JP2015059122A - Antioxidant and anti-inflammatory agent using extract of sea urchin test - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agent or composition for an active oxygen elimination action and an inflammatory cytokine-inhibiting action using extract of sea-urchin test.SOLUTION: The invention provides functional food materials, and compositions for pharmaceuticals given to humans or non-human animals (therapeutic agents for animals are also included), and feeds or pet foods relating to antioxidation and anti-inflammation which have an active oxygen elimination action and an inflammatory cytokine-inhibiting action, and containing extract of sea urchin tests as an active ingredient.

Description

The present invention relates to an active oxygen scavenger and an inflammatory cytokine inhibitor of sea urchin shell extract. The present invention means functional food materials related to antioxidants and anti-inflammatory, pharmaceuticals (including animal therapeutics) given to humans or non-human animals, and feed or pet food compositions.

It is known that reactive oxygen species (ROS) and inflammatory cytokines are closely related to various lifestyle-related diseases and other diseases.
On the other hand, uveitis, which is an eye disease, is a disease that accounts for about 10% of the causes of blindness in advanced countries over 40 years of age. Many are due to collagen diseases or related diseases such as Behcet's disease and inflammatory bowel disease. In a study that surveyed 25 locations around the world, there is still a harsh reality that a quarter of patients with Behcet's disease uveitis leads to blindness (Kitaichi N et al. Br J Ophthalmol, 2007). The average onset age of 1,240 patients with uveitis who first visited Hokkaido University Hospital for 10 years from 1994 to 2003 was 41.7 years for men and 45.7 years for women. We reported low (Kitamei H et al. Acta Ophthalmol, 2009). Uveitis has a large incidence especially in the youth, and it can be said that it is an extremely important problem not only for the patient but also for society and economy.

Until now, steroid drugs, anti-inflammatory analgesics (NSAIDs) and immunosuppressive drugs have been mainly used for the treatment of uveitis. However, in daily clinical practice, we often experience cases of severe visual impairment even with current treatment. In addition, treatment is often interrupted due to systemic side effects. Targeting factors that control inflammation in the eye is considered important to develop more effective therapies without concern for systemic effects. Therefore, in recent years, anti-tumor necrosis factor (TNF) -α antibody (Ohno S et al. J Rheumatol, 2004) and granulocyte adsorption therapy (Namba K et al. J Clin Apher, 2006) for patients with refractory Behcet's disease, Developmental research and clinical application of treatments targeting inflammatory cells and cytokines are advancing. Although these treatments have been able to control refractory uveitis that resists conventional treatments more effectively than before, there are still many instances where inflammation reignites.

An object of the present invention is to provide pharmaceuticals, functional foods or food materials, and feeds for preventing, ameliorating, and treating ophthalmic diseases that have active oxygen suppression and inflammatory cytokine suppression effects with few side effects.

In order to achieve the above-mentioned object, the inventor paid attention to a functional component in the natural world.
Oxidative stress pathway is involved in the development of inflammatory eye diseases. Focusing on the suppression of uveitis by antioxidant substances, elucidating the pathology of uveitis, an eye disease, and developing new therapies As an animal model of meningitis, “endotoxin-induced uveitis model (EIU)” which is a model of nonspecific anterior ocular inflammation by exotoxin and autoimmune panuveitis model “ As a result of conducting basic research using experimental autoimmune uveoretinitis (EAU) and earnestly researching it, Echinochrome (2) was found in sea urchin shell extract and its main component. , 3,5,6,8-pentagiroxi-7-ethyl And we have found that: a) there is the activity.

The present invention has been completed based on such findings. That is, the antioxidant and anti-inflammatory actions of the present invention are characterized in that the outer shell extract and its main component, echinochrome, are the active ingredients.

The outer shell extract and echinochrome are not commercially available, and the effect on inflammatory diseases is completely unknown. Since it is naturally derived, it is considered that it is easy to apply clinically in terms of safety.

That is, the present invention provides the following.

[1] Sea urchin shell extract active oxygen scavenger.

[2] Inflammatory cytokine inhibitor of sea urchin extract.

[3] An agent wherein the active oxygen scavenger or inflammatory cytokine inhibitor according to [1] or [2] comprises echinochrome.

[4] A food and functional food material comprising the antioxidant and the inflammation inhibitor according to [1] or [2].

[5] A document or pet food comprising the antioxidant and inflammation inhibitor according to [1] or [2].

[6] A pharmaceutical composition comprising the antioxidant and inflammation inhibitor according to [1] or [2].

The active oxygen inhibitor and the inflammatory cytokine inhibitor of the present invention, or a composition containing them provides a pharmaceutical, a functional food or a food material, and a feed for preventing, improving, or treating an eye disease with few side effects. Can do. Furthermore, since it is possible to produce the agent or composition of the present invention from ingredients with food experience, it is safe to take.

The active oxygen inhibitor and the inflammatory cytokine inhibitor of the present specification are an agent and a composition having an active oxygen inhibitory activity and an inflammatory cytokine inhibitory activity containing echinochrome as an active ingredient in sea urchin shell extract as an active ingredient. is there. Although content of said compound is not limited, it should just be contained in the range which can exhibit an active oxygen suppression and an inflammation cytokine suppression effect.

The composition for eating and drinking of the present invention is a composition containing the above-mentioned active oxygen inhibitor and inflammatory cytokine inhibitor, and these are mixed into general foods. Further, capsules, tablets, granules and the like that are easy to take may be used by using appropriate carriers and auxiliaries as known foods. The food and drink here refers to, for example, general foods, health functional foods (special health foods, nutritional functional foods), health foods, nutritional supplements, pet foods, and the like. General food as used herein includes, but is not limited to, beverages, dairy products, fermented milk, lactic acid bacteria beverages, processed milk, coffee beverages, juices, ice creams, strawberries, biscuits, wafers, jellies, soups, and noodles. is not. Preferably, beverages, dairy products, processed milk, fermented milk, lactic acid bacteria beverages, wafers, and jelly are included.

The pharmaceutical composition of the present invention is a composition containing the active oxygen inhibitor and the inflammatory cytokine inhibitor described above, and may be the agent itself or, if desired, a pharmaceutically acceptable carrier. It may be a composition. The use is not limited, and examples thereof include readily available drugs such as over-the-counter drugs (OTC) or quasi drugs. The form of the pharmaceutical composition is not limited, and examples thereof include pills, solutions, powders, granules, tablets, capsule tablets, troches, syrups, and dry syrups. Preferably, capsules, liquids, elixirs, tablets, cachets, suppositories and the like are used. A pharmaceutically acceptable carrier is any material suitable for oral, enteral, transdermal, and subcutaneous administration, such as water, gelatin, gum arabic, lactose, microcrystalline cellulose, starch. Sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talc, colloidal silicon dioxide, and the like.

The echinochrome, which is the main component of urchin shell extract, and the composition are formulated as active ingredients of active oxygen inhibitors and inflammatory cytokine inhibitors, but formulated as active oxygen inhibitors and inflammatory cytokine inhibitors When doing, arbitrary dosage forms, such as a powder form, a granular form, and a tablet form, are employable as a dosage form. At that time, in order to facilitate storage and handling, carriers such as dextrin and cyclodextrin, preservatives and other optional auxiliaries can be blended as necessary. Moreover, the form is not limited, The composition for food and drink and the composition for medicine are included. Although these content is not limited, it should just be contained in the range which can exhibit an effect with respect to an active oxygen suppression and an inflammatory cytokine suppression effect.

The active oxygen inhibitor and the inflammatory cytokine inhibitor can inhibit active oxygen production and inflammatory cytokine production so that various eye diseases and lifestyle-related diseases do not develop.

The functional food or food material for preventing or improving active oxygen production and inflammatory cytokine production according to the present invention, which contains echinochrome as an active ingredient in the sea urchin shell extract as an active ingredient, is the activity of the present invention. It can be obtained by using an oxygen suppressor and an inflammatory cytokine inhibitor as a part of a raw material for food and drink, or by adding and blending them after the production process or production. Such functional foods are not particularly limited, and specific examples include seasonings, sprinkles, confectionery, snacks, noodles, fish paste products, dairy products, beverages, and the like.

EXAMPLES Examples are given below to describe the present invention in more detail, but the present invention is not limited by these.

Experimental animals were 6-8 week old Lewis rats.
As an eye inflammation inducer, 200 μg of E. coli-derived lipopolysaccharide (LPS) was used per mouse.
Equinochrome extracted from sea urchin shells was used.
A phosphate buffer solution (PBS, PH = 7.4) was used for dilution of LPS and echinochrome.

Experiments were performed using a rat endotoxin-induced uveitis (EIU) model.
Lewis rats were given 200 μg LPS intraperitoneally to induce endotoxin-induced uveitis (EIU). Simultaneously with LPS administration, 10,1,0.1 mg / kg (body weight) of echinochrome was intravenously administered. After 24 hours, an anterior aqueous humor was collected under a microscope using a 30G needle under intoxication. The amount of ocular aqueous humor recovered from one animal was 25-50 μl. As controls, naive rats (negative control) and LPS administration group (positive control) not administered with echinochrome were set. Ocular inflammation was assessed by inflammatory cytokine concentration in the anterior chamber.

In this test, measurement was performed by a conventional method using a TNF-α • ELISA kit manufactured by Thermo Fisher Scientific.

The concentration of the inflammatory cytokine TNF-α in the collected anterior aqueous humor was measured, and the cytokine concentration of the test sample was calculated. The measurement sample was triplicate (three-point measurement).

Inflammatory cytokines were evaluated by measuring TNF-α of the aqueous humor. The result is shown in the figure.

This is a graph showing the measurement of TNF-α, an inflammatory cytokine of aqueous humor after intraperitoneal administration of echinochrome since the shell extract, and showed inhibitory activity compared to LPS administration control. . As a result of investigating the effect of echinochrome (ECH) administration using a naive (Naive: negative control) and an LPS administration group (positive control) to which echinochrome was not administered as a control, Equinochrome is an inflammatory cytokine TNF- α was reduced in a dose-dependent manner.

Claims (6)

Active oxygen scavenger for sea urchin shell extract. Inflammatory cytokine inhibitor of sea urchin shell extract. The active oxygen scavenger or inflammatory cytokine inhibitor described in [1] or [2] is an agent comprising echinochrome. A food and functional food material comprising the antioxidant and the inflammation inhibitor according to [1] or [2]. Documents and pet food comprising the antioxidant and the anti-inflammatory agent according to [1] or [2]. A pharmaceutical composition comprising the antioxidant and the inflammation inhibitor according to [1] or [2].

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