WO2008142619A1 - Utilisation de compositions à base de plantes dans la protection et l'amplification des composants de la matrice extracellulaire - Google Patents
Utilisation de compositions à base de plantes dans la protection et l'amplification des composants de la matrice extracellulaire Download PDFInfo
- Publication number
- WO2008142619A1 WO2008142619A1 PCT/IB2008/051915 IB2008051915W WO2008142619A1 WO 2008142619 A1 WO2008142619 A1 WO 2008142619A1 IB 2008051915 W IB2008051915 W IB 2008051915W WO 2008142619 A1 WO2008142619 A1 WO 2008142619A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- extract
- herbal
- centella asiatica
- extracellular matrix
- composition
- Prior art date
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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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to the use of herbal formulations containing either single herbal extracts or mixtures of different herbal extracts, for the protection and enhancement of extracellular matrix (ECM) components such as collagen and hyaluronic acid.
- ECM extracellular matrix
- the present invention is useful for the treatment of conditions that would benefit from increased production or strength of the extracellular matrix such as in degenerative conditions of the joints, skin, or mucosa, and wound healing, and for cosmetic applications.
- the ECM is composed of various types of glycoproteins, proteoglycans and polysaccharides.
- the ECM is crucial for supporting and anchoring cells and sequestering the growth factors that act upon them. Intercellular communication is therefore very much dependent upon an intact and healthy ECM.
- Collagens are among the most abundant glycoproteins in the ECM and confer strength and integrity to the connective tissue.
- Hyaluronic acid is a polysaccharide that forms a major constituent of the ECM of connective tissue. Hyaluronic acid is also found in large amounts in the synovial fluid of joints, and the vitreous humor of the eyes. Among its many functions it is known as a binding, lubricating, and protective agent. Degenerative conditions affecting the joints are a major cause of morbidity. Breakdown of the integrity of the synovial fluid and connective tissue elements in the joints are a major component of these conditions regardless of their etiology. Therapeutic agents that protect synovial fluid and connective tissue elements are therefore expected to be of benefit for the treatment of these conditions.
- the eyeball between the retina and the lens is bathed in a clear gelatinous substance known as the vitreous humor, of which collagen and hyaluronic acid are important components. Agents that enhance these factors would be of benefit for acute and chronic conditions affecting the integrity of the eye.
- a further purpose of the present invention is to provide a cosmetic composition containing certain herbal extracts as the cosmetically-active ingredients. Further objects and advantages of the present invention will become apparent as the description proceeds.
- compositions comprising an extract of Centella asiatica alone, an extract of Sambucus nigra alone, or a mixture of extracts of Sambucus nigra, Centella asiatica and Echinacea species are effective in the treatment of conditions characterized by degeneration of collagen and certain other extracellular matrix components such as hyaluronic acid.
- conditions include degenerative joint diseases such as those caused by arthritis (osteoarthritis or rheumatoid arthritis), ocular conditions such as keratoconjunctivitis, skin conditions such as age related changes such as wrinkles, and wound healing of all types .
- the present invention is thus primarily directed to a method for treating and/or preventing degeneration of collagen and/or other extracellular matrix components (in particular, hyaluronic acid) , wherein said method comprises administering a herbal composition comprising an extract of Centella asiatica and/or Sambucus nigra as the active component (s) to a mammalian subject in need of such treatment.
- the mammalian subject is a human subject.
- the composition used in the present invention may also comprise extracts of additional plants.
- additional plants may include any of the plants commonly used in herbal remedies.
- a preferred additional plant is a plant of the Echinacea genus.
- the method comprises the administration of a herbal composition comprising a mixture of extracts of plants selected from the group consisting of Sarnbucus nigra, Centella asiatica and one or more Echinacea species.
- the method involves the use of a composition containing the aforementioned three plant extracts, wherein said composition is the mixture of Sambucus nigra, Centella asiatica and Echinacea purpurea that is described in co-owned international patent application no. PCT/IL02/00402 (published as WO 02/094300), the disclosure of which is incorporated herein in its entirety.
- the method involves the administration of a composition containing Centella asiatica as the sole active ingredient.
- the method involves the administration of a composition containing Sambucus nigra as the sole active ingredient .
- the present invention is also directed to the use of a herbal composition comprising an extract of Centella asiatica and/or an extract of Sambucus nigra as the active component (s) in the preparation of a medicament and/or cosmetic agent for treating and/or preventing degeneration of collagen and/or other extracellular matrix components.
- a herbal composition comprising an extract of Centella asiatica and/or an extract of Sambucus nigra as the active component (s) in the preparation of a medicament and/or cosmetic agent for treating and/or preventing degeneration of collagen and/or other extracellular matrix components.
- the herbal composition, and the medical and cosmetic indications for the use of the medicament and/or cosmetic agent are as disclosed hereinabove (in relation to the method of treatment) and as described in more detail hereinbelow.
- the present invention further provides a composition suitable for cosmetic use comprising an extract of Centella asiatica and/or an extract of Sambucus nigra as the cosmetically-active component ( s ).
- said composition comprises a mixture of extracts of Centella asiatica, Sambucus nigra and an Echinacea species (such as Echinacea purpurea) .
- the present invention is also directed to topical dosage forms containing the above-disclosed cosmetic composition, wherein said dosage form is particularly suitable for delivering said composition to the dermal and sub-dermal tissues.
- Fig. 1 graphically depicts the strong dose-dependent inhibition of hyaluronidase activity displayed by the Centella extract
- Fig. 2 graphically depicts the synergy of action of Centella when added to Sambucus/Echinacea in a hyaluronidase inhibition model
- Fig. 3 graphically depicts the stimulatory effects on collagen synthesis in cultured fibroblasts upon the addition of three different herbal extracts/combinations;
- Fig. 4 graphically depicts the stimulatory effects of the various herbal extracts on IL-6 release from cultured fibroblasts .
- the present invention is primarily directed to the use of the herbal compositions described hereinabove in the preparation of medicaments for treating conditions characterized by degeneration of collagen and/or other extracellular matrix components.
- compositions comprising individual plant extracts or combinations thereof (as described above) may be administered to the subject being treated by any suitable route.
- the compositions are generally given by local or topical administration.
- suitable dosage forms for use in the presently disclosed method include (but are not limited to) liquids, gels, sprays, creams, ointments, pastes, lotions, solutions, and sustained release formulations.
- the compositions may also be formulated for administration by injection (via various routes including intradermal, subcutaneous, submucosal, intramuscular, intraarticular etc.).
- the compositions may be incorporated into transmucosal or transdermal delivery systems. Examples of suitable transmucosal delivery systems may be found in co- owned international patent applications PCT/IL02/00402 (published as WO 02/094300) and PCT/IL2003/00159 (published as WO 04/047813) .
- compositions of the present invention may also contain one or more excipients including, but not limited to zinc, zinc oxide, silicones, calcium silicate, aluminum hydroxide, polyethylene glycols, methacrylate polymers and co-polymers, povidone derivatives, carbomers, magnesium stearate, fats of animal or vegetable origin, oils, waxes gums, starch and cellulose or cellulose derivatives. Further details regarding the manufacture of suitable formulations and the excipients used therein may be found in "Remington's Pharmaceutical Sciences", Mack Publishing Co, Easton, Pa, USA (1980) .
- compositions of the present invention are based on mixtures of plant extracts.
- extract is used herein to include all of the many types of preparations containing some or all of the active ingredients found in the relevant plants.
- the extracts may be produced by cold extraction techniques using a variety of different extraction solvents including, but not limited to, water, fatty solvents (such as olive oil), and alcoholic solvents (e.g. 70 % ethanol).
- Cold extraction techniques are usefully applied to softer parts of the plant such as leaves and flowers, or in cases wherein the desired active components of the plant are heat labile.
- the aforementioned solvents may be used to produce extracts of the desired plants by a hot extraction technique, wherein said solvents are heated to a high temperature, the precise value of said temperature being dependent on the properties of the chosen solvent, and maintained at that temperature throughout the extraction process.
- Hot extraction techniques are more commonly applied to the harder, tougher parts of the plant, such as bark, woody branches and larger roots. In some cases, sequential extractions need to be performed in more than one solvent, and at different temperatures.
- compositions may be prepared using single extracts of either Sambucus nigra or Centella asiatica, or using a mixture of extracts of different plant species. In the latter case, the composition may be prepared using different ratios of each extract.
- the aforementioned three-herb composition may comprise extracts of Centella asiatica, Echinacea purpurea and Sambucus nigra in the following range of percentage (weight/weight) ratios:
- these extracts are present in the percentage composition ratio of 20% : 10%: 70%
- a therapeutically-effective amount that is, in an amount that will provide a concentration of the herbal extracts at the treatment site that is capable of exerting the desired therapeutic effect.
- the compositions of the present invention need to be administered in amounts such that, typically, each topical dose contains between 0.1 mg and 10 mg (dry weight) of each herbal extract, the precise values depending on the particular combination of extracts used, and on the mode of topical delivery.
- the weights of the original plant material used to prepare a composition suitable for incorporation in a controlled-release delivery device are:
- Centella asiatica 1.6 mg Echinacea purpurea 1.6 mg Sambucus nigra 7.56 mg
- compositions intended primarily for topical use e.g. on the skin for cosmetic use, to promote acclerated wound healing or - when placed above a joint - to treat degenerative joint disease
- a controlled-release device such as hydrogel, dermal patches, sprays, creams or ointments
- said device needs to remain in contact with the lesion (e.g. skin lesion) to be treated for a period of between 30 minutes and 5 hours. This treatment may be repeated up to 5 times each day, as required, and as determined by a competent clinician.
- Hydrogels containing the compositions of the present invention should be taken in quantities of between 0.1 g and 15 g and allowed to remain in contact with the lesions to be treated for periods of between 1 minute and five hours. This treatment regime may be repeated up to 5 times per day.
- Dermal patches, creams, ointments and other solid, soluble formulations are to be placed, if possible on the lesion or in close proximity to the lesions to be treated, and allowed to dissolve at the natural rate determined by the additives present in said formulations.
- the three-herb mixture mentioned hereinabove and used in the experimental investigations reported hereinbelow was prepared from a mixture of extracts of Centella asiatica, Echinacea purpurea and Sarnbucus nigra.
- This composition was prepared by mixing 6 ml of a 1:4 hydroalcoholic extract of Centella asiatica with 1.5 ml of a 1:1 hydroalcoholic extract of Echinacea purpurea and 35 ml of a 1:5 hydroalcoholic extract of Sambucus nigra.
- the weight ratio of C. asiatica : E. purpurea : S. nigra in this mixture is 15:15:70.
- hydroalcoholic extracts of Centella asiatica and Echinacea purpurea were purchased from Herbal Apothecary, Syston, Leicester, U.K. or from Pentapharm, Basil, Switzerland, while the hydroalcoholic extract of Sambucus nigra was purchased from Analit Extracts Ltd., M. P. Hefer 38100, Israel, or from Pentapharm, Basil, Switzerland. It is be noted that the abovementioned extract values of the form l:x indicate that 1 g of the plant material was dissolved in x liters of solvent.
- hydroalcoholic extract indicates that the plant material was extracted using ethanol at concentrations of between 25% and 50% in water.
- Hyaluronic acid (also known as Hyaluronan) is a chief component of the extracellular matrix of connective tissue and epithelial and neural tissue. Hyaluronan is also a cell signaling molecule and has been strongly implicated in the healing of tissue.
- Centella asiatica extract possesses the ability to significantly inhibit the enzymatic degradation of hyaluronic acid by hyaluronidase. To measure the inhibition plastic wells were coated with human hyaluronic acid, the unbound sites on the wells blocked and the wells were then exposed to purified hyaluronidase in the absence or presence of various herbal extracts.
- Centella displays a strong dose dependent inhibition of hyaluronidase activity whereas Sambucus nigra, Echinacea purpurea, and Marshmallow root inhibit only weakly.
- Collagen production of confluent fibroblast monolayers was assessed by Sirius Red staining.
- the method is based on the interactions of anionic dye of Sirius Red with the side chain groups of the basic amino acids present in collagen molecule.
- Fibroblasts were seeded in 24-well tissue culture plates in ImI of supplemented DMEM/10% FCS until confluence. Herbal extracts in ImI of DMEM, containing 0.1% BSA were added, and the cultures were incubated for 24 hr . The cell layers were extensively washed with PBS and fixed with ImI Bouin's fluid for lhr . The fluid was removed by suction and culture plates were washed in running tap water for 15 min . Then staining was done by addition of ImI of Sirius Red dye reagent for lhr under mild shaking on a micro plate shaker.
- Sambucus nigra alone, and by a composition containing Sambucus nigra, Centella asiatica and Echinacea purpurea
- Gingival primary fibroblasts (passage 7) were seeded in 96- microwell tissue plates at a density of 10 4 cell/well in 200 ⁇ l of DMEM growth medium, containing 2mM-glutamine, 100 u/ml penicillin, lOO ⁇ g/ml streptomycin, (supplemented DMEM) and 10% heat-inactivated fetal calf serum (FCS).
- Cells were cultured at 37°C in a humidified atmosphere of 5% CO 2 overnight. Then the cells were stimulated with IL-l ⁇ (5pg/ml) with or without the addition of herbal extracts at lmg/ml in DMEM supplemented with 0.1 % BSA. Cells were incubated for an additional 24 hours.
- IL-I induced release of IL-6 was determined using a quantitative ELISA assay to measure IL-6.
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Abstract
La présente invention a pour objet un procédé de traitement et/ou de prévention de la dégénérescence du collagène et/ou d'autres composants de la matrice extracellulaire chez un sujet mammalien, où ledit procédé comprend l'administration au dit sujet d'une composition à base de plantes renfermant un extrait de Centella asiatica et/ou un extrait de Sambucus nigra en tant que composé(s) actif(s).
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US93846207P | 2007-05-17 | 2007-05-17 | |
US60/938,462 | 2007-05-17 |
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WO2008142619A1 true WO2008142619A1 (fr) | 2008-11-27 |
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PCT/IB2008/051915 WO2008142619A1 (fr) | 2007-05-17 | 2008-05-15 | Utilisation de compositions à base de plantes dans la protection et l'amplification des composants de la matrice extracellulaire |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITMI20090240A1 (it) * | 2009-02-20 | 2010-08-21 | O T I S R L Officine Terapie Inno Vative | Composizione comprendente esteri dell'acido caffeico per l'inibizione dell'enzima ialuronidasi umana |
EP2345405A1 (fr) * | 2005-10-28 | 2011-07-20 | BASF Beauty Care Solutions France SAS | Substance pour restaurer une co-expression et une interaction normales entre les protéines LOX et NRAGE |
TWI498118B (zh) * | 2012-04-27 | 2015-09-01 | Ind Tech Res Inst | 促進傷口癒合及血管新生的醫藥組合物與接骨木屬(蒴藋屬)(Sambucus)植物及菘藍屬(Isatis)植物之萃取物用於製備促進傷口癒合及血管新生之藥物的用途 |
WO2020089920A1 (fr) * | 2018-11-04 | 2020-05-07 | Izun Pharmaceuticals Corp. | Traitement de plaie par hydrogel |
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GB400302A (en) * | 1932-05-04 | 1933-10-26 | Frederick Charles Tidbury | Improvements relating to herbal preparations, more particularly applicable as an external remedy for rheumatic ailments and arthritis |
JPH11147832A (ja) * | 1997-11-18 | 1999-06-02 | Noevir Co Ltd | 好中球エラスターゼ阻害剤 |
WO2001019365A1 (fr) * | 1999-09-15 | 2001-03-22 | Roche Consumer Health Ag | Compositions pharmaceutiques et/ou cosmetiques |
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EP1602364A1 (fr) * | 2004-05-25 | 2005-12-07 | Cognis IP Management GmbH | Microcapsules (XXX), comprenant des extraits végétaux et procédé pour leur préparation |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2345405A1 (fr) * | 2005-10-28 | 2011-07-20 | BASF Beauty Care Solutions France SAS | Substance pour restaurer une co-expression et une interaction normales entre les protéines LOX et NRAGE |
ITMI20090240A1 (it) * | 2009-02-20 | 2010-08-21 | O T I S R L Officine Terapie Inno Vative | Composizione comprendente esteri dell'acido caffeico per l'inibizione dell'enzima ialuronidasi umana |
TWI498118B (zh) * | 2012-04-27 | 2015-09-01 | Ind Tech Res Inst | 促進傷口癒合及血管新生的醫藥組合物與接骨木屬(蒴藋屬)(Sambucus)植物及菘藍屬(Isatis)植物之萃取物用於製備促進傷口癒合及血管新生之藥物的用途 |
WO2020089920A1 (fr) * | 2018-11-04 | 2020-05-07 | Izun Pharmaceuticals Corp. | Traitement de plaie par hydrogel |
CN113271987A (zh) * | 2018-11-04 | 2021-08-17 | 伊祖恩制药公司 | 水凝胶伤口治疗 |
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