US20160199338A1 - Compositions containing monoacetyldiacylglycerol compound as an active ingredient for preventing or treating rheumatoid arthritis - Google Patents
Compositions containing monoacetyldiacylglycerol compound as an active ingredient for preventing or treating rheumatoid arthritis Download PDFInfo
- Publication number
- US20160199338A1 US20160199338A1 US14/912,049 US201414912049A US2016199338A1 US 20160199338 A1 US20160199338 A1 US 20160199338A1 US 201414912049 A US201414912049 A US 201414912049A US 2016199338 A1 US2016199338 A1 US 2016199338A1
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- United States
- Prior art keywords
- compound
- rheumatoid arthritis
- formula
- monoacetyldiacylglycerol
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Definitions
- the present invention relates to pharmaceutical compositions, as well as health functional food compositions and quasi-drug compositions, for preventing, treating, or improving rheumatoid arthritis, comprising a monoacetyldiacylglycerol compound as an active ingredient.
- Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation by attacking joints or other parts of the body.
- Rheumatoid arthritis causes a painful swelling of fingers, hands, feet, wrists, ankles, knees and sometimes can affect other organs of the body such as muscle, skin, lungs and eyes.
- the underlying cause of rheumatoid arthritis remains unclear and has been investigated continuously.
- known methods for treating or preventing rheumatoid arthritis are not effective and better treatments are needed.
- Many hormone medications such as steroids have been widely used to treat arthritis. However, because the use of the hormone medications is not a fundamental treatment and can cause several side effects, the treatment is limited.
- Drugs currently used for the treatment of arthritis have several limitations including side effects preventing long-term use of the drugs, the absence of anti-inflammatory effect and the lack of efficacy for treating the arthritis that has already occurred.
- side effects preventing long-term use of the drugs
- the absence of anti-inflammatory effect and the lack of efficacy for treating the arthritis that has already occurred.
- the development of an effective therapeutic agent for arthritis has been constantly needed.
- Most of currently used medications for treating arthritis have a certain degree of side effect, although it is varied among medications and patients. Especially, because it is necessary to take medications for a long period of time for the treatment of rheumatoid arthritis, it is very important and urgent problem to develop a novel pharmaceutic agent with low side effect.
- EC18 is a monoacetyldiglyceride and has been separated from deer antler. It has been reported that EC-18 increases survivability ratio of animals in sepsis animal model experiment using cecal-ligation-puncture, and shows no toxicity in a GLP (Good Laboratory Practice) toxicity test. However, the effect of the monoacetyldiacylglycerol compounds including EC-18 on rheumatoid arthritis is not known or disclosed in the prior art.
- the present inventors aimed to find a compound derived from natural products or a novel compound for the treatment of rheumatoid arthritis and found that the monoacetyldiacylglycerol compound inhibits STAT-3, a therapeutic target for rheumatoid arthritis and can be used to prevent or treat rheumatoid arthritis.
- An object of the present invention is to provide pharmaceutical compositions, health functional food compositions and quasi-drug compositions, for preventing, treating, or improving rheumatoid arthritis, comprising a monoacetyldiacylglycerol of Formula 1 as an active ingredient.
- R 1 and R 2 are independently a fatty acid residue of 14 to 20 carbon atoms.
- Another object is to provide methods for preventing or treating rheumatoid arthritis, comprising administering a compound of formula 1 to a patient that suffers from rheumatoid arthritis or can develop rheumatoid arthritis.
- the present invention provides pharmaceutical compositions for preventing or treating rheumatoid arthritis, comprising a monoacetyldiacylglycerol of Formula 1 as an active ingredient.
- R 1 and R 2 are independently a fatty acid residue of 14 to 20 carbon atoms.
- fatty acid residue refers to the acyl moiety resulting from formation of an ester bond by reaction of a fatty acid and an alcohol.
- the pharmaceutical composition for preventing or treating rheumatoid arthritis of the present invention comprises a monoacetyldiacylglycerol of Formula 1.
- the term “monoacetyldiacylglycerol compound” means a glycerol derivative containing an acetyl group and two acyl groups and is also referred to as MADG.
- R 1 and R 2 are independently a fatty acid residue of 14 to 20 carbon atoms.
- Non-limiting examples of R 1 and R 2 thus include palmitoyl, oleoyl, linoleoyl, linolenoyl, stearoyl, myristoyl, arachidonoyl, and so on.
- R 1 and R 2 include oleoyl/palmitoyl, palmitoyl/oleoyl, palmitoyl/linoleoyl, palmitoyl/linolenoyl, palmitoyl/arachidonoyl, palmitoyl/stearoyl, palmitoyl/palmitoyl, oleoyl/stearoyl, linoleoyl/palmitoyl, linoleoyl/stearoyl, stearoyl/linoleoyl, stearoyl/oleoyl, myristoyl/linoleoyl, myristoyl/oleoyl, myristoyl/oleoyl, and so on.
- the monoacetyldiacylglycerol derivatives of Formula 1 can be (R)-form, (S)-form or a racemic mixture, and may include their stereoiso
- the monoacetyldiacylglycerol is a compound of the following Formula 2:
- the compound of Formula 2 is 1-palmitoyl-2-linoleoyl-3-acetylglycerol, sometimes referred as “EC-18” in this disclosure.
- R 1 and R 2 of the compound of Formula 2 are palmitoyl and linoleoyl, respectively.
- the monoacetyldiacylglycerol compounds can be separated and extracted from the natural deer antler or can be produced by known organic synthesis methods (Korean Registered Patents No. 10-0789323). More specifically, deer antler is extracted with hexane, followed by extracting the residue with chloroform and removing the chloroform to provide chloroform extracts. The volume of the solvents for this extraction is just enough to immerse the deer antler. In general, about 4-5 liters of hexane and/or chloroform for 1 kg of deer antler is used, but not limited thereto.
- the extracts obtained by this method is further fractionated and purified using series of silica gel column chromatograph and TLC method to obtain the monoacetyldiacylglycerol compound for the present invention.
- a solvent for the extraction is selected among chloroform/methanol, hexane/ethylacetate/acetic acid, but not limited thereto.
- a chemical synthetic method for the preparation of monoacetyldiacylglycerol compounds is shown in Korean Registered Patents No. 10-0789323. Specifically, the method comprises (a) a step of preparing 1-R1-3-protecting group-glycerol by adding a protecting group in the position 3 of 1-R1-glycerol; (b) a step of preparing 1-R1-2-R2-3-protecting group-glycerol by introducing R2 in the position 2 of the 1-R1-3-protecting group-glycerol; and (c) a step of preparing the desired monoacetyldiacylglycerol compound by performing a deprotection reaction and the acetylation reaction of the 1-R1-3-protecting group-glycerol at the same time.
- the monoacetyldiacylglycerol compound may be further purified if necessary.
- monoacetyldiacylglycerol compounds can be prepared by acid decomposition of phosphatidylcholine (acetolysis) but is not limited thereto.
- Stereoisomers of the compounds of formula (I) are also within the scope of the invention.
- the monoacetyldiacylglycerol compound inhibits the phosphorylation of STAT-3, thus effective in preventing or treating rheumatoid arthritis.
- rheumatoid arthritis is a chronic inflammatory disease of unknown cause characterized by polyarthritis. Inflammation initially appears in the synovium surrounding the joint but gradually spreads to the periphery of the cartilage and bone, leading to damage and deformity of the joint. In addition to the joint, rheumatoid arthritis can attack other body parts.
- the symptoms of rheumatoid arthritis include anemia, dry syndromes, subcutaneous nodules, pulmonary fibrosis, vasculitis and skin ulcers.
- Medicines used for the treatment of rheumatoid arthritis include nonsteroidal anti-inflammatory agents, steroids, an anti-rheumatic drug and TNF blocking agents, but are known to present a risk of various side effects.
- prevention includes any activity to suppress or delay the onset of rheumatoid arthritis by administering the composition of the present invention.
- treatment includes prophylaxis, mitigation, amelioration, delay or reduction of symptoms, as well as partial or complete elimination or prevention of symptoms, of rheumatoid arthritis by administering the composition of the present invention.
- Th17 cells that produce interleukin-17 (IL-17) play a leading role in the pathogenesis of rheumatoid arthritis.
- Th17 cells induce joint inflammation and bone destruction directly.
- STAT-3 known as a key transcription factor for the differentiation and the activity of Th17 cells can regulate the locus of IL-17 and play an essential role in the expression of many transcriptional factors involved in the differentiation of TH17 cells.
- STAT-3 can be activated by a phosphorylation. It has been known that the inhibition of STAT-3 activation in TH17 cells can control TH17 cells and increase the activity of immunoregulatory T cells, thus preventing or treating rheumatoid arthritis. Thus, STAT-3 has become a therapeutic target for rheumatoid arthritis.
- the pharmaceutical composition comprising a monoacetyldiacylglycerol of the invention may include conventional pharmaceutically acceptable carriers, excipients, or diluents.
- the amount of monoacetyldiacylglycerol in the pharmaceutical composition can be widely varied without specific limitation, and is specifically 0.0001 to 100 weight %, preferably, 0.001 to 50 weight %, more preferably 0.01 to 20 weight %, with respect to the total amount of the composition.
- the pharmaceutical composition may be formulated into solid, liquid, gel or suspension form for oral or non-oral administration, for example, tablet, bolus, powder, granule, capsule such as hard or soft gelatin capsule, emulsion, suspension, syrup, emulsifiable concentrate, sterilized aqueous solution, non-aqueous solution, freeze-dried formulation, suppository, and so on.
- conventional excipients or diluents such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants can be used.
- the solid formulation for oral administration includes tablet, bolus, powder, granule, capsule and so on, and the solid formulation can be prepared by mixing one or more of the active components and at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and so on. Besides the excipient, a lubricant such as Magnesium stearate and talc can also be used.
- the liquid formulation for oral administration includes emulsion, suspension, syrup, and so on, and may include conventional diluents such as water and liquid paraffin or may include various excipients such as wetting agents, sweeting agents, flavoring agents, and preserving agents.
- the formulation for non-oral administration includes sterilized aqueous solution, non-aqueous solution, freeze-dried formulation, suppository, and so on, and solvent for such solution may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ester for syringe injection such as ethyl oleate.
- Base materials of the suppository may include witepsol, macrogol, tween 61, cacao butter, Laurin and glycerogelatin.
- the monoacetyldiacylglycerol compound can be administered in a pharmaceutically effective amount.
- pharmaceutically effective amount is used to refer to an amount that is sufficient to achieve a desired result in a medical treatment.
- the “pharmaceutically effective amount” can be determined according to the subject's category, age, sex, severity and type of disease, activity of drug, sensitivity to drug, administration time, administration route, excretion rate, and so forth.
- the composition of the present invention can be administered alone or with other therapeutic agents sequentially or simultaneously.
- the composition of the present invention can be administered once or multiple times.
- the preferable amount of the composition of the present invention can be varied according to the condition and weight of patient, severity of disease, formulation type of drug, administration route and period of treatment.
- An appropriate total amount of administration per 1 day can be determined by a physician, and is generally about 0.001 to about 1000 mg/kg, preferably about 0.05 to 200 mg/kg, more preferable about 0.1 to about 100 mg/kg once a day or can be administered in divided doses multiple times daily.
- the composition of the present invention can be administered to any subject that requires the prevention or treatment of rheumatoid arthritis.
- the composition of the present invention can be administered to not only human but also non-human animal (specifically mammals) such as monkey, dog, cat, rabbit, guinea pig, rat, mouse, cow, sheep, pig, goat, and so on.
- composition of the present invention can be administered by conventional various methods, for example, by oral or rectum administration, or by intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.), intrauterine dural or cerebrovascular injection.
- i.v. intravenous
- i.m. intramuscular
- s.c. subcutaneous
- intrauterine dural or cerebrovascular injection intrauterine dural or cerebrovascular injection.
- the present invention provides health functional food compositions for preventing or improving rheumatoid arthritis, which comprises a monoacetyldiacylglycerol of formula 1 as an active ingredient:
- R 1 and R 2 are independently a fatty acid residue of 14 to 20 carbon atoms, but are not limited thereto.
- the monoacetyldiacylglycerol of the invention can be included in health functional food compositions for preventing or improving rheumatoid arthritis.
- the monoacetyldiacylglycerol and rheumatoid arthritis are the same as explained above.
- the term “improvement” or “improving” includes any activity to improve or ameliorate the symptoms of rheumatoid arthritis by administering the composition of the present invention.
- the health functional food composition of the present invention for preventing or improving rheumatoid arthritis may consist of only or substantially pure monoacetyldiacylglycerols, or may include the monoacetyldiacylglycerol and other conventional ingredients of health functional food.
- the amount of monoacetyldiacylglycerol in the health food composition can be determined suitably according to the intended use. Generally, the amount of monoacetyldiacylglycerol is preferably less than 15 weight %, more preferably less than 10 weight %, with respect to the total amount of the health functional food composition when the monoacetyldiacylglycerol is included in food or beverages.
- the amount of monoacetyldiacylglycerol may be increased or decreased. In case of a long term use for the purpose of the health control and hygiene, the amount of the monoacetyldiacylglycerol can be less than the above range. Since there is no problem in terms of safety, the monoacetyldiacylglycerol may be used in an amount greater than the above range.
- Foods to which the compound of the present invention can be added are not limited and include various foods, for example, meats, sausages, breads, chocolates, candies, snacks, pizzas, noodles, gums, daily products such as ice creams, soups, beverages, teas, drinks, alcoholic beverages, vitamin complexes and any health functional food.
- the beverage product may include sweeting agents, flavoring agents or carbohydrates.
- carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol.
- the amount of carbohydrate in the beverage composition can be widely varied without specific limitation, and is preferably 0.01 to 0.04 g, more preferably, 0.02 to 0.03 g per 100 ml of the beverage.
- sweeting agents include natural sweeteners such as thaumatin and stevia extract and artificial sweeteners such as saccharin and aspartame.
- the health functional food composition of the present invention may include various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickening agents, pH controlling agents, stabilizing agents, preserving agents, glycerin, alcohol, carbonizing agents used in carbonated beverages and so on.
- the health functional food composition of the present invention may include fruits, as used in preparing natural fruit juices and fruit juice beverages and vegetable beverages.
- the present invention provides quasi-drug compositions for preventing or improving rheumatoid arthritis, which comprises a monoacetyldiacylglycerol of formula 1 as an active ingredient:
- R 1 and R 2 are independently a fatty acid residue of 14 to 20 carbon atoms, but are not limited thereto.
- the monoacetyldiacylglycerol of the invention can be included in quasi-drug compositions for preventing or improving rheumatoid arthritis.
- quadsi-drug means a product which falls under any of the followings: (a) Fibers, rubber products or similar products used for the purpose of treating, alleviating, or preventing human or animal diseases; (b) Non-appliance, non-machinery or similar products which have insignificant influences on or do not directly act upon human bodies; and (c) Preparations used for sterilization, insecticide and purposes similar thereto in order to prevent communicable diseases.
- Quasi-drug does not include (a) products used for the purposes of diagnosis, medical care, alleviation, treatment or prevention of diseases of human beings or animals, excluding appliances, machinery and equipment; or (b) products, other than appliances, machinery or equipment, used for the purpose of exerting pharmacological effects upon the structure or functions of human beings or animals.
- Quasi-drugs include the external preparations for skin and personal care products.
- the quasi-drug composition of the present invention for preventing or improving rheumatoid arthritis may consist of only or substantially pure monoacetyldiacylglycerols, or may include the monoacetyldiacylglycerol and other conventional ingredients of quasi-drugs.
- the amount of monoacetyldiacylglycerol in the quasi-drug composition can be determined suitably in accordance with the intended use.
- the skin external preparations to which the compound of the present invention can be added include, for example, ointments, lotions, spray agents, patches, creams, powders, suspensions, and gels but are not limited thereto.
- the present disclosure provides methods for preventing or treating rheumatoid arthritis, comprising administering a composition comprising a compound of formula 1 to a patient in need thereof.
- patient in need includes any animal including human that suffers from rheumatoid arthritis or can develop rheumatoid arthritis.
- Rheumatoid arthritis can be treated or prevented by administering an effective amount of a compound of formula 1 to a patient in need thereof.
- administration means introducing the pharmaceutical composition of the present invention to a patient in need by any suitable method.
- the composition of the present disclosure can be administered by conventional various methods, for example, by oral or non-oral administration.
- the present disclosure provides methods for preventing or treating rheumatoid arthritis, comprising administering an effective amount of a pharmaceutical composition comprising a compound of formula 1 to a patient in need thereof.
- An appropriate total amount of administration per 1 day can be determined by a physician, and is generally about 0.001 to about 1000 mg/kg, preferably, about 0.05 to 200 mg/kg, more preferably about 0.1 to about 100 mg/kg.
- the total administration amount per day can be administered once a day or can be administered in divided doses multiple times daily.
- the specific therapeutically effective amount of the monoacetyldiacylglycerol administered to a particular patient can be varied depending on the type and degree of the response to be achieved in the treatment, the specific composition, including whether another agent is included in the composition, the patient's age, body weight, general health status, sex, diet, administration time, administration route, the ratio of composition, treatment period, other drugs used together in the treatment and a variety of factors well known in the medical field.
- the monoacetyldiacylglycerol of the invention is effective in inhibiting the phosphorylation of STAT-3 known to be a therapeutic target for rheumatoid arthritis.
- the monoacetyldiacylglycerol is an effective therapeutic agent without toxicity
- the monoacetyldiacylglycerol can overcome the side effects of the medicines currently used in the treatment of rheumatoid arthritis.
- the monoacetyldiacylglycerol can be used for preventing, treating or improving rheumatoid arthritis.
- FIG. 1 is the result of western blot analysis showing the inhibition of STAT-3 phosphorylation induced by IL-6 in U937 cells with the treatment of EC-18 in different concentrations.
- EC-18 is treated for 15 minutes.
- EC-18 is treated for 60 minutes.
- FIG. 2 is the result of western blot analysis showing the inhibition of STAT-3 phosphorylation (A) and STAT-1 phosphorylation (B) induced by PMA (Phorbol 12-myristate 13-acetate) in NK-92 cells with the treatment of EC-18 in different concentrations.
- A STAT-3 phosphorylation
- B STAT-1 phosphorylation
- FIG. 3 is the result of luciferase fluorescence representing STAT-3 activity in A549 cells (A) and HepG2 cells (B).
- FIG. 4 is the measurement of the concentration of interleukin-6 in serum corrected at the day of tissue excision in normal group, negative control group, EC-18 treatment groups and positive control group.
- FIG. 5 is arthritis score measured by the examination with the naked eye in normal group, negative control group, EC-18 treatment groups and positive control group.
- FIG. 6 is the result of histopathological arthritis score of knee joint in normal group, negative control group, EC-18 treatment groups and positive control group.
- FIGS. 7 and 8 show microscopic images of stained arthritic tissue in normal group, negative control group, EC-18 treatment groups and positive control group.
- NK-92, U937, A549 and HepG2 Human cell lines NK-92, U937, A549 and HepG2 (American Type Culture Collection, ATCC, Rockville, Md.) were cultured at 37° C. under 5% CO 2 humid conditions.
- NK-92 cells were cultured in alpha-MEM media (Life Technologies, Düsseldorf, Germany) containing 10% Fetal Calf Serum (FCS, HyClone, Logan, Utah), 2 mM L-glutamate, 100 ⁇ g/ml penicillin, 100 m/ml streptomycin (Life Technologies).
- FCS Fetal Calf Serum
- HyClone HyClone
- Ecomycin 100 ⁇ g/ml
- streptomycin streptomycin
- the membrane was incubated with poly rabbit-anti-(STAT1, STAT3) or poly rabbit-anti-phospho (STAT1, STAT3) antibody (Cell Signaling Technology, USA (1:1000) as a primary antibody for 60 minutes at room temperature.
- the membrane was incubated with horseradish peroxidase-conjugated goat anti-rabbit IgG antibody (Santa Cruz Biotechnology, USA) (1:3000) as a secondary antibody for 60 minutes at room temperature.
- the same amount of cellular proteins was confirmed by poly rabbit anti- (STAT1, STAT3) antibody.
- ECL solution Micropore, Billerica, Mass., USA
- the amount of phosphorylated STAT-3 was measured in the band on the film.
- FIG. 1A shows that the inhibitory effect of EC18 on STAT-3 phosphorylation is maintained after 1 hour.
- the membrane was incubated with poly rabbit-anti-STAT3, poly rabbit-anti-STAT1, or poly rabbit-anti-phospho-STAT3 antibody (Cell Signaling Technology, USA (1:1000) as a primary antibody for 60 minutes at room temperature.
- the membrane was incubated with horseradish peroxidase-conjugated goat anti-rabbit IgG antibody (Santa Cruz Biotechnology, USA) (1:3000) as a secondary antibody for 60 minutes at room temperature.
- horseradish peroxidase-conjugated goat anti-rabbit IgG antibody Santa Cruz Biotechnology, USA
- the same amount of cellular proteins was confirmed by poly rabbit anti-STAT3.
- membrane was incubated with ECL solution (Millipore, Billerica, Mass., USA) and exposed to X-ray film. The amount of phosphorylated STAT was measured in the band on the film.
- the pGL4.47 [luc2P/SIE/Hygro] vector Promega was introduced into A549 cells and HepG2 cells. Inhibition of the STAT-3 activation by EC-18 was measured by pre-treating the cells with EC-18 and then treating the cells with IL-10.
- A549 cells and HepG2 cells were split to the culture plate.
- Attractene Transfection Reagent Qiagen
- cells were transfected with pGL4.47[luc2P/SIE/Hygro] vector and incubated at 37° C. under 5% CO 2 conditions for a day.
- the cells were collected from the culture plate and 0.1 ml of cells were transferred to 96-well plate in a concentration of 5 ⁇ 10 4 cells/well and incubated at 37° C. under 5% CO 2 conditions for a day.
- the cells were pre-treated with different concentrations of EC-18 for one hour and then treated with 10 ng/ml of IL-10.
- Luciferease activity was measured using ONE-Glo Luciferase Assay System (Promega). Specifically, 0.1 ml of a 1:1 mixture of ONE-Glo Luciferase Assay System and Substrate was added to each well. After three minutes, the fluorescence was measured using VICTOR X Multilabel Plate Reader (PerkinElmer) during 0.5 second.
- Luciferase fluorescence is decreased in cells pre-treated with different concentrations of EC-18, compared to cells treated with IL-10 alone, indicating decreased STAT-3 activity in cells pre-treated with EC-18 ( FIGS. 3A and 3B ).
- the result shows that STAT-3 activation induced by IL10 is decreased by the treatment of EC-18 in A549 cells and HepG2 cells
- Olive oil was administered to normal group (G1) and negative control group (G2) as an excipient. In all groups, administration was made once a day for five weeks (a total of 35 administrations). Remicade (G6) was administered intraperitoneally, whereas EC-18, methotrexate and olive oil were administered orally in force.
- normal Group (G1) arthritis was induced by immunizing animals twice with bovine type II collagen and complete Freund's adjuvant or incomplete Freund's adjuvant emulsion. During the observation period, common arthritis symptoms were observed once a day, weigh measured once a week, arthritic score evaluation made with the naked eye twice a week, foot thickness measured twice a week.
- FIG. 4 The concentration of IL-6 in serum collected at the day of tissue excision is shown in FIG. 4 .
- the concentration of IL-6 is significantly increased in Group 2 (negative control group) in which arthritis is induced by collagen and the concentration of IL-6 is reduced in EC-18 treatment groups (G3, G4 and G5), similar to the positive control groups (Remicade and Methothrexate treatment group, G6 and G7).
- FIG. 5 shows arthritis score evaluated by the examination with naked eye.
- arthritis score in EC-18 treatment groups (G3, G4 and G5) is significantly decreased, compared to the negative control group (G2).
- FIG. 6 shows arthritis score measured by the histopathological examination of the extracted knee joint of both hind legs. As shown in FIG.
- FIGS. 7 and 8 show microscopic images of stained arthritic tissue of normal group (G1), negative control group (G2), 500 mg/kg EC-18 treatment group (G4) and Remicade treatment group (G6) ( FIG. 7 ; 40 ⁇ , FIG. 8 : ⁇ 100). As shown in FIGS.
- arthritis model was established as arthritis indexes such as arthritis score evaluated with naked eye, foot thickness, interleukin-6 (IL-6) level in serum, the concentration of anti-type II collagen (anti-CII) IgG and histopathological arthritis score are significantly increased in the negative control group, compared to the normal group.
- arthritis indexes such as arthritis score evaluated with naked eye, foot thickness, interleukin-6 (IL-6) level in serum, the concentration of anti-type II collagen (anti-CII) IgG and histopathological arthritis score are significantly increased in the negative control group, compared to the normal group.
- anti-CII anti-type II collagen
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CN (2) | CN105530930A (ja) |
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US20190350890A1 (en) * | 2016-10-13 | 2019-11-21 | Enzychem Lifesciences Corporation | Composition for preventing or treating hepatitis containing monoacetyl diacylglycerol compound |
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US20160199338A1 (en) | 2013-08-19 | 2016-07-14 | Enzychem Lifesciences Corporation | Compositions containing monoacetyldiacylglycerol compound as an active ingredient for preventing or treating rheumatoid arthritis |
CN106535887A (zh) | 2014-05-15 | 2017-03-22 | 株式会社Enzychem生命科学 | 治疗白细胞减少症和血小板减少症的方法 |
US9808438B2 (en) * | 2015-11-09 | 2017-11-07 | Enzychem Lifesciences Corporation | Method for treating mucositis |
KR101836822B1 (ko) * | 2016-10-17 | 2018-03-09 | 주식회사 엔지켐생명과학 | 모노아세틸디아실글리세롤 화합물을 함유하는 건선의 예방 또는 치료용 조성물 |
KR101883252B1 (ko) | 2016-10-26 | 2018-07-30 | 김창희 | 앵글 캡 |
EP3632435A4 (en) | 2017-05-30 | 2021-01-13 | Kao Corporation | BONE REGENERATION AGENT |
RU2020121489A (ru) | 2017-11-30 | 2021-12-30 | Энзикем Лайфсайенсиз Корпорейшн | Композиции для профилактики или лечения острой лучевой болезни |
KR102076314B1 (ko) * | 2018-07-16 | 2020-02-11 | (주) 에프엔지리서치 | 녹용에서 분리한 신규 화합물 및 이의 약학적 용도 |
CN113194940A (zh) * | 2019-03-07 | 2021-07-30 | Enzychem生命科学株式会社 | 治疗脂肪肝的包含单乙酰基二酰基甘油化合物的组合物 |
KR102218542B1 (ko) * | 2019-04-16 | 2021-02-22 | 주식회사 엔지켐생명과학 | 모노아세틸디아실글리세롤 화합물을 함유하는 통풍 치료용 조성물 및 통풍의 치료 방법 |
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- 2014-08-18 CN CN201480050098.XA patent/CN105530930A/zh active Pending
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US9895337B2 (en) | 2018-02-20 |
EP3037090A4 (en) | 2017-04-26 |
CN108420812A (zh) | 2018-08-21 |
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JP6081024B2 (ja) | 2017-02-15 |
CA2921845C (en) | 2018-07-10 |
AU2014309637A1 (en) | 2016-03-10 |
JP2016532701A (ja) | 2016-10-20 |
KR20150021465A (ko) | 2015-03-02 |
EP3037090A1 (en) | 2016-06-29 |
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