the molar ratio of zinc to growth hormone is from 10:1 to 1:1.
21. The composition of claim 10 , comprising:
a sucrose acetate isobutyrate to solvent ratio from 50:50 w/w to 85:15 w/w, wherein the sucrose acetate isobutyrate and solvent together form a liquid; and
a zinc to growth hormone molar ratio from 100:1 to 1:1, wherein the zinc and growth hormone together form a complex.
22. The composition of claim 21 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 75:25 w/w.
23. The composition of claim 21 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
24. The composition of claim 21 , wherein the molar ratio of zinc to growth hormone is from 20:1 to 1:1.
25. The composition of claim 21 , wherein the molar ratio of zinc to growth hormone is from 10:1 to 1:1.
26. A method of administering growth hormone, comprising:
injecting the composition of claim 1 into a patient in need of said growth hormone.
27. The method of claim 26 , wherein less than 0.2% of the growth hormone is released within 24 hours of administration.
28. The method of claim 26 , wherein the percentage of the growth hormone released within a 24 hour period is from 0.05% to 3%.
29. The method of claim 26 , wherein the percentage of the growth hormone released within a 24 hour period is from 1% to 3%.
30. A method of administering growth hormone, comprising:
injecting the composition of claim 10 into a patient in need of said growth hormone.
31. The method of claim 30 , wherein less than 0.2% of the growth hormone is released within 24 hours of administration.
32. The method of claim 30 , wherein the percentage of the growth hormone released within a 24 hour period is from 0.05% to 3%.
33. The method of claim 30 , wherein the percentage of the growth hormone released within a 24 hour period is from 1% to 3%.
34. A method of administering growth hormone, comprising:
injecting the composition of claim 21 into a patient in need of said growth hormone.
35. The method of claim 34 , wherein less than 0.2% of the growth hormone is released within 24 hours of administration.
36. The method of claim 34 , wherein the percentage of the growth hormone released within a 24 hour period is from 0.05% to 3%.
37. The method of claim 34 , wherein the percentage of the growth hormone released within a 24 hour period is from 1% to 3%.
38. A method of making a sustained release composition, comprising:
mixing a complex and a liquid carrier to form said sustained release composition;
wherein said liquid carrier comprises sucrose acetate isobutyrate; and
wherein said complex comprises growth hormone and Zn 2+ ;
wherein said sustained release composition releases at most 4% of the growth hormone in vitro within the first 24 hours as determined by Release Rate Determination.
39. The method of claim 38 , wherein said sustained release composition has a viscosity less than 1000 cP at room temperature.
40. The method of claim 38 , wherein said sustained release composition has a viscosity less than 200 cP at room temperature.
41. The method of claim 38 , wherein the molar ratio of zinc to growth hormone is from 100:1 to 1:1.
42. The method of claim 38 , wherein the molar ratio of zinc to growth hormone is from 10:1 to 1:1.
43. The method of claim 38 , wherein said liquid carrier further comprises a solvent.
44. The method of claim 43 , wherein said solvent is ethanol, benzyl benzoate, miglyol, propylene carbonate, or benzyl alcohol.
45. The method of claim 43 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 85:15 w/w.
46. The method of claim 43 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
47. The method of claim 43 , wherein said sustained release composition comprises:
a sucrose acetate isobutyrate to solvent ratio from 50:50 w/w to 85:15 w/w, wherein the sucrose acetate isobutyrate and solvent together form said liquid carrier;
a zinc to growth hormone molar ratio from 100:1 to 1:1, wherein the zinc and growth hormone together form said complex; and
a liquid carrier to complex ratio from 95:5 v/w to 85:15 v/w.
48. The method of claim 47 , wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
49. The method of claim 47 , wherein the molar ratio of zinc to growth hormone is from 10:1 to 1:1.