WO2007046125A2 - Utilisation d'extraits de myrte et d'autres especes vegetales mediterraneennes, a teneur standardisee en molecules polyphenoliques, comme nouvel agent antifongique actif contre les levures et les micro-organismes de type levure d'interet biomedical - Google Patents

Utilisation d'extraits de myrte et d'autres especes vegetales mediterraneennes, a teneur standardisee en molecules polyphenoliques, comme nouvel agent antifongique actif contre les levures et les micro-organismes de type levure d'interet biomedical Download PDF

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Publication number
WO2007046125A2
WO2007046125A2 PCT/IT2006/000743 IT2006000743W WO2007046125A2 WO 2007046125 A2 WO2007046125 A2 WO 2007046125A2 IT 2006000743 W IT2006000743 W IT 2006000743W WO 2007046125 A2 WO2007046125 A2 WO 2007046125A2
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WO
WIPO (PCT)
Prior art keywords
yeast
extracts
myrtle
deriving
species
Prior art date
Application number
PCT/IT2006/000743
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English (en)
Other versions
WO2007046125A3 (fr
Inventor
Annalisa Romani
Pietro Buzzini
Innocenza Chessa
Flavia Franconi
Patrizia Pinelli
Benedetta Turchetti
Giovanni Nieddu
Original Assignee
Annalisa Romani
Pietro Buzzini
Innocenza Chessa
Flavia Franconi
Patrizia Pinelli
Benedetta Turchetti
Giovanni Nieddu
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.)
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Publication date
Application filed by Annalisa Romani, Pietro Buzzini, Innocenza Chessa, Flavia Franconi, Patrizia Pinelli, Benedetta Turchetti, Giovanni Nieddu filed Critical Annalisa Romani
Priority to EP06810032A priority Critical patent/EP1945237A2/fr
Publication of WO2007046125A2 publication Critical patent/WO2007046125A2/fr
Publication of WO2007046125A3 publication Critical patent/WO2007046125A3/fr

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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)
    • 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)
    • A61K36/22—Anacardiaceae (Sumac family), e.g. smoketree, sumac or poison oak
    • 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)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics

Definitions

  • the ecosystem Mediterranean maquis is recognized as "excellent of plant biological diversity. A great variability is also expressed at intraspecies level, due to the plant species adaptability to the heterogeneous environmental conditions, which characterize the territories around the Mediterranean Basin. Among the distinctive plant species, the following are regarded as a valuable opportunity for* the sustainable development of many areas in the Mediterranean Basin:
  • RAPD and microsatellites The characterization of different wild population and selected genotypes, applying the molecular markers technique (RAPD and microsatellites) is directed to: i) acquire knowledge on the species genetic variability and relatedness among and within population from different growing areas, ii) to identify genotypes showing useful morphological traits for utilization, and iii) as a tool in the selection of the genetic material within wild populations to be propagated for cultivation (Nieddu et al., 2005) Despite the use of above plants as food or pharmaceutical preparations is known since antiquity (Craig, 1999, Eisenberg et al., 1993), only recent studies aimed at characterizing their phytochemical composition and biological activity have allowed to discover the role of some potentially beneficial molecules.
  • flavonoids seems to phlogosis or inflammation control (Katiyar et al., 1992), the platelet function (Duffy et al., 2001), the vascular tone (Duarte et al., 2001 ; Burs et al., 2000), the angiogenesis (Cao e Cao, 1999), the arteriosclerosis (Stenvold et al., 1992), and the carcinogenesis (Y an 9. 1997).
  • the different flavonoids can express different biological activities: sometirhes, the single flavonoid molecule is characterized by a less significant activity than the mixture of different compounds, thus suggesting the existence of a (possible) synergistic activity.
  • Galloyl derivatives particularly catechins and epigallocatechins occurring in green tea composition, apparently act by reducing the activity of inducible nitroxyde sintetase (iNOS). Additional activity of these classes of molecules are: i) the neutralization of the peroxynitrite; ii) the neutralization of the activity of ROS-producing NADPH oxydase of the blood vessels; and iii) the reduction of the activity of metalloproteinase (which is considered a key enzyme for remodeling).
  • Myricetin is considered a potent inhibitor of Ca- ATPase.
  • Enzymes inhibited by the polyphenols occurring in green tea composition are associated with the pathogenesis of some cardiovascular diseases (Cahilly et al., 2000; Griendling et al., 2000).
  • catechins and the epigallocatechins, as well as a*number of other bioflavonoids act by directly neutralizing the ROS (whose role on phenomena of apoptosis and expression of stress protein in cell of cardiovascular apparatus is well documented).
  • the invention genetically relates to utilization of natural extracts of myrtle, cistus, arbutus, lentisk and other Mediterranean plant species containing galloyl derivatives and hydrolysable tannins deriving from artisan or industrial manufactures as preparations exhibiting antimycotic activity towards yeasts and yeast-like microorganisms belonging to species considered as known or emerging pathogen for humans and animals.
  • FIG. 1 shows in Figs. 1 ;and 2 diagrams relating to antimycotic spectrum of myrtle extracts: killing curve towards Candida glabrata DBVPG 3828.
  • the invention relates to the preparation of myrtle extracts (standardized in the content of polyphenols) from different plant tissues and from by-products deriving from artisan or industrial manufactures carried out over the same species and their utilization as antimycotic agents active towards yeast and yeast-like microorganisms of biomedical interest.
  • the present invention has considered the following phases: I) Selection of myrtle genotypes, their propagation and cultivation. The adoption of crop management systems characterized by a low-environmental impact is recommended. The growing of selected varieties will assure the ripening control and the reproducibility of the mean quality characteristics from one year to the other and from different growing locations. The aims of a direct domestication of wild plants species and the crop management are essentially directed to standardize the final product quality and to lessen the energy input, as well as to reduce environmental and operational costs.
  • Type strain - T type strains belonging to species considered as known or emerging pathogens for humans and animals.
  • type strain - T type strains belonging to species considered as known or emerging pathogens for humans and animals.
  • myrtle extracts (above cited) as preparations exhibiting antimycotic activity towards yeasts and yeast-like microorganisms belonging to species considered known or emerging pathogens for humans and animals.
  • the preliminary determination of antimycotic activity obtained through the combined use of myrtle extracts (above cited) with Amphotericin B has been carried out by using the Agar Diffusion Well Bioassay (ADWB) (Hammond e Lambert, 1978) .
  • ADWB Agar Diffusion Well Bioassay
  • myrtle extracts (above cited) as a mixed preparations with Amphotericin B in order to obtain a product characterized by a high antimycotic activity towards yeast and yeast-like microorganisms, but containing reduced concentration of Amphotericin B .
  • V derivatives and/or hydrolysable tannins in association with cistus, arbutus, lentisk, and phillyrea extracts in order to obtain mixed preparations exhibiting antimycotic activity towards yeasts and yeast-like microorganisms belonging to species considered as known or emerging pathogen for humans and animals.
  • extracts obtained through aqueous or low-temperature hydroalcoholic extraction procedures) from all above Mediterranean plants (in all possible combinations) as mixed preparations exhibiting antimycotic activity towards yeasts and yeast-like microorganisms belonging to species considered as known or emerging pathogen for humans and animals.
  • the invention also relates to other plant species selected varieties as sources of raw material for the production of extracts characterized by a high concentration of hydrolysable tannins for antimycotic use.
  • myrtle, cistus, arbutus, lentisk, and phillyrea will benefit from the application of farming methods with low and energetic inputs.
  • a cultivation system based on the agroforestry techniques is hopeful to maintain the dynamic natural balance of the plant growing environment.
  • leaves and berry from wild plants. The regulation of harvesting time and methods is recommended to increase the supply of biomass, at trie same time avoiding the plant over- exploitation and the habitats disturbance.
  • the invention also foresees the use of extract deriving from leaves of Vitis vinifera L. (grape seed, skin, and marc), Pinus. marittima L and other species of the genus Pinus containing condensed and hydrolysed tannins as raw preparations exhibiting antimycotic activity for cosmetic, pharmaceutical and veterinary use.
  • the invention has also foreseen the use of a set of yeasts and yeast-like microorganisms including type strains (type strain - T) belonging to species considered known or emerging pathogens for humans and animals.
  • type strains type strain - T
  • the type strain represents its reference strain internationally recognized and conserved in all most important world collections of microbial germplasm. Accordingly, since the biological variability observed within strains belonging to a same species, results obtained by using worldwide available strains (e.g. type strains) gave the advantage of their high comparability within and among laboratories.
  • the invention also foresees the combined use of extracts of myrtle, cistus, arbutus, lentisk, and phillyrea, as well as commercial extracts of plants of the genera Vitis and Pinus, among them or in association with Amphotericin B or Ketoconazole, in order to induce a synergistic effect among different active principles. This should be interesting in reducing the risk of overexposition of patients to high dosages of antibiotics. Analogously to above we also foresee the combined use of polyene antibiotics other than Amphotericin B (characterized by synthetic or biological origin).
  • type strain - T type strains belonging to species considered known or emerging pathogens for humans and animals. Accordingly, the use of type strains as target microorganisms may be considered an additional innovative point.
  • the type strain of a given species represents its internationally recognized reference strain. Type strains are conserved in all worldwide collections of microbial germplasm. Accordingly, since the biological variability observed within strains belonging to a same species, results obtained by using worldwide available strains (e.g. type strains) gave the advantage of their high comparability within and among laboratories.
  • MIC Minimal Inhibitory Concentration
  • Myrtle extract exhibited the ability to inhibit growth of of strains belonging to the species Candida albicans, Candida glabrata, Candida parapsilosis, Candida zeylanoides, Clavispora lusitaniae, lssatchenkia orientalis, Kluyveromyces marxianus, Pichia guillermondi, Saccharomyces cerevisiae, Cryptococcus laurentii, Filobasidiella neoformans, Prototheca wickeramii, and Prototheca zopfii: values ranging from 2 to 10 mg extract/mL substrate have been observed (Table 3, Fig.
  • MIC Minimal Inhibitory Concentration
  • MIC Minimal Inhibitory Concentration
  • myrtle extracts + Amphotericin B may be potentially exploitable through the use of preparations containing a mixture of both active principles (extract + antibiotic) characterized by a reduced concentration of Amphotericin B, but by an improved antimycotic activity of polyene antibiotics currently used in clinical practice.
  • the polyphenols galloyl derivatives occurring in the composition of myrtle leaves
  • the polyphenols may represent the class of molecules responsible of synergistic activity between the . myrtle extract and Amphotericin B, in agreement with published studies reporting the synergistic interaction between synthetic di-galloyl glucosides and Amphotericin B (Romani et al., 2005). Therefore, the extracts obtained by tissues of myrtle, as well as by tissues of above cited Mediterranean plants, could be utilized for phytotherapy exploitations in order to considerably increase
  • One interesting aspect of the invention is that related to the possibility to obtain plant tissues from selected genotypes of myrtle, propagated and cultivated through cultural models characterized by a low-environmental impact and with the possible control of harvesting time.
  • the present supply of leaves and berries obtained through harvest of spontaneous plants causes ecological damages determining the reduction of plant biodiversity of "Mediterranean maquis"), and represents a limit in view of the potential exploitation of myrtle leaves in a industrial scale.
  • the seasonal variation of plant productivity don't warrant a quality of plant raw material (leaves) suitable for industrial exploitation.
  • the possibility to use plant biomass for alternative utilization e.g.
  • Prototheca zopfii DBVPG 8830 mastitis milk Italy Table 2: Antimycotic spectrum of myrtle extracts determined by the ADWB. Ketoconazole and Amphotericin B have been used as control antibiotic.
  • Myrtle extracts Ketoconazole Amphotericin B (30 mg/ml) (100 ⁇ g/ml) (100 ⁇ g/ml)
  • Table 3 MICs of myrtle extracts. Amphotericin B has been used as control antibiotic.
  • Cryptococcus laurentii DBVPG 6265 4.4 2.0 Filobasidiella neoformans DBVPG 6010 3.2 1.5

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne la préparation d'extraits naturels de myrte, de ciste, d'arbousier, de lentisque et d'autres extraits d'espèces végétales méditerranéennes (à teneur standardisée en molécules polyphénoliques), isolés à la fois à partir de divers tissus végétaux et de sous-produits issus de la fabrication artisanale ou industrielle faisant intervenir les mêmes espèces. L'utilisation des extraits susmentionnés comme agents antifongiques repose sur leur action contre les levures et les micro-organismes de type levure d'intérêt biomédical.
PCT/IT2006/000743 2005-10-20 2006-10-17 Utilisation d'extraits de myrte et d'autres especes vegetales mediterraneennes, a teneur standardisee en molecules polyphenoliques, comme nouvel agent antifongique actif contre les levures et les micro-organismes de type levure d'interet biomedical WO2007046125A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP06810032A EP1945237A2 (fr) 2005-10-20 2006-10-17 Utilisation d'extraits de myrte et d'autres especes vegetales mediterraneennes, a teneur standardisee en molecules polyphenoliques, comme nouvel agent antifongique actif contre les levures et les micro-organismes de type levure d'interet biomedical

Applications Claiming Priority (2)

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IT000219A ITFI20050219A1 (it) 2005-10-20 2005-10-20 Uso di estratti di mirto e di altre piante di macchia mediterranea standardizzati in contenuto polifenolico quali agenti ad attivita' antimicotica nei confronti di lieviti e di microrganismi lievito-simili
ITFI2005A000219 2005-10-20

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WO2007046125A2 true WO2007046125A2 (fr) 2007-04-26
WO2007046125A3 WO2007046125A3 (fr) 2007-09-20

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3541949A1 (de) * 1985-11-27 1987-06-04 Chemolux Gmbh Verfahren zur verwertung der abfaelle von citrusfruechten
WO1997018823A1 (fr) * 1995-11-17 1997-05-29 Pierre Fabre Dermo-Cosmetique Association extrait de myrte et antifongiques
GR1003541B (el) * 1999-05-11 2001-03-07 Αντιμικροβιακη και αντιμυκητιακη δραση του εξαγομενου απο τα κλαδια, φυλλα και καρπο της μαστιχας χιου -pistacia lentiscus var chia-, μαστιχελαιου, για χρηση σε καλλυντικες, φαρμακευτικες και παραφαρμακευτικεσς εφαρμογες καθως και στην παραγωγη οδοντοτσι
WO2001015680A1 (fr) * 1999-09-01 2001-03-08 Van Beek Global/Ninkov L.L.C. Composition destinee au traitement d'infections chez des etres humains et des animaux
WO2001045650A2 (fr) * 1999-12-22 2001-06-28 Cognis France, S.A. Utilisation de residus de la fabrication du vin
GR1003832B (el) * 2001-04-30 2002-03-04 Γεωργιος Σοδης Χρηση του μαστιχελαιου και της φυσικης μαστιχας για την παραγωγη φαρμακευτικων, παραφαρμακευτικων και καλλυντικων προιοντων
WO2003080006A1 (fr) * 2002-03-22 2003-10-02 Gognis Deutschland Gmbh & Co. Kg Utilisation d'extraits d'olivier comme agent antipelliculaire
EP1352905A1 (fr) * 2000-12-22 2003-10-15 Consejo Superior De Investigaciones Cientificas Conjugues a base de flavanols et de cysteamine
EP1602704A1 (fr) * 2002-11-25 2005-12-07 Nichirei Corporation Antioxydant, preparation pour la peau a usage externe cosmetiques et produits alimentaires

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3541949A1 (de) * 1985-11-27 1987-06-04 Chemolux Gmbh Verfahren zur verwertung der abfaelle von citrusfruechten
WO1997018823A1 (fr) * 1995-11-17 1997-05-29 Pierre Fabre Dermo-Cosmetique Association extrait de myrte et antifongiques
GR1003541B (el) * 1999-05-11 2001-03-07 Αντιμικροβιακη και αντιμυκητιακη δραση του εξαγομενου απο τα κλαδια, φυλλα και καρπο της μαστιχας χιου -pistacia lentiscus var chia-, μαστιχελαιου, για χρηση σε καλλυντικες, φαρμακευτικες και παραφαρμακευτικεσς εφαρμογες καθως και στην παραγωγη οδοντοτσι
WO2001015680A1 (fr) * 1999-09-01 2001-03-08 Van Beek Global/Ninkov L.L.C. Composition destinee au traitement d'infections chez des etres humains et des animaux
WO2001045650A2 (fr) * 1999-12-22 2001-06-28 Cognis France, S.A. Utilisation de residus de la fabrication du vin
EP1352905A1 (fr) * 2000-12-22 2003-10-15 Consejo Superior De Investigaciones Cientificas Conjugues a base de flavanols et de cysteamine
GR1003832B (el) * 2001-04-30 2002-03-04 Γεωργιος Σοδης Χρηση του μαστιχελαιου και της φυσικης μαστιχας για την παραγωγη φαρμακευτικων, παραφαρμακευτικων και καλλυντικων προιοντων
WO2003080006A1 (fr) * 2002-03-22 2003-10-02 Gognis Deutschland Gmbh & Co. Kg Utilisation d'extraits d'olivier comme agent antipelliculaire
EP1602704A1 (fr) * 2002-11-25 2005-12-07 Nichirei Corporation Antioxydant, preparation pour la peau a usage externe cosmetiques et produits alimentaires

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; AN: PREV198478006596 E. DOMINGUEZ ET AL: "Effect of seed extract of Myrtus Communis on teh growth of Candida Utilis and Saccharomyces Cerevisiae" XP002424588 *
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; AN: PREV198987074168 S. C. GARG ET AL: "Antifungal activity of the essential oil of Myrtus-Communis-Var-Microphylla" XP002424587 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; AN: 1990:548855 G. A. EL HOSSARY ET AL: "Phytochemical study of the leaves of Myrtus communis L. grown in Egypt" XP002424589 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; AN: 2004:140578 A. ROMANI ET AL: "Evaluation of Antioxidant effect of different extracts of Myrtus communis L." XP002424590 cited in the application *

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Publication number Publication date
ITFI20050219A1 (it) 2007-04-21
EP1945237A2 (fr) 2008-07-23
WO2007046125A3 (fr) 2007-09-20

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