KR101423316B1 - Composition for prevention or treatment of osteoarthritis including extracts of Phyllanthus tenellus - Google Patents

Abstract

The present invention relates to a composition for preventing and treating osteoarthritis containing an extract of Pilotous tenelrus. The composition of the present invention can be used particularly for the prevention and treatment of osteoarthritis.

Description

[Technical Field] The present invention relates to a composition for prevention or treatment of osteoarthritis containing an extract of Phillantus tenellus,

The present invention relates to a pharmaceutical composition and a functional health supplement for preventing or treating osteoarthritis containing an extract of Phyllanthus tenellus .

Phyllanthus tenellus is a herbaceous plant of the Phyllanthus family of Euphorbiaceae, a plant species introduced from the island of Mauritius, located in the eastern part of Africa, southwest of the Indian Ocean, And many others in South America. The Rural Development Administration introduced it for the first time in 2005 from Brazil. The botanical features of the leaves are short or no petiole, and red stamens are present in the stem. The flower features long flower stalks (flower stamens) and is a monogamous flower with female flower flora, while female flower and male flower hang on one plant. The number of petals (number of flowers) and the number of stamen (gut) are each 5.

Osteoarthritis (Osteoarthritis) is a degenerative arthritis, which is caused by a degenerative change in the cartilage and surrounding bone in the lubricated joint. The gradual loss of articular cartilage, hypertrophy of the bone located below the cartilage, osteogenesis at the joint edge, and nonspecific synovial It is a disease characterized by inflammation. The osteoarthritis is a fibrillation stage (stage 2) in which the cartilage surface is cracked and fractured and the bone is exposed and the joints are narrowed. , Cartilage cells begin to produce cartilage to restore cartilage, cartilage destruction occurs more rapidly than cartilage production, so cartilage is generally reduced (stage 3), bone changes and bone changes leading to joint malformation and dysfunction (Step 4) and a joint soft tissue change step (step 5) where the soft tissue is thickened. On the other hand, rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation and proliferation of synovial cells, and unlike osteoarthritis, osteoporosis and osteoporosis of the periarticular bone occur. Rheumatoid arthritis is a condition in which inflammation of the synovial membrane is spread to the joint capsule, ligament, tendon (stage 1), gradual destruction of the joint cartilage, (Stage 2) in which the tension of the joints and ligaments disappears (step 3), in which the inflammation penetrates into the bones, resulting in partial erosion of the bones (step 3), and the step of loss of joint function (step 4). As described above, osteoarthritis and rheumatoid arthritis are completely different from each other in the cause and progress of the invention, and the treatment method thereof is also different. Yet there has been no invention for the prevention or treatment of Philontus tenelor's optic atrophy.

The inventors of the present invention have conducted studies to develop a novel preventive or therapeutic agent for osteoarthritis and found that the extract of Pilatus tennelus has an excellent prevention, improvement and / or therapeutic effect of osteoarthritis, thus completing the present invention .

The present invention relates to a method for preventing or treating osteoarthritis comprising, as an active ingredient, an extract of Phyllanthus tenellus , preferably a C _{1 -4} alcohol extract, alone or in combination with a pharmaceutically or pharmacologically acceptable excipient ≪ / RTI >

The present invention also provides a food additive, a health supplement, or a pharmaceutical composition showing the preventive, ameliorating or therapeutic effect of osteoarthritis containing the composition comprising the extract of Pilotus tenelrus. The health supplement or pharmaceutical composition is preferably selected from the group consisting of tablets, capsules, powders, granules, liquids and pills.

In the present invention, the extract of Phyllantus tenellus can be used to produce an extract using the ground part of Phyllanthus tenellus , but the extract can be prepared using the phyllanthus tenellus .

Hereinafter, the present invention will be described in detail by way of an example of the extraction process of filantus tenelrus.

In the present invention, the peel Lantus tenel loose with methanol, ethanol, propanol, isopropanol, or C _{1 -4} alcohol such as butanol, preferably a C _{1 -3} alcohol, more preferably methanol, ethanol, or the alcohol solvent Extraction with an ordinary extraction method such as ultrasonic extraction, and concentration under reduced pressure to obtain an alcoholic extract.

The extract of Phyllotus tenellus of the present invention exhibits an excellent preventive or therapeutic effect of osteoarthritis. To this end, the extract of Phyllintus tenellus may be administered by itself or the extract may be fractionated with an organic solvent or water, or subjected to column chromatography May be administered separately or simultaneously.

The composition of the present invention may be formulated by a known method in the pharmaceutical or food science field and may be formulated into pharmaceutical or food acceptable formulations by mixing with itself or a pharmaceutically acceptable carrier, For example, they may be formulated into liquids, syrups, capsules and the like, and they may be administered orally or parenterally.

The term "health supplementary food" used in the present invention refers to a nutritional supplement which is obtained by using a raw material or ingredient having a useful function in the human body, Refers to a functional food such as a health food or beverage, yogurt, or cheese prepared and processed in the form of a capsule, a powder, a granule, a liquid agent, or a pill.

The composition of the present invention is appropriately selected according to the degree of absorption of the active ingredient in the body, the excretion rate, the age and weight of the patient, the sex and condition of the patient, the severity of the disease to be treated and the like, but is generally from 0.03 to 1500 mg per day, It is preferable to administer it at 0.3 to 600 mg. The unit dosage formulations thus formulated may be administered several times at predetermined time intervals as necessary.

The extract of Pilotous Tenelleus of the present invention exhibits excellent prevention, improvement and / or therapeutic effect of osteoarthritis.

FIG. 1 is a diagram showing histopathological arthritis index of knee cartilage of MIA-induced osteoarthritic rats,
FIG. 2 is a graph showing the content of cartilage collagenase (MMP1) in serum isolated from MIA-induced osteoarthritic rats,
FIG. 3 is a graph showing the content of cartilage collagenase (MMP13) in serum isolated from MIA-induced osteoarthritic rats,
Figure 4 is a diagram showing histopathologic damage of knee cartilage isolated from MIA induced osteoarthritic rats.

Hereinafter, the present invention will be described in more detail with reference to the following examples. These embodiments are for the purpose of illustrating the present invention and are not intended to limit the scope of protection of the present invention.

Example . Philantus Teneluth  Preparation of extract

The Pilotus tenelus extract of this example was prepared using a 95% alcohol. The detailed extraction method is as follows. After adding 3 liters of 95% fermented liquor into 1 kg of pulverized Pellantus tenelorus powder which was dried and dried at 45 ° C, it was sonicated 5 times for 30 minutes and then extracted 3 times for 60 minutes. , And concentrated. The final extract concentration was 89 g, and the final extract yield was 8.9%.

Experimental Example

MIA Rat  Arthritis induction

Male Sprague-Dawley rats (Orient Bio, Korea) with a body weight of about 160 g were purchased and used for the experiment after being acclimated for 1 week in a clean animal breeding room (temperature 23 ± 1 ° C, humidity 55 ± 5%). Feed and water were freely consumed during the experiment. Osteoarthritis was induced by modifying the method of Guzman (Toxicologic Pathology, 31: 619-624, 2003). Monosodium iodoacetate (MIA, Sigma, USA) was dissolved in physiological saline solution at a concentration of 5 mg / ml to prepare an MIA solution. On the first day of the experiment, Zoletile: Rumpun (2: 1) was intramuscularly anesthetized and the front of both knees was disinfected. Each MIA solution (1 mg / 50 μl) was taken into Hemolytic Syringe (26 gauge) The drug was injected exactly by injecting the medial cartilage (between the cartilages). The normal group was injected with 50 μl of physiological saline solution in both knees.

Administration of Test Substance, Control Substance

Oral doses were given once a day at 10-11 am daily for 14 days. Oral doses and doses were adjusted according to body weight measurement. Test substances and control substances were prepared as shown in Table 1 below, and the test group composition and administration dose are shown in Table 2 below.

Positive control group Mushroom extract (Goodhealth Co) White powder, 300 mg / capsule Negative control group Carboxymethyl cellulose (Sigma-aldrich Co) White powder, 99% (90 kDa) Test substance group Pilotus tenelus 95% alcohol extract of Example Cyan-colored viscous extract

group Inducing substance process Volume
(mg / kg) volume
(2 ml / head) Experimental animal
(Marie) One MIA + The control (0.5% CMC) 2 8 2 MIA + Green mussel extract 150 2 8 3 MIA + Pilotus tenelus extract of the Examples 200 2 8 4 MIA - Normal group 2 8

* MIA (osteoarthritis inducer); +: Administration, -: Not yet.

Organizational Analysis

The serum was separated and stored at -70 ° C. The knee cartilage of each individual induced MIA induced osteoarthritis was separated, fixed and demineralized, and then subjected to H & E Hematoxyline & Eosin). After staining, articular cartilage was observed through a microscope. Histopathologic examination items include subchondral bone change, chondrocyte necrosis, cartilage erosion, osteophyte and cartilage cleft, with 0-5 points per item Toxic pathology experts. The results of the spectroscopic scores were expressed as means and standard deviations, and the results were tested using Kruskal-Wallis test, a nonparametric statistical method. Kruskal-Wallis test was used to determine the significance level of p <0.05. Statistical analysis was performed using Dunn's multiple comparison test. Statistical analysis of each group was performed using GraphPad PRISM ^® Version 4.0 (GraphPad Software, USA).

The histopathological arthritis index of the knee cartilage of the MIA-induced osteoarthritic rat is shown in Fig. 1, and the content of cartilage collagenase (MMP1) in the serum isolated from the MIA-induced osteoarthritic rat is shown in Fig. 2, FIG. 3 shows the content of cartilage collagenase (MMP13) in the serum isolated from MIA-induced osteoarthritic rats and FIG. 4 shows the histopathological damage of the knee cartilage isolated from the mice.

1 to 3, G 1 is a group administered with MIA + 0.5% carboxymethyl cellulose 200 mg / kg, G 2 is a group administered with 150 mg / kg of MIA + green mussel oil extract, G 3 is a group administered with MIA + 200 mg / kg of Pilotus tenelus extract of this example.

As can be seen from FIG. 1, in the group treated with Pilotus tenelulus extract (G3), the arthritis index improvement effect was statistically significantly improved compared to the negative control group (G1) and the positive control group (G2) The arthritis index was reduced to about 82% of the control group. On the other hand, the green lipped mussel oil extract (a functional ingredient for improving joint health) used as a positive control (G2) showed no improvement in arthritis index.

As can be seen from FIG. 2, the effect of reducing the content of cartilage collagenase (MMP1) was inhibited statistically in the group treated with Pilotus tenelus (G3) as compared with the negative control group (G1) And decreased the content of bone collagenase (MMP1) by 78% compared to the negative control group. This effect was somewhat weaker than the green lipped mussel oil extract (a functional ingredient for improving joint health) used as a positive control (G2).

As can be seen from Fig. 3, the effect of reducing the content of cartilage collagenase (MMP13) was inhibited statistically in the group treated with Pilotus tenelulus (G3) as compared with the negative control group (G1) And decreased the content of cartilage collagenase (MMP13) to 72% of that of the negative control group. These effects were statistically similar to those of the green lipped mussel oil extract (a functional ingredient for improving joint health) used as a positive control (G2).

In FIG. 4, A is a normal group, B is a negative control (MIA + 0.5% cobboximethylcellulose 200 mg / kg), C is a positive control (MIA + green mussel oil extract 150 mg / kg) MIA + 200 mg / kg of Pilotus tenelrus extract of this example.

As can be seen from FIG. 4, in the negative control group (B), osteoarthritis was induced by MIA, and the cartilage tissue was severely damaged and destroyed. On the other hand, in the group treated with Pilotus tenellus extract (D), the damage of the cartilage tissue was recovered and it was observed that the cartilage tissue was better than the negative control group.

The above results show that the extract of Pilotus tenelelus of the present invention is effective in suppressing cartilage destruction and improving osteoarthritis.

Composition Example

Composition Example 1. Preparation of capsules

200 mg of Phyllotus tenellus extract in Example

Lactose 100mg

Starch 93mg

Talc 2mg

Magnesium stearate qs

The above components are mixed and filled in gelatin capsules according to the conventional preparation method of capsules to prepare capsules.

Composition example 2. Preparation of liquid agent

200 mg of Phyllotus tenellus extract in Example

Sugar 20g

20g per isomer

Lemon incense quantity

Purified water was added to the entire 100 ml

The above components are mixed according to a conventional method for preparing a liquid agent, filled in a 100 ml brown bottle, and sterilized to prepare a liquid agent.

Composition Example 3. Preparation of beverage

Composition containing 5% by weight of the extract of Phyllotus tenellus extract of the Example, 0.05% by weight of food coloring agent, 0.05% by weight of orange essence, 5.0% by weight of fructose, 0.1% by weight of citric acid and 0.05% by weight of vitamin C And then, an appropriate amount of purified water was added to prepare a beverage.

Claims (5)

Phyllanthus tenellus A dietary supplement for the prevention or amelioration of osteoarthritis, which comprises an extract of the ground alone or in combination with a pharmaceutically acceptable excipient. The dietary supplement according to claim 1, wherein the extract of Phillantus tenelucus is a C _1-4 alcohol extract, for the prevention or amelioration of osteoarthritis. delete The dietary supplement according to claim 1 or 2, wherein the dietary supplement is selected from the group consisting of tablets, capsules, powders, granules, liquids and pills. A pharmaceutical composition for the prevention or treatment of osteoarthritis, comprising an extract of Phyllanthus tenellus above ground alone or in combination with a pharmaceutically acceptable excipient.

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