US20020182269A1 - Cucumis melo extract coated and/or microencapsulated in a fat-soluble agent based on a fatty substance - Google Patents

Cucumis melo extract coated and/or microencapsulated in a fat-soluble agent based on a fatty substance Download PDF

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US20020182269A1
US20020182269A1 US09/850,037 US85003701A US2002182269A1 US 20020182269 A1 US20020182269 A1 US 20020182269A1 US 85003701 A US85003701 A US 85003701A US 2002182269 A1 US2002182269 A1 US 2002182269A1
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composition according
fat
plant extract
composition
advantageously
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Alain Dreyer
Jean-Paul Ginoux
Philippe Roch
Dominique Lacan
Christian Yard
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Bio Obtention SC
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Assigned to BIO-OBTENTION SC reassignment BIO-OBTENTION SC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DREYER, ALAIN, GINOUX, JEAN-PAUL, LACAN, DOMINIQUE, ROCH, PHILIPPE, YARD, CHRISTIAN
Publication of US20020182269A1 publication Critical patent/US20020182269A1/en
Priority to US10/446,672 priority Critical patent/US7132118B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/446—Superoxide dismutase (1.15)
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/42—Cucurbitaceae (Cucumber family)
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    • 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)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/11—Encapsulated compositions
    • A—HUMAN NECESSITIES
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    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
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    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns

Definitions

  • the present invention relates to a novel composition
  • a novel composition comprising an active plant extract containing superoxide dismutase, in particular a protein extract of cucumis melo. It relates in particular to active plant extracts coated and/or microencapsulated in a fat-soluble agent based on a fatty substance and which may be useful in oral or topical application.
  • reactive oxygen species comprise free radicals such as the superoxide radical (0 2 . ⁇ ), the hydroxyl radical (OH.), nitrogen monoxide (NO.) or peroxyl radicals of lipid origin (L-OO.).
  • free radicals are atoms or molecules whose electron configuration is characterized by the presence of an unpaired electron. This characteristic feature makes them unstable and, to become stabilized, they can rapidly oxidize new biological molecules such as nucleic acids (DNA), enzymatic proteins or membrane lipids and particularly polyunsaturated fatty acids (PUFA).
  • the superoxide ion is the free radical most commonly and most abundantly generated in cells. It therefore represents a considerable danger for the body. Its toxicity depends in particular on its transformation to other more aggressive reagents such as the hydroxyl radical (OH.).
  • SOD superoxide dismutase
  • Mn SOD manganese
  • Fe SOD° SOD containing iron
  • SOD plays a key role in combating free radicals since it allows the elimination of the superoxide ion.
  • Superoxide dismutases are enzymes capable of inducing dismutation of the superoxide ions according to the reaction:
  • the second line of defense is provided by two enzymes: catalase and selenium-dependent glutathione peroxidase (SeGPx) which destroys H 2 O 2 .
  • Patent FR 2 287 899 has described, for example, the application in cosmetology of superoxide dismutase enzymes and in particular the use of these enzymes in the preparation of cosmetic compositions for skin and hair care.
  • SOD has therefore been used in pathological conditions induced by free radicals, in particular in the case of chronic inflammations such as, for example, in the treatment of Crohn's disease (Emerit et al., 1991, Free Rad. Res. Comms, 12-13, 563-569) or in the case of radio-induced fibroses (Delanian et al., 1994, Radiotherapy and Oncology, 32, 12-20).
  • patent application FR 2 716 884 describes a protein extract of Cucumis melo having improved superoxide dismutase enzymatic activity, their method of preparation and their use in pharmaceutical or cosmetic compositions for external topical use.
  • a protein extract is difficult to use as the enzymes which it contains (superoxide dismutase in particular) are inactivated in the presence of external attacks (UV in particular) or while taking in formulations for oral use (gastric juice). It is therefore advisable to develop specific formulations which offer this protection so as to optimize the action of the antioxidant active agents.
  • SOD-PEG polyethylene glycol
  • SOD-Heparin SODs conjugated with heparin
  • SOD-albumin SODs conjugated with albumin
  • patent application FR 2 729 296 also describes a particular pharmaceutical composition which is well suited to oral administration of superoxide dismutase essentially comprising, in combination, a superoxide dismutase and a compound selected from the group consisting of ceramides, prolamines and polymeric films based on said prolamines.
  • a composition is not suitable for use by the topical route and, in addition, cannot be used by people allergic to gluten.
  • the inventors have discovered, surprisingly, that when an active plant extract containing superoxide dismutase (SOD) was coated and/or microencapsulated in a fat-soluble agent based on a fatty substance, it could be used by the topical or oral route and its active agents, in particular SOD, were protected against external attacks (UV or gastric juice for example).
  • SOD superoxide dismutase
  • the present invention therefore relates to a composition
  • a composition comprising an active plant extract containing superoxide dismutase, said extract being coated and/or microencapsulated in a fat-soluble agent based on a fatty substance.
  • active plant extract containing superoxide dismutase is understood to mean, for the purposes of the present invention, any extract obtained from plants having superoxide dismutase enzymatic activity.
  • it is a protein extract of cucumis melo, in particular in powdered form, advantageously freeze-dried. More advantageously still, the cucumis melo is a progeny of the cell line 95LS444 or of one of the hybrid lines derived from 95LS444.
  • the superoxide dismutase enzymatic activity of the plant extract is at least equal to 5 enzymatic units per mg of extract, advantageously at least equal to 50 enzymatic units per mg of extract.
  • the plant extract may be obtained by methods well known to persons skilled in the art, in particular by the method described in patent application FR 2 716 884. It is also commercially available from the company BIONOV under the trademark EXTRAMEL®.
  • the plant extract according to the present invention may, in addition, have a catalase enzymatic activity. It may also comprise a coenzyme Q10, vitamins, lipoic acid, gluthathione, inorganic elements present in the plant, such as potassium, magnesium, calcium and selenium, and the like.
  • fat-soluble agent based on a fatty substance is understood to mean, for the purposes of the present invention, any agent containing at least one fatty substance and having an index of balance between the hydrophilic part and the lipophilic part of the molecule (HLB) of less than 10.
  • the fat-soluble agent according to the present invention has a melting point of between about 40 and about 80° C., more advantageously still of between about 55 and about 60° C.
  • the fat-soluble agent according to the present invention is of plant origin.
  • it is chosen from the group consisting of hydrogenated oils; palm oil or oil from the heart of palm fruit; hydrogenated seeds; stearates, in particular chosen from stearins, stearic acid and its derivatives; waxes; fatty acid monodiglycerides; saturated C 14 -C 20 fatty acid triglycerides and mixtures thereof.
  • the fat-soluble agent according to the present invention is hydrogenated oil based on plant oil, in particular chosen from the group consisting of hydrogenated coconut oil, hydrogenated palm oil, hydrogenated soybean oil or hydrogenated rapeseed oil and mixtures thereof. More advantageously still, it is hydrogenated palm oil.
  • the fat-soluble agent prefferably contains water-soluble substances of the sugar or polyol type.
  • the plant extract according to the invention is present at a concentration of between 1 and 90% by weight relative to the total weight of the composition, advantageously between 20 and 50% by weight relative to the total weight of the composition.
  • the present invention also relates to a method for manufacturing the compositions according to the present invention comprising the following steps:
  • step b) depositing the liquid obtained in step a) on the active plant extract containing superoxide dismutase.
  • the plant extract is present of the form of a powder and step b) is carried out in a fluidized bed, more advantageously still at low temperature and a low moisture content.
  • the temperature of step b) is less than the melting point of the fat-soluble agent and is advantageously about 40° C.
  • the present invention also relates to a pharmaceutical or cosmetic composition
  • a pharmaceutical or cosmetic composition comprising a composition according to the invention and an excipient appropriate for oral or topical use for human or animal administration.
  • These compositions may be formulated for administration to mammals, including humans.
  • the dosage varies according to the treatment and according to the condition in question.
  • the pharmaceutical or cosmetic composition according to the present invention may be formulated for administration by the oral route.
  • the active ingredient may be administered in unit forms for administration, mixed with conventional pharmaceutical carriers, to animals or to human beings.
  • the appropriate unit forms for administration comprise the forms such as tablets, gelatin capsules, powders, granules and oral solutions or suspensions.
  • it comprises, in addition, yogurt and/or fibers, more advantageously still so as to form a homogeneous mixture with the composition comprising an active plant extract containing superoxide dismutase, said extract being coated and/or microencapsulated in a fat-soluble agent based on a fatty substance according to the present invention.
  • the pharmaceutical or cosmetic composition may also be formulated for administration by the topical route.
  • They may be provided in the forms which are customarily known for this type of administration, that is to say in particular lotions, foams, gels, dispersions, sprays, shampoos, serums, masks, body milks or creams for example, with excipients allowing in particular skin penetration so as to improve the properties and the accessibility of the active ingredient.
  • These compositions generally contain, in addition to the composition according to the present invention, a physiologically acceptable medium, in general based on water or solvent, for example alcohols, ethers or glycols.
  • They may also contain surfactants, preservatives, stabilizing agents, emulsifiers, thickeners, other active ingredients leading to an additional or potentially synergistic effect, trace elements, essential oils, perfumes, colorants, collagen, chemical or mineral filters, moisturizing agents or thermal waters.
  • the present invention also relates to a composition according to the present invention as a medicament.
  • composition according to the present invention as a medicament intended for treating or for preventing allergies or for protection the epidermis from UV radiation.
  • the present invention also relates to the use of a composition according to the present invention for the manufacture of a medicament for topical use intended for treating allergies, eczema, vitiligo, psoriasis, lupus, skin fibrosis, for eliminating melanomas, for improving cicatrizations of transplants, for preventing allergies or for protecting the epidermis from UV radiation.
  • compositions according to the present invention for the manufacture of a medicament intended for protecting the epidermis from UV radiation, for treating or preventing allergies, for treating asthma, anemia, male sterility, inflammatory diseases such as anthropathy or degenerative diseases due to cellular and/or organic degeneration, in particular chosen from the group consisting of Crohn's disease, Parkinson's disease, Alzheimer's disease, colorectal cancers, fibroses of varied origins, degenerations due to an infectious agent such as AIDS or hepatitis C or degenerations linked to the use of a medicament.
  • inflammatory diseases such as anthropathy or degenerative diseases due to cellular and/or organic degeneration, in particular chosen from the group consisting of Crohn's disease, Parkinson's disease, Alzheimer's disease, colorectal cancers, fibroses of varied origins, degenerations due to an infectious agent such as AIDS or hepatitis C or degenerations linked to the use of a medicament.
  • the present invention also relates to the use of a food composition
  • a food composition comprising the composition according to the present invention as an energy source, as a tonic source or as an aid for recuperation and for regaining fitness.
  • composition according to the present invention as a medicament, in particular for topical use, intended for treating or for preventing allergies, advantageously for protecting the epidermis against allergies.
  • composition according to the present invention for the manufacture of a medicament, in particular for topical use, intended for treating or for preventing allergies, advantageously for protecting the epidermis against allergies.
  • FIG. 1 represents a skeleton diagram of the process for the preparation of the compositions according to the present invention.
  • FIG. 2 represents the effects evaluated 72 hours after irradiation of the composition of the present invention administered 24 hours before irradiation on keratinocytic apoptosis induced by UV radiation as a function of its SOD concentration.
  • FIG. 3 represents the effects evaluated 72 hours after irradiation of the composition according to the present invention containing 30 units per ml of SOD on keratinocytic apoptosis induced by UV radiation as a function of its time of administration.
  • FIG. 4 represents the degradation time in gastric medium of the composition according to the present invention (B) compared with the uncoated active plant extract (A).
  • FIG. 5 represents the degradation time in gastric medium of the composition according to the present invention (B) compared with the composition according to the present invention homogeneously mixed with fibers (C) or yogurt (D).
  • FIG. 6 represents the effect in vivo evaluated 48 hours after irradiation of the composition according to the present invention (B) taken orally by mice on inflammation induced by UV radiation compared with the uncoated active plant extract (A) and with a control (E).
  • FIG. 7 represents the effect in vivo evaluated 48 hours after irradiation of the composition according to the present invention (B) taken orally on inflammation induced by UV radiation compared with the composition according to the present invention homogeneously mixed with fibers (C) or yogurt (D) and with a control (E).
  • FIG. 8 represents the effect of the semisolid preparation for local application containing a composition according to the present invention on inflammation induced by UV radiation according to the dose of cream applied and compared with a control.
  • the active plant extract prepared above in the form of a freeze-dried powder which is also sold by the company BIONOV under the trademark EXTRAMEL® is used.
  • This extract after coating, has an SOD activity of 14 units per mg of extract and also contains catalase and coenzyme Q10.
  • the fat-soluble agent used is hydrogenated palm oil.
  • the melting of this agent is carried out in the container ( 1 ) (FIG. 1) by heating.
  • the liquid agent thus obtained is deposited by spraying with the aid of a bifluid Schlick nozzle ( 2 ) onto the powder of the active plant extract suspended in a fluidized bed ( 7 ) at low temperature (“skin” temperature less than 40° C.) and a low moisture content.
  • the low melting point of this coating agent (58 to 61° C.) allows instant solidification of the material without burning the active plant extract.
  • a ventilator ( 3 ), a heater ( 4 ), a desaturation device ( 5 ) and a filter ( 6 ) are used.
  • composition thus obtained contains 20% by weight of the active plant extract and 80% by weight of the fat-soluble agent.
  • the preparation (oil-in-water emulsion) is produced in a manner well known to persons skilled in the art using the ingredients and the proportions indicated in Table 1.
  • TABLE 1 Ingredients and proportions for the semisolid preparation INGREDIENTS % by weight Refined macadamia oil (Soetenaey 33% Laboratoire, Fécamp) Kosteran - S/1 G (Verfilco - 3.8% Fontenay S/Bois) Kotilen - S/1 (Verfilco-Fontenay 1.2% S/Bois) Water QS 100% Composition according to Example 1 2.2% Preservative (Sepicide; Seppic; 0.3% Castres)
  • a semisolid preparation for local application is obtained which has the characteristics indicated in the following Table 2. TABLE 2 Characteristics of the semisolid preparation for local application according to Example 2 Appearance Fine emulsion pH 6.93 Stability Stable at room temperature Stable at 40° C. Stable in heat cycle
  • the object of this study is to evaluate the protective effect of the composition according to Example 1 in relation to UV radiation which has as principle consequences in the epidermis the induction of premature death of the keratinocytes by apoptosis (Sun Burn Cell) as well as a release of soluble mediators which contribute to the development of a local inflammation.
  • IL-1 ⁇ IL-1 ⁇
  • TNF- ⁇ IL-6
  • NO free radical
  • the keratinocytes are obtained from primary cultures of foreskins and are allowed to proliferate in a conditioned medium (Keratinocyte Growth Medium (KGM)) for two weeks before use. At confluence, the pure keratinocytes are cultured in 24-well plates at 10 6 cells/ml in a medium free of growth factors in the presence or in the absence of the product to be tested for 24 h and are then stimulated by UV radiation.
  • KGM Keratinocyte Growth Medium
  • the cells are cultured in Iscove medium supplemented with antibiotics (100 SOD units (U)/ml of penicillin and 100 ⁇ g/ml of streptomycin) and fetal calf serum (5%), and they are brought into contact with the composition according to Example 1 at various concentrations (0.1 to 1000 ⁇ g/ml) and then stimulated by UV radiation.
  • antibiotics 100 SOD units (U)/ml of penicillin and 100 ⁇ g/ml of streptomycin
  • fetal calf serum 5%
  • the cells were irradiated with ′′1 ⁇ 4 m Oriel Monochromator, 1 KW mercury-xenon arc lamp with a pass band of 5 nm and focused through a luminous liquid guide (5 nm ⁇ 1 m).
  • the irradiation is carried out at 14.4 Kj/m 2 at 310 nm for a period of 10 min, this type of irradiation corresponding to a UVB-type irradiation.
  • the number of cells undergoing apoptosis is evaluated by counting the number of fluorescent cells out of a total of 200 cells.
  • the assays of the cytokines TNF- ⁇ and IL-6 are carried out on culture supernatants using ELISA assay kits, the detection thresholds being each time less than 10 pg/ml.
  • the stable derivatives i.e. the nitrites, which are measured by a calorimetric technique using the Griess reagent.
  • composition according to Example 1 tested in a concentration range of between 1 and 30 SOD units, is added 24 h before irradiation. Each experiment is carried out in triplicate.
  • composition according to the invention has a protective activity against the phenomenon of induction of apoptosis post-UV irradiation, when it is added preventively, that is to say before the irradiation phenomenon.
  • the use of the active plant extract Extramel® at a dose of 30 SOD units produces an effect equivalent to 0.3 SOD units of the composition according to Example 1 which suggests that the active plant extract, when it is delivered intracellularly by the use of the protection in the form of a coating with the aid of a fat-soluble agent according to the present invention, is 100 times more effective than the free active plant extract.
  • the concentration of the composition according to Example 1 selected for this study is 30 SOD units/ml (FIG. 3).
  • composition according to the present invention to modulate the production of proinflammatory mediators was evaluated according to the following experimental conditions: introduction of the composition according to Example 1 24 h before irradiation or at the beginning of irradiation or 24 h after irradiation.
  • ROS free oxygen radicals
  • composition according to the present invention added before the UV stress inhibits the expression of the proinflammatory mediators and simultaneously reduces the entry of the cells into apoptosis.
  • composition according to the present invention exerts a protective effect on the cellular metabolism.
  • the keratinocytic apoptosis induced by UV irradiation appears to be significantly reduced.
  • the increase in the production of proinflammatory mediators induced by UV irradiation appears to be greatly attenuated (TNF- ⁇ , IL-6 and NO).
  • the composition according to the present invention protects the skin tissue from the degeneration phenomena generated by oxidative stress, regardless of the origin thereof, whether physical (UV radiation) or chemical (environmental pollutants such as ozone, carbon monoxide or heavy metals, and the like), in particular when it is administered preventively.
  • the object of this study is to evaluate the effect, by the oral route, of an active plant extract alone (Extramel®) or coated with a composition according to the present invention containing SOD against inflammation induced in the skin by UV radiation whose main consequence in the epidermis is to induce a release of soluble mediators which contribute to the development of a local inflammation.
  • TNF- ⁇ tNF- ⁇
  • NO oxidative conversion of arginine to citrulline in the presence of oxygen via inducible NO-Synthase which is expressed following UV stress.
  • NO appears to be the main agent responsible for tissue degradations linked to the inflammatory state.
  • mice carrying human skin were irradiated with ′′1 ⁇ 4 m Oriel Monochromator, 1 KW mercury-xenon arc lamp with a pass band of 5 nm and focused through a luminous liquid guide (5 nm ⁇ 1 m).
  • the irradiation is carried out at 14.4 Kj/m 2 at 310 nm for a period of 10 min, this type of irradiation corresponding to a UVB-type irradiation.
  • the assay of the cytokines TNF- ⁇ is carried out on culture supernatants using ELISA assay kits, the detection thresholds being each time less than 10 pg/ml.
  • the stable derivatives i.e. the nitrites, which are measured by a colorimetric technique using the Griess reagent.
  • FIG. 4 A comparison was made (FIG. 4) between the degradation of the active plant extract marketed by the company BIONOV under the trademark EXTRAMEL® (A) and the composition according to Example 1 (B) (that is to say the same active plant extract, but this time protected by means of its coating with a fat-soluble agent). If the active plant extract is degraded in the minutes following its introduction into a medium mimicking the gastric juice (pH 1, trypsin and pepstatin), the composition according to Example 1 has an increased resistance. Indeed, this composition releases SOD progressively between 5 and 30 min (FIG. 4).
  • composition does not exhibit absolute protection with respect to the digestive process, it appears nevertheless that it can be used as a food additive, in particular in fibers (C) and/or yogurts (D), because in this case the protection of the SOD activity is optimized (FIG. 5).
  • compositions according to the present invention which may, in addition, be mixed with some food products (such as yogurt and/or fibers) and thus protect the SOD activity.
  • This oral delivery mode should therefore make it possible to demonstrate the functional activity of this SOD activity in the functional food.
  • the type of treatment followed is the following: the animals are treated with 10 SOD units/mouse each day for 2 weeks before irradiation with UV radiation.
  • composition according to the present invention complexed with other food products (fibers and yogurts) produces a protective effect in vivo against the development of a skin inflammation induced by UV radiation.
  • results strengthen the functional food concept by developing dietary principles which protect the dietary active agents from degradation: thus the composition according to the present invention has a maximum protective activity (although such an activity also exists for the composition according to the present invention alone by the oral route) when it is combined with other food products and therefore positions itself as a functional food additive.
  • the object of this study is to evaluate the protective effect of the active plant extract alone or protected in the composition according to the present invention, in relation to inflammation induced by allergenic substances, chemical compounds of any nature.
  • the inflammatory response which results from the synergy between multiple biochemical mechanisms is triggered by the release, at the level of the site attacked, of numerous proinflammatory mediators (TNF- ⁇ NO, IL-1, IL-8, IL-6, and the like) some of which, like NO, contribute toward increasing cell death by apoptosis.
  • TNF- ⁇ NO, IL-1, IL-8, IL-6, and the like proinflammatory mediators
  • the latter a major proinflammatory mediator, appears moreover to be the main agent responsible for tissue degradations linked to the inflammatory state.
  • the products used are: the composition according to Example 1 and an active plant extract of Cucumis Melo obtained from the company BIONOV (EXTRAMEL®). This is therefore the free extract and the extract protected by coating with a fat-soluble agent according to the present invention.
  • the keratinocytes are obtained from primary cultures of foreskins and are allowed to proliferate in a conditioned medium (KGM medium) for two weeks before use. At confluence, the pure keratinocytes are cultured in 24-well plates at 10 8 cells/ml in a growth medium in the presence or in the absence of the product to be tested for 24 h, and are then stimulated.
  • KGM medium conditioned medium
  • the cells are cultured in Iscove medium supplemented with antibiotics (100 SOD units/ml of penicillin and 100 ⁇ g/ml of streptomycin) and fetal calf serum (5%), and they are brought into contact with the products studied at various concentrations (0.01 to 100 ⁇ g/ml) and then stimulated under the conditions presented below.
  • antibiotics 100 SOD units/ml of penicillin and 100 ⁇ g/ml of streptomycin
  • fetal calf serum 5%
  • the cells are preactivated with IL-4 (10 ng/ml) for 48 h so as to induce CD23 (receptor with low affinity for IgE) and then challenged stimulated with the IgE (IgE/anti-IgE) immune complexes.
  • the cells thus activated are then maintained in culture for 48 h before collecting the supernatants in order to assay the mediators TNF- ⁇ , IL-6 and NO.
  • the percentage of apoptotic cells is evaluated 72 h after stimulation.
  • the assays of the cytokines TNF- ⁇ and IL-6 are carried out on culture supernatants using ELISA assay kits, the detection thresholds being each time less than 10 pg/ml.
  • the stable derivatives i.e. the nitrites, which are measured by a colorimetric technique using the Griess reagent.
  • the allergic stress stimulates the production of the cytokines TNF- ⁇ and IL-6 and the production of NO, via the activation of inducible NO-Synthase in these cells.
  • Example 1 The composition according to Example 1 was tested under the experimental conditions described above and, in the same quantity, exhibits better efficacy than the active plant extracts alone EXTRAMEL®. The results are assembled in Table 8. TABLE 8 Comparison of the effect of the active plant extract alone EXTRAMEL ® and the composition according to Example 1 Toxicity Treatment % mortality TNF (pg/ml) NO 2 ⁇ ( ⁇ M) None Active plant 5 Not detectable Mean: 0.8 extract alone 5 Not detectable Mean: 1.00 EXTRAMEL ® Composition 5 Mean: 50 Mean: 1.0 according to Example 1 IgE IC 35 Mean: 508 Mean: 19.3 IgE IC 20 Mean: 168 Mean: 5.6 Active plant extract alone EXTRAMEL ® IgE IC 10 Mean: 62 Mean: 0.8 Composition according to Example 1
  • composition according to the invention significantly reduces cellular apoptosis induced by allergic stress.
  • composition according to the invention significantly reduces the production of TNF- ⁇ , of IL-6 and of NO by the sensitized keratinocytes.
  • composition according to the invention protects the skin tissue from inflammation caused by allergenic compounds, chemical substances of any nature (metals such as nickel, protein substances, cosmetic excipients, and the like) present in products for daily use as well as in environmental pollutants.
  • the evaluation model is performed on a normal skin explant irradiated or otherwise with UV radiation (A+B).
  • TNF TNF
  • the product tested is the semisolid preparation for local application according to Example 2, that is to say containing a composition according to Example 1.
  • SOD1 1 mg/cm 2 of skin
  • SOD4 0.05 mg/cm 2 of skin.
  • TNFs are measured after exposure to UV radiation with the aid of an ELISA assay kit.
  • the results demonstrate a protective skin activity of the composition according to the present invention formulated for topical application against inflammation induced by UV irradiation, in particular at doses greater than 0.05 mg/cm 2 of skin.
US09/850,037 2001-03-20 2001-05-08 Cucumis melo extract coated and/or microencapsulated in a fat-soluble agent based on a fatty substance Abandoned US20020182269A1 (en)

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FR01/03750 2001-03-20

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EP1747786A3 (en) * 2005-07-25 2007-04-25 Perdix Eurogroup S.L. Natural product in cream with anti-vitiligo therapeutic properties
US20080050355A1 (en) * 2004-10-22 2008-02-28 Compagnie Gervais Danone Protection of bioactive food ingredients by means of encapsulation
US20080050354A1 (en) * 2004-10-22 2008-02-28 Compagnie Gervais Danone Protecting bioactive food ingredients using microorganisms having reduced metabolizing capacity
US20110052741A1 (en) * 2009-09-02 2011-03-03 Brumbaugh Ernest H Composition and Method for Skin Repair
DE102015102499A1 (de) * 2015-02-20 2016-08-25 Ass-Einrichtungssysteme Gmbh Möbelgleiter und Verfahren zur Herstellung eines Möbelgleiters
CN107949377A (zh) * 2015-09-09 2018-04-20 帝斯曼知识产权资产管理有限公司 生产包含治疗活性或营养性植物提取物的制剂的方法
WO2022253981A1 (en) 2021-06-03 2022-12-08 Bionov Association of a vegetal active extract containing superoxide dismutase (sod) and a fenugreek extract and uses thereof

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FR3032721B1 (fr) * 2015-02-12 2020-03-27 Bionov Melange de sod purifiees d'origine vegetale

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US20080050354A1 (en) * 2004-10-22 2008-02-28 Compagnie Gervais Danone Protecting bioactive food ingredients using microorganisms having reduced metabolizing capacity
EP1747786A3 (en) * 2005-07-25 2007-04-25 Perdix Eurogroup S.L. Natural product in cream with anti-vitiligo therapeutic properties
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DE102015102499A1 (de) * 2015-02-20 2016-08-25 Ass-Einrichtungssysteme Gmbh Möbelgleiter und Verfahren zur Herstellung eines Möbelgleiters
CN107949377A (zh) * 2015-09-09 2018-04-20 帝斯曼知识产权资产管理有限公司 生产包含治疗活性或营养性植物提取物的制剂的方法
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WO2022253981A1 (en) 2021-06-03 2022-12-08 Bionov Association of a vegetal active extract containing superoxide dismutase (sod) and a fenugreek extract and uses thereof

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US7132118B2 (en) 2006-11-07
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FR2822381A1 (fr) 2002-09-27
JP2003002840A (ja) 2003-01-08
US20030203052A1 (en) 2003-10-30

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