반응 #2254168

ord-ea165849b33c47658c121f0523af428f

반응 방정식

CC#N
acetonitrile
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
MAN
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
MAN
→
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC.OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
TAC MAN

반응물

CC#N
acetonitrile
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
mannitol
—
solids
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
MAN
OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
MAN

시약

없음

용매

O
water

반응 조건

온도
-50°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The composition was prepared
  2. 2
    온도is cooled
  3. 3
    기타The frozen compositions were then collected
  4. 4
    기타the solvent was removed by lyophilization
  5. 5
    기타were stored at room temperature under vacuum
  6. 6
    기타The result of XRD characterization (
  7. 7
    기타The result of SEM (

실험 절차

A formulation of tacrolimus (TAC) was produced using TAC and mannitol (MAN) in ratio 1:1. The TAC:MAN 1:1 formulation was prepared using the ultra-rapid freezing (URF) process. The composition was prepared by dissolving TAC and MAN at a 1:1 ratio and 0.75% solids in a 60/40 mixture of acetonitrile and water. The solution of drug and excipient was applied to the surface of a solid substrate, which is cooled using a cryogenic substrate maintained at −50° C. The frozen compositions were then collected and the solvent was removed by lyophilization using a VirTis Advantage Lyophilizer (VirTis Company, Inc. Gardiner, N.Y.). The dried powders were stored at room temperature under vacuum. The result of XRD characterization (following the procedure in example 2) is that the composition is amorphous. The result of SEM (following the procedure in example 4) is that the morphology is nanostructured aggregates with small primary particles consisting of TAC and MAN with primary particle sizes of about 100-200 nm.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09044391B2uspto-grants-2015_06