WO2000006182A1 - Use of extracts from aristolochia in the treatment of aids - Google Patents
Use of extracts from aristolochia in the treatment of aids Download PDFInfo
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- WO2000006182A1 WO2000006182A1 PCT/US1999/002194 US9902194W WO0006182A1 WO 2000006182 A1 WO2000006182 A1 WO 2000006182A1 US 9902194 W US9902194 W US 9902194W WO 0006182 A1 WO0006182 A1 WO 0006182A1
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- use according
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- methoxy
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
Definitions
- This invention relates to compounds derived from the plant Aristotochia taliscana and their analogues, and the uses of such compounds in medicine.
- Aristolochia taliscana a climbing shrub found in the jungles of the southern coastal region of Mexico, is part of a family of climbing herbs and shrubs called Aristolochiaceae, numbering about six hundred species divided into eleven genera, and found mostly in tropical and sub-tropical regions. It is believed that the species Aristolochia taliscana is found only in Mexico.
- Aristolochiaceae are known for their ability to synthesise phenanthrene alkaloids, and in particular the aristolactam alkaloids and the aristolochic acids, and arylpropanoid compounds such as the lignans and neolignans.
- Such compounds are disclosed in, for example, R. Hegnauer “Chemotaxonomie der convinced”, Vol. Ill, pp 1 84-1 99, Birkhauser Verlag, Basel und Stuttgart, 1 964; R. Hegnauer “Chemotaxonomie der pfianzen", Vol. VII, pp 75-83, Birkhauser Verlag, Basel - Boston - Berlin, 1 989 and F.E. Correa et al.
- aristolactam and aristolochic acid compounds isolated from Aristolochia longa have antibacterial activity and cytotoxic activity against P-388 lymphocytic leukaemia and human bronchial epidermoid carcinoma cells.
- taliscanine an extract from the root of Aristolochia taliscana, alleviates the symptoms of Parkinsonism and related neurological disorders. It is also indicated in US 4782077 that taliscanine may be useful in the treatment of various other neurological disorders, including Alzheimer's disease, impotency, and neurological disorders associated with viral, bacterial, fungal and parasitic infections.
- taliscanine has since been tested for its ability to interact with neurotransmitter receptors, and, somewhat surprisingly, exhibited 50% inhibition in only one receptor (the opiate mu receptor) out of twenty seven common receptor types tested, and exhibited very poor levels of inhibition with the remaining receptors.
- taliscanine exhibited negligible activity at the dopami ⁇ e, GABA and serotonin receptors.
- the invention provides the use of an extract from an Aristolochia species, preferably Aristolochia taliscana, or one or more compounds isolable therefrom, for the manufacture of a medicament for the treatment of AIDS.
- the invention provides the use of an extract or compound as hereinbefore defined for the manufacture of a medicament for preventing or reversing cachexia, for example in AIDS patients, or in patients suffering from neoplastic diseases such as cancers.
- the extracts from the Aristolochia species can be prepared by extracting the roots, stems, leaves or other parts of officethe plant with an organic solvent such as ethanol.
- Extracts from Aristolochia taliscana have also been found to be useful in the treatment of male impotence.
- the invention provides for the use of a compound or compounds isolable from Aristolochia taliscana for the manufacture of a medicament for the treatment of male impotence.
- taliscanine contains a substantial number of compounds other than aristolactams, in particular certain benzofuran neolignans, many of which are novel.
- Benzofuran compounds isolated from taliscanine have been tested and have been found to be active as anti-mutagenic agents, as cytotoxic agents, and some have been found to have good antifungal activity. On this basis, it is anticipated that the compounds in question will find use in the treatment of tumours and other neoplastic diseases, as well as fungal infections.
- the invention provides the use of an extract of Aristolochia taliscana or one or more anti-mutagenically active components isolable therefrom for the manufacture of a medicament for the treatment of disease states mediated by mutagenesis.
- the invention also provides the use of an extract of an Aristolochia species, preferably Aristolochia taliscana or one or more component compounds isolable therefrom, for the manufacture of a medicament for the treatment of chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, synovitis and psoriasis.
- Aristolochia species preferably Aristolochia taliscana or one or more component compounds isolable therefrom
- component compounds oi Aristolochia taliscana have also been found to have good antifungal activity, and in a still further aspect, the invention provides the use of an extract oi Aristolochia taliscana or one or more antifungally active compounds isolable therefrom for the manufacture of a composition for antifungal use, for example in the treatment of plants or animals.
- the invention also provides pharmaceutical compositions comprising benzofuran compounds of the type found in Aristolochia taliscana or benzofuran compounds analogous thereto, for example benzofuran compounds in which an aryl ring (such as an oxygenated phenyl ring) is attached to the heterocyclic ring of the benzofuran, and the uses of such compounds in medicine.
- benzofuran compounds of the type found in Aristolochia taliscana or benzofuran compounds analogous thereto, for example benzofuran compounds in which an aryl ring (such as an oxygenated phenyl ring) is attached to the heterocyclic ring of the benzofuran, and the uses of such compounds in medicine.
- the invention also provides a novel group of benzofuran compounds having an oxygenated aryl ring (such as an oxygenated phenyl ring) attached to the heterocyclic ring of the benzofuran.
- an oxygenated aryl ring such as an oxygenated phenyl ring
- the invention provides the use of a compound for the manufacture of a medicament for use in any one or more of the therapeutic uses selected from the treatment or alleviation of AIDS or the symptoms thereof, or the alleviation or reversal of cachexia, or the treatment of neoplastic diseases or diseases mediated or intiated by mutagenesis or abnormal cellular proliferation, or as a cytotoxic agent, or the treatment of chronic inflammatory conditions, or the treatment of neurological disorders such as Parkinsonism, or the treatment of male impotence; the compound being of the formula (I):
- n 0, 1 , 2 or 3
- A is a monocyclic aryl ring containing up to two heteroatoms and being optionally substituted by one or more substituent groups which may be the same or different and are selected from R 3 0, R 3 , R 3 S, halogen; aryl and heteroaryl, wherein R 3 is hydrogen, or a hydrocarbyl group optionally substituted by a hydroxy or hydrocarbyloxy group
- B is selected from carboxy, carboxaldehyde, hydrocarbyl and hydrocarbyloxy groups wherein the hydrocarbyl group is acyclic or cyclic, and optionally contains one or more heteroatoms, and is optionally substituted by one or more hydroxy, alkoxy, alkenyloxy, alkynyloxy, aryloxy, aldehyde, alkanoyl, acetal, hemiacetal and carboxy groups; R 1 is hydrogen or a hydrocarbyl group optionally
- the monocyclic aryl ring A is attached to the 2- position of the furan ring, and it is particularly preferred that the aryl ring is a phenyl group.
- the phenyl ring can contain up to five substituent groups but preferably contains no more than three substituents.
- the group B is attached to the 5-position of the benzofuran group.
- the dotted line signifies a double bond.
- the invention provides the use of a compound for the manufacture of a medicament for use in the treatment of the conditions described above in relation to formula (I), the compound having the formula (II):
- R 1 and R 2 are as hereinbefore defined, R 4 and R 5 are the same or different and each is selected from hydrogen, C, ⁇ hydrocarbyl, C 5 . 20 aryl, or C 5 . 20 oxygen- containing heteroaryl; R 6 is selected from C, ⁇ hydrocarbyl or C 20 hydrocarbyloxy optionally substituted by one or more hydroxy, alkoxy or aralkyloxy groups; or R 6 is C 5 . 25 aryl or oxygen or nitrogen-containing heteroaryl.
- R 4 and R 5 are preferably selected from hydrogen, or C 1-6 alkyl, or R 4 and R 5 together define an alkylene group such as -CH 2 -. Preferably, at least one of R 4 and R 5 is hydrogen.
- Particularly preferred compounds are those in which the dotted line signifies a double bond and one of R 4 and R 5 is hydrogen.
- groups R 6 are hydrogen, halogen, C . 6 alkoxy (e.g. methoxy), a 2-benzofuranyl ring, or an aristolactam group.
- hydrocarbyl groups are aliphatic, alicyclic and aromatic groups such as alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenyl, cycloalkenyialkyl, cycloalkenylalkenyl, aryl, aralkyl, aralkenyl, aralkynyl.
- the hydrocarbyl groups can be optionally interrupted by one or more heteroatoms such as oxygen and sulphur.
- alkyl groups are C,. 6 alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl.
- cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicycloheptanyl, decalinyl, adamantyl, norbornyl and bicyclooctyl.
- alkenyl and alkynyl groups examples include vinyl, ethynyl, allyl, 1 - propenyl, propargyl, but-1 -enyl, but-2-enyl, but-3-enyl and 3-methylbutenyl.
- cycloalkenyl groups are cyclopentenyl, cyclohexenyl, cycloheptenyl, and monocyclic, bicyclic and tricylic terpene groups.
- aryl groups are phenyl and naphthyl.
- phenylalkyl and phenylalkenyl groups are benzyl, phenethyl, phenylpropyl, phenylbutyl and styryl groups.
- the invention provides a compound of the formula (I) or (II) as hereinbefore defined for use in medicine, for example for use in any one or more of the therapeutic uses selected from the treatment or alleviation of AIDS or the symptoms thereof, or the alleviation or reversal of cachexia, or the treatment of neoplastic diseases or diseases mediated or intiated by mutagenesis or abnormal cellular proliferation, or as a cytotoxic agent, orthe treatment of chronic inflammatory conditions, or the treatment of neurological disorders such as Parkinsonism, or the treatment of male impotence, or as an anti-fungal agent in the treatment of plants or animals; but provided that when R 1 is 3-methyl, R 2 is a single methoxy group at the 7-position, and either (i) the furan ring is unsaturated and is substituted at the 2-position with a 4-hydroxy-3-methoxyphenyl group or a 3,
- the present invention also provides novel compounds per se of the formula
- R 1 1 is hydrogen or alkyl
- R 12 is selected from hydrogen, C-. 6 alkyl; a cyclic terpenoid group or a group of the formula E, G or J;
- R 13 is selected from hydrogen; C-. 3 alkyl or hydroxy-C ⁇ alkyl;
- R 15 is hydrogen or C 6 alkyl;
- R 16 is hydrogen, a group M or an aristolactam group; and R 17 is hydrogen or a group T; wherein the groups E, G, L, J, M and T
- R 11 , R 12 , R 13 R 14 , R 15 and R 17 are as hereinbefore defined and X is a group:
- R 18 is hydrogen, benzyl or alkyl
- R 19 to R 24 are the same or different and are selected from hydrogen, hydroxy, alkoxy, alkyl and hydroxy-C ⁇ . 6 alkyl; or any two adjacent groups together form an alkylene dioxy group.
- the invention provides novel compounds of the formula (V):
- Y is a monocyclic or bicyclic terpenoid group and in particular a group of the structure:
- the invention provides tetralone compounds for use in medicine, the tetralone compounds being of the formula (VI):
- R 25 and R 27 are the same or different and each is C 1-6 alkyl, or R 25 and R 26 together form an alkylene group (such as methylene); and R 26 is hydrogen or C ⁇ alkyl.
- R 25 , R 26 and R 27 are all methyl.
- Tetralone compounds of the formula (VI) have biocidal activity, and in particular cytotoxic, antibacterial and antifungal activity. It is therefore anticipated that they will be useful in the treatment of proliferative and infective diseases and conditions such as cancers and bacterial and fungal infections.
- the invention also provides a compound of the formula (VI) for use in the treatment of bacterial or fungal infections, or for use in the treatment of cancers and other proliferative diseases such as psoriasis.
- Compounds of the formula (VI) have previously been reported as synthetic intermediates (see loie et al. Chem. Pharm. Bull. 38, 1851-56 (1990).
- novel compounds of the invention are: ( ⁇ )-5-(1 -Hydroxy allyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-3- methylbenzofuran (Compound 9);
- Certain compounds of the formulae I to VI can be obtained by solvent extraction of plant material, such as roots, bark, leaves and twigs, from Aristolochia taliscana using solvents such as benzene followed by chromatographic separation of the components of the solvent extract.
- solvents such as benzene
- a typical extraction protocol is described in detail below.
- compounds of the formulae (I) or (II) can be prepared by means of the reaction scheme set out in Figure 1 .
- reaction conditions and reagents employed in the scheme set out in Figure 1 can be substantially as described in M. Watanabe et al. Chem. Pharm. Bull. 37, 2884 ( 1 989); ibid. 38, 41 ( 1 990), and ibid. 39, 31 23 ( 1 991 ), the contents of which are incorporated herein by reference.
- the methoxymethylaryl ketone is reacted with the substituted o-hydroxybenzaldehyde in an acidic medium (for example a mixture of hydrochloric acid and acetic acid) to give a benzpyryllium salt which is then subjected to oxidation and rearrangement in the presence of hydrogen peroxide and methanol at pH 5.8 to give a benzfuran 3-carboxy ester.
- an acidic medium for example a mixture of hydrochloric acid and acetic acid
- the benzfuran 3-carboxyester can then be treated successively with (i) lithium aluminium hydride in an ether such as diethyl ether; (ii) manganese dioxide in a non-polar solvent such as benzene; (iii) 1 ,2 ethyiene-dithiol, acetic acid and boron trifluoride etherate; and (iv) Raney nickel in an alcohol such as ethanol.
- ether such as diethyl ether
- manganese dioxide in a non-polar solvent such as benzene
- 1 ,2 ethyiene-dithiol, acetic acid and boron trifluoride etherate
- Raney nickel in an alcohol such as ethanol
- the extracts and compounds of the invention are useful in a number of medical aspects. For example, as indicated above, they are useful in the treatment and management of AIDS.
- the compounds or extracts can be administered in standard manner, for example orally, parenterally, transdermally, rectally, via inhalation or via buccal administration. Preferably, however, they are administered orally.
- the dosage employed will depend on the nature and purity of the extract and the concentrations of the active principles.
- the concentration administered can be in the range from 0.5mg to 500mg (dry weight) of extract per patient per day, more usually 1 mg to 1 0Omg per day.
- the dosages of such compounds administered typically will be similarly in the range 0.5mg to 500mg per patient per day, more usually 1 mg to 100mg per day.
- the extracts or compounds may be administered as single doses or multiple doses as desired.
- the dosages of the extracts or compounds of the invention administered will depend upon inter alia the potency of the extract or compound, and the nature and severity of the disease state or condition under treatment but ultimately, however, will be at the discretion of the physician.
- the extracts and compounds of the invention can be formulated as solutions, syrups, tablets, capsules, lozenges, inserts, patches, powders, pills, solutions for injection or drops, or aerosols such as dry powder aerosols or liquid aerosols, by way of example.
- Such formulations can be prepared in accordance with methods well known per se.
- compositions of the invention can take the form of solid or semi-solid unit dosage form.
- the compositions can take the form of tablets, granules, lozenges or capsules.
- a solid or semi-solid dosage form according to the present invention can contain, for example, from 1 0mg to 1 000mg of the extract or compounds of the invention, more typically 50mg to 500mg, e.g. 100mg to 400mg, and in particular 1 50mg to 350mg, particular unit dosages being approximately 200mg and 300mg.
- a tablet composition will typically contain one or more pharmaceutically acceptable solid diluents, examples of which include sugars such as sucrose and lactose, and sugar alcohols such as xylitol, sorbitol and mannitol; lactose and sorbitol being particular examples.
- sugars such as sucrose and lactose
- sugar alcohols such as xylitol, sorbitol and mannitol
- lactose and sorbitol being particular examples.
- the tablets will also typically contain one or more excipients selected from granulating agents, binders, lubricants and disintegrating agents.
- disintegrants include starch and starch derivatives, and other swellable polymers, for example cross-linked polymeric disintegrants suc h as c ross-lin ked c arboxymethylcel l u lose , cross-l in ked polyvinylpyrrolidone and starch glycolates.
- lubricants examples include stearates such magnesium stearate and stearic acid.
- a capsule composition typically will comprise an outer shell or casing which may, for example, be formed from hard or soft forms of gelatin or gelatin-equivalents in conventional fashion.
- the outer shell is filled with an extract or a compound in accordance with the invention.
- the capsule filling may be in the form of a powder, or granules, or beads, or may be in the form of a liquid or semi-solid.
- the granules can consist of the extract or compound of the invention alone, or granulated together with a granulating agent, or they can additionally comprise a solid diluent, for example of the type set forth above.
- the granules can be wet granulated or dry granulated as desired.
- the extract or compound can be dissolved or suspended in a semi-solid carrier material such as a polyethylene glycol or a liquid carrier such as a glycol, e.g. propylene glycol, or glycerol.
- a semi-solid carrier material such as a polyethylene glycol or a liquid carrier such as a glycol, e.g. propylene glycol, or glycerol.
- the capsule is in solid or semi-solid form when hard gelatin capsules are used; liquid or semi-solid forms being preferred with soft gelatin capsules.
- EIMA were obtained at 70 eV; DCIMS with NH 3 or isobutane, respectively. Apart from key ions, the only ions listed are those with relative intensities > 1 0% and m/z > 100.
- CC column chromatography
- MPLC medium pressure liquid chromatography
- Roots oi Aristolochia taliscana Hook were collected by Jorge Perez de la Rosa (Instituto Tecnologico y de Estudios Superiores de Monterrey, ITESM) from Colima (Mexico) and identified by Prof. H. Sanchez.
- a voucher specimen is held at the Universidad de Guadalajara, Instituto de Botanica, Guadalajara (Mexico).
- Air dried, pulverized roots and rhizomes (3.5kg) of Aristolochia taliscana were extracted with benzene at room temperature to give 1 6g of a red-brown extract after removal of solvent.
- This extract was separated by column chromatoraphy on Fractogel TSK HW 40 (S) with methanol to give 10 fractions (designated A.t.1 to A.t 10), which were then subjected to further chromatographic separation by repeated MPLC or CC using the following systems (a) silica gel, cyclohexane-ethyl acetate gradients, (b) LiChroprep RP 1 8, MeOH-H 2 0 gradients, (c) Fractogel PVA 500, methanol.
- the separation scheme followed is set out in Figure 3, and the experimental conditions employed in each of the separation steps are set out in Table 2 below.
- aristolactams referred to in the table have the following structural formulae:
- the four major constituents of the benzene extract from Aristolochia taliscana roots - eupomatenoid-7 (7), eupomatenoid-1 (8), eupomatenoid-8 ( 17), Licarin-A (16) - were tested for their mutagenic and antimutagenic properties using the Ames bio-assay (Maron, D.M. and Ames, B.N., Mutation reasearch, 1 983, 1 13, 1 73) .
- the test compounds have the following structural formula:
- Salmonella typhimurium strain TA 100 was used as the test organism and 2-amino-anthracene (2-AA) and 2-nitrofluorene (2-NF) as standard mutagens, of which 1 ⁇ g were added to each test plate.
- 2-AA 2-amino-anthracene
- 2-NF 2-nitrofluorene
- Eupomatenoid-7 (7) exhibited strong antimutagenic effects against 2- aminoanthracene as well as against 2-nitrofluorene (Tab. 4) .
- Licarin-A ( 16) and eupomatenoid-1 (8) were found to be antimutagenically active only in the experiment against 2-AA but not against 2-NF (Tab. 5).
- eupomatenoid-8 ( 17) did not show any antimutagenic effect in the test systems used (Tab. 6).
- Table 7 Results from the experiments on antimutagenic activity of eupomatenoid-8 ( 1 7) .
- the antifungal activities of compounds of the invention was determined using a plate diffusion method. Plates containing medium and a fungal species were made up and 1 50 microgramme aliquots of a test compound of the invention were spotted onto the plate. The diameter of inhibition of fungal growth around the test compound was then determined. The results of the tests are shown in Table 9 below. Table 9: Antifungal Activity
- An aqueous alcoholic extract was prepared by extracting roots from Aristolochia taliscana with aqueous ethanol and concentrating the resulting solution to 65% solids content by evaporation under reduced pressure. Ethanol was then added to the solution to give a concentration equivalent to 1 litre of solution for every kilogramme of raw material. The result was a brown liquid which was administered without further purification.
- Patient I whose identity cannot be revealed for medical confidentiality reasons, had been diagnosed as suffering from AIDS, and had previously been treated with azidothymidine (AZT), dideoxycytidine (DDC) and dideoxyinosine (DDI) but had been forced to discontinue the treatment because of the side effects.
- AZT azidothymidine
- DDC dideoxycytidine
- DAI dideoxyinosine
- Patient I was treated by daily oral administration of several drops of the alcoholic extract of Aristolochia taliscana. After forty five days, the gastrointestinal problems had disappeared, the scaip infection had gone, and he had gained seven kilogrammes in weight.
- Patient number II a resident of Mexico City, and who had been diagnosed as being HIV positive, was treated by daily oral administration of the alcoholic extract oi Aristolochia taliscana over a period of nearly five years. At the end of that period, Patient ll's CD4 count was approximately 60. When the CD4 count falls below about 200, the immune system is generally unable to cope with infection of bacterial or fungal origin and patients with such a reduced immune function typically die from infections of one kind or another. It owuld therefore have been expected that Patient II, having such a low CD4 count, would have succumbed to infection during the five year period. However, despite the low CD4 count, Patient II remained healthy and active and free from the symptons of AIDS during the period of treatment. It would therefore appear that the Aristolochia taliscana extract does not function by stimulating the immune sytem, but by some other, at present unknown, mechanism.
Abstract
Description
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Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99905622A EP1117415A1 (en) | 1998-07-31 | 1999-02-02 | Use of extracts from aristolochia in the treatment of aids |
AU25746/99A AU2574699A (en) | 1998-07-31 | 1999-02-02 | Use of extracts from aristolochia in the treatment of aids |
US09/774,769 US20020099086A1 (en) | 1998-07-31 | 2001-01-31 | Use of extracts from aristolochia in the treatment of AIDS |
US10/322,305 US20030147973A1 (en) | 1998-07-31 | 2002-12-18 | Use of extracts from aristolochia in the treatment of aids |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBPCT/GB98/02317 | 1998-07-31 | ||
PCT/GB1998/002317 WO1999006388A2 (en) | 1997-07-31 | 1998-07-31 | Pharmaceutical compounds isolated from aristolochia taliscana |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US09/774,769 Continuation US20020099086A1 (en) | 1998-07-31 | 2001-01-31 | Use of extracts from aristolochia in the treatment of AIDS |
Publications (1)
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WO2000006182A1 true WO2000006182A1 (en) | 2000-02-10 |
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PCT/US1999/002194 WO2000006182A1 (en) | 1998-07-31 | 1999-02-02 | Use of extracts from aristolochia in the treatment of aids |
Country Status (3)
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EP (1) | EP1117415A1 (en) |
AU (1) | AU2574699A (en) |
WO (1) | WO2000006182A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8003137B2 (en) | 2008-05-09 | 2011-08-23 | Fastrack Pharmaceuticals, Inc. | Extracts of Aristolochia paucinervis pomel and uses thereof |
CN117379420A (en) * | 2023-12-12 | 2024-01-12 | 中国中医科学院中药研究所 | Use of aristololactam BII in preparation of leukocyte-increasing products |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0304294A2 (en) * | 1987-08-20 | 1989-02-22 | Monoclonetics International, Inc. | Taliscanin and other Aristolactams for treating neurological disorders, Parkinson's disease, Alzheimer disease and impotence |
CH688787A5 (en) * | 1995-09-05 | 1998-03-31 | Dieter Linsig | Synergistic mixture of essential oils or essences |
WO1999006388A2 (en) * | 1997-07-31 | 1999-02-11 | Proteome Sciences Plc. | Pharmaceutical compounds isolated from aristolochia taliscana |
-
1999
- 1999-02-02 WO PCT/US1999/002194 patent/WO2000006182A1/en not_active Application Discontinuation
- 1999-02-02 EP EP99905622A patent/EP1117415A1/en not_active Withdrawn
- 1999-02-02 AU AU25746/99A patent/AU2574699A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0304294A2 (en) * | 1987-08-20 | 1989-02-22 | Monoclonetics International, Inc. | Taliscanin and other Aristolactams for treating neurological disorders, Parkinson's disease, Alzheimer disease and impotence |
CH688787A5 (en) * | 1995-09-05 | 1998-03-31 | Dieter Linsig | Synergistic mixture of essential oils or essences |
WO1999006388A2 (en) * | 1997-07-31 | 1999-02-11 | Proteome Sciences Plc. | Pharmaceutical compounds isolated from aristolochia taliscana |
Non-Patent Citations (3)
Title |
---|
CHAMBERLAIN ET AL: "Investicaion on fungicides", ANN APPL BIOL, vol. 88, no. 1, 1978, England, pages 57 - 64 * |
CHEMICAL ABSTRACTS, vol. 78, no. 29, 23 October 1993, Columbus, Ohio, US; abstract no. 141713, CHAMBERLAIN ET AL: "Investigation on fungicides" XP002085373 * |
ENRIQUEZ R G ET AL: "Phytochemical investigations of plants of the genus Aristolochia, 1. Isolation and NMR spectral characterization of eupomatenoid derivatives", JOURNAL OF NATURAL PRODUCTS, vol. 47, no. 5, 1 September 1984 (1984-09-01), pages 896 - 899, XP002085369 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8003137B2 (en) | 2008-05-09 | 2011-08-23 | Fastrack Pharmaceuticals, Inc. | Extracts of Aristolochia paucinervis pomel and uses thereof |
CN117379420A (en) * | 2023-12-12 | 2024-01-12 | 中国中医科学院中药研究所 | Use of aristololactam BII in preparation of leukocyte-increasing products |
CN117379420B (en) * | 2023-12-12 | 2024-02-13 | 中国中医科学院中药研究所 | Use of aristololactam BII in preparation of leukocyte-increasing products |
Also Published As
Publication number | Publication date |
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EP1117415A1 (en) | 2001-07-25 |
AU2574699A (en) | 2000-02-21 |
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