Reaction #1483117

ord-75d558ae9381413bafa6cd500e091d1b

Reaction equation

CC(=O)O.CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
Oxytocin acetate
O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O.[Na+]
disodium pamoate
→
CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
Oxytocin
Yield 79.0%

Reactants

—
PLGA
CC(=O)O.CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
Oxytocin acetate
O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O.[Na+]
disodium pamoate

Reagents

None

Solvents

CCOC(C)=O
EtOAc
CO
MeOH

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.ADDITIONadded to the polymer solution
  2. 2
    Otheryielding a milky suspension as the organic phase
  3. 3
    Otherto provide an emulsion
  4. 4
    OtherThe emulsion was collected directly into a 0.3% PVA solvent extraction solution (150 mL)
  5. 5
    Extractionto extract EtOAc
  6. 6
    FiltrationHardened microparticles were collected by filtration
  7. 7
    Washwashed with water, air
  8. 8
    Otherdried
  9. 9
    Otherstored at 4° C

Procedure

PLGA polymer (MW 24,000, 180 mg) was dissolved in EtOAc (1800 μL). Oxytocin acetate (40 mg) was dissolved in MeOH (200 μL) and added to the polymer solution yielding a milky suspension as the organic phase. The resulting organic phase was combined with a 1% PVA aqueous phase containing 10 mM disodium pamoate to provide an emulsion. The emulsion was collected directly into a 0.3% PVA solvent extraction solution (150 mL) and stirred for four hours to extract EtOAc. Hardened microparticles were collected by filtration, washed with water, air dried and stored at 4° C. This provided formulation BM (158 mg, 79.0% yield) with a median particle size 144 μm. The core load (8.9%), encapsulation efficiency (44.5%) and in vitro burst (21.1%) were determined by RP-HPLC assay.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08900636B2uspto-grants-2014_12