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WO2002013840A1 - Huiles essentielles et especes chimiquement associees utilisees dans le traitement des maladies associees a l'augmentation de la resorption osseuse - Google Patents

Huiles essentielles et especes chimiquement associees utilisees dans le traitement des maladies associees a l'augmentation de la resorption osseuse Download PDF

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Publication number
WO2002013840A1
WO2002013840A1 PCT/CH2001/000395 CH0100395W WO0213840A1 WO 2002013840 A1 WO2002013840 A1 WO 2002013840A1 CH 0100395 W CH0100395 W CH 0100395W WO 0213840 A1 WO0213840 A1 WO 0213840A1
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Prior art keywords
monoterpene
essential oil
metabolite
chemically related
derived
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PCT/CH2001/000395
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English (en)
Inventor
Roman MÜHLBAUER
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University Of Bern
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Priority to AU2001273759A priority Critical patent/AU2001273759A1/en
Publication of WO2002013840A1 publication Critical patent/WO2002013840A1/fr

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    • 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
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease

Definitions

  • IPC International Patent Classification
  • the present invention relates to the use of cosmetical, nutritional or pharmaceutical compositions comprising essential oils extracted from plants, monoterpenes de- rived thereof, their metabolites and/or chemically related species that are useful in the treatment or prevention of diseases or conditions characterized by increased bone resorption, such as Paget's disease, tumor-induced bone disease or particularly osteoporosis.
  • Said compositions are particularly beneficial for mammals, i.e. humans and companion animals.
  • the invention further comprises a method for the preparation of said compositions.
  • Osteoporotic fractures besides causing suffering to the patient, are a major burden to health care as the direct expenditure for osteoporosis and associated fractures is around US$ 14 billion/year in the 'USA and exceeds US$ 10 billion/year .in Europe; novel strategies to prevent osteoporosis are therefore required.
  • This most common bone disorder can be generally defined as the reduction in the quantity of bone, either from the reduction in bone formation or the acceleration of bone resorption, in either event the result is a de- crease in the amount of skeletal tissue.
  • Osteoclasts bone resorbing cells
  • Osteoclasts are responsible for the excavation of a portion of bone during the resorption process. After resorption, osteoblasts (bone forming cells) appear, which then refill the resorbed portion with new bone.
  • estrogens, bisphosphonates and calcitonin are known as inhibitors of bone resorption.
  • One ac- cepted method for the treatment of postmenopausal osteoporosis is estrogen replacement therapy. Although therapy is generally successful, patient compliance with the therapy is low, primarily because estrogen treatment may produce undesirable side effects.
  • An ad- ditional method of treatment is the administration of a bisphosphonate compound, such as, for example, Fosamax® (Merck & Co. , Inc. ) .
  • Pine-oil baths are recommended to elderly people to reduce the back pain due to osteoporosis. Furthermore, the consumption of tea infusions made from dried leaves of sage is recommended to post-menopausal women suffering from hot flushes, as monoterpenes from sage are known to inhibit sweat production. Both procedures are recommended to alleviate the symptoms but not to treat the cause (R. Gladstar; Natural Health; 46-50 (1992) .
  • Yamaguchi et al. (Biosci. Biotechnol. Biochem., 63 (4), 731-735, 1999) isolated and characterized a single monoterpene and have been able to show that oral administration of said monoterpene "significantly suppressed the decrease in bone weight caused by ovariec- tomized mice". However, they have not been able to show the mechanism behind this suppressive effect caused by said monoterpene.
  • essential oils extracted from plants and their components are potent inhibitors of bone resorption, i.e. that the use of essential oils and monoterpenes inhibit the functionality of osteoclasts and/or influence the number of osteoclasts present, for osteoclasts are known to be responsible for the excavation of bone material during the resorption process.
  • the main aspect of the present invention is the use of essential oils extracted from plants and monoterpenes derived thereof, having an inhibitory effect on bone resorption and the use of said compounds at least in the preparation of a pharmaceutical, cos- metical or nutritional composition for the prophylaxis or treatment of a disease or condition characterized by increased bone resorption, such as Paget ' s disease, tumor-induced bone disease or particularly osteoporosis.
  • a disease or condition characterized by increased bone resorption such as Paget ' s disease, tumor-induced bone disease or particularly osteoporosis.
  • the invention further provides a method for the treatment or prophylaxis of a disease or condition which is characterized by increased bone resorption, such as Paget' s disease, tumor-induced bone disease or particularly osteoporosis, comprising the administration of a medicament or nutritional or cosmetical formulation to a human or other mammal, said medicament or nutritional formulation or cosmetics comprising essential oils extracted from plants and/or monoterpenes derived thereof, in an amount, which is effective for inhibiting bone resorption.
  • a disease or condition which is characterized by increased bone resorption, such as Paget' s disease, tumor-induced bone disease or particularly osteoporosis
  • the present invention also foresees the use of essential oils extracted from plants and monoterpenes de- rived thereof, having an inhibitory effect on bone resorption and the use of said compounds in the preparation of a pharmaceutical, cosmetical or nutritional composition for the treatment or prophylaxis of a dis- ease or condition characterized by increased bone resorption, such as Paget ' s disease, tumor-induced bone disease or particularly osteoporosis.
  • Osteoporosis as used herein includes osteoporosis in- prised by hormone deficiency (e.g. postmenopausal) and old age, as well as secondary Osteoporosis such as osteoporosis secondary to steroid treatment or secondary to malnutrition caused by anorexia nervosa.
  • hormone deficiency e.g. postmenopausal
  • secondary Osteoporosis such as osteoporosis secondary to steroid treatment or secondary to malnutrition caused by anorexia nervosa.
  • essential oil volatile oils are meant that occur in plants and in general give the plants their characteristic odors and flavors.
  • Essential oils are complex mixtures of organic compounds.
  • Essential oils may be derived from plants with the following processes:
  • o harvesting resin from plants, essential oils and oleoresins are then separated, o by mechanical pressure; in this method, the plant or different parts of a plant are pressed to push out the essential oil.
  • Hydro distillation also known as water distillation, is a process in which water and plant material are boiled together in a common tub.
  • Steam distillation uses dry steam to vaporize and extract the oil. Steam distillation is used by commercial ventures seeking to process large quantities of essential oils economically.
  • Solvent extraction uses organic solvents to extract both essential oils and oleoresins, which are then separated.
  • o Supercritical extraction is another form of solvent extraction in which carbon dioxide is used under extremely high pressure to extract both essential oils and oleoresins.
  • Essential oils can be extracted from different parts of a plant, such as leaves and tops, leaves and twigs, leaves and young branches, needles, flowers, flowering tops, flowering herbs, fruits, unripe fruits, dried ripe fruits, seeds, berries, root, rhizome, bulb, rind, wood, peel or entire plant.
  • a preferred group of essential oils can be harvested from plants from members of the following botanical families: Araceae, Aristolochiaceae, Bureraceae, Che- nopodiaceae, Compositae, Euphorbiaceae, Geraniaceae, Gramineae, Labiateae, Lauraceae, Magnoliaceae, Myristi- caceae, Myrtaceae, Pinaceae, Piperaceae, Rosaceae, Ru- taceae, Umbelliferae, Valerianaceae, Zingiberaceae.
  • the active ingredient which is an essential oil extracted from a plant such as cited in the following list ciclicaA" (Latin name in brackets), called oil of: Angelica (Angelica officinalis Moench.), Anise (Pimpi- nella anisum L., or Illicium verum Hook. Fil.), Anise- Japanese (Illicium anisatum L.), Asaru (Asaru cana- dense L.), Balm (Melissa officinalis L.), Basil (Ocimum basilicum L.), Bay (Pimenta (Myrcia) acris Kostel.), Bergamot (Citrus aurantium L., var. bergamia Wight &
  • Camphor Cinnamomum camphora T.
  • Nees & Eberm. ) Caraway (Carum carvi L.), Cardamom (Elettaria cardamomum Maton), Cascarilla (Croton elute- ria (L.) Sw. ) , Cedar Leaf (Thuja occidentalis L.), Cedar Wood (Juniperus virginiana L.), Celery (Apium gra- veolens L.), Chenopodium (Chenopodium ambrosioides L. var.
  • Geranium Pelargonium odora- tissimum Ait. and the like
  • Geranium-East Indian An- dropogon schoenanthus L. and the like
  • Ginger Zingi- ber officinale Roscoe
  • Hyssop Hyssopus officinalis L.
  • Juniper Juniper
  • Lavender Lavandu- la officinalis Chaix (L. vera DC.)
  • Lemon Ciitrus li- onium (L.) Risso (C. medica var.
  • Suitable methods of obtaining or chemically synthesi- zing monoterpenes are known in the art. Suitable monoterpenes are isolated from their natural sources by distillation of the plant matter with steam. They are volatile oils, less dense than water, and have normal boiling points in the range 150°-185° C (300°-365° F) . Purification is usually achieved by fractional distillation at reduced pressures or by regeneration from a crystalline derivative.
  • acyclic monoterpenes such as ocimen, myrcen, citronel- lal, linalool, geraniol, nerol, citronellol
  • monocyclic monoterpene such as ⁇ -Terpinen, Limonene, ⁇ -Phellandrene, ⁇ -Phellandrene, p-Cymene (p-Cymol)
  • Menthol, ⁇ -Terpineol, Terpinen-4-ol Carveol, Thymol, Carvacrol, Menthone, Piperitone, Piperitenone, Pule- gone, Carvone, Menthofurane, Cuminal, Safranal, 1,8- Cineol (Eukalyptole) , Ascaridol
  • bicyclic monoterpenes such as Sabinen, ⁇ -Thujen, Santen, ⁇ -Pinen
  • the amount of essential oil and/or monoterpenes to be supplied may vary within wide ranges, depending on the 10
  • Suitable nutritional compositions comprising the above mentioned essential oils or monoterpenes or a combination thereof represent a further object of the invention. They are characterized in that they comprise
  • the nutritional formulations of the invention may comprise nutritionally acceptable components such as vitamins, minerals, trace elements, fibers, flavors, pre- servatives, colorants, sweeteners, emulsifiers and the like.
  • the inventive nutritional formulations may be formulated and administered in any form suitable for enteral administration, for example oral administration or tube feeding.
  • the inventive nutritional compositions may be in form of a complete formula diet, such that, when used as sole nutrition source essentially all daily caloric nitrogen, fatty acids, vitamin, mineral and trace element requirements are met.
  • compositions as used herein comprises i.a:
  • Semi-luxuries including but not limited to baked products, biscuits and cakes, candies, cereal and/or fruit bars, chewing gums, chocolate compositions, confectionery products, dairy and dairy substitute foods, desserts, savoury snacks, yogurts and the like.
  • Food products which are likely to be classified as “functional foods” or “novel foods”, i.e. foods that are similar in appearance to conventional foods and are intended to be consumed as part of a normal diet or a supplement, but have been modified to physiological roles beyond the provision of simple nutrient require- ments.
  • the term "food products” is intended to cover the whole variety of foods and beverages, including but 12
  • yogurts ice creams, cheeses
  • baked products such as fresh or frozen bread, crisp bread sandwiches, biscuits and cakes, dairy and dairy substitute foods, desserts, confectionery products, edible oil compositions, spreads, cereal and/or fruit bars, breakfast cereals, savoury snacks, juices, soups, sauces and the like.
  • Dietary foods for special medical purposes which means a category of foods for particular nutritional uses, specially processed or formulated and intended for the dietary management of patients and to be used under medical supervision which are intended for exclusive or partial feeding of patients with a limited, impaired or disturbed capacity to take, digest, absorb, metabolize or excrete ordinary foodstuffs or certain nutrition requirements, whose dietary management cannot be achieved only by modification of the normal diet, by other foods for particular nutritional uses or by a combination of the two.
  • These foods are either nutritionally complete foods with a nutrient-adapted formulation specific for a disease, disorder or medical condition which, used in accordance with the manufacturer's instructions, may constitute the sole source of nourishment for the persons for whom they are intended, or they may be nutritionally incomplete foods with a nutrient-adapted formulation for a disease, disorder or medical condition which are not suitable to be used as the sole source of nourishment and are thus used as partial replacement or as a supplement to the patient's diet. 13
  • One mandatory active ingredient of a), b) and c) is an essential oil extracted from a plant and/or a monoterpene derived thereof or mixtures thereof.
  • Suitable nutritional compositions may be in liquid form or in solid form and comprise (in % by weight) for example, from approximately 0.01 % to 50 %, preferably from approximately 0.1 to approximately 25 %.
  • the invention further relates to pharmaceutical compositions in single dose unit form comprising
  • compositions as used herein comprises i.a. compositions for enteral administration, such as oral, nasal or rectal administration.
  • Suitable pharmaceutical compositions may be in liquid form or preferentially in solid form and comprise (in % by weight) for example, from approximately 0.001 % to 100 %, preferably from approximately 0.1 to approximately 50 % active ingredient.
  • the active ingredient is an essential oil extracted from a plant and/or a monoterpene derived thereof or mixtures thereof. It is also possible to have a mixture of two or more of said essential oils and monoterpenes.
  • compositions for enteral administration are, for example, those in single dose forms, such as dragees, tablets, capsules or sachets. They are prepared in a manner known per se, for example by means of conventional mixing (with suitable carriers), granulating, confectioning, dissolving or lyophilising proc- esses. 15
  • compositions comprise the active ingredients (that is an essential oil extracted from a plant and/or monoterpene derived thereof or mixtures thereof) together with one or more pharmaceutically acceptable carriers and optionally other therapeutic and/or prophylactic ingredients.
  • the carrier (s) must be acceptable in the sense of being compatible with the other ingredients of the formula and not deleterious to the recipient thereof.
  • compositions include those suitable for oral, topical (including dermal, buccal and sublin- gual), rectal and parenteral (including subcutaneous, intradermal, intramuscular and intravenous) , admini- stration as well as administration by naso-gastric tube.
  • the formulation may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.
  • compositions suitable for oral administration wherein the carrier is a solid are most preferably presented as unit dose formulations such as boluses, capsules or tablets each containing a predetermined amount of the active ingredients.
  • a tablet may be made by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be 16
  • Capsules may be prepared by filling the active ingredients, either alone or in admixture with one or more accessory ingredients, into the capsule shells and then sealing them in the usual manner. Cachets are analogous to capsules wherein the active ingredients together with any accessory ingredient (s) are sealed in a rice paper envelope.
  • the active ingredients may also be formulated as dispersible granules, which may for example be suspended in water before administration, or sprinkled on food.
  • the granules may be packaged e.g. in a sachet.
  • Formulations suitable for oral administration wherein the carrier is a liquid may be presented as a solution or a suspension in an aqueous liquid or a non- aqueous liquid or as an oil-in-water liquid emulsion.
  • Formulations for oral administration include controlled release dosage forms e.g. tablets wherein the active ingredients are formulated in an appropriate release— controlling matrix, or are coated with a suitable release-controlling film. Such formulations may be par- ticularly convenient for prophylactic use. 17
  • the active ingredients may also be formulated as a solution or suspension suitable for administration via a naso-gastric tube.
  • compositions suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories.
  • Suitable carriers include cocoa butter and other materials commonly used in the art.
  • the suppositories may be conven- iently formed by admixture of the active combination with the softened or melted carrier (s) followed by chilling and shaping in moulds.
  • compositions suitable for parenteral ad- ministration include sterile solutions or suspensions of the active combination in aqueous or oleaginous vehicles.
  • injectible preparations may be adapted for bolus injection or continuous infusion. Such preparations are conveniently presented in unit dose or multi-dose containers, which are sealed after introduction of the formulation until required for use.
  • the active ingredients may be in powder form, which are constituted with a suitable vehicle, such as sterile, pyrogen-free water, before use.
  • the active ingredients may also be formulated as a long- acting depot preparation, which may be administered by intramuscular injection or by implantation e.g. subcu- taneously or intramuscularly.
  • Depot preparations may include, for example, suitable polymeric or hydrophobic materials, or ion-exchange resins. Such long-acting formulations are particularly convenient for prophylactic use.
  • the pharmaceutical formulations for the various routes of administration described above may include, as appropriate one or more additional carrier ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives (including anti- oxidants) and the like, and substances included for the purpose of rendering the formulation isotonic with the blood of the intended recipient.
  • additional carrier ingredients such as diluents, buffers, flavouring agents, binders, surface active agents, thickeners, lubricants, preservatives (including anti- oxidants) and the like, and substances included for the purpose of rendering the formulation isotonic with the blood of the intended recipient.
  • compositions suitable for veterinary use include those adapted for oral, parenteral, and intrarumenal administration.
  • compositions as used herein com- prises i.a. compositions for topical applications, that is, for applications of the active component through the skin.
  • Suitable cosmetical compositions may be in liquid form or in solid form and comprise (in % by weight) for example, from approximately 0.1 % to 100 %, preferably 19
  • the active ingredient is an essential oil extracted from a plant and/or a monoterpene derived thereof or mixtures thereof.
  • the invention further relates to cosmetical compositions in single dose unit form comprising
  • Cosmetical compositions for local topical administration are, for example, those in ointments, liniments or in liquid form. They are prepared in a manner known per 20
  • Suitable cosmetical compositions administrable through a large proportion of the body surface are, for example, bath products such as foam baths or therapeutic bath products that consist of a combination of the active ingredient with a base material prepared in a manner known per se.
  • the present invention relates to a process for preparing a cosmetical formulation containing an essential oil extracted from a plant and/or a monoterpene derived thereof or mixtures thereof, in the form of an ointment and its use.
  • Carrier materials may be aqueous solutions of alcohols, all types of emulsions, gels, foaming compositions and fatty carriers.
  • Use of one specific carrier selected from the group of the above mentioned substances allows formulation of various types of cosmetic preparations according to the invention, such as tonics, creams, balsams, cleaning milks etc. for daily body care as well as shampoos, hair balms, foaming bath compositi- ons, all with the addition of an essential oil extracted from a plant and/or a monoterpene derived thereof or mixtures thereof.
  • the above described nutritional, pharmaceutical and cosmetical composition are used for the treatment of mammals, i.e. humans and companion animals. 21
  • Figure lb Effect of bitter orange peel oil, DL-limonene, and trans-anethol on bone resorption. Applied dose: 100 mg/rat/day. For further details see description of Fig- ure la.
  • Bone resorption was assessed by the urinary excretion of [ 3 H]-Tetracycline from prelabeled rats, a model sen- sitive to inhibitors of bone resorption used clinically.
  • 3 H-labeled tetracycline [ 3 H]-Tc) is deposited in hard tissues during their formation. [ 3 H]-Tc is released when bone is resorbed, circulates in blood, is only poorly reutilized during bone turnover and is then excreted into urine where it can be assessed by counting the 3 H.
  • rats are injected subcutaneously from the first week of their life for 6 weeks with a solution containing 10 ⁇ Ci/ml of 7- [3H] (N) tetracycline (New England Nuclear, Boston, MA) dissolved in 0.15 M NaCl .
  • 7- [3H] (N) tetracycline New England Nuclear, Boston, MA
  • the rats are housed in individual metabolic cages.
  • 24-hour urine collections are started.
  • Dur- ing the first 10 days baseline bone resorption is assessed. Thereafter the rats are treated during 10 days.
  • 3 H in urine is determined by liquid scintillation counting. Aliquots of 1 ml urine are counted in 10 ml of Irga-Safe Plus TM scintillator (Packard International, Zurich, Switzerland) and the result (dpm) is multiplied by the urine volume.
  • the essential oil or monoterpene or combinations thereof of the invention are capable of considerably decreasing the cumulative 3 H-labeled tetracycline excretion in urine of rats which indicates a high inhibitory effect on bone resorption. Accordingly, the claimed nutritional, cosmetical and pharmaceutical compositions are useful for the treatment and prophylaxis of all kinds of diseases or conditions which are characterized by increased bone resorption, such as Paget' s disease, tumor-induced bone disease or particularly osteoporosis.
  • the inhibitory effect of the essential oil or monoterpene or combination thereof of the invention may also be assessed by an in vitro assay.
  • Osteoclasts are harvested from one day old rats, set- tied onto mammoth ivory as the mineral substrate and incubated for 24 hours at 37 C in a 5% CO ? /air atmosphere.
  • One 4x4 mm ivory slice is incubated per well of a 48-well plate in 250 ml of medium containing the onion extract. For each dose 8 slices are used.
  • the ef- feet of the- monoterpene borneol on osteoclast number and resorption pits is assessed by counting the number 25
  • Lanes 7, 8 and 25 of figure la show that low doses are effective when administered for 10 days, and, as shown on figure 2a, the curves of the 30 and 100 mg doses of pine oil appears to converge during the course of the administration of the modified diet, suggesting an accumulation of active components in some body compartment. Thus, when chronically used, lower doses may be effective.
  • Pine oil protects the animals from the loss of both trabecular BMD (by 70%) and total BMC (by 60%; Table 1).
  • the observed loss in total BMC is more than that which can be attributed to the trabecular bone compartment, as trabecular bone only contributes 8% to the bone mineral mass in the proximal metaphysis of rat 28
  • cis-verbenol inhibits osteoclast resorption activity, the parent compound ⁇ - pinene does, ' however, not. Therefore, the finding that the 3 main components of pine oil, ⁇ -pinene, ⁇ -pinene and bornylacetate, although effective in vivo, are ineffective in vitro, strongly suggests that they are me- tabolised to active compounds.
  • actin rings indicates polarisation of osteoclasts; in osteoclasts atta- ched to the bone surface, actin rings appear in the sealing zone surrounding the area to be resorbed (Lak- kakorpi, P.T. and Vanaanen , H.K., j. Bone Mineer. Res. 6, 817-826 (1991), Nakamura et al . , J. Bone Miner. Res. 11, 1873-1879 (1996); Suzuki, H. et al . , Endocrinology 137, 4686-4690 (1996). As shown in Fig. 3a, about 40 % of disaggregated osteoclasts attached to glass cover 30
  • Oil of cumin (oleum carvi, rect.), oil of eucalyptus (oleum eucalypti, >80% Ph. Eur.), oil of fennel (oleum foeniculi), oil of juniper berries (oleum juniperi e baccis, purum), bitter orange oil (oleum auratii ama- rum) , pine oil (oil of fir; oleum pini sibiricum) , dwarf-pine oil (oleum pini pumilionis) , oil of rosemary (oleum rosmarini, DAB) and sage oil (oleum salviae, Dalmation) were purchased from Carl Roth Inc., Reinach, Switzerland.
  • Sweet orange-peel oil (oleum auratii dulcis) was purchased from a local drugstore.
  • Thujone (mixture of » 60% ⁇ -isomere and «10% ⁇ - isomere) , eucalyptol (99%, purum), (+) -camphor (>99%), Borneol (>98%, mixture of isomers) , menthol (>98%, Chinese), (-) - ⁇ -pinene (>97%) and ⁇ -pinene, D,L-limonene (depur) were purchased from Carl Roth, Reinach, Switzerland, thymol (puriss.) from E. Merck, Darmstadt, Germany, (-) ⁇ -bornyl acetate (97%) and (S) -cis verbe- nol were purchased from Aldrich, Buchs, Switzerland.
  • the bisphosphonate clodronate (dichloromethylene)bis- phosphonate was administered by gavage 0.5 hours before food administration at the daily dose of 58.2 mg/kg body weight .
  • [ 3 H] -Tetracycline [ 3 H]- Tc) (Mtihlbauer, R.C. and Fleisch, H., Am. J. Physiol. 259, 679-689 (1990)).
  • [ 3 H]-Tc is deposited into bone and is released when bone is resorbed. After discon- tinuation of labelling, the rats were housed in metabolic cages and bone resorption was monitored by measuring the daily urinary [ 3 H] -excretion (Mtihlbauer, R.C. and Fleisch, H., Am. J. Physiol. 259, 679-689 (1990), Egger, CD. et al., J.Bone Miner. Res.
  • BMC and BMD was measured in the proximal metaphysis of the left tibia by quantitative computed tomography (XCT 34
  • a cross-section starting 5 mm distal to the joint space was evaluated, using a threshold for trabecular bone of 400 mg/cm 3 .
  • the peptide was measured in plasma using an immunoradi- ometric assay (IRMA) kit for rat osteocalcin (Immutop- ics, San Clemente, USA) .
  • IRMA immunoradi- ometric assay
  • Osteoclasts were isolated from femora and tibiae of 1-2 day old rats and settled for 40 minutes onto 4x4 mm ivory slices used as the mineral substrate. After washing off non-adherent cells they were incubated for 24 hours at 37°C in a 5% C0 2 /air atmosphere (Arnett, T.R. and Spowage M. Bone 18, 277-279 (1996); Jones, S.J. et al., Anat. Embryol. 170, 247-256 (1984)).

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Abstract

La présente invention concerne des compositions cosmétiques, nutritionnelles ou pharmaceutiques comprenant des huiles essentielles extraites de plantes et/ou de monoterpènes dérivés, leurs métabolites et les espèces chimiquement associées. Lesdites huiles essentielles et leurs monoterpènes sont utilisés dans le traitement ou la prévention de maladies ou d'états pathologiques caractérisés par l'augmentation de la résorption osseuse, par exemple la maladie de Paget, les maladies osseuses induites par une tumeur ou, en particulier, l'ostéoporose. L'invention concerne également une méthode de préparation desdites compositions ainsi que leurs utilisations.
PCT/CH2001/000395 2000-08-18 2001-06-26 Huiles essentielles et especes chimiquement associees utilisees dans le traitement des maladies associees a l'augmentation de la resorption osseuse WO2002013840A1 (fr)

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Cited By (6)

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WO2003053167A1 (fr) * 2001-12-11 2003-07-03 Societe Des Produits Nestle S.A. Composition destinee a favoriser la croissance osseuse et l'entretien de la sante osseuse
FR2869230A1 (fr) * 2004-04-23 2005-10-28 Alessio Patrizia D Composition pour prevenir ou traiter la degenerescence cellulaire en utilisant au moins une molecule capable de maintenir la reversibilite de l'expression des molecules d'adherence et la polymerisation des fibres d'actine
WO2012029148A1 (fr) 2010-09-01 2012-03-08 株式会社オステオファーマ Préparation cryodesséchée de protéine morphogénétique osseuse humaine recombinante 2
CN102688294A (zh) * 2012-06-13 2012-09-26 浙江农林大学 一种含红茴香的抗病毒外用软膏及其制备方法和用途
CN102935119A (zh) * 2012-11-21 2013-02-20 吉林鑫水科技开发有限公司 一种治疗腰椎间盘突出膏剂的制备方法
CN108601806A (zh) * 2016-01-27 2018-09-28 西贝柳斯有限公司 具有延长时序寿命活性的药用鼠尾草的植物组合物及使用方法

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WO1998050054A1 (fr) * 1997-05-06 1998-11-12 Muehlbauer Roman Conrad Extraits de plantes pour le traitement de l'augmentation de la resorption osseuse
WO2000020015A1 (fr) * 1998-10-05 2000-04-13 Muehlbauer Roman Conrad Extraits vegetaux utilises pour traiter une resorption osseuse accentuee
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Cited By (13)

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EP2263480A1 (fr) * 2001-12-11 2010-12-22 Société des Produits Nestlé S.A. Composition pour la promotion de la croissance des os et le maintien de la santé des os, comprenant de la menthe ou des extraits de Mentha
EP1325681A1 (fr) * 2001-12-11 2003-07-09 Société des Produits Nestlé S.A. Composition pour la promotion de la croissance osseuse et la conservation de la santé osseuse
EP2272382A1 (fr) * 2001-12-11 2011-01-12 Société des Produits Nestlé S.A. Composition pour la promotion de la croissance des os et le maintien de la santé des os, comprenant des fèves de soja ou des extraits de fève de soja
WO2003053167A1 (fr) * 2001-12-11 2003-07-03 Societe Des Produits Nestle S.A. Composition destinee a favoriser la croissance osseuse et l'entretien de la sante osseuse
AU2002366734B2 (en) * 2001-12-11 2008-12-11 Societe Des Produits Nestle S.A. Composition for promotion of bone growth and maintenance of bone health
WO2005105074A3 (fr) * 2004-04-23 2006-01-12 Alessio Patrizia D Composition pour prevenir ou traiter la degenerescence cellulaire en utilisant au moins une molecule capable de mantenir la reversibilite de l’expression des molecules d’adherence et la polymerisation des fibres d’actine de l’endothelium vasculaire
FR2869230A1 (fr) * 2004-04-23 2005-10-28 Alessio Patrizia D Composition pour prevenir ou traiter la degenerescence cellulaire en utilisant au moins une molecule capable de maintenir la reversibilite de l'expression des molecules d'adherence et la polymerisation des fibres d'actine
US8912230B2 (en) 2004-04-23 2014-12-16 Aisa Therapeutics Method for treating cell degeneration using at least one molecule capable of inhibiting adhesion molecule expression and vascular endothelium actin fibre polymerization
WO2012029148A1 (fr) 2010-09-01 2012-03-08 株式会社オステオファーマ Préparation cryodesséchée de protéine morphogénétique osseuse humaine recombinante 2
CN102688294A (zh) * 2012-06-13 2012-09-26 浙江农林大学 一种含红茴香的抗病毒外用软膏及其制备方法和用途
CN102935119A (zh) * 2012-11-21 2013-02-20 吉林鑫水科技开发有限公司 一种治疗腰椎间盘突出膏剂的制备方法
CN108601806A (zh) * 2016-01-27 2018-09-28 西贝柳斯有限公司 具有延长时序寿命活性的药用鼠尾草的植物组合物及使用方法
EP3407904B1 (fr) * 2016-01-27 2021-08-25 Sibelius Limited Compositions botaniques de salvia officinalis à activité prolongeant la durée de vie chronologique et leur utilisation

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