Pharmaceutical containing HIF-1alpha alpha and HIF-2alpha alpha expression inhibitor
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A technology of HIF-1 and HIF-2, which can be used in medical preparations, drug combinations, genetic material components, etc. containing active ingredients, and can solve problems such as unreported
Active Publication Date: 2010-10-20
SENJU PHARMA CO LTD
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[0005] Currently, it has been reported that siRNA or antisense of HIF-1α is used as a therapeutic drug for age-related macular degeneration or diabetic retinopa
Method used
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[0130] Examples are given below to further describe the present invention in detail, but the present invention is not limited thereto.
preparation example 1
[0131] Preparation example 1: Injection for intravitreal administration
[0132] Injections for intravitreal administration shown below were prepared according to conventional methods.
[0133] HIF-1α siRNA:
[0134] Sense-GGA ACC UGA UGC UUU AAC UTT (SEQ ID NO.5) 1mg
[0137] Sense-CGG AGG UGU UCU AUG AGC UTT (SEQ ID NO.9) 1mg
[0138] Antisense-AGC UCA UAG AAC ACC UCC GTC (SEQ ID NO.15) 1mg
[0139] Sodium dihydrogen phosphate 0.1g
[0140] Sodium chloride 0.9g
[0141] Appropriate amount of sodium hydroxide
[0142] Appropriate amount of sterile purified water
[0143]
[0144] Total 100mL
[0145] (pH7)
preparation example 2
[0146] Formulation example 2: Injection for intravitreal administration
[0147] Injections for intravitreal administration shown below were prepared according to conventional methods.
[0148] HIF-1α siRNA:
[0149] Sense-GGG UAA AGA ACA AAA CAC A TT (SEQ ID NO.6) 0.1mg
[0150] Antisense - UGU GUU UUG UUC UUU ACC C TT (SEQ ID NO.12) 0.1mg
[0151] HIF-2α siRNA:
[0152] Sense-GGU UUU GUU GCU AGC CCU U TT (SEQ ID NO.10) 0.1mg
[0153] Antisense-AAG GGC UAG CAA CAA AAC C TT (SEQ ID NO.16) 0.1mg
[0154] Sodium dihydrogen phosphate 0.1g
[0155] Glycerin 2.5g
[0156] Appropriate amount of sodium hydroxide
[0157] Appropriate amount of sterile purified water
[0158]
[0159] Total 100mL
[0160] (pH 7)
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Abstract
It is intended to provide a pharmaceutical product with a high therapeutic effect in the treatment of a retinal disease accompanied by angiogenesis such as age-related macular degeneration or diabetic retinopathy. A therapeutic agent for a retinal disease containing a substance that specifically inhibits the expression of HIF-1alpha and a substance that specifically inhibits the expression of HIF-2alpha. The inhibitor which is an active ingredient of the therapeutic agent of the invention is an RNAi-inducible nucleic acid, an antisense nucleic acid, or a ribozyme against HIF-1a and HIF-2a, or an expression vector therefor.
Description
technical field [0001] The present invention relates to medicaments containing HIF-1α and HIF-2α expression inhibitory substances. Specifically, it relates to a therapeutic agent for retinal diseases containing a nucleic acid capable of inducing RNA interference. Background technique [0002] Hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) are heterodimers containing α and β subunits that share a basic helix-loop-helix (bHLH) domain and a PAS domain transcription factor. The expression and transcriptional activity of HIF increased significantly when the intracellular oxygen concentration decreased. Target genes transactivated by HIF have been identified including genes encoding VEGF (vascular endothelial growth factor), erythropoietin, glucose transporter, and glycolytic enzymes (see Non-Patent Document 1). [0003] Diabetic retinopathy and age-related macular degeneration are diseases that cause acquired blindness, and the development of drugs for inhibiting neovascu...
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