Reaktion #1483114

ord-bcbd7a6521a2452f90b7041c464c39a7

Reaktionsgleichung

CC(=O)O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
Leuprolide acetate
O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O.[Na+]
disodium pamoate
→
CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
Leuprolide
Ausbeute 78.5%

Edukte

—
PLGA
CC(=O)O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
Leuprolide acetate
O=C(O)c1cc2ccccc2c(Cc2c(O)c(C(=O)O)cc3ccccc23)c1O.[Na+]
disodium pamoate

Reagenzien

Keine

Lösungsmittel

ClCCl
CH2Cl2
OCc1ccccc1
BnOH

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.ADDITIONadded to the polymer solution
  2. 2
    Sonstigeyielding a homogeneous organic phase
  3. 3
    Sonstigeto provide an emulsion
  4. 4
    SonstigeThe emulsion was collected directly into a 0.3% PVA solvent extraction solution (100 mL)
  5. 5
    workup.ADDITIONwas added
  6. 6
    workup.STIRRINGstirred for an additional four hours
  7. 7
    FiltrationHardened microparticles were collected by filtration
  8. 8
    Waschenwashed with water, air
  9. 9
    Sonstigedried
  10. 10
    Sonstigestored at 4° C

Vorschrift

PLGA polymer (MW 24,000, 160 mg) was dissolved in CH2Cl2 (1000 μL). Leuprolide acetate (40 mg) was dissolved in BnOH (1000 μL) and added to the polymer solution yielding a homogeneous 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 (100 mL) and stirred for 10 minutes. A secondary extraction solution consisting of 2% isopropanol (200 mL) was added and stirred for an additional four hours. Hardened microparticles were collected by filtration, washed with water, air dried and stored at 4° C. This provided formulation BJ (157 mg, 78.5% yield) with a median particle size 54.0 μm. The core load (9.4%), encapsulation efficiency (47.0%) and in vitro burst (5.31%) were determined by RP-HPLC assay.

Quelle

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