초록 ▼

멜리사잎으로 부터 제조한 천연물 신약 ALS-L1023을 이용한 경구용 망막증식성 치료제 개발을 위하여 다음과 같은 연구를 시행하였다.
ALS-L1023의 대량생산 방법, 기준 및 시험방법, 최적제형을 확립하였으며, 확립된 기준 및 시험방법을 이용한 18개월의 안정성 시험결과를 확보하였다. 효력과 관련하여서는 혈관신생억제작용(MMP 억제작용) 및 VEGF induced huvec proliferation 및 tube formation을 억제하는 기본 메커니즘을 바탕으로 맥락막 신생혈관 동물모델에서 유효성을 입증하였다. 독성시험

멜리사잎으로 부터 제조한 천연물 신약 ALS-L1023을 이용한 경구용 망막증식성 치료제 개발을 위하여 다음과 같은 연구를 시행하였다.
ALS-L1023의 대량생산 방법, 기준 및 시험방법, 최적제형을 확립하였으며, 확립된 기준 및 시험방법을 이용한 18개월의 안정성 시험결과를 확보하였다. 효력과 관련하여서는 혈관신생억제작용(MMP 억제작용) 및 VEGF induced huvec proliferation 및 tube formation을 억제하는 기본 메커니즘을 바탕으로 맥락막 신생혈관 동물모델에서 유효성을 입증하였다. 독성시험과 관련하여서는 설치류 6개월 반복투여 독성시험과 비설치류 9개월 반복투여독성시험을 완료하였으며 이들 독성시험자료는 임상시험뿐만 아니라 품목허가까지 가능한 시험기간을 산정하여 실시하였다. 이외에 임상2상 IND에 필요한 모든 자료를 확보하였으며, 현재 임상 2상 IND 신청을 완료하였다. 이 외에 품목허가 및 시판을 고려한 약동력학 연구 및 약물상호작용에 대한 연구도 진행하였다.

Abstract ▼

- Large scale manufacturing process of drug substance was developed and prototype of ALS-L1023 was manufactured in GMP manufacturing facility.
- Confirmation of anti-angiogenic activity of large scale manufactured ALS-L1023 by comparing activity with phase 2 clinical trial ALS-L1023 sample using

- Large scale manufacturing process of drug substance was developed and prototype of ALS-L1023 was manufactured in GMP manufacturing facility.
- Confirmation of anti-angiogenic activity of large scale manufactured ALS-L1023 by comparing activity with phase 2 clinical trial ALS-L1023 sample using HUVEC tube formation assay, and MMP inhibition assay
- Establishment of standard and test method of ALS-L1023
- Decision of ALS-L1023 formulation
- 26-week repeated dose toxicity test in rats
ALS-L1023 was well tolerated when administered as a feed admixture to male and female Sprague Dawley rats at dose levels of 500, 1000, and 2000 mg/kg/day for a period of 26 weeks. ALS-L1023 showed no remarkable treatment-related clinical observations and did not reveal systemic toxic effects by postmortem evaluations.
- 39-week repeated dose toxicity test in beagle dogs
ALS-L1023 was well tolerated when administered to male and female beagle dogs at dose levels of 500mg/kg/day for a period of 39 weeks
- Long-term stability test was performed for 18 months
-PK study was performed
-HPLC fingerprints according to the country of origin
-Efficacy test in streptozotocin-induced diabetic retinopathy animal model showed ALS-L1023 decreased blood vessel leakage and protected retinal cells
- Efficacy test in Choroid Neovascularization (CNV) rat model showed ALS-L1023 decreased CNV thickness dose-dependently measured by OCT (Optical Coherence Tomography), and CNV area dose-dependently measured by choroidal flat mount.
Histological analysis of retinal-retinal pigment epithelium-choroid
cross section showed ALS-L1023 decreased CNV thickness, and CNV/choroid ratio. Oral administration of ALS-L1023 decreased clinically significant leakage(grade 2B) dose-dependently measured by Fluorescein Angiography.
- Efficacy test in Choroid Neovascularization (CNV) mouse model showed ALS-L1023 decreased CNV thickness dose-dependently.
- Phase 2 clinical trial protocol was determined and submitted to MFDS.