KR20150106995A - Composition of preventing or treating for myocardial damage containing echinochromea - Google Patents
Composition of preventing or treating for myocardial damage containing echinochromea Download PDFInfo
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- KR20150106995A KR20150106995A KR1020140028994A KR20140028994A KR20150106995A KR 20150106995 A KR20150106995 A KR 20150106995A KR 1020140028994 A KR1020140028994 A KR 1020140028994A KR 20140028994 A KR20140028994 A KR 20140028994A KR 20150106995 A KR20150106995 A KR 20150106995A
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- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
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Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
- A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
Abstract
The present invention relates to a pharmaceutical composition for preventing or treating damage to myocardial muscle comprising echinocorm A as an active ingredient, and is useful as a pharmaceutical composition for preventing or treating damage to myocardial cells caused by cardiac toxic drugs such as anticancer drugs, vasodilators, And suppression of myocardial cell mitochondrial function.
Through this, it is possible to prevent or inhibit mitochondrial membrane voltage change, decrease of oxygen consumption and decrease of ATP synthesis, and inhibit the phosphorylation of factors of cytotoxic signal process induced by toxic drug, Thus, myocardial damage can be prevented or treated from toxic drugs.
Description
The present invention relates to a composition capable of preventing or treating myocardial damage and cardiomyocyte damage containing echinocorm A, which is a pigment extracted from sea urchins.
Myocardium is extremely active metabolically by the muscles that constitute the heart and become the body of the heart contraction. These myocytes contain more than 30% of the individual fiber volume of mitochondria, and thus the preparation of high energy phosphates is very poor and aerobic metabolism is essential.
Cardiomyocyte apoptosis progresses as the level of adenosine triphosphate (ATP) is very low and the anaerobic response is substantially halted. In particular, drugs such as doxorubicin, an anticancer drug, and disodium nitroferricyanide (SNP), a vasodilator, have been shown to increase the intracellular reactive oxygen species and increase mitochondrial function To induce myocardial cell death. This can lead to heart failure and various heart diseases.
Echinochrome is a naphthoquinone pigment present in the echinoderms of the echinoderms. There are some differences depending on the species, depending on where the same species exist, or on the seasons. Echinochrome is thought to play an important role in the modification of sea urchin eggs and is known to be involved in the electron transport system as a redox pigment.
Two such species of echinocochromes are known, Echinochrome A and B, among which Echinocrome A of the
In addition, it has been reported that it has various physiological activities and reduces the cardiac damage due to ischemic reperfusion, but it has not been clearly clarified.
Accordingly, the present inventors have completed the present invention by confirming the effect of protecting the myocardial cells against drug toxicity, which has a negative effect on the heart, while studying the effect of echinocorm A on the heart.
The present invention provides a composition containing echinocorm A as an active ingredient to protect cardiomyocytes from toxic drugs by inhibiting the increase of active oxygen induced by cardiac toxic drugs and the deterioration of mitochondrial function of cardiac myocytes, And a composition capable of preventing or treating heart disease.
The present invention provides a pharmaceutical composition for preventing or treating myocardial injury comprising echinocorm A as an active ingredient.
The myocardial damage may be myocardial cell damage due to a cardiac toxic drug.
The drug may be selected from the group consisting of anticancer drugs and vasodilators.
The above-mentioned echinocrome A suppresses the increase of active oxygen species induced by drug toxicity and the deterioration of mitochondria function, and inhibits phosphorylation of signal transduction genes ERK1 / 2, JNK and p38 to inhibit myocardial cell death .
The above-mentioned equinochrome A may be contained in an amount of 0.01 to 90 parts by weight based on 100 parts by weight of the total amount of the pharmaceutical composition.
The present invention also provides a health food composition for preventing or ameliorating myocardial injury caused by drug toxicity comprising echinocorm A as an active ingredient.
The pharmaceutical composition containing the inventive echinocrome A as an active ingredient can be used for the treatment of diseases such as an increase in active oxygen species in the myocardial cell caused by a cardiac toxic drug such as an anticancer agent, a vasodilator or a drug that induces reactive oxygen species and a decrease in function of myocardial mitochondria Can be suppressed.
Through this, it is possible to prevent or suppress changes in membrane voltage, decrease in oxygen consumption and decrease in ATP synthesis of mitochondria. In addition, it can inhibit myocardial cell death by inhibiting the phosphorylation of the factors of cytotoxic signal process induced by toxic drug, so that myocardial damage can be prevented or treated from toxic drug.
Fig. 1 shows the formula of echinocorm A.
FIG. 2 shows the results of confirming the cell survival rate after 24 hours of treatment with 0, 1 or 3 μM of Echinochrome A in a rat heart myocardial cell, H9c2 cells, with a cardiac toxic drug,
FIG. 3 is a graph showing changes in the amount of active oxygen species and changes in membrane potential of mitochondria after treatment of H9c2 cells with 0, 1 or 3 μM of Echinochrome A, 5 μM of tBHP,
FIG. 4 is a graph showing changes in the amount of active oxygen in the mitochondria and mitochondrial membrane potential (Tm) after treatment of cardiac
FIG. 5 shows the results of examining mitochondrial oxygen consumption and ATP changes of H9c2 cells treated with cardiac
Figure 6 shows the Western blot results of the signaling factors ERK1 / 2, JNK and p38.
The present invention provides a pharmaceutical composition for preventing or treating myocardial injury comprising echinocorm A as an active ingredient.
The myocardial damage may be myocardial cell damage due to a cardiac toxic drug.
According to one embodiment of the present invention, cardiac toxic drugs 5 μM doxorubicin, 2 mM sodium nitrile fu- sid (SNP) or 50 μM tart-butyl hydroperoxide The seeds (tBuOOH; tBHP) were each treated for 24 hours.
As a result, as shown in Fig. 2, it was confirmed that the decrease of cell death by the toxic drug was suppressed depending on the concentration of echinocrome A concentration.
The drug may be selected from the group consisting of anticancer drugs and vasodilators.
The above-mentioned echinocrome A suppresses the increase of active oxygen species induced by drug toxicity and the deterioration of mitochondria function, and inhibits phosphorylation of signal transduction genes ERK1 / 2, JNK and p38 to inhibit myocardial cell death .
According to one embodiment of the present invention, sodium nitrile fusid (SNP) or 50 μM tart-butyl hydroperoxide was treated with H9c2, a cardiac muscle cell, and the changes in mitochondria were examined. As a result, The drug, doxorubicin, sodium nitroprusside (SNP) or tartobutylhydroperoxide, decreased the mitochondrial membrane voltage of myocardial cells and increased reactive oxygen species, but mitochondrial membrane voltage reduction in myocardial cells administered with echinocrome A And the increase of active oxygen species was effectively inhibited. As a result of confirming mitochondrial function-lowering effect by cardiac toxic drug, it was confirmed that reduction of oxygen consumption and reduction of ATP synthesis in mitochondria were inhibited as shown in FIG.
According to another embodiment, as shown in FIG. 6, in the signal process leading to myocardial cell death, echinocrome A inhibits phosphorylation of ERK1 / 2, JNK or p38 by a cardiac toxic drug, And inhibit myocardial damage.
The above-mentioned equinochrome A may be contained in an amount of 0.01 to 90 parts by weight based on 100 parts by weight of the total amount of the pharmaceutical composition.
The pharmaceutical composition may be any one selected from the group consisting of injections, granules, tablets, pills, capsules, gels, syrups, suspensions, emulsions, drops, and solutions.
The pharmaceutical compositions according to the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the production of pharmaceutical compositions.
Examples of the carrier, excipient or diluent which can be used in the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose sucrose), lactose, gelatin, and the like.
In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
The dosage of the pharmaceutical composition according to the present invention may vary depending on the age, sex and body weight of the patient, but it may be administered in an amount of 0.05 mg / day to 10.0 mg / day of echinocrome A once a day or several times a day .
Such dosage may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
In addition, the echinocromium A constituting the pharmaceutical composition according to the present invention has already been prescribed for other medical uses, and thus has safety.
The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
The present invention also provides a health food composition for preventing or ameliorating myocardial injury caused by drug toxicity comprising echinocorm A as an active ingredient.
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 reference example is provided to provide a reference example commonly applied to each embodiment according to the present invention.
< Reference Example > Result Analysis
All experiments were repeated 3 times and the results were expressed as mean ± standard error (SEM). Student's t-tests were used to compare the values between groups and p ≤ 0.05 was considered significant.
< Example 1> Chemicals and cell culture
1-1. chemical substance
(TbuOOH; tBHP), sodium nitropurssde (disodium nitroprusside, SNP) and doxorubicin (Dox) were purchased from Sigma-aldrich (USA) Professor Valentin A. Stonik.
1-2. Cell culture
Rat heart muscle cell H9c2 cells (American Type of Culture collection, USA) were inoculated into DMEM containing 10% fetal bovine serum, 50 U / ml penicillin (Lonza, USA) and 50 μM streptomycin (Lonza, USA) Dulbecco ' s Modified Eagle Medium).
< Example 2> Echinochrome A study on inhibition of cell death by cardiac toxic drugs
H9c2 cells in a 96-well tissue culture plates were seeded per well in a 2 × 10 4 cells. After 16 hours of inoculation, 50 μM tBHP, 2 mM SNP or 5 μM doxorubicin was treated for 24 hours in the presence of 0, 1 or 3 μM of Echinochrome A.
Cell viability was measured by MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide; Sigma-aldrich, USA], and the mitochondrial activity of the surviving cells was measured.
The optical density was measured at 570 nm using a microplate reader to determine the degree of inhibition of intracellular formation of formazan.
As a result, as shown in FIG. 2, cell survival rate was decreased in cardiomyocytes treated with 50 μM tBHP, 2 mM SNP, or 5 μM doxorubicin as shown in FIG. 2. However, in the case of cells treated with 1 or 3 μM of chinochrome A, The cell viability did not decrease.
< Example 3> Echinochrome A by cardiac toxic drugs Myocardial cell Mitochondrial damage reduction effect
3-1. Mitochondrial membrane potential analysis
Black bottom clean 96-well tissue culture plates per well H9c2 cells were inoculated with 2 × 10 4 cells. After 16 hours of inoculation, 50 μM tBHP, 2 mM SNP or 5 μM doxorubicin was treated for 1 hour in the presence of 0, 1, or 3 μM of Echinochrome A.
The mitochondrial inner membrane potential of each of the cells treated with tBHP, SNP or doxorubicin in the presence of echinocrome A was measured using a fluorescent dye, tetramethylrhodamine, ethyl ester (TMRE), excitation / emission = 549 nm / 574 nm; Invitrogen).
Each cell was stained with 200 nM TMRE for 30 min at 37 ° C, washed twice with PBS, and the relative signal intensity of intracellular TMRE was measured using a multiplate reader (Molecular Device, USA).
3-2. Active oxygen species ( ROS ) analysis
The levels of ROS were measured using CM-H 2 DCF-DA (excitation / emission = 492 nm / 517 nm; Invitrogen) in cells treated with control cells, tBHP, SNP or doxorubicin in the presence of echinocrome A. In general, ROS is used as an index for evaluating intracellular oxidative stress.
Cells treated with each drug were treated with 10 μM CM-H 2 DCF-DA, incubated at 37 ° C. for 30 minutes, washed twice with PBS, and incubated with a CM plate (Molecular Device, USA) The relative signal intensity of -H 2 DCF-DA was measured.
As a result, cardiac toxic drugs such as tBHP, SNP, or doxorubicin decreased mitochondrial membrane voltage and ROS as shown in Fig. 3, whereas mitochondrial membrane voltage and ROS increased in cells treated with echinocorm A I did.
< Example 4> Echinochrome A by cardiac toxic drugs Myocardial cell Confirmation of damage inhibition effect
4-1. Single from the rat heart Myocardial cell detach
The heart of the rat was collected by the method reported previously and the NT solution was stabilized by perfusion for 15 minutes. NT solution without Ca 2 + in the heart was then perfused for 7 minutes and NT solution (Caul, Japan) without Ca 2 + added with 0.01% collagenase was perfused for 9-13 minutes. After the heart was washed with oxygenated KB solution for 10 minutes, the atrium was removed and the left ventricular wall and diaphragm were cut into small pieces and the heart muscle cells were separated by stirring in KB solution. Isolated single myocardial cells were used to measure ROS levels and △ Ψm.
4-2. Mitochondrial inner membrane potential analysis
To confirm the cardioprotective effect of echinocrome A on cardiac toxic drugs in mitochondria, mitochondrial endothelial potential (DELTA Ψm) of cells treated with control cells, tBHP, SNP or doxorubicin in the presence of echinocrome A was measured using a fluorescent dye Tetramethylrhodamine, ethyl ester (TMRE; excitation / emission = 549 nm / 574 nm; Invitrogen).
1 × 10 6 single myocardial cells isolated from the rat heart were stained with 200 nM TMRE at 37 ° C. for 30 minutes and then washed with PBS and incubated with 50 μM tBHP, 2 mM SNP or 5 μM doxorubicin in the presence of 0, 1, or 3 μM echinocorm A Was treated at 37 < 0 > C for 1 hour.
Cells were then washed with PBS and the relative signal intensity of TMRE was analyzed using a LSM700 confocal microscope (Carl Zeiss, Germany) and images were obtained using ZEN 2009 (Carl Zeiss, Germany).
4-3. Active oxygen species ( ROS ) analysis
ROS of cells treated with control cells, tBHP, SNP or doxorubicin in the presence of echinocrome A was analyzed using CM-H 2 DCF-DA (excitation / emission = 492 nm / 517 nm; Invitrogen). In general, ROS is used as an index for evaluating intracellular oxidative stress.
Single heart myocytes isolated from rat hearts were treated with 10 μM CM-H 2 DCF-DA, incubated at 37 ° C. for 30 minutes, washed with PBS, and incubated in the presence of 0, 1, or 3 μM echinocorm A with 50 μM tBHP, 2 mM SNP Or 5 [mu] M doxorubicin was treated at 37 [deg.] C for 1 hour. Cells were then washed with PBS and the relative signal intensity of CM-H 2 DCF-DA was analyzed using an LSM 700 confocal microscope (Carl Zeiss, Germany) and images were obtained using ZEN 2009 (Carl Zeiss, Germany) .
As a result, as shown in Fig. 4, when the cardiac toxic drug of rat myocardial cells was treated, decrease of mitochondrial membrane voltage and increase of reactive oxygen species were confirmed. On the other hand, when the echinocorm A and the toxic drug were treated together, the mitochondrial membrane voltage was drastically decreased, and the rapid increase of reactive oxygen species was also suppressed, confirming that the result was similar to the result of Fig. 3 of Example 3 above.
< Example 5> from damage by cardiac toxic drug Echinochrome Confirmation of the protective effect of A on mitochondrial function
5-1. Mitochondria ATP Level analysis
Mitochondrial ATP levels were measured using the Mitochondrial ToxGlo ™ assay (Promega, USA) according to the manufacturer's instructions.
First, it was inoculated with one H9c2 cells per well in 60mm tissue culture plates with 2 × 10 5 cells. After 16 hours of cell inoculation, 50 μM tBHP, 2 mM SNP or 5 μM doxorubicin was treated for 1 hour in the presence of 0, 1, or 3 μM Echinocorm A. The drug treated cells were harvested and pipetted to resuspend the cells until uniformly dispersed.
The resuspended H9c2 cells were inoculated into 2 × 10 4 cells per well in a 96-well white clear bottom culture plate and centrifuged at 200 × g for 10 minutes. The medium was then removed and 50 μl of a fresh glucose-free medium containing 10 mM of galactose .
The plates were then incubated in a 37 ° C wet CO 2 incubator for 90 minutes.
After the incubation, 100 μl of the assay solution was added to the plate, followed by incubation at room temperature for 30 minutes, and the luminescence was measured using a luminescence meter (Molecular Device, USA).
5-2. Oxygen consumption rate analysis
Oxygen consumption rate (OCR) was analyzed by the method (20) reported using XF24 analyzer (Seahorse Bioscience, USA).
H9c2 cells were inoculated with 2x10 4 cells per well in an XF24 cell culture plate (Seahorse Bioscience, USA), 16 hours later, various concentrations of echinocorm A were treated for 1 hour, and the medium was cultured in XF Assay Medium-modified DMEM (Seahorse Bioscience, USA), incubated at 37 ° C for 1 hour without CO 2 , and the OCR was measured with an XF24 analyzer and XF24 software.
After OCR measurement, XF24 analysis results were normalized to the cell number. The number of cells in each well was counted using a LunaTM automated cell counter (Logos, USA).
As a result, as shown in FIG. 5, mitochondrial oxygen consumption and ATP decrease were observed in cells treated with cardiac toxic drugs, tBHP, SNP or doxorubicin alone, while mitochondrial function decreased and ATP was decreased. In the cells, mitochondrial oxygen consumption and ATP decrease were inhibited.
< Example 6> Echinochrome A signaling process confirmation
Western blot analysis was performed to confirm the effect of echinocorm A on intracellular signal transduction of toxic drugs.
First, the cell lysate was centrifuged at 4 ° C at 14,000 rpm for 15 minutes. Protein concentrations of cell lysates were determined using a Bradford proteins assay (Bio-Rad, USA) kit and loaded with 30 μg of protein per lane of 10% SDS polyacrylamide gel.
The gel was transferred onto a nitrocellulose membrane (Whatman TM , Germany) and reacted with ERK1 / 2, pERK1 / 2, JNK, pJNK, p38, pp38 and cell-signaling (USA) specific antibodies.
Proteins were then identified using Western blotting detection kit Ab signalTM (AbClon, Korea) and LAS-3000 Plus (Fuji Photo Film Company, Japan).
As a result, as shown in FIG. 6, cardiac toxic drugs induce phosphorylation of ERK1 / 2, JNK and p38, which are intracellular signal transduction factors. Echinocorm A inhibits phosphorylation of these factors, To inhibit apoptosis induced by apoptosis.
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
3.5 mg of Echinochrome A, 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 and adjusted to a final volume of 2 ml by a conventional method, Ampicillin and sterilized to prepare an injection.
< Formulation example 2> Preparation of tablets
3.5 mg of Echinochrome A, 100 mg of lactose, 100 mg of starch and an appropriate amount of magnesium stearate were mixed and tableted according to a conventional preparation method.
< Formulation example 3> Preparation of capsules
3.5 mg of Echinochrome A, 50 mg of lactose, 50 mg of starch, 2 mg of talc, and an appropriate amount of magnesium stearate were mixed and filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules.
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 (6)
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017155129A1 (en) * | 2016-03-07 | 2017-09-14 | 인제대학교 산학협력단 | Composition for inducing differentiation of cardiomyocyte containing echinochrome a as active ingredient |
| KR20230154499A (en) | 2022-05-02 | 2023-11-09 | 인제대학교 산학협력단 | Composition for preventing or treating atopic dermatitis comprising echinochrome A |
| WO2024085700A1 (en) * | 2022-10-21 | 2024-04-25 | 한국식품연구원 | Composition for ameliorating, preventing, or treating myocardial damage, containing cirsium setidens, capsella, or saururus chinensis extract |
-
2014
- 2014-03-12 KR KR1020140028994A patent/KR20150106995A/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017155129A1 (en) * | 2016-03-07 | 2017-09-14 | 인제대학교 산학협력단 | Composition for inducing differentiation of cardiomyocyte containing echinochrome a as active ingredient |
| KR20230154499A (en) | 2022-05-02 | 2023-11-09 | 인제대학교 산학협력단 | Composition for preventing or treating atopic dermatitis comprising echinochrome A |
| WO2024085700A1 (en) * | 2022-10-21 | 2024-04-25 | 한국식품연구원 | Composition for ameliorating, preventing, or treating myocardial damage, containing cirsium setidens, capsella, or saururus chinensis extract |
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