Reaction #961268

ord-896d61cbb7894948b4a509a66e7154cd

Reaction equation

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
O=S(=O)([O-])[O-].[NH4+].[NH4+]
ammonium sulfate
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
O=S(=O)([O-])[O-].[NH4+].[NH4+]
ammonium sulfate
→
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.O=S(=O)([O-])[O-]
doxorubicin sulfate

Reactants

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
O=S(=O)([O-])[O-].[NH4+].[NH4+]
ammonium sulfate
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.Cl
doxorubicin hydrochloride
O=S(=O)([O-])[O-].[NH4+].[NH4+]
ammonium sulfate

Reagents

None

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otheris prepared
  2. 2
    workup.DISSOLUTIONis dissolved in a suitable buffer solution (as described above)
  3. 3
    Otherto get a concentration of at least 25 mM

Procedure

A preferred non-pegylated liposome of the present invention is loaded with doxorubicin hydrochloride and is prepared using methods described above. In one embodiment, when loading doxorubicin hydrochloride using the active loading procedure described above, the drug is dissolved in a suitable buffer solution (as described above) before loading to get a concentration of at least 25 mM. When the active loading process involves an ammonium sulfate gradient, the ammonium sulfate reacts with doxorubicin hydrochloride to form doxorubicin sulfate. Doxorubicin sulfate is insoluble and remains inside the liposomes after loading. Once any unentrapped or free drug is removed from loaded liposomes, the drug loaded liposomes are diluted using aqueous buffer solution to achieve the required drug concentration. The preferred buffer solution used is sucrose-histidine buffer solution as discussed previously.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08980310B2uspto-grants-2015_03