Reaktion #1483116

ord-ad58bda64d674ce1aa41b2fa12c6883f

Reaktionsgleichung

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
→
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
Ausbeute 71.5%

Edukte

—
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

Reagenzien

Keine

Lösungsmittel

CCOC(C)=O
EtOAc
CO
MeOH
CCOC(C)=O
EtOAc

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.ADDITIONadded to the polymer solution
  2. 2
    Sonstigeyielding a milky suspension as the organic phase
  3. 3
    Sonstigeto provide an emulsion
  4. 4
    SonstigeThe emulsion was collected directly into a 10 mM sodium phosphate (pH 8, 0° C., 150 mL) solvent extraction solution
  5. 5
    Extraktionto extract EtOAc
  6. 6
    FiltrationHardened microparticles were collected by filtration
  7. 7
    Waschenwashed with water, air
  8. 8
    Sonstigedried
  9. 9
    Sonstigestored at 4° C

Vorschrift

PLGA polymer (MW 13,000, 180 mg) was dissolved in EtOAc (900 μL). Oxytocin acetate (20 mg) was dissolved in MeOH (100 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 5% EtOAc to provide an emulsion. The emulsion was collected directly into a 10 mM sodium phosphate (pH 8, 0° C., 150 mL) solvent extraction solution and stirred for four hours while warming to room temperature to extract EtOAc. Hardened microparticles were collected by filtration, washed with water, air dried and stored at 4° C. This provided formulation BL (143 mg, 71.5% yield) with a median particle size 44.0 μm. The core load (1.67%), encapsulation efficiency (16.7%) and in vitro burst (46.3%) were determined by RP-HPLC assay.

Quelle

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