초록 ▼

● 합성공정개선: 수율 16% 향상(3.74% → 4.34%), 순도 개선 98.90%(max impurity 0.92%) → 99.95%(max impurity 0.02%), 합성공정 단축(8STEP →6 STEP)을 통해 상업적 경제성을 가지는 합성공정을 확보함.
● 최적제형 선정 및 안정성 확보: 최적 수용성 점안제형을 선정하여 18 개월 안정성 시험 진행한 결과 냉장(2~8℃), 25± 2℃, 40± 5% RH 조건에서 임상시험계획서 승인에 요구된 18개월까지 성상, pH, 삼투압 및 함량은 유의적 변화가 없고 일정하게

● 합성공정개선: 수율 16% 향상(3.74% → 4.34%), 순도 개선 98.90%(max impurity 0.92%) → 99.95%(max impurity 0.02%), 합성공정 단축(8STEP →6 STEP)을 통해 상업적 경제성을 가지는 합성공정을 확보함.
● 최적제형 선정 및 안정성 확보: 최적 수용성 점안제형을 선정하여 18 개월 안정성 시험 진행한 결과 냉장(2~8℃), 25± 2℃, 40± 5% RH 조건에서 임상시험계획서 승인에 요구된 18개월까지 성상, pH, 삼투압 및 함량은 유의적 변화가 없고 일정하게 유지되었음.
● 약리효능 검증 : 질환동물모델을 활용하여 대조약물인 루센티스와 HL217 점안제를 비교한 결과 비교 동등한 효능을 입증하였으며, 후속 타깃 질환으로 당뇨병성 망막증에 대한 효능도 입증함.
● 허가용 독성시험 수행(임상1상 승인용)
- 독성 시험 : 단회, 반복(설치류,비설치류), 국소, 유전독성에서 저독성을 입증함
- 안정성 약리 : 일반행동 및 체온, 호흡, hERG assay 항목에서 특이적 사항 없음
- ADME : 점안 투여에 따른 안구내 약물 전달 경로 확인 및 뇌로 약물 이행 없음을 입증하였으며, 본 약물의 흡수, 분포, 배설자료를 확보함.
● 임상 프로토콜 확립 (임상 1상 IND승인): HL217 점안제의 임상 프로토콜을 확립하였으며, 11/24자로 IND 신청 완료함. 식약처와 신속한 협의를 통해 승인완료 시키고자함.

Abstract ▼

Ⅰ Object
: This study is to develop HL217, which has effect of inhibiting angiogenesis and therefore is anticipated to have efficacy of treating angiogenic ocular disease, as ophthalmic medicines for age related macular degeneration and related ocular disease.

Ⅱ. Contents
1) Process imp

Ⅰ Object
: This study is to develop HL217, which has effect of inhibiting angiogenesis and therefore is anticipated to have efficacy of treating angiogenic ocular disease, as ophthalmic medicines for age related macular degeneration and related ocular disease.

Ⅱ. Contents
1) Process improvement for the synthesis of HL217 2) Optimization in pharmaceutics, formulation and long term stability study 3) Efficacy 4) Toxicity 5) Safety Pharmacology 6) ADME 7) Establish the clinical trial protocol

Ⅲ. Results
1) Process improvement for the synthesis of HL217: 16% improved yield (3.74% → 4.34%), improve purity: 98.90%(max impurity 0.92%) → 99.95%(max impurity 0.02%), reduction of HL217 synthesis process (8 →6 STEP) 2) Optimization in pharmaceutics, formulation and long term stability study: Physical and chemical properties, pH, osmotic pressure, content of HL217 were not changed in the condition of cold temp(2~8℃), 25± 2℃, 40± 5% RH for the 18 m. 3) Efficacy : we have studied the effect of HL217 on subretinal neovascularization in Vldlr-/- K/O mice, which is a mouse model for neovascular AMD and DR mouse model. The most important finding of our study was that the topical application of HL217 is effective for the treatment of subretinal neovascularization. 4) Toxicity: As the results of single and repeat IV administration of the HL217, to SD rat and beagle dog at various dose levels, there were no test article related changed or finding in mortality. And, the results of the genetic toxicity, acute eye irritation test were no test article related changed or finding in toxicity 5) Safety Pharmacology: HL217 did not produce any significant effects on Irwin behavior & body temp, telemetry, respiratory, hERG assay. 6) ADME : The highest levels of radioactivity,14C-HL217, in the eye were detected in the ciliary body/iris and the cornea. In the brain very low levels of radioactivity, below the limit of quantification, were detected. Thus this results were confirmed the ADME of topical application of HL217 7) Establish the clinical trial protocol (for the Phase I approval): Development of clinical trial protocol for using HL217 eye drop for treatment of AMD and IND application was submitted by MFDS on Nov. 24. We will to speed up to the IND approval process.

Ⅳ. Application plan of the research results
1) Initiated clinical trial for development of novel therapeutics for AMD using HL217, angiogenesis inhibitor.
2) Contribute to the growth of korean pharmaceutical industry and national competitiveness by developing a novel therapeutics foe AMD