KR20170005951A - Pharmaceutical composition for preventing or treating IL-1 related diseases comprising Michelia compressa extract - Google Patents

Abstract

The present invention relates to pharmaceutical composition for preventing or treating 1L-1 related diseases comprising michelia compressa extract. The michelia compressa extract was discovered to have excellent effects which suppress transfer of a receptor signal without cytotoxicity. Accordingly, the composition comprising the michelia compressa extract as a main component of the present invention can be presented as the pharmaceutical composition for preventing or treating the 1L-1 related inflammatory diseases and autoimmune diseases.

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating IL-1 [beta] -related diseases,

The present invention relates to a composition for preventing or treating an IL-1β-related disease, which comprises an extract of a promoter as an active ingredient.

Autoimmune diseases and inflammatory diseases are characterized by the chronic expression of inflammatory cytokines. Interleukin-1β (IL-1β), which plays a key role in inflammatory cytokines, binds to specific receptors and activates inflammatory transcription factors such as NF-κB, thereby activating inflammatory cytokines including IL-1β Synthesis and secretion, and secreted inflammatory cytokines activate immune cells to induce and sustain an inflammatory response. Thus, inflammatory cytokines such as IL-1 [beta] are increased in autoimmune diseases and inflammatory diseases, and the quantitative increase of these inflammatory cytokines leads to the problem of hypersensitivity to IL-1 [beta].

Rheumatoid arthritis, gout, type 2 diabetes, ischemic disease, smoldering myeloma, Cryopyrin Associated Periodic Syndrome (CAPS) (ILD), recurrent pericarditis, familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), systemic lupus erythematosus, multiple sclerosis , Psoriasis, etc., and when symptoms are alleviated when IL-1β is neutralized or antagonized by specific receptors (Charles A. Dinarello. Blood. 2011; Patrick J. Shaw, et al. Trends in Molecular Medicine. 2011.; Silvia Federici, et al., Frontiers in Immunology, 2013 .; Dimitrios vassilopoulos et al., International journal of cardiology, 2012. Mori F. et al., Neuromolecular medicine. Alzheimer's disease, atherosclerosis, allergic contact dermatitis (allergic contact dermatitis), allergic contact dermatitis (allergic contact dermatitis), allergic contact dermatitis IL-1β is a central mediator in the pathogenesis of mutations in related immune diseases such as dermatitis, Crohn's disease, Addison's disease and non-tropical celiac disease. (Patrick J. Shaw, et al. Trends in Molecular Medicine. 2011 .; Villani A.C. et al. Nature Genetics. 2009.).

In the case of IL-1β receptor antagonists currently used, protein drugs are very expensive and can be applied to more patients by lowering the unit cost and increasing the production using natural plant-derived extracts to solve this problem.

Michelia compressa ) is a Magnoliaceae plant mainly distributed in Heuksan-do and Jeju-do, and its effect on immune diseases such as suppression of IL-1β reactivity of the primordial extract has not been reported at present.

1. Korean Patent Publication No. 10-2013-0069542.

The present invention provides a pharmaceutical composition or a health food that can prevent or treat inflammatory diseases or autoimmune diseases induced by IL-1 [beta] using a composition containing an extract of ancillary agents showing an inhibitory effect on IL-1 beta reactivity .

The present invention provides a pharmaceutical composition for preventing or treating an IL-1β-related disease, which comprises an extract of a promoter as an active ingredient.

The present invention also provides a health food for preventing or ameliorating an IL-1? -Related disease, which comprises an extract of a promoter as an active ingredient.

According to the present invention, since the priming extract has no cytotoxicity and has an excellent effect of inhibiting the signal transduction of IL-1? Receptor, the composition containing the promoter extract of the present invention as an active ingredient is useful as an anti-inflammatory and autoimmune diseases Or as a health food.

FIG. 1 shows the results of confirming the IL-1β signaling inhibitory effect of the primordial extract in the IL-1β signal transduction-detecting cell line model.
Fig. 2 shows the result of confirming cytotoxicity of the ginseng extract.

The present invention can provide a pharmaceutical composition for preventing or treating IL-1β-related diseases containing an activator of an accelerator.

The germ extract may be extracted with water, C1-C4 alcohol or a mixed solvent thereof using an oriental leaf, more preferably a methanol extract, but is not limited thereto.

The IL-1β-related diseases may be selected from the group consisting of inflammatory diseases and autoimmune diseases. More particularly, the inflammatory diseases are selected from the group consisting of cryopyrin-related periodic syndrome, gout, type 2 diabetes, ischemic diseases, Atherosclerosis, inflammatory bowel disease, allergic contact dermatitis, and tumor necrosis factor receptor related periodic syndrome, wherein said autoimmune disease is selected from the group consisting of arthritis, Crohn's disease, multiple sclerosis, lupus, But are not limited to, hypertension, Alzheimer's disease, Addison's disease, non-tropical sprue, psoriasis and multiple myeloma.

According to one embodiment of the present invention, when the transcription factors NF-kB and AP-1 are activated due to IL-1? Signaling, the secretory embryonic alkaline phosphatase (SEAP) As shown in FIG. 1, when the extract was treated, the amount of SEAP expressed in the IL-1β-treated experimental group was about 2.5 times higher than that of the IL-1β treated group, and the expression level of SEAP in the experimental group treated with the extract The extracts of the seedlings were reduced by about 45% compared to the untreated control group.

From these results, it can be seen that the composition comprising the extract of the primate can be effectively used for preventing or treating IL-1β-induced inflammatory diseases and autoimmune diseases.

In one embodiment of the present invention, the pharmaceutical composition for preventing or treating IL-1β-related diseases containing the ginseng extract as an active ingredient may be administered orally or parenterally in the form of injections, granules, powders, tablets, pills, capsules, suppositories, , Suspensions, emulsions, drops, or liquid preparations can be used.

In another embodiment of the present invention, a pharmaceutical composition for preventing or treating IL-1β-related diseases containing an activator of an agonist extract may be prepared by mixing together suitable carriers, excipients, disintegrants, sweeteners, The lubricant may further include at least one additive selected from the group consisting of a lubricant, a lubricant, a lubricant, a flavoring agent, an antioxidant, a buffer, a bacteriostatic agent, a diluent, a dispersant, a surfactant, a binder and a lubricant.

Specific examples of carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration may be in the form of tablets, pills, powders, granules, capsules These solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

According to one embodiment of the present invention, the pharmaceutical composition may be administered orally, intraarterally, intraperitoneally, intramuscularly, intraarterally, intraperitoneally, intrasternally, transdermally, nasally, inhaled, topically, rectally, ≪ / RTI > can be administered to the subject in a conventional manner.

The preferred dose of the immunoglue extract may vary depending on the condition and body weight of the subject, the type and degree of the disease, the drug form, the administration route and the period, and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, the daily dose may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg, though it is not limited thereto. The administration may be performed once a day or divided into several times, and thus the scope of the present invention is not limited thereto.

In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.

In addition, the present invention can provide a health food for preventing or ameliorating an IL-1? -Related disease, which contains an extract of a promoter as an active ingredient.

The health food may be used in combination with other foods or food additives in addition to the accelerator extract, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose, for example, prevention, health or therapeutic treatment.

The effective dose of the compound contained in the above-mentioned health food may be used in accordance with the effective dose of the therapeutic agent, but may be less than the above range for health and hygiene purposes or for long-term intake for health control purposes, It is clear that the component can be used in an amount of more than the above range since there is no problem in terms of safety.

There is no particular limitation on the type of the health food, and examples thereof include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, Drinks, alcoholic beverages and vitamin complexes.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> IL- 1β  Confirm signaling inhibition effect

In the case of the transcription factor NF-κB and AP-1 activated by the IL-1β signaling, the lyophilized ginseng leaf extract (Korean plant extract bank) was dissolved and dissolved in DMSO. HEK-Blue ^占 IL-1? (Invivogen) cell line prepared for expression of the SEAP gene was cultured, and then the cell extract was treated with 40 占 퐂 / ml of the priming extract. After treatment, IL-1? Was treated to 1 ng / mL and cultured for 24 hours.

In order to detect the amount of secreted SEAP in culture, each culture was collected and reacted with SEAP to add QUANTI-Blue ^™ , a specific color-changing substrate, for 30 minutes, and the absorbance was measured at 650 nm.

As a result, as shown in FIG. 1, the SEAP expression level was increased about 3.3-fold in the IL-1β 1 ng / mL-treated experimental group compared to the untreated experimental group, and the SEAP expression level in the treated group Which was about 46% lower than that of the untreated experimental group.

< Example  2> Cytotoxicity of the primordial extract

In order to confirm that the SEAP expression inhibition effect confirmed in the previous experiment is not a phenomenon caused by cell death, the culture solution of Example 1 was collected and treated with CCK-8 solution (Dojindo) to 10% After incubation for one hour, the cells were reacted with live cells and the extent of color development was determined by measuring absorbance at 450 nm.

As a result, it was confirmed that the cell viability of the experimental group treated with the primer extract was higher than that of the IL-1β treated group, as shown in FIG. 2, and was not cytotoxic.

From the above results, it was confirmed that the primordial extract inhibited the reactivity to IL-1? Without cytotoxicity.

Meanwhile, the ginseng extract according to the present invention can be formulated into various forms according to the purpose. Hereinafter, some formulation methods in which the ginseng extract according to the present invention is contained as an active ingredient are exemplified, and the present invention is not limited thereto.

< Formulation example  1 > Prescription example

< Formulation example  1-1> Preparation of injection

10 mg of the primordial extract, 3.0 mg of sodium metabisulfite, 0.8 mg of methylparaben, 0.1 mg of propylparaben and an appropriate amount of sterilized distilled water for injection were mixed to prepare a final volume of 2 ml by a conventional method, And sterilized to prepare an injection.

< Formulation example  2-1> Preparation of tablets

100 mg of starch, 100 mg of lactose and 100 mg of magnesium stearate, and tableting was carried out by tableting according to a conventional tablet preparation method.

< Formulation example  3-1> Preparation of capsules

Starch extract, 10 mg of lactose, 50 mg of lactose, 50 mg of starch, 2 mg of talc, and magnesium stearate, and filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules.

< Formulation example  2> Manufacture of health food

(Vitamin E acetate, 70 mg of vitamin E, 0.13 mg of vitamin B 1, 0.15 mg of vitamin B 2, 0.5 mg of vitamin B 6, 0.2 쨉 g of vitamin B 12, 10 mg of vitamin C, 10 mg of biotin 10 mg of nicotinic acid amide, 1.7 mg of nicotinamide, 50 쨉 g of folic acid, and 0.5 mg of calcium pantothenate) and an appropriate amount of mineral mixture (1.75 mg of ferrous sulfate, 0.82 mg of zinc oxide, 25.3 mg of magnesium carbonate, 15 mg of potassium phosphate, 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg) were mixed to prepare a granule, and a health food was prepared according to a conventional method.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims (6)

A pharmaceutical composition for preventing or treating an IL-1? -Related disease containing an extract of an oriental herb as an active ingredient. [Claim 2] The pharmaceutical composition for preventing or treating IL-1β-related diseases according to claim 1, wherein the extract is derived from water, C1-C4 alcohol or a mixed solvent thereof. [Claim 2] The pharmaceutical composition according to claim 1, wherein the IL-1 [beta] -related disease is selected from the group consisting of inflammatory diseases and autoimmune diseases. The method of claim 3, wherein the inflammatory disease is selected from the group consisting of cryopyrin related cyclic syndrome, gout, type 2 diabetes, ischemic disease, pericarditis, familial Mediterranean fever, arteriosclerosis, inflammatory bowel disease, allergic contact dermatitis and tumor necrosis factor receptor Related periodic syndrome. &Lt; RTI ID = 0.0 &gt; 21. &lt; / RTI &gt; The method of claim 3, wherein the autoimmune disease is selected from the group consisting of arthritis, Crohn's disease, multiple sclerosis, lupus, essential hypertension, Alzheimer's disease, Addison's disease, non- tropical sprue, psoriasis and multiple myeloma. -1? Associated diseases. A health food for preventing or ameliorating IL-1β-related diseases containing an agonist extract as an active ingredient.

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