تفاعل #1483113

ord-24bf91850e6548a7ade645c227b81ec0

معادلة التفاعل

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

→

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

المردود 70.0%

المتفاعلات

—

PLGA

Leuprolide acetate

الكواشف

لا شيء

المذيبات

CH2Cl2

BnOH

ظروف التفاعل

الظروف التفصيلية

See reaction.notes.procedure_details.

المعالجة

1
workup.ADDITIONadded to the polymer solution
2
أخرىyielding a homogeneous organic phase
3
أخرىto provide an emulsion
4
أخرىThe emulsion was collected directly into a 0.3% PVA solvent extraction solution (150 mL)
5
استخلاصto extract EtOAc
6
ترشيحHardened microparticles were collected by filtration
7
غسيلwashed with water, air
8
أخرىdried
9
أخرىstored at 4° C

الإجراء التجريبي

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 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 BI (140 mg, 70.0% yield) with a median particle size 50.1 μm. The core load (1.99%), encapsulation efficiency (9.95%) and in vitro burst (1.63%) were determined by RP-HPLC assay.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08900636B2uspto-grants-2014_12