KR20230110176A - Composition for prevention, improvement or treatment of arthritis and joint pain comprising Tilia insularis extract as effective component - Google Patents

Abstract

The present invention relates to a composition for the prevention, improvement, or treatment of arthritis and joint pain containing an extract of cinnamon tree as an active ingredient, and in detail, the extract of cinnamon tree of the present invention inhibits the expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which are cartilage matrix decomposition enzymes, and reduces the content of glycosaminoglycan (GAG), a product of cartilage proteoglycan degradation, Since it exhibits an analgesic effect in pain-induced animal models and has an effect of alleviating edema due to inflammation, 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 Tilia insularis extract as effective component

The present invention relates to a composition for the prevention, improvement or treatment of arthritis and joint pain containing an extract of cinnamon tree as an active ingredient.

As we enter an aging society, inflammatory diseases including arthritis are socially emerging regardless of gender. Inflammatory diseases caused by this inflammatory response include gastritis, colitis, arthritis, nephritis, hepatitis, arteriosclerosis, cancer, or degenerative diseases. Among them, effective drugs or treatments for the prevention and treatment of arthritis diseases have not been developed so far. Arthritis refers to an inflammatory change in a joint due to various causes such as aging, mechanical damage, and immune abnormality.

Among the above-mentioned arthritis, osteoarthritis (osteoarthritis) is a kind of arthritis, also called degenerative arthritis, refers to arthritis caused by degenerative changes in cartilage and surrounding bones in synovial joints. That is, osteoarthritis is a disease characterized by gradual loss of articular cartilage, hypertrophy of bones located below the cartilage, bone formation at the joint edge, and non-specific synovial inflammation. Osteoarthritis is a disease caused by damage to cartilage due to aging or excessive physical pressure (eg, obesity, trauma, etc.). Therefore, osteoarthritis shows severe pain and movement disorders in joints that receive a lot of weight, that is, knee (knee) joints, hip (hip) joints, etc., and even causes deformation of the joints when left unattended for a long period of time.

In addition, gouty arthritis is inflammation caused by the deposition of uric acid in the spaces and tissues within the joint. As the concentration of uric acid (a product left after the human body metabolizes a substance called purine consumed through food) increases, uric acid (uric acid is present in the form of uric acid in the blood, body fluids, and joint fluid) is a disease in which crystals are deposited in the cartilage, tendon, and surrounding tissues of the joint. This phenomenon causes inflammation of the joint, resulting in recurrent attacks with excruciating pain.

On the other hand, Tilia insularis Nakai is a deciduous tree belonging to the family Pinaceae and grows in Ulleungdo, reaching 30m in height and 1m in diameter. The bark is grayish white, and there are white terminal hairs on young branches, but they are lost at the back. Leaves are alternate, 8-9cm long, ovate or circular, with a sharp apex, and the base is cordate. On the surface, there are hairs on the veins, but they gradually disappear, and the back side is grayish green, with white or brown hairs densely growing on the veins and sparse. The bract is a lanceolate type and has a virgin hair along with the hwagyeong. Flowers bloom in July, fruits have short hairs, and ripen in September-October. It is a major water resource in Ulleungdo and a nectar plant. Bark is used as a fiber substitute.

Arthritis-related technology is disclosed in Korean Patent Publication No. 2022-0000185 for 'a pharmaceutical composition for preventing or treating arthritis containing a mixed extract of peony and licorice', and in Korean Patent No. 1941183 'A composition for preventing or improving arthritis containing an extract of Schisandra chinensis and a method for producing the same' are disclosed. However, the 'composition for the prevention, improvement or treatment of arthritis and joint pain containing an extract of the present invention as an active ingredient' has not yet been disclosed.

The present invention has been derived from the above needs, and the present invention provides a composition for preventing, improving or treating arthritis and joint pain containing an extract of cinnamon tree as an active ingredient, and an extract of cinnamon tree of the present invention inhibits the expression of cartilage matrix degrading enzymes MMP-1 (Matrix metalloproteinase-1) and MMP-13 (Matrix metalloproteinase-13), and cartilage proteoglycan (Proteoglycan) decomposition product, GAG (Glyco saminoglycan), exhibiting an analgesic effect in pain-induced animal models, and confirming that there is an effect of relieving edema due to inflammation, the present invention was completed.

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 an extract of cinnamon tree as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of arthritis and joint pain containing the extract of chinensis as an active ingredient.

In addition, the present invention provides a feed additive for the prevention or improvement of arthritis and joint pain containing the extract of chinensis as an active ingredient.

In addition, the present invention provides a veterinary composition for the prevention or treatment of arthritis and joint pain, containing an extract of cinnamon tree as an active ingredient.

The present invention relates to a composition for the prevention, improvement, or treatment of arthritis and joint pain containing an extract of cinnamon tree as an active ingredient, and in detail, the extract of cinnamon tree of the present invention inhibits the expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which are cartilage matrix decomposition enzymes, and reduces the content of glycosaminoglycan (GAG), a product of cartilage proteoglycan degradation, It exhibits an analgesic effect in pain-induced animal models and has the effect of alleviating edema caused by inflammation.

Figure 1 is the result of confirming the change in the content of MMP-1 and MMP-13 according to the treatment of the extract of the present invention. #### indicates that the MMP-1 and MMP-13 contents of the IL-1β treated group were significantly increased compared to the untreated control group (Con), p<0.0001. *** and **** indicate that the MMP-1 or MMP-13 content of the island extract treatment group of the present invention was significantly decreased compared to the IL-1β treatment group, *** is p <0.001, and **** is p <0.0001.
Figure 2 is the result of confirming the change in GAG content according to the treatment of the extract of the present invention. ## indicates that the GAG content of the IL-1β treated group was significantly increased compared to the control group (Con) not treated with anything, and ## is p<0.01. * indicates that the GAG content of the island extract treatment group of the present invention was significantly decreased compared to the IL-1β treatment group, p <0.05.
Figure 3 is a result of confirming the analgesic effect according to the administration of the extract of the present invention in the pain-induced animal model by acetic acid induction. The control group (con) was a group in which pain was induced by intraperitoneal administration of acetic acid (10 ml/kg), and the PC was a positive control group and was administered with diclofenac (10 mg/kg). *, **, *** is that the experimental group administered with the positive control group (PC) or the present invention (150 mg / kg and 300 mg / kg) compared to the control group (con) inducing pain due to intraperitoneal administration of acetic acid (150 mg / kg and 300 mg / kg) twisted the body for 10 minutes. That is, * is p <0.05, ** is p <0.01, and *** is p <0.001.
Figure 4 is the result of confirming the effect of relieving foot edema according to the administration of cinnamon tree extract in an animal model inducing inflammation by carrageenan. The control group (con) is a group administered only with carrageenan, and the PC is a positive control group, which is a group administered with indomethacin (5 mg/kg). **, ***, **** indicate that the foot edema of the positive control group or the island extract administration group was significantly reduced compared to the carrageenan alone administration group (con), ** is p <0.01, *** is p <0.001, and **** is p <0.0001.

The present invention relates to a health functional food composition for the prevention or improvement of arthritis and joint pain containing an extract of cinnamon tree as an active ingredient.

Preferably, the arthritis is osteoarthritis, and the joint pain is joint pain caused by osteoarthritis, but is not limited thereto, and the active ingredient inhibits the expression of MMP-1 (Matrix metalloproteinase-1) and MMP-13, and reduces the content of GAG (glycosaminoglycan).

The island extract may be prepared by a method comprising the following steps, but is not limited thereto:

1) extracting by adding an extraction solvent to the cedar 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, C ₁ ~ C ₄ lower alcohol, or a mixture thereof, more preferably an ethanol extract, and even more preferably a 70% (v / v) ethanol extract, but is not limited thereto.

In the above production method, all conventional methods known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction, can be used for extraction of cinnamon tree. 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 reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.

The composition is preferably prepared in any 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 island extract may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, when preparing 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 material. However, in the case of long-term intake for the purpose of health and hygiene or health control, 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 above the above range. There is no particular limitation on the type of food. Examples of foods to which the extract or its fraction may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, and includes all health functional foods in a 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 components, like conventional drinks. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclotenstrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used. The proportion 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 may contain various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, the composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

In addition, the present invention relates to a pharmaceutical composition for the prevention or treatment of arthritis and joint pain, containing an extract of cinnamon tree as an active ingredient.

Preferably, the arthritis is osteoarthritis, and the joint pain is 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 a pharmaceutically acceptable carrier, excipient, or diluent in addition to the above active ingredient, and may be in various oral or parenteral formulations. 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 are prepared by mixing one or more compounds with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, emulsions, syrups, aerosols, etc., and various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included in addition to water and liquid paraffin, which are commonly used simple diluents. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending solvents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used. In the case of parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection method.

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 a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the level of the effective amount may be determined according to the type of patient's disease, severity, drug activity, sensitivity to the drug, administration time, administration route and discharge rate, treatment period, factors including concurrently used drugs, and other factors well known in the medical field. 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 single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

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

The present invention also relates to a feed additive for the prevention or improvement of arthritis and joint pain, containing an extract of cinnamon tree 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 refer to any natural or artificial diet, one meal, etc., or a component of the one meal meal, suitable for or suitable for consumption by animals. The type of feed is not particularly limited, and feeds commonly used in the art may be used. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.

The present invention also relates to a veterinary composition for the prevention or treatment of arthritis and joint pain, containing an extract of cinnamon tree as an active ingredient.

The veterinary composition containing the cinnamon 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 cinnabar extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate yate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben and mineral oil.

The veterinary composition containing the cinnabar extract according to the present invention may further include a filler, an anticoagulant, a lubricant, a wetting agent, a spice, an emulsifier, a preservative, and the like. The veterinary composition according to the present invention may be formulated using a method well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, and the formulation may be a powder, granule, tablet, capsule, suspension, emulsion, solution, syrup, aerosol, It may be in the form of soft or hard gelatin capsules, suppositories, sterile solutions for injection, sterile external preparations, and the like.

The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but may be administered once or several times a day, and the dosage may increase or decrease depending on the route of administration, severity of disease, sex, weight, age, etc. Accordingly, the dosage is not intended to limit the scope of the present invention in any way.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for explaining 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. Manufacture of extract of cinnamon tree

For 1kg of the present invention, 15 L of 70% (v / v) ethanol was added, extracted at 85 ° C. for 3 hours, and the filtered solution was concentrated under reduced pressure at 45 ° C.

Example 2. Evaluation of anti-inflammatory efficacy in chondrocytes

Expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which are cartilage matrix degrading enzymes activated by the increase in inflammatory cytokines following treatment with cinnabar extract, in human chondrocytes (SW1353) and cartilage proteoglycan. Changes in the content of GAG (glycosaminoglycan), a degradation product, were confirmed.

[Cell culture]

Human chondrocytes (SW1353) were cultured using a culture medium in which 10% Fetal Bovine Serum (FBS) was added to DMEM/F12 (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12), and then treated with extract (25 or 50 μg/ml) and cultured for 2 hours, followed by treatment with IL-1β (10 ng/ml) for 24 hours.

(1) Confirmation of IL-1β-mediated expression reduction effect of MMP-1 and MMP-13

The activation and synthesis of MMPs according to the secretion of inflammatory cytokines causes the decomposition of cartilage matrix molecules (extracellular matrix, ECM) constituting cartilage tissue. It was confirmed using an ELISA kit (R & D Systems) to determine whether the extract of cinnamon tree extract affects the production of MMPs.

As a result, the expression levels of MMP-1 and MMP-13 increased in the culture supernatant treated with IL-1β for 24 hours, but the expression levels of MMP-1 and MMP-13 were significantly decreased by IL-1β in cells pretreated with the extract of the present invention (FIG. 1).

(2) Confirmation of GAG (Glycosaminoglycan) secretion effect induced by IL-1β

GAG is a component constituting cartilage tissue and is a material produced by decomposition of proteoglycan, and changes in the content of GAG were confirmed to determine whether the extract of the present invention affects the degradation of proteoglycan. Specifically, after treatment with IL-1β for 24 hours, the culture supernatant was reacted with blyscan dye to measure absorbance at 656 nm to measure the amount of GAG.

As a result, it was confirmed that cartilage decomposition was promoted by IL-1β and the increased amount of GAG was reduced by the treatment with the present invention of the extract of the present invention (FIG. 2).

Example 3. Evaluation of analgesic efficacy in pain-induced animal models by acetic acid induction

After 7-week-old ICR mice were acclimatized for one week, cinnabar extract (150mg/kg, 300mg/kg) and positive control diclofenac (diclofenac, 10mg/kg) were orally administered, respectively. 1 hour after administration, 0.75% (v/v) acetic acid (acetic acid) was intraperitoneally administered to the mouse at a dose of 10 ml/kg, and fasted for at least 18 hours for intraperitoneal administration of acetic acid. Five minutes after administration of acetic acid, the number of times the mouse twisted its body was observed for 10 minutes.

As a result, intraperitoneal administration of acetic acid caused capillary damage and pain, resulting in an increased number of twists of the mouse, but when the island extract was administered, the number of turns of the mouse was significantly reduced (FIG. 3).

Example 4. Efficacy evaluation of relieving foot edema in an animal model inducing inflammation by carrageenan

7-week-old ICR mice were acclimatized for one week, and then cedar extract (150mg/kg, 300mg/kg) and indomethacin (5mg/kg) as a positive control group were orally administered. 1 hour after administration, 50 μl of 1% carrageenan was administered to the sole of the right hind limb, and then the amount of edema in the right hind limb at 1, 3, and 5 hour intervals was compared using a edema meter (Plethysmometer, Bioseb, USA).

As a result, in the carrageenan-induced foot edema animal model, it was confirmed that foot edema was significantly reduced at 5 hours after edema induction due to the administration of the cedar extract.

Claims (11)

A health functional food composition for preventing or improving arthritis and joint pain, containing an extract of Tilia insularis as an active ingredient. The 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. According to claim 1, wherein the active ingredient inhibits the expression of MMP-1 (Matrix metalloproteinase-1) and MMP-13, and reduces the content of GAG (Glycosaminoglycan) for preventing or improving arthritis and joint pain Health functional food composition. The functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the extraction solvent of the extract of cinnamon tree is water, C ₁ ~ C ₄ lower alcohol, or a mixture thereof. The functional food composition for preventing or improving arthritis and joint pain according to claim 1, wherein the composition is prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage. A pharmaceutical composition for the prevention or treatment of arthritis and joint pain, containing an extract of Tilia insularis 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 6, 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 Tilia insulari s extract as an active ingredient. A veterinary composition for the prevention or treatment of arthritis and joint pain, containing an extract of Tilia insularis as an active ingredient.