WO2009121155A2 - Use of one or more benzopyranones, phamaceutical composmon and method for preventing or treating diseases, dysfunctions and disturbances associated to monoamine oxidase - Google Patents
Use of one or more benzopyranones, phamaceutical composmon and method for preventing or treating diseases, dysfunctions and disturbances associated to monoamine oxidase Download PDFInfo
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- WO2009121155A2 WO2009121155A2 PCT/BR2009/000089 BR2009000089W WO2009121155A2 WO 2009121155 A2 WO2009121155 A2 WO 2009121155A2 BR 2009000089 W BR2009000089 W BR 2009000089W WO 2009121155 A2 WO2009121155 A2 WO 2009121155A2
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- 0 *c1cc(C(Oc2c3c(O)c(*)c(O)c2*)=CC3=O)ccc1O Chemical compound *c1cc(C(Oc2c3c(O)c(*)c(O)c2*)=CC3=O)ccc1O 0.000 description 2
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the object of the present invention is the use of benzopyranones of formula (I) in the manufacture of a medicament that is useful in the treatment of diseases, dysfunctions and disturbances associated to monoamine oxidase, pharmaceutical compositions containing said compounds and method for preventing or treating said diseases, dysfunctions and disturbances.
- Monoamines are important neurotransmitters of the nervous system, whose concentrations in the extracellular and intracellular environment must be well controlled. This control is performed by the monoamine oxidases (MAO), which are enzymes having the function of degrading MA, thus avoiding the accumulation, in the case of endogens MA, such as the hormones dopamine, serotonin, noradrenaline a nd a drenaline, or undesirable effects, in the case of exogens MA, such as tyramine which is present in certain foods. .
- MAO monoamine oxidases
- MAO-A preferably inactivates serotonin, melatonin, epinephrine an d norepinephrine.
- MAO-B preferably deaminates phenylethylamine and residual amines. The two isoforms inactivate dopamine.
- Increased or decreased levels of activity of MAO in individuals may be related to a series of neuropsychiatric disturbances and neurodegenerative diseases, such as depression and diseases related to depression, such as phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease, migraine, among others. These diseases affect a considerable portion of the population.
- MAO inhibitors which reversibly or irreversibly inhibit, selectively or not, the two isoforms of the enzyme and, therefore, preventing breakage of the neurotransmitters of the monoamine kind and increasing its availability in the organism.
- the Filing Applicant verified that the benzopyranone compounds of formula (I) defined below act upon the IMAOs, making them useful active principles in the preparation of medicament s intended for the treatment or prevention of diseases, dysfunctions and disturbances associated to MAO.
- R 1 and R 2 independently represent hydrogen, radicals arabinose, xylose, glucose, galactose, glucose-glucose (sophorose), galactose- galactose or ramnose and R 3 represents hydrogen or hydroxyl.
- these benzopyranone compounds of formula (I) are C-glycosylated flavonoids, more particularly one or more from among: schaftoside, isoschaftoside, vitexin, isovitexin, isovitexin-2"-O-beta- glucopyranoside, isoorientin-2"-O-beta-glucopyranoside.
- the benzopyranone compounds according to the present invention can be obtained synthetically by conventional chemical routes or be contained in a standardized pharmaceutical product, in a particular embodiment, from roots, stalks, leaves and fruits of plants of the genus Passifloraceae, more particularly, from the genus Passiflora incarnata (Li et al.: J. Chromatogr. 1991; 526(1 -2):435-46).
- the benzopyranone compounds of formula (I) are effective in inhibiting the two MAO isoforms (MAO-A and MAO-B), thus increasing the synaptic concentration thereof and causing greater excitation of the neurons that have receptors for these mediators.
- the medicament s according to the present invention are suitable for the prevention or treatment of neuropsychiatric disturbances and neurodegenerative diseases or dysfunctions.
- the dysfunctions, disturbances or diseases include depression and diseases related to depression, phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease and migraine.
- the disease includes major depression or depressant symptoms that do not respond to conventional treatment with other anti-depressants.
- the appropriate dosage of one or more active principles according to the present invention may vary between about 0.001 to about 5000 mg/kg/day, particularly between about 200 to about 400 mg/kg/day, divided into one or more times per day.
- Another object of the present invention consists of a pharmaceutical composition containing an effective quantity of one or more benzopyranone compounds of formula (I), as defined previously and pharmaceutically acceptable excipients.
- the pharmaceutical compositions according to the present invention can be liquid, semi-solid or solid and can be adopted for any enteral or parenteral administration route, be it immediate or sustained release.
- said pharmaceutical composition is adapted for oral administration, more particularly in the form of tablets, capsules, dyes, emulsions, liposomes, microcapsules or nanoparticles.
- the quantity of active principle present in each dosage unit may vary between about 1 to 500 mg.
- Suitable excipients for the invention are, for example, and without any limitation, those cited in the book entitled Remington's Pharmaceutical Sciences, by North American firm Mack Publishing, Farmacopeia Europeia or Farmacopeia Brasileira.
- Another object according to the present invention includes a method for preventing or treating diseases, dysfunctions and disturbances associated to MAO which comprises supplying to a patient in need an effective quantity of one or more benzopyranone compounds defined by formula (I) or a pharmaceutical composition containing said benzopyranone compounds.
- the product is purified by chromatography at average pressure, using as eluent system a mixture of acetonitryl (MeCN) and water with 2 Mn of triethylamine (Et3N) in gradient mode (5% to 100% in 3 days), and the stationary phase and the inverse phase (Lichroprep C18, 15-25 m, Merck) in a column of 460 mm in length by 70 mm in diameter.
- the compounds were detected by ultraviolet at 254 nm.
- the fractions obtained were re-submitted to various chromatography techniques including medium-pressure chromatography (MPLC), high performance liquid chromatography (HPLC) 1 leading to the isolation of 6 C-glycosylated flavonoids, identified by classic techniques of structural elucidation including ultraviolet, nuclear magnetic resonance (RMN) and mass spectrometry (MS) as being: isorientin-2"-O-beta- glucopyranoside (1), isoschaftoside (2), schaftoside (3), isovitexin -2"-O-beta- glucopyranoside (4), vitexin (5) and isovitexin (6).
- MPLC medium-pressure chromatography
- HPLC high performance liquid chromatography
- kynuramine was obtained from Sigma-Aldrich Chemical (St. Louis, MA, USA).
- DMSO selected for molecular biology
- 4- hydroxyquinoline salts of potassium phosphate, potassium chlorate and sodium hydroxide were supplied by the company Fluka AG (Buchs, Switzerland).
- human SupersomesTM of MAO were acquired from the company Becton & Dickinson Gentest (Woburn, MA, USA). These are fractions of mitochondrial membranes containing recombinant MAO A or MAO B, respectively. The SupersomesTM were stored at -80 0 C.
- the MAO inhibition assays were carried out using a method based on fluorescence (reading of end point) using kynuramine as substrate.
- the reactions were performed on flat-bottom microtier polystyrene plates with 96 tubes (FluoroNunc/LumiNunc, MaxiSorpTM surface, NUNC, Roskild, Denmark) containing potassium phosphate buffer, a normal aqueous solution normal of kynuramine and an inhibiting solution of DMSO.
- This assay mixture was pre- incubated at 37°C, and then the diluted recombinant human enzyme was supplied to obtain a final concentration of protein of 0.015mg/ml_ for MAO A and 0.009mg/ml_ for MAO B. The incubation was carried out at 37°C and the reaction was finalized by adding NaOH. All the manual liquid operations were carried out at the Caliper-Zymark SciClone ALH500 mechanized station.
- 4-hydroxyquinoline was quantified by a fluorescent 96 microplate reader (FLx 800, Bio-Tek Instruments, Inc., Winooski, USA) in wavelengths of excitation/emission of 310/400 nm (20 nm in width of the gap for excitation, 30 nm in width of the gap for emission).
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Abstract
The object of the present invention is the use of benzopyranone compounds of formula (I) in the manufacture of a medicament that is useful in the treatment of diseases, dysfunctions and disturbances associated to monoamine oxidase, pharmaceutical compositions containing said compounds and method for preventing or treating said diseases, dysfunctions and disturbances.
Description
"USE OF ONE OR MORE BENZOPYRANONES, PHAMACEUTICAL
COMPOSITION AND METHOD FOR PREVENTING OR TREATING
DISEASES, DYSFUNCTIONS AND DISTURBANCES ASSOCIATED TO
MONOAMINE OXIDASE" FIELD OF THE INVENTION
The object of the present invention is the use of benzopyranones of formula (I) in the manufacture of a medicament that is useful in the treatment of diseases, dysfunctions and disturbances associated to monoamine oxidase, pharmaceutical compositions containing said compounds and method for preventing or treating said diseases, dysfunctions and disturbances.
BACKGROUND OF THE INVENTION
Monoamines (MA) are important neurotransmitters of the nervous system, whose concentrations in the extracellular and intracellular environment must be well controlled. This control is performed by the monoamine oxidases (MAO), which are enzymes having the function of degrading MA, thus avoiding the accumulation, in the case of endogens MA, such as the hormones dopamine, serotonin, noradrenaline a nd a drenaline, or undesirable effects, in the case of exogens MA, such as tyramine which is present in certain foods. . There are two known MAO isoforms: MAO-A and MAO-B. MAO-A preferably inactivates serotonin, melatonin, epinephrine an d norepinephrine. MAO-B preferably deaminates phenylethylamine and residual amines. The two isoforms inactivate dopamine.
Increased or decreased levels of activity of MAO in individuals may be related to a series of neuropsychiatric disturbances and neurodegenerative diseases, such as depression and diseases related to depression, such as phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease, migraine, among
others. These diseases affect a considerable portion of the population.
In order to treat the problems listed above, some drugs with an action mechanism based on the interaction with MAO have been used. These include MAO inhibitors (IMAO), which reversibly or irreversibly inhibit, selectively or not, the two isoforms of the enzyme and, therefore, preventing breakage of the neurotransmitters of the monoamine kind and increasing its availability in the organism.
Although these drugs are important in the treatment of these problems, currently there is no variety of products available on the market, precisely because it is a complex technical field. Examples of drugs currently in use are: tranylcypromine (Parnate and Stelapar), moclobemide (Aurorix) and selegiline (Elepril and Jumexil). With this purpose, some herbal medicament s have also been studied (Schaufelberger and Hostettmann: Chemistry and
Pharmacology of Gentiana lactea. Planta Med 1988; 54:219-221 and international patent application WO2005086937).
Consequently, there is a need for new compounds that are useful in the preparation of medicament s for the treatment of neuropsychiatric disturbances and neurodegenerative diseases and dysfunctions, particularly acting upon the IMAOs. DESCRIPTION OF THE INVENTION
The Filing Applicant verified that the benzopyranone compounds of formula (I) defined below act upon the IMAOs, making them useful active principles in the preparation of medicament s intended for the treatment or prevention of diseases, dysfunctions and disturbances associated to MAO.
In a particular embodiment, these benzopyranone compounds of formula (I) are C-glycosylated flavonoids, more particularly one or more from among: schaftoside, isoschaftoside, vitexin, isovitexin, isovitexin-2"-O-beta- glucopyranoside, isoorientin-2"-O-beta-glucopyranoside.
The benzopyranone compounds according to the present invention can be obtained synthetically by conventional chemical routes or be contained in a standardized pharmaceutical product, in a particular embodiment, from roots, stalks, leaves and fruits of plants of the genus Passifloraceae, more particularly, from the genus Passiflora incarnata (Li et al.: J. Chromatogr. 1991; 526(1 -2):435-46).
As evidenced in the examples presented herein, the benzopyranone compounds of formula (I) are effective in inhibiting the two MAO isoforms (MAO-A and MAO-B), thus increasing the synaptic concentration thereof and causing greater excitation of the neurons that have receptors for these mediators.
The medicament s according to the present invention are suitable for the prevention or treatment of neuropsychiatric disturbances and neurodegenerative diseases or dysfunctions. In a particular embodiment, the dysfunctions, disturbances or diseases include depression and diseases related to depression, phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease and migraine. In an even more particular embodiment, the disease includes major depression or depressant symptoms that do not respond to conventional treatment with other anti-depressants.
The appropriate dosage of one or more active principles according
to the present invention may vary between about 0.001 to about 5000 mg/kg/day, particularly between about 200 to about 400 mg/kg/day, divided into one or more times per day.
Another object of the present invention consists of a pharmaceutical composition containing an effective quantity of one or more benzopyranone compounds of formula (I), as defined previously and pharmaceutically acceptable excipients. The pharmaceutical compositions according to the present invention can be liquid, semi-solid or solid and can be adopted for any enteral or parenteral administration route, be it immediate or sustained release. In a particular embodiment, said pharmaceutical composition is adapted for oral administration, more particularly in the form of tablets, capsules, dyes, emulsions, liposomes, microcapsules or nanoparticles.
The quantity of active principle present in each dosage unit may vary between about 1 to 500 mg. Suitable excipients for the invention are, for example, and without any limitation, those cited in the book entitled Remington's Pharmaceutical Sciences, by North American firm Mack Publishing, Farmacopeia Europeia or Farmacopeia Brasileira.
Another object according to the present invention includes a method for preventing or treating diseases, dysfunctions and disturbances associated to MAO which comprises supplying to a patient in need an effective quantity of one or more benzopyranone compounds defined by formula (I) or a pharmaceutical composition containing said benzopyranone compounds.
The examples below are intended to illustrate aspects of the present invention, yet do not have any limiting character. Below is a presentation of tests carried out with a standardized pharmaceutical Passiflora incarnata product merely for ease of demonstration, without limitation to this product only.
EXAMPLES PREPARING AN ACTIVE FRACTION OF PASSIFLORA INCARNATA
Into a vat of an extractor having mechanical agitation were added
1.5 kg of Passiflora incarnate leaves and shoots, having been previously dried in a warming drawer, at a controlled temperature of 6O0C and ground in an electric grinder. Next, 9 liters of ethyl alcohol in water were added, with frequent agitation, for the period of 70 to 150 hours. The product obtained was vacuum filtered through 100μm filters. After evaporation of the solvent under reduced pressure in a rotative evaporator, 20 g of a concentrated product was obtained.
Next, the product is purified by chromatography at average pressure, using as eluent system a mixture of acetonitryl (MeCN) and water with 2 Mn of triethylamine (Et3N) in gradient mode (5% to 100% in 3 days), and the stationary phase and the inverse phase (Lichroprep C18, 15-25 m, Merck) in a column of 460 mm in length by 70 mm in diameter. The compounds were detected by ultraviolet at 254 nm. The fractions obtained were re-submitted to various chromatography techniques including medium-pressure chromatography (MPLC), high performance liquid chromatography (HPLC)1 leading to the isolation of 6 C-glycosylated flavonoids, identified by classic techniques of structural elucidation including ultraviolet, nuclear magnetic resonance (RMN) and mass spectrometry (MS) as being: isorientin-2"-O-beta- glucopyranoside (1), isoschaftoside (2), schaftoside (3), isovitexin -2"-O-beta- glucopyranoside (4), vitexin (5) and isovitexin (6).
STUDY OF INHIBITION OF HUMAN MONOAMINE OXIDASE The product previously prepared was partially dissolved in DMSO at a concentration of 10 mg/ml and tested in vitro in relation to its capacity to inhibit human monoamine oxidases A and B.
For the present test, kynuramine was obtained from Sigma-Aldrich
Chemical (St. Louis, MA, USA). DMSO (selected for molecular biology), 4- hydroxyquinoline, salts of potassium phosphate, potassium chlorate and sodium hydroxide were supplied by the company Fluka AG (Buchs, Switzerland).
For the biological assays, human Supersomes™ of MAO were acquired from the company Becton & Dickinson Gentest (Woburn, MA, USA). These are fractions of mitochondrial membranes containing recombinant MAO A or MAO B, respectively. The Supersomes™ were stored at -800C.
The MAO inhibition assays were carried out using a method based on fluorescence (reading of end point) using kynuramine as substrate. In short, the reactions were performed on flat-bottom microtier polystyrene plates with 96 tubes (FluoroNunc/LumiNunc, MaxiSorp™ surface, NUNC, Roskild, Denmark) containing potassium phosphate buffer, a normal aqueous solution normal of kynuramine and an inhibiting solution of DMSO. This assay mixture was pre- incubated at 37°C, and then the diluted recombinant human enzyme was supplied to obtain a final concentration of protein of 0.015mg/ml_ for MAO A and 0.009mg/ml_ for MAO B. The incubation was carried out at 37°C and the reaction was finalized by adding NaOH. All the manual liquid operations were carried out at the Caliper-Zymark SciClone ALH500 mechanized station.
The formation of 4-hydroxyquinoline was quantified by a fluorescent 96 microplate reader (FLx 800, Bio-Tek Instruments, Inc., Winooski, USA) in wavelengths of excitation/emission of 310/400 nm (20 nm in width of the gap for excitation, 30 nm in width of the gap for emission).
The analysis of the data was performed with Prism V4.0 (GraphPad Software. Inc.). The degree of inhibition was evaluated in terms of inhibition percentage.
The inhibition percentages were determined for the two MAO isoforms in a final concentration of 0.1mg/ml. Figure 1 shows the results of inhibition percentage. As can be seen, the product inhibited the two MAO
isoforms. Since the product was not entirely dissolved in DMSO in the concentration test, the real potency may be slightly higher.
Claims
CLAIMS 1. USE of one or more benzopyranone compounds of formula (I):
Formula (I) wherein R1 and R2 independently represent hydrogen, radicals arabinose, xylose, glucose, galactose, glucose-glucose (sophorose), galactose- galactose or ramnose and R3 represents hydrogen or hydroxyl in the manufacture of a medicament that is useful in the prevention or treatment of diseases, dysfunctions and disturbances associated to monoamine oxidase.
2. USE, according to claim 1 , wherein diseases, dysfunctions and disturbances associated to monoamine oxidase include one or more from among depression and diseases related to depression, phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease and migraine.
3. USE, according to either of claims 1 or 2, wherein the diseases, dysfunctions and disturbances associated to monoamine oxidase include major depression or depressant symptoms that do not respond to conventional treatment with other anti-depressants.
4. USE, according to any of claims 1 to 3, wherein the benzopyranone compounds of formula (I) are C-glycosylated flavonoids.
5. USE, according to any of claims 1 to 4, wherein the benzopyranone compounds of formula (I) are schaftoside, isoschaftoside, vitexin, isovitexin, isovitexin-2"-0-beta-glucopyranoside, isoorientin-2"-O-beta- glucopyranoside.
6. PHAMACEUTICAL COMPOSITION for the prevention or treatment of diseases, dysfunctions and disturbances associated to monoamine oxidase comprising an effective amount of one or more benzopyranone compounds of formula (I):
Formula (I) wherein R1 and R2 independently represent hydrogen, radicals arabinose, xylose, glucose, galactose, glucose-glucose (sophorose), galactose- galactose or ramnose and R3 represents hydrogen or hydroxyl and pharmaceutically acceptable excipients.
7. PHAMACEUTICAL COMPOSITION, according to claim 6, wherein the benzopyranone compounds of formula (I) are C-glycosylated flavonoids.
8. PHAMACEUTICAL COMPOSITION, according to either of claims 6 or 7, wherein the benzopyranone compounds of formula I are schaftoside, isoschaftoside, vitexin, isovitexin, isovitexin-2"-O-beta-glucopyranoside, isoorientin- 2"-O-beta-glucopyranoside.
9. PHAMACEUTICAL COMPOSITION, according to any of claims 6 to 8, wherein the quantity of active principle present in each dosage unit may vary between about 1 to 500 mg.
10. ME THOD FOR PREVENTING OR TREATING DISEASES, DYSFUNCTIONS AND DISTURBANCES ASSOCIATED TO MONOAMINE
OXIDASE consisting of providing a patient in need an effective quantity of one or more benzopyranone compounds of formula (I) defined in any of claims 1 to 5 or a pharmaceutical composition defined in any of claims 6 to 9.
11. METHOD, according to claim 10, wherein the diseases, dysfunctions and disturbances associated to monoamine oxidase include one or more from among depression and diseases related to depression, phobias, attention deficit, drug abuse, behavioral maladjustment, Parkinson's disease, Alzheimer's disease and migraine.
12. METHOD, according to either of claims 10 or 11, wherein the diseases, dysfunctions and disturbances associated to monoamine oxidase include major depression or depressant symptoms that do not respond to conventional treatment with other anti-depressants.
13. METHOD, according to any of claims 10 to 12, wherein the effective quantity varies between about 0.001 to about 5000 mg/kg/day, divided into one or more times per day.
14. METHOD, according to claim 13, wherein the effective quantity varies between about 200 to about 400 mg/kg/day, divided into one or more times per day.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BRPI0801239-3 | 2008-04-01 | ||
| BRPI0801239-3A BRPI0801239A2 (en) | 2008-04-01 | 2008-04-01 | use of one or more benzopyranones, pharmaceutical composition and method for the prevention or treatment of monoamine oxidase-associated diseases, disorders and disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2009121155A2 true WO2009121155A2 (en) | 2009-10-08 |
| WO2009121155A3 WO2009121155A3 (en) | 2009-11-26 |
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|---|---|---|---|
| PCT/BR2009/000089 WO2009121155A2 (en) | 2008-04-01 | 2009-04-01 | Use of one or more benzopyranones, phamaceutical composmon and method for preventing or treating diseases, dysfunctions and disturbances associated to monoamine oxidase |
Country Status (2)
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| BR (1) | BRPI0801239A2 (en) |
| WO (1) | WO2009121155A2 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102329312A (en) * | 2011-07-26 | 2012-01-25 | 苏州宝泽堂医药科技有限公司 | Method for purifying schaftoside |
| WO2015023142A1 (en) * | 2013-08-14 | 2015-02-19 | 대화제약 주식회사 | Pharmaceutical composition for treating or preventing neuropsychitric disease, containing flavone-6-c-glucose derivatives as active ingredients |
| WO2017046777A1 (en) | 2015-09-19 | 2017-03-23 | Indus Biotech Private Limited | Composition and methods thereof |
| KR101818084B1 (en) * | 2015-04-14 | 2018-01-15 | 대구가톨릭대학교산학협력단 | A composition comprising extract of Lycopodiella cernua or compound isolated therefrom for preventing or treating of Alzheimer disease-Ⅱ |
| WO2021225343A1 (en) * | 2020-05-06 | 2021-11-11 | 한국한의학연구원 | Composition for preventing or treating cognitive disorder, comprising iris lactea extract |
| WO2022052016A1 (en) * | 2020-09-11 | 2022-03-17 | Liu Hsuan Miao | Pharmaceutical compositions and uses thereof in treating parkinson's disease |
| US11879115B2 (en) | 2018-11-26 | 2024-01-23 | Roar Holding Llc | Methods to improve beverage quality |
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| WO1995005169A1 (en) * | 1993-08-17 | 1995-02-23 | The University Of Strathclyde | Flavonoid and biflavonoid derivatives, their pharmaceutical compositions, their anxiolytic activity |
| JPH0873360A (en) * | 1994-09-01 | 1996-03-19 | Yoshihide Hagiwara | Suppressing agent against brain nerve cell injury |
| GB2348371A (en) * | 2000-03-14 | 2000-10-04 | Soares Da Silva Patricio | Compositions comprising L-DOPA renal cell transfer blocking compounds suitable for the treatment of Parkinson's disease |
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| US6806257B1 (en) * | 1999-10-20 | 2004-10-19 | Board Of Trustees Of Southern Illinois University | Flavones as inducible nitric oxide synthase inhibitors, cyclooxygenase-2 inhibitors and potassium channel activators |
| US20050004046A1 (en) * | 2003-06-13 | 2005-01-06 | Praag Henriette Van | Method for increasing cognitive function and neurogenesis |
| WO2007137380A1 (en) * | 2006-05-25 | 2007-12-06 | Aché Laboratórios Farmacêuticos S/A | Pharmaceutical product based on passiflora incarnata l., uses therefor and method to treat anxiety and insomnia |
| WO2008011538A2 (en) * | 2006-07-19 | 2008-01-24 | The Salk Institute For Biological Studies | Methods of using flavonoids to enhance memory |
-
2008
- 2008-04-01 BR BRPI0801239-3A patent/BRPI0801239A2/en not_active Application Discontinuation
-
2009
- 2009-04-01 WO PCT/BR2009/000089 patent/WO2009121155A2/en active Application Filing
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995005169A1 (en) * | 1993-08-17 | 1995-02-23 | The University Of Strathclyde | Flavonoid and biflavonoid derivatives, their pharmaceutical compositions, their anxiolytic activity |
| JPH0873360A (en) * | 1994-09-01 | 1996-03-19 | Yoshihide Hagiwara | Suppressing agent against brain nerve cell injury |
| US6806257B1 (en) * | 1999-10-20 | 2004-10-19 | Board Of Trustees Of Southern Illinois University | Flavones as inducible nitric oxide synthase inhibitors, cyclooxygenase-2 inhibitors and potassium channel activators |
| GB2348371A (en) * | 2000-03-14 | 2000-10-04 | Soares Da Silva Patricio | Compositions comprising L-DOPA renal cell transfer blocking compounds suitable for the treatment of Parkinson's disease |
| WO2002066032A1 (en) * | 2001-02-20 | 2002-08-29 | Randy Ziegler | Treatment of schizophrenia |
| US20050004046A1 (en) * | 2003-06-13 | 2005-01-06 | Praag Henriette Van | Method for increasing cognitive function and neurogenesis |
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| WO2015023142A1 (en) * | 2013-08-14 | 2015-02-19 | 대화제약 주식회사 | Pharmaceutical composition for treating or preventing neuropsychitric disease, containing flavone-6-c-glucose derivatives as active ingredients |
| US20160206640A1 (en) * | 2013-08-14 | 2016-07-21 | Dae Hwa Pharma. Co., Ltd. | Pharmaceutical composition for treating or preventing neuropsychiatric disease, containing flavone-6-c-glucose derivatives as active ingredients |
| CN105848659A (en) * | 2013-08-14 | 2016-08-10 | 大化制药株式会社 | Pharmaceutical composition for treating or preventing neuropsychitric disease, containing flavone-6-c-glucose derivatives as active ingredients |
| US10251902B2 (en) | 2013-08-14 | 2019-04-09 | Dae Hwa Pharma Co., Ltd. | Pharmaceutical composition for treating or preventing neuropsychiatric disease, containing flavone-6-C-glucose derivatives as active ingredients |
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| WO2017046777A1 (en) | 2015-09-19 | 2017-03-23 | Indus Biotech Private Limited | Composition and methods thereof |
| US10493088B2 (en) | 2015-09-19 | 2019-12-03 | Indus Biotech Private Limited | Composition of trigofoenoside and flavonoids and methods thereof |
| US11879115B2 (en) | 2018-11-26 | 2024-01-23 | Roar Holding Llc | Methods to improve beverage quality |
| WO2021225343A1 (en) * | 2020-05-06 | 2021-11-11 | 한국한의학연구원 | Composition for preventing or treating cognitive disorder, comprising iris lactea extract |
| WO2022052016A1 (en) * | 2020-09-11 | 2022-03-17 | Liu Hsuan Miao | Pharmaceutical compositions and uses thereof in treating parkinson's disease |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0801239A2 (en) | 2009-11-17 |
| WO2009121155A3 (en) | 2009-11-26 |
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