KR20170086166A - Pharmaceutical Composition for Prevention or Treatment of Stroke - Google Patents
Pharmaceutical Composition for Prevention or Treatment of Stroke Download PDFInfo
- Publication number
- KR20170086166A KR20170086166A KR1020160005478A KR20160005478A KR20170086166A KR 20170086166 A KR20170086166 A KR 20170086166A KR 1020160005478 A KR1020160005478 A KR 1020160005478A KR 20160005478 A KR20160005478 A KR 20160005478A KR 20170086166 A KR20170086166 A KR 20170086166A
- Authority
- KR
- South Korea
- Prior art keywords
- pharmaceutical composition
- stroke
- compound
- group
- present
- Prior art date
Links
Images
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/56—Loganiaceae (Logania family), e.g. trumpetflower or pinkroot
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a pharmaceutical composition for prevention and treatment of stroke and a method for producing the same. The pharmaceutical composition for the prevention and treatment of stroke according to the present invention has a remarkable effect on prevention and treatment of stroke. In particular, the pharmaceutical composition for the prevention and treatment of stroke according to the present invention has the advantage of remarkably reducing the disadvantages of herbal medicine extracts including hepatotoxicity. The present invention also provides the first use for the prevention and treatment of strokes of single substances identified and isolated in wheat.
Description
The present invention relates to a pharmaceutical composition for prevention and treatment of stroke and a method for producing the same.
Stroke is the second most important cause of death among Koreans. Stroke can be divided into ischemic stroke and hemorrhagic stroke. Hemorrhagic stroke is mainly caused by traffic accidents. Most strokes are ischemic strokes, and the interruption of blood supply to a portion of the brain is the cause of ischemic stroke.
If transient cerebral ischemia is induced in the cerebrum, ATP depression and edema occur in the neuron, resulting in extensive damage of the brain due to neuronal death. Neuronal death occurs after a considerable period of time following cerebral ischemia, which is called delayed neuronal death. In the transient forebrain ischemic model using the Mongolian gerbil, the neuronal cell death was observed in the CA1 region of the
There are two known mechanisms of neuronal death due to cerebral ischemia. One is the accumulation of excess glutamate outside the cell by cerebral ischemia. This glutamate enters the cell and eventually causes excessive accumulation of intracellular calcium, resulting in neuronal death (Kang TC, et al. J. Neurocytol., 30: 945-955, 2001) and the other is the oxidative neuronal cell cycle that is caused by damage to DNA and cytoplasm due to an increase of in vivo radicals due to abrupt oxygen supply during ischemia-reperfusion Flowers F, Zimmerman JJ, New Horiz., New York, New York, NY, 1984; 6: 169-180,1998).
Recently, based on these studies, many researches have been conducted to search for a substance that effectively inhibits neuronal cell death in cerebral ischemia or to clarify the mechanism of substance. However, to date there are few substances that effectively inhibit neuronal cell death caused by cerebral ischemia.
Drugs that have been used in stroke so far include mainly thrombolytic agents and anti-blood coagulants (plasminogen activator or adenylyl cyclase activator), which are not direct drugs of cell protection due to stroke, Most of my therapies are.
In addition, a clinical test was conducted in the case of MK-801, a calcium channel blocker for effectively inhibiting early influx of calcium, but the drug was discarded due to its side effects.
On the other hand, the domestic patent discloses a pharmaceutical composition derived from a herbal medicine, but it has not been disclosed how many of the components present in the herbal extract exert a direct and pharmacologically beneficial effect on the stroke.
Specifically, Korean Patent Laid-Open Publication No. 2006-0019222 entitled " Composition for the Prevention and Treatment of Degenerative Brain Disease Containing an Extract of Wheat Starch with Neuronal Cell Protection Activity " The present invention relates to a pharmaceutical composition for preventing and treating degenerative brain diseases containing a whey crude extract having cell protection activity as an active ingredient and containing a pharmaceutically acceptable carrier, diluent or excipient.
However, the above invention is only a rough measurement of the efficacy of the extract of wheat, and there is no suggestion or comment as to which ingredient has its effective activity.
Korean Patent No. 1423875 discloses a composition for preventing or treating cerebral stroke or degenerative brain diseases containing a complex extract. The term " Sceptridium ternatum, Buddleja officinalis, And a pharmaceutical composition for the prevention or treatment of stroke or degenerative brain diseases comprising a composite extract of scutellaria baicalensis as an active ingredient ".
However, the above-mentioned invention has a necessity to include a mixed extract of various herbal medicines including wheat-thymus, so that it is not known whether wheat remedy improves degenerative brain disease by the sole action of wheat monohydrate, There is no suggestion or comment as to whether it has such pharmacological activity.
As described above, in the conventional invention, identification of the active ingredient of wheat starch has not been made. Therefore, not only the possibility of development as a new drug in the future was very low, but also it was difficult to apply the precise mechanism for industrial application. In addition, the herbal medicine extract has a problem that the toxicity thereof is significantly higher than that of a single component compound due to the limitations of its inherent limit that many pharmacological components are contained in large amounts.
Therefore, among the thousands to tens of thousands of ingredients contained in wheat, it is necessary to identify what ingredients are effective for stroke.
Accordingly, the inventors of the present invention have recognized that it is necessary to industrially utilize the efficacy of wheat-growing in order to identify a single active ingredient by extracting, identifying and evaluating a component effective for cerebral stroke from wheat- .
It is intended to provide a pharmaceutical composition for the prevention and treatment of stroke comprising a compound represented by the following formula (1) or a salt thereof as an active ingredient.
[Chemical Formula 1]
It is another object of the present invention to provide a method for preparing a pharmaceutical composition for the prevention and treatment of stroke, which comprises extracting, isolating and formulating an active ingredient in wheat milk.
In order to accomplish the object of the present invention, the present invention provides a pharmaceutical composition for preventing and treating stroke, comprising a compound represented by the following formula (1) or a salt thereof as an active ingredient.
[Chemical Formula 1]
The present invention also provides a method for preparing a pharmaceutical composition for the prevention and treatment of stroke, which comprises extracting, isolating and formulating an active ingredient in wheat milk.
The pharmaceutical composition for the prevention and treatment of stroke according to the present invention has a remarkable effect on prevention and treatment of stroke. In particular, the pharmaceutical composition according to the present invention has an advantage of remarkably reducing the disadvantages of herbal medicine extracts including hepatotoxicity.
The present invention also provides the first use for the prevention and treatment of strokes of single substances identified and isolated in wheat.
BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a diagram showing an example of the process for obtaining an extract and a fraction for obtaining the compound of the present invention. Fig.
2 is a view showing an example of a purification process for obtaining the compound of the present invention.
Fig. 3 shows another example of the purification process for obtaining the compound of the present invention.
FIG. 4 shows 1 H-NMR of
5 shows 13 C-NMR of
FIG. 6 shows 1 H-NMR of
7 shows 13 C-NMR of
8 is a diagram showing 1 H-NMR of
9 is a diagram showing 13 C-NMR of
10 is a diagram showing a structural formula of
FIG. 11 is a chart showing the cytotoxicity of the methanol extract obtained in the purification (extraction) of the
12 is a graph showing the inhibitory activity of PHD activity of the methanol extract obtained in the purification (extraction) of
FIG. 13 is a chart for confirming the cytotoxicity of fractions obtained according to the respective solvents obtained in the purification (fractionation) of the
FIG. 14 is a graph showing the ability of the fractions obtained in the purification (fractionation) step of
15 is a chart for confirming the cytotoxicity of the silica gel chromatography fraction obtained in the purification process of
16 is a graph showing the ability of the silica gel chromatography fraction obtained in the purification process of
Fig. 17 is a chart for confirming the cytotoxicity of the
18 is a graph showing the ability of
19 shows the effect of
20 shows the effect of
Hereinafter, the present invention will be described in more detail.
The present invention relates to a pharmaceutical composition for the prevention and treatment of stroke comprising a compound represented by the following formula (1) or a salt thereof as an active ingredient.
≪ Formula 1 >
The term " pharmaceutical composition " of the present invention means an article used for diagnosis, treatment, alleviation, treatment or prevention of a disease of a human or an animal, and any composition necessary for maintaining, improving or improving the health of an animal or a human. do.
The compound of the
Stroke is the second most important cause of death among Koreans. Stroke can be divided into ischemic stroke and hemorrhagic stroke.
&Quot; Stroke " as used in the present invention means ischemic or hemorrhagic stroke, and all lesions caused by the ischemic state of the brain are included in the scope of the present invention.
In ischemic conditions, the cells produce many responses to overcome this. The most important factor is the HIF protein. HIF-1 can be divided into α and β forms, among which HIF-1α is sensitive to oxygen and is degraded by PHD2. However, in the ischemic state, PHD can not digest HIF-1α, binds to HIF-1β to form HIF-1 complex, and expresses the target protein. The target proteins of HIF-1 are VEGF, EPO, HO-1 and Glut-1, which play a role in regulating damaged cells by participating in angiogenesis, iron metabolism, vasomotor regulation and glucose metabolism.
Therefore, finding a substance that activates HIF or increases the expression level, or acts to inhibit PHD or decrease the expression level is very important for the treatment and prevention of stroke, especially ischemic stroke.
It was confirmed that
This means that
The salt of
Examples of the inorganic acid include hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid. The organic acids include citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, , Glycolic acid, succinic acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid or aspartic acid, but are not limited thereto.
The
The inventors of the present invention conducted a screening for substances that reduce PHD through luciferase assay using 400 herbal medicine libraries in order to find a substance that inhibits PHD, and selected the whey assimilation among them.
Therefore, when extracting 3 of the present invention from a natural product, it is preferable to separate it from the wheat dream ( Buddleja officinalis ).
Wheatgrass buds are traditional herbs in Korea and China, and flavonoids, triterpenoids, saponins, and phenylethanoids have been isolated in previous studies (Tai, BH , Nhiem, NX, Quang, TH, Ngan, NTT, Tung, NH, Kim, Y., Lee, JJ, Myung, CS, Cuong, NM, & Kim, YH A new iridoid and effect on the rat aortic vasular smooth musle Cell proliferation of isolated compounds from Buddleja officinalis. Bioorg. Med. Chem. Lett., 2011, 21, 3462-3466, etc.). However, none of these compounds has been clearly identified as effective for stroke.
The present invention provides a method for the preparation of a pharmaceutical composition for the prevention and treatment of stroke, which comprises extracting, isolating and formulating
When the
The separation of the
The solvent used for the extraction is preferably 50 to 100% (v / v), more preferably 50% (v / v) to 99% (v / v) diluted water.
The extract obtained by extracting the wheat seed with one or more solvents selected from the group consisting of methanol, ethanol, propanol and isopropanol is subjected to extraction after removing the whey residue, filtering with a filter paper, and then filtrating the filtrate using a vacuum rotary concentrator or a vacuum dryer It can be concentrated and stored at room temperature.
The extract may be simultaneously or sequentially fractionated using at least one solvent selected from the group consisting of hexane, methylene chloride, ethyl acetate, butanol and water.
The solvent used for the fraction is preferably diluted water of 50% (v / v) to 100% (v / v), more preferably 50% (v / v) to 99% (v / v).
The fractions may be concentrated using a vacuum rotary evaporator or a vacuum drier and stored at room temperature.
The fractions obtained by simultaneous or sequential fractionation using one or more solvents selected from the group consisting of hexane, methylene chloride, ethyl acetate, butanol and water can be purified by silica gel chromatography or MPLC, Which can be additionally separated.
The solvent used in the above-mentioned chromatography method is not limited, but preferably at least one solvent selected from the group consisting of methanol, hexane, acetone, ethyl acetate, acetonitrile and methylene chloride is exemplified.
Examples of the inert carrier or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, corn starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, microcrystalline cellulose, polyvinylpyrrolidone, citric acid, tartaric acid, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, And the like, but the present invention is not limited thereto.
The pharmaceutical composition according to the present invention can be formulated into an oral or parenteral preparation including the above-exemplified carrier, additives including a diluent.
Formulations for oral administration include tablets, capsules, pills, powders, granules, suspending agents, and syrups. The form for parenteral administration may be in the form of a cream, a lotion, an ointment, a liquid, a gel, a cataplasma, a patch, an aerosol, a fluid extract, an elixir, an infusion, a sachet,
In addition, the pharmaceutical composition according to the present invention can be used as a conventional pharmaceutical composition, in addition to conventional fillers, extenders, binders, disintegrants, anticoagulants, lubricants, wetting agents, pH adjusters, nutrients, vitamins, electrolytes, alginic acid and its salts, Colloids, glycerin, fragrances, emulsifiers or preservatives, and the like. Other suitable lubricants and additional excipients that may be used are described in the following references. [Handbook of Pharmaceutical Excipients, 7th Edition, American Pharmaceutical Association; The Theory and Practice of Industrial Pharmacy, 3rd Edition, Lachman, Leon, 1976; Pharmaceutical Dosage Forms:
The pharmaceutical composition for the prevention and treatment of
The dose to be administered may be determined in consideration of the subject, method of administration, age, sex, severity of the subject, condition of the subject, absorption of the active ingredient in the body, inactivity, (Body weight) to 500 mg / kg (body weight), preferably 0.1 mg / kg (body weight), in the case of animals other than humans, Kg body weight) to 400 mg / kg body weight or more preferably 1 mg / kg body weight to 300 mg / kg body weight.
The administration can be carried out once or several times, but is not limited thereto.
The content of
The pharmaceutical composition for the prevention and treatment of stroke according to the present invention may additionally contain substances known in the art as well as the above-mentioned
Examples include blood coagulation inhibitors including coumarin derivatives, heparin derivatives and vitamin K antagonists; A cyclooxygenase inhibitor including aspirin and the like, a phosphodiesterase inhibitor including cilostazol and the like, an anti-serotonin agent including adenylate cyclase and clopidogrel, including sapoglylate, Prostaglandin derivatives including prostates, etc., anti -platelet agents including GPIIb-IIIa antagonists including tyrosine and the like ; Thrombolytic agents including europine kinase and the like; Thrombin inhibitors including darbigatran and the like; Apixaban, ginkgo extract, napamostat, ribaquivan, ticlopidine, ticagrella, and the like. More preferably, the compound of the formula (I) is selected from the group consisting of aspirin, cilostazol, clopidogrel, sapoglylate, veraprost, tyropivan, europine, dabigatran, apixaban, ginkgo x, napamostat, ribaroxan, ticlopidine, , But is not limited thereto.
Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
Example
One.
Wheat
Preparation of Extracts and Fraction Extracts
One.
Wheat
Preparation of methanol or ethanol extracts
To 4 kg of the wheat remnants with impurities removed, 90% methanol was added, and the mixture was immersed at room temperature for 24 hours. After filtration through a filter paper, the filtrate was concentrated using a vacuum rotary evaporator (EYELA). This process was repeated three times and the concentrate was stored at 4 [deg.] C until use to give a total of 432 g of methanol extract (see Figure 1).
Alternatively, 90% ethanol was added to 1 kg of the wheat wheat with impurities removed, and 98 g of the extract was obtained through the same process as above.
2.
Wheat
Preparation of fraction extract
The concentrated whey methanol or ethanol extract was fractionated with two solvents that did not mix using polarity differences. The mixture was successively fractionated with hexane, methylene chloride, ethyl acetate, n-butanol and water layers and concentrated. This procedure was repeated three times. The concentrate was stored at 4 ° C until use. The extract had 72.5 g of hexane layer, 52 g of methylene chloride layer, 120 g of ethyl acetate layer, 80 g of n-butanol layer and 100 g of water layer, respectively (see Fig. 1).
Example
2.
Separation of
The above fractionated hexane layer extract (72.5 g) was applied primarily to silica gel open column chromatography. The mobile phases were 100% acetone in 100% hexane and a total of 8 fractions were obtained (BOH 1-8). Based on the results of luciferase assay and MTT assay, additional silica gel column chromatography of BOH4 and BOH5 was carried out (see FIGS. 2 and 3).
In the case of
In the case of
Example
3.
Identification of Structure of
According to the natural product extraction method according to the present invention, three kinds of compounds (
[Chemical Formula 1]
Experimental Example
One.
Cytotoxicity of methanol extracts
MTT-based cytotoxicity assay was performed to evaluate the toxicity of the methanol extract of Example 1 to cells. Hypoxia was induced by treatment with CoCl 2 for 2 hours after PHD-CHO (PHD overexpressed CHO cell) cells were cultured for 8 hours in a 96-well plate. Cells were cultured for 18 hours and then treated with 5 mg / ml MTT solution was added and cultured for 3 hours. After removing the medium and dissolving in DMSO for 30 minutes, the absorbance was measured at 540 nm using an Emax precision microplate reader (Molecular Devices, CA, USA). As a result, it was confirmed that even at a concentration of 100 ug / ml of 90% methanol extract, there was no cytotoxicity (see FIG. 11).
Experimental Example
2.
Methanol extract
PHD
activation
Inhibition
Confirm
The PHD luciferase assay was performed to evaluate the ability of the methanol extract extracted in Example 1-1 to inhibit PHD activity. PHD-CHO cells cultured on a 96-well plate for 8 hours were treated with the drug, followed by CoCl 2 treatment for 2 hours, followed by incubation for 18 hours, followed by Luciferase Assay. After removing the medium, cells were lysed with lysis buffer, and 100 μl of reaction buffer was added to each well. Then, the cells were transferred to a luminometer plate and measured using a Centro XS3 LB 960 Microplate Luminometer.
As a result, PHD activity was inhibited in a concentration-dependent manner, and PHD activity was inhibited to a level corresponding to that of the control group (no treatment other than DMSO) at a concentration of 100 ug / ml in the experimental group (see FIG. 12).
Experimental Example
3.
Toxicity of fraction extracts
MTT-based cytotoxicity assay was performed to evaluate the cytotoxicity of the fraction extract of Example 1-2. Experimental example 1 was repeated except that the concentration of the test group was set to 20 ug / ml, 50 ug / ml and 100 ug / ml, respectively.
As a result, it was confirmed that there was no cytotoxicity at 20 ug / ml of hexane, methylene chloride, ethyl acetate and total concentration of butanol (see FIG. 13).
Experimental Example
4.
Of the fraction extract
PHD
activation
Inhibition
Confirm
The PHD luciferase assay was performed to evaluate the ability of the fraction extract of Example 1-2 to inhibit PHD activity. Based on the cytotoxicity results of Experimental Example 3, it was evaluated only in the range of non-toxicity. As a result, the best effect was confirmed at 20 ug / ml of hexane (see FIG. 14).
Experimental Example
5.
Silica gel open
Column chromatography
Fraction
Cytotoxicity and
PHD
activation
Inhibition
evaluation
The cytotoxicity and inhibition of PHD activity of the eight fractions (BOH 1-8) obtained from the silica gel open column chromatography of the hexane layer were evaluated. Experiments on cytotoxicity and inhibition of PHD activity were carried out in the same manner as Experimental Examples 1 and 2 except for the application concentration in the experimental group. Eight fractions proceeded at a concentration of 20 ug / ml.
Experimental Example
6.
Cytotoxicity Evaluation of
The cytotoxicity of the isolated
Experimental Example
7.
Experimental Example
8.
Western blot analysis of HIF-1α and HIF-1α, an important protein for the protection of neurons in ischemic conditions, was performed.
As a result, the expression level of PHD2 was decreased in inverse proportion to the concentration of
Claims (13)
[Chemical Formula 1]
Wherein the stroke is an ischemic stroke.
Wherein the salt is a physiologically acceptable salt with an inorganic acid, an organic acid, an inorganic base or an organic base.
Wherein the compound of Chemical Formula 1 is chemically synthesized or extracted from natural products.
Characterized in that, when extracted from the natural product, it is obtained by isolating it from the buddhera officinalis .
Wherein said separation is accomplished by extracting the wheat monomers with at least one solvent selected from the group consisting of methanol, ethanol, propanol and isopropanol.
Wherein the solvent extraction is accomplished by simultaneous or sequential fractionation with one or more solvents selected from the group consisting of hexane, methylene chloride, ethyl acetate, butanol and water.
Wherein said fraction is applied to a silica gel chromatography or a medium pressure liquid chromatography (MPLC) to achieve a single material separation.
The pharmaceutical composition comprises an inert carrier, a diluent, or both.
Wherein said pharmaceutical composition is formulated into an oral or parenteral formulation.
The pharmaceutical composition may be in the form of tablets, capsules, pills, powders, granules, suspending agents, syrups, creams, lotions, ointments, liquids, gels, cataplasms, patches, aerosols, Wherein the pharmaceutical composition is formulated as a single preparation selected from the group consisting of a sachet and an injection.
Wherein said pharmaceutical composition is selected from the group consisting of aspirin, cilostazol, clopidogrel, sapoglylate, veraprost, tyropivan, urokinase, darbigatran, apixaban, ginkgo extract, napamostat, ribaroxan, ticlopidine, ≪ / RTI > or a pharmaceutically acceptable salt thereof.
ii) simultaneously or sequentially fractionating the extract obtained in the above step with at least one solvent selected from the group consisting of hexane, methylene chloride, ethyl acetate, butanol and water;
iii) applying the fraction obtained in the above step to silica gel chromatography or medium pressure liquid chromatography (MPLC); And
iv) Formulating the compound of formula (1) separated in the above step so that it can be administered to a patient
Lt; RTI ID = 0.0 > 1, < / RTI >
[Chemical Formula 1]
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020160005478A KR101940372B1 (en) | 2016-01-15 | 2016-01-15 | Pharmaceutical Composition for Prevention or Treatment of Stroke |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020160005478A KR101940372B1 (en) | 2016-01-15 | 2016-01-15 | Pharmaceutical Composition for Prevention or Treatment of Stroke |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20170086166A true KR20170086166A (en) | 2017-07-26 |
KR101940372B1 KR101940372B1 (en) | 2019-01-21 |
Family
ID=59426864
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020160005478A KR101940372B1 (en) | 2016-01-15 | 2016-01-15 | Pharmaceutical Composition for Prevention or Treatment of Stroke |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR101940372B1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111579685A (en) * | 2020-05-29 | 2020-08-25 | 南京品生医疗科技有限公司 | Kit for detecting anticoagulant drugs in blood plasma and application thereof |
CN111812223A (en) * | 2020-06-01 | 2020-10-23 | 南京品生医学检验实验室有限公司 | Method for detecting antiplatelet drugs in plasma by ultra-high performance liquid chromatography tandem mass spectrometry technology |
CN111812219A (en) * | 2020-05-29 | 2020-10-23 | 南京品生医学检验实验室有限公司 | Method for detecting concentration of anticoagulant drug in blood plasma |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060007861A (en) * | 2004-07-22 | 2006-01-26 | 재단법인서울대학교산학협력재단 | A method for preparing purified extract for the prevention and treatment of stroke and ischemia from ginkgo biloba leaves extract and the composition containing the same |
KR20060019222A (en) | 2004-08-27 | 2006-03-03 | 경희대학교 산학협력단 | Composition comprising the extract of buddleja officinalis having neuronal cell-pretecting activity for preventing and treating degenerative brain disease |
KR20130107947A (en) * | 2012-03-23 | 2013-10-02 | 제주대학교 산학협력단 | Composition comprising diphlorethohydroxycarmalol for protecting nerve cells |
KR101423875B1 (en) | 2013-04-10 | 2014-08-01 | 경희대학교 산학협력단 | A composition comprising the complex extract for preventing or treating stroke and degenerative brain disease |
-
2016
- 2016-01-15 KR KR1020160005478A patent/KR101940372B1/en active IP Right Grant
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060007861A (en) * | 2004-07-22 | 2006-01-26 | 재단법인서울대학교산학협력재단 | A method for preparing purified extract for the prevention and treatment of stroke and ischemia from ginkgo biloba leaves extract and the composition containing the same |
KR20060019222A (en) | 2004-08-27 | 2006-03-03 | 경희대학교 산학협력단 | Composition comprising the extract of buddleja officinalis having neuronal cell-pretecting activity for preventing and treating degenerative brain disease |
KR20130107947A (en) * | 2012-03-23 | 2013-10-02 | 제주대학교 산학협력단 | Composition comprising diphlorethohydroxycarmalol for protecting nerve cells |
KR101423875B1 (en) | 2013-04-10 | 2014-08-01 | 경희대학교 산학협력단 | A composition comprising the complex extract for preventing or treating stroke and degenerative brain disease |
Non-Patent Citations (1)
Title |
---|
Bioorganic & Medicinal Chemistry Letters., 2011., Vol.21., pp 3462-3466 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111579685A (en) * | 2020-05-29 | 2020-08-25 | 南京品生医疗科技有限公司 | Kit for detecting anticoagulant drugs in blood plasma and application thereof |
CN111812219A (en) * | 2020-05-29 | 2020-10-23 | 南京品生医学检验实验室有限公司 | Method for detecting concentration of anticoagulant drug in blood plasma |
CN111812223A (en) * | 2020-06-01 | 2020-10-23 | 南京品生医学检验实验室有限公司 | Method for detecting antiplatelet drugs in plasma by ultra-high performance liquid chromatography tandem mass spectrometry technology |
Also Published As
Publication number | Publication date |
---|---|
KR101940372B1 (en) | 2019-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH0543469A (en) | Beta-glucuronidase inhibitor | |
KR101940372B1 (en) | Pharmaceutical Composition for Prevention or Treatment of Stroke | |
KR101841092B1 (en) | Fraction of Zanthoxylum piperitum leaf extracts with the effect of analgesic | |
KR20160122928A (en) | - A composition comprising extract of Lycopodiella cernua or compound isolated therefrom for preventing or treating of Alzheimer disease- | |
KR101793503B1 (en) | Composition for prevention or treatment of neurodegenerative diseases | |
KR101755097B1 (en) | Pharmaceutical Composition for Regeneration of Damaged Brain by Alzheimer's Disease | |
KR100979459B1 (en) | Tetracera scandens extracts and 4H-chromen-4-one derivatives isolated therefrom increasing glucose uptake in differentiated L6 muscle cells | |
KR101193558B1 (en) | An anti-inflammatory pharmaceutical composition comprising of extracts as an effective component from Laminaria japonica | |
KR101060909B1 (en) | Composition comprising plantain extract comprising brain neuronal cell protective material | |
KR101418164B1 (en) | A pharmaceutical composition comprising extract of UV-induced rice for preventing or treating a colon cancer | |
KR100965305B1 (en) | Composition for preventing or treating a disease mediated by overexpression of heat shock protein 27 | |
KR20180058072A (en) | Pharmaceutical composition for preventing or treating Cognitive Impairment or neurodegenerative disease comprising Castanea crenata inner shell extracts or scopoletin isolated therefrom | |
KR20170120021A (en) | Composition for Analgesic | |
EP3698805A1 (en) | Fraction ofzanthoxylum piperitum | |
KR102086632B1 (en) | Compositions for preventing or treating cognitive impairment-related disease comprising chebulanin | |
KR101332074B1 (en) | Composition Comprising Esculetin for Inhibition of Bone Loss | |
KR20160089930A (en) | A composition for memory enhancement, comprising 5-HMF, paeoniflorin and betaine | |
KR20200117501A (en) | Composition for improving damages of neuronal cells or inhibiting apoptosis of neuronal cells | |
KR100965304B1 (en) | Composition for preventing or treating a disease mediated by overexpression of heat shock protein 27 | |
KR102021453B1 (en) | Pharmaceutical Composition for Prevention or Treatment of Alzheimer's Disease Including Dendrobium nobile Extract | |
KR101772486B1 (en) | Composition for protecting neuronal cells comprising Centipeda minima extract | |
KR20160150232A (en) | Pharmaceutical Composition for Prevention or Treatment of Alzheimer's disease | |
KR100625766B1 (en) | Compound showing apoptosis-inhibitive effect purified from Saussureae radix and a method for preparing the said compound | |
KR20240073178A (en) | Composition for improving memory, inhibiting neuroinflammation, inhibiting neuronal apoptosis, or promoting autophagy, containing Dioscorea nipponica Makino extract or diosin | |
KR101756905B1 (en) | A composition comprising extract of Lycopodiella cernua or compound isolated therefrom for preventing or treating of Alzheimer disease-Ⅱ |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |