WO2021116443A1 - Composition comprising propolis particles - Google Patents
Composition comprising propolis particles Download PDFInfo
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- WO2021116443A1 WO2021116443A1 PCT/EP2020/085829 EP2020085829W WO2021116443A1 WO 2021116443 A1 WO2021116443 A1 WO 2021116443A1 EP 2020085829 W EP2020085829 W EP 2020085829W WO 2021116443 A1 WO2021116443 A1 WO 2021116443A1
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- WO
- WIPO (PCT)
- Prior art keywords
- propolis
- composition according
- composition
- emulsion
- ethanol
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 98
- 241000241413 Propolis Species 0.000 title claims abstract description 88
- 229940069949 propolis Drugs 0.000 title claims abstract description 88
- 239000002245 particle Substances 0.000 title claims description 54
- 235000010489 acacia gum Nutrition 0.000 claims abstract description 28
- 229920000084 Gum arabic Polymers 0.000 claims abstract description 27
- 239000000205 acacia gum Substances 0.000 claims abstract description 27
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 26
- 239000000843 powder Substances 0.000 claims abstract description 16
- 238000001035 drying Methods 0.000 claims abstract description 10
- 241000978776 Senegalia senegal Species 0.000 claims abstract 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 76
- 239000000839 emulsion Substances 0.000 claims description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 20
- 239000000725 suspension Substances 0.000 claims description 18
- 238000001704 evaporation Methods 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 10
- 235000013824 polyphenols Nutrition 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 238000000889 atomisation Methods 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 9
- 239000008346 aqueous phase Substances 0.000 claims description 8
- 230000008020 evaporation Effects 0.000 claims description 8
- 238000010008 shearing Methods 0.000 claims description 7
- 238000000265 homogenisation Methods 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 6
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- 108090000623 proteins and genes Proteins 0.000 claims description 4
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- 239000003826 tablet Substances 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 239000003349 gelling agent Substances 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 230000008719 thickening Effects 0.000 claims description 2
- 239000002562 thickening agent Substances 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims 1
- 244000215068 Acacia senegal Species 0.000 description 23
- 238000009826 distribution Methods 0.000 description 20
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- 238000002360 preparation method Methods 0.000 description 12
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- 238000000034 method Methods 0.000 description 6
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- 238000009472 formulation Methods 0.000 description 5
- 102000011632 Caseins Human genes 0.000 description 4
- 108010076119 Caseins Proteins 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000008192 Lactoglobulins Human genes 0.000 description 3
- 108010060630 Lactoglobulins Proteins 0.000 description 3
- 241000219000 Populus Species 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- RTIXKCRFFJGDFG-UHFFFAOYSA-N chrysin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 RTIXKCRFFJGDFG-UHFFFAOYSA-N 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
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- 239000007788 liquid Substances 0.000 description 3
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- 239000000047 product Substances 0.000 description 3
- 229940080237 sodium caseinate Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000257303 Hymenoptera Species 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
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- 238000004581 coalescence Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
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- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- VCCRNZQBSJXYJD-UHFFFAOYSA-N galangin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=CC=C1 VCCRNZQBSJXYJD-UHFFFAOYSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
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- 238000001000 micrograph Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
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- 239000002994 raw material Substances 0.000 description 2
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- 238000004062 sedimentation Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- NYCXYKOXLNBYID-UHFFFAOYSA-N 5,7-Dihydroxychromone Natural products O1C=CC(=O)C=2C1=CC(O)=CC=2O NYCXYKOXLNBYID-UHFFFAOYSA-N 0.000 description 1
- 241000132016 Baccharis Species 0.000 description 1
- 241001252600 Baccharis dracunculifolia Species 0.000 description 1
- 235000018185 Betula X alpestris Nutrition 0.000 description 1
- 235000018212 Betula X uliginosa Nutrition 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 235000019499 Citrus oil Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000218657 Picea Species 0.000 description 1
- FGUBFGWYEYFGRK-HNNXBMFYSA-N Pinocembrin Natural products Cc1cc(C)c2C(=O)C[C@H](Oc2c1)c3ccccc3 FGUBFGWYEYFGRK-HNNXBMFYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000033809 Suppuration Diseases 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 229920001284 acidic polysaccharide Polymers 0.000 description 1
- 150000004805 acidic polysaccharides Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229940043370 chrysin Drugs 0.000 description 1
- 235000015838 chrysin Nutrition 0.000 description 1
- 239000010500 citrus oil Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- CIPSYTVGZURWPT-UHFFFAOYSA-N galangin Natural products OC1=C(Oc2cc(O)c(O)cc2C1=O)c3ccccc3 CIPSYTVGZURWPT-UHFFFAOYSA-N 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- SUYJZKRQHBQNCA-UHFFFAOYSA-N pinobanksin Natural products O1C2=CC(O)=CC(O)=C2C(=O)C(O)C1C1=CC=CC=C1 SUYJZKRQHBQNCA-UHFFFAOYSA-N 0.000 description 1
- URFCJEUYXNAHFI-ZDUSSCGKSA-N pinocembrin Chemical compound C1([C@@H]2CC(=O)C3=C(O)C=C(C=C3O2)O)=CC=CC=C1 URFCJEUYXNAHFI-ZDUSSCGKSA-N 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- -1 sodium caseinate Chemical compound 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 229940126672 traditional medicines Drugs 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
- A61K35/644—Beeswax; Propolis; Royal jelly; Honey
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
Definitions
- the invention relates to a novel composition of a kinetically stable propolis suspension and its preparation process.
- the composition comprises at least propolis particles of micrometric size dispersed in an aqueous solution in the presence of at least one amphiphilic polymeric agent of animal or plant origin, such as gum arabic.
- the invention also relates to the drying of said suspension to obtain a powder redispersible in water.
- Propolis is a resinous, gummy and balsamic substance which consists of wax and salivary secretions from bees mixed with substances collected from the bark and buds of plants or trees, such as poplar, birch, willow, l 'spruce, fir and coconut.
- propolis constitutes a composition rich in polyphenols, flavonoids, trace elements and parabens, which gives the substance properties on health and in particular antibacterial, antibiotic, antifungal and healing properties.
- Flavonoids are plant pigments that act as antimicrobials, antifungals, antispasmodics, and antioxidants like chrysin, pinocembrin, and galangin. Modern science and in particular pharmaceutical companies are increasingly interested in propolis and recent studies have confirmed its therapeutic virtues known since Antiquity. The Egyptians used it for embalming, the Greeks used it against skin infections, wounds and suppurations, the Romans used it to disinfect and facilitate healing and medieval Europeans used it for treat diseases of the mouth and breathing. Besides medicine, propolis was also used in the manufacture of varnishes, especially musical instruments, but also as an anti-rust product.
- propolis is mainly marketed in the form of a hydro-alcoholic solution.
- hydro-alcoholic solutions severely limit the market for medical, religious or age-related reasons, but can also cause many symptoms in the event of ingestion or projection such as: irritation, allergies, drowsiness. , restlessness, headache, nausea, and dizziness.
- Propolis is also marketed in raw form, in the form of a gum, an oral spray, in syrup and in capsules.
- the objective of the present invention is to provide a new formulation making it possible to reconcile the therapeutic virtues of propolis and to eliminate the undesirable effects linked to the presence of ethanol which de facto limit the targeted market.
- the invention relates to a composition
- a composition comprising at least propolis and at least one amphiphilic polymeric agent of natural origin.
- the invention relates to a composition for its use as a food supplement.
- consumers ideally turn to these food supplements to the detriment of traditional medicines, especially for fragile populations such as children, the elderly and pregnant women.
- FIG. 1 is a microscopy image (panel A) and a particle size (panel B) of the composition comprising a concentration of 8.5% by weight of propolis relative to the total mass of the dispersion (46% relative to the total weight of dry matter) according to Example 1.
- FIG. 2 is a microscopy image (panel A) and a particle size (panel B) of the composition comprising a concentration of 6.375% by weight of propolis relative to the total mass of the dispersion (40% relative to the total weight dry matter) according to Example 1.
- Figure 3A is a particle size of the composition according to Example 3 before the evaporation of the ethanol.
- FIG. 3B is a particle size distribution of the composition according to Example 3 after evaporation of the ethanol.
- Figure 4A is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 400 bars.
- Figure 4B is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 600 bar.
- Figure 4C is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 800 bar.
- Figure 5 shows the change in the average diameter at the surface of the emulsions according to Example 5 as a function of the concentration of gum arabic expressed as% of the total mass.
- Figure 6A1 is a particle size of the composition according to Example 7 in the form of a dry dispersion before lyophilization and redispersion in distilled water prepared using a microfluidizer.
- Figure 6A2 is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion after lyophilization and redispersion in distilled water prepared using a microfluidizer.
- Figure 6B1 is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion before lyophilization and redispersion in distilled water prepared using an Ultra-Turrax.
- Figure 6B2 is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion after lyophilization and redispersion in distilled water prepared using an Ultra-Turrax.
- Figure 7A is a particle size of the composition according to Example 8 in the form of a dry dispersion before atomization.
- FIG. 7B is a particle size distribution of the composition according to Example 8 in the form of a dry dispersion after atomization.
- propolis means a resinous, gummy and balsamic substance consisting of wax and salivary secretions from bees mixed with substances collected from the bark and buds of plants or trees.
- the propolis can be indifferently the raw or transformed substance but also an extract of propolis or particles of propolis.
- propolis extract any harvested propolis transformed by a process extraction making it possible to remove the impurities present in the crude extract and / or to concentrate the propolis in one or more of its constituents.
- Propolis extract can come in many forms. Preferably, it is in the form of a powder.
- propolis-in-water suspension means a dispersion obtained with moderate or accelerated stirring at room temperature or higher of at least propolis, of the amphiphilic polymeric agent such as gum arabic or sodium caseinate or beta-lactoglobulin, and water, in which the drops or particles of propolis are suspended in the water.
- propolis particles or equally “drop of propolis” is understood to mean propolis coated with an amphiphilic polymeric agent.
- amphiphilic polymeric agent means an agent capable of adsorbing at the interface between the propolis and the aqueous phase during the preparation of the composition, thus preventing drops or particles in suspension propolis do not recombine (coalescence phenomenon) and precipitate.
- amphiphilic polymeric agent of natural origin means an amphiphilic polymeric agent extracted from a natural raw material.
- the term “average size” is understood to mean the average diameter of the propolis particles.
- the average diameter being the addition of all the diameters of the propolis particles present in the composition divided by the number of particles present in the composition.
- the subject of the invention is therefore a composition comprising at least propolis and at least one amphiphilic polymeric agent of natural origin.
- the content of amphiphilic polymeric agent of natural origin is between 15% and 70% by weight relative to the weight of the dry materials of the composition.
- the amphiphilic polymeric agent of natural origin can be chosen from gum arabic, a protein and a mixture of proteins of animal or vegetable origin, preferably casein, such as sodium caseinate, or beta-lactoglobulin. , or serum proteins.
- the amphiphilic polymeric agent is adsorbed at the interface between the propolis and the aqueous phase during the preparation of the composition in order to prevent the drops / particles in suspension of propolis from recombining (coalescence phenomenon) and don't rush.
- water is preferably added to the hydro-alcoholic solution comprising dissolved propolis until precipitation of the latter.
- the amphiphilic polymeric agent is gum arabic, preferably gum arabic Eficacia TM XE marketed by the company Nexira.
- the amphiphilic polymeric agent is sodium caseinate or beta-lactoglobulin.
- Gum arabic is a solidified descending sap exudate, produced naturally or following an incision on the trunk and at the foot of trees of the genus Acacia sensu lato (family Fabaceae). More specifically, gum arabic is a highly branched, edible, acidic polysaccharide harvested mainly in Saharan Africa (Maghreb, Mali, Senegal, Chad, Egypt, Sudan, etc.). Gum arabic is an essential raw material for the food industry and serves mainly as an emulsifier, especially for citrus oils, as a protective colloid in emulsions and as a carrier for flavorings. Gum arabic is soluble in water and in hydro-alcoholic solutions and is a food additive referenced under the number E414. Its CAS number is 9000-01-5.
- the content of gum arabic according to the invention is between 15% and 70% by weight relative to the total weight of the dry materials of the composition.
- the content of gum arabic is between 50% and 60% by weight relative to the total weight of the dry materials of the composition.
- the composition according to the invention comprises propolis.
- the propolis used can come from any well identified botanical origin.
- it may be poplar propolis or Baccharis propolis (green propolis from Brazil), in particular Baccharis dracunculifolia.
- the composition comprises poplar propolis.
- the proportion of polyphenols determines the biological activity of the composition and it is therefore appropriate to maximize this proportion in the propolis.
- the amount of polyphenols in the final composition can be adjusted as a function of the content of propolis particles in the aqueous phase.
- the propolis present in the composition according to the invention comprises a large amount of polyphenols.
- the amount of polyphenols is at least 15% by weight relative to the total weight of propolis, preferably at least 30% of polyphenols by weight relative to the total weight of propolis, even more preferably at least 40% of polyphenols in weight relative to the total weight of propolis.
- the composition according to the invention comprises between 30% and 85% of propolis by weight relative to the total weight of dry matter of the composition, preferably between 40% and 60%.
- the composition according to the invention is in the form of a suspension, in particular in the form of a suspension of propolis-in-water type.
- the suspension comprises particles of propolis.
- the propolis particles are advantageously fine particles coated with the amphiphilic polymeric agent.
- the composition according to the invention comprises propolis particles, the average size of the propolis particles of which is less than 10 miti, preferably less than 2 miti. Particularly preferably, the composition according to the invention comprises propolis particles, the average size of the propolis particles of which is less than Imiti. An average size of said particles of less than 10 miti, preferably 2 miti, more preferably Imiti makes it possible to obtain good stability, in particular very slow sedimentation kinetics.
- the composition according to the invention is in the form of a dry powder, said dry powder being advantageously redispersible in water.
- the composition may be in particular in the form of a powder, tablet or capsule to be ingested.
- the composition according to the invention can also comprise other constituents, such as in particular active ingredients or excipients. They may, for example, be constituents such as saccharides, polysaccharides, water-soluble aromatic agents, thickening or gelling agents.
- the composition according to the invention comprises a final ethanol content of strictly less than 1% relative to the mass of the liquid phase.
- the composition according to the invention does not include ethanol or comprises a final ethanol content strictly less than 0.1% relative to the mass of the liquid phase, in order to avoid the effects. undesirable and disadvantages of the products of the prior art.
- the term “final ethanol content” means the ethanol content present in the composition at the end of the manufacturing process, in particular after the step of evaporating the ethanol.
- the invention relates to a method of manufacturing the composition according to the invention comprising at least the implementation of the following steps: mixing an aqueous solution and at least one amphiphilic polymeric agent of natural origin to obtain a solution aqueous, mix this aqueous solution with a hydro-alcoholic solution comprising at least water, ethanol and propolis, the mass ratio of the hydro-alcoholic solution relative to the total mass of the mixture preferably being between 30% and 60%, and the amphiphilic polymeric agent of natural origin representing between 15% and 70% by weight of the dry matter of the mixture, optionally, during or after the previous mixing phase, apply a shear to obtain a pre- emulsion consisting of drops of propolis and ethanol in an aqueous phase, preferably using a rotor-stator device, for a period preferably of between 1 min.
- te and 30 minutes at a shear rate preferably greater than 10 4 s 1 to obtain a pre-emulsion apply a shear to the pre-emulsion or to the mixture if there has been no pre-emulsion, for a period of duration preferably between 1 minute and 30 minutes, preferably using a rotor type device at a shear rate preferably greater than 2.10 4 s 1 or using a high pressure homogenizer at a pressure of homogenization greater than 100 bars or using a channel microfluidizer preferably at a homogenization pressure preferably greater than 100 bars to obtain an emulsion of the propolis-in-water type.
- the homogenization pressure is greater than 240 bars, from particularly advantageously, the pressure is greater than 400 bars.
- a homogenization pressure at least greater than 240 bars makes it possible to obtain drops of propolis suspended in water, the size distribution of which is narrow (monomodal) and the average size of which is at least less than IOmiti, preferably Imiti .
- the system resulting from the previous steps is an emulsion consisting of fine liquid drops of propolis mixed with ethanol and a continuous phase also containing ethanol.
- the manufacturing process according to the invention can also comprise an additional step of evaporating the ethanol by distillation after the shearing step applied to the pre-emulsion or to the mixture. More particularly, a step of evaporating 50% of the mass of emulsion is necessary to obtain a composition comprising a final ethanol content of less than 0.1%. This results in a suspension of solid particles of propolis in an aqueous continuous phase with a very low ethanol content.
- the techniques for determining the ethanol content are well known to those skilled in the art. In the context of the invention, the content is determined by distillation and by electronic densitometry or by ebulliometry.
- the evaporation step is carried out at a pressure between 0.05 and 0.3 bar and at a temperature between 25 and 50 ° C. It is known that a liquid evaporates at all temperatures. However, in the context of the invention, the evaporation process needs to be rapid. Therefore, the liquid must be brought to a boil to accelerate evaporation, while adopting a temperature as low as possible in order to preserve and avoid the degradation of the polyphenols in propolis.
- the evaporation step is preferably carried out at a pressure equal to 0.01 bar and at a temperature equal to 30 ° C.
- a sterilization step is not necessary because of the natural antibacterial characteristics of propolis.
- the manufacturing process according to the invention can also comprise an additional step of drying the suspension after the step of shearing the pre-emulsion or after the step of evaporating the ethanol.
- the step of drying the suspension makes it possible to obtain a dry powder, which is particularly advantageous for preservation or formulation purposes, in particular in the form of a powder, capsule or tablet.
- the drying step can be carried out by lyophilization or atomization. When the drying step is carried out by lyophilization, the prior evaporation of the ethanol by distillation is not necessary.
- the step of drying by freeze-drying makes it possible to redisperse the formulation previously dried in water.
- the finer the propolis-in-water suspension the more resistant the suspension to the lyophilization process (preservation of the initial particle distribution) and the more easily the suspension can be redispersed in water.
- the suspension when the drying step is carried out by atomization, the suspension is nebulized in the presence of a current of hot air and consequently a preliminary distillation step is necessary as a safety measure, the ethanol being a very flammable compound.
- atomization makes it possible to better preserve the size of the drops of the propolis-in-water suspension.
- the hydro-alcoholic propolis solution was supplied by Pollenergy and comprises 17% by weight of propolis, 47.4% ethanol and 35.6% water.
- Eficacia TM XE arabic gum was supplied by Nexira.
- the emulsion was produced using 2 different techniques: a turbulent rotor-stator system, the Ultra-Turrax IKA T25, an M110S microfluidizer consisting of a microfluidic channel: the emulsion is forced to pass through this channel under pressure and the phenomena of cavitation and turbulence make it possible to refine the emulsion drops.
- the ethanol removal was carried out with a RE300 rotary evaporator.
- the suspensions were dehydrated using a Niro Atomizer or an FTS Lyophilizer.
- the emulsions were observed using an Olympus phase contrast optical microscope and their particle size distribution was measured by laser diffraction with a Mastersizer 2000.
- Example 1 for the preparation of a composition according to the invention.
- the hydro-alcoholic solution supplied by Pollenergy is diluted with an aqueous phase.
- the concentration of gum arabic is set at 10% of the total mass.
- the shearing stage was performed with the Ultra-Turrax at a speed of 25,000 rpm for 3 minutes. Only a 1/2 and 3/8 dilution makes it possible to obtain a stable, fine and monodisperse emulsion.
- the particle size distribution of the drops is narrow ( Figure 1 and Figure 2).
- Example 2 for the preparation of a composition according to the invention.
- the hydro-alcoholic solution supplied by Pollenergy is diluted 1/2 with the aqueous phase.
- the concentration of gum arabic is set at 10% of the total mass.
- the shearing step is performed with the Ultra-Turrax. Only the parameters of the shear rate and the duration vary. The results are shown in Table 1 entitled particle size characteristics of emulsions of the same concentration as a function of time and of Ultra-Turrax shear rate.
- the emulsions are fine and monodisperse; the drops have an average diameter smaller than Imiti.
- the particle size distribution of the drops is narrow.
- the drops At a shear speed of 20000rpm and a duration of 30sec, 1min, 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti.
- the distribution particle size of the drops is narrow.
- the drops At a shear speed of 15000rpm and a duration of 1min, 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti. The particle size distribution of the drops is narrow. At a shear rate of 100000rpm and a duration of 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti. The particle size distribution of the drops is narrow.
- a rotary evaporator was used.
- a volume of 100 ml of an emulsion sheared for 1 min in Ultra-Turrax at 25,000 rpm is used for this purpose. It contains a concentration of 10% gum arabic and 8.5% by weight of propolis (dilution by a factor of 2 of the mother hydro-alcoholic solution) relative to the total mass.
- Panel A of Figure 3 shows its particle size distribution. It is kept for 2h30 at a temperature of 45 ° C and a pressure of 0.15 bar. This time allows 50% of the initial solution to evaporate.
- panel B of FIG. 3 the distribution of the propolis particles varied very little compared to that of the emulsion before the distillation step.
- the emulsion is passed through the ebulliometer. This makes it possible to determine the alcoholic degree of a solution by comparing its boiling point with that of pure water. In this case, the temperatures obtained for pure water and the emulsion are equal (100.5 plus or minus 0.5) ° C. Therefore, ethanol was removed from the emulsion.
- Example 4 for the preparation of a composition according to the invention.
- Example 5 for the preparation of a composition according to the invention.
- the composition can comprise at least a concentration of 2.5% of gum arabic, preferably 10% to 15% of gum arabic in the mixture (FIG. 5).
- the rotary evaporator test is performed on the emulsions from the microfluidizer.
- a coarse emulsion is prepared with a concentration of gum arabic equal to 10% and 8.5% by weight of propolis. It is sheared at 5000 rpm for 1 min then passed through a microfluidizer at 600 bars (3 passes). It is then introduced into the rotary evaporator in order to remove the ethanol.
- the same protocol as described in Example 4 is then applied.
- the extraction is interrupted after having removed 50% of the initial mass of solution. As before, the emulsion remains intact. To determine if the ethanol is completely removed, the emulsion is also boiled. In this case, the temperatures obtained for the water and the emulsion are close to 100 ° C. Apart from the measurement uncertainties, it can therefore be said that the ethanol has been removed from the emulsion.
- Example 7 of the preparation of a composition according to the invention in the form of a redispersible dry dispersion.
- An IL emulsion comprising a concentration of 10% gum arabic and 6.375% by weight of propolis. It is prepared by Ultra-Turrax shear for 3 minutes at 25000rpm. Then, in order to remove the ethanol, the emulsion is passed through a rotary evaporator for 2 hours 30 minutes, at 45 ° C. and 0.15 bar. The atomizer is then preheated until it reaches 210 ° C at the inlet and 90 ° C at the air outlet. The sample is then completely introduced into the apparatus. Thus, the powder obtained is fine and does not stick to the walls. It is then interesting to measure its particle size profile and to observe it under a microscope to see if the emulsion is still monodisperse and fine.
- FIG. 7 shows that the emulsion remained almost intact before and after atomization.
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Abstract
The invention relates to a composition comprising at least propolis and at least one natural amphiphilic polymeric agent, preferably gum arabic. The invention also relates to the drying of said composition to obtain a water-redispersible powder.
Description
COMPOSITION COMPRENANT DES PARTICULES DE PROPOLIS COMPOSITION CONTAINING PARTICLES OF PROPOLIS
L'invention concerne une nouvelle composition d'une suspension de propolis cinétiquement stable et son procédé de préparation. La composition comprend au moins des particules de propolis de taille micrométrique dispersées dans une solution aqueuse en présence d'au moins un agent polymérique amphiphile d'origine animale ou végétale, tel que la gomme arabique. L'invention concerne aussi le séchage de ladite suspension pour obtenir une poudre redispersable dans l'eau. The invention relates to a novel composition of a kinetically stable propolis suspension and its preparation process. The composition comprises at least propolis particles of micrometric size dispersed in an aqueous solution in the presence of at least one amphiphilic polymeric agent of animal or plant origin, such as gum arabic. The invention also relates to the drying of said suspension to obtain a powder redispersible in water.
La propolis est une substance résineuse, gommeuse et balsamique qui est constituée de cire et sécrétions salivaires des abeilles mélangées aux substances récoltées sur l'écorce et les bourgeons de plantes ou d'arbres, tels que le peuplier, le bouleau, le saule, l'épicéa, le sapin et le cocotier. A la fin du processus de maturation organique, la propolis constitue une composition riche en polyphénols, flavonoïdes, oligo-éléments et parabène, ce qui confère à la substance des propriétés sur la santé et notamment des propriétés antibactériennes, antibiotiques, antifongiques, cicatrisantes. Propolis is a resinous, gummy and balsamic substance which consists of wax and salivary secretions from bees mixed with substances collected from the bark and buds of plants or trees, such as poplar, birch, willow, l 'spruce, fir and coconut. At the end of the organic maturation process, propolis constitutes a composition rich in polyphenols, flavonoids, trace elements and parabens, which gives the substance properties on health and in particular antibacterial, antibiotic, antifungal and healing properties.
Les flavonoïdes sont des pigments végétaux qui jouent le rôle d'antimicrobiens, antifongiques, antispasmodiques et antioxydants comme la chrysine, la pinocembrine et la galangine. La science moderne et notamment les firmes pharmaceutiques s'intéressent de plus en plus à la propolis et des études récentes ont confirmé ses vertus thérapeutiques connues depuis l'Antiquité. Les égyptiens s'en servaient pour embaumer, les grecs l'utilisaient contre les infections de la peau, les plaies et suppurations, les romains s'en servaient pour désinfecter et faciliter la cicatrisation et les européens du moyen-âge s'en servaient pour traiter les maladies de la bouche et de la respiration. Outre la médecine, la propolis servait également dans la fabrication des vernis, notamment des instruments de musique, mais également comme produit antirouille. Flavonoids are plant pigments that act as antimicrobials, antifungals, antispasmodics, and antioxidants like chrysin, pinocembrin, and galangin. Modern science and in particular pharmaceutical companies are increasingly interested in propolis and recent studies have confirmed its therapeutic virtues known since Antiquity. The Egyptians used it for embalming, the Greeks used it against skin infections, wounds and suppurations, the Romans used it to disinfect and facilitate healing and medieval Europeans used it for treat diseases of the mouth and breathing. Besides medicine, propolis was also used in the manufacture of varnishes, especially musical instruments, but also as an anti-rust product.
Cependant, la majorité des principes actifs contenus dans la propolis sont insolubles dans l'eau, mais parfaitement solubles dans l'éthanol, l'acétone, le benzène et l'éther. Par conséquent, la propolis est commercialisée majoritairement sous la forme d'une solution hydro-alcoolique. Or, les solutions hydro-alcooliques limitent fortement le marché pour des raisons médicales, religieuses ou liées à l'âge des patients, mais peuvent également entraîner de nombreux symptômes en cas d'ingestion ou projection tels que : irritations, allergies, états de somnolence, agitation, maux de tête, nausées, et vertiges.
La propolis est également commercialisée sous forme brute, sous forme de gomme, de spray buccal, en sirop et en gélules. However, the majority of the active ingredients contained in propolis are insoluble in water, but perfectly soluble in ethanol, acetone, benzene and ether. Consequently, propolis is mainly marketed in the form of a hydro-alcoholic solution. However, hydro-alcoholic solutions severely limit the market for medical, religious or age-related reasons, but can also cause many symptoms in the event of ingestion or projection such as: irritation, allergies, drowsiness. , restlessness, headache, nausea, and dizziness. Propolis is also marketed in raw form, in the form of a gum, an oral spray, in syrup and in capsules.
Il est donc nécessaire de développer une nouvelle formulation permettant de limiter les effets indésirables, notamment des produits à base de solution hydro-alcooliques tout en conservant les vertus thérapeutiques de la propolis. It is therefore necessary to develop a new formulation making it possible to limit the undesirable effects, in particular products based on hydro-alcoholic solutions while retaining the therapeutic properties of propolis.
Actuellement, il n'est pas connu de solution satisfaisante. Currently, no satisfactory solution is known.
L'objectif de la présente invention est de proposer une nouvelle formulation permettant de concilier les vertus thérapeutiques de la propolis et de supprimer les effets indésirables liés à la présence d'éthanol qui limitent de fait le marché visé. The objective of the present invention is to provide a new formulation making it possible to reconcile the therapeutic virtues of propolis and to eliminate the undesirable effects linked to the presence of ethanol which de facto limit the targeted market.
Ainsi, l'invention concerne une composition comprenant au moins de la propolis et au moins un agent polymérique amphiphile d'origine naturelle. Thus, the invention relates to a composition comprising at least propolis and at least one amphiphilic polymeric agent of natural origin.
Avantageusement, l'invention vise une composition pour son utilisation comme complément alimentaire. En effet, les consommateurs se tournent idéalement vers ces compléments alimentaires au détriment des médicaments traditionnels notamment pour les populations fragiles telles que les enfants, personnes âgées, femmes enceintes. Advantageously, the invention relates to a composition for its use as a food supplement. Indeed, consumers ideally turn to these food supplements to the detriment of traditional medicines, especially for fragile populations such as children, the elderly and pregnant women.
L'invention est à présent décrite en détails en regard des figures décrites ci-après. Les figures ne sont qu'illustratives de certains modes de réalisation de l'invention et ne sont pas limitatives. The invention is now described in detail with reference to the figures described below. The figures are only illustrative of certain embodiments of the invention and are not limiting.
Figures Figures
[Figure 1] est une image de microscopie (panel A) et une granulométrie (panel B) de la composition comprenant une concentration de 8,5% en poids de propolis par rapport à la masse totale de la dispersion (46% par rapport au poids total des matières sèches) selon l'exemple 1. [Figure 1] is a microscopy image (panel A) and a particle size (panel B) of the composition comprising a concentration of 8.5% by weight of propolis relative to the total mass of the dispersion (46% relative to the total weight of dry matter) according to Example 1.
[Figure 2] est une image de microscopie (panel A) et une granulométrie (panel B) de la composition comprenant une concentration de 6,375% en poids de propolis par rapport à la masse totale de la dispersion (40% par rapport au poids total des matières sèches) selon l'exemple 1. [Figure 2] is a microscopy image (panel A) and a particle size (panel B) of the composition comprising a concentration of 6.375% by weight of propolis relative to the total mass of the dispersion (40% relative to the total weight dry matter) according to Example 1.
[Figure 3A] est une granulométrie de la composition selon l'exemple 3 avant l'évaporation de l'éthanol. [Figure 3A] is a particle size of the composition according to Example 3 before the evaporation of the ethanol.
[Figure 3B] est une granulométrie de la composition selon l'exemple 3 après évaporation de l'éthanol.
[Figure 4A] est une granulométrie de la composition selon l'exemple 4 avec une émulsion préparée au microfluidiseur à une pression de 400 bars. [Figure 3B] is a particle size distribution of the composition according to Example 3 after evaporation of the ethanol. [Figure 4A] is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 400 bars.
[Figure 4B] est une granulométrie de la composition selon l'exemple 4 avec une émulsion préparée au microfluidiseur à une pression de 600 bars. [Figure 4B] is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 600 bar.
[Figure 4C] est une granulométrie de la composition selon l'exemple 4 avec une émulsion préparée au microfluidiseur à une pression de 800 bars. [Figure 4C] is a particle size distribution of the composition according to Example 4 with an emulsion prepared in a microfluidizer at a pressure of 800 bar.
[Figure 5] représente l'évolution du diamètre moyen en surface des émulsions selon l'exemple 5 en fonction de la concentration en gomme arabique exprimée en % de la masse totale. [Figure 5] shows the change in the average diameter at the surface of the emulsions according to Example 5 as a function of the concentration of gum arabic expressed as% of the total mass.
[Figure 6A1] est une granulométrie de la composition selon l'exemple 7 sous forme d'une dispersion sèche avant lyophilisation et redispersion dans de l'eau distillée préparé à l'aie d'un microfluidiseur. [Figure 6A1] is a particle size of the composition according to Example 7 in the form of a dry dispersion before lyophilization and redispersion in distilled water prepared using a microfluidizer.
[Figure 6A2] est une granulométrie de la composition selon l'exemple 7 sous forme d'une dispersion sèche après lyophilisation et redispersion dans de l'eau distillée préparé à l'aie d'un microfluidiseur. [Figure 6A2] is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion after lyophilization and redispersion in distilled water prepared using a microfluidizer.
[Figure 6B1] est une granulométrie de la composition selon l'exemple 7 sous forme d'une dispersion sèche avant lyophilisation et redispersion dans de l'eau distillée préparé à l'aie d'un d'un Ultra-Turrax. [Figure 6B1] is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion before lyophilization and redispersion in distilled water prepared using an Ultra-Turrax.
[Figure 6B2] est une granulométrie de la composition selon l'exemple 7 sous forme d'une dispersion sèche après lyophilisation et redispersion dans de l'eau distillée préparé à l'aie d'un d'un Ultra-Turrax. [Figure 6B2] is a particle size distribution of the composition according to Example 7 in the form of a dry dispersion after lyophilization and redispersion in distilled water prepared using an Ultra-Turrax.
[Figure 7A] est une granulométrie de la composition selon l'exemple 8 sous forme d'une dispersion sèche avant atomisation. [Figure 7A] is a particle size of the composition according to Example 8 in the form of a dry dispersion before atomization.
[Figure 7B] est une granulométrie de la composition selon l'exemple 8 sous forme d'une dispersion sèche après atomisation . [FIG. 7B] is a particle size distribution of the composition according to Example 8 in the form of a dry dispersion after atomization.
Définitions Definitions
Par « propolis » au sens de l'invention on entend une substance résineuse, gommeuse et balsamique constituée de cire et de sécrétions salivaires des abeilles mélangées aux substances récoltées sur écorces et bourgeons de plantes ou arbres. La propolis pouvant être indifférament la substance brute ou transformée mais également un extrait de propolis ou des particules de propolis. For the purposes of the invention, the term “propolis” means a resinous, gummy and balsamic substance consisting of wax and salivary secretions from bees mixed with substances collected from the bark and buds of plants or trees. The propolis can be indifferently the raw or transformed substance but also an extract of propolis or particles of propolis.
Par « extrait de propolis » on entend toute propolis récoltée transformée par un procédé
d'extraction permettant d'enlever les impuretés présentes dans l'extrait brut et/ou de concentrer la propolis en un ou plusieurs de ses constituants. L'extrait de propolis peut se présenter sous plusieurs formes. Préférentiellement, il se présente sous forme de poudre. By "propolis extract" is meant any harvested propolis transformed by a process extraction making it possible to remove the impurities present in the crude extract and / or to concentrate the propolis in one or more of its constituents. Propolis extract can come in many forms. Preferably, it is in the form of a powder.
Par « suspension de type propolis-dans-eau » on entend au sens de l'invention une dispersion obtenue sous agitation modérée ou accélérée à température ambiante ou plus élevée d'au moins de la propolis, de l'agent polymérique amphiphile tel que la gomme arabique ou le caséinate de sodium ou la béta-lactoglobuline, et de l'eau, dans laquelle les gouttes ou particules de propolis sont en suspension dans l'eau. For the purposes of the invention, the term “propolis-in-water suspension” means a dispersion obtained with moderate or accelerated stirring at room temperature or higher of at least propolis, of the amphiphilic polymeric agent such as gum arabic or sodium caseinate or beta-lactoglobulin, and water, in which the drops or particles of propolis are suspended in the water.
On entend au sens de l'invention, « particules de propolis » ou indifféremment « goutte de propolis », de la propolis enrobée d'un agent polymérique amphiphile. For the purposes of the invention, “propolis particles” or equally “drop of propolis” is understood to mean propolis coated with an amphiphilic polymeric agent.
Par « agent polymérique amphiphile » on entend au sens de l'invention, un agent capable de s'adsorber à l'interface entre la propolis et la phase aqueuse lors de la préparation de la composition pour ainsi éviter que les gouttes ou particules en suspension de propolis ne se recombinent (phénomène de coalescence) et précipitent. Par « agent polymérique amphiphile d'origine naturelle » on entend au sens de l'invention, un agent polymérique amphiphile extrait d'une matière première naturelle. For the purposes of the invention, the term “amphiphilic polymeric agent” means an agent capable of adsorbing at the interface between the propolis and the aqueous phase during the preparation of the composition, thus preventing drops or particles in suspension propolis do not recombine (coalescence phenomenon) and precipitate. For the purposes of the invention, the term “amphiphilic polymeric agent of natural origin” means an amphiphilic polymeric agent extracted from a natural raw material.
Par « taille moyenne », on entend au sens de l'invention le diamètre moyen des particules de propolis. Le diamètre moyen étant l'addition de l'ensemble des diamètres des particules de propolis présentes dans la composition divisé par le nombre de particules présentes dans la composition. Description détaillée de l'invention For the purposes of the invention, the term “average size” is understood to mean the average diameter of the propolis particles. The average diameter being the addition of all the diameters of the propolis particles present in the composition divided by the number of particles present in the composition. Detailed description of the invention
L'invention a donc pour objet une composition comprenant au moins de la propolis et au moins un agent polymérique amphiphile d'origine naturelle. The subject of the invention is therefore a composition comprising at least propolis and at least one amphiphilic polymeric agent of natural origin.
Avantageusement la teneur en agent polymérique amphiphile d'origine naturelle est comprise entre 15% et 70% en poids par rapport au poids des matières sèches de la composition. L'agent polymérique amphiphile d'origine naturelle peut-être choisi parmi la gomme arabique, une protéine et un mélange de protéines d'origine animale ou végétale, préférentiellement de la caséine, tel que le caséinate de sodium, ou de la béta-lactoglobuline, ou des protéines sériques.
Préférentiellement, l'agent polymérique amphiphile s'adsorbe à l'interface entre la propolis et la phase aqueuse lors de la préparation de la composition afin d'empêcher que les gouttes/particules en suspension de propolis ne se recombinent (phénomène de coalescence) et ne précipitent. Advantageously, the content of amphiphilic polymeric agent of natural origin is between 15% and 70% by weight relative to the weight of the dry materials of the composition. The amphiphilic polymeric agent of natural origin can be chosen from gum arabic, a protein and a mixture of proteins of animal or vegetable origin, preferably casein, such as sodium caseinate, or beta-lactoglobulin. , or serum proteins. Preferably, the amphiphilic polymeric agent is adsorbed at the interface between the propolis and the aqueous phase during the preparation of the composition in order to prevent the drops / particles in suspension of propolis from recombining (coalescence phenomenon) and don't rush.
En effet, lors de la préparation de la composition, on ajoute préférentiellement de l'eau dans la solution hydro-alcoolique comprenant de la propolis dissoute jusqu'à précipitation de cette dernière. In fact, during the preparation of the composition, water is preferably added to the hydro-alcoholic solution comprising dissolved propolis until precipitation of the latter.
Selon un mode de réalisation préféré, l'agent polymérique amphiphile est la gomme arabique, préférentiellement la gomme arabique Eficacia™ XE commercialisée par la société Nexira. According to a preferred embodiment, the amphiphilic polymeric agent is gum arabic, preferably gum arabic Eficacia ™ XE marketed by the company Nexira.
Selon une variante, l'agent polymérique amphiphile est le caséinate de sodium ou la béta- lactoglobuline. La gomme arabique est un exsudât de sève descendante solidifié, produit naturellement ou à la suite d'une incision sur le tronc et au pied d'arbres du genre Acacia sensu lato (famille des Fabaceae). Plus particulièrement, la gomme arabique est un polysaccharide acide fortement ramifié, comestible et récolté principalement en Afrique saharienne (Maghreb, Mali, Sénégal, Tchad, Égypte, Soudan, etc.). La gomme arabique est une matière première essentielle pour l'industrie agro-alimentaire et sert principalement d'émulsifiant, spécialement pour les huiles d'agrumes, de colloïde protecteur dans les émulsions et de supports pour les arômes. La gomme arabique est soluble dans l'eau et dans des solutions hydro-alcooliques et est un additif alimentaire référencé sous le numéro E414. Son numéro CAS est 9000-01-5. According to one variant, the amphiphilic polymeric agent is sodium caseinate or beta-lactoglobulin. Gum arabic is a solidified descending sap exudate, produced naturally or following an incision on the trunk and at the foot of trees of the genus Acacia sensu lato (family Fabaceae). More specifically, gum arabic is a highly branched, edible, acidic polysaccharide harvested mainly in Saharan Africa (Maghreb, Mali, Senegal, Chad, Egypt, Sudan, etc.). Gum arabic is an essential raw material for the food industry and serves mainly as an emulsifier, especially for citrus oils, as a protective colloid in emulsions and as a carrier for flavorings. Gum arabic is soluble in water and in hydro-alcoholic solutions and is a food additive referenced under the number E414. Its CAS number is 9000-01-5.
Préférentiellement, la teneur en gomme arabique selon l'invention est comprise entre 15% et 70% en poids par rapport au poids total des matières sèches de la composition. Preferably, the content of gum arabic according to the invention is between 15% and 70% by weight relative to the total weight of the dry materials of the composition.
Encore plus préférentiellement, la teneur en gomme arabique est comprise entre 50% et 60% en poids par rapport au poids total des matières sèches de la composition. Even more preferably, the content of gum arabic is between 50% and 60% by weight relative to the total weight of the dry materials of the composition.
Selon un autre aspect, la composition selon l'invention comprend de la propolis. La propolis utilisée peut provenir de toute origine botanique bien identifiée. Par exemple il peut s'agir de propolis de peuplier ou de propolis de Baccharis (propolis verte du Brésil), notamment de Baccharis dracunculifolia. Préférentiellement la composition comprend de la propolis de peuplier. According to another aspect, the composition according to the invention comprises propolis. The propolis used can come from any well identified botanical origin. For example, it may be poplar propolis or Baccharis propolis (green propolis from Brazil), in particular Baccharis dracunculifolia. Preferably, the composition comprises poplar propolis.
La proportion de polyphénols détermine l'activité biologique de la composition et il convient donc de maximiser cette proportion dans la propolis. La quantité de polyphénols dans la composition finale est ajustable en fonction de teneur en particules de propolis dans la phase aqueuse.
Avantageusement, la propolis présente dans la composition selon l'invention comprend une quantité importante de polyphénols. Ainsi, la quantité de polyphénols est d'au moins 15% en poids par rapport au poids total de propolis, préférentiellement au moins 30% de polyphénols en poids par rapport au poids total de propolis, encore plus préférentiellement au moins 40% de polyphénols en poids par rapport au poids total de propolis. The proportion of polyphenols determines the biological activity of the composition and it is therefore appropriate to maximize this proportion in the propolis. The amount of polyphenols in the final composition can be adjusted as a function of the content of propolis particles in the aqueous phase. Advantageously, the propolis present in the composition according to the invention comprises a large amount of polyphenols. Thus, the amount of polyphenols is at least 15% by weight relative to the total weight of propolis, preferably at least 30% of polyphenols by weight relative to the total weight of propolis, even more preferably at least 40% of polyphenols in weight relative to the total weight of propolis.
Préférentiellement, la composition selon l'invention comprend entre 30% et 85% de propolis en poids par rapport au poids total de matières sèches de la composition, préférentiellement entre 40% et 60%. Preferably, the composition according to the invention comprises between 30% and 85% of propolis by weight relative to the total weight of dry matter of the composition, preferably between 40% and 60%.
Selon un mode de réalisation, la composition selon l'invention se présente sous forme d'une suspension, en particulier sous forme d'une suspension de type propolis-dans-eau. According to one embodiment, the composition according to the invention is in the form of a suspension, in particular in the form of a suspension of propolis-in-water type.
Avantageusement, à l'état final, la suspension comprend des particules de propolis. Les particules de propolis sont avantageusement des particules fines enrobées par l'agent polymérique amphiphile. Advantageously, in the final state, the suspension comprises particles of propolis. The propolis particles are advantageously fine particles coated with the amphiphilic polymeric agent.
La propolis ayant une densité supérieure à celle de l'eau, les particules en suspension tendent à sédimenter au cours du stockage. Cette sédimentation rend la suspension inhomogène. La suspension est toutefois redispersable par simple agitation manuelle. La composition selon l'invention comprend des particules de propolis dont la taille moyenne des particules de propolis est inférieure à 10 miti, préférentiellement inférieure à 2 miti. De façon particulièrement préférée, la composition selon l'invention comprend des particules de propolis dont la taille moyenne des particules de propolis est inférieure à Imiti. Une taille moyenne desdites particules inférieure à 10 miti, préférentiellement 2 miti, plus préférentiellement Imiti permet d'obtenir une bonne stabilité, notamment une cinétique de sédimentation très lente. Since propolis has a density greater than that of water, suspended particles tend to sediment during storage. This sedimentation makes the suspension inhomogeneous. The suspension is however redispersible by simple manual stirring. The composition according to the invention comprises propolis particles, the average size of the propolis particles of which is less than 10 miti, preferably less than 2 miti. Particularly preferably, the composition according to the invention comprises propolis particles, the average size of the propolis particles of which is less than Imiti. An average size of said particles of less than 10 miti, preferably 2 miti, more preferably Imiti makes it possible to obtain good stability, in particular very slow sedimentation kinetics.
Selon un autre mode de réalisation, la composition selon l'invention se présente sous forme de poudre sèche, ladite poudre sèche étant avantageusement redispersable dans l'eau. La composition peut se présenter en particulier sous forme de poudre, de comprimé, de gélule à ingérer. Eventuellement, la composition selon l'invention peut également comprendre d'autres constituants, tels que notamment des principes actifs ou des excipients. Il peut s'agir par exemple de constituants tels que des saccharides, des polysaccharides, des agents aromatiques hydrosolubles, des agents épaississants ou gélifiants. According to another embodiment, the composition according to the invention is in the form of a dry powder, said dry powder being advantageously redispersible in water. The composition may be in particular in the form of a powder, tablet or capsule to be ingested. Optionally, the composition according to the invention can also comprise other constituents, such as in particular active ingredients or excipients. They may, for example, be constituents such as saccharides, polysaccharides, water-soluble aromatic agents, thickening or gelling agents.
La composition selon l'invention comprend une teneur finale en éthanol strictement inférieure à 1%
par rapport à la masse de la phase liquide. Préférentiellement, quelle que soit sa forme, la composition selon l'invention ne comprend pas d'éthanol ou comprend une teneur finale en éthanol strictement inférieure à 0,1% par rapport à la masse de la phase liquide, afin d'éviter les effets indésirables et inconvénients des produits de l'art antérieur. Par « teneur finale en éthanol », on entend au sens de l'invention, la teneur en éthanol présent dans la composition à la fin du procédé de fabrication, en particulier après l'étape d'évaporation de l'éthanol. The composition according to the invention comprises a final ethanol content of strictly less than 1% relative to the mass of the liquid phase. Preferably, whatever its form, the composition according to the invention does not include ethanol or comprises a final ethanol content strictly less than 0.1% relative to the mass of the liquid phase, in order to avoid the effects. undesirable and disadvantages of the products of the prior art. For the purposes of the invention, the term “final ethanol content” means the ethanol content present in the composition at the end of the manufacturing process, in particular after the step of evaporating the ethanol.
Selon un autre aspect, l'invention concerne un procédé de fabrication de la composition selon l'invention comprenant au moins la mise en oeuvre des étapes suivantes : mélanger une solution aqueuse et au moins un agent polymérique amphiphile d'origine naturelle pour obtenir une solution aqueuse, mélanger cette solution aqueuse avec une solution hydro-alcoolique comprenant au moins de l'eau, de l'éthanol et de la propolis, le ratio massique de la solution hydro-alcoolique par rapport à la masse totale du mélange étant préférentiellement compris entre 30% et 60%, et l'agent polymérique amphiphile d'origine naturelle représentant entre 15% et 70% en poids des matières sèches du mélange, éventuellement, pendant ou après la précédente phase de mélange, appliquer un cisaillement pour obtenir une pré-émulsion constituée de gouttes de propolis et d'éthanol dans une phase aqueuse, préférentiellement à l'aide d'un dispositif rotor-stator, pendant une durée préférentiellement comprise entre 1 minute et 30 minutes à une vitesse de cisaillement préférentiellement supérieure à 104 s 1 pour obtenir une pré-émulsion, appliquer un cisaillement sur la pré-émulsion ou sur le mélange s'il n'y a pas eu de pré émulsion, pendant une durée préférentiellement comprise entre 1 minute et 30 minutes, préférentiellement à l'aide d'un dispositif de type rotor à une vitesse de cisaillement préférentiellement supérieure à 2.104 s 1 ou à l'aide d'un homogénéisateur haute pression à une pression d'homogénéisation supérieure à 100 bars ou à l'aide d'un microfluidiseur à canal préférentiellement à une pression d'homogénéisation préférentiellement supérieure à 100 bars pour obtenir une émulsion de type propolis-dans-eau. According to another aspect, the invention relates to a method of manufacturing the composition according to the invention comprising at least the implementation of the following steps: mixing an aqueous solution and at least one amphiphilic polymeric agent of natural origin to obtain a solution aqueous, mix this aqueous solution with a hydro-alcoholic solution comprising at least water, ethanol and propolis, the mass ratio of the hydro-alcoholic solution relative to the total mass of the mixture preferably being between 30% and 60%, and the amphiphilic polymeric agent of natural origin representing between 15% and 70% by weight of the dry matter of the mixture, optionally, during or after the previous mixing phase, apply a shear to obtain a pre- emulsion consisting of drops of propolis and ethanol in an aqueous phase, preferably using a rotor-stator device, for a period preferably of between 1 min. te and 30 minutes at a shear rate preferably greater than 10 4 s 1 to obtain a pre-emulsion, apply a shear to the pre-emulsion or to the mixture if there has been no pre-emulsion, for a period of duration preferably between 1 minute and 30 minutes, preferably using a rotor type device at a shear rate preferably greater than 2.10 4 s 1 or using a high pressure homogenizer at a pressure of homogenization greater than 100 bars or using a channel microfluidizer preferably at a homogenization pressure preferably greater than 100 bars to obtain an emulsion of the propolis-in-water type.
Selon un mode de réalisation préféré, la pression d'homogénéisation est supérieure à 240 bars, de
façon particulièrement avantageuse, la pression est supérieure à 400 bars. Une pression d'homogénéisation au moins supérieure à 240 bars permet d'obtenir des gouttes de propolis en suspension dans l'eau, dont la distribution des tailles est resserrée (monomodale) et dont la taille moyenne est au moins inférieure à IOmiti, préférentiellement Imiti. Le système issu des étapes précédentes est une émulsion constituée de fines gouttes liquides de propolis mélangées à l'éthanol et une phase continue contenant également de l'éthanol. According to a preferred embodiment, the homogenization pressure is greater than 240 bars, from particularly advantageously, the pressure is greater than 400 bars. A homogenization pressure at least greater than 240 bars makes it possible to obtain drops of propolis suspended in water, the size distribution of which is narrow (monomodal) and the average size of which is at least less than IOmiti, preferably Imiti . The system resulting from the previous steps is an emulsion consisting of fine liquid drops of propolis mixed with ethanol and a continuous phase also containing ethanol.
Le procédé de fabrication selon l'invention peut également comprendre une étape supplémentaire d'évaporation de l'éthanol par distillation après l'étape de cisaillement appliquée sur la pré-émulsion ou sur le mélange. Plus particulièrement, une étape d'évaporation de 50% de la masse d'émulsion est nécessaire pour obtenir une composition comprenant une teneur finale en éthanol inférieure à 0,1%. Il en résulte une suspension de particules solides de propolis dans une phase continue aqueuse à teneur très faible en éthanol. Les techniques pour déterminer la teneur en éthanol sont bien connues de l'homme du métier. Dans le cadre de l'invention, la teneur est déterminée par distillation et par densitométrie électronique ou par ébulliométrie. Avantageusement, l'étape d'évaporation est réalisée à une pression comprise entre 0,05 et 0,3 bar et à une température comprise entre 25 et 50°C. Il est connu qu'un liquide s'évapore à toutes les températures. Toutefois, dans le contexte de l'invention, le processus d'évaporation nécessite d'être rapide. Par conséquent, le liquide doit être porté à ébullition pour accélérer l'évaporation, tout en adoptant une température aussi faible que possible afin de préserver et éviter la dégradation des polyphénols de la propolis. The manufacturing process according to the invention can also comprise an additional step of evaporating the ethanol by distillation after the shearing step applied to the pre-emulsion or to the mixture. More particularly, a step of evaporating 50% of the mass of emulsion is necessary to obtain a composition comprising a final ethanol content of less than 0.1%. This results in a suspension of solid particles of propolis in an aqueous continuous phase with a very low ethanol content. The techniques for determining the ethanol content are well known to those skilled in the art. In the context of the invention, the content is determined by distillation and by electronic densitometry or by ebulliometry. Advantageously, the evaporation step is carried out at a pressure between 0.05 and 0.3 bar and at a temperature between 25 and 50 ° C. It is known that a liquid evaporates at all temperatures. However, in the context of the invention, the evaporation process needs to be rapid. Therefore, the liquid must be brought to a boil to accelerate evaporation, while adopting a temperature as low as possible in order to preserve and avoid the degradation of the polyphenols in propolis.
Selon un mode de réalisation particulièrement adapté, l'étape d'évaporation est préférentiellement réalisée à une pression égale à 0,01 bar et à une température égale à 30°C. According to a particularly suitable embodiment, the evaporation step is preferably carried out at a pressure equal to 0.01 bar and at a temperature equal to 30 ° C.
Dans le contexte de l'invention, une étape de stérilisation n'est pas nécessaire du fait des caractéristiques naturelles antibactériennes de la propolis. Le procédé de fabrication selon l'invention peut également comprendre une étape supplémentaire de séchage de la suspension après l'étape de cisaillement de la pré-émulsion ou après l'étape d'évaporation de l'éthanol. L'étape de séchage de la suspension permet d'obtenir une poudre sèche, particulièrement avantageuse à des fins de conservation ou de formulation, notamment sous forme de poudre, de gélule ou de comprimé.
Dans le cadre de l'invention, l'étape de séchage peut être réalisée par lyophilisation ou atomisation. Lorsque l'étape de séchage est mise en oeuvre par lyophilisation, l'évaporation préalable de l'éthanol par distillation n'est pas nécessaire. In the context of the invention, a sterilization step is not necessary because of the natural antibacterial characteristics of propolis. The manufacturing process according to the invention can also comprise an additional step of drying the suspension after the step of shearing the pre-emulsion or after the step of evaporating the ethanol. The step of drying the suspension makes it possible to obtain a dry powder, which is particularly advantageous for preservation or formulation purposes, in particular in the form of a powder, capsule or tablet. In the context of the invention, the drying step can be carried out by lyophilization or atomization. When the drying step is carried out by lyophilization, the prior evaporation of the ethanol by distillation is not necessary.
Avantageusement, l'étape de séchage par lyophilisation permet de redisperser la formulation préalablement séchée dans l'eau. Plus la suspension propolis-dans-eau est fine, plus la suspension est résistante au processus de lyophilisation (préservation de la distribution des particules initiale) et plus la suspension pourra être facilement redispersée dans l'eau. Advantageously, the step of drying by freeze-drying makes it possible to redisperse the formulation previously dried in water. The finer the propolis-in-water suspension, the more resistant the suspension to the lyophilization process (preservation of the initial particle distribution) and the more easily the suspension can be redispersed in water.
Selon un mode de réalisation particulier, lorsque l'étape de séchage est réalisée par atomisation, la suspension est nébulisée en présence d'un courant d'air chaud et par conséquent une étape de distillation préalable est nécessaire par mesure de sécurité, l'éthanol étant un composé très inflammable. Avantageusement, l'atomisation permet de mieux préserver la taille des gouttes de la suspension de propolis-dans-eau. According to a particular embodiment, when the drying step is carried out by atomization, the suspension is nebulized in the presence of a current of hot air and consequently a preliminary distillation step is necessary as a safety measure, the ethanol being a very flammable compound. Advantageously, atomization makes it possible to better preserve the size of the drops of the propolis-in-water suspension.
Exemple de composition de propolis selon l'invention. Example of propolis composition according to the invention.
Matériel et méthodes. Material and methods.
La solution hydro-alcoolique de propolis a été fournie par Pollenergie et comprend 17% en poids de propolis, 47,4% d'éthanol et 35,6% d'eau. La gomme arabique Eficacia™ XE a été fournie par Nexira. The hydro-alcoholic propolis solution was supplied by Pollenergie and comprises 17% by weight of propolis, 47.4% ethanol and 35.6% water. Eficacia ™ XE arabic gum was supplied by Nexira.
L'émulsion a été réalisée à l'aide de 2 techniques différentes : un système rotor-stator turbulent, l'Ultra-Turrax IKA T25, un microfluidiseur M110S constitué d'un canal microfluidique : l'émulsion est forcée à passer à travers ce canal sous pression et les phénomènes de cavitation et de turbulence permettent d'affiner les gouttes d'émulsion. The emulsion was produced using 2 different techniques: a turbulent rotor-stator system, the Ultra-Turrax IKA T25, an M110S microfluidizer consisting of a microfluidic channel: the emulsion is forced to pass through this channel under pressure and the phenomena of cavitation and turbulence make it possible to refine the emulsion drops.
L'élimination de l'éthanol a été effectuée avec un évaporateur rotatif RE300. The ethanol removal was carried out with a RE300 rotary evaporator.
Les suspensions ont été déshydratées à l'aide d'un Atomiseur Niro ou d'un Lyophilisateur FTS. Les émulsions ont été observées à l'aide d'un microscope optique à contraste de phase Olympus et leur distribution granulométrique a été mesurée par diffraction laser au Mastersizer 2000. The suspensions were dehydrated using a Niro Atomizer or an FTS Lyophilizer. The emulsions were observed using an Olympus phase contrast optical microscope and their particle size distribution was measured by laser diffraction with a Mastersizer 2000.
Exemple 1 de préparation d'une composition selon l'invention. Example 1 for the preparation of a composition according to the invention.
La solution hydro-alcoolique fournie par Pollenergie est diluée avec une phase aqueuse. La concentration de gomme arabique est fixée à 10% de la masse totale. L'étape de cisaillement a été
réalisée avec l'Ultra-Turrax à une vitesse de 25000 rpm pendant 3 minutes. Seule une dilution au 1/2 et au 3/8 permet d'obtenir une émulsion stable, fine et monodisperse. La distribution granulométrique des gouttes est étroite (Figure 1 et Figure 2). The hydro-alcoholic solution supplied by Pollenergie is diluted with an aqueous phase. The concentration of gum arabic is set at 10% of the total mass. The shearing stage was performed with the Ultra-Turrax at a speed of 25,000 rpm for 3 minutes. Only a 1/2 and 3/8 dilution makes it possible to obtain a stable, fine and monodisperse emulsion. The particle size distribution of the drops is narrow (Figure 1 and Figure 2).
Exemple 2 de préparation d'une composition selon l'invention. La solution hydro-alcoolique fournie par Pollenergie est diluée au 1/2 avec la phase aqueuse. La concentration de gomme arabique est fixée à 10% de la masse totale. L'étape de cisaillement est réalisée avec l'Utra-Turrax. Seuls les paramètres de la vitesse de cisaillement et la durée varient. Les résultats sont représentés dans le tableau 1 intitulé caractéristiques granulométriques des émulsions de même concentration en fonction du temps et de la vitesse de cisaillement à l'Ultra- Turrax. Example 2 for the preparation of a composition according to the invention. The hydro-alcoholic solution supplied by Pollenergie is diluted 1/2 with the aqueous phase. The concentration of gum arabic is set at 10% of the total mass. The shearing step is performed with the Ultra-Turrax. Only the parameters of the shear rate and the duration vary. The results are shown in Table 1 entitled particle size characteristics of emulsions of the same concentration as a function of time and of Ultra-Turrax shear rate.
[Tableau 1]
[Table 1]
A une vitesse de cisaillement de 25000rpm et une durée de 15sec, 30sec, 1min, 2min et 3min, les émulsions sont fines et monodisperses ; les gouttes ont un diamètre moyen inférieur à Imiti. La distribution granulométrique des gouttes est étroite. At a shear rate of 25000rpm and a duration of 15sec, 30sec, 1min, 2min and 3min, the emulsions are fine and monodisperse; the drops have an average diameter smaller than Imiti. The particle size distribution of the drops is narrow.
A une vitesse de cisaillement de 20000rpm et une durée de 30sec, 1min, 2min et 3min, les émulsions sont fines et monodisperses, les gouttes ont un diamètre inférieur à Imiti. La distribution
granulométrique des gouttes est étroite. At a shear speed of 20000rpm and a duration of 30sec, 1min, 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti. The distribution particle size of the drops is narrow.
A une vitesse de cisaillement de 15000rpm et une durée de 1min, 2min et 3min, les émulsions sont fines et monodisperses, les gouttes ont un diamètre inférieur à Imiti. La distribution granulométrique des gouttes est étroite. A une vitesse de cisaillement de lOOOOrpm et une durée de 2min et 3min, les émulsions sont fines et monodisperses, les gouttes ont un diamètre inférieur à Imiti. La distribution granulométrique des gouttes est étroite. At a shear speed of 15000rpm and a duration of 1min, 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti. The particle size distribution of the drops is narrow. At a shear rate of 100000rpm and a duration of 2min and 3min, the emulsions are fine and monodisperse, the drops have a diameter smaller than Imiti. The particle size distribution of the drops is narrow.
Exemple 3 de préparation d'une composition selon l'invention avec élimination de l'éthanol résiduel. Example 3 of preparation of a composition according to the invention with elimination of residual ethanol.
Un évaporateur rotatif a été utilisé. Un volume de lOOmL d'une émulsion cisaillée pendant 1 min à l'Ultra-Turrax à 25000 rpm est utilisé à cet effet. Elle contient une concentration de 10% en gomme arabique et 8.5% en poids de propolis (dilution d'un facteur 2 de la solution hydro-alcoolique mère) par rapport à la masse totale. Le panel A de la Figure 3 montre sa distribution granulométrique. Elle est gardée pendant 2h30 à une température de 45°C et à une pression de 0,15 bar. Cette durée permet d'évaporer 50% de la solution initiale. D'après le panel B de la Figure 3, la distribution des particules de propolis a très peu varié par rapport à celle de l'émulsion avant l'étape de distillation. Afin de déterminer si l'éthanol est complètement éliminé, l'émulsion est passée à l'ébulliomètre. Celui-ci permet de déterminer le degré alcoolique d'une solution en comparant sa température d'ébullition à celle de l'eau pure. Dans ce cas, les températures obtenues pour l'eau pure et l'émulsion sont égales (100,5 plus ou moins 0,5) °C. Par conséquent, l'éthanol a été éliminé de l'émulsion. A rotary evaporator was used. A volume of 100 ml of an emulsion sheared for 1 min in Ultra-Turrax at 25,000 rpm is used for this purpose. It contains a concentration of 10% gum arabic and 8.5% by weight of propolis (dilution by a factor of 2 of the mother hydro-alcoholic solution) relative to the total mass. Panel A of Figure 3 shows its particle size distribution. It is kept for 2h30 at a temperature of 45 ° C and a pressure of 0.15 bar. This time allows 50% of the initial solution to evaporate. According to panel B of FIG. 3, the distribution of the propolis particles varied very little compared to that of the emulsion before the distillation step. In order to determine if the ethanol is completely removed, the emulsion is passed through the ebulliometer. This makes it possible to determine the alcoholic degree of a solution by comparing its boiling point with that of pure water. In this case, the temperatures obtained for pure water and the emulsion are equal (100.5 plus or minus 0.5) ° C. Therefore, ethanol was removed from the emulsion.
Exemple 4 de préparation d'une composition selon l'invention. Example 4 for the preparation of a composition according to the invention.
Quatre émulsions à une concentration de 10 % en gomme arabique et 8.5 % en poids de propolis (dilution d'un facteur 2 de la solution hydroalcoolique mère), sont préparées à une vitesse de 5 000 rpm pendant 1 minute à l'Ultra-Turrax. L'émulsion obtenue est grossière et polydisperse. Les quatre émulsions sont alors passées 5 fois au microfluidiseur aux pressions respectives de 240, 400, 600 et 800 bars. Les émulsions deviennent plus fines et plus monodisperses quand la pression augmente. Comme le montre la figure 4, à partir de 400 bars et au-delà de cette pression, leur granulométrie ne semble plus évoluer.
Exemple 5 de préparation d'une composition selon l'invention. Four emulsions at a concentration of 10% gum arabic and 8.5% by weight of propolis (dilution by a factor of 2 of the mother hydroalcoholic solution), are prepared at a speed of 5000 rpm for 1 minute using Ultra-Turrax . The emulsion obtained is coarse and polydisperse. The four emulsions are then passed through the microfluidizer 5 times at the respective pressures of 240, 400, 600 and 800 bars. The emulsions become finer and more monodisperse as the pressure increases. As shown in Figure 4, from 400 bars and beyond this pressure, their particle size does not seem to change. Example 5 for the preparation of a composition according to the invention.
Trois nouvelles émulsions à une concentration de 2.5%, 5% et 15% de gomme arabique par rapport à la masse totale sont réalisées dans les mêmes conditions à 400 bars, en maintenant la concentration de propolis égale à 8.5%. L'étude de la granulométrie permet alors d'analyser l'évolution du diamètre moyen en surface des émulsions (D[3,2]) en fonction de la concentration en gomme arabique. La définition de ce diamètre moyen est connue de l'homme de l'art. La valeur la plus faible de D[3,2] est atteinte à une concentration de 15% (0,21miti). A 2,5%, la valeur de D[3,2] est égale à 0,55miti. Ainsi, la composition peut comprendre au moins une concentration de 2,5% de gomme arabique, préférentiellement 10% à 15% de gomme arabique dans le mélange (Figure 5). Three new emulsions at a concentration of 2.5%, 5% and 15% of gum arabic relative to the total mass are produced under the same conditions at 400 bars, while maintaining the concentration of propolis equal to 8.5%. The study of the particle size distribution then makes it possible to analyze the change in the mean surface diameter of the emulsions (D [3,2]) as a function of the concentration of gum arabic. The definition of this mean diameter is known to those skilled in the art. The lowest value of D [3.2] is reached at a concentration of 15% (0.21miti). At 2.5%, the value of D [3.2] is equal to 0.55miti. Thus, the composition can comprise at least a concentration of 2.5% of gum arabic, preferably 10% to 15% of gum arabic in the mixture (FIG. 5).
Exemple 6 de préparation d'une composition selon l'invention avec élimination de l'éthanol. Example 6 of preparation of a composition according to the invention with elimination of ethanol.
Le test de l'évaporateur rotatif est réalisé sur les émulsions issues du microfluidiseur. Une émulsion grossière est préparée de concentration en gomme arabique égale à 10% et 8.5% en poids de propolis. Elle est cisaillée à 5000 rpm pendant 1min puis passée au microfluidiseur à 600 bars (3 passages). Elle est ensuite introduite dans l'évaporateur rotatif afin d'éliminer l'éthanol. Le même protocole tel que décrit dans l'exemple 4 est alors appliqué. L'extraction est interrompue après avoir éliminé 50% de la masse de solution initiale. Comme précédemment, l'émulsion reste intacte. Afin de déterminer si l'éthanol est complètement éliminé, l'émulsion est aussi passée à l'ébulliomètre. Dans ce cas, les températures obtenues pour l'eau et l'émulsion sont proches de 100°C. Aux incertitudes de mesure près, il peut donc être affirmé que l'éthanol a été éliminé de l'émulsion. The rotary evaporator test is performed on the emulsions from the microfluidizer. A coarse emulsion is prepared with a concentration of gum arabic equal to 10% and 8.5% by weight of propolis. It is sheared at 5000 rpm for 1 min then passed through a microfluidizer at 600 bars (3 passes). It is then introduced into the rotary evaporator in order to remove the ethanol. The same protocol as described in Example 4 is then applied. The extraction is interrupted after having removed 50% of the initial mass of solution. As before, the emulsion remains intact. To determine if the ethanol is completely removed, the emulsion is also boiled. In this case, the temperatures obtained for the water and the emulsion are close to 100 ° C. Apart from the measurement uncertainties, it can therefore be said that the ethanol has been removed from the emulsion.
Exemple 7 de préparation d'une composition selon l'invention sous forme d'une dispersion sèche redispersable. Example 7 of the preparation of a composition according to the invention in the form of a redispersible dry dispersion.
Deux émulsions à une concentration de 10% de gomme arabique et à 8.5% en poids de propolis ont été préparées. L'une a été obtenue par cisaillement à l'Ultra-Turrax pendant 1 minute à 25000 rpm et l'autre est cisaillée pendant 1 minute à 5000 rpm puis passée au microfluidiseur à 960 bars (3 passages). Les deux émulsions sont lyophilisées pendant 4 jours à -89°C et à une pression de 95mTorr. Chacune des deux poudres est redispersée dans de l'eau distillée à une concentration de 20%. L'émulsion passée au microfluidiseur montre une granulométrie monodisperse, même si sa distribution s'est élargie (Figure 6, panel A). Cela indique que plus l'émulsion est fine, mieux elle résistera à la lyophilisation. Cependant, dans les deux cas, la poudre était parfaitement redispersable dans l'eau.
Exemple 8 de préparation d'une composition selon l'invention sous forme d'une dispersion sèche redispersable. Two emulsions at a concentration of 10% gum arabic and 8.5% by weight of propolis were prepared. One was obtained by shearing in an Ultra-Turrax for 1 minute at 25,000 rpm and the other is sheared for 1 minute at 5,000 rpm and then passed through a microfluidizer at 960 bars (3 passes). The two emulsions are lyophilized for 4 days at -89 ° C. and at a pressure of 95 mTorr. Each of the two powders is redispersed in distilled water at a concentration of 20%. The emulsion passed through the microfluidizer shows a monodisperse particle size, even if its distribution has widened (FIG. 6, panel A). This indicates that the thinner the emulsion, the better it will resist freeze drying. However, in both cases the powder was perfectly redispersible in water. Example 8 of the preparation of a composition according to the invention in the form of a redispersible dry dispersion.
Une émulsion de IL est préparée comprenant une concentration de 10% en gomme arabique et 6.375% en poids de propolis. Elle est préparée par cisaillement à l'Ultra-Turrax pendant 3 minutes à 25000rpm. Puis, afin d'éliminer l'éthanol, l'émulsion est passée à l'évaporateur rotatif pendant 2 heures 30 minutes, à 45°C et 0.15 bar. L'atomiseur est alors préchauffé jusqu'à atteindre 210°C en entrée et 90°C en sortie d'air. L'échantillon est alors complètement introduit dans l'appareil. Ainsi, la poudre obtenue est fine et ne colle pas aux parois. Il est alors intéressant de mesurer son profil granulométrique et de l'observer au microscope pour voir si l'émulsion est toujours monodisperse et fine. La poudre est alors redispersée dans de l'eau distillée à une concentration de 20% et la première observation est qu'elle parfaitement redispersable dans l'eau. La figure 7 montre que l'émulsion est restée quasi-intacte avant et après atomisation. Les profils granulométriques sont très proches et le volume moyen des émulsions ne varie que très légèrement (D[4,3] = 0.61 miti avant et 0.67 miti après atomisation ; la définition du diamètre moyen en volume, D[4,3], est bien connue de l'homme de l'art)). Par conséquent, l'atomisation n'a que peu eu d'effet sur la formulation sous forme d'une dispersion sèche et la poudre se redisperse dans l'eau parfaitement sans sédimenter.
An IL emulsion is prepared comprising a concentration of 10% gum arabic and 6.375% by weight of propolis. It is prepared by Ultra-Turrax shear for 3 minutes at 25000rpm. Then, in order to remove the ethanol, the emulsion is passed through a rotary evaporator for 2 hours 30 minutes, at 45 ° C. and 0.15 bar. The atomizer is then preheated until it reaches 210 ° C at the inlet and 90 ° C at the air outlet. The sample is then completely introduced into the apparatus. Thus, the powder obtained is fine and does not stick to the walls. It is then interesting to measure its particle size profile and to observe it under a microscope to see if the emulsion is still monodisperse and fine. The powder is then redispersed in distilled water at a concentration of 20% and the first observation is that it is perfectly redispersible in water. FIG. 7 shows that the emulsion remained almost intact before and after atomization. The particle size profiles are very close and the mean volume of the emulsions varies only very slightly (D [4.3] = 0.61 miti before and 0.67 miti after atomization; the definition of the mean diameter by volume, D [4.3], is well known to those skilled in the art)). Therefore, atomization had little effect on the formulation as a dry dispersion and the powder redisperses in water perfectly without settling.
Claims
[Revendication 1] Composition comprenant au moins des particules de propolis et au moins un agent polymérique amphiphile d'origine naturelle, caractérisée en ce que la taille moyenne des particules de propolis est inférieure à lOpm. [Claim 1] Composition comprising at least propolis particles and at least one amphiphilic polymeric agent of natural origin, characterized in that the average size of the propolis particles is less than 10 pm.
[Revendication 2] Composition selon la revendication précédente, caractérisée en ce que la taille moyenne des particules de propolis est inférieure à lpm. [Claim 2] Composition according to the preceding claim, characterized in that the average size of the propolis particles is less than 1pm.
[Revendication B] Composition selon l'une des revendications précédentes, caractérisée en ce qu'elle comprend une teneur en agent polymérique amphiphile d'origine naturelle compris entre 15% et 70% par rapport au poids des matières sèches de la composition. [Claim B] Composition according to one of the preceding claims, characterized in that it comprises a content of amphiphilic polymeric agent of natural origin of between 15% and 70% relative to the weight of the dry matter of the composition.
[Revendication 4] Composition selon l'une des revendications précédentes, caractérisée en ce que l'agent polymérique amphiphile d'origine naturelle est choisi parmi la gomme arabique, une protéine et un mélange de protéines d'origine animale ou végétale. [Claim 4] Composition according to one of the preceding claims, characterized in that the amphiphilic polymeric agent of natural origin is chosen from gum arabic, a protein and a mixture of proteins of animal or plant origin.
[Revendication 5] Composition selon l'une des revendications précédentes, caractérisée en ce qu'elle comprend une teneur en gomme arabique comprise entre 50% et 60% en poids par rapport au poids total des matières sèches de la composition. [Claim 5] Composition according to one of the preceding claims, characterized in that it comprises a content of gum arabic of between 50% and 60% by weight relative to the total weight of the dry matter of the composition.
[Revendication 6] Composition selon l'une des précédentes revendications, caractérisée en ce qu'elle comprend au moins 30% de propolis en poids par rapport au poids total de matières sèches de la composition. [Claim 6] Composition according to one of the preceding claims, characterized in that it comprises at least 30% of propolis by weight relative to the total weight of dry matter of the composition.
[Revendication 7] Composition selon l'une des précédentes revendications, caractérisée en ce qu'elle se présente sous forme d'une suspension de particules de propolis dans une phase aqueuse. [Claim 7] Composition according to one of the preceding claims, characterized in that it is in the form of a suspension of propolis particles in an aqueous phase.
[Revendication 8] Composition selon l'une des revendications 1 à 6, caractérisée en ce qu'elle se présente sous forme de poudre sèche et en ce que ladite poudre est dispersable dans l'eau. [Claim 8] Composition according to one of claims 1 to 6, characterized in that it is provided in the form of a dry powder and in that the said powder is dispersible in water.
[Revendication 9] Composition selon la précédente revendication, caractérisée en ce qu'elle se présente sous forme de poudre, de comprimé, de gélule à ingérer. [Claim 9] Composition according to the preceding claim, characterized in that it is provided in the form of powder, tablet or capsule to be ingested.
[Revendication 10] Composition selon l'une des précédentes revendications, caractérisée en ce qu'elle comprend également des saccharides, des polysaccharides, des agents aromatiques hydrosolubles, des agents épaississants ou gélifiants.
[Claim 10] Composition according to one of the preceding claims, characterized in that it also comprises saccharides, polysaccharides, water-soluble aromatic agents, thickening or gelling agents.
[Revendication 11] Composition selon l'une des précédentes revendications, caractérisée en ce que la propolis présente dans la composition comprend au moins 15% de polyphénols en poids par rapport au poids total de propolis. [Claim 11] Composition according to one of the preceding claims, characterized in that the propolis present in the composition comprises at least 15% of polyphenols by weight relative to the total weight of propolis.
[Revendication 12] Composition selon l'une des précédentes revendications, caractérisée en ce que la propolis présente dans la composition comprend au moins 40% de polyphénols en poids par rapport au poids total de propolis. [Claim 12] Composition according to one of the preceding claims, characterized in that the propolis present in the composition comprises at least 40% of polyphenols by weight relative to the total weight of propolis.
[Revendication 13] Composition selon l'une des précédentes revendications, caractérisée en ce qu'elle comprend une teneur finale en éthanol inférieure à 1%. [Claim 13] Composition according to one of the preceding claims, characterized in that it comprises a final ethanol content of less than 1%.
[Revendication 14] Composition selon l'une des précédentes revendications, caractérisée en ce qu'elle comprend une teneur finale en éthanol inférieure à 0,1%. [Claim 14] Composition according to one of the preceding claims, characterized in that it comprises a final ethanol content of less than 0.1%.
[Revendication 15] Procédé de fabrication d'une composition selon l'une des précédentes revendications, caractérisé en ce qu'il comprend au moins la mise en oeuvre des étapes suivantes :[Claim 15] A method of manufacturing a composition according to one of the preceding claims, characterized in that it comprises at least the implementation of the following steps:
- mélanger une solution aqueuse et au moins un agent polymérique amphiphile d'origine naturelle pour obtenir une solution aqueuse, - mixing an aqueous solution and at least one amphiphilic polymeric agent of natural origin to obtain an aqueous solution,
- mélanger cette solution aqueuse avec une solution hydro-alcoolique comprenant au moins de l'eau, de l'éthanol et de la propolis, - mix this aqueous solution with a hydro-alcoholic solution comprising at least water, ethanol and propolis,
- éventuellement, pendant ou après la précédente phase de mélange, appliquer un cisaillement pour obtenir une pré-émulsion constituée de gouttes de propolis et d'éthanol dans une phase aqueuse, - optionally, during or after the previous mixing phase, apply a shear to obtain a pre-emulsion consisting of drops of propolis and ethanol in an aqueous phase,
- appliquer un cisaillement sur le mélange pour affiner la pré-émulsion. - apply a shear to the mixture to refine the pre-emulsion.
[Revendication 16] Procédé de fabrication d'une composition selon la précédente revendication, caractérisé en ce qu'il comprend au moins la mise en oeuvre des étapes suivantes : [Claim 16] A method of manufacturing a composition according to the preceding claim, characterized in that it comprises at least the implementation of the following steps:
- mélanger une solution aqueuse et au moins un agent polymérique amphiphile d'origine naturelle pour obtenir une solution aqueuse, - mixing an aqueous solution and at least one amphiphilic polymeric agent of natural origin to obtain an aqueous solution,
- mélanger cette solution aqueuse avec une solution hydro-alcoolique comprenant au moins de l'eau, de l'éthanol et de la propolis, le ratio massique de la solution hydro-alcoolique par rapport à la masse totale du mélange étant compris entre 30 et 60%, et l'agent polymérique amphiphile représentant au moins 15% en poids des matières sèches du mélange, - mix this aqueous solution with a hydro-alcoholic solution comprising at least water, ethanol and propolis, the mass ratio of the hydro-alcoholic solution relative to the total mass of the mixture being between 30 and 60%, and the amphiphilic polymeric agent representing at least 15% by weight of the dry matter of the mixture,
- éventuellement, pendant ou après la précédente phase de mélange, appliquer un cisaillement à l'aide d'un dispositif rotor-stator pendant une durée comprise entre 1 minute et 30 minutes à une vitesse de cisaillement supérieure à 104 s 1 pour obtenir une pré-émulsion,
- appliquer un cisaillement sur la pré-émulsion pendant une durée comprise entre 1 minute et 30 minutes, à l'aide d'un dispositif de type rotor à une vitesse de cisaillement supérieure à 2.104 s 1 ou à l'aide d'un homogénéisateur haute pression à une pression d'homogénéisation supérieure à 100 bars ou à l'aide d'un microfluidiseur à canal à une pression d'homogénéisation supérieure à 100 bars afin d'affiner la taille des gouttes. - optionally, during or after the previous mixing phase, apply shear using a rotor-stator device for a period of between 1 minute and 30 minutes at a shear speed greater than 10 4 s 1 to obtain a pre-emulsion, - apply a shear to the pre-emulsion for a period of between 1 minute and 30 minutes, using a rotor-type device at a shear rate greater than 2.10 4 s 1 or using a High pressure homogenizer at a homogenization pressure greater than 100 bars or using a channel microfluidizer at a homogenization pressure greater than 100 bars in order to refine the size of the drops.
[Revendication 17] Procédé de fabrication selon l'une des revendications 15 ou 16, caractérisé en ce qu'il comprend également une étape d'évaporation de l'éthanol après l'étape de cisaillement appliquée sur la pré-émulsion afin d'obtenir une suspension de particules de propolis. [Claim 17] The manufacturing method according to one of claims 15 or 16, characterized in that it also comprises a step of evaporating the ethanol after the shearing step applied to the pre-emulsion in order to obtain a suspension of propolis particles.
[Revendication 18] Procédé de fabrication selon la précédente revendication, caractérisé en ce que l'étape d'évaporation est réalisée à une pression comprise entre 0,05 et 0,3 bar et à une température comprise entre 25 et 50°C. [Claim 18] The manufacturing method according to the preceding claim, characterized in that the evaporation step is carried out at a pressure between 0.05 and 0.3 bar and at a temperature between 25 and 50 ° C.
[Revendication 19] Procédé de fabrication selon l'une des revendications 15 à 18, caractérisé en ce qu'il comprend une étape supplémentaire de séchage après l'étape de cisaillement de la pré émulsion, ou après l'étape d'évaporation de l'éthanol. [Revendication 20] Procédé de fabrication selon la revendication 19, caractérisé en ce que l'étape de séchage est réalisée par lyophilisation ou atomisation.
[Claim 19] The manufacturing method according to one of claims 15 to 18, characterized in that it comprises an additional step of drying after the step of shearing the pre-emulsion, or after the step of evaporating the ethanol. [Claim 20] The manufacturing method according to claim 19, characterized in that the drying step is carried out by freeze-drying or atomization.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FRFR1914266 | 2019-12-12 | ||
| FR1914266A FR3104415B1 (en) | 2019-12-12 | 2019-12-12 | Composition in the form of an aqueous suspension of propolis. |
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| PCT/EP2020/085829 WO2021116443A1 (en) | 2019-12-12 | 2020-12-11 | Composition comprising propolis particles |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH09299044A (en) * | 1996-05-17 | 1997-11-25 | Saitama Youhou Kk | Water-dispersible propolis composition and its production |
| FR3006589A1 (en) * | 2013-06-11 | 2014-12-12 | Pollenergie | USE OF PROPOLIS TO COMBAT PATHOLOGIES ASSOCIATED WITH OBESITY |
| FR3037799A1 (en) * | 2015-06-29 | 2016-12-30 | Sine Sileo | HYDRODISPERSIBLE SOLID PARTICLES BASED ON PROPOLIS |
| RU2697839C1 (en) * | 2018-11-14 | 2019-08-21 | Александр Александрович Кролевец | Method of producing nanocapsules of a dry extract of propolis |
-
2019
- 2019-12-12 FR FR1914266A patent/FR3104415B1/en active Active
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2020
- 2020-12-11 WO PCT/EP2020/085829 patent/WO2021116443A1/en active Application Filing
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| JPH09299044A (en) * | 1996-05-17 | 1997-11-25 | Saitama Youhou Kk | Water-dispersible propolis composition and its production |
| FR3006589A1 (en) * | 2013-06-11 | 2014-12-12 | Pollenergie | USE OF PROPOLIS TO COMBAT PATHOLOGIES ASSOCIATED WITH OBESITY |
| FR3037799A1 (en) * | 2015-06-29 | 2016-12-30 | Sine Sileo | HYDRODISPERSIBLE SOLID PARTICLES BASED ON PROPOLIS |
| RU2697839C1 (en) * | 2018-11-14 | 2019-08-21 | Александр Александрович Кролевец | Method of producing nanocapsules of a dry extract of propolis |
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