KR20230161340A - Composition for prevention, improvement or treatment of arthritis and joint pain comprising Staphylea bumalda extract as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating arthritis and joint pain containing a pepper tree extract as an active ingredient. The pepper tree extract of the present invention has the effect of inhibiting the expression of cartilage matrix degrading enzyme (MMP-13). It is excellent, increases weight bearing rate in animal models with pain, and induces inflammatory factors (TNF-α, IL-6, IL-1β, 5-LOX, COX-2, LTB4, and PGE ₂ ) and cartilage degeneration. Since it has the effect of reducing the expression level of factors (MMP-2, MMP-9), the composition of the present invention can be usefully used for preventing, improving, or treating arthritis and joint pain.

Description

Composition for prevention, improvement or treatment of arthritis and joint pain comprising Staphylea bumalda extract as effective component}

The present invention relates to a composition for preventing, improving or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

As we enter an aging society, inflammatory diseases, including arthritis, are becoming a social issue regardless of gender. Inflammatory diseases caused by this inflammatory reaction include gastritis, colitis, arthritis, nephritis, hepatitis, arteriosclerosis, cancer, and degenerative diseases. Among them, effective drugs or treatments for preventing and treating arthritis diseases have not been developed to date. Arthritis refers to inflammatory changes occurring within the joint due to various causes such as aging, mechanical damage, and immune abnormalities.

Among the above-mentioned arthritis, osteoarthritis is a type of arthritis, also called degenerative arthritis, and refers to arthritis that occurs due to degenerative changes in the cartilage and surrounding bone in synovial joints. In other words, osteoarthritis is a disease characterized by gradual loss of joint cartilage, hypertrophy of the bone located below the cartilage, bone formation at the joint edge, and non-specific synovial inflammation. Osteoarthritis is a disease that occurs when cartilage is damaged due to aging or excessive physical pressure (eg, obesity, trauma, etc.). Therefore, osteoarthritis causes severe pain and movement disorders in joints that receive a lot of weight, such as knee joints and hip joints, and if left untreated for a long period of time, it can even lead to deformation of the joints.

In addition, gouty arthritis is an inflammation that occurs when uric acid is deposited in the spaces and tissues within joints. As the concentration of uric acid (a product left over from the human body metabolizing a substance called purine ingested through food) increases in the blood, uric acid salts increase. (Uric acid exists in the form of urate in blood, body fluids, and joint fluid) It is a disease in which crystals are deposited in the cartilage, tendons, and surrounding tissues of joints. This phenomenon causes inflammation of the joints, causing recurrent attacks accompanied by extreme pain.

Meanwhile, the pepper tree ( Staphylea bumalda ) is a deciduous tree of the Staphylea family distributed in Korea, China, and Japan. The height is 3~5m, the branches are round and grey-green, and white flowers bloom in panicles at the ends of the branches from May to June. The wood is used as chopsticks or firewood, and the young leaves are edible. Although there are no pharmacological effects of the pepper tree reported in academic journals, there are reports that the young leaves of the pepper tree alleviate respiratory diseases and inflammation in folk medicine.

As prior art related to arthritis, Korean Patent No. 1380970 discloses ‘Pharmaceutical composition for preventing or treating arthritis and anti-blood cancer agent containing herbal extracts’, and Korean Patent Publication No. 2008-0106770 discloses ‘Natural A composition for preventing and treating arthritis containing herbal extracts is disclosed. However, the present invention's 'composition for preventing, improving or treating arthritis and joint pain containing pepper tree extract as an active ingredient' has not yet been disclosed.

The present invention was developed in response to the above-mentioned needs. The present invention provides a composition for preventing, improving or treating arthritis and joint pain containing a pepper tree extract as an active ingredient, and the pepper tree extract of the present invention provides a cartilage matrix. It has an excellent effect in inhibiting the expression of decomposition enzyme (MMP-13), increases weight bearing rate in pain-induced animal models, and reduces inflammatory factors (TNF-α, IL-6, IL-1β, 5-LOX, The present invention was completed by confirming that the expression levels of COX-2, LTB4, and PGE ₂ ) and cartilage degeneration inducers (MMP-2, MMP-9) were reduced.

In order to achieve the above object, the present invention provides a health functional food composition for preventing or improving arthritis and joint pain containing pepper tree extract as an active ingredient.

Additionally, the present invention provides a pharmaceutical composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

Additionally, the present invention provides a feed additive for preventing or improving arthritis and joint pain containing pepper tree extract as an active ingredient.

Additionally, the present invention provides a veterinary composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

In addition, the present invention provides a herbal composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

The present invention relates to a composition for preventing, improving or treating arthritis and joint pain containing a pepper tree extract as an active ingredient. The pepper tree extract of the present invention has the effect of inhibiting the expression of cartilage matrix degrading enzyme (MMP-13). It is excellent, increases weight bearing rate in animal models with pain, and induces inflammatory factors (TNF-α, IL-6, IL-1β, 5-LOX, COX-2, LTB4, and PGE ₂ ) and cartilage degeneration. It has the effect of reducing the expression level of factors (MMP-2, MMP-9).

Figure 1 shows the results of confirming the change in the content of MMP-13 according to treatment of the pepper tree extract of the present invention. Con is the untreated control group, IL-1β is the group treated with IL-1β (10ng/ml) alone, and IL-1β+pepper tree is the group treated with IL-1β (10ng/ml) and pepper tree extract (100㎍/ml). ) is the treatment group. #### indicates a significant increase in MMP-13 content in the group treated with IL-1β alone compared to the control group (Con), p<0.0001. * indicates a significant decrease in MMP-13 content in the group treated with IL-1β and pepper tree extract compared to the group treated with IL-1β alone, * indicates p<0.05.
Figure 2 shows the results of confirming the change in weight bearing ratio due to pepper tree extract in an osteoarthritis animal model for 21 days. Con is the untreated control group, MIA is the MIA-induced osteoarthritis group, MIA+GLM is the positive control group, which is the MIA (monosodium iodoacetate) and GLM (green lipped mussel) administered group, and MIA+pepper tree is the MIA and 200 This is the group administered ㎎/kg of pepper tree extract. #### indicates that the weight-bearing ratio of the osteoarthritis induction group was significantly reduced compared to the untreated control group, p<0.0001, *, **** are the MIA+GLM or MIA+pepper tree extract group compared to the osteoarthritis induction group. This means that the weight bearing rate increased statistically significantly, * means p<0.05, and **** means p<0.0001.
Figure 3 shows the results of confirming changes in the expression of inflammatory factors (TNF-α, IL-6, IL-1β, 5-LOX, COX-2, LTB4, and PGE ₂ ) caused by pepper tree extract in an osteoarthritis animal model. Con is the untreated control group, MIA is the MIA-induced osteoarthritis group, MIA+GLM is the positive control group, which is the MIA (monosodium iodoacetate) and GLM (green lipped mussel) administered group, and MIA+pepper tree is the MIA and 200 This is the group administered ㎎/kg of pepper tree extract. ##, ###, #### indicate that the expression level of inflammatory factors in the osteoarthritis induced group was significantly increased compared to the untreated control group, ## is p<0.01, and ### is p<0.001. and #### is p<0.0001. *, ***, **** indicate that the expression level of inflammatory factors was significantly decreased in the MIA+GLM or MIA+pepper tree extract group compared to the osteoarthritis induction group, * is p<0.05, and *** is p<0.001, and **** is p<0.0001.
Figure 4 shows the results of confirming the expression of cartilage degeneration-inducing factors (MMP-2, MMP-9) by pepper tree extract in an osteoarthritis animal model. MIA is the MIA-induced osteoarthritis induction group, MIA+GLM is the positive control group, which is the group administered MIA (monosodium iodoacetate) and GLM (green lipped mussel), and MIA+pepper tree is the group administered MIA and 200 mg/kg of pepper tree extract. . #, #### indicate that the expression level of cartilage degeneration-inducing factors in the osteoarthritis-induced group was significantly increased compared to the untreated control group, # is p < 0.05, and #### is p < 0.0001. *, **** indicate a statistically significant decrease in the expression level of cartilage degeneration-inducing factors in the MIA+GLM or MIA+pepper tree extract group compared to the osteoarthritis induction group, * means p<0.05, and **** means p<0.0001.

The present invention relates to a health functional food composition for preventing or improving arthritis and joint pain containing pepper tree extract as an active ingredient.

Any part of the pepper tree can be used as the pepper tree, preferably leaves, but it is not limited thereto.

The arthritis is osteoarthritis, and the joint pain is preferably joint pain caused by osteoarthritis, but the present invention is not limited thereto, and the active ingredient is characterized by inhibiting the expression of MMP-13 (Matrix metalloproteinase-13).

The pepper tree extract may be prepared by a method including the following steps, but is not limited to this:

1) Extracting by adding an extraction solvent to the pepper tree;

2) filtering the extract of step 1); and

3) Preparing an extract by concentrating the filtered extract of step 2) under reduced pressure and drying it.

In step 1), the extraction solvent is preferably water, a lower alcohol of C ₁ to C ₄ or a mixture thereof, more preferably ethanol, and even more preferably 70% (v/v) ethanol, but is not limited thereto. .

In the above production method, the extraction of the pepper tree can be performed using all conventional methods known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. The vacuum concentration in step 3) is preferably performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably performed by reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.

The composition is preferably manufactured in a dosage form selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.

When using the health functional food composition of the present invention as a food additive, the pepper tree extract can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention or improvement). Generally, when producing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, 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 are no special restrictions on the types of foods above. Examples of foods to which the extract can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, These include alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense.

When the composition of the present invention is used as a health drink, it may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as textrin and cyclotenstrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 g of the composition of the present invention. The composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal neutralizer, pH adjuster, stabilizer, preservative, glycerin, alcohol, carbonic acid. It may contain carbonating agents used in beverages. In addition, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. Although the ratio of these additives is not very important, the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

Additionally, the present invention relates to a pharmaceutical composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient. The arthritis is preferably osteoarthritis, and the joint pain is preferably joint pain caused by osteoarthritis, but is not limited thereto.

The composition of the present invention is preferably prepared in any one formulation selected from capsules, powders, granules, tablets, suspensions, emulsions, syrups, and aerosols, but is not limited thereto.

The composition of the present invention may further include pharmaceutically acceptable carriers, excipients, or diluents in addition to the above active ingredients, and may be in various oral or parenteral dosage forms. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include capsules, powders, granules, tablets, pills, etc. These solid preparations contain one or more compounds and at least one excipient, such as starch, calcium carbonate, sucrose, or lactose ( It is prepared by mixing lactose, gelatin, etc. Additionally, in addition to simple excipients, lubricants such as magnesium stearate, talc, etc. are also used. Liquid preparations for oral administration include suspensions, emulsions, syrups, and aerosols. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspension solvents may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurel, glycero gelatin, etc. can be used. When administering parenterally, it is preferable to choose external application through the skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dura, or intracerebrovascular injection.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the level of the effective amount is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the field of medicine. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of the disease, and the daily dosage is based on the amount of pepper tree extract. As a standard, it is 0.01 to 2,000 mg/kg, preferably 30 to 500 mg/kg, and more preferably 50 to 300 mg/kg, and can be administered 1 to 6 times a day. The composition of the present invention can be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response modifiers.

Additionally, the present invention relates to a feed additive for preventing or improving arthritis and joint pain containing pepper tree extract as an active ingredient.

The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. In the present invention, the term 'feed' may mean any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals. The type of feed is not particularly limited, and feed commonly used in the art can be used. Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, oils and fats, single-cell proteins, zooplanktons or foods. These may be used alone or in combination of two or more types.

Additionally, the present invention relates to a veterinary composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

The veterinary composition containing the pepper tree extract of the present invention may further include appropriate excipients and diluents according to conventional methods. Excipients and diluents that may be included in the veterinary composition containing the pepper tree extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, and gelatin. , calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid. Examples include paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

The veterinary composition containing the pepper tree extract according to the present invention may further include fillers, anti-coagulants, lubricants, wetting agents, spices, emulsifiers, preservatives, etc., and the veterinary composition according to the present invention is administered to animals after being administered. Can be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient, and the dosage forms can be powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, It may be in the form of soft or hard gelatin capsules, suppositories, sterile injectable solutions, sterile external preparations, etc.

The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but can be administered once or several times a day, and the dosage increases or decreases depending on the route of administration, degree of disease, sex, weight, age, etc. It can be. Accordingly, the above dosage does not limit the scope of the present invention in any way.

In addition, the present invention provides a herbal composition for preventing or treating arthritis and joint pain containing pepper tree extract as an active ingredient.

The herbal medicine composition of the present invention means that it is manufactured according to an oriental medicine prescription, but is not limited thereto.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for illustrating the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.

Example 1. Preparation of pepper tree extract

To 1 kg of Staphylea bumalda leaves of the present invention, 15 liters of 70% (v/v) ethanol was added, extracted at 85°C for 3 hours, and the filtered liquid was concentrated under reduced pressure at 45°C and dried to produce pepper. Wood extract was obtained.

Example 2. Evaluation of anti-inflammatory efficacy in chondrocytes

In human chondrocytes (SW1353), changes in the expression of MMP-13 (Matrix metalloproteinase-13), a cartilage matrix degrading enzyme activated by an increase in inflammatory cytokines following treatment with pepper tree extract, were confirmed.

[Cell culture]

After culturing human chondrocytes (SW1353) using DMEM/F12 (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12) culture medium supplemented with 10% FBS (Fetal Bovine Serum), 100㎍/㎖ of Capsicum ginseng was added. After processing the extract and culturing it for 2 hours, it was treated with IL-1β (10ng/ml) for 24 hours.

(1) Confirmation of the effect of reducing the expression of MMP-13 mediated by IL-1β

The extracellular matrix (ECM) that makes up cartilage tissue is decomposed due to increased expression and activation of MMPs due to the secretion of inflammatory cytokines. To determine whether pepper tree extract affects the expression of MMPs, an ELISA kit was used. (R&D Systems) conducted the analysis.

As a result, the expression level of MMP-13 increased in the culture supernatant treated with IL-1β for 24 hours, but the expression level of MMP-13 due to IL-1β was significantly decreased in cells pretreated with the pepper tree extract of the present invention ( Figure 1).

Example 3. Confirmation of the effect of pepper tree extract on weight bearing in an animal model of osteoarthritis induced by MIA (monosodium iodoacetate)

To determine the effect of pepper tree extract on weight bearing in an animal model of MIA-induced osteoarthritis, MIA (diluted with 0.9% saline to a concentration of 60 mg/ml), an osteoarthritis-causing substance, was placed in the joint space of the right hind limb of 7-week-old SD rats. ) After inducing osteoarthritis by administering 50 ㎕, 200 mg/kg of pepper tree extract was orally administered once a day for a total of 21 days, and the weight-bearing ratio was measured at 7-day intervals. As a positive control group, green lipped mussel oil (GLM, 100 mg/kg) was orally administered.

Hind limb weight bearing was measured using a paw weight tester (Incapacitance tester, Linton instrument Co., UK, Ser No. 01/45/25). The rat with osteoarthritis induced in the tester's holder stood on its normal foot to which MIA had not been administered due to pain, so the weight of both feet was unbalanced, and the weight of the foot to which MIA had been administered was measured to be relatively lighter compared to the weight of the normal foot. When measuring the weight of the feet, the weight (g) of both feet was measured while the SD rat's abdomen did not touch the sensor of the device, and using the measured weight of the feet, the weight bearing ratio (%) was calculated using the method of Equation 1 below. . The weight bearing is the force of supporting and pressing with the foot. Normally, the weight of both feet is balanced and the weight bearing rate of one foot is 50%. However, as the pain becomes worse due to osteoarthritis, the weight bearing rate (%) of the hind limb caused by osteoarthritis decreases.

[Equation 1]

Weight bearing ratio (%) = [Weight of hind limbs causing osteoarthritis / (Weight of both hind limbs)] × 100

As a result, it was confirmed that compared to the normal SD rat group (Con), the weight bearing ratio (%) of the group in which osteoarthritis was induced by administering MIA significantly decreased over time. In contrast, the weight bearing ratio (%) of the positive control group (GLM) or the pepper tree extract administered group was significantly increased (Figure 2).

Example 4. Confirmation of the effect of pepper tree extract on inflammatory factors and cartilage degeneration factors in an animal model of osteoarthritis induced by MIA (monosodium iodoacetate)

Inflammatory factors (TNF-α, IL-6, IL-1β, 5-LOX, COX-2, LTB4, and PGE ₂ ) and cartilage degeneration factors (MMP-2 and MMP) in the blood and joints of animals with osteoarthritis. The expression level of -9) was confirmed using ELISA technique.

As a result, it was confirmed that when osteoarthritis was induced by MIA, the expression level of inflammatory factors and cartilage degeneration-inducing factors increased, whereas when pepper tree extract was administered, the expression level of increased inflammatory factors and cartilage degeneration-inducing factors decreased. (Figures 3 and 4). Through this, it was found that pepper tree extract suppresses inflammation and joint cartilage damage caused by osteoarthritis.

Claims (12)

A health functional food composition for preventing or improving arthritis and joint pain containing Staphylea bumalda extract as an active ingredient. The health functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the arthritis is osteoarthritis, and the joint pain is joint pain caused by osteoarthritis. The health functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the composition reduces the expression of MMP-13 (Matrix metalloproteinase-13). The health functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the extraction solvent of the pepper tree extract is water, C ₁ to C ₄ lower alcohol, or a mixture thereof. The health functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the composition is manufactured in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup, and beverage. . A pharmaceutical composition for preventing or treating arthritis and joint pain containing an extract of Staphylea bumalda as an active ingredient. The pharmaceutical composition for preventing or treating arthritis and joint pain according to claim 6, wherein the arthritis is osteoarthritis, and the joint pain is joint pain caused by osteoarthritis. The pharmaceutical composition for preventing or treating arthritis and joint pain according to claim 6, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient, or diluent in addition to the active ingredient. The pharmaceutical composition for preventing or treating arthritis and joint pain according to claim 7, wherein the composition is prepared in any one formulation selected from capsules, powders, granules, tablets, suspensions, emulsions, syrups and aerosols. A feed additive for preventing or improving arthritis and joint pain containing pepper tree ( Staphylea bumalda ) extract as an active ingredient. A veterinary composition for preventing or treating arthritis and joint pain containing an extract of Staphylea bumalda as an active ingredient. A herbal medicine composition for preventing or treating arthritis and joint pain containing an extract of Staphylea bumalda as an active ingredient.