US20010000326A1 - Extracts of hypericum perforatum and formulations containing them - Google Patents

Extracts of hypericum perforatum and formulations containing them Download PDF

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US20010000326A1
US20010000326A1 US09725938 US72593800A US2001000326A1 US 20010000326 A1 US20010000326 A1 US 20010000326A1 US 09725938 US09725938 US 09725938 US 72593800 A US72593800 A US 72593800A US 2001000326 A1 US2001000326 A1 US 2001000326A1
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extract
method
alcohol
hypericum perforatum
solution
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US6428820B2 (en )
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Ezio Bombardelli
Bruno Gabetta
Paolo Morazzoni
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Indena SpA
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/38Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78Separation; Purification; Stabilisation; Use of additives

Abstract

The invention relates to a method for extracting Hypericum perforatum (St.-Johns-wort) by fractioning water-alcohol, alcohol, or acetone extracts of the plant with esters of water-immiscible C1-C5 alcohols. The extracts have high activity and are stable over time. The invention also relates to formulations containing the extract.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • 1. The application is a continuation of the U.S. national stage of international application PCT/EP99/03881 filed Jun. 4, 1999, the content of which is expressly incorporated herein by reference thereto.
  • FIELD OF THE INVENTION
  • 2. The present invention relates to a method for preparing an extract of Hypericum perforatum (St. Johns wort) by fractioning water-alcohol, alcohol, or acetone extracts of the plant with esters of water-immiscible C1-C5 alcohols. The invention also relates to formulations containing the extract.
  • BACKGROUND OF THE INVENTION
  • 3. Flowering tops of Hypericum perforatum contain a number of classes of structurally different substances that can act directly or indirectly on the central nervous system. Hypericum perforatum is known to contain active compounds such as hypericin, hyperforin, and dimeric flavones that exert antidepressive and anxiolytic activities on animals and humans. The mechanisms of action of these compounds are different and include for example anti-MAO action, action on serotonin release, and activity on benzodiazepine receptors.
  • 4. The activity of hypericin has been extensively discussed in the literature and includes conflicting reports on the activity of hypericin. The controversial antidepressive activity of hypericin, however, was recently confirmed in pharmacological models in vivo. It has been proven that hypericin is active when administered in the presence of dimeric procyanidins contained in the extracts of Hypericum perforatum (45th Annual Congress of the Society for Medicinal Plant Research, Sep. 7th-12th, 1997, Regensburg, Germany, V. Butterwecke et al., Abstract No. 011).
  • 5. Hyperforin has recently been the subject of numerous studies that have established its role as antidepressant. Studies carried out by the Applicant have proven that hyperforin has serotonin-mimetic activity.
  • 6. Other components of Hypericum perforatum that are considered important are dimeric flavones derived from apigenin which are considered to be natural benzodiazepines, as reported in “Naturally Occurring Benzodiazepines Structure, Distribution and Function”, I. Izquierdo and J. Medicine Eds., 1993, page 33.
  • 7. These components, and particularly hyperforin, are not stable under typical extraction conditions and storage conditions. WO 97/13489 (Schwabe) discloses that the hyperforin content of a water-alcohol extract of St.-John's-wort falls to almost zero after only a few weeks. According to WO 97/13489, in order to obtain stable extracts with a constant hyperforin content it is necessary to perform the extraction, purification and storage in the presence of antioxidants such as vitamin C and the esters thereof, sulfurated amino acids, and the like.
  • 8. EP 0599307 (Schwabe) discloses the removal of hypericin, responsible for undesired photo-sensitizing effects, by means of polyvinylpyrrolidone and other chemicals. The patent describes extracts obtained without using antioxidants and having a hyperforin content of at least 5%.
  • 9. Comparative pharmacological and clinical data between conventional methanolic extracts or extracts prepared according to the monograph of Commission E with the extracts prepared according to EP 0599307 and WO 97113489 are not available. It is recognized, however, that conventional extract of Hypericum perforatum contain large amounts of flavonoids, which are potent radical scavengers and therefore natural stabilizing agents for easy-to-oxidize substances, together with other substances which can significantly contribute to the activity of the extract.
  • SUMMARY OF THE INVENTION
  • 10. The invention relates to a method of preparing stable extracts of Hypericum perforatum. The method includes the steps of extracting flowering tops of Hypericum perforatum with alcohol or acetone solvent to provide a first extract solution; filtering the first extract solution; concentrating the first extract solution to provide a concentrate; diluting the concentrate with a water or a water-alcohol solvent to provide an aqueous solution; extracting the aqueous solution with one or more aliphatic ester solvents to provide an ester extract; filtering the ester extract; and g) evaporating the solvents from the ester extract to provide a stable extract of Hypericum perforatum.
  • 11. The method may further include the step of solubilizing the stable extract of Hypericum perforatum in a solvent comprising an acid in aqueous ethanol to provide an aqueous ethanol solution and evaporating the solvents from the aqueous ethanol solution at a temperature of less than 40° C. The organic acid may be citric acid, malic acid, acetylaspartic acid, phosphoric acid, or a mixture thereof. The aqueous ethanol solution may be 95 percent ethanol.
  • 12. The alcohol or acetone solvent used in step (a) may be one or more of methanol or ethanol or it may be acetone. The ratio of the weight of the flowering tops to the alcohol or acetone solvent in step (a) may be from 1:2 to 1:20.
  • 13. The concentrate in step (d) may be diluted with an equal volume of water or water-alcohol solvent. The concentrate may be diluted with a water-alcohol solvent having an alcohol to water volume ratio of from 1:2 to 1:5. The water-alcohol solution in step (d) may contain one or more of methanol or ethanol
  • 14. The volume ratio of the aqueous solution to the one or more aliphatic ester solvents in step (e) may be from 1:0.5 to 1:2. The aliphatic ester solvent in step (e) maybe ethyl acetate, methyl acetate, butyl acetate, or mixtures thereof. The aliphatic ester solvent may be ethyl acetate.
  • 15. The invention also relates to an extract of Hypericum perforatum obtained by the process of the invention. The extract may have an IC50 for inhibition of serotonin uptake of less than 0.32 μg/ml or an lC50 for inhibition of dopamine uptake of less than 2.72 μg/ml. The hyperforin content of the extract may be from 10 to 50 percent by weight of the extract, the total hypericin content of the extract may be greater than 0.5 percent by weight of the extract, and dimeric flavones content of the extract may be from 1 to 2 percent by weight. In another embodiment the hyperforin content is from 10 to 50 percent by weight of the extract, the total hypericin content is from 0.5 to 1.2 percent by weight of the extract, and dimeric flavones content is from 1 to 2 percent by weight.
  • 16. The invention also relates to pharmaceutical compositions containing the extract of Hypericum perforatum prepared by the process of the invention and a pharmaceutically acceptable excipient or carrier. The pharmaceutical composition may be formulated to be a ready-to-use solution, a soft-gelatin capsule, a hard-gelatin capsule, a tablet, or a controlled-release tablet. When the pharmaceutical composition is formulated to be a ready-to-use solution, a soft-gelatin capsule, a hard-gelatin capsule, or a tablet and the extract of Hypericum perforatum may be present in an amount of from 10 to 100 mg. When the pharmaceutical composition is formulated to be a controlled-release tablet and the extract of Hypericum perforatum may be present in an amount of from 10 to 300 mg.
  • 17. The invention further relates to a method of treating or preventing depression and anxiety in humans and animals by administering to a human or animal a therapeutically effective amount of the extract prepared by the process of the invention.
  • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • 18. It has now been found that stable, highly active extracts of Hypericum perforatum, containing the main compounds responsible for pharmacological activity, in particular hypericin, hyperforin, flavonoids, and xanthones, can be prepared by a process that comprises:
  • 19. a) extracting the flowering tops of Hypericum perforatum with alcohol or acetone;
  • 20. b) filtering the extracts and concentrating the extract;
  • 21. c) diluting the concentrate from step (b) with water or a water/alcohol mixture;
  • 22. d) extracting the aqueous mixture from step (c) with aliphatic esters;
  • 23. e) filtering and evaporating the ester extracts from step (d) to dryness; and, optionally,
  • 24. f) solubilizing the dry residue from (e) in a solution of an organic acid in aqueous ethanol and evaporating the solvent at a temperature below 40° C.
  • 25. Preferably the first extraction (step a) is carried out with methanol or ethanol; a weight/volume ratio for the flowering tops to solvent ranging from 1:2 to 1:20, preferably from 1:2 to 1:10; and a temperatures ranging from room temperature to the reflux temperature of the solvent, preferably between room temperature and 40° C.
  • 26. Aliphatic esters for use in step (d) are preferably ethyl acetate, methyl acetate, and butyl acetate.
  • 27. The extraction (step d) is carried out after treating the concentrated alcohol or acetone extract with an equal volume of water or with alcohol/water mixtures having alcohol:water volume ratios ranging from 1:2 to 1:5. The volume ratio of aqueous mixture to ester is not critical and can range within wide limits, but typically ranges from 1:0.5 to 1:2. The extraction is preferably carried out repeatedly, generally at least three times, using fresh aliquots of solvent.
  • 28. Optional step (f) is effected by dissolving the concentrate from (e) in a solution of an organic acid such as citric, malic, acetylaspartic, or phosphoric acids in 95% ethanol.
  • 29. The resulting extract of the invention, analyzed according to the procedure described in M. Brolis et al., J. of Chromatography, 825, (1998), 9-16, contains hyperforin in amounts ranging from 5 to 20% by weight when using spontaneous vegetable biomasses and in amounts from 10 to 50% by weight when using selected vegetable biomasses. In both cases, the total hypericin content is higher than 0.5% and dimeric flavones are present in amounts from 1 to 2% by weight. The content of hyperforin, hypericin, and dimeric flavones shows wide variability depending on the time at which the plant is collected, the seed content in the flowering tops, and the amount of stems present in the biomass.
  • 30. This extract, compared to the total extract, surprisingly has high activity in various pharmacological models used for evaluating antidepressive and anxiolytic effects and is stable over time without further treatment. The process of the invention provides stable extracts with no need for further processing. The extracts, however, should be shielded from light to avoid photo-degradation.
  • 31. Table I shows the activity of the extract of the invention compared to other extracts and compounds on the inhibition of serotonin (5-HT) and dopamine (DA) uptake.
    TABLE I
    Effect Hypericum perforatum Extract Prepared According to
    Example 1 at Inhibiting 3H 5-HT and DA Uptake.
    IC50 μg/ml
    Substance 3H DA 3H-5 HT
    Alcoholic extract 4.05 ± 0.93 28.0 ± 1.7 
    Hexane extract 0.86 ± 0.02 3.08 ± 0.62
    Example 1 0.32 ± 0.04 2.72 ± 1.1 
    Hyperforin 1.54 ± 0.23 4.75 ± 0.79
    Hypericin >50 >50
    Pseudo-hypericin 1.40 ± 0.13  27.0 ± 1.1020
  • 32. The data in Table I shows that the extract of the invention has a potency several times higher than hyperforin and other known extracts.
  • 33. The extract of the invention showed a higher activity in in vivo tests than known products, such as alcoholic, methanolic, and hexane extracts, with or without hypericin. Moreover, the extract has proved to be more reproducible and to exhibit greater stability over time. The in vivo tests used to verify the antidepressive effect were the escape deficit development test and the inhibition of the ethanol consumption in Sardinia alcohol preferring rats, according to procedure known in literature.
  • 34. In the escape deficit development test, the extract of the invention surprisingly showed a higher activity than known extracts and an activity comparable with that of known medicaments, such as imipramine. In the escape deficit development test rats are fastened and subjected to mild, short, unavoidable electric shocks for 50 min (pre-test). Twenty-four hours later, animals are tested for their ability to avoid the same stimuli on their tails, in a situation in which escape is impossible. On the average a rat makes 26 escapes out of 30 stimuli (naive controls), whereas an animal subjected to pre-test only makes 1-3 escapes (ED controls). Hyporeactivity induced by the pre-test does not take place in rats pre-treated for 1-3 weeks with antidepressants such as imipramine or fluoxetine. The St.-John's-wort extracts orally administered to rats one hour before exposure to the unavoidable stress cause an increase in reactivity to the escape test, which is further enhanced when pre-treatment is effected for 1-2 weeks. Table II summarizes the antidepressive effect of Hypericum perforatum extracts and fractions thereof in rats in the escape test with a 2 week pre-treatment.
    TABLE II
    Antidepressive Effect of Hypericum perforatum Extracts and Fractions
    Thereof in Rats in the Escape Test with a 2 week Pre-treatment.
    Substance Dose (mg/kg) Number of escapes
    Hypericum alcoholic extract 1000  16.6 ± 2.8
    Hexane extract 600 17.2 ± 1.6
    Example 1 200 23.3 ± 0.4
    Example 1 100 18.3 ± 0.2
    Example 1  50 13.3 ± 0.4
    ED Controls  1.6 ± 0.1
    Naive controls 24.1 ± 0.1
    Statistical analysis: Kruskal-Wallis non
    parametric ANOVA
    KW = 13.462 p = 0.0012
    Hypericum alcoholic extract vs naive p < 0.01
    Hypericum extracted as in Example 1, 200 mg/kg n.s.
    vs naive
    Naive vs AND p < 0.01
  • 35. In the test of the reduction of alcohol consumption in Sardinia rats according to procedures known in literature (which is an index of depression and anxiety), the extracts of the invention, after three days administration, induced a 75% decrease in alcohol consumption in favor of water compared with controls, whereas the reduction in alcohol consumption after treatment with methanolic or hexane extracts was 30 and 40%, respectively.
  • 36. The extract of the invention can be included in formulations for oral use, such as ready-to-use solutions, soft- or hard-gelatin capsules, tablets, and controlled-release tablets. The dosage of extract in the formulations range from 10 to 100 mg per dose in the usual formulations and up to 300 mg in the controlled-release formulations, in this case the preferred dose is 300 mg per dose daily.
  • EXAMPLES
  • 37. The examples reported hereinbelow illustrate the preferred embodiments of the present invention in greater detail but should not be construed to limit the invention in any way.
  • Example 1 Preparation of a Dry Extract of Hypericum perforatum Standardized in the Active Components
  • 38. 4 Kg of Hypericum perforatum flowering tops were extracted with 4×15 L of methanol in an extraction apparatus of 25 L capacity. The combined methanol extracts were concentrated under vacuum to 2.5 L, the concentrate diluted with an equal volume of water, and counter-extracted with 3×1.5 L of ethyl acetate. The organic phase was filtered and concentrated to dryness under vacuum and the resulting residue was dissolved in a solution of 2 g of citric acid in 1.3 L of 95% ethanol. The organic phase was then evaporated to dryness under vacuum at a temperature of less than 40°C. to provide 0.32 kg of a brown-yellow extract containing 20% of hyperforin, 0.9% of total hypericins (hypericin plus pseudohypericin), and 1% of diapigenin.
  • Example 2 Preparation of an Extract of Hypericum perforatum Standardized in the Active Components
  • 39. 60 kg of Hypericum perforatum flowering tops were collected and mechanically dried at a temperature less than 60° C. and were extracted under mild reflux with 4×20 L of acetone. The combined extracts were filtered to remove biomass residues and concentrated under vacuum to dryness to provide 3 kg of an extract containing 0.4% of total hypericins and about 25% of hyperforin. The extract was suspended in 10 L of a methanol/water mixture (3:7) and counter-extracted with butyl acetate to completely extract the polyphenols. Extraction of the polyphenols was monitored by thin layer chromatography using a silica gel support and eluting with ethyl acetate/methanol/H2O (100:13.5:10). The aqueous phase was removed, and the organic phase dried (Na2SO4) and concentrated to dryness under vacuum at a temperature of less than 40°C. to provide 1.6 kg of dry extract containing 0.7% of total hypericins, about 40% of hyperforin, and 1.4% of dimeric flavones.
  • Example 3 Preparation of a Multicomponent Extract of Hypericum perforatum, Standardized in the Active Components
  • 40. 60 kg of Hypericum perforatum flowering tops were collected and mechanically dried at a temperature of less than 60° C. and were continuously extracted with 98% methanol until all the extractables were removed. The methanolic extract was then concentrated to 30 L and the concentrate diluted with an equal volume of water. Insolubles that separated during dilution were removed by filtration and the resulting clear solution was extracted with 3×30 L of water-saturated ethyl acetate, dried (Na2SO4), and the solvent removed under vacuum to provide 3.8 kg of a brown extract containing 25% of hyperforin, 1.2% of total hypericin, and 1.2% of dimeric diflavones.
  • Example 4 Solution Containing the Lipophilic Extract of Hypericum perforatum Prepared According to Example 1
  • 41.
    Extract of Hypericum perforatum 10.0 g
    prepared according to Example 1
    Ammonium glycyrrhizinate  0.5 g
    Propylene glycol 35.0 g
    70% Sorbitol solution 25.0 g
    Purified water q.s. to 100 ml
  • Example 5 Coated Tablets Containing the Extract of Hypericum perforatum Prepared According to Example 2
  • 42.
    Extract of Hypericum perforatum 300.00 mg 
    prepared according to Example 2
    Soy polysaccharides 54.75 mg 
    Lactose 46.00 mg 
    Cross-linked sodium 40.00 mg 
    carboxymethyl cellulose
    Silica 20.00 mg 
    Polyvinylpyrrolidone 5.00 mg
    Talc 2.50 mg
    Magnesium stearate 1.75 mg
    Coating:
    Hydroxypropyl methylcellulose 10.00 mg 
    Talc 8.50 mg
    Titanium dioxide 5.00 mg
    Triacetin 2.00 mg
    Polysorbate 80 0.50 mg
    Red iron oxide 1.00 mg
  • Example 6 Soft-gelatin capusles
  • 43.
    Extracts of Hypericum perforatum 100 mg
    of Example 1
    Saccharose monopalmitate 100 mg
    Polyethylene glycol 400 220 mg
    Glycerin  15 mg
    Purified water  15 mg

Claims (20)

    What is claimed is:
  1. 1. A method of preparing stable extracts of Hypericum perforatum comprising:
    extracting flowering tops of Hypericum perforatum with alcohol or acetone solvent to provide a first extract solution;
    filtering the first extract solution;
    concentrating the first extract solution to provide a concentrate;
    diluting the concentrate with a water or a water-alcohol solvent to provide an aqueous solution;
    extracting the aqueous solution with one or more aliphatic ester solvents to provide an ester extract;
    filtering the ester extract; and
    evaporating the solvents from the ester extract to provide a stable extract of Hypericum perforatum.
  2. 2. The method of
    claim 1
    , further comprising solubilizing the stable extract of Hypericum perforatum in a solvent comprising an acid in aqueous ethanol to provide an aqueous ethanol solution and evaporating the solvents from the aqueous ethanol solution.
  3. 3. The method of
    claim 2
    , wherein the organic solvents are evaporated from the aqueous ethanol solution at a temperature of less than 40°C., the organic acid is selected from the group consisting of citric acid, malic acid, acetylaspartic acid, phosphoric acid, and mixtures thereof, and the aqueous ethanol solution is 95 percent ethanol.
  4. 4. The method of
    claim 1
    , wherein the alcohol or acetone solvent is one or more of methanol or ethanol.
  5. 5. The method of
    claim 1
    , wherein the alcohol or acetone solvent is acetone.
  6. 6. The method of
    claim 1
    , wherein the flowering tops are present at a weight relative to the volume of alcohol or acetone solvent to provide a ratio of from 1:2 to 1:20.
  7. 7. The method of
    claim 1
    , wherein the concentrate is diluted with an equal volume of water or water-alcohol solvent.
  8. 8. The method of
    claim 1
    , wherein the concentrate is diluted with a water-alcohol solvent having an alcohol to water volume ratio of from 1:2 to 1:5.
  9. 9. The method of
    claim 1
    , wherein the water-alcohol solution comprises one or more of methanol or ethanol.
  10. 10. The method of
    claim 1
    , wherein the aqueous solution and one or more aliphatic ester solvents are present in a volume ratio from 1:0.5 to 1:2.
  11. 11. The method of
    claim 1
    , wherein the aliphatic ester solvent is selected from the group consisting of ethyl acetate, methyl acetate, butyl acetate, and mixtures thereof.
  12. 12. The method of
    claim 11
    , wherein the aliphatic ester solvent is ethyl acetate.
  13. 13. A stable extract of Hypericum perforatum obtainable by the process of
    claim 1
    .
  14. 14. The extract of
    claim 13
    , wherein the extract has an IC50 for inhibition of serotonin uptake of less than 0.32 μg/ml or an IC50 for inhibition of dopamine uptake of less than 2.72 μg/ml.
  15. 15. The extract of
    claim 13
    , wherein the hyperforin content is from 10 to 50 percent by weight of the extract, the total hypericin content is greater than 0.5 percent by weight of the extract, and the dimeric flavones content is from 1 to 2 percent by weight.
  16. 16. The extract of
    claim 13
    , wherein the hyperforin content is from 10 to 50 percent by weight of the extract, the total hypericin content is from 0.5 to 1.2 percent by weight of the extract, and the dimeric flavones content is from 1 to 2 percent by weight.
  17. 17. A pharmaceutical composition comprising the extract of Hypericum perforatum of
    claim 12
    and a pharmaceutically acceptable excipient or carrier.
  18. 18. The pharmaceutical composition of
    claim 17
    , wherein the composition is formulated to be a ready-to-use solution, a soft-gelatin capsule, a hard-gelatin capsule, or a tablet and the extract of Hypericum perforatum is present in an amount of from 10 to 100 mg.
  19. 19. The pharmaceutical composition of
    claim 17
    , wherein the composition is formulated to be a controlled-release tablet and the extract of Hypericum perforatum is present in an amount of from 10 to 300 mg.
  20. 20. A method of treating or preventing depression and anxiety in humans and animals which comprises administering to a human or animal a therapeutically effective amount of the extract of
    claim 1
    .
US09725938 1998-06-10 2000-11-30 Extracts of Hypericum perforatum and formulations containing them Expired - Fee Related US6428820B2 (en)

Priority Applications (3)

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ITMI98A001311 1998-06-10
IT1301678B1 IT1301678B1 (en) 1998-06-10 1998-06-10 Extracts of Hypericum perforatum and formulations containing them.
PCT/EP1999/003881 WO1999064027A1 (en) 1998-06-10 1999-06-04 Extracts of hypericum perforatum and formulations containing them

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050208156A1 (en) * 2002-03-26 2005-09-22 Lichtwer Pharma Gmbh Plants extracts and the use thereof
US20060115555A1 (en) * 2004-12-01 2006-06-01 Foulger Sidney W Nutritional supplements containing xanthone extracts
US20060115556A1 (en) * 2004-12-01 2006-06-01 Foulger Sidney W Nutritional supplement drink containing xanthone extracts
US20060127349A1 (en) * 2000-05-23 2006-06-15 Andreas Kubin Novel of preparation hypericin bonded with poly-n-vinylamides

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ES2159270B1 (en) 2000-03-06 2002-04-01 Asac Compania De Biotecnologia Hypericum perforatum L oleoresin., Procedure obtention and uses.
FR2908997B1 (en) * 2005-11-25 2014-03-14 R Et D Pharma New therapeutic compositions and the method of producing the active ingredients
FR2908996A1 (en) * 2005-11-25 2008-05-30 R & D Pharma New method of extracting the active ingredients and the use thereof in therapeutics
US20080267899A1 (en) * 2007-04-30 2008-10-30 Mr. Hamit Leskaj Plant extract composition for hair growth
US7974647B2 (en) * 2008-05-16 2011-07-05 Mediatek Inc. Mobile apparatus and method of timing synchronization
RU2541134C2 (en) * 2012-12-06 2015-02-10 Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Профессионального Образования "Дагестанский Государственный Технический Университет" (Дгту) Method for preparing dry herbal extract of st. john's wort

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Publication number Priority date Publication date Assignee Title
DE4239959A1 (en) * 1992-11-27 1994-06-01 Schwabe Willmar Gmbh & Co St. John's wort dry extract, process for its preparation and its use
DE19646977A1 (en) * 1995-09-29 1998-01-15 Schwabe Willmar Gmbh & Co Stable dry extract of Hypericum perforatum L., Saint John's wort
DE19818001C1 (en) * 1998-04-22 1999-08-05 Plantamed Arzneimittel Gmbh Preparing extract fractions of Hypericum perforatum, for treatment of depression

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060127349A1 (en) * 2000-05-23 2006-06-15 Andreas Kubin Novel of preparation hypericin bonded with poly-n-vinylamides
US7390510B2 (en) * 2000-05-23 2008-06-24 Sanochemia Pharmazeutika Ag Preparation of hypericin bonded with poly-N-vinylamides
US20050208156A1 (en) * 2002-03-26 2005-09-22 Lichtwer Pharma Gmbh Plants extracts and the use thereof
US20060115555A1 (en) * 2004-12-01 2006-06-01 Foulger Sidney W Nutritional supplements containing xanthone extracts
US20060115556A1 (en) * 2004-12-01 2006-06-01 Foulger Sidney W Nutritional supplement drink containing xanthone extracts

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CA2334625A1 (en) 1999-12-16 application
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CN1304314A (en) 2001-07-18 application
WO1999064027A1 (en) 1999-12-16 application

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