EP2996702A1 - Extracts of astragalus membranaceus, their preparation and use as antihyperalgesic and antiallodynic drugs - Google Patents
Extracts of astragalus membranaceus, their preparation and use as antihyperalgesic and antiallodynic drugsInfo
- Publication number
- EP2996702A1 EP2996702A1 EP13730658.5A EP13730658A EP2996702A1 EP 2996702 A1 EP2996702 A1 EP 2996702A1 EP 13730658 A EP13730658 A EP 13730658A EP 2996702 A1 EP2996702 A1 EP 2996702A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pain
- extracts
- astragalus membranaceus
- extraction
- extracts according
- 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- Withdrawn
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
- A61K36/481—Astragalus (milkvetch)
-
- 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]
Definitions
- Extracts of Astragalus membranaceus their preparation and use as antihyperalgesic and antiallodynic drugs
- the present invention relates to the field of plant product extracts.
- neuropathic pain As: "An unpleasant sensory and emotional experience that is associated with actual or potential tissue damage or otherwise described as such”. It is a major problem in neurology as it is frequent and often debilitating on account of its chronic nature.
- oxaliplatin is a third generation platinum-organic compound that induces the appearance of a neuropathic syndrome characterised by paresthesia and dysesthesia of the extremities accompanied by cramps. These symptoms occur in 85-95% of patients treated. While the acute toxicity disappears within a few days of administration, repeated treatment induces a chronic form that does not subside in the interval between the treatment cycles (Gamelin et al., Semin Oncol 29, 2002; Extra et al. Semin Oncol 25, 1998; Andre et al., J Clin Oncol 17, 1999; Cersosimo Ann Pharmacother 39, 2005).
- Oxa!iplatin induces two types of peripheral neuropathy, an acute and a chronic type both characterised by hyperalgesia and allodynia until there is impairment of daily activities.
- This painful symptomatology is the main reason for suspension of antitumor therapy (Extra et alirri 1998; Andre et al., 1999; Gamelin et al., 2002; Cersosimo et al., 2005).
- taxane-based antineoplastic therapy contemplates a distal, symmetrical, axonal, predominantly sensory neuropathy among the side effects (Argyriou, et al.. Critical Reviews in Oncology/Hematology 66:218-228, 2008).
- Some epidemiological data reports an onset of peripheral neuropathy in 60% of patients taking taxanes. Even in this case, the symptoms most frequently reported by patients include paresthesia and motor peripheral neuropathies that determine pain in distal segments of the limbs.
- Figure 1 shows the IR spectrum of the extract according to the invention
- Figure 2 shows the spectrum obtained by nuclear magnetic resonance technique
- Figure 3 shows the profile of the two-dimensional HETCOR spectrum (called HMQC).
- Hydroalcoholic extracts of Astragalus membranaceus useful as antihyperalgesic and antiallodynlc drugs, are described.
- Astragalus membranaceus is a plant belonging to the Fabacease family that has powerful antioxidant properties (Sheng et al., Chin. Med. J. 5:43-49, 2005, Li et al, Urol. Res. 34:277-282, 2006, Luo et al. Phytother. Res. 23:761-767, 2009) of which the dried root is used.
- the extracts according to the invention are hydroalcoholic extracts substantially obtained following the methodologies known in this field.
- Alcohols for the extraction Water or alcohol/water mixtures can be used as alcohols for the extraction; ethanol is one example of alcohol that can be used for the extraction.
- the amount of alcohol is normally between 0 - 80% (calculated in volume with respect to the total volume of the mixture), preferably 70%.
- Extraction is carried out at room temperature by maceration and under stirring for a few days in order to obtain an exhaustive extraction of the phytocomplex, possibly by renewing the solvent employed one or more times.
- the extraction can be performed by percolation with hydroalcoholic solutions as defined above or for decoction.
- the alcohol is subsequently evaporated and the aqueous solution is lyophilized thus obtaining the desired product.
- the resulting solutions are pooled and the ethanol is evaporated with a rotary evaporator at low pressure.
- the resulting aqueous solution is lyophilized thus obtaining a white-pale yellow powder that is analysed by various methods to obtain a fingerprint.
- the powder obtained was analysed by infrared, by the nuclear magnetic resonance technique thus respectively obtaining the spectra set out in Figure 1 and 2.
- HMQC profile of the two-dimensional HETCOR spectrum
- the sample is prepared by mixing with nujol to obtain a preparation of semisolid consistency which under IR analysis has the following fingerprint:
- HMQC profile of the two-dimensional HETCOR spectrum
- the anomeric proton at 5.3 ppm has a cross-peak with an anomeric carbon ⁇ 92.0 ppm
- the group of carbinolic proton signals in the area between 3 and 4 ppm has characteristic cross-peaks with the carbons falling within the area between 60.0 and 82.0 ppm, which correspond to the carbinolic carbons of the saccharides.
- the signals at 60.0 ppm belong to the free methylenes (-CH2), while the signals at 82.0 ppm belong to the carbons on the positions of bonds in the polysaccharide chain.
- the lyophilized extract thus obtained can then be formulated for administration, preferably in oral form and, if necessary, can see the addition of the usual excipients used in this type of formulation such as for example inorganic excipients (such as for example silica gel) or excipients of a polysaccharide nature (such as for example: maltodextrin or lactose).
- excipients used in this type of formulation such as for example inorganic excipients (such as for example silica gel) or excipients of a polysaccharide nature (such as for example: maltodextrin or lactose).
- hydroalcoholic extract only exerts its pain threshold increasing action in the cold plate test. It is interesting to observe that the hydroalcoholic extract of Astragalus membranaceus does not induce analgesia per se in the absence of a painful condition (Tab. 1 a, 1 b, 1 c).
- the hydroalcoholic extract is also capable of improving the motor coordination of rats subjected to treatment with oxaliplatin.
- Tab. 2 shows the antihyperalgesic effect of the hydroalcoholic extract under analysis at the dose of 300 mg kg '1 p.o. on paclitaxel-induced hyperalgesia evaluated in rats in the paw pressure test.
- the hydroalcoholic extract of Astragalus membranaceus in animals is free of antihyperalgesic effect as regards some neuropathic pains such as for example pain induced by antiviral agents, loose ligation of the sciatic nerve and by experimental osteoarthritis induced by monoiodoacetate.
- the histopathological analysis carried out on liver and kidney samples from rats subjected to co-treatment with oxaliplatin and hydroalcoholic extract of Astragalus membranaceus has shown an appreciable protective effect on the part of the plant extract under analysis in respect of the alterations consequent to the cytotoxic effect of the chemotherapeutic drug.
- the pathological picture indicative of the presence of acute crescentic and/or focal segmental glomerulonephritis caused by treatment with oxaliplatin is significantly reduced by the administration of the hydroalcoholic extract of Astragalus membranaceus.
- the administration of the hydroalcoholic extract of Astragalus membranaceus at a dose of 300 mg/kg p.o. once/day, in conjunction with oxaliplatin, has shown to have a statistically significant protective effect, in respect to the damage induced by chemotherapeutic drugs, at the level of the basal ganglia attached to the posterior roots.
- the immunohistochemical evaluation has allowed us to use to highlight that the treatment in question was capable of increasing neuofilament expression levels (NF200) that were reduced due to the chemotherapeutic drug.
- a normalisation of the increased expression in the nuclei of ganglion neurons induced by chemotherapy has also been highlighted for transcription factor ATF3 (activating transcription factor 3), which is subject to nuclear dislocation in the course of damage.
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Alternative & Traditional Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
Claims
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IB2013/053914 WO2014184615A1 (en) | 2013-05-14 | 2013-05-14 | Extracts of astragalus membranaceus, their preparation and use as antihyperalgesic and antiallodynic drugs |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2996702A1 true EP2996702A1 (en) | 2016-03-23 |
Family
ID=48670636
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP13730658.5A Withdrawn EP2996702A1 (en) | 2013-05-14 | 2013-05-14 | Extracts of astragalus membranaceus, their preparation and use as antihyperalgesic and antiallodynic drugs |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP2996702A1 (en) |
WO (1) | WO2014184615A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109432162A (en) * | 2018-12-27 | 2019-03-08 | 大理大学 | Bhotan milkvetch herb extract and its pharmaceutical composition and preparation method and application |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100482237C (en) * | 2004-11-18 | 2009-04-29 | 高普 | Polysaccharid glucoside Chinese medicinal oral preparation and its making method thereof |
CN100574785C (en) * | 2007-08-03 | 2009-12-30 | 司马蕾 | A kind of herbal mixture for the treatment of neuropathic pain |
-
2013
- 2013-05-14 WO PCT/IB2013/053914 patent/WO2014184615A1/en active Application Filing
- 2013-05-14 EP EP13730658.5A patent/EP2996702A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO2014184615A1 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109432162A (en) * | 2018-12-27 | 2019-03-08 | 大理大学 | Bhotan milkvetch herb extract and its pharmaceutical composition and preparation method and application |
Also Published As
Publication number | Publication date |
---|---|
WO2014184615A1 (en) | 2014-11-20 |
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Legal Events
Date | Code | Title | Description |
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AX | Request for extension of the european patent |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: BILIA, ANNARITA Inventor name: PACINI, ALESSANDRA Inventor name: KARIOTI, ANASTASIA Inventor name: MUGELLI, ALESSANDRO Inventor name: GALLO, EUGENIA ROSARIA Inventor name: GHELARDINI, CARLA Inventor name: FIRENZUOLI, FABIO Inventor name: ZANARDELLI, MATTEO Inventor name: DI CESARE MANNELLI, LORENZO Inventor name: VANNACCI, ALFREDO |
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DAX | Request for extension of the european patent (deleted) | ||
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 |
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18D | Application deemed to be withdrawn |
Effective date: 20160719 |