US20030086949A1 - Method for testing a substance which is potentially active in the field of lipolysis and its mainly cosmetic use - Google Patents

Method for testing a substance which is potentially active in the field of lipolysis and its mainly cosmetic use Download PDF

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US20030086949A1
US20030086949A1 US09/888,824 US88882401A US2003086949A1 US 20030086949 A1 US20030086949 A1 US 20030086949A1 US 88882401 A US88882401 A US 88882401A US 2003086949 A1 US2003086949 A1 US 2003086949A1
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extract
substance
activity
lipoprotein lipase
composition
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Eric Perrier
Delphine Rival
Valerie Lamy
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BASF Beauty Care Solutions France SAS
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Coletica SA
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Assigned to BASF BEAUTY CARE SOLUTIONS FRANCE SAS reassignment BASF BEAUTY CARE SOLUTIONS FRANCE SAS CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: ENGELHARD LYON
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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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
    • 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
    • A61K36/02—Algae
    • A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus
    • 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
    • A61K36/02—Algae
    • A61K36/04—Rhodophycota or rhodophyta (red algae), e.g. Porphyra
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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)
    • A61K36/355—Lonicera (honeysuckle)
    • 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)
    • A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • 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)
    • A61K36/42—Cucurbitaceae (Cucumber family)
    • 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)
    • A61K36/74—Rubiaceae (Madder family)
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/44—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving esterase
    • 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
    • A61Q19/06—Preparations for care of the skin for countering cellulitis

Definitions

  • the invention relates to a method of testing a substance which is potentially active in the field of lipolysis and its mainly cosmetic use.
  • the present invention essentially relates to a method of testing a substance which is potentially active in the field of lipolysis, the substances which are active in the field of lipolysis thus detected, and their use in the cosmetic or pharmaceutical field, especially for providing slimming care, for increasing the blood microcirculation, for improving the appearance of the skin and especially for diminishing ⁇ orange peel>> appearance.
  • Veinotonic active products have an action on the skin blood microcirculation. They have been used for a long time in the treatment of heavy legs and of oedemas or even for increasing capillary resistance and for participating in anti-inflammatory reactions.
  • the veinotonic products thus constitute the active products of choice 1) for increasing the blood microcirculation and 2) for improving the appearance of the skin (diminishing ⁇ orange peel>> appearance).
  • the key enzyme of lipolysis is hormono-sensitive lipase (HSL) which is an intracellular enzyme of the adipocytes.
  • HSL hormono-sensitive lipase
  • This lipase enables the destocking of adipocyte triglycerides by hydrolysis (by the HSLs) and degradation of the amino acids formed (by the cell).
  • the lipolytic cosmetic active products thus seek to activate this enzyme with the aid of cofactors, or to prevent its inhibition.
  • HSL exists in two forms: the active form corresponds to the phosphorylation of the inactive form, the phosphorylation is effected by an enzyme, protein kinase (PKA) which is c-AMP-dependent, i.e. which needs cAMP in order to be active itself.
  • PKA protein kinase
  • the lipolytic cosmetic active products thus seek to activate this enzyme by attempting to have more cAMP produced in the cell, or in seeking to prevent the degradation of this cAMP.
  • cAMP is formed in the cell by virtue of a membrane enzyme, adenyl cyclase, which can be activated by stimulatory G-proteins (Gs) which are sensitive to beta-3 adrenergic receptors, or which can be inhibited by inhibitory G-proteins (Gi) which are sensitive to alpha-2 adrenergic receptors.
  • Gs stimulatory G-proteins
  • Gi inhibitory G-proteins
  • a certain number of cosmetic active products have been developed so as to be able to interact with one or another of these receptors, so as to stimulate the adenyl cyclase and so as to increase the level of intracellular cAMP.
  • cAMP can also be hydrolyzed in the cell by virtue of an intracellular enzyme, phosphodiesterase (PDE) and other cosmetic active products have been developed so as to be able to inhibit this enzyme and so as to conserve a raised intracellular cAMP level.
  • PDE phosphodiesterase
  • the aim of the present invention is to provide a novel method of testing a substance which is potentially active in the field of lipolysis, which is safe and reliable and which enables the degree of lipolytic activity of a substance, and thus its capacity to act upon lipolysis, to be determined, to thus enable fatty deposits to be diminished, to be slowed down or to be reabsorbed, to enable having a slimming activity, to enable increasing the blood microcirculation, to enable improving the appearance of the skin and in particular to enable diminishing the particularly ugly ⁇ orange peel>> appearance.
  • Another main aim of the present invention is to solve the novel technical problem consisting of providing a test method which is capable of finding substances which are active in the field of lipolysis, by a test method which has the lowest number of steps as possible, which is not expensive, which can be used on an industrial scale, especially in research laboratories, preferably automatically, and which thus enables the skill of the person carrying out the test to be freed as much as possible.
  • Yet another main aim of the present invention is to solve the novel technical problem consisting of providing a test method which enables finding novel substances which are active in the field of lipolysis, which has a great efficiency and which can be used for the preparation of novel cosmetic compositions, or even pharmaceutical compositions, which make use of such a lipolytic activity, especially within the context of an activity of diminishing, slowing down or reabsorption of fatty deposits, or of a slimming activity, or for improving the tone of the skin.
  • the present invention enables the whole of the aims set forth above to be met in a particularly unexpected manner, which was not obvious to the person skilled in the art.
  • the present invention provides a novel method of testing a substance which is potentially active in the field of lipolysis, which is based upon the capacity of inhibition of the enzyme lipoprotein lipase by a substance which is potentially active in the field of lipolysis that it tested.
  • the enzyme lipoprotein lipase or LPL is an enzyme which is produced by the adipocytes and which is secreted by exocytosis towards the endothelial cells of the blood capillaries, and which has the capacity to hydrolyse the ester bonds in position 1 , 3 of the triacylglycerols borne by the chylomicrons and the very low density lipoproteins (VLDL) circulating in the lumen of the blood vessels as described by I. J.
  • the fatty acids transferred through the plasma membrane of the adipose cell will be 1o taken up by the internal biochemical systems of the adipocyte in order to be stored again in the form of triacylglycerols, as demonstrated by B. Féve in the article “L'adipocyte, une cellule Series active que I'on commence à reference driver”, published in Cosmetologie, N°21, 30-33 (1999).
  • the present invention is based on the novel concept which is firstly to provide a method of testing a substance which is potentially active in the field of lipolysis, preferably which is capable of acting upon the inhibition of the lipoprotein lipase, and secondly to make use of any substance having such an activity in the field of lipolysis, and in particular capable of inhibiting the activity of lipoprotein lipase, as a novel means of action for limiting the storage in the adipocyte.
  • the present invention provides a method of testing a substance which is potentially active in the field of lipolysis, characterized in that it comprises the following steps:
  • test method makes use of a determination of the fatty acids which are released from the acylated part or triacylated part of the triacylglycerol, or non-esterified fatty acids.
  • this method is characterized in that the lipoprotein lipase used originates from bovine milk or is of bacterial origin.
  • the method is characterized in that the triacylglycerol mentioned above comprises an acyl part which is obtained from a long chain fatty acid, preferably comprising 12 to 30 saturated or unsaturated carbon atoms in a straight or branched chain, more preferably mainly present in food.
  • the triacylglycerol comprises or is constituted of triolein.
  • the method is characterized in that the lipoprotein lipase is present with said cofactor which comprises or is constituted of apolipoprotein C-II, preferably of human origin.
  • the method is characterized in that the lipoprotein is placed in contact with the substrate in the presence of a fatty acid-acceptor substance or fatty acid-sequestering substance which prevents the blockage of the enzymatic activity of the lipoprotein lipase.
  • the fatty acid-acceptor substance or fatty acid-sequestering substance comprises or is constituted by bovine or human albumin.
  • the method is characterized in that the capacity of inhibition of the lipoprotein lipase by the potentially active substance is carried out in several steps:
  • the lipoprotein lipase is incubated for a determined period of time in the presence of the substance which is potentially active as inhibitor,
  • the substrate which contains the triacylglycerol is incubated in the presence of the lipoprotein lipase cofactor, which preferably comprises or is constituted by apolipoprotein C-II,
  • a comparison is made of the capacity of inhibition of the release of a fatty acid of the triacylglycerol, or non-esterified fatty acid, resulting from the activity of the lipoprotein lipase in the presence of the potentially active substance tested, compared with the result obtained in the absence of the potentially active substance tested, or compared with the result obtained in the presence of a known inhibitor acting as reference.
  • the determination of the non-esterified fatty acids is made upon the reaction medium by an enzymatic technique, preferably in order to be followed by colorimetry at a wavelength determined by the enzymatic technique selected, and in this case the lowering of the optical density obtained at this wavelength is determined with respect to the control or to the reference inhibitor.
  • the determination of the non-esterified fatty acids is made upon the reaction medium by an enzymatic technique which can be followed by colorimetry at 550 nm and an inhibition is determined of the optical density at 550 nm which expresses a decrease in the fatty acids synthesized in the reaction medium, which is compared with the control or with a reference inhibitor, and the positive or negative activity is determined of said substance tested within the context of the observation of a significant or non-significant inhibition effected by said substance tested with respect to the control or to a reference inhibitor.
  • the test is carried out of a substance which is potentially active in the field of lipolysis selected from the group consisting of an extract of fucus; an extract of dulse palmaria palmata; an extract of wheat proteins; an extract of spiruline; an extract of honeysuckle; an extract of St. John's wort; an extract of rice proteins; an extract of liana; an extract of potato; an extract of shiitake; an extract of fresh salmon; an extract of pumpkin; and an extract of lemon.
  • a substance which is potentially active in the field of lipolysis selected from the group consisting of an extract of fucus; an extract of dulse palmaria palmata; an extract of wheat proteins; an extract of spiruline; an extract of honeysuckle; an extract of St. John's wort; an extract of rice proteins; an extract of liana; an extract of potato; an extract of shiitake; an extract of fresh salmon; an extract of pumpkin; and an extract of lemon.
  • extracts are advantageously obtained by a solvent extraction procedure which preferably comprises an aqueous or water extraction, or an alcoholic extraction, or a hydro alcoholic extraction, or a hydro glycolic extraction, in particular with ethylene glycol, propylene glycol or butylene glycol, or any mixtures of these solvents.
  • a solvent extraction procedure which preferably comprises an aqueous or water extraction, or an alcoholic extraction, or a hydro alcoholic extraction, or a hydro glycolic extraction, in particular with ethylene glycol, propylene glycol or butylene glycol, or any mixtures of these solvents.
  • the above-mentioned test is carried out with an extract of St. John's wort.
  • the test is carried out with an extract of liana, preferably an extract of Peruvian liana, known as liana Uncaria tomentosa.
  • the method is characterized in that a substance is identified for its lipolytic activity, in particular its slimming activity, from the test of inhibition mentioned above.
  • the present invention also covers the use of the test method mentioned above for evaluating the activity of a substance which can be used in a cosmetic composition or for preparing a medicament with a view to treating fatty deposits, especially by lipolysis, or for a slimming activity, as well as for evaluating the effectiveness of a slimming care or treatment applied to a subject.
  • the present invention also covers any substance which is active in the field of lipolysis characterized in that its activity in the field of lipolysis has been evaluated by a test method as defined above or as resulting from the following description.
  • the present invention also covers the use of a substance the activity of which in the field of lipolysis has been evaluated by the test method described above or described in the following description, as one of the lipolytic active agents in a cosmetic composition for decreasing, slowing down or reabsorbing fatty deposits, for a slimming activity, or for increasing the blood microcirculation, for improving the appearance or the tone of the skin, in particular for diminishing ⁇ orange peel>> appearance.
  • the present invention even covers the use of a substance the activity of which in the field of lipolysis has been evaluated by the test method mentioned above or resulting from the following description, as one of the lipolytic active agents for preparing a medicament with a view to treating a pathology resulting from an excess of fatty deposits.
  • the invention further covers the use of an extract of liana Uncaria tomentosa as one of the principles having lipolytic or slimming activity in a cosmetic composition.
  • the invention further covers the use of an extract of St. John's wort as one of the active agents having lipolytic or slimming activity in a cosmetic composition.
  • the present invention further covers a cosmetic composition, characterized in that it comprises an effective amount of liana Uncaria tomentosa as one of the active agents having lipolytic or slimming activity in a cosmetically acceptable excipient.
  • the invention further covers a cosmetic composition, characterized in that it comprises an effective amount of an extract of St. John's wort as one of the agents having lipolytic or slimming activity.
  • the invention further covers a method of cosmetic care, characterized in that a cosmetic composition, comprising an active substance having lipolytic or slimming activity, the activity of which has been determined by the test method as defined above or as resulting from the following description taken as a whole, is applied topically on the skin.
  • the invention further covers a method of cosmetic care, characterized in that a cosmetic composition comprising an extract of liana Uncaria tomentosa as one of the active agents having lipolytic or slimming activity is applied topically on the skin.
  • the invention further covers a method of cosmetic care characterized in that a lo cosmetic composition comprising an extract of St. John's wort as one of the active agents having lipolytic or slimming activity is applied topically on the skin.
  • the substance active in the field of lipolysis can be used in an amount which is sufficient for obtaining the lipolytic effect sought after for decreasing, slowing down or reabsorbing fatty deposits, for a slimming activity, for increasing the blood microcirculation, for improving the appearance or the tone of the skin, in particular for diminishing ⁇ orange peel>> appearance.
  • concentration of use of said substance will vary as a function of the nature of the substance itself. In general, the concentration of the substance or of a plant extract comprising or constituting the active substance, in a broad sense, will be between 0.01% and 70% by weight, better between 0.01% by weight and 30% by weight, preferably between 0.5% and 20% by weight.
  • the commercial concentrations will generally be from 0.01% to 30% by weight as shown in the formulation Examples 2 to 6.
  • the examples of cosmetic or pharmaceutical composition will similarly also be given in an illustrative manner. In the Examples, all the percentages are given by weight, unless indicated otherwise, the temperature is in degrees C. unless indicated otherwise, and the pressure is atmospheric pressure, unless indicated otherwise.
  • FIG. 1 shows inhibition of a lipoprotein lipase in function of the concentration in an aqueous-alcohol extract of liana Uncaria tomentosa , showing in abscissa the concentration of use in weight percent and in ordinate the inhibition of lipoprotein lipase obtained in relative percent; the said determination being performed of the non esterified fatty acids or NEFAs with commercial NEFA-C determination kit from Wako from oxoid, 69571 Dardilly cedex France
  • FIG. 2 represents the results obtained in the same conditions as FIG. 1 but the fatty acids released in the reaction medium are analyzed by gas phase chromatography or GPC.
  • FIG. 3 shows the comparison of inhibiting activity of the extract of liana Uncaria tomentosa subject matter of FIGS. 1 and 2 with the results obtained under the same testing conditions with an extract of St John's wort obtained by extraction with an aqueous glycolic solvent mixture, consisting of 40 weight percent of water/60 weight percent of butylene glycol, under the action of lipoprotein lipase, the concentration of active substance in formulation being shown in abscissa and the relative percentage of inhibition being shown in ordinate, the result with the extract of Uncaria tomentosa being shown on the right blocks with oblique lines uprising in the right direction whereas the results obtained with the St John's wort being shown on the left blocks with oblique lines going downwardly in the right direction.
  • an aqueous glycolic solvent mixture consisting of 40 weight percent of water/60 weight percent of butylene glycol
  • Triolein is the most representative substrate of the situation encountered in vivo since a study of the analysis of the fatty acids present in the adipocyte reveals (T. Raclot, et al, “Selective release of human adipocyte fatty acids according to molecular structure” published in Biochem. J., 324, 911-915, (1997); “Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids” Clinica Chimica Acta, 248, 157-174, (1996)) that oleic acid is mainly present therein and thus constitutes the main product of hydrolysis of the lipoprotein lipase.
  • apolipoprotein C-II (apoCII) of human origin, which has a determining role in the hydrolysis of triacylglycerols by LPL (Posner et al, “Kinetics of product inhibition and mechanisms of lipoprotein lipase activation by apolipoprotein CII” published in Biochemistry, 26, 3771-3717, (1987)).
  • ApoCII is fixed onto the triacylglycerols of the blood and enables a change in the conformation of the LPL to be induced which is indispensable for the recognition of the substrate by the active site of the enzyme (Santamarina-Fojo S. and Dugi K. A. “Structure, function and role of lipoprotein lipase in lipoprotein metabolism published in Current Opinion in Lipidology, 5, 117-125, (1994)).
  • LPL is an enzyme which has a significant affinity for its reaction product. The fatty acids released will in fact aggregate around the enzyme which will as it were be sequestered by the fatty acids and will therefore be no longer accessible to the substrate.
  • albumin which has a very high affinity for fatty acids enables the enzymatic activity of the LPL not to be blocked (Bengtsson-Olivecrona G. and Olivecrona T. “Phospholipase activity of milk lipoprotein lipase” published in Methods in enzymology, 197, 345-356, (1991)).
  • the enzyme is incubated for a determined period of time in the presence of its inhibitor while the triolein is incubated in the presence of apoCII so as to mimic the situation encountered in vivo.
  • triolein/ApoCII mixture is then incubated in the presence of the medium constituted by the enzyme ⁇ inhibitor.
  • NEFA non-esterified fatty acids
  • a control corresponding to the LPL activity in the absence of inhibitor is effected.
  • the use of an active product which is capable of modifying the enzymatic activity will be expressed as a lowering of the OD at 550 nm, i.e. a decrease in the fatty acids synthesized in the medium with respect to the control.
  • the results are expressed in percentage inhibition with respect to the control.
  • inhibitors cited in the literature do not seem to be extremely potent inhibitors of LPL since the levels of inhibition observed at the concentrations tested are relatively modest; they are described in the scientific literature for being inhibitors which act by competition with the substrate of the enzyme.
  • Cat's Claw is a plant belonging to the Rubiaceae family, named Uncaria tomentosa .
  • Cat's Claw is a liana which attaches itself to the trees of Amazonian forest with the aid of claws which are situated at the base of the leaves and which resemble those of a cat, hence its name. The plant is harvested above all in Peru and in the center of South America. The plant lives in moist media at an altitude ranging between 400 and 800 meters.
  • Uncaria tomentosa exists in the United States under several forms of product for therapeutic application: asthma, cancer, illness prevention, fever, gastric ulcers, haemorrhages, inflammations, rheumatism, inflammation of the urinary passages, impurity of the skin . . . (Keplinger Klaus, et al, “ Uncaria tomentosa (Willd.) DC-Ethnomedicinal use and new pharmacological, toxicological and botanical results” published in Journal of Ethnopharmacology, 64, 23-34, (1999)). Numerous pieces of research work are carried out on this liana over the last ten years.
  • Uncaria tomentosa exists as two chemical types, which contain either tetracyclic oxindole alkaloids (rynchophylline and isorhyncophylline), or pentacyclic oxindole alkaloids (pteropodine, isopteropodine, speciophylline, uncarine F, mitraphylline and isomitraphylline) in their roots.
  • tetracyclic oxindole alkaloids rynchophylline and isorhyncophylline
  • pentacyclic oxindole alkaloids pentacyclic oxindole alkaloids
  • isopteropodine speciophylline
  • uncarine F mitraphylline
  • isomitraphylline isomitraphylline
  • Uncaria tomentosa possesses an anti-inflammatory activity. This property would mainly be due to the quinovic acid glycosides which are present in the bark of this liana.
  • An aqueous extract of the bark of Cat's Claw enables the cell toxicity, induced by peroxynitrite in degrading it, to be inhibited. It inhibits the expression of inducible nitric oxide synthase (iNOS) inhibiting the activation of NF- ⁇ B which diminishes the production of NO.
  • iNOS inducible nitric oxide synthase
  • Uncaria tomentosa of the pentacyclic oxindole alkaloids (POA) type increases the level of phagocytosis by the granulocytes. Moreover, it increases the proliferation of the human B and T lymphocytes via the endothelial cells. The POAs induce the endothelial cells in vitro in order to release a factor into the supernatant which regulates the proliferation of the lymphocytes. Uncaria tomentosa inhibits the proliferation of the lymphoblasts and the lymphoblastoid cell lines.
  • alkaloids act as a regulator of human immune responses (Wurm Martin, et al, “Pentacyclic Oxindole Alkaloids form Uncaria tomentosa induce human endothelial cells to release a lymphocyte-proliferation-regulating factor” published in Planta Medica, 64, 701-704, (1998)).
  • Uncaria tomentosa would stimulate also the production of interleukins IL1 and IL6 by macrophages. It would thus possess an immuno-stimulant action (Lemaire I. et al, “Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (u ⁇ a de gato) published in Journal of Ethnopharmacology 64, 109-115, (1999)).
  • An alcoholic extract is prepared from the bark and/or the roots of the entire Peruvian liana plant Uncaria tomentosa , which is commercially available, in the following manner:
  • the insoluble material is removed by centrifugation and the supernatant obtained in the form of an aqueous solution can be used preferably as such and especially for preparing a cosmetic composition.
  • the insoluble material is removed by centrifugation and the aqueous-glycolic supernatant obtained can be used preferably as such and especially for preparing a cosmetic composition.
  • the liana extract is consequently positioned as a very potent active product and very innovative in the field of slimming agents.
  • the oleic acid is extracted from the reaction medium of the enzymatic determination with ethanol, and then injected onto a commercial column from DBJW scientific: reference DB FFAP, 15 m in length, 0.32 mm internal diameter, 0.25 ⁇ m thickness in splitless mode.
  • the temperatures of the injector and of the detector are 280° C.
  • the programming in temperature starts at 50° C. for 1 minute and then rises by 40° C./minute up to 200° C. and then by 15° C. par minute up to 250° C. for 3 minutes.
  • the retention time of oleic acid under these conditions is 7.74 minutes.
  • the GPC has a high sensitivity in the low percentages of inhibition. In fact, the inhibitions obtained for the reference inhibitors and tannic acid are higher.
  • An extract of St. John's wort is prepared from flower heads (flowers and/or buds) of the plant St. John's wort, which is commercially available, according to the following procedure:
  • the insoluble material is removed by centrifugation and the supernatant obtained in the form of an aqueous solution can be used preferably as such especially for preparing a cosmetic composition.
  • the insoluble material is removed by centrifugation and the aqueous-glycolic supernatant obtained is used preferably as such especially for preparing a cosmetic composition.
  • the invention brings about particularly unexpected technical advantages which are not obvious to the person skilled in the art and which enable a novel method of tests to be provided which enable active products which are capable of being active upon lipoprotein lipase or LPL, to be selected.
  • the invention also covers cosmetic formulations which contain such active products, and their use as slimming creams.
  • the invention also covers the selection of pharmaceutically active products by the test method, which products can be the same active products or not as those which could have been selected within the context of a cosmetic activity, as well as the pharmaceutical formulations which contain such active products and their uses within the context of the treatment of a pathology in the field of lipolysis.
  • Formulation 2a A Water qsp 100 Butylene Glycol 2 Glycerine 3 Sodium Dihydroxycetyl 2 Phosphate, Isopropyl Hydroxycetyl Ether B Glycol Stearate SE 14 Triisononanoine 5 Octyl Cocoate 6 C Butylene Glycol, 2 Methylparaben, Ethylparaben, Propylparaben, pH adjusted to 5.5 D Products of the invention 0.01-30%
  • Phases A and B are heated separately to 75° C., B is then added to A under vigorous stirring; C then D are then added, during the cooling of the cream thus formed.
  • Formulation 2b A Water qsp 100 Butylene Glycol 2 Glycerine 3 Polyacrylamide, Isoparaffin, 2.8 Laureth-7 B Butylene Glycol, 2 Methylparaben, Ethylparaben, Propylparaben; Phenoxyethanol, 2 Methylparaben, Propylparaben, Butylparaben, Ethylparaben Butylene Glycol 0.5 C Products of the invention 0.01-30%
  • Phase A is heated to 75° C.; B and then C are added to A with stirring, during the cooling of the formula thus prepared.
  • Formulation 2c A Carbomer 0.50 Propylene Glycol 3 Glycerol 5 Water qsp 100 B Octyl Cocoate 5 Bisabolol 0.30 Dimethicone 0.30 C Sodium Hydroxide 1.60 D Phenoxyethanol, 0.50 Methylparaben, Propylparaben, Butylparaben, Ethylparaben E Perfume 0.30 F Products of the invention 0.01-30%
  • Phases A and B are heated separately to 75° C., and then B is added to A with vigorous stirring; C and then D then E then F are then added successively, during the cooling of the cream thus formed.
  • Phases A and B are heated separately to 75° C., and then B is added to A with vigorous stirring; C and then D then E are then added, during the cooling of the cream thus formed.
  • Phases A and B are prepared separately at ambient temperature, and then B is added to A with stirring ; C and then D then E are then added, with moderate stirring.
  • Phases A and B are heated separately to 80° C., and then B is added to A with stirring.
  • Phase A is prepared by adding all the ingredients and by heating the whole to 80° C. up to the obtaining of a homogenous mixture. B is then added to A with vigorous stirring during the cooling of the gel thus formed.
  • the toxicology tests were carried out on the two compounds retained, namely the extract of liana and the extract of St. John's wort, which are used pure, by an ocular evaluation in the rabbit, by a study of the absence of abnormal toxicity by a single oral administration in the rat, and by a study of the sensitizing power in the guinea pig.
  • the LD0 and LD50 are found to be greater than 5,000 mg/Kg. The preparations tested are thus not classed amongst preparations which are dangerous by ingestion.
  • the preparations are classified as being non-sensitizing by contact with the skin.

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US20050053712A1 (en) * 2003-09-10 2005-03-10 Zima George Chester Process for the recovery of a phytolipid composition
WO2006024120A3 (en) * 2004-09-01 2006-09-28 Herbarium Lab Botan Ltda Topical phytotherapeutic compound for the treatment of herpes based on uncaria tomentosa and extraction process for obtaining a vegetal extract from uncaria tomentosa
US20100184721A1 (en) * 2009-01-22 2010-07-22 Caster Extract of Lentinus for Its Action on Cellulite and Accumulations of Fat
EP2604254A1 (en) 2007-06-28 2013-06-19 BASF Beauty Care Solutions France SAS Slimming composition
CN103383382A (zh) * 2013-06-28 2013-11-06 上海相宜本草化妆品股份有限公司 用于检测化妆品中尼泊金酯类及其复配防腐剂的方法
WO2014027163A2 (fr) 2012-08-13 2014-02-20 Basf Beauty Care Solutions France Sas Ingredient hydratant cosmetique ou pharmaceutique
WO2014155012A1 (fr) 2013-03-27 2014-10-02 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de polygonum bistorta
WO2015036704A1 (fr) 2013-09-12 2015-03-19 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de tapirira guyanensis
EP2896430A1 (fr) 2013-08-23 2015-07-22 BASF Beauty Care Solutions France SAS Utilisation cosmétique ou dermatologique d'un extrait de Quassia amara
US9308161B2 (en) 2005-10-28 2016-04-12 Basf Beauty Care Solutions France S.A.S. Substance for restoring normal co-expression and interaction between the LOX and NRAGE proteins
WO2021152250A1 (fr) 2020-01-30 2021-08-05 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique ou dermatologique d'un extrait de tamarindus indica l. et / ou d'une composition le comprenant
FR3110415A1 (fr) 2020-05-20 2021-11-26 Basf Beauty Care Solutions France Sas Utilisation d’un extrait d’adansonia digitatapour maintenir et / ou diminuer la communication bacterienne
FR3117340A1 (fr) 2020-12-15 2022-06-17 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique ou dermatologique d’une souche deLactobacillus crispatus et / ou d’une composition la comprenant
FR3133312A1 (fr) 2022-03-08 2023-09-15 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique de Sphingomonas glacialis et/ou d’une composition la comprenant
WO2023180661A1 (fr) 2022-03-23 2023-09-28 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de dendrobium officinale pour maintenir et/ou augmenter l'epaisseur de la peau
WO2023186945A1 (fr) 2022-03-30 2023-10-05 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique et/ou dermatologique d'une souche de lactobacillus crispatus et/ou d'une composition la comprenant
FR3135899A1 (fr) 2022-03-23 2023-12-01 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d’un extrait de Dendrobium officinale pour maintenir et/ou augmenter l’épaisseur de la peau
WO2024008647A1 (fr) 2022-07-04 2024-01-11 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d'un extrait de pyracantha fortuneana
FR3138039A1 (fr) 2022-07-21 2024-01-26 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d’un extrait de Pyracantha fortuneana
WO2024023440A1 (fr) 2022-07-26 2024-02-01 Basf Beauty Care Solutions France Sas Nouvelle utilisation cosmetique ou dermatologique d'un extrait de gentiana crassicaulis
FR3138615A1 (fr) 2022-08-02 2024-02-09 Basf Beauty Care Solutions France Sas Nouvelle utilisation cosmétique ou dermatologique d’un extrait de Gentiana crassicaulis

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US20050051419A1 (en) * 2003-09-10 2005-03-10 Zima George Chester Process for the recovery of a phytolipid composition
US20080138450A1 (en) * 2003-09-10 2008-06-12 Eastman Chemical Company Process for the recovery of a phytolipid composition
US20050053712A1 (en) * 2003-09-10 2005-03-10 Zima George Chester Process for the recovery of a phytolipid composition
WO2006024120A3 (en) * 2004-09-01 2006-09-28 Herbarium Lab Botan Ltda Topical phytotherapeutic compound for the treatment of herpes based on uncaria tomentosa and extraction process for obtaining a vegetal extract from uncaria tomentosa
US20070248703A1 (en) * 2004-09-01 2007-10-25 Herbarium Laboratorio Botanico Ltda. Topical Phytotherapeutic Compound for the Treatment of Herpes Based on Uncaria Tomentosa and Extraction Process for Obtaining a Vegetal Extract from Uncaria Tomentosa
US8906423B2 (en) 2004-09-01 2014-12-09 Herbarium Laboratorio Botanico Ltda. Topical phytotherapeutic compound for the treatment of herpes based on Uncaria tomentosa and extraction process for obtaining a vegetal extract from Uncaria tomentosa
US9308161B2 (en) 2005-10-28 2016-04-12 Basf Beauty Care Solutions France S.A.S. Substance for restoring normal co-expression and interaction between the LOX and NRAGE proteins
EP2604254A1 (en) 2007-06-28 2013-06-19 BASF Beauty Care Solutions France SAS Slimming composition
US9084736B2 (en) * 2009-01-22 2015-07-21 Caster Extract of Lentinus for its action on cellulite and accumulations of fat
US20100184721A1 (en) * 2009-01-22 2010-07-22 Caster Extract of Lentinus for Its Action on Cellulite and Accumulations of Fat
WO2014027163A2 (fr) 2012-08-13 2014-02-20 Basf Beauty Care Solutions France Sas Ingredient hydratant cosmetique ou pharmaceutique
WO2014155012A1 (fr) 2013-03-27 2014-10-02 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de polygonum bistorta
CN103383382A (zh) * 2013-06-28 2013-11-06 上海相宜本草化妆品股份有限公司 用于检测化妆品中尼泊金酯类及其复配防腐剂的方法
EP2896430A1 (fr) 2013-08-23 2015-07-22 BASF Beauty Care Solutions France SAS Utilisation cosmétique ou dermatologique d'un extrait de Quassia amara
WO2015036704A1 (fr) 2013-09-12 2015-03-19 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de tapirira guyanensis
WO2021152250A1 (fr) 2020-01-30 2021-08-05 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique ou dermatologique d'un extrait de tamarindus indica l. et / ou d'une composition le comprenant
FR3106756A1 (fr) 2020-01-30 2021-08-06 BASF Beauty Care Solutions France Utilisation cosmétique, nutraceutique ou dermatologique d'un extrait deTamarindus indicaL. et / ou d’une composition le comprenant
FR3110415A1 (fr) 2020-05-20 2021-11-26 Basf Beauty Care Solutions France Sas Utilisation d’un extrait d’adansonia digitatapour maintenir et / ou diminuer la communication bacterienne
FR3117340A1 (fr) 2020-12-15 2022-06-17 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique ou dermatologique d’une souche deLactobacillus crispatus et / ou d’une composition la comprenant
WO2022129775A1 (fr) 2020-12-15 2022-06-23 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique ou dermatologique d'une souche de lactobacillus crispatus et/ou d'une composition la comprenant
FR3133312A1 (fr) 2022-03-08 2023-09-15 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique de Sphingomonas glacialis et/ou d’une composition la comprenant
WO2023180661A1 (fr) 2022-03-23 2023-09-28 Basf Beauty Care Solutions France Sas Utilisation cosmetique ou dermatologique d'un extrait de dendrobium officinale pour maintenir et/ou augmenter l'epaisseur de la peau
FR3135899A1 (fr) 2022-03-23 2023-12-01 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d’un extrait de Dendrobium officinale pour maintenir et/ou augmenter l’épaisseur de la peau
WO2023186945A1 (fr) 2022-03-30 2023-10-05 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique et/ou dermatologique d'une souche de lactobacillus crispatus et/ou d'une composition la comprenant
FR3134010A1 (fr) 2022-03-30 2023-10-06 Basf Beauty Care Solutions France Sas Utilisation cosmétique, nutraceutique et/ou dermatologique d’une souche de Lactobacillus crispatus et/ou d’une composition la comprenant
WO2024008647A1 (fr) 2022-07-04 2024-01-11 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d'un extrait de pyracantha fortuneana
FR3138039A1 (fr) 2022-07-21 2024-01-26 Basf Beauty Care Solutions France Sas Utilisation cosmétique ou dermatologique d’un extrait de Pyracantha fortuneana
WO2024023440A1 (fr) 2022-07-26 2024-02-01 Basf Beauty Care Solutions France Sas Nouvelle utilisation cosmetique ou dermatologique d'un extrait de gentiana crassicaulis
FR3138615A1 (fr) 2022-08-02 2024-02-09 Basf Beauty Care Solutions France Sas Nouvelle utilisation cosmétique ou dermatologique d’un extrait de Gentiana crassicaulis

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JP2005343900A (ja) 2005-12-15
FR2824334A1 (fr) 2002-11-08
JP4790333B2 (ja) 2011-10-12
US20120269910A1 (en) 2012-10-25
JP4135859B2 (ja) 2008-08-20
KR20020084883A (ko) 2002-11-13
JP2002335996A (ja) 2002-11-26
US8741359B2 (en) 2014-06-03
FR2824334B1 (fr) 2003-10-10
KR100444933B1 (ko) 2004-08-18

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