WO2018212548A1 - Composition comprising zedoary extract as effective ingredient for preventing, alleviating, or treating vasculitis - Google Patents

Abstract

The present invention relates to a composition comprising a zedoary extract as an effective ingredient for preventing, alleviating, or treating vasculitis. A zedoary extract according to the present invention exhibits the outstanding effect of suppressing high cholesterol diet-promoted plaque formation in blood vessels and lipid storage in the aorta, decreasing the expression of cathepsin in the aorta, suppressing expression of the vascular inflammation marker HMGB1, and suppressing the expression of vascular inflammation factors, so that the composition comprising a zedoary extract as an effective ingredient according to the present invention can be useful as a vasculitis therapeutic agent or a health functional food for preventing or alleviating vasculitis.

Description

A composition for the prevention, improvement or treatment of vasculitis containing the extract of Achul as an active ingredient

The present invention relates to a composition for the prevention, improvement or treatment of vasculitis containing an extract of the extract as an active ingredient, and more specifically to the prevention of vasculitis containing an extract of the extract which can be used as a functional food or pharmaceutical composition as an active ingredient. , To improve or treat compositions.

Vasculitis is one of the intractable conditions commonly recognized for autoimmune diseases and is characterized by inflammation of the blood vessel wall and thus tissue damage. Inflammation of the vessel wall causes ischemia in tissues that have been fed through the vessels, resulting in tissue damage. Since all types of blood vessels and blood vessels of all organs can be invaded, the symptoms and symptoms vary depending on the location and characteristics of the involved vessels. It may occur primary without underlying disease, or secondary with rheumatic arthritis such as rheumatoid arthritis or systemic lupus erythematosus.

Collagen vasculitis (rheumatic vasculitis, lupus vasculitis), multiple nodular arteritis, microscopic multiple vasculitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu's arteritis, Henoch-Scholine purpura, urticaria, depending on the size and extent of the involved vessels Vasculitis includes diseases such as vasculitis, irritable vasculitis, giant cell arteritis (temporal arteritis) and Behcet's vasculitis.

The cause of vasculitis is thought to be due to immune dysfunction or allergic reaction of our body. The process of vasculitis begins when the immune system that recognizes its cells as an antigen first releases antibodies in a steady state. The binding of an antibody to an antigen is called an immunocomplex, which is attached to the blood vessel wall, causing inflammation of the blood vessel wall. Blood flows to the other side of the vascular wall thickened by the inflammatory response, causing the vascular wall to expand, causing an aneurysm.

Patients with vasculitis have systemic symptoms such as fever, weight loss, loss of appetite, and weakness, and symptoms such as spots or nodules on the skin, pain in the limbs caused by exercise, difficulty breathing, kidney failure, gastrointestinal bleeding, and neurological disorders. appear. Clinical findings and course vary greatly depending on the type of vasculitis, and even the same vasculitis appears in various ways depending on the patient. Complications can include vision disorders, heart disease, myocardial infarction, dyspnea, pulmonary hemorrhage, nephritis, intestinal bleeding, intestinal necrosis, skin necrosis, and infection.

Most treatments for vasculitis use steroids or immunosuppressants. However, the treatment principles, such as treatment or duration of treatment will vary depending on each disease. Both steroids and immunosuppressive agents used for vasculitis are drugs that can cause various side effects, including infections, so they need to be careful about the occurrence of side effects, and development of substances to replace them is required.

On the other hand, Curcuma zedoaria is dried root stem of Curcuma phaeocaulis of Zingiberaceae, and has been traditionally used for indigestion, gusts, colic, menstrual irregularities, stomach and digestive action, anticancer Action, hepatocyte protective action, etc. have been reported. It is also known to be effective in controlling pepper anthrax, and to have macrophage activating activity and pancreatic lipase inhibitory activity.

On the other hand, Korean Patent No. 1710081 discloses a composition and its use, including the extract of Achul which can increase the activity of TLR4 and TLR7 / 8, and induce the production of interferon β, and Korean Patent Publication No. 1287688 Although a composition for treating atopic dermatitis using a natural substance including azu is disclosed, there is no disclosure regarding a composition for preventing, improving or treating vasculitis containing the azu extract of the present invention as an active ingredient.

The present invention has been made by the above-described requirements, and provides a composition for the prevention, improvement or treatment of vasculitis, which contains the extract of Achul as an active ingredient, the expression of cathepsin known as the atherosclerosis-induced vascular inflammation markers The present invention was completed by inhibiting vascular plaque formation and lipid accumulation in the aorta, and inhibiting the expression of vascular inflammatory factors.

In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of vasculitis, which contains the extract extract as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or improving vasculitis, which contains the extract of Ashal as an active ingredient.

The present invention relates to a composition for the prevention, improvement or treatment of vasculitis containing the extract of Achul as an active ingredient, the extract of the present invention inhibited plaque formation of blood vessels and lipid accumulation of the aorta increased by a high cholesterol diet, It is effective in reducing cathepsin expression in the aorta, suppressing the expression of the vascular inflammation marker HMGB1, and inhibiting the expression of the vascular inflammation factors CX3CL1, VCAM-1, ICAM-1, TNF-α and IL-6. The composition of the present invention containing the extract extract as an active ingredient can be used as a functional material for preventing, improving or treating vasculitis.

1 is a schematic diagram of an animal test method for confirming the vascular inflammation inhibitory effect by the administration of Achul extract in ApoE deficient mice induced with vasculitis through a high cholesterol diet.

2 is a result of H & E staining of tissues by extracting the aorta and the liver of ApoE deficient mice induced with vasculitis through a high cholesterol diet. Control is a normal diet group, HCD is a high cholesterol diet group, C2E is a high cholesterol diet and Achul extract group, statin is a high cholesterol diet and statin (positive control group).

Figure 3 is a result of oil-red-O (Oil-Red-O) staining the tissue in the aorta of the ApoE deficient mice induced vasculitis through a high cholesterol diet. (A) is a micrograph, (B) is a result of quantifying a staining site. Control is a normal diet group, HCD is a high cholesterol diet group, C2E is a high cholesterol diet and Achul extract administration group. # Indicates that the fat accumulation of the high cholesterol diet group was significantly increased compared to the general diet group, p <0.05. * Indicates that the fat accumulation of the high cholesterol diet and the Achul extract group was significantly reduced compared to the high cholesterol diet group, p <0.05.

Figure 4 is an image of the expression level of cathepsin in the aorta of ApoE deficient mice induced with vasculitis through a high cholesterol diet. Control is a general diet group, HCD is a high cholesterol diet group, C2E-1 ~ 3 is a high cholesterol diet and Achul extract administration group, statin is a high cholesterol diet and statin (positive control group).

5 is an image of the expression level of cathepsin in the liver, lung, kidney, heart and spleen of ApoE deficient mice induced with vasculitis through a high cholesterol diet. Control is a general diet group, HCD is a high cholesterol diet group, C2E-1 ~ 3 is a high cholesterol diet and Achul extract administration group, statin is a high cholesterol diet and statin (positive control group).

Figure 6 is a result of confirming the expression of the vascular inflammation marker HMGB1 by immunohistostaining by extracting the aorta of ApoE deficient mice induced by vasculitis through a high cholesterol diet. (A) is a micrograph, (B) is a result of quantifying a staining site. Control is a normal diet group, HCD is a high cholesterol diet group, C2E is a high cholesterol diet and Achul extract administration group. # Indicates that the expression of HMGB1 in the high cholesterol diet group was significantly increased compared to the general diet group, p <0.05. * Indicates that the expression of HMGB1 in the high cholesterol diet and the Achul extract administration group was significantly decreased compared to the high cholesterol diet group, p <0.05.

Figure 7 is a result of confirming the expression of vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF-α and IL-6) by extracting the aorta of the ApoE-deficient mouse induced vasculitis through a high cholesterol diet. (A) is the result of developing protein expression through Western blot, (B) is the result of quantifying VCAM-1 protein expression. Con is a general diet group, HCD is a high cholesterol diet group, C2E is a high cholesterol diet and Achul extract administration group, statin is a positive control group administered a high cholesterol diet and statin (statin). * Indicates a significant increase in VCAM-1 expression in the high cholesterol diet group compared to the normal diet group, p <0.05. # Indicates that VCAM-1 expression was significantly decreased in the high cholesterol and achal extract or high cholesterol and statin-administered groups compared to the high cholesterol diet group, p <0.05.

The present invention relates to a pharmaceutical composition for the prevention or treatment of vasculitis, which contains the extract of Achul as an active ingredient.

Ahchul to the extract, it is preferable to extract using a lower alcohol, water or a mixture of C ₁ to C ₄ as a solvent, more preferably, of extracting with water.

The vasculitis of the present invention is preferably a vasculitis induced by a high cholesterol diet, and a vasculitis caused by a high cholesterol increases the concentration of blood cholesterol through a high cholesterol diet, resulting in a hypercholesterolemia state, and vascular endothelial cells are damaged. May be vasculitis caused by deposition of fat.

The vasculitis includes rheumatoid vasculitis, lupus vasculitis, multiple nodular arteritis, microscopic multiple vasculitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu's arteritis, Henoch-Scholine purpura, urticaria vasculitis, irritable vasculitis, giant cell arteritis and Behcet's vasculitis It may be any one selected from the group consisting of, but is not limited thereto.

In the pharmaceutical composition according to an embodiment of the present invention, the composition may inhibit the expression of cathepsin or HMGB1.

The composition may further comprise a suitable carrier, excipient or diluent commonly used in the manufacture of pharmaceutical compositions.

The pharmaceutical composition according to the present invention may be used in the form of capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols and the like, oral formulations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be. Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate And various compounds or mixtures including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like in the pharmaceutical composition. Mix is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, utopsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Suitable dosages of the pharmaceutical compositions of the present invention may be prescribed in various ways depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration and the like.

The present invention also relates to a nutraceutical composition for the prevention or improvement of vasculitis, which contains the extract of Ashal as an active ingredient.

The dietary supplement composition of the present invention may be one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.

When the health functional food composition of the present invention is used as a food additive, the health functional food composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The active ingredient may be appropriately used depending on the purpose of use (prevention or improvement). In general, in the preparation of food or beverages, the nutraceutical composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less with respect to the raw material. However, in the case of long-term intake for health purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There is no particular limitation on the type of dietary supplement. Examples of foods to which the health functional food composition may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, drinks, tea Drinks, alcoholic beverages and vitamin complexes, and the like includes all of the health food in the conventional sense.

In addition, the nutraceutical composition of the present invention may be prepared as a food, in particular a functional food. The functional food of the present invention may include ingredients that are commonly added. Examples include proteins, carbohydrates, fats, nutrients and seasonings. For example, when prepared with a drink, natural carbohydrates or flavors may be included as additional ingredients in addition to the active ingredient. The natural carbohydrates can be monosaccharides (e.g. glucose, fructose, etc.), disaccharides (e.g. maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g. dextrins, cyclodextrins, etc.) or sugar alcohols (e.g. , Xylitol, sorbitol, erythritol and the like). The flavourant may be a natural flavourant (eg, taumartin, stevia extract, etc.) and a synthetic flavourant (eg, saccharin, aspartame, etc.).

Various nutritional supplements, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid The carbonation agent etc. which are used for a drink can be contained further. Although the ratio of the above-mentioned ingredients is not critical, it is generally selected from 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Preparation Examples and Examples. These preparations and examples are only intended to explain the present invention more specifically, it is apparent to those skilled in the art that the scope of the present invention is not limited thereto.

Preparation Example 1 Preparation of Achul Extract

The dried extract was pulverized by drying, and then, by adding reflux of 10 L to 1 kg of extract, and reflux-cooled once at 100 ° C. for 3 hours. Thereafter, the filtrate obtained using the filter paper was prepared by extracting the solvent by using a vacuum condenser to remove the solvent.

Example 1 Confirmation of Plaque and Fat Accumulation Inhibitory Effects of Achul Extract

ApoE deficient mice that induced vasculitis in a high cholesterol diet, ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet Morphology of the aorta and liver was confirmed by H & E staining, and the degree of lipid accumulation was confirmed by oil-red-O staining.

ApoE deficient mice were subjected to a high cholesterol diet or a general diet for a total of 12 weeks, as shown in FIG. 1, and the daily extracts of Achul extract (100 mg / kg / day) or statin (10 mg / kg / day) of Preparation Example 1 Oral administration.

Mice were anesthetized with ketamine and xylazine after the diet, and the aortic vessels and livers were removed from the anesthetized mice, and the tissues were fixed with 4% (v / v) formaldehyde. Thereafter, the immobilized tissue was embedded with paraffin to make a block, and then the tissue was sectioned with a microtome for H & E (haematoxylin and eosin) staining or oil-red-O staining. Was carried out.

As a result, as shown in Figure 2, the formation of plaques in the aortic vessels of the high cholesterol diet group (HCD) intensified, it was confirmed that lipid accumulation deteriorated in the liver, plaques in the high cholesterol diet and Achul extract administration group (C2E) Formation and fat accumulation were confirmed to be inhibited.

In addition, as shown in FIG. 3, it was confirmed that lipid accumulation of aortic vessels increased by high cholesterol diet (HCD) was suppressed when the azu extract was administered in parallel (C2E).

Example 2. Confirmation of the inhibitory effect of cathepsin expression of Achul extract

ApoE deficient mice that induced vasculitis in a high cholesterol diet, ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet The expression level of cathepsin in the aortic vessels was analyzed using a probe.

As a result, as shown in FIG. 4, it was confirmed that the expression of cathepsin induced by high cholesterol diet in the aorta was suppressed upon administration of the extract. In addition, as shown in FIG. 5, cathepsin expression in the liver induced by the high cholesterol diet was also markedly reduced, confirming that the anti-inflammatory effect in the liver induced by the high cholesterol as well as blood vessels was shown.

Example 3. Confirmation of the inhibitory effect of HMGB1 expression of Achul extract

Expression of HMGB1 as an inflammatory marker in the blood vessels of ApoE deficient mice that induced vasculitis in a high cholesterol diet, ApoE deficient mice that received the high cholesterol diet and the Achul extract of Preparation Example 1 and ApoE deficient mice that did not induce vasculitis in a normal diet Was confirmed through immunohistostaining.

The tissue was sliced in the same manner as in Example 1, and immunohistostaining was performed. As a result, as shown in FIG. 6, the expression of HMGB1 increased by high cholesterol diet (HCD) was concurrently administered with the extract (C2E). When it was confirmed that significantly reduced.

Example 4. Confirmation of the inhibitory effect of vascular inflammatory factor expression of Achul extract

ApoE deficient mice that induced vasculitis in a high cholesterol diet, ApoE deficient mice administered with a high cholesterol diet and the Achul extract of Preparation Example 1 or statin, a positive control, and ApoE deficient mice that did not induce vasculitis in a normal diet After the blood vessels were extracted, the protein was extracted by dissolving the tissue through a tissue mill. The extracted protein was confirmed the expression level of vascular inflammatory factors through Western blot. As a result, the expression of vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF-α and IL-6) increased by the high cholesterol diet as shown in FIG. Decreased.

Therefore, the extract of the present invention can effectively improve vasculitis induced by a high cholesterol diet.

Claims (7)

1. A pharmaceutical composition for the prevention or treatment of vasculitis, containing the extract of Achul as an active ingredient.
2. The method of claim 1 wherein the solvent extract of ahchul is C ₁ ~ C ₄ lower alcohol, water, or preventing or pharmaceutical composition of vasculitis, characterized in that a mixture thereof.
3. The pharmaceutical composition for preventing or treating vasculitis according to claim 1, wherein the vasculitis is induced by hypercholesterolemia.
4. The method of claim 1, wherein the vasculitis is rheumatoid vasculitis, lupus vasculitis, multiple nodular arteritis, microscopic multiple vasculitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu's arteritis, Henoch-Scholine purpura, Hives vasculitis, hypersensitivity vasculitis, Pharmaceutical composition for the prevention or treatment of vasculitis, characterized in that any one selected from the group consisting of giant cell arteritis and Behcet vasculitis.
5. The pharmaceutical composition for preventing or treating vasculitis according to claim 1, wherein the Achul extract inhibits the expression of cathepsin or HMGB1 (high-mobility group box 1).
6. Health functional food composition for the prevention or improvement of vasculitis, containing the extract of Achul as an active ingredient.
7. The health functional food composition for preventing or improving vasculitis according to claim 6, wherein the composition is any one selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage.

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