KR20210016163A - Composition for preventing and treating osteoarthritis comprising curcumin and polyunsaturated fattyacids - Google Patents

Abstract

Curcumin and polyunsaturated fatty acids omega 3 fatty acids or omega 6 fatty acids are treated in combination to relieve pain caused by arthritis, have a cartilage protection effect, and have an effect of inhibiting inflammatory cytokines and cartilage destruction. Therefore, curcumin and polyunsaturated fatty acids omega 3 fatty acids or omega 6 fatty acids can be usefully used as a composition for preventing or treating arthritis or osteoporosis.

Description

Composition for prevention and treatment of arthritis containing curcumin and polyunsaturated fatty acids as active ingredients {COMPOSITION FOR PREVENTING AND TREATING OSTEOARTHRITIS COMPRISING CURCUMIN AND POLYUNSATURATED FATTYACIDS}

The present invention relates to an effect of preventing or treating arthritis by the combination treatment of curcumin and polyunsaturated fatty acids.

The human body is made up of about 200 joints. A joint is the area where bone and bone meet. Joints are composed of cartilage, joint capsule, synovium, ligaments, tendons, muscles, etc. to allow smooth movement between bones and bones, and play a role in absorbing shocks generated by movement. Inflammatory diseases appearing in these joints are chronic joint rheumatism, which is understood to be caused by autoimmunity, infectious arthritis due to bacterial infection, degenerative arthritis in which joint cartilage or bone degeneration or destruction due to various causes, and degenerative changes in connective tissue. It can be broadly classified into crystalline arthritis, in which soluble metabolites are deposited as crystals in the connective tissue around the joint. In degenerative arthritis, that is, osteoarthritis, degeneration such as aging occurs in the chondrocytes constituting the joint, and the synthesis of the substrate substances of the joint, type II collagen and proteoglycan, is inhibited from the chondrocytes. As inflammatory cytokines such as interleukin-1 and tumor necrosis factor-α are produced, the synthesis of matrix metalloproteinase (MMP) that degrades joint matrix and It is a disease caused by destruction of joint tissue due to increased activity in joint cells. In addition, arthritis is further exacerbated by the production of nitrogen monoxide by inflammatory cytokines and the synthesis of more MMPs due to the production of self-amplifying cytokines by the generated nitrogen monoxide, thereby promoting the decomposition of joint substrates. At the same time, inflammatory cytokines increase the production of prostaglandin E2, a lipid metabolite, leading to an inflammatory response in arthritis. Osteoarthritis is a type of arthritis, also referred to as degenerative arthritis, and occurs mainly in old age without a specific organic cause. If it progresses chronically, it is accompanied by movement disorders such as gait disorder due to deformation of the joint structure. Osteoarthritis is mainly due to gradual damage or degenerative changes in the articular cartilage, causing damage to the bones and ligaments that make up the joint, resulting in inflammation and pain. When osteoarthritis progresses, the production of inflammatory cytokines such as TNF-α and IL-1 increases, and the secretion of MMPs such as collagenase and stromelysin increases, leading to the destruction of articular cartilage. Will come true. In addition, MMPs induce IL-1 and TNF-α, which in turn affects tissues such as muscles, tendons, and ligaments, causing severe pain.

MMPs are proteolytic enzymes that destroy matrix components of bone and cartilage, and are expressed in cartilage tissue stimulated by inflammatory cytokines when in inflammatory disease state and increase their activity. MMPs consist of at least 21 enzymes, collagenase (MMP-1,8,13), stromelysin (MMP-3,10,11), gelatinase (MMP-2,9) and matrix type-1 metalloproteinase (MMP-14). ) Are subdivided into subgroups.

Rheumatoid and degenerative arthritis are characterized by inflammatory cell infiltration into the synovial tissue of the joint, which is mediated by chemokine. In synovial tissues of arthritis, chemokines such as MCP-1 (monocyte chemoattractant protein-1) are expressed, and they are known to be produced by synovial fibroblasts. Excessive MCP-1 produced by arthritis invites monocytes and macrophages to the inflammatory site, and by activating these cells, it promotes the production of inflammatory cytokines and plays a role in further circumventing inflammation.

Currently, for the treatment of osteoarthritis, drugs such as acetaminophen, tramadol, nonsteroidal anti-inflammatory drugs (NSAIDs), diaserine, and glucosamine are used, but only temporarily alleviate the pain of osteoarthritis. Accordingly, there is a need for a treatment that can effectively alleviate pain while treating osteoarthritis.

On the other hand, curcumin is a compound having a chemical formula of C ₂₁ H ₂₀ O ₆ and a molecular weight of 368.38, extracted from the root of Curcuma longa Linn (Zingiberaceae), a plant belonging to the ginger family of East India, and widely used in Indian food. It is a yellow spice composed of whole polyphenols and is a curcuminoid of turmeric. It is used as a yellow pigment in food additives and as a spice. Curcumin has anti-tumor, antioxidant, anti-amyloid and anti-inflammatory effects, and inhibits the formation and promotion of skin cancer, gastric cancer, and oral cancer induced by benzopyrene, 7,12-dimethylbenz anthracen, phorbol ester in mouse experiments, and N- It has been reported to inhibit the formation of gastric cancer caused by methyl-N'-nitro-N-nitrosoguanidin.

Korean Patent Registration No. 0626358

An object of the present invention is to provide a pharmaceutical composition for preventing or treating arthritis.

In addition, an object of the present invention is to provide a pharmaceutical composition for preventing or treating osteoporosis.

In addition, it is an object of the present invention to provide a food composition for preventing or improving arthritis.

In addition, an object of the present invention is to provide a food composition for preventing or improving osteoporosis.

In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating arthritis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In addition, the present invention provides a pharmaceutical composition for preventing or treating osteoporosis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In addition, the present invention provides a food composition for preventing or improving arthritis comprising curcumin and polyunsaturated fatty acids.

In addition, the present invention provides a food composition for preventing or improving osteoporosis comprising curcumin and polyunsaturated fatty acids.

According to the present invention, curcumin and polyunsaturated fatty acids omega 3 fatty acids or omega 6 fatty acids are treated in combination to reduce pain caused by arthritis, have cartilage protection, and inhibit inflammatory cytokines and cartilage destruction. It can be usefully used as a composition for preventing or treating arthritis or osteoporosis.

1 is a diagram confirming the pain suppression effect in an osteoarthritis animal model by Curcumin and Omega3 by PWL (paw withdrawal latency).
Figure 2 is a diagram confirming the pain suppression effect in an osteoarthritis animal model by curcumin and omega 3 by PWT (paw withdrawal threshold).
3 is a diagram confirming the pain suppression effect in an osteoarthritis animal model by curcumin and omega 3 by weight bearing.
Figure 4 is a diagram confirming the cartilage protection effect in an osteoarthritis animal model by curcumin and omega 3 through bone volume.
5 is a diagram confirming the cartilage protection effect in an osteoarthritis animal model by curcumin and omega 3 through safranin O staining, OARSI score, Mankin score, number of cartilage cells, cartilage destruction, and tidemark integrity. to be.
6 is a diagram confirming the change in MCP-1 expression by curcumin and omega 3.
7 is a diagram illustrating the effect of curcumin and linoleic acid on pain suppression in an animal model of osteoarthritis by PWL (paw withdrawal latency).
Figure 8 is a diagram confirming the pain suppression effect in an osteoarthritis animal model by curcumin and linoleic acid by PWT (paw withdrawal threshold).
9 is a diagram confirming the pain suppression effect in an osteoarthritis animal model by weight bearing by curcumin and linoleic acid.
10 is a view confirming the cartilage protection effect in an osteoarthritis animal model by curcumin and linoleic acid through bone volume.
Figure 11 is a diagram confirming the cartilage protection effect in an osteoarthritis animal model by curcumin and linoleic acid through safranin O staining, OARSI score, Mankin score, number of cartilage cells, cartilage destruction, and tidemark integrity. .
Figure 12 is a diagram confirming the changes in the expression of MMP1, MMP3 and MMP13 by curcumin, omega 3 and linoleic acid:
Nil: control not treated with IL-1β.

Hereinafter, the present invention will be described in detail as an embodiment of the present invention with reference to the accompanying drawings. However, the following embodiments are presented as examples of the present invention, and if it is determined that a detailed description of a technique or configuration well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description may be omitted. However, the present invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of equivalents interpreted from the description of the claims to be described later and therefrom.

In addition, terms used in the present specification are terms used to properly express preferred embodiments of the present invention, which may vary depending on the intention of users or operators, or customs in the field to which the present invention belongs. Accordingly, definitions of these terms should be made based on the contents throughout the present specification. Throughout the specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary.

All technical terms used in the present invention, unless otherwise defined, are used in the same sense as those of ordinary skill in the art generally understand in the related field of the present invention. In addition, although preferred methods or samples are described in the present specification, those similar or equivalent are included in the scope of the present invention. The contents of all publications referred to herein by reference are incorporated into the present invention.

In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating arthritis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In one embodiment, the polyunsaturated fatty acids may be omega 3 fatty acids, omega 6 fatty acids or omega 3 fatty acids and omega 6 fatty acids.

In one embodiment, the omega-3 fatty acid is made into FFA (free fatty acid) form in the process of increasing the content of omega-3 by purifying purified fish oil containing omega-3 and other fatty acids, and selectively purifying only omega-3 After that, in order to increase stability, it may be in the form of omega 3 EE with an ethyl ester group attached to the end of the FFA.

In one embodiment, the omega 3 fatty acid is eicosapentaenoic acid (EPA) or a straight or branched C1-C6 alkyl ester thereof, a triglyceride or phospholipid thereof, docosahexaenoic acid. , DHA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof, alpha-linolenic acid (ALA) or straight or branched C1-C6 alkyl esters thereof, these Triglycerides or phospholipids of, stearidonic acid (SDA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof, and eicosatetraenoic acid (ETA) Or they may be any one or more selected from the group consisting of straight-chain or branched-chain C1-C6 alkyl esters, triglycerides or phospholipids thereof.

In one embodiment, the omega 6 fatty acid is linoleic acid or a straight or branched C1-C6 alkyl ester thereof, a triglyceride or phospholipid, arachidonic acid or a straight or branched C1- C6 alkyl esters, triglycerides or phospholipids thereof, 7,10-hexadecadienoate (7,10-hexadecadienoate), 10-hexadecatrinoate (7,10-hexadecadienoate) or straight or branched chain C1-C6 thereof Selected from the group consisting of alkyl esters, triglycerides or phospholipids thereof, and dihomo-gamma-linolenic acid (DHGLA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof It may be any one or more.

In one embodiment, curcumin and omega 3 and/or linoleic acid may be included as active ingredients.

In one embodiment, curcumin and omega 3 may be mixed in a weight ratio of 10:11, curcumin and linoleic acid may be mixed in a weight ratio of 5:11, and curcumin, omega 3 and linoleic acid may be mixed in a weight ratio of 10:11:22 Can be mixed with.

In one embodiment, the arthritis is senile arthritis, degenerative arthritis, autoimmune arthritis, osteoarthritis, rheumatoid arthritis, spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, gout, bacterial arthritis, childhood rheumatoid arthritis, lupus, scleroderma, multiple sclerosis, fibromyalgia , Polymyositis, dermatomyositis, Behcet's disease, Reiter's syndrome, Lyme arthritis, adhesion arthritis, frozen shoulder, tendon synovitis, elbow head pouchitis, dequevain tendon synovitis, recurrent rheumatism, rheumatoid multiple muscle pain and adult Still's disease. It may be any one or more selected from the group.

In one embodiment, the composition of the present invention inhibits the expression of MCP-1, a chemokine that exacerbates inflammation due to arthritis, and suppresses the expression of cartilage destruction factors MMP1, MMP3 and MMP13, thereby reducing cartilage destruction.

In one embodiment, the composition of the present invention comprises curcumin at a concentration of 2 mg/kg to 5000 mg/kg, omega 3 fatty acids at a concentration of 2.2 mg/kg to 5500 mg/kg, and omega 6 fatty acids at 4.4 mg/kg It may be included in a concentration of kg to 11000mg / kg.

In one embodiment, the composition of the present invention may be a composition for reducing pain caused by arthritis.

In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating osteoporosis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In one embodiment, the polyunsaturated fatty acid may be omega 3 or linoleic acid.

The curcumin according to the present invention may be used in the form of a salt, preferably a pharmaceutically acceptable salt. As the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is preferable, and an organic acid and an inorganic acid may be used as the free acid. The organic acid is not limited thereto, but citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, metasulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, Includes glutamic acid and aspartic acid. In addition, the inorganic acids include, but are not limited to, hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid. The curcumin compound according to the present invention may be isolated from nature or prepared by a chemical synthesis method known in the art.

The pharmaceutical composition of the present invention may further include an adjuvant. Any of the adjuvants known in the art may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase its immunity.

The term "treatment" of the present invention, unless otherwise stated, reverses, alleviates, or inhibits the progression of the disease or disease to which the term applies, or one or more symptoms of the disease or disease, or It means to prevent, and the term treatment as used herein refers to an act of treating. Therefore, the treatment or treatment of immune diseases such as osteoarthritis in mammals may include one or more of the following:

(1) inhibiting the growth of immune diseases, ie, inhibiting their development;

(2) preventing the spread of immune diseases, ie, preventing metastasis;

(3) alleviate immune diseases;

(4) preventing recurrence of immune diseases; And

(5) Alleviating symptoms of immune disease (palliating)

The term "mammal" as used herein refers to a mammal that is the subject of treatment, observation or experimentation, and preferably refers to a human.

If the recipient animal is able to tolerate administration of the composition, or if administration of the composition to that animal is suitable, the composition indicates "pharmaceutically or physiologically acceptable". If the amount administered is physiologically important, the agent can be said to have been administered in a "therapeutically effective amount". If the presence of the agent results in a physiologically detectable change in the recipient patient, the agent is physiologically meaningful.

The therapeutically effective amount of the composition of the present invention may vary depending on various factors, for example, the method of administration, the target site, the condition of the patient, and the like. Therefore, when used in the human body, the dosage should be determined as an appropriate amount in consideration of safety and efficiency. It is also possible to estimate the amount used in humans from the effective amount determined through animal experiments. These considerations when determining the effective amount are described, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; And E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not cause side effects, and the effective dose level is the patient's Health status, type of disease, severity, drug activity, sensitivity to drugs, method of administration, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field Can be determined according to. The composition of the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. In consideration of all the above factors, it is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects, which can be easily determined by a person skilled in the art.

The compositions of the present invention may also contain carriers, diluents, excipients or combinations of two or more commonly used in biological preparations. The pharmaceutically acceptable carrier is not particularly limited as long as it is suitable for delivery of the composition in vivo. For example, Merck Index, 13th ed., Merck & Co. Inc. Compounds described in, saline, sterilized water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components can be mixed and used, and antioxidants, buffers, bacteriostatic agents, etc. Conventional additives can be added. In addition, a diluent, a dispersant, a surfactant, a binder, and a lubricant may be additionally added to form an injectable formulation such as an aqueous solution, a suspension, an emulsion, and a pill, capsule, granule, or tablet. Further, it may be preferably formulated according to each disease or component by an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

The pharmaceutical compositions of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, or sterile injectable solutions according to a conventional method. have.

As used herein, the term "pharmaceutically acceptable" means exhibiting a property that is not toxic to cells or humans exposed to the composition.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, and calcium hydrogen phosphate. , Lactose, mannitol, syrup, arabic rubber, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, Opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, sucrose, dextrose, sorbitol, talc, and the like can be used. The pharmaceutically acceptable additive according to the present invention is preferably contained in an amount of 0.1 parts by weight to 90 parts by weight based on the composition, but is not limited thereto.

As used herein, the term "administration" means providing a predetermined substance to a patient by any suitable method, and parenteral administration (for example, intravenous, subcutaneous, intraperitoneal or topical administration) according to the desired method. It can be applied as an injection formulation) or can be administered orally, and the dosage range varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.

The composition of the present invention can be administered parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) or orally administered according to a desired method, and the dosage may be the age, weight, sex, physical condition of the individual, etc. It is selected in consideration of It is obvious that the concentration of the active ingredient contained in the pharmaceutical composition can be selected in various ways depending on the subject, and is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg/ml. When the concentration is less than 0.01 μg/ml, pharmaceutical activity may not appear, and when the concentration exceeds 5,000 μg/ml, toxicity to humans may occur.

The pharmaceutical composition of the present invention can be formulated in various oral or parenteral dosage forms. Formulations for oral administration include, for example, tablets, pills, hard, soft capsules, solutions, suspensions, emulsifiers, syrups, and granules. These formulations include diluents (e.g., lactose, dextrose, water) in addition to the active ingredients. Krose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg, silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol). In addition, the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, in some cases starch, agar, alginic acid Or disintegrants or boiling mixtures and/or absorbents, colorants, flavors and sweeteners such as sodium salts thereof. The formulation can be prepared by conventional mixing, granulating or coating methods. In addition, a representative formulation for parenteral administration is a formulation for injection, and as a solvent for the formulation for injection, water, Ringer's solution, isotonic physiological saline or suspension may be mentioned. The sterile fixed oil of the injectable preparation can be used as a solvent or suspension medium, and any non-irritating fixed oil including mono- and di-glycerides can be used for this purpose. In addition, the injectable formulation may use a fatty acid such as oleic acid.

In the present invention, the term "prevention" refers to all actions of inhibiting or delaying the occurrence, spread, and recurrence of arthritis or osteoporosis by administration of the pharmaceutical composition according to the present invention.

In one aspect, the present invention relates to a food composition for preventing or improving arthritis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In one embodiment, the polyunsaturated fatty acid may be an omega 3 fatty acid or an omega 6 fatty acid, more preferably omega 3 and/or linoleic acid.

In one aspect, the present invention relates to a food composition for preventing or improving osteoporosis comprising curcumin and polyunsaturated fatty acids as active ingredients.

In one embodiment, the polyunsaturated fatty acid may be an omega 3 fatty acid or an omega 6 fatty acid, more preferably omega 3 and/or linoleic acid containing a large amount of DHA.

When the composition of the present invention is used as a food composition, the composition may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method. In addition to the active ingredient, the composition may contain food additives acceptable for food, and the amount of the active ingredient mixed may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).

The term "food supplementary additive" used in the present invention refers to a component that can be added auxiliary to food, and is added to the manufacture of health functional foods of each formulation, and can be appropriately selected and used by those skilled in the art. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavors, coloring agents and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners. , pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, etc. are included, but the types of food additives of the present invention are not limited by the above examples.

The food composition of the present invention may contain a health functional food. The term "health functional food" used in the present invention refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills using raw materials or ingredients having useful functions for the human body. Here, "functionality" means obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be manufactured by a method commonly used in the general technical field, and at the time of manufacture, it can be manufactured by adding raw materials and ingredients commonly added in the general technical field. In addition, the formulation of the health functional food may be prepared without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be prepared in various forms of formulation, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material, and is excellent in portability. Health functional foods can be consumed as an adjuvant to enhance the effectiveness of arthritis or osteoporosis drugs.

In addition, there is no limitation on the kind of health food in which the composition of the present invention can be used. In addition, the composition comprising the extract of the present invention or a fraction thereof as an active ingredient may be prepared by mixing appropriate other auxiliary ingredients and known additives that may be contained in the health functional food according to the choice of a person skilled in the art. Examples of foods that can 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 There are vitamin complexes and the like, and can be prepared by adding the extract according to the present invention as a main component, such as juice, tea, jelly, and juice.

Since the composition of the present invention is made of natural ingredients, even when used as a pharmaceutical composition or a food composition, side effects may be less than that of a general synthetic compound, so it can be safely included in pharmaceutical compositions and health functional foods and used usefully.

In one aspect, the present invention relates to a kit comprising the composition of the present invention in one or more unit dosage forms.

In one embodiment, the dosage forms described herein can be packaged in bottles or as blister packs with instructions for use of the dosage form. For example, the instructions may be provided as a package insert or may be provided directly on a blister pack, a label affixed to a bottle, or a blister pack or bottle on a secondary packaging that has been provided to a human subject. Instructions may include, for example, the number of dosing, administration of a dosage form administered with or without food, the active ingredients constituting the dosage form, and cardiovascular conditions or disorders that benefit from administration of the dosage form.

In one embodiment, curcumin and omega 3 fatty acids and/or omega 6 fatty acids may be administered simultaneously or sequentially.

The present invention will be described in more detail through the following examples. However, the following examples are only for embodiing the contents of the present invention and the present invention is not limited thereto.

Example 1. Osteoarthritis animal model production

To create an osteoarthritis animal model, a 5-week-old male Wistar rat, weighing 200-250 g, was reared at a temperature of 21-22℃ in a light-dark cycle every 12 hours, and sterilized water and feed were supplied. I raised it. Subsequently, for osteoarthritis induction, osteoarthritis was induced by administering Monosodium iodoacetate (MIA, Sigma, ST. Louis, MO) to the right knee of the rat at a dose of 3 mg/50 μl. MIA was administered by dissolving in physiological saline.

Example 2. Confirmation of the effect of curcumin and omega 3 on osteoarthritis treatment

2-1. Checking the pain relief effect

Vehicle (untreated control), curcumin 100mg/kg, curcumin 100mg/kg+ omega3 EE (free fatty acid) form in the process of increasing the content of omega-3 by purifying purified fish oil containing omega-3 and other fatty acids After selectively purifying only omega-3, an ethyl ester group was attached to the end of FFA to increase stability) 110mg/kg and Celecoxib 30mg/kg (positive control) for arthritis were administered orally 6 times a week, respectively. After one day, pain was measured using a dynamic plantat aesthsiometer (Ugo Basile, Comerio, Italy). To measure the pain of the machine, a net plate was placed on the measuring machine, and a rat was placed in an animal holding frame made of acrylic on it, and then pierced into the right foot injected with the drug by the measuring machine. Paw withdrawal latency (s, seconds) and how much weight (paw withdrawal threshold) (g) were measured and a pain measurement graph was drawn. . In addition, an Incapacitance tester was used to compare and measure the force applied to the left and right feet of the rat. The rat was placed in a plastic chamber, and the left and right feet of the rat were placed on each plate on the separate plate of the incapacitance tester, and the average value of the force applied to each foot for 3 seconds was obtained. The weight bearing (%) obtained in this way was substituted into Equation 1 below to obtain a result.

As a result, compared to the group administered only MIA (control group, vehicle), the group administered with omega 3 and curcumin showed a remarkable effect on pain relief than the conventional treatment for osteoarthritis. It was found that the pain relief effect persisted even after the administration passed (FIGS. 1 and 2 ). In addition, weight bearing was also found to have the best effect of the group administered with omega 3 and curcumin (FIG. 3).

2-2. Confirmation of cartilage protection effect

In order to check the degree of cartilage damage in each administration group after administration of the drugs as in Example 2-1, after collecting the rat's femur and tibia, the bone volume (%) was determined by micro-CT. The degree of cartilage destruction was confirmed by analysis. In addition, the collected and separated joints were subjected to safranin O staining, a staining method that can determine the degree of cartilage destruction, to observe the shape of cartilage, OARSI score, Mankin score, cartilage cell number, Cartilage destruction and tidemark integrity were analyzed.

As a result, it was observed that the reduction of inflammatory cells and destruction of cartilage in cartilage were suppressed in the combined administration of omega 3 and curcumin, and the degree of cartilage maintenance was well maintained close to normal tissues. Specifically, the group administered with omega 3 and curcumin showed remarkably high bone volume even in the conventional osteoarthritis treatment group (FIG. 4), and when both omega 3 and curcumin were administered, the OARSI score, Mankin score, and cartilage Cell count, cartilage destruction and tidemark integrity were all found to be significantly reduced (Fig. 5). Through this, it was found that when omega 3 and curcumin were administered together, cartilage destruction was significantly suppressed.

2-3. Confirmation of inflammatory cytokine control effect

Realtime PCR whether treatment with omega 3 + curcumin affects the expression of MCP-1 (monocyte chemoattractant protein-1), a chemokine that further exacerbates inflammation by promoting the production of inflammatory cytokines by overexpressing it in synovial tissue due to arthritis. Investigated. Specifically, in an in vitro experiment, human-derived chondrocytes were pretreated for 24 hours to stabilize cells, and then stimulated with IL-1β to make the state similar to osteoarthritis cartilage, and vehicle, omega 3 (Omega 3 is treated in cells because it is in OIL state. Since it is difficult to do, the cells were treated with DHA, which is a major component of omega 3) 50uM + 100uM of curcumin and 10uM of Celecoxib, respectively. After culturing the cells for one day, RNA was extracted, cDNA was synthesized, and realtime PCR analysis was performed.

As a result, it was found that omega 3 + curcumin significantly suppressed the expression of MCP-1 than Celecoxib, which is a conventional arthritis treatment (FIG. 6 ).

Example 3. Checking the effect of curcumin and linoleic acid on osteoarthritis treatment

3-1. Checking the pain relief effect

As in Example 2-1, vehicle (untreated control), curcumin 100mg/kg, curcumin 100mg/kg + linoleic acid 220mg/kg, and arthritis treatment Celecoxib 30mg/kg (positive control) were each orally administered and 2 days later Dynamic Pain was measured using a plantat aesthsiometer (Ugo Basile, Comerio, Italy). To measure the pain of the machine, a net plate was placed on the measuring machine, and a rat was placed in an animal holding frame made of acrylic on it, and then pierced into the right foot injected with the drug by the measuring machine. Paw withdrawal latenvy (s, seconds) and how much weight it took (paw withdrawal threshold) (g) were measured and a pain measurement graph was drawn. . In addition, an Incapacitance tester was used to compare and measure the force applied to the left and right feet of the rat. The rat was placed in a plastic chamber, and the left and right feet of the rat were placed on each plate on the separate plate of the incapacitance tester, and the average value of the force applied to each foot for 3 seconds was obtained. The weight bearing (%) obtained in this way was substituted into Equation 1 to obtain a result.

As a result, it was found that the pain of the experimental groups was relieved compared to the group administered with only MIA (control group, vehicle), and the group administered with linoleic acid and curcumin showed pain relief effects similar to those of conventional osteoarthritis treatments. It was found that the pain relief effect persisted even after the lapse of time (Figs. 7 and 8). In addition, in weight bearing, the effect of the group administered with linoleic acid and curcumin was similar to that of the conventional osteoarthritis treatment (FIG. 9).

3-2. Confirmation of cartilage protection effect

In order to check the degree of cartilage damage in each administration group after administration of the drugs as in Example 3-1, after collecting the rat's femur and tibia, the bone volume (%) was determined by micro-CT. The degree of cartilage destruction was confirmed by analysis. In addition, the collected and separated joints were subjected to safranin O staining, which is a staining method that can determine the degree of cartilage destruction, to observe the shape of cartilage, OARSI score, Mankin score, cartilage cell number, Cartilage destruction and tidemark integrity were confirmed as in Example 2-2 above.

As a result, the group administered with linoleic acid and curcumin showed significantly higher bone volume than the group administered with conventional osteoarthritis treatment (FIG. 10 ), and when linoleic acid and curcumin were administered together, OARSI score, Mankin score, number of cartilage cells, cartilage destruction And tidemark integrity were both significantly reduced (FIG. 11). Through this, it was found that when linoleic acid and curcumin were administered together, cartilage destruction was significantly suppressed.

Example 4. Checking the effect of curcumin, omega 3 and linoleic acid on osteoarthritis treatment

It was confirmed by Realtime PCR whether the combination treatment of curcumin, omega 3 and linoleic acid affects the expression of MMP1 (metalloproteinase1), MMP3 and MMP13, which are catabolic-related molecules related to cartilage destruction. Specifically, in an in vitro experiment, human-derived chondrocytes were pretreated for 24 hours to stabilize cells, and then stimulated with IL-1β to make a state similar to osteoarthritis cartilage, and treated with vehicle, Omega 3 + Curcumin + Linoleic acid and Celecoxib, respectively. And then cultured for 24 hours. After that, RNA was obtained from the cells and the expression of MMP1, MMP3 and MMP13 was observed by real time PCR.

As a result, in the case of the group treated with omega 3 + curcumin + linoleic acid, the expression of MMP1, MMP3 and MMP13 was remarkably reduced, and in particular, the expression of MMP1, MMP3 and MMP13 was remarkably compared to Celecoxib, a conventional arthritis treatment. It was found to be reduced (Fig. 12). Through this, it was found that the combination treatment of omega 3, curcumin, and linoleic acid of the present invention reduced catabolism, thereby exhibiting excellent effects on cartilage protection and regeneration.

Claims (16)

Curcumin (Curcumin) and a pharmaceutical composition for the prevention or treatment of arthritis comprising as an active ingredient a polyunsaturated fatty acid. The pharmaceutical composition for preventing or treating arthritis according to claim 1, wherein the polyunsaturated fatty acids are omega 3 fatty acids, omega 6 fatty acids or omega 3 fatty acids and omega 6 fatty acids. The method of claim 2, wherein the omega 3 fatty acid is eicosapentaenoic acid (EPA) or a straight or branched C1-C6 alkyl ester thereof, a triglyceride or phospholipid thereof, docosahexaenoic acid. , DHA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof, alpha-linolenic acid (ALA) or straight or branched C1-C6 alkyl esters thereof, these Triglycerides or phospholipids of, stearidonic acid (SDA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof, and eicosatetraenoic acid (ETA) Or a pharmaceutical composition for preventing or treating arthritis, which is any one or more selected from the group consisting of straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof. The method of claim 2, wherein the omega 6 fatty acid is linoleic acid or a straight or branched C1-C6 alkyl ester thereof, a triglyceride or phospholipid, arachidonic acid, or a straight or branched C1- C6 alkyl esters, triglycerides or phospholipids thereof, 7,10-hexadecadienoate (7,10-hexadecadienoate), 10-hexadecatrinoate (7,10-hexadecadienoate) or straight or branched chain C1-C6 thereof Selected from the group consisting of alkyl esters, triglycerides or phospholipids thereof, and dihomo-gamma-linolenic acid (DHGLA) or straight or branched C1-C6 alkyl esters thereof, triglycerides or phospholipids thereof Any one or more arthritis prevention or treatment pharmaceutical composition. The pharmaceutical composition for preventing or treating arthritis according to claim 1, wherein the polyunsaturated fatty acid is DHA or linoleic acid. The method of claim 1, wherein the arthritis is senile arthritis, degenerative arthritis, autoimmune arthritis, osteoarthritis, rheumatoid arthritis, spondyloarthropathy, ankylosing spondylitis, psoriatic arthritis, gout, bacterial arthritis, childhood rheumatoid arthritis, lupus, scleroderma, multiple sclerosis, fibromyalgia , Polymyositis, dermatomyositis, Behcet's disease, Reiter's syndrome, Lyme arthritis, adhesion arthritis, frozen shoulder, tendon synovitis, elbow head pouchitis, dequevain tendon synovitis, recurrent rheumatism, rheumatoid multiple muscle pain and adult Still's disease. Any one or more arthritis prevention or treatment pharmaceutical composition selected from the group. The pharmaceutical composition for preventing or treating arthritis according to claim 1, which inhibits the expression of MCP-1, a chemokine that worsens inflammation caused by arthritis. The pharmaceutical composition for preventing or treating arthritis according to claim 1, which reduces cartilage destruction by inhibiting the expression of cartilage-destructive factors MMP1 (metalloproteinase 1), MMP3 (metalloproteinase 3), and MMP13 (metalloproteinase 13). The pharmaceutical composition for preventing or treating arthritis according to claim 1, comprising curcumin at a concentration of 2mg/kg to 5000mg/kg. The pharmaceutical composition for preventing or treating arthritis according to claim 2, wherein the omega 3 fatty acid is contained in a concentration of 2.2 mg/kg to 5500 mg/kg, and the omega 6 fatty acid is contained in a concentration of 4.4 mg/kg to 11000 mg/kg. A pharmaceutical composition for preventing or treating osteoporosis comprising curcumin and polyunsaturated fatty acids as active ingredients. The pharmaceutical composition for preventing or treating osteoporosis according to claim 11, wherein the polyunsaturated fatty acid is DHA or linoleic acid. A food composition for preventing or improving arthritis comprising curcumin and polyunsaturated fatty acids as active ingredients. 14. The food composition for preventing or improving arthritis according to claim 13, wherein the polyunsaturated fatty acid is DHA or linoleic acid. A food composition for preventing or improving osteoporosis, comprising curcumin and polyunsaturated fatty acids as active ingredients. The food composition for preventing or improving osteoporosis according to claim 15, wherein the polyunsaturated fatty acid is DHA or linoleic acid.

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