STABLE COMPOSITIONS OF NEUROACTIVE PEPTIDES
The disclosure relates to intravenous formulations of GLYX peptides for treating CNS Disorders such as depression, neuropathic pain, or anxiety.
1 . A stable, aqueous composition suitable for intravenous injection, comprising:
60 mg/mL to about 200 mg/mL of a pharmaceutically active compound having the formula:
or a pharmaceutically acceptable salt thereof;
water for injection; and
an acid; wherein the stable, aqueous composition has a pH of from about 3.9 to about 5.5 at 25° C.
2 . The stable, aqueous composition of claim 1 , comprising from about 125 mg/mL to about 175 mg/mL of the pharmaceutically active compound.
3 . The stable, aqueous composition of claim 1 , comprising about 150 mg/mL of the pharmaceutically active compound.
4 . The stable, aqueous composition of claim 1 , comprising about 75 mg/mL of the pharmaceutically active compound.
5 - 13 . (canceled)
14 . The stable, aqueous composition of claim 1 , wherein upon administration of a dose of the stable, aqueous liquid composition that comprises about 150 mg/mL of the pharmaceutically active compound and has a volume of about 3 mL to a patient, a physiological osmolality of from about 800 mOsmol/kg to about 900 mOsmol/kg is obtained in said patient.
15 . The stable, aqueous composition of claim 1 , upon administration of a dose of the stable, aqueous liquid composition that comprises about 75 mg/mL of the pharmaceutically active compound and has a volume of about 3 mL to a patient, a physiological osmolality of from about 375 mOsmol/kg to about 475 mOsmol/kg is obtained in said patient.
16 . The stable, aqueous composition of claim 1 , wherein the composition has a minimal amount of one or more of degradation products each selected from the group consisting of cyclo proline-threonine (diketopiperazine), Thr-Pro-Pro-Thr (SEQ ID NO: 13 Pro-Pro-Thr (SEQ ID NO: 15), Pro-Pro-Thr-NH2 (SEQ ID NO: 15), Thr-Pro, Pro-Thr, Pro-Thr-NH2, proline and/or threonine (SEQ ID NO: 18) after 10 days at room temperature or after 20 days at room temperature.
17 . The stable, aqueous composition of claim 1 , wherein the composition has minimal amounts of one or more of degradation products each selected from the group consisting of diketopiperazine, Thr-Pro-Pro-Thr (SEQ ID NO: 13), Pro-Pro-Thr (SEQ ID NO: 15), Pro-Pro-Thr-NH2 (SEQ ID NO: 15), Thr-Pro, Pro-Thr, Pro-Thr-NH2, proline and/or threonine (SEQ ID NO: 18) after 1 month at 0° C. or below
18 - 22 . (canceled)
23 . A pre-filled syringe comprising a single dose of the stable, aqueous liquid composition of claim 1 .
24 . The pre-filled syringe of claim 23 , wherein the single dose has a volume of about 1 mL to about 4 mL.
25 . The pre-filled syringe of claim 23 , wherein the single dose has a volume of about 3 mL.
26 . A composition comprising:
about 150 mg/mL of a compound represented by:
water for injection; and
and hydrochloric acid, wherein the composition has a pH of about 4.1 to about 4.7 at 25° C.
27 . A pharmaceutically acceptable dose suitable for injection comprising:
about 450 mg of a compound represented by:
water; and
an acid providing chloride ions in the aqueous composition, wherein the dose has a pH of about 4.5 and a volume of about 3 mL.
28 . A pharmaceutically acceptable dose suitable for injection comprising:
about 225 mg of a compound represented by:
water for injection; and
hydrochloric acid, wherein the does has a pH of about 4.5 and a volume of about 3 mL.
29 - 33 . (canceled)