EP1183039A1 - Preparations pharmaceutiques de substances bioactives extraites de sources naturelles - Google Patents

Preparations pharmaceutiques de substances bioactives extraites de sources naturelles

Info

Publication number
EP1183039A1
EP1183039A1 EP00944604A EP00944604A EP1183039A1 EP 1183039 A1 EP1183039 A1 EP 1183039A1 EP 00944604 A EP00944604 A EP 00944604A EP 00944604 A EP00944604 A EP 00944604A EP 1183039 A1 EP1183039 A1 EP 1183039A1
Authority
EP
European Patent Office
Prior art keywords
species
extraction
formula
extracted
bioactive substance
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00944604A
Other languages
German (de)
English (en)
Inventor
Michael Z. Martin
Mehdi Ashraf-Khorassani
Larry Taylor
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Armadillo Pharmaceuticals Inc
Original Assignee
Armadillo Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Armadillo Pharmaceuticals Inc filed Critical Armadillo Pharmaceuticals Inc
Publication of EP1183039A1 publication Critical patent/EP1183039A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • 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)
    • 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)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • 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)
    • A61K36/32—Burseraceae (Frankincense family)
    • 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)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • 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)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/734—Crataegus (hawthorn)
    • 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)
    • A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • This invention relates to methods of extracting and purifying bioactive substances from various plants and herbs More specifically the invention relates to methods of extracting and separating bioactive substances from various plants and herbs using supercritical fluid extraction and/or fluorocarbon solvent extract The present invention further relates to separation of bioactive substances contained in extracts using packed column supercritical fluid chromatography The present invention also relates to formulations, pharmaceutical preparations and dietary supplements which may be prepared with the extracted bioactive substances and use of such pharmaceutical preparations and dietary supplements to treat various human ailments 2. Description of the Background
  • Kava Root K Schubel J Soc Chem Ind , 43, 766 (1924)
  • Kava root consists of the dried rootstock and/or shoots of Piper methysticum Forst (Family Piperaceae)
  • the Kava root is most typically ingested by drinking an aqueous macerate (pulverized Kava root mixed with water) known as the beverage Kava
  • kavalactones also known as kavapyrones
  • kavapyrones More than ten kavalactones as well as four other substances have been identified in the Kava root to date, including kavain, dihydrokavain (a k.a marindinin), methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin V.
  • kavalactones in a Kava root extract vary depending upon its origin Different species of kavalactones have been found to have varying physiological effects in vivo depending on their molecular structure All naturally occurring kavalactones contain an enolic double bond between C3 and C4
  • the dienolides of the yangonin type appear to be pharmacologically inert In the enolides, the effective optimum varies as a function of the hydrogenation of the double-bonded C7
  • kavain has the strongest effect as a local anesthetic, dihydromethysticin as a spasmolytic, and dihydrokavain as an intensifier of narcosis R Hansel, Characterization and Physiological Activity of Some Kava Constituents Pacific Science, July 1968, Vol XXII pp293-313
  • the particular kavalactones present depend upon whether, in addition to rhizome parts, roots and stems of the plant are included in the extract High quality extracts of the Kava root are sold based upon the total kavalactone content, rather than upon analysis of the individual lactones contained therein
  • concentration ranges of total kavalactone levels in the Kava root extracts employed, e g in Germany are generally within the range of 30 to 55 weight percent
  • Extracts of Crataegus and Aesculus species are commonly prepared using various solvents, such as methanol, ethanol or acetone
  • the extracts are taken from the leaves and flowers of Cratageus species and from the seeds, leaves and bark of the Aesculus species
  • the plant Simmondsia chinensis also known as Jojoba
  • Jojoba is native to the desert areas of the Southeastern United States and Mexico
  • Jojoba has a unique wax ester oil which is 50 to 60% of its seed weight This oil is currently used in cosmetics and lubricants The remainder of the seed is not used as much as the oil although it contains about 25% crude protein after the oil is removed
  • the defatted meal contains sugars and 11 to 15% of a unique group of natural products Simmondsin, one of the natural products contained in Jojoba meal, has been shown to be an effective hunger satiation agent by reducing food intake in mice, rats, and chickens Cokeleare et al (1995, Ind Crops Prod , 4 91-96)
  • Pfaffia paniculata commonly called Brazilian ginseng
  • Extracts of the plant have been shown to contain allantoin, daucosterol, b-ecdysone, pfaffic acid, pfaffosides A, B, C, D, E, and F, polypodine B, ⁇ -sitosterol, stigmasterol, and stigmasterol-3-O- ⁇ -D-glucoside
  • Turnera diffusa and other Turnera species commonly called damiana, hierba del venado, and other names, are small, herbaceous perennials ranging from California to South America
  • the plant has been used since pre-Columbian times as an aphrodisiac and sexual tonic, expectorant, diuretic, antidiabetic, to increase fertility, treat spermatorrhea, orchitis, nephritis, chronic coughing, and as a stimulant, digestive aid, and laxative Laboratory tests of various Turnera preparations have shown cytotoxic and antihyperglycemic effects
  • the plant extract has been found to be non-mutagenic Turnera species are known to contain arbutin, caffeine, gonzalitosin, ⁇ -sitosterol, an acetovanillin-like benzenoid compound, hexacosan-1-ol, tetraphyllin B, N-triacontane, tricosan-2-one, an essential
  • Perezia produces perezone (2-(l,5-dimethyl-4-hexenyl)-3-hydroxymethyl-p-benzoquinone)
  • Perezone is a sesquiterpenic benzoquinone which exhibits oxido-reduction characteristics
  • Certain species ofthe perezia genus have been used as laxatives in Mexican folk medicine
  • perezone inhibits mitochondrial electron transport in rat liver mitochondria differently than rotenone, amytal, and Antimycin A Carabez A et al , The Action ofthe Sesquiterpenic Benzoquinone, Perezone, on Electron Transport in Biological Membranes Arch Biochem Biophys 1988 Jan, 260(1) 293-300 The low respiration of rat liver mitochondria depleted of coenzyme Ql 0 (CoQ) was shown to be increased by perezone
  • Heimia salicifolia was used as a traditional medicine in the Americas to treat inflammation
  • two alkaloids from Heimia salicifolia, cryogenine and nesodine were discovered to be more than twice as potent as aspirin as inhibitors of prostoglandin synthetase prepared from bovine seminal vesicles
  • An extraction method which removes high concentrations of multiple bioactive substances is desirable
  • a separation method which permits efficient separation of the substances to obtain purified, therapeutically effective quantities of bioactive substances is also desired. Such methods would provide new extracts from known plant species, the ability to isolate useful quantities of specific bioactive substances, new uses of extracts from known plant species, and more efficient extraction
  • Supercritical fluid extraction and supercritical fluid chromatography have been used in the chemical arts for many years Gases such as carbon dioxide or propane have proven to have excellent solvating properties when pressurized, particularly above their critical point This so-called supercritical region occurs when a gas is pressurized to a point where it would normally liquify, but is simultaneously heated above its now greatly reduced boiling point to prevent liquification
  • This "supercritical fluid” is neither a liquid nor a gas, but exhibits properties of both
  • supercritical fluids possess excellent solvating properties with high selectivity for particular analytes This selectivity can be further adjusted by variations of pressure, temperature and use of mixed gases
  • one embodiment ofthe invention is directed to methods for the preparative and/or commercial scale extraction of bioactive substances comprising the step of using supercritical fluid extraction (SFE) or near-critical extraction (NCE) for said preparative and/or commercial-scale extraction
  • SFE supercritical fluid extraction
  • NCE near-critical extraction
  • the SFE or NCE may be accomplished with CO 2 or CO 2 modified with various other volatile substances
  • the SFE or NCE may further be accomplished as a batch-wise extraction, continuous- cascading extraction, or count ercurrent- solvent extraction
  • Another embodiment is directed to methods for the preparative and/or commercial scale processing of bioactive substances comprising coupling SFE or NCE and supercritical fluid chromatography (SFC), with or without modifiers, for said preparative and/or commercial scale processing
  • SFC supercritical fluid chromatography
  • isopropyl amine may be used as a modifier in SFC
  • Another embodiment of the invention is directed to methods for the preparative and/or commercial scale extraction of bioactive substances comprising the step of using dense gases in the supercritical, near critical, or subcritical state with or without modifiers, for said preparative and/or commercial scale extraction
  • the dense gas may be any non-chlorinated fluorocarbon solvent and the modifiers may be any other volatile substance
  • the extraction may be performed under a pressure of 0-10 bar, or under supercritical or near critical fluid conditions
  • Dense gas extraction may further be accomplished as a batch-wise extraction, continuous-cascading extraction or countercurrent-solvent extraction
  • Another embodiment of the invention is directed to methods for the separation of bioactive substances comprising the step of SFC
  • the step of using SFC preferably comprises the use of HH 2 and/or C4 columns, singly or in combination, in the SFC separation
  • Another embodiment ofthe invention is directed to compositions comprising medicinal formulations of extracts of Byrsonima species recovered with supercritical fluid extraction and/or dense gases or with various organic solvents and/or water, and to methods of administering therapeutically effective amounts of these formulations to patents in need of treatment.
  • compositions may comprise extracts or isolated products of Aesculus californica and Crataegus mexicana, either on their own, in combination with one another, or in combination with extracts from various Bursera species
  • Another embodiment ofthe invention is directed to extraction of simmondsin compounds from Jojoba (Simmondsia chinensis) and use of these compounds as a human weight loss agent.
  • Another embodiment ofthe invention is directed to formula and compositions comprising a combination of extracted phytochemicals from Turnera species and Pfaffia species, with or without muira puama (a crude drug derived from various species including Ptychopetalum olacoides, Liriosma ovata, and Chaunochiton kappleri) for use as a health tonic and to support sexual function
  • muira puama a crude drug derived from various species including Ptychopetalum olacoides, Liriosma ovata, and Chaunochiton kappleri
  • Another embodiment ofthe invention is directed to formula and compositions comprising a combination of extracted phytochemicals from, for example, Heimia salicifolia, for use as a Non-steroidal Anti-inflammatory Drug (NSAID).
  • NSAID Non-steroidal Anti-inflammatory Drug
  • Figures 15-17 Results of experiments wherein kavalactone extracts were subjects to SFC using NH2, DIOL, and CN columns
  • Figure 18 Results of an experiment wherein kavalactone SFE extracts were separated with SFC at a higher temperature (80°C) using the CN column All other chromatography conditions were the same as described for CN above
  • Figure 24 Chemical structure of seven identified kavalactones
  • Figure 25 SFC separation of kavalactone extract Column NH 2 (250 x 4 6 mm 5 ⁇ m dp) Pressure 125 atm, 60°C, 2 mL/min Modifier program 98/2% CO 2 /MeOH for 3 min and then increased to 90/10 CO 2 /MeOH at rate of 9 4%/min
  • Figure 26 SFC separation of kavalactone extract Column NH 2 (250 x 4 6 mm, 5 ⁇ m dp) Pressure 125 atm, 80°C, 2 mL/min Modifier program 98/2% CO 2 MeOH hold for 3 mm and then increased to 90/10 CO 2 /MeOH at rate of 0 4%/min
  • Figure 27 SFC separation of kavalactone extract Column NH 2 (250 x 4 6 mm, 5 ⁇ m dp) Pressure 125 atm, 60°C, 2 mL/min Modifier program 93/7% CO 2 /MeOH for 3
  • Carbon dioxide is a commonly used volatile substance for supercritical fluid extractions At temperatures of 39 °C and above (its critical temperature) and at pressures between 200 and 600 bar, CO 2 is capable of removing caffeine from coffee and tea, some fragrances and flavor oils from certain plants and spices (U S Pat Nos 5,512,285 and 5,120,558), and some pharmacological active principles from certain plants and herbs Depending on the temperature and pressure used, whether the temperature and pressure are varied during extraction, and the extraction method, different substances can be selectively removed or isolated from a plant species using supercritical fluid extraction
  • CO 2 supercritical fluid extraction is used to extract bioactive substances from various natural sources including, but not limited to Piper methysticum, Byrsonima species, Aesculus californica, Crataegus mexicana, Simmondsia chinensis, Pfaffia species, Bursera species, Turnera species, and Heimia salicifolia, Psidium species, Enterlobium species, Ptychopeta
  • Supercritical fluid extraction can be applied to a quantity of the root, leaf, bark, or any other part of a plant or herb, or combinations thereof, containing bioactive substances Generally the specific part or parts are ground to form a powder or paste
  • the powder or paste may be extracted with CO 2 at one or more temperatures, preferably a minimum of 45 °C, and at least two pressures, preferably a minimum pressure between 200 and 400 bar and a maximum pressure between 400 and 600 bar
  • Use of more than one pressure, and more than one temperature, during extraction permits extraction of various bioactive substances which may be soluble in the CO 2 at specific pressure and temperature levels
  • the extraction may be performed with a mixture of CO 2 and at least one other volatile substance such as butane, propane, ethanol, hexane, or any other appropriate volatile substance known to those of skill in the art
  • the gases may be used at any optimum ratio relative to one another
  • the extraction is performed with a combination of CO 2 and ethanol in a ratio of 17 3
  • the plant or herb may be crushed, macerated, or mixed with a solvent and the solvated mixture may then be extracted with supercritical fluid CO 2 See for example U S Pat No 4,985,265 Under the heavy pressures of supercritical fluid extraction, the CO 2 -cosolvent mixture remains in the liquid monophase state This type of liquid-liquid extraction improves elution of certain analytes
  • solvents appropriate for solvating various bioactive substances in natural sources may be used including, but not limited to, alcohols, weak acids, ketones, chloro derivatives, hydrocarbons, fluorinated hydrocarbons, acetates, ethers, or combinations thereof.
  • the extraction of the present invention is carried out for a minimum of 5 minutes, preferably at least 30 minutes and more preferably 60 minutes, during which extracted analytes are collected in a collection receptacle, preferably a solid phase trap packed with C 18
  • the trap may be rinsed with a solvent appropriate for solvating the bioactive substances that have been extracted, such as, for example, 50/50 ethanol/methylene chloride for kavalactones, to collect most of the analytes in the trap
  • a solvent appropriate for solvating the bioactive substances that have been extracted such as, for example, 50/50 ethanol/methylene chloride for kavalactones
  • Similar methods ofthe present invention are outlined in Example 1 and Example 2 below wherein seven different kavalactones were extracted from a Kava root
  • the methods of the present invention can be used to extract bioactive substances from one natural source at a time, or from multiple natural sources in one extraction
  • a supercritical fluid extraction ofthe present invention can be performed as a batch extraction, as a continuous cascading extraction, as a countercurrent solvent extraction, or a combination thereof
  • the majority of supercritical fluid extractions in the field of natural products has involved configurations of equipment which are batch loaded systems
  • extraction vessels are loaded with raw material, sealed, and the pressure and temperature increased to the desired supercritical processing range After extraction is completed, the pressure and temperature are decreased, the vessel opened, and the spent natural source removed before the process can be repeated
  • this process has not proven to be economically viable except in instances where it is performed at sufficiently large scale (e g the decaffeination of coffee) or the target compound is of sufficiently high value
  • a continuous cascading extraction multiple extraction vessels are sequentially entered on-line in a continuous manner, with the supercritical fluid passing from vessel to vessel, collecting specific targeted compounds in each vessel See U S Pat o 5,120,558, see also Stahle, et al , Dense Gases for Extraction and Refining, Springer- Verlag, Berlin,
  • CO 2 Due to it's non-flammable nature, as opposed to propane or butane, and excellent solvating properties for a wide range of target analytes, CO 2 has become the most common volatile substance used in the art of supercritical fluid extraction
  • CO 2 is effective as an extraction medium only at extreme pressures This results in a high cost of equipment to perform the extraction and to inherent dangers associated with extreme pressure vessels
  • the cost of scaling up such equipment is prohibitive so the equipment tends to remain small scale
  • supercritical CO 2 extraction systems operate at temperatures in excess of 39 ° C Holding labile natural materials at such temperatures for long periods during processing may result in thermally or enzymatically induced spoilage
  • non-chlorinated fluorocarbon solvents including, but not limited to, trifluoromethane, difluoromethane, fluoromethane, pentafluoroethane, 1 , 1 , 1 ,-trifluoroethane, 1 , 1 -difluoroethane,
  • 1,1,1,2-tetrafluoroethane may be used
  • the solvent used in the present invention may be a mixture of these solvents to tailor the boiling point ofthe mixture to a particular process and facilitate the selective elution of specific bioactive substances
  • the solvent may be further modified by mixing with another volatile substance such as butane, hexane, ethanol or any other appropriate substance
  • the non-fluorocarbon solvent used for extraction is a tetrafluoroethane, preferably 1,1,1 ,2-tetrafluoroethane
  • the tetrafluoroethane is unmodified
  • ground or crushed natural sources such as plants and/or herbs are contacted with a non-chlorinated fluorocarbon solvent in the liquid phase so as to charge the solvent with analyte Charged solvent is collected and removed to isolate the analyte
  • the herb or plant material is contacted with a non-chlorinated fluor
  • the extraction may be carried out as a supercritical fluid extraction at increased pressures and varied temperatures
  • increased pressures and temperatures may be used to properly elute desired analytes
  • the plant or herb may be crushed, macerated, or mixed with a solvent and the solvated mixture may then be extracted with fluoronated hydrocarbon solvents or modified fluoronated hydrocarbon solvents
  • fluoronated hydrocarbon solvents or modified fluoronated hydrocarbon solvents This type of liquid-liquid extraction may improve elution of certain analytes
  • solvents appropriate for solvating various bioactive substances in natural sources may be used including, but not limited to, alcohols, weak acids, ketones, chloro derivatives, hydrocarbons, fluorinated hydrocarbons, acetates, ethers, or a combination thereof Extraction may be carried out batch-wise, as a continuous-cascading extraction, or as a countercurrent-solvent extraction.
  • bioactive substances are extracted from plants and/or herbs using fluorocarbon solvents in a continuous cascading extraction.
  • the extractor may communicate with an evaporator.
  • the solvent may be allowed to pass intermittently from the reactor to the evaporator to maintain a level of liquid and a gas-filled head space in the evaporator.
  • Evaporation ofthe solvent may be achieved by withdrawal of gaseous solvent from the head space ofthe evaporator.
  • the withdrawn gaseous solvent may be transferred to a compressor or some similar device to reliquify the solvent, thereby economically reusing the solvent.
  • the evaporator may have one or more sources of heat to control the temperature of the evaporator during evaporation of the solvent.
  • the heat source may be thermostatically controlled to provide constant evaporation temperature.
  • the non-chlorinated fluorinated hydrocarbon solvents generally boil off before the desired analytes and it is therefore not necessary to elevate the temperature of distillation of the solution during the solvent recovery phase of the process. Extracts produced in this manner contain very low levels of solvent residues.
  • the vapor pressure of most fluorocarbon solvents is greater than atmospheric pressure at room temperature. For example, the vapor pressure of 1,1,1,2-tetrafluoroethane is 5.6 bar at 20oC.
  • extraction is thus carried out at a pressure from 0-10 bar and preferably 3.5-6.0 bar.
  • this equipment is a fraction ofthe cost of equivalent equipment required for handling supercritical CO 2 , and a fraction of the degree of sophistication or hazard inherent in a manufacturing plant for handling liquefied hydrocarbon gases under pressure. 3.
  • packed column supercritical fluid chromatography is used to separate the bioactive substances in extracts obtained from various natural sources
  • Bioactive substances that can be separated from such sources include terpenes, terpenoids, flavones and flavonoids, steroids, sterols, saponins and sapogenins, alkanes, alkaloids, amines, amino acids, aldehydes, alcohols, fatty acids, lipids, lignans, phenols, pyrones, butenolides, lactones, chalcones, ketones, benzenes, cyclohexanes, glucosides, glycosides, cyanidins, furans, phorbols, quinones and phloroglucinols
  • the invention can also be applied to the recovery of bioactive substances that are large molecular weight materials such as proteins, peptides, enzymes, polysaccharides and carbohydrates
  • Sources from which bioactive substances can be isolated include, but are not limited to various plant
  • compounds can be recovered from such biological sources as algae, bacteria, fungi, lichens, mosses, and marine organisms such as corals, sponges, tunicates or other invertebrate or vertebrate organisms.
  • extracts of Byrsonima species such as Byrsonima crassifolia, comprising a variety of triterpenes, amino acids, and/or flavonoids are prepared
  • These extracts may be prepared using water, non-aqueous solvents such as methanol, ethanol, or ethyl acetate, a mix of water with a non-aqueous solvent, or using one of the extraction methods described above
  • the extracts of Byrsonima may be administered to humans in therapeutic quantities to treat a variety of ailments including, but not limited to, gastrointestinal disorders (e g diarrhea, Chron's disease, irritable bowel syndrom), and neurological and vascular disorders such as stroke, Parkinson's disease, and Alzheimer's disease
  • the extracts of Byrsonima may further be combined with extracts from other plant species including, but not limited to, Psidium species such as Psidium Guajava, and Enterolobium species such as Enterolobium cyclocarpum
  • the extracts of these other species may
  • extracts of Aesculus species such as Aesculus californica comprising aescin and a variety oftriterpene glycosides
  • Crataegus species such as Crataegus mexicana comprising a variety of flavonoids and oligomeric procyanidins
  • These extracts may be prepared using water, non-aqueous solvents such as methanol, ethanol, or ethyl acetate, a mix of water with a non-aqueous solvent, or using one of the extraction methods described above
  • the extracts of Aesculus californica and Crataegus mexicana may be administered to humans, either each on their own or in combination, in therapeutic quantities to treat a variety of ailments including, but not limited to, cardiac and vascular disorders
  • These extracts may also be given as a dietary supplement to provide a cardio and vascular protective effect, particularly in case of cardiac ischeimia and life-threatening reperfusion-induced cardiovascular lesions See U S Pat No 5,925
  • the extracts of the Aesculus californica and Crataegus mexicana species and/or any other extracts to be mixed with either or both of the Aesculus and Crataegus extracts may be separated to isolate specific bioactive substances to treat specific ailments
  • hydroquinone may be isolated from the extracts of Aesculus californica The separation may be performed using any separation technique known to those of skill in the art, or a packed column supercritical fluid chromatography separation method as described herein
  • the hydroquinone acid may be administered by itself, or in combination with other bioactive substances from Aesculus californica, Crataegus mexicana, or other plant extracts, in therapeutic quantities to treat cardiac and vascular disorders
  • extracts ofthe Aesculus and Crataegus species alone or in combination with extracts from other plant or herb species, or isolated bioactive substances ofthe Aesculus and Crataegus species alone or in combination with bioactive substance of other plants or herbs may be made into a capsule, pill, pastille, or elixir, in combination with other inert or pharmacological ingredients to be administered to patients iii) Extracts of Jojoba
  • extracts of Simmondsia chinensis also known as S californica and Jojoba
  • extracts of defatted Jojoba meal comprising simmondsin
  • water, non-aqueous solvents such as methanol, ethanol, or ethyl acetate, a mix of water with a non-aqueous solvent, water and non-aqueous solvents in sequence, or using one ofthe extraction methods described above
  • the extracts of Simmondsia may be administered to humans in therapeutic quantities as hunger satiation and weight reduction agents
  • Extracts of Simmondsia may further be combined with extracts from other plant species
  • the extracts ofthe other species may be prepared by any method known in the art or any of the methods described above
  • simmondsin is separated from other substances in the Simmondsia extract The separation may be performed using any separation technique known to those of skill in the art, or a packed column supercritical fluid chromatography separation method as described herein
  • simmondsin may be administered by itself, or in combination with other bioactive substances from Simmondsia or other plant extracts, in therapeutic quantities as a hunger satiation or weight reduction agent
  • Therapeutically effective amount to satiate hunger are between 5 and 500 mg/kg body weight, preferably between 10 and 250 mg/kg body weight, more preferably between 20 and 100 mg/kg body weight and even more preferably between 25 and 50 mg/kg body weight
  • extracts of Turnera species such as Turnera diffusa
  • Pfaffia species such as Pfaffia paniculata
  • these extracts may be prepared using water, non-aqueous solvents such as methanol, ethanol, or ethyl acetate, a mix of water with a non-aqueous solvent, or using one of the extraction methods described above.
  • the extracts of Turnera species and Pfaffia species may be administered to humans, either each alone or in combination with one another, in therapeutic quantities to treat a variety of ailments including, but not limited to, diabetes, rheumatism, ulcers, various cancers such as leukemia, chronic coughing, nephritis, orchitis, and spermatorrhea. These extracts may also be administered as a dietary supplement or health tonic to increase sexual drive, aid digestion, and increase fertility.
  • Extracts of Turnera and Pfaffia species may further be combined with extracts from other plant species including, but not limited to muira puama (a crude drug derived from various species including Ptychopetalum olacoides, Liriosma ovata and
  • the extracts of these other species may be prepared by any method known in the art or any ofthe methods described above.
  • the extracts of the Turnera and Pfaffia species and/or any other extracts to be mixed with the Turnera and/or Pfaffia extracts may be separated to isolate specific bioactive substances to treat specific ailments.
  • ⁇ -sitosterol may be isolated from the extracts of Turnera diffusa and/or Pfaffia paniculata. The separation may be performed using any separation technique known to those of skill in the art, or s packed column supercritical fluid chromatography separation method as described herein.
  • the ⁇ -sitosterol may be administered by itself, or in combination with other bioactive substances from Turnera, Pfaffia, or other plant extracts, in therapeutic quantities as a health tonic to support either or both, male and/or female sexual function
  • extracts ofthe Turnera and Pfaffia species alone or in combination with extracts from other plant or herb species, or isolated bioactive substances of the Turnera and Pfaffia species alone or in combination with bioactive substance of other plants or herbs may be made into a capsule, pill, pastille, or elixir, in combination with other inert or pharmacological ingredients to be administered to patients v) Extracts of Heimia Species
  • extracts of Heimia species such as Heimia solicifolia, comprising a variety of alkaloids and quinones are prepared
  • These extracts may be prepared using water, non-aqueous solvents such as methanol and ethanol, a mix of water with a non-aqueous solvent, or using one of the extraction methods described above
  • the extracts of Heimia species may be administered to humans, either each alone or in combination, in therapeutic quantities to treat a variety of ailments including, but not limited to, joint and muscle inflammation
  • extracts of Heimia species may be administered to humans, either each alone
  • Extracts of Heimia species may further be combined with extracts from other plant species
  • the extracts of these other species may be prepared by any method known in the art or any ofthe methods described above
  • the extracts of a Heimia species and/or any other extracts to be mixed with other Heimia extracts may be separated to isolate specific bioactive substances to treat specific ailments
  • the alkaloids cryogenine and nesodine may be isolated from Heimia salicifolia
  • the separation may be performed using any separation technique known to those of skill in the art, or the packed column supercritical fluid chromatography separation method described herein
  • cryogenine and nesodine may be administered by themselves, in combination, or in combination with other bioactive substances from Heimia salicifolia, or other plant extracts, in therapeutic quantities to treat inflammation of joints, muscles, or other tissue
  • extracts of the Heimia species alone or combined with extracts from other plant or herb species, or isolated bioactive substances ofthe Heimia species also alone or combined with bioactive substance of other plants or herbs may be made into a capsule, pill, pastille, or elixir, in combination with other inert or pharmacological ingredients to be administered to patients
  • Kavalactone Standards Because no pure kavalactone standards were available, the SFE extracts were compared with Kava root extracts obtained by conventional sonication methods For this purpose 0 5 gram of Kava root was sonicated for 30 minutes in 25 mL of 50/50 CH 2 C 12 /MeOH as an extraction solvent The extract was then filtered through a 2 ⁇ m filter paper The extract was then analyzed with a
  • Figure 1 shows the Gas Chromatograph/Mass Spectroscopy (GC MS) separation of kavalactones extracted using SFE
  • Figures 2-8 show mass spectra of each kavalactone listed in Table 2
  • Table 3 shows retention times and four most intense ions for the mass spectra of other peaks that eluted earlier than the major kavalactones
  • Figures 15-17 show results of experiments wherein kavalactone extracts were subjected to SFC using NH 2 , DIOL, and CN columns
  • the chromatography conditions for the NH 2 column was Column Material NH 2 with water, Brand Name Altec Sphenosorb, Length 25cm, Inner Diameter 4 6mm ID, Pressure 125 atm,
  • the modifier programming started with 2/98% MeOH/CO 2 hold for 3 min , and then increased to 10/90%) MeOH/CO 2 at a rate of 0 4% min
  • the chromatography conditions for the DIOL column was Column Material DIOL, Brand Name Vydac Model Supleco, Length 25cm, Inner Diameter 4 6mm ID, Pressure 125 atm,
  • Modifier programming started with 2/98% MeOH/CO 2 hold for 3 min , and then increased to 10/90% MeOH/CO 2 at a rate of 0 4% min
  • the chromatography conditions for the Cyano (CN) column was Column Material CN, Brand Name Altec,
  • Rate 2 mL/min liquid CO 2 Modifier programming started with 2/98% MeOH/CO 2 at a rate of 0 4% min
  • Figure 18 shows the results of an experiment wherein kavalactone SFE extracts were separated with SFC at a higher temperature (80°C) using the CN column All other chromatography conditions were the same as described for CN above
  • the 7 peaks which were obtained using the NH 2 column are the kavalactones that were identified using the supercritical fluid extraction of Kava root and GC/MS
  • the area percentage of each peak in the chromatogram was as follows 3, 9 5, 50, 6 9, 5 8, 4 0 and 20%
  • Table 5 lists the columns and the corresponding vendors that were used in this study.
  • Seven kavalactones were identified in the supercritical extract using GC/MS (Hewlett Packard 5890 gas chromatography equipped with 5971 A mass selective detector, and 7673 autosampler, Wilmington, DE) All GC separations were obtained on a 30 m x 0.25 mm i.d.
  • Figure 25 shows the separation of kavalactone extract using an Alltech Sperisorb NH2 column Separation was obtained isobarically at 125 atm and 60°C using a gradient of methanol-modified CO 2
  • the initial methanol concentration in CO 2 was 2% which was held constant for 3 minutes, and then MeOH was increased to 10% at a rate of 0 4%/minute
  • a separation of all kavalactones was obtained
  • the sixth peak eluted as a shoulder in front ofthe last major peak
  • both lower and higher temperatures were tested
  • Lowering the column temperature to 40°C caused co-elution of several peaks
  • Increasing the pressure to 275 atm from 125 atm caused the kavalactones to elute as only four peaks It appeared that peaks 1 and 2, peaks 4 and 5, and
  • Figure 31 shows the SFC separation of kavalactones using an Altima CN column from Alltech at 125 atm, 60°C, and modifier programming starting with 98/2% CO 2 /MeOH hold for 3 minutes and then increased to 90/10% CO 2 /MeOH at a rate of 04%/min

Abstract

La présente invention concerne des procédés d'extraction et de purification de substances bioactives à partir de plantes et d'herbes variées. Plus spécifiquement, cette invention concerne des procédés d'extraction et de séparation de substances bioactives à partir de plantes et d'herbes variées, telles que les racines de Kava, l'espèce Byrsonima, Aesculus californica, Crataegus mexicana, Simmondsia chinensis, l'espèce Pfaffia, Alternanthera repens, l'espèce Bursera, l'espèce Turnera, l'espèce Perezia, Heimia salicifolia, l'espèce Psidium, l'espèce Enterlobium, Ptychopetalum olacoides, Liriosma ovata, et Chaunochiton kappleri, en utilisant l'extraction avec fluide supercritique et/ou un extrait de solvant fluorocarboné. En outre, cette invention concerne la séparation de substances bioactives contenues dans les extraits en utilisant la chromatographie à fluide supercritique sur colonne garnie, ou HPLC, où le gaz dense avec ou sans modificateurs représente la phase mobile. En outre, cette invention concerne des préparations pharmaceutiques et des suppléments alimentaires pouvant être préparés avec ces substances bioactives extraites, et concerne enfin l'utilisation de ces préparations pharmaceutiques et suppléments alimentaires pour traiter des aliments humains variés.
EP00944604A 1999-05-27 2000-05-25 Preparations pharmaceutiques de substances bioactives extraites de sources naturelles Withdrawn EP1183039A1 (fr)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US13640999P 1999-05-27 1999-05-27
US136409P 1999-05-27
US40892299A 1999-09-30 1999-09-30
US408922 1999-09-30
US51819100A 2000-03-03 2000-03-03
US518191 2000-03-03
PCT/US2000/014503 WO2000072861A1 (fr) 1999-05-27 2000-05-25 Preparations pharmaceutiques de substances bioactives extraites de sources naturelles

Publications (1)

Publication Number Publication Date
EP1183039A1 true EP1183039A1 (fr) 2002-03-06

Family

ID=27384857

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00944604A Withdrawn EP1183039A1 (fr) 1999-05-27 2000-05-25 Preparations pharmaceutiques de substances bioactives extraites de sources naturelles

Country Status (5)

Country Link
EP (1) EP1183039A1 (fr)
JP (1) JP2003500452A (fr)
AU (1) AU779928B2 (fr)
CA (1) CA2414094A1 (fr)
WO (1) WO2000072861A1 (fr)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010024664A1 (en) * 1999-03-19 2001-09-27 Obukowicz Mark G. Selective COX-2 inhibition from edible plant extracts
GB0027047D0 (en) 2000-11-06 2000-12-20 Ici Plc Process for reducing the concentration of undesired compounds in a composition
EP1401460A2 (fr) * 2000-12-15 2004-03-31 Pharmacia Corporation Inhibition s lective de la cox-2 au moyen d'extraits v g taux
US7029707B2 (en) 2001-10-03 2006-04-18 Herbalscience, Llc Method of producing a processed kava product having an altered kavalactone distribution and processed kava products produced using the same
US7105185B2 (en) 2001-10-03 2006-09-12 Herbalscience, Llc Kavalactone profile
US7037524B2 (en) 2001-10-03 2006-05-02 Herbalscience, Llc Oral delivery of a botanical
US7291352B2 (en) 2001-10-03 2007-11-06 Herbalscience Llc Methods and compositions for oral delivery of Areca and mate' or theobromine
US7138134B2 (en) * 2001-12-18 2006-11-21 Arizona Health Consulting Group, Llc Preparation and administration of jojoba product for reducing weight, fat and blood lipid levels
US6852342B2 (en) * 2002-03-26 2005-02-08 Avoca, Inc. Compounds for altering food intake in humans
ITMI20020990A1 (it) * 2002-05-10 2003-11-10 Indena Spa Formulazioni utili nel trattamento dell'impotenza maschile e femminile
WO2004023889A2 (fr) * 2002-09-12 2004-03-25 Armadillo Pharmaceuticals Supplements alimentaires complets obtenus a partir de vegetaux et procedes pour leur production
US7294353B2 (en) 2003-10-24 2007-11-13 Herbalscience, Llc Methods and compositions comprising ilex
US7279184B2 (en) 2003-10-24 2007-10-09 Herbalscience, Llc Methods and compositions comprising Ilex
US7384654B2 (en) * 2004-02-05 2008-06-10 Access Business Group International Llc Anti-Allergy composition and related method
CN100443579C (zh) * 2006-06-07 2008-12-17 中国农业科学院蜜蜂研究所 超临界流体萃取蜂花粉油脂的方法
JP5220346B2 (ja) * 2007-05-28 2013-06-26 丸善製薬株式会社 皮膚化粧料
CL2010000119A1 (es) * 2010-02-10 2010-08-06 Naturaleza Y Fe Ltda Uso de una composicion fitofarmacologica conformada por encelia canescens lam (coronilla de fraile) y excipientes farmaceuticamente aceptables para prevenir o tratar enfermedades neoplasicas, metabolicas o ralacionadas con estrés oxidativo.
CA2810000A1 (fr) 2010-08-31 2012-03-08 Trans Union Llc Systemes et procedes d'amelioration de la precision de devis d'assurance
DK2648809T3 (da) 2010-12-09 2019-07-15 Y&B Mothers Choice Ltd Naturlige formuleringer
US10434058B2 (en) 2010-12-09 2019-10-08 Y&B Mother's Choice Ltd. Natural formulations
KR20140019307A (ko) 2010-12-09 2014-02-14 와이앤드비 마더스 초이스 엘티디. 사포닌을 포함하는 제형 및 이의 용도
TWI448295B (zh) 2011-11-15 2014-08-11 Univ Kaohsiung Medical 抗人類泌尿上皮癌之香桂超臨界萃取物、製備方法及用途
CN102367256B (zh) * 2011-11-22 2014-06-04 中国科学院西北高原生物研究所 一种从羌活中提取异欧前胡素的方法
IL229836A0 (en) 2013-12-08 2014-03-31 Y & B Mother S Choice Ltd Formulations to reduce or suppress irritation to eye tissue
GB201414820D0 (en) 2014-08-20 2014-10-01 Brown Sebastian M Improvements to anaesthetic recycling methods and systems
KR102518631B1 (ko) 2016-05-02 2023-04-07 와이앤드비 마더스 초이스 엘티디. 사포닌 및 식물 추출물의 조성물
CN106266702A (zh) * 2016-09-12 2017-01-04 四川聚豪生物科技有限公司 一种用于治疗肾阴虚型腰肌劳损的中药组合物
EP3298897A1 (fr) * 2016-09-21 2018-03-28 Gyogynövenykutato Kft Produits à base de plantes pour l'amélioration et protection des plants, procédé de production et utilisation
WO2019164783A1 (fr) * 2018-02-20 2019-08-29 Monsoon Beverages LLC Extrait amélioré de kava et procédé de fabrication de celui-ci et compositions correspondantes et concentré et produits contenant du kava et leurs procédés de fabrication
CN108760953B (zh) * 2018-06-11 2021-02-19 梧州市食品药品检验所 同时检测复方感冒灵片中对乙酰氨基酚、氯苯那敏、咖啡因和绿原酸含量的快速检测方法
CN110579559B (zh) * 2019-10-26 2022-03-08 无锡济煜山禾药业股份有限公司 一种测定细胞基质中尿囊素浓度的衍生化结合lc-ms方法
CN111254013B (zh) * 2020-02-21 2023-07-21 福建中烟工业有限责任公司 含有细梗香草提取物的香料组合物
CN112898446B (zh) * 2021-03-11 2021-11-30 江西中医药大学 一种葛根多糖提取物及其提取方法和应用
CN115261867A (zh) * 2022-06-01 2022-11-01 贵州师范大学 一种环保型植物缓蚀剂及其制备方法和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9406423D0 (en) * 1994-03-31 1994-05-25 Ici Plc Solvent extraction process
GB2288552A (en) * 1994-04-19 1995-10-25 Ici Plc Solvent extraction process

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0072861A1 *

Also Published As

Publication number Publication date
AU5867600A (en) 2000-12-18
WO2000072861A1 (fr) 2000-12-07
AU779928B2 (en) 2005-02-17
CA2414094A1 (fr) 2000-12-07
JP2003500452A (ja) 2003-01-07

Similar Documents

Publication Publication Date Title
US6746695B1 (en) Pharmaceutical preparations of bioactive substances extracted from natural sources
AU779928B2 (en) Pharmaceutical preparations of bioactive substances extracted from natural sources
Yalavarthi et al. A review on identification strategy of phyto constituents present in herbal plants
BRPI0616319A2 (pt) composiÇço e mÉtodo para extrair uma espÉcie de panax
Engelbertz et al. Bioassay-guided fractionation of a thymol-deprived hydrophilic thyme extract and its antispasmodic effect
WO2008070783A2 (fr) Compositions et procédés comprenant des espèces de gingembre
US20080275117A1 (en) Compositions and Methods Comprising Boswellia Species
Günther et al. Quantitative determination of triterpenes in extracts and phytopreparations of Centella asiatica (L.) Urban
Qiburi et al. Bioactive components of ethnomedicine Eerdun Wurile regulate the transcription of pro-inflammatory cytokines in microglia
US20050118293A1 (en) Methods and compositions comprising Ilex
US7294353B2 (en) Methods and compositions comprising ilex
Ammor et al. In vitro litholytic activity of extracts and phenolic fractions of some medicinal plants on urinary stones
Ghalib et al. The investigation of some phytochemical compounds found in Anchusa strigosa L. grown naturally in Iraq
WO2020012447A1 (fr) Formulation à base de plusieurs plantes médicinales et son procédé de production
CN115634187A (zh) 铁皮石斛花提取物及制备方法和应用、铁皮石斛花提取液及应用、舒缓面霜及制备方法
Dhoble et al. Formulation, development and evaluation of sennoside enriched Senna extract tablets of different concentrations
CN117255627A (zh) 水飞蓟植物物质中生物活性化合物的提取及应用
Kristó et al. Comprehensive evaluation of different Solidaginis herba extracts
CN114478661A (zh) 一种由肉苁蓉萃取物中富集及分离苯乙醇苷类化合物的方法
KR20040067022A (ko) 감초로부터 글라브리딘을 추출하는 방법
KR100420767B1 (ko) 고미 성분을 선별적으로 제거한 인진쑥추출액 및 이를이용한 기능성 액상식품의 제조방법
Nasser Phytochemical study of Cynara scolymus L.(Artichoke)(Asteraceae) cultivated in Iraq, detection and identification of phenolic acid compounds cynarin and chlorogenic acid
Khaleefa et al. Isolation, Structural Characterization and Identification of Major Constituents in Ephedra foliata Naturally Growing in Iraq by TLC, GC-MS and UPLC-ESI-MS/MS
Gaikwad et al. Comparative HPLC analysis of different samples of Tribhuvankirti Rasa
CN106749490A (zh) 一种鹰嘴豆提取物及其制备方法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20011221

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

17Q First examination report despatched

Effective date: 20030829

17Q First examination report despatched

Effective date: 20030829

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20070522