KR20180125396A - Composition for preventing, improving or treating vasculitis comprising Curcuma zedoaria extract as effective component - Google Patents

Abstract

The present invention relates to a composition containing a curcuma zedoaria extract as an effective component for preventing, improving or treating vasculitis. The curcuma zedoaria extract has excellence in suppressing lipid storage in an aorta and plaque formation in a blood vessel due to a high-cholesterol meal, decreasing expression on cathepsin in the aorta, suppressing expression on HMGB1 which is a vasculitis marker, and suppressing expression on a vasculitis factor, thereby advantageously using the composition for a vasculitis therapeutic agent or a health functional food for preventing or improving vasculitis.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing, ameliorating or treating vasculitis,

The present invention relates to a composition for preventing, ameliorating or treating vasculitis containing an extract as an active ingredient, and more particularly, to a composition for preventing, ameliorating or treating vasculitis, which comprises an extract, which can be used as a health functional food or a pharmaceutical composition, , ≪ / RTI >

Vasculitis is one of the intractable conditions common to autoimmune diseases, and is a disease characterized by inflammation of the blood vessel wall and subsequent tissue damage. When inflammation of the blood vessel wall occurs, ischemia also occurs in the tissue that has been supplied through this blood vessel, resulting in tissue damage. Because all types of blood vessels in the body and blood vessels of all organs can be invaded, symptoms and symptoms vary widely depending on the location and characteristics of the involved blood vessels. There may be cases of primary disease without underlying disease, secondary to rheumatic diseases such as rheumatoid arthritis or systemic lupus erythematosus.

Depending on the size and extent of invaded blood vessels, it may be possible to treat a variety of conditions including collagen vasculitis (rheumatic vasculitis, lupus vasculitis), multiple nodular arteriitis, microscopic multiple vasculitis, Wegener's granulomatosis, Chuck- Strauss syndrome, Takayasu's arteritis, Diseases such as vasculitis, hypersensitivity vasculitis, giant cell arteritis (temporal arteritis), and Behcet's vasculitis belong to vasculitis.

It is thought that the cause of vasculitis is due to immune function abnormality or allergic reaction in our body. The process in which vasculitis occurs is first that the immune system, which recognizes self cells as an antigen, starts by exiting the antibody in a normal state. The binding of an antibody to an antigen is called an immunocomplex. The complex builds up in the blood vessel wall, causing irritation of the blood vessel wall. An inflammatory reaction causes blood flow to the opposite side of the thickened wall of the vessel, resulting in an increase in the wall of the blood vessels and an aneurysm.

Patients with vasculitis have systemic symptoms such as fever, weight loss, loss of appetite, weakness, and symptoms such as spots or nodules on the skin, limb pain, dyspnea, kidney failure, gastrointestinal bleeding and neuropathy appear. According to the type of vasculitis, the clinical findings and course are very diverse, and even the same vasculitis is manifested by various patients, making clinical diagnosis difficult. Complications include visual impairment, heart disease, myocardial infarction, dyspnea, pulmonary hemorrhage, nephritis, intestinal bleeding, intestinal necrosis, skin necrosis, and infection.

Treatment of vasculitis usually involves steroids or immunosuppressants. However, depending on the individual disease, the therapeutic principle such as the therapeutic agent and the treatment period will be different. Both steroids and immunosuppressants used in vasculitis are medicines that can cause various side effects including infection. Therefore, attention should be paid to the occurrence of side effects, and development of a substitute substance is required.

On the other hand, Curcuma zedoaria has dried roots of Curcuma phaeocaulis (Zingiberaceae) and has traditionally been used for indigestion, worms, colic, and menstrual irregularities. It has gastric and digestive action, , Hepatocyte protective action, etc. have been reported. It is also known to be effective for controlling anthrax of pepper, having macrophage activation ability and pancreatic lipase inhibiting activity.

Meanwhile, Korean Patent No. 1710081 discloses a composition comprising an overexpression extract capable of increasing the activity of TLR4 and TLR7 / 8 and inducing the production of interferon beta, and its use, and Korean Patent Publication No. 1287688 A composition for treating atopic dermatitis using a natural substance containing an extract is disclosed, but a composition for preventing, improving or treating vasculitis containing the extract of the present invention as an active ingredient has not been disclosed.

The present invention provides a composition for preventing, ameliorating or treating vasculitis, which comprises an extract as an active ingredient, the composition comprising an extract of Caterpillar, which is known as an arteriosclerosis-induced vascular inflammation marker, And inhibited plaque formation of the blood vessels and lipid accumulation of the aorta, and inhibited the expression of vascular inflammatory factors, thus completing the present invention.

In order to solve the above-mentioned problems, the present invention provides a pharmaceutical composition for preventing or treating vasculitis containing an extract as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or ameliorating vasculitis, which comprises an extract as an active ingredient.

The present invention relates to a composition for preventing, ameliorating or treating vasculitis containing an extract as an active ingredient. The extract of the present invention inhibits plaque formation and a lipid accumulation of aorta, which are increased by high cholesterol diet, Inhibits the expression of HMGB1, which is a vascular inflammation marker, and inhibits expression of vascular inflammatory factors CX3CL1, VCAM-1, ICAM-1, TNF-a and IL-6, The composition of the present invention containing an extract as an active ingredient can be used as a functional material for preventing, ameliorating or treating vasculitis.

FIG. 1 is a schematic diagram of an animal test method for confirming vascular inflammation-inhibiting effect by administration of an extract from an ApoE-deficient mouse induced by vasculitis through a high cholesterol diet.
FIG. 2 shows H & E staining of tissues by extracting the aorta and liver of ApoE-deficient mice induced by vasculitis through high cholesterol diet. Control is the normal diet group, HCD is the high cholesterol diet group, C2E is the high cholesterol diet and the extract extract group, statin is the high cholesterol diet and statin.
FIG. 3 is a result of extracting the aorta of ApoE-deficient mice induced by vasculitis through high cholesterol diet and staining the fat in the tissues with Oil-Red-O. (A) is a photograph of a microscope, and (B) is a result of quantifying a staining site. Control is the dietary group, HCD is the high cholesterol dietary group, and C2E is the high cholesterol dietary supplement. # Indicates that fat accumulation in hypercholesterolemic group was significantly increased compared to the general dietary group, and p <0.05. * Indicates a significant decrease in fat accumulation in the high cholesterol diet and the extract extract group compared to the high cholesterol diet group, p <0.05.
FIG. 4 is a photograph showing the extent of expression of cathepsin in the aorta of ApoE deficient mice induced by vasculitis through a high cholesterol diet. Control is the normal diet group, HCD is the high cholesterol diet group, C2E-1 ~ 3 is the high cholesterol diet and the extract extract group, statin is the high cholesterol diet and statin.
FIG. 5 is a photograph showing the degree of expression of cathepsin in liver, lung, kidney, heart, and spleen of ApoE-deficient mice induced by vasculitis through a high cholesterol diet. Control is the normal diet group, HCD is the high cholesterol diet group, C2E-1 ~ 3 is the high cholesterol diet and the extract extract group, statin is the high cholesterol diet and statin.
FIG. 6 shows the result of immunohistochemical staining for the expression of HMGB1, a vascular inflammation marker, in aorta of a mouse suffering from vasculitis induced by high cholesterol diet. (A) is a photograph of a microscope, and (B) is a result of quantifying a staining site. Control is the dietary group, HCD is the high cholesterol dietary group, and C2E is the high cholesterol dietary supplement. # Indicates that the expression of HMGB1 in the high cholesterol diet group was significantly increased compared to the normal diet group, and p <0.05. * Indicates that the expression of HMGB1 in the high cholesterol diet and the high fat cholesterol diet group was significantly lower than that in the high cholesterol diet group, p <0.05.
FIG. 7 shows the results of confirming the expression of vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF-α and IL-6) by extracting the aorta of ApoE deficient mice induced by vasculitis through a high cholesterol diet. (A) is the result of developing protein expression through Western blotting, and (B) is the result of quantifying VCAM-1 protein expression. Con is a normal control group, HCD is a high cholesterol diet group, C2E is a high cholesterol diet and an extract group, statin is a high cholesterol diet and statin. * Indicates a significant increase in VCAM-1 expression in the high cholesterol diet group compared to the general dietary group, p <0.05. # Indicates a significant decrease in VCAM-1 expression in high cholesterol and high-cholesterol and high-cholesterol and statin-treated groups compared to high cholesterol diet group, p <0.05.

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

Preferably, the extract is extracted using a lower alcohol of C ₁ to C ₄ , water or a mixture thereof as a solvent, more preferably water.

The vasculitis of the present invention is preferably a vasculitis induced by a high cholesterol diet, and vasculitis caused by hypercholesterolemia leads to elevation of blood cholesterol concentration through hypercholesterolemia, hypercholesterolemia, and damage of vascular endothelial cells It may be a vasculitis caused by the deposition of fat.

The vasculitis may be selected from the group consisting of rheumatic vasculitis, lupus vasculitis, multiple nodular arteriitis, microscopic polyangiitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu arteritis, Henoch-Schönlein purpura, urticaria, irritable vasculitis, , But is not limited thereto.

In a 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 suitable carriers, excipients or diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical composition according to the present invention may be formulated into oral formulations such as capsules, powders, granules, tablets, suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method . Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Various compounds or mixtures including cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, . 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, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. 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. Examples of the suppository base include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

A suitable dose of the pharmaceutical composition of the present invention may be variously prescribed by factors such as the formulation method, the administration method, the age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient .

The pharmaceutical composition of the present invention may be administered orally or parenterally. In the case of parenteral administration, the composition may be administered topically to the skin, intravenously, subcutaneously, intramuscularly, intraperitoneally, or transdermally.

Further, the present invention relates to a health functional food composition for preventing or ameliorating vasculitis containing an extract as an active ingredient.

The health functional food composition of the present invention may be a single formulation selected from powders, granules, pills, tablets, capsules, candies, syrups and beverages, 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 may be used together with other food or food ingredients, and suitably used according to a conventional method. The active ingredient may be suitably used depending on its intended use (prevention or improvement). Generally, the health functional food composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight based on the raw material, when the food or beverage is produced. However, in the case of long-term consumption intended for health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount of more than the above range.

There is no particular limitation on the kind of the health functional food. Examples of the foods to which the health functional food composition can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, soups, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

In addition, the health functional food composition of the present invention can be produced as a food, particularly a functional food. The functional food of the present invention may contain ingredients that are conventionally added. For example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, in the case of a drink, a natural carbohydrate or a flavoring agent may be included as an additional ingredient in addition to the active ingredient. The natural carbohydrate may be selected from the group consisting of monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose etc.), oligosaccharides, polysaccharides (e.g., dextrin, cyclodextrin, , Xylitol, sorbitol, erythritol, etc.). The flavoring agent may be a natural flavoring agent (e.g., tau Martin, stevia extract, etc.) and a synthetic flavoring agent (e.g., saccharin, aspartame, etc.).

In addition to the above-mentioned health functional food composition, various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, A carbonating agent used in beverages, and the like. Although the ratio of the above-mentioned ingredients is not critical, it is generally selected in the range of 0.01 to 0.1 part 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. It is to be understood by those skilled in the art that these preparations and examples are merely intended to explain the present invention more specifically and that the scope of the present invention is not limited thereto.

Manufacturing example  One. Out  Preparation of extract

After the outflow was dried and pulverized, 10 L of water was added to 1 kg of the outflow, and the mixture was refluxed once at 100 캜 for 3 hours and extracted. Subsequently, the filtrate obtained using the filter paper was subjected to removal of the solvent by using a reduced pressure concentrator to prepare an extract.

Example  One. Out  Identification of plaque and fat accumulation inhibitory effect of extract

ApoE deficient mice in which high cholesterol diet induced vasculitis was induced, high-cholesterol diets and an outbreak extract of Preparation Example 1 or statin, which is a positive control, and ApoE-deficient mice that did not induce vasculitis in the general diet Aortic and hepatic morphology was confirmed by H & E staining and lipid accumulation was confirmed by Oil-Red-O staining.

ApoE-deficient mice were fed a high cholesterol diet or a general diet for a total of 12 weeks as shown in Fig. 1, and daily supplementation of the extract (100 mg / kg / day) or statin (10 mg / kg / day) Orally.

Mice were anesthetized with ketamine and xylazine at the end of the meal, and the aortic vessels and liver were extracted from anesthetized mice and the extracted tissues were fixed with 4% (v / v) formaldehyde. Then, the fixed tissue was embedded with paraffin to form a block, and the tissue was sectioned with a microtome to perform haematoxylin and eosin (H & E) staining or Oil-Red-O staining Respectively.

As a result, as shown in FIG. 2, plaque formation in the aortic blood vessels of the high cholesterol diet group (HCD) was intensified and lipid accumulation in the liver deteriorated. In the high cholesterol diet and C2 extract group, Formation and fat accumulation were inhibited.

In addition, as shown in Fig. 3, it was confirmed that lipid accumulation of aorta blood vessels increased by high cholesterol diet (HCD) was suppressed when C2 extracts were administered simultaneously.

Example  2. Out  Confirming the inhibitory effect of extract on cathepsin expression

ApoE deficient mice in which high cholesterol diet induced vasculitis was induced, high-cholesterol diets and an outbreak extract of Preparation Example 1 or statin, which is a positive control, and ApoE-deficient mice that did not induce vasculitis in the general diet The degree of expression of cathepsin in aortic blood 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 inhibited when the extract extract was administered. In addition, as shown in FIG. 5, the expression of cathepsin in the liver induced by the high cholesterol diet was also markedly decreased, confirming that it was accompanied by inflammation-suppressing effect in the liver induced by high cholesterol as well as blood vessels.

Example  3. Out  Extract HMGB1  Confirming expression suppression effect

Expression of HMGB1, an inflammatory marker in the blood vessels of ApoE-deficient mice that did not induce vasculitis due to apoE-deficient mice that were administered with the hypercholesterolemic diet, the hypercholesterol diet, and the extract of Preparation 1, Were identified by immunohistochemical staining.

As shown in FIG. 6, the expression of HMGB1 increased by high cholesterol diet (HCD) was increased by C2E (C2E) treatment in the same manner as in Example 1, , And it was confirmed that the decrease was remarkable.

Example  4. Out  Inhibitory Effect of Extracts on Vascular Inflammatory Factor Expression

ApoE deficient mice in which high cholesterol diet induced vasculitis was induced, high-cholesterol diets and an outbreak extract of Preparation Example 1 or statin, which is a positive control, and ApoE-deficient mice that did not induce vasculitis in the general diet After the blood vessels were extracted, the proteins were dissolved by dissolving the tissue through a tissue grinder. The extracted protein was expressed by Western blot to determine the degree of vascular inflammatory factor expression. As a result, the expression of the vascular inflammatory factors (CX3CL1, VCAM-1, ICAM-1, TNF-α and IL-6) increased by the high cholesterol diet was increased by C2E Respectively.

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

Claims (7)

A pharmaceutical composition for the prevention or treatment of vasculitis which comprises an extract as an active ingredient. The pharmaceutical composition for preventing or treating vasculitis according to claim 1, wherein the solvent of the extract is C ₁ -C ₄ lower alcohol, water or a mixture thereof. The pharmaceutical composition for preventing or treating vasculitis according to claim 1, wherein the vasculitis is induced by hypercholesterolemia. The method of claim 1, wherein the vasculitis is selected from the group consisting of rheumatic vasculitis, lupus vasculitis, multiple nodular arteriitis, microscopic polyangiitis, Wegener's granulomatosis, Chuck-Strauss syndrome, Takayasu arteritis, Henoch-Schönlein purpura, Giant cell arteritis and Behcet's vasculitis. &Lt; Desc / Clms Page number 24 &gt; The pharmaceutical composition for preventing or treating vasculitis according to claim 1, wherein the ascending extract inhibits the expression of cathepsin or HMGB1 (high-mobility group box 1). A composition for health functional food for preventing or ameliorating vasculitis containing an extract as an active ingredient. [Claim 7] The composition according to claim 6, wherein the composition is one of powder, granule, ring, tablet, capsule, candy, syrup and beverage.

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