Nanoemulsion comprising imidazoquinoline-based material and use thereof

A technology of imidazoquinoline and nanoemulsion, which is applied in the field of adjuvants or vaccines, can solve problems such as inappropriateness, toxicity and side effects, and achieve the effect of enhancing cellular immunity and solving systemic toxicity problems

Inactive Publication Date: 2019-11-08
DANDI BIOSCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, imidazoquinoline-based drugs in salt form (e.g. HCl) can be dissolved in aqueous solutions, but are absorbed systemically and thus cause many toxic effects and side effects, so they are not suitable for use in vaccine adjuvant forms

Method used

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  • Nanoemulsion comprising imidazoquinoline-based material and use thereof
  • Nanoemulsion comprising imidazoquinoline-based material and use thereof
  • Nanoemulsion comprising imidazoquinoline-based material and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Example 1. Preparation of squalene solution comprising imiquimod (R837)

[0093] 20 mg of imiquimod (TCI, Tokyo, Japan) was treated at room temperature with a bath sonicator (Branson MH Mechanical Bath 5800, Emerson, St. Louis MO) was dissolved in 100 mg oleic acid (SigmaAldrich, USA) until the solution became transparent. Thereafter, 1 mL of squalene (5% v / v, Sigma Aldrich, USA) was added thereto and stirred using a stirrer (Vortex-Genie 2, Scientific Industries, USA) to obtain a uniform squalene solution.

Embodiment 2

[0094] Example 2. Preparation and Characterization of Squalene Nanoemulsions (NE-IQ) Including Imiquimod

[0095] Squalene (5% v / v, Sigma Aldrich, USA) containing imiquimod prepared according to Example 1, Tween 80 (0.5% v / v, Sigma Aldrich, USA) and Span 85 (0.5% v / v, Sigma Aldrich, USA) was dissolved in 2mL phosphate buffered saline (PBS, 0.0067M PO 4 ), and then completely dispersed in phosphate buffered saline (PBS) for 1 min using an ultrasonic disperser (Tip sonicator). Then, the mixture was stirred using a tube rotator for about 2 h, and then stored in a refrigerator at 4 °C until use. The size of the emulsion was analyzed by dynamic light scattering (DLS, Otsuka, Japan). As a result of dynamic light scattering (DLS) measurement, diameters of 106.16±5.4 and 148.54±18.5 nm were confirmed (see FIG. 2 and Table 1).

[0096] [Table 1]

[0097]

Embodiment 3

[0098] Example 3. Introduction of NE-IQ into immune cells and its localization in cells

[0099] Bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMMCs) were treated with squalene containing imiquimod (R837) for 24 hours and then evaluated using fluorescence microscopy. Such as image 3 As shown in the fluorescence image of , lysotracker (green) and DID (red) were found to co-localize at the same location in the cell. From these results, it was confirmed that the squalene nanoemulsion containing imiquimod (NE-IQ) was localized in endosomes and lysosomes.

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Abstract

The present invention relates to a nano emulsion comprising an oil layer comprising imidazoquinoline-based toll-like receptor 7 or 8 agonist and an oil, and a use thereof as an adjuvant and vaccine. According to the present invention, it is possible to provide a vaccine adjuvant in the form of a nano emulsion that can dissolve an insoluble imidazoquinoline-based material in oil using a dispersionmedium material and disperse the oil solution easily and reproducibly in a water-soluble manner.

Description

technical field [0001] The present invention relates to a nanoemulsion comprising an oil layer containing an imidazoquinoline-based toll-like receptor 7 or 8 agonist and oil, and to its use as an adjuvant or vaccine. Background technique [0002] Vaccine adjuvants are immunostimulatory adjuvants that activate immune cells and thus play an important role in vaccines for the prevention / treatment of infectious diseases and anticancer therapy. Aluminum salts (alum) or squalene-based nanoemulsions (MF59, AS03, AF03, etc.) as immune adjuvants used in conventional vaccines are effective in inducing improvement in humoral immunity, which contributes to antigenic responses, but has fatal deficient because of their limitations in inducing cellular immunity against viral and cancer antigens. Therefore, the use of nanoemulsion-based adjuvants is limited to influenza vaccines only. [0003] In recent years, the development of vaccine adjuvants capable of efficiently inducing humoral im...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/4745A61K39/39A61K47/44A61K47/14A61K39/00
CPCA61K31/4745A61K39/39A61K47/14A61K47/44A61P31/00A61K2039/55566A61K2039/55511A61K2039/55577A61K2039/55572A61K2039/55561A61P35/00A61K9/1075Y02A50/30A61K31/437A61K31/55A61K47/06A61K47/12
Inventor 林容泽金善永
Owner DANDI BIOSCI INC
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