KR20170003148A - Composition for preventing or treating gout comprising -carotene - Google Patents
Composition for preventing or treating gout comprising -carotene Download PDFInfo
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- KR20170003148A KR20170003148A KR1020150093426A KR20150093426A KR20170003148A KR 20170003148 A KR20170003148 A KR 20170003148A KR 1020150093426 A KR1020150093426 A KR 1020150093426A KR 20150093426 A KR20150093426 A KR 20150093426A KR 20170003148 A KR20170003148 A KR 20170003148A
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- South Korea
- Prior art keywords
- carotene
- beta
- gout
- crystals
- present
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Images
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
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Abstract
The present invention relates to a pharmaceutical composition and a health food composition for preventing or treating gout which contain beta-carotene as an active ingredient. More particularly, the present invention relates to a pharmaceutical composition for preventing or treating gout, ) Crystals. In particular, the inhibition of the inflammatory response induced by the urate crystals is inhibited by inhibiting the production of IL-1 [beta] and inhibiting NLRP3 inflammamma activity. . Accordingly, the beta-carotene of the present invention can be used as a pharmaceutical composition and a health food composition for preventing or treating gout caused by inflammation induced by MSU crystals.
Description
The present invention relates to a pharmaceutical composition and a health food composition for preventing or treating gout containing beta-carotene as an active ingredient.
Gout is a metabolic disorder in which the crystals of uric acid formed by persistent high uric acid in the blood can not be discharged out of the body and accumulate in various tissues to cause various symptoms. Increased serum uric acid may occur due to excessive production of uric acid and failure to properly discharge due to abnormal excretion through the kidneys.
High uric acid in the blood does not cause gout immediately, but uric acid crystals are easily formed by high uric acid, and when the state of being deposited in various tissues persists for 10 to 20 years, it is caused by induction factors. It is commonly found in men aged 40 to 50, but the age at onset is gradually decreasing with changes in diet and environment. Women are women who have had a long-term use of immunosuppressants after menopause or after organ transplantation, The possibility of developing the disease is high.
The cause of this gout is that most of the cells that make up our body have nuclei, which are made up of nucleic acids that contain genetic information. Nucleic acid is composed of purine or pyrimidine. When the cell reaches its end of life, it breaks down and the purine body in the nucleus is decomposed to produce a large amount of uric acid. The crystals of sodium urate precipitate in the tissues and cause inflammation. Hyperuricemia, gouty, Stomatitis and the like.
Currently, these gout treatments mainly use colchicine, non-steroidal anti-inflammatory drugs or steroids, but no medicines have been developed to radically treat gout. However, allopurinol, an inhibitor of uric acid uric acid production, and probenecid, a uric acid kidney excretion promoter, are known. However, allopurinol has serious side effects such as skin rash, gastrointestinal disorder, bone marrow suppression, itching and muscle pain Therefore, there is a demand for the development of a therapeutic agent capable of preventing or treating gout while being safe to the human body and reducing side effects.
The present invention relates to a composition for treating gout induced by uric acid crystals deposited on the body, and a therapeutic agent which has been used in the past has a problem of excessive side effects, so that it is possible to prevent inflammation induced by uric acid crystals Which is effective to inhibit or prevent gout.
In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating gout comprising beta-carotene as an active ingredient.
The present invention also provides a health food composition for prevention or improvement of gout comprising beta-carotene as an active ingredient.
According to the present invention, when a composition containing beta-carotene as an active ingredient is administered to a gout animal model in which the release of an inflammatory mediator is promoted by a monosodium urate monohydrate (hereinafter referred to as "MSU ") crystal , It was confirmed that the increase level of the cytokine induced by the MSU determination was markedly decreased. In particular, by inhibiting the production of IL-1 [beta] and inhibiting NLRP3 inflammamma activity, inflammation induced by MSU crystals And the effect of inhibiting the reaction was confirmed. Therefore, the beta-carotene of the present invention can be used as a pharmaceutical composition and a health food composition for prevention or treatment of gout induced by MSU crystals.
1 is a C57BL / 6 mouse beta-carotene (β-carotene) a rat animal model of local inflammation produced after oral administration of 30 mg / kg injected in the MSU crystals (Murine air - pouch model ) , the effect of beta-carotene on changes in neutrophil and cytokine-induced changes induced by MSU determination. 1A-1D are results of a decrease in the amount of cytokine-induced increase induced by MSU crystals after oral administration of beta-carotene or PBS. FIG. 1E shows that the inflammatory enzyme increased by MSU crystals is beta carotene ), Respectively.
Figures 1F and 1G illustrate the effect of beta-carotene on NLRP3 inflammase in a gout animal model. As a result, 1F was induced to MSU crystals after oral administration of beta-carotene or PBS The results of the ELISA analysis confirmed the effect of β-carotene on the amount of IL-1β secretion induced by MSU crystals in a gout animal model. 1G shows the effect of β-carotene on the increase of caspase-1 activation induced by MSU crystals. β-carotene was confirmed by using Caspase-1 activity kit.
The present invention provides a pharmaceutical composition for prevention or treatment of gout comprising beta-carotene represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
The ventilation of the present invention may be caused by monosodium urate monohydrate (MSU) crystals, and more particularly, it may be induced by deposition of MSU crystals on the body, but is not limited thereto.
The β-carotene can inhibit the production of IL-1β activated by urate (MSU) crystals and the activity of NLRP3 inflammasome.
According to one embodiment of the present invention, C57BL / 6 mice local inflammation animal model (Murine air-pouch model) in urate (MSU) making the ventilation animal model induced by injecting crystal suspension, and beta-carotene (β-carotene ) 30 mg / kg was orally injected into an animal model, it was confirmed that IL-1β secretion and NLRP3 inflammasome activity, which are inflammatory reaction substances induced by urate (MSU) crystals, are inhibited. Accordingly, the composition containing beta -carotene as an active ingredient according to the present invention is useful as a pharmaceutical composition or a health food composition for preventing or treating gout by inhibiting the inflammatory reaction induced by urate (MSU) crystals .
The pharmaceutical composition of the present invention may contain, but is not limited to, 0.01 to 90 parts by weight of beta-carotene, based on 100 parts by weight of the total amount of the pharmaceutical composition.
In one embodiment of the present invention, the pharmaceutical composition for prevention or treatment of gout containing the beta-carotene as an active ingredient can be administered orally or parenterally in the form of injections, granules, powders, tablets, pills, capsules, suppositories, Gels, suspensions, emulsions, drops, or liquid preparations may be used.
In another embodiment of the present invention, a pharmaceutical composition for prevention or treatment of gout comprising beta-carotene as an active ingredient may be formulated with a suitable carrier, excipient, disintegrant, sweetener, A lubricant, a lubricant, a flavoring agent, an antioxidant, a buffer, a bacteriostatic agent, a diluent, a dispersant, a surfactant, a binder and a lubricant.
Specific examples of carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration may be in the form of tablets, pills, powders, granules, capsules These solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
According to one embodiment of the present invention, the pharmaceutical composition may be administered orally, intraarterally, intraperitoneally, intramuscularly, intraarterally, intraperitoneally, intrasternally, transdermally, nasally, inhaled, topically, rectally, ≪ / RTI > can be administered to the subject in a conventional manner.
The preferred dose of the beta -carotene may vary depending on the condition and body weight of the subject, the type and degree of disease, the drug form, the administration route and the period, and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, the daily dose may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg, though it is not limited thereto. The administration may be performed once a day or divided into several times, and thus the scope of the present invention is not limited thereto.
In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.
The present invention also provides a health food composition for prevention or improvement of gout comprising beta-carotene as an active ingredient.
The health food may be provided in the form of powder, granules, tablets, capsules, syrups or beverages. The health food may be used in combination with other food or food additives other than the active ingredient β-carotene according to the present invention , And can be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose, for example, prevention, health or therapeutic treatment.
The effective dose of beta-carotene contained in the above-mentioned health food can be used in accordance with the effective dose of the above pharmaceutical composition, but in the case of long-term consumption intended for health and hygiene purposes or for health control purposes And the active ingredient may be used in an amount of more than the above range since there is no problem in terms of safety.
There is no particular limitation on the type of the health food, and examples thereof include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, Drinks, alcoholic beverages and vitamin complexes.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
The following experimental examples are intended to provide experimental examples that are commonly applied to the respective embodiments according to the present invention.
< Experimental Example >
1. Animals
The mice used in the present invention were purchased from Orient Bio (Seoul, Korea), and the management and experimental protocols of the purchased animals were performed according to the guidelines of the Institutional Animal Care and Use Committee (IACUC) of the Catholic University of Korea (permission) # 2012-5-001).
The mice were adapted to sterile conditions for at least a week before the experiment and maintained a temperature of 23 ± 3 ° C and 40-60% relative humidity.
2. Reagents
Beta-carotene was purchased from Sigma-Aldrich (St. Louis, Mo.). MSI was purchased from Invivogen (San Diego, USA), interleukin-1β was purchased from R & D Systems (Minneapolis, MN, USA) and Caspase-1 activity kit was purchased from bio-vision (califoornia, USA).
<
Example
1> urate in animal models (
monosodium
urate
monohydrate
Beta-carotene (beta-carotene) < / RTI >
carotene
)
1. Modeling of gustatory animals
C57BL / 6 mice were used to derive a model of air-pouch, a local inflammatory response model. First, 5 ml of sterilized air was injected into the subcutaneous tissues of mice and then 5 ml of the second sterilized air was injected by the same method 3 days later.
Seven days after the first air injection, MSU crystals suspended in 1 ml of sterilized non-toxin PBS were injected into the air bag to prepare a ventilated animal model. Beta-carotene (30 mg / kg) Control group PBS was injected into mouse mouth.
After 6 hours of injection of MSU crystals, the mice were euthanized, and the liquid in the air-pouch was collected by washing with 2 ml of PBS containing 5 mM EDTA, centrifuged at 12,000 rpm for 2 minutes, The sample was cooled and stored before measurement.
2. Beta-carotene (β- carotene ) Check the effect
In order to confirm the effect of beta-carotene on the ventilation induced by MSU, the animal model of the air bag prepared in Example 1-1 was used.
The animal model was prepared by injecting 1 ml of PBS suspended in MSU crystals in an air bag into a space available along a membrane such as a macrophage-like macrophage and a lubricant membrane containing fibroblasts, As a model, PBS was orally administered at 30 mg / kg beta-carotene or a
As a result, as shown in Fig. 1, MSU-induced acute gout is caused by cytokines such as IL-1α and IL-6 and MCP-1 (CCL2) And chemokines such as KC (CXCL1), but the increase in the level of cytokines induced by MSU crystals was significantly increased in the gout model in which beta carotene was administered Respectively.
< Example 2> MSU Beta-carotene < / RTI > (beta-carotene) carotene ) On inflammation
As mononuclear cells exposed to MSU crystals were reported to induce IL-1β activation and activated IL-1β to induce the production of NLRP3 inflammatory mediators, the cells were collected from the gout animal model of Example 1 IL-1β secretion was confirmed by ELISA analysis (Koo JE et al, 2012) in PBS containing liquid in the bladder.
As a result, IL-1β secretion was increased by MSU crystals in the PBS containing the liquid in the air bladder of the animal model in which PBS was orally administered, as shown in FIG. 1F, whereas the air of the animal model of β-carotene In the PBS containing the liquid in the bag, it was confirmed that the secretion of IL-1β by the MSU crystal was remarkably reduced.
In addition, as in 1G, when PBS was orally administered, the MSU crystal increased caspase-1 activity in the PBS containing the liquid in the bladder of the animal model, whereas the caspase-1 activity was increased in the bladder of the animal model of the beta-carotene In the PBS containing liquid, caspase-1 activity was significantly decreased.
Hereinafter, formulation examples of the pharmaceutical composition of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically explained.
< Formulation example 1> Preparation of injection
10 mg of β-carotene, 3.0 mg of sodium metabisulfite, 0.8 mg of methylparaben, 0.1 mg of propylparaben and an appropriate amount of sterilized distilled water for injection were mixed to prepare a final volume of 2 ml by a conventional method, An ampoule of 2 ml capacity was filled and sterilized to prepare an injection.
< Formulation example 2> Preparation of tablets
10 mg of beta-carotene, 100 mg of lactose, 100 mg of starch and an appropriate amount of magnesium stearate were mixed and tableted according to a conventional tablet preparation method.
≪ Formulation Example 3 > Preparation of capsules
Beta -carotene was mixed with 50 mg of lactose, 50 mg of starch, 2 mg of talc and an appropriate amount of magnesium stearate, and filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules.
Hereinafter, an example of production of health food using beta-carotene according to the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
< Manufacturing example 1> Manufacture of health food
< Manufacturing example 2> Health drink Produce
1000 mg of citric acid, 100 g of oligosaccharide, 2 g of a plum concentrate, 1 g of taurine and purified water were added to make a total of 900 ml, and the above components were mixed according to a conventional health drink manufacturing method , And the mixture was stirred and heated at 85 ° C for about 1 hour. Then, the resulting solution was filtered and sterilized in a sterilized 2 L container, followed by refrigerated storage.
While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
Claims (4)
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