JP-7856958-B2 - Immunostimulant composition and expression induction composition

Inventors

• 伊藤 智広
• 竹中 裕行
• 山口 裕司

Assignees

• マイクロアルジェコーポレーション株式会社
• 国立大学法人三重大学

Dates

Publication Date

20260512

Application Date

20230522

Claims (4)

1. An immunostimulatory composition containing extracellular membrane vesicles derived from at least one microalga selected from the thallus of the diatom class (pennate order), the thallus of the cyanobacteria class (Nostocales order), and the thallus of the haptophyceae class ( coccolithophores order) as an active ingredient.
2. The immunostimulatory composition according to claim 1, wherein the particle size of the extracellular membrane vesicles is 450 nm or less.
3. The immunostimulatory composition according to claim 2, wherein the average particle size of the extracellular membrane vesicles is 150 nm or more and 250 nm or less.
4. A composition for inducing the expression of inducible nitric oxide synthase, An expression-inducing composition containing, as an active ingredient, extracellular membrane vesicles derived from at least one microalga selected from the thallus of the diatom class (pennate order), the thallus of the cyanobacteria class (Nostocales order), and the thallus of the haptophyceae class (coccolithophores order).

Description

This invention relates to immunostimulant compositions and expression-inducing compositions. In living organisms, nitric oxide is synthesized from alginate and oxygen by nitric oxide synthase. Three isoforms of nitric oxide synthase are known: inducible nitric oxide synthase, neuronal nitric oxide synthase, and endothelial nitric oxide synthase. Inducible nitric oxide synthase is induced at the transcriptional level by interferon-γ and interleukin-1, which are induced by infections, etc. Inducible nitric oxide synthase synthesizes nitric oxide, which plays a crucial role in inflammatory responses, and also activates a series of biological defense mechanisms. Extracellular membrane vesicles are particulate membrane vesicles secreted by cells. These vesicles contain a variety of biomolecules, such as nucleic acids and proteins. These biomolecules function as signaling molecules. Recently, research has been conducted on regulating biological functions using extracellular membrane vesicles. For example, Patent Document 1 discloses a technique for suppressing apoptosis using extracellular membrane vesicles derived from bovine milk. Patent Document 2 discloses a technique for protecting the skin from external stimuli such as ultraviolet light and heat using extracellular membrane vesicles derived from yeast. Japanese Patent Publication No. 2016-56119Japanese Patent Publication No. 2022-31173 This graph shows the relationship between the administration of extracellular membrane vesicles derived from microalgae and NO production.This is a Western blot analysis showing the relationship between the administration of extracellular membrane vesicles derived from microalgae and the expression level of iNOS. The following describes one embodiment of the present invention. The composition of this embodiment (hereinafter referred to as "this composition") contains extracellular membrane vesicles derived from microalgae as an active ingredient. [Microalgae] First, we will describe the microalgae that secrete extracellular membrane vesicles contained in this composition. Microalgae are algae with a microscopic size of approximately 1 μm to 1 mm. Specific examples of microalgae include thalli of the Volvoxales order of Chlorophyceae, thalli of the Pinnate order of Diatoms, thalli of the Oscillariales order of Cyanobacteriaceae, thalli of the Nostocales order of Cyanobacteriaceae, and thalli of the Coccolithophores order of Haptophyceae. However, microalgae are not limited to these thalli. Examples of thallus belonging to the order Volvoxales of the class Chlorophyceae include thallus belonging to the genus Dunaliella, such as Dunaliella salina, Dunaliella tertiolecta, and Dunaliella bardawil, and thallus belonging to the genus Chlorogonium, such as Chlorogonium sp., Chlorogonium capillatum, Chlorogonium euchlorum, Chlorogonium elegans, Chlorogonium elongatum, Chlorogonium fusiforme, Chlorogonium kasakii, and Chlorogonium neglectum. Examples of diatoms belonging to the pinnate order include thallus of the genus Nitzchia in the family Nitzchiaceae, such as Nitzchia acicularis, Bacillaria paxillifer, Cylindrotheca Closterium, Neodenticula seminae, Nitzchia levidensis, Nitzchia martiana, Nitzchia pungens, Nitzchia tenuiarcuata, Pseudo-nitzschia multistriata, and Pseudoeunotia doliolus, as well as thallus of the genus Pheodactylum in the family Nitzchiaceae, such as Phaeodactylum tricornutum. Examples of thalli belonging to the order Oscillarianes of the class Cyanobacteria include those belonging to the genus Arthrospira, such as Arthrospira (Spirulina) platensis and Arthrospira (Spirulina) subsalsa. Examples of thalli belonging to the Nostocales order of the class Cyanobacteria include thalli belonging to the genus Nostoc, such as Nostoc commune, Nostoc flagelliforme, Nostoc sphaericum, Nostoc verrucosum, Nostoc linckia, Nostoc muscorum, and Nostoc punctiforme, and thalli belonging to the genus Aphanizomenon, such as Aphanizomenon flosaquae. Examples of thalli in the order Coccolithophytes of the class Haptophyceae include thalli belonging to the genus Pleurochrysis, such as Pleurochrysis carterae and Pleurochrysis roscoffensis. Microalgae may be naturally occurring algal bodies or artificially cultured algal bodies. However, using artificially cultured algal bodies is industrially preferable due to the ability to ensure a stable supply and ease of maintaining quality. [Extracellular membrane vesicles] Next, the extracellular membrane vesicles contained in this composition will be described. Extracellular vesicles are particulate substances secreted by the microalgae mentioned above, and are membrane vesicles covered with a membrane mainly composed of phospholipids. Extracellular vesicles contain biomolecules such as nucleic acids and proteins inside. Examples of nucleic acids include miRNA, mRNA, and DNA. The size of extracellular vesicles is not particularly limited. Extracellular vesicles include sEVs (small extracellular ves