Cholic Acid → Pamoic Acid

HRID 539414

반응식

[CH:1]1[CH:6]=[C:5]2[CH:7]=[C:8]([C:27]([OH:29])=[O:28])[C:9]([O-:26])=[C:10]([CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[C:14]([C:22]([OH:24])=[O:23])[C:13]=3[O-:25])[C:4]2=[CH:3][CH:2]=1.[Na+].[Na+].C[C@@H]([C@@H]1[C@@]2(C)[C@@H](O)C[C@@H]3[C@@]4(C)CC[C@@H](O)C[C@H]4C[C@@H](O)[C@H]3[C@@H]2CC1)CCC(O)=O>>[CH:1]1[CH:2]=[CH:3][C:4]2[C:5](=[CH:7][C:8]([C:27]([OH:29])=[O:28])=[C:9]([OH:26])[C:10]=2[CH2:11][C:12]2[C:13]([OH:25])=[C:14]([C:22]([OH:24])=[O:23])[CH:15]=[C:16]3[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]3)[CH:6]=1

참가 물질

반응물 2

HCID 221493Cholic Acid

HCID 54676156Disodium pamoate

생성물 1

HCID 8546Pamoic Acid

실험 절차

Alternative organic ions in addition to pamoate were investigated to explore the general utility of the present invention. Microparticle formulations were prepared by an oil-in-water emulsion/solvent extraction method. PLGA polymer (MW 24,000, 160 mg) was dissolved in EtOAc (1000 μL). Octreotide acetate (40 mg) was dissolved in BnOH (1000 μL) and added to the polymer solution yielding a homogenous organic phase. The resulting organic phase was combined with a 1% PVA aqueous phase containing 10-20 mM organic acid as its sodium salt 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 resulted in microparticle formulations with octreotide core loads between 6.8 and 15.3% as measured by RP-HPLC (Table 8). The effects of the tested organic ions on core load are revealing. Formulations AM-AP show no increase in the measured core load relative to control containing sodium pamoate (Formulations AT, AU, AY, Table 8). In contrast formulations AQ-AS, AV-AX and AZ-BB, which employed organic acids ranging from cholic acid to bicylic aromatics, provided peptide core loads comparable to pamoic acid (Table 8). These results imply that organic acids with appropriate physiochemical properties can be substituted for pamoic acid to produce comparable microparticle formulations.

후처리

temperatureno increase in the measured core load relative to control

출처 및 근거

ORD 기록: ord-3140a0dee4984ddd8fa44507f66bb16b
출처 데이터셋: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US08871269B2

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