WO2009043988A2 - Procede de preparation de compositions pulverulentes stables - Google Patents
Procede de preparation de compositions pulverulentes stables Download PDFInfo
- Publication number
- WO2009043988A2 WO2009043988A2 PCT/FR2008/001069 FR2008001069W WO2009043988A2 WO 2009043988 A2 WO2009043988 A2 WO 2009043988A2 FR 2008001069 W FR2008001069 W FR 2008001069W WO 2009043988 A2 WO2009043988 A2 WO 2009043988A2
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- Prior art keywords
- powder
- sensitive substance
- agent
- substance
- sensitive
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Classifications
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/189—Enzymes
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/195—Antibiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K40/00—Shaping or working-up of animal feeding-stuffs
- A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K40/00—Shaping or working-up of animal feeding-stuffs
- A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
Definitions
- the invention relates to a new process for the preparation of stable powdery compositions.
- the invention relates to a new process for preparing powdery compositions comprising a sensitive substance, especially at temperature and / or pressure and / or relative humidity.
- Sensitive substances are frequently active substances used in pharmacology or in compositions used in different fields such as food or feed, detergents, etc.
- proteins in particular enzymes, vitamins, bacteria, yeasts, antioxidants, carotenoids, essential oils or else pharmacologically active substances such as antibiotics.
- patent EP 0 569 468 proposes a method for preparing granules containing an enzyme (s) intended for animal feed and which are coated with a fat or a wax having a high melting point, in order to increase resistance to granulation conditions.
- a coating has the disadvantage of causing a long dissolution time of the granules, which decreases the bioavailability of the enzymes for the animal.
- the application WO 00/47060 describes a process for preparing granules containing an enzyme (s) coated with polyethylene glycol.
- This coating then makes it possible to increase the stability of the enzymes during a granulation step but only in the presence of additives such as water-soluble inorganic salts (for example ZnSO 4 ) or else trehalose.
- additives such as water-soluble inorganic salts (for example ZnSO 4 ) or else trehalose.
- a method for preparing granules containing one or more enzymes coated with a polyolefin has also been developed in application WO 03/059087, in particular for use in the field of animal nutrition.
- the coating used then makes it possible to increase the stability of the enzyme (s) during the granulation steps in particular.
- this requires the use of polymeric derivatives which are not necessary for feeding the animal and which increase the cost of manufacturing the granules.
- the application WO2005 / 074707 describes stabilized formulations of phosphatase, the stabilizing agent being chosen exclusively from agar-agar, alginate, carrageenan, furcelleran, gum ghatti, gum tragacanth, gum karya, gum guarana, locust bean gum, tamarind gum, arabinogalactan and xanthan gum.
- These formulations may be coated with polymers chosen in particular from cellulose derivatives having a molecular weight of between 6000 and 80000. This demand remains silent on the viscosity of the products used.
- the coating composition comprising a film-forming agent which may especially be a cellulose derivative such as cellulose acetate, ethylcellulose or methylcellulose and a pore-forming agent which allows rapid destruction of said coating composition by constituting preferential access points to biological fluids.
- a film-forming agent which may especially be a cellulose derivative such as cellulose acetate, ethylcellulose or methylcellulose and a pore-forming agent which allows rapid destruction of said coating composition by constituting preferential access points to biological fluids.
- One of the aspects of the invention is therefore to propose a new process for the preparation of powder compositions containing at least one sensitive substance which can withstand conditions of high temperatures, pressures and relative humidity and which is stable during transport and storage, this method being easy to implement and inexpensive.
- the present invention especially relates to the use of at least one viscous compound having a viscosity greater than 5 Pa.s, "to substantially prevent the degradation of a substance sensitive to temperatures of 20 ° C to 100 ° C and / or at pressures of 10 6 to 10 7 Pa and / or a relative humidity of 60% to 100% contained in a powder composition, said powder composition containing particles comprising:
- a heart containing said sensitive substance and at least one viscous compound as an agent for impregnating the sensitive substance and
- a coating of the core which coating contains at least one viscous compound as a sticking agent.
- the viscous compounds used in the present invention have the advantage of being almost hydrophobic when subjected to high pressures, which are of the order of 10 6 to 10 7 Pa, but recover all their solubility properties when they are put back into solution. This thus makes it possible to protect the sensitive substances during the preparation of granules by a granulation step while at the same time guaranteeing a good bioavailability of the sensitive substances thanks to short dissolution times of the particles of the pulverulent composition.
- the sensitive substance which is also the active ingredient, will be released directly into the digestive tract of the animal.
- granulation is meant a step for the preparation of granules in the form of cylinders 1 to 10 mm in diameter and 1 to 5 cm in length per passage in a die. This step is characterized by high temperature and pressure and shear stresses, as well as by the presence of water vapor, these stresses can deteriorate sensitive substances.
- the viscosity measurements are made using a BROOKFIELD model LVDV-E viscometer equipped with a coaxial cylinder system, using the no. 18 or 31 mobiles according to the viscosities, in a temperature controlled temperature chamber. using a thermostatic bath. These measurements are carried out at 20 ° C. for aqueous solutions containing 10% solids content of the viscous compound, at different rotational speeds of the rolls from 10 to 100 rpm.
- the viscosity values used are the values obtained at the highest speeds of rotation by integrating the limit values of the torsion torque (80% maximum) of the device.
- the viscous compound is chosen from vegetable or fermentation-derived gums, starch bases, chitins or cellulose derivatives, such as carboxymethylcellulose (CMC), methylcellulose, ethylcellulose, propylcellulose and hydoxymethylcellulose. , hydroxyethylcellulose, hydoxypropylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, or microcrystalline cellulose.
- CMC carboxymethylcellulose
- methylcellulose methylcellulose
- ethylcellulose propylcellulose and hydoxymethylcellulose.
- hydroxyethylcellulose, hydoxypropylcellulose hydroxypropylmethylcellulose
- ethylhydroxyethylcellulose hydroxyethylcellulose
- microcrystalline cellulose microcrystalline cellulose
- the viscous compound is carboxymethylcellulose (CMC).
- CMC carboxymethylcellulose
- Sensitive substance means any substance that is likely to lose some or all of its activity when subjected to high temperatures and / or pressures and / or relative humidity. These constraints may be encountered especially during the preparation of compositions containing said substance, and more particularly during the granulation steps. This substance may be in particular a mixture of sensitive substances.
- Degradation means any transformation of the said sensitive substance which causes a loss of activity, partial or total, whether by denaturing the said substance or by changing the proportions in a composition comprising several substances, some of which are especially volatile (for example in the case of an essential oil).
- the sensitive substance may be chosen in particular from proteins, in particular enzymes, vitamins, bacteria, yeasts, antioxidants, carotenoids, essential oils or pharmacologically active substances such as antibiotics.
- enzymes superoxydismutase, for vitamins, riboflavin or ascorbic acid, for bacteria, lactobacillus, for yeasts, saccharomyces cerevisiae, for antioxidants, polyphenols or vitamin E, for carotenoids, lutein, astaxanthin, lycopene, xanthophyll or carotenes, for natural essential oils, those derived from garlic, thyme or rosemary and for antibiotics, Pamoxycicline or tylosin.
- This sensitive substance may be used in particular in the field of animal or human nutrition, in the pharmaceutical or veterinary field, in the field of detergents, cleaning and washing products, especially clothing.
- pulverulent composition denotes powders comprising particles having an average particle size of 30 to 3,000 ⁇ m on average.
- the particles of the powder composition comprise two distinct parts: a core and a coating of this core which forms a protective film.
- the heart consists of the sensitive substance and at least one viscous compound that serves as an impregnating agent.
- the coating contains at least one viscous compound which serves as a sticking agent. The viscous compound therefore intervenes at two levels since it is present both in the heart and the coating. It is possible to use two different viscous compounds, one contained in the heart and the other in the coating.
- the viscous compound used as an impregnating agent ensures a homogeneous mixture without demixing the constituent elements of the composition while binding all the grains together.
- the viscous compound used as a sticking agent makes it possible to achieve the final protection.
- it provides, on the one hand, protection against the high humidity and temperature conditions encountered during the heating of the composition with water vapor during the mixing with the feed, and on the other hand, protection against the high pressure and shear conditions encountered during the die run.
- the core of the particles of said powdery composition contains at least one support of said sensitive substance.
- the support by its absorbent nature is a material chosen to be already in the dry state. It protects the sensitive substance by stabilizing the activity of the water when the support is in contact with the sensitive substance in liquid form, sprayed during drying phases.
- This support may be in particular starch, flours, especially wheat, maize, cassava or rice, talc, beet pulp, maltodextrin, salts such as calcium carbonate or corn curd.
- the impregnating agent and the tackifier are identical.
- the viscous compound however, has very different functions if it is used as an impregnating agent or as a sticking agent, as already stated above, even if it is the same compound.
- the impregnating agent and the sticking agent comprise or consist of carboxymethylcellulose (CMC).
- the sensitive substance represents from 5 to 40%, preferably from 10 to 30% of dry extract of the pulverulent composition
- the support represents from 10 to 60%, preferably from 20 to 50% of extract.
- the impregnating agent represents from 5 to 40%, preferably from 10 to 30% of solids content of the pulverulent composition
- the sticking agent represents from 5 to 30%, preferably from 10 to 30% by weight. at 20% of dry extract of the powdery composition.
- the sensitive substance consists of a mixture of enzymes consisting mainly of ⁇ -glucanase, xylanase and cellulase
- the support consists of wheat flour
- the impregnating agent and the sticking agent consists of carboxymethylcellulose (CMC).
- the present invention also relates to a stable powdery composition containing particles comprising:
- a core containing at least one substance that is sensitive to temperatures of 20 ° C. to 100 ° C. and / or at pressures of 10 6 to 10 7 Pa and / or at a relative humidity of 60% to 100% and at least one viscous compound having a viscosity greater than 5 Pa.s.s -1 as an impregnating agent for the sensitive substance, and
- a coating of the heart which coating contains at least one viscous compound having a viscosity greater than 5 Pa.s 4 as sticking agent.
- the sensitive substance can not be an enzyme intended for feeding non-human animals.
- “Stable powdery composition” means compositions in which the sensitive substance undergoes less than 20% degradation when said powdery composition is subjected to temperatures of from 60 ° C. to 100 ° C. and / or to pressures of from 2.10.degree. 6 to 10 7 Pa and / or at a relative humidity of 60% to 100%.
- the viscous compound is chosen from vegetable or fermentation-derived gums, starch bases, chitins or derivatives thereof.
- cellulosics such as carboxymethylcellulose (CMC), methylcellulose, ethylcellulose, propylcellulose, hydoxymethylcellulose, hydoxyethylcellulose, hydoxypropylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, or microcrystalline cellulose.
- CMC carboxymethylcellulose
- methylcellulose methylcellulose
- ethylcellulose propylcellulose
- hydoxymethylcellulose hydoxyethylcellulose
- hydoxypropylcellulose hydroxypropylmethylcellulose
- ethylhydroxyethylcellulose or microcrystalline cellulose.
- the viscous compound is carboxymethylcellulose (CMC).
- the sensitive substance may be chosen in particular from proteins, vitamins, bacteria, yeasts, antioxidants, carotenoids, essential oils or pharmacologically active substances such as antibiotics.
- the heart contains at least one support for the sensitive substance.
- This support may be chosen in particular from starch, flours, in particular wheat, maize, cassava or rice, talc, beet pulp, maltodextrin, salts such as calcium carbonate or dried grains. of corn.
- the impregnating agent and the binder agent are identical.
- the impregnating agent and the sticking agent comprise or consist of carboxymethylcellulose (CMC).
- CMC carboxymethylcellulose
- the pulverulent composition consists of: 5 to 40%, preferably 10 to 30% solids content of a sensitive substance, 10 to 60%, preferably 20 to 50% solids content of a carrier From 5 to 40%, preferably from 10 to 30% by solids content of an impregnating agent and from 5 to 30%, preferably from 10 to 20%, by solids content of a masticating agent.
- the present invention also relates to a process for preparing a stable powdery composition containing particles comprising:
- a core containing at least one substance that is sensitive to temperatures of 20 ° C. to 100 ° C. and / or at pressures of 10 6 to 10 7 Pa and / or at a relative humidity of 60% to 100% and at least one viscous compound having a viscosity greater than 5 Pa.s.s -1 as an impregnating agent for the sensitive substance, and
- a coating of the heart which coating contains at least one viscous compound having a viscosity above 5 Pa ⁇ s "as sticking agent, said method comprising: a step of microgranulating a mixture of said sensitive substance and said impregnating agent to obtain the core, and a step of coating said core with said binder.
- the present invention also relates to a process for preparing a stable powdery composition containing particles comprising:
- a heart comprising at least one substance sensitive to temperatures of 20 0 C to 100 ° C and / or 10 ⁇ pressures to 10 7 Pa and / or at a relative humidity of 60% to 100%, at least one viscous compound having a viscosity greater than 5 Pa.s.s -1 as an impregnating agent for the sensitive substance and at least one carrier for the sensitive substance, and
- a coating of the core which coating contains at least one viscous compound whose viscosity is greater than 5 Pa ⁇ s -1 as a sticking agent, said process comprising: a step of micro granulation of a mixture of said a sensitive substance, said carrier and said impregnating agent for obtaining the core, and a step of coating said core with said binder.
- the core of the particles of this powdery composition is obtained from a mixture of three ingredients, the sensitive substance, a support and the impregnating agent, by a step of micro granulation.
- the core of the particles is then coated with the masticating agent to form a protective film around the particle and thus protect the sensitive substance from future stresses that it will have to undergo, in particular during the formation of granules in the pelletizing presses. . This also helps preserve it during transport or storage.
- the stable pulverulent composition obtained consists of particles embedded in a protective film giving it new properties.
- the pulverulent composition has hydrophobic properties and the sensitive substance contained in said composition becomes resistant to temperature and pressure and remains stable during transport or storage.
- the pulverulent composition is rehydrated again and therefore becomes bioavailable when it is redissolved.
- the microgranulation step may be carried out from a mixture of said sensitive substance and said previously co-dried support and all of the impregnating agent.
- the sensitive substance and the support previously co-dried is in the form of a totally homogeneous product, with a controlled particle size and dispersion, suitable for mixing with the impregnating agent.
- the micro granulation step may also be carried out from a mixture of said sensitive substance, said support and all of the impregnating agent co-dried beforehand.
- This method advantageously allows to have a live product perfectly homogeneous while reducing an expensive step of mixing.
- the micro granulation step may also be performed from a mixture of said sensitive substance, said support and a part of the impregnating agent co-dried and the remainder of the impregnating agent.
- This method gives an intermediate powder, whose particle sizes are controlled with reduced dispersion. Most of the impregnating agent is already present, it is then sufficient to supplement with the rest of the impregnating agent to start the next phase.
- said method comprises a step of co-drying, before the microgranulation step, a mixture containing the sensitive substance, the support of the sensitive substance and optionally all or part of the agent of impregnation, the co-drying being carried out at an outlet air temperature of less than 60 ° C. and at a powder temperature below 45 ° C.
- the sensitive substance will be used in liquid form and the support in dry form.
- said method comprises: a step of co-drying a mixture containing the sensitive substance and at least one support of the sensitive substance, the co-drying being carried out at an air temperature of output lower than 60 ° C and at a powder temperature lower than 45 ° C, to obtain an intermediate homogeneous powder, a step of microgranulation of the intermediate homogeneous powder with the impregnating agent to obtain a densified microgranulated powder consisting of uncoated particles corresponding to the aforesaid core,
- the sensitive substance will be used in liquid form, the carrier in dry form and the impregnating agent in solid form.
- the co-drying step is carried out at low temperature, which allows a retention of more than 95% of the sensitive substance and leads to the production of a homogeneous powder whose average particle size measured by D (v, o, 5) can be adjusted from 50 to 250 ⁇ m.
- the homogeneous intermediate powder then contains from 10 to 100%, in particular from 40 to 65%, in particular 55% of sensitive substance in dry extract.
- the final moisture of the intermediate homogeneous powder varies from 0% to especially from 5 to 12% and the water activity is less than 0.6 to prevent any development of microorganisms.
- the micro-granulation step is generally carried out at a maximum temperature of 45 ° C. so as not to damage the sensitive substance and at a given water content, ie about 5 to 20% of water added per total dry extract implemented. and preferably 10%, so that the impregnation and consistency of the product is achieved, and this by controlling the particle homogeneity and by monitoring the moisture content and by a visual inspection using a binocular loupe or by image analysis.
- the densified powder is characterized in that a change in the state of the product, initially in the form of a powder, is observed owing to the aggregation of the particles with each other, and this just before obtaining the consistency a pasty product, which is monitored either by the temperature which increases very rapidly, or by the intake of amperage of the main engine of the microgranulator.
- the densified powder obtained then has a mean particle size measured by D (v, o, 5) of 100 to 200 microns and a water content of 5 to 10%.
- This densified powder consists of from 5 to 50%, preferably from 10 to 35%, of sensitive substance in dry extract, from 10 to 70%, preferably from 20 to 60%, of support in dry extract and from 5 to 50%. %, preferably from 10 to 30%, of impregnating agent.
- the process of the invention for preparing the pulverulent composition comprises: a step of co-drying a mixture containing the sensitive substance and at least one support for the sensitive substance, the co-drying being carried out at an outlet air temperature below 60 ° C.
- the sensitive substance will be used in liquid form, the support in dry form, the impregnating agent in solid form and the sludge-forming agent in liquid form, especially in solution in the water.
- the rate of deposition of sticking agent around the core of the particles depends on the desired final particle size of the stable powdery composition. It varies in particular from 5 to 30%, preferably from 10 to 20% of dry extract of the powdery composition.
- the binder is deposited in particular in liquid form, from a solution of 4 to 10% solids in water.
- the solution containing the masticating agent is such that it has a viscosity compatible with a spray for coating the densified grain-to-grain powder, without aggregating the particles together.
- the coated powder obtained has a mean particle size measured by D (v, o, 5) of 300 to 400 ⁇ m and a water content of 5 to 12%.
- This coated powder consists of 5 to 40%, preferably 10 to 30%, of sensitive substance in dry extract, of 10 to 60%, preferably of 20 to 50%, of support in dry extract, of 5 to 40%. %, preferably from 10 to 30%, impregnating agent in dry extract and from 5 to 30%, preferably from 10 to 20%, of tacking agent in dry extract.
- the method comprises:
- a step of co-drying a mixture containing the sensitive substance and at least one support for the sensitive substance the co-drying being carried out at an outlet air temperature below 60 ° C. and at a powder temperature; less than 45 ° C, to obtain an intermediate homogeneous powder, a step of microgranulation of the intermediate homogeneous powder with the impregnating agent to obtain a densified microgranulated powder consisting of uncoated particles corresponding to the aforementioned core, optionally a drying step at a low temperature of the densified microgranulated powder at a temperature below 45 ° C., to obtain a dried densified microgranulated powder, optionally a sieving step to obtain a sieved densified microgranulated powder, a step of coating the uncoated particles with the powder densified microgranulate, optionally dried and optionally sieved, with the agent of icing to obtain a coated powder,
- low temperature drying is meant a drying step where the temperature does not exceed 45 ° C.
- This drying step is carried out after the microgranulation step if the densified powder obtained after this microgranulation step has a water content greater than 10% and in order to obtain a water content of less than 9%, and preferably less than 10%. 7%.
- the sieving step is carried out after the micro granulation step in order to have particles of equivalent size before coating.
- the densified microgranulated powder optionally dried and optionally sieved obtained before the coating step then has a mean particle size measured by D (v, o, 5) of 100 to 200 microns and a water content of 10% maximum.
- the particle size of the stable powdery composition is mainly in the range of 100 to 500 ⁇ m.
- the stable powdery composition thus obtained can be directly marketed as a raw material to be introduced in particular into pellets for purposes including animal feed, because this particle size is one that avoids any disbanding in the formulated products intended for animal feed.
- the viscous compound is chosen from vegetable or fermentation-derived gums, starch bases, chitins or cellulose derivatives, such as carboxymethylcellulose (CMC), methylcellulose, ethylcellulose, propylcellulose, hydroxymethylcellulose, and hydroxyethylcellulose. hydroxypropylmethylcellulose, ethyl hydroxyethylcellulose, or microcrystalline cellulose.
- CMC carboxymethylcellulose
- methylcellulose methylcellulose
- ethylcellulose propylcellulose
- hydroxymethylcellulose hydroxymethylcellulose
- hydroxyethylcellulose hydroxypropylmethylcellulose
- microcrystalline cellulose microcrystalline cellulose
- the viscous compound will be carboxymethylcellulose (CMC).
- the sensitive substance may be chosen in particular from proteins, in particular enzymes, vitamins, bacteria, yeasts, antioxidants, carotenoids, essential oils or pharmacologically active substances such as antibiotics.
- the support of the sensitive substance may in particular be chosen from starch, flour, in particular wheat, maize, cassava or rice flour, talc, beet pulp, maltodextrin, salts such as calcium, corn curds.
- the impregnating agent and the binder agent are identical.
- the impregnating agent and the sticking agent comprise or consist of carboxymethylcellulose (CMC).
- CMC carboxymethylcellulose
- the sensitive substance represents from 5 to 40%, preferably from 10 to 30% of dry extract of the pulverulent composition
- the support represents from 10 to 60%, preferably from 20 to 50% of extract.
- the impregnating agent represents from 5 to 40%, preferably from 10 to 30% of solids content of the pulverulent composition
- the sticking agent represents from 5 to 30%, preferably from 10 to 30% by weight. % to 20% dry extract of the powdery composition.
- the present invention also relates to a pulverulent composition obtained by a method of the invention as defined above.
- the present invention also relates to a pharmaceutical composition
- a pharmaceutical composition comprising, as active substance, a stable powdery composition containing particles comprising:
- a core containing at least one substance that is sensitive to temperatures of 20 ° C. to 100 ° C. and / or at pressures of 10 6 to 10 7 Pa and / or at a relative humidity of 60% to 100% and at least one viscous compound having a viscosity greater than 5 Pa.s.s -1 as an impregnating agent for the sensitive substance, and
- a coating of the core which coating contains at least one viscous compound whose viscosity is greater than 5 Pa ⁇ s -1 as a sticking agent, in which the sensitive substance has at least 80%, in particular at least 90%; % of its initial activity, in association with a pharmaceutically acceptable vehicle.
- This pharmaceutical composition may in particular be intended for the animal.
- the present invention also relates to a food composition
- a food composition comprising a stable powdery composition as defined in the present invention, wherein the sensitive substance has at least 80%, in particular at least 90% of its initial activity, and is not an enzyme intended feeding non-human animals, and at least one food product.
- This food composition may especially be intended for the animal.
- This food composition may further be characterized in that it is in the form of pellets or granules.
- the present invention also relates to a process for the preparation of food compositions comprising a stable powdery composition as defined in the present invention, and at least one food product, said process comprising a wet compression stage, in particular at 14% humidity, with an applied pressure of 2.10 6 to 10 7 Pa, a mixture of the stable powdery composition with the food product.
- the co-drying step mentioned above is carried out continuously, in particular on a spray drying tower and / or fluidized bed.
- the sensitive substance is introduced, during this step, by nozzles arranged around the arrival of the dry support or by a central injection nozzle, or a dynamic mixer type Shugi® or Bepex® (marketed by the company HOSOKAWA) on industrial towers.
- the co-drying step may be carried out in particular continuously by spraying the sensitive substance in the form of a mono-dispersed aerosol, directly onto the support powder by an appropriate device thus making it possible to obtain a better efficiency and obtain perfectly homogeneous particles.
- the microgranulation step mentioned above is carried out by wet microgranulation and shearing, in particular on a fluidized bed.
- This step consists in particular of an impregnation of the homogeneous intermediate powder with the impregnating agent and a discontinuous densification in a static or continuous mixer, for example in a SHUGI® dynamic mixer (marketed by HOSOKAWA) by a rotary device as a quick mixer for wet and pasty products (cutter) or a wet granulator used in pharmacy DIOSNA®, TURBOSPHERE® or GLATT® (marketed by the companies DIOSNA, Pierre GUERIN and GLATT, respectively) equipped with a suitable spraying system.
- a SHUGI® dynamic mixer marketed by HOSOKAWA
- a rotary device as a quick mixer for wet and pasty products (cutter) or a wet granulator used in pharmacy DIOSNA®, TURBOSPHERE® or GLATT® (marketed by the companies DIOSNA, Pierre GUERIN and GLATT, respectively) equipped with a suitable spraying system.
- the micro granulation step mentioned above is carried out continuously by wetting with a monodispersed aerosol, thereby allowing better efficiency and obtaining homogeneous particles.
- the low-temperature drying step mentioned above is carried out either in a discontinuous fluidized bed, or directly if the impregnation step was carried out continuously or on a drying tower using co-drying devices by tube or shugi.
- the coating step mentioned above consists in depositing a sufficient film of masticating agent and then drying the product obtained.
- the film is usually deposited by suitable spray nozzles on fluidized air bed dryers.
- the step of coating by spraying a film is carried out continuously with a mono-dispersed aerosol, thereby allowing better efficiency and obtaining homogeneous particles in order to to improve the density of the particles and to limit the amount of deposited debris.
- innovative impregnating powder containment systems developed on INNO JET® equipment (marketed by INNOJET) with ROTOJET® nozzles (marketed by INNOJET) can be used to to improve the density of the particles and to limit the amount of deposited debris.
- This system allows homogeneity of the passage of the particles in front of the nozzle with a high flow rate.
- the coated powder is then dried in successive batches on a conventional GLATT or AEROMATIC bottom spray fluidized bed (marketed by GLATT and GEA, respectively), INNOJET®, top spray or tangential, or continuously with a continuous fluidized bed with a ramp. of nozzles or with a SHUGI agglomerator or batch (batch), the purpose being to reduce the water content of the coated powder to a value of less than 10% and preferably less than 8%.
- FIG. 1 schematically shows the various steps of the process for preparing a stable powdery composition according to the invention, the raw materials being indicated in a gray rectangle, the operations carried out being indicated in a white rhombus and the material and the parameters used being indicated in a gray oval.
- the code used is shown below
- Figures 2 to 7 show different photos of particles of a powder composition observed by scanning electron microscope.
- Figures 2 (x50 magnification), 3 (x200 magnification) and 4 (x800 magnification) relate to particles obtained by a conventional fluidized bed coating method.
- Figures 5 (x50 magnification), 6 (x200 magnification) and 7 (x800 magnification) represent particles obtained by the method of the invention using innovative impregnation systems developed on INNO JET® material.
- the experimental protocol below describes a process for the preparation of a stable powdery composition in which the sensitive substance is a mixture of enzymes, the support is flour and the impregnating and sticking agents are constituted by the CMC. .
- the enzyme mixture is a concentrated filtered fermentation mash obtained from the fermentation of Penicillium funiculosum (IMI 378536) which contains 19 enzymatic activities, the main ones being cellulase, xylanase and ⁇ -glucanase.
- Penicillium funiculosum used is protected by the patent EP 1 007 743 and was deposited on March 24, 1998 by the company ADISSEO under the number IMI 378536 at IMI (International Mycological Institute, Bakeham Lane, Englefield Green, Egham, Surrey, TW20 9TY, Great Britain), recognized international depositary authority under the Budapest Treaty.
- the homogeneous powder obtained at this stage has a fineness-free powder character of less than 63 ⁇ m, which makes it a product that can be handled in a second impregnation phase of said powder with an impregnating agent.
- the average particle size in D (v, 0.5) is 117 ⁇ m and the humidity is 7.5%.
- This step makes it possible to obtain an intermediate homogeneous powder. pre-stabilized dry.
- the impregnation is carried out in a rapid mixer for wet and pasty products (cutter) and comprises the following steps: o 30 seconds of premixing of the ingredients (0.77 kg of dry extract of
- the object at this stage is to obtain particles of the order of 150 to 200 ⁇ m on average, with a humidity of 14%, while maintaining the product at a temperature below 45 ° C so as not to degrade the sensitive substance.
- the product is thus dried on a fluid bed dryer with an inlet temperature of 55 ° C. and an outlet temperature of 25 ° C.
- the densified microgranulated powder obtained has 7 to 8% moisture.
- An aqueous solution of 7 to 7.5% CMC is heated to a temperature of 60 ° C to 70 ° C, before being sprayed on the densified microgranulated powder.
- the amount of CMC deposited is 0.25 kg dry extract of CMC per kilogram of dry extract of densified micro granulated powder to be coated.
- the powder obtained at this stage has an average particle size of 300 to 400 ⁇ m and has a humidity of 10 to 11%.
- the coated product is then dried continuously on a fluidized bed or in batches (batch), the purpose being to reduce the product to a water content of less than 10% and preferably less than 8%.
- the stable powdery composition obtained as final product then has the following composition: 25% dry extract of enzymes, 20% of dry extract of support, 55% of solids of CMC (35% being used for the impregnation stage and 20% being used for the coating step).
- the pulverulent composition also has a water content of 7.6%, a density of 450 g / l and the following granulometry: o greater than 800 ⁇ m -> 0% o between 500 and 800 ⁇ m -> 12% o between 300 and 500 ⁇ m - »46% o between 200 and 300 ⁇ m -> 26% o between 100 and 200 ⁇ m -» 16% o less than 100 ⁇ m - »0%
- the experimental protocol below describes a process for the preparation of a stable powdery composition in which the sensitive substance is a superoxydismutase enzyme, the support is wheat maltodextrin and the impregnating and sticking agents are constituted by the CMC. .
- the distribution of the dry extract is thus the following: 50% of pure enzyme and 50% of maltodextrin support of wheat.
- the average particle size of the powder obtained in D (v, 0.5) is 95 ⁇ m and the moisture is 4.5%.
- This step makes it possible to obtain a pre-stabilized dry intermediate homogeneous powder.
- the impregnation is carried out in a rapid mixer for wet and pasty products (cutter) and comprises the following steps: o 60 seconds of premixing of the ingredients (0.25 kg of dry extract of
- the product is dried on a fluid bed dryer with an inlet temperature of 0 ° C and an outlet temperature of 40 ° C.
- the densified microgranulated powder obtained has 8% moisture.
- An aqueous solution of 7% CMC is heated to a temperature of 60 0 C to 70 ° C.
- the amount of CMC deposited is 0.5 kg dry extract of CMC per kilogram of dry extract of densified microgranulated powder to be coated.
- the powder obtained at this stage has an average particle size of 300 ⁇ m and has a moisture content of 9%.
- the stable powdery composition obtained as final product then has the following composition: 20% dry extract of enzyme, 20% of dry extract of support, 60% of solids of CMC (10% being used for the impregnation stage and 50% being used for the coating step).
- the pulverulent composition also has a water content of 9%, a density of 400 g / l and the following particle size: o greater than 800 ⁇ m -> 0% o between 500 and 800 ⁇ m -> 7% o between 300 and 500 ⁇ m - »35% o between 200 and 300 ⁇ m -> 38% o between 100 and 200 ⁇ m -_> 20% o less than 100 ⁇ m -> 0%
- the distribution of the dry extract is therefore as follows: 20% dry extract of pure bacterium and 80% of starch support.
- the average particle size of the powder obtained in D (v, 0.5) is 45 ⁇ m and the humidity is 4%.
- This step makes it possible to obtain a pre-stabilized dry intermediate homogeneous powder.
- the impregnation is carried out in a rapid mixer in a controlled atmosphere and comprises the following steps: o 30 seconds of premixing of the ingredients (0.2 kg of CMC solids per kilogram of intermediate powder solids) o 30 seconds of water addition, at a rate of 0.4 kg of water per kilogram of dry powder of intermediate powder, with stirring, and 30 seconds of terminal mixing.
- the product is dried on a fluid bed dryer with inlet air at less than 2 g of water per kilogram of air, an inlet temperature of 50 ° C and an outlet temperature of 40 ° C maximum.
- the densified microgranulated powder obtained has 7% moisture.
- An aqueous solution of 7% CMC is heated to a temperature of 60 0 C to 70 ° C.
- the amount of CMC deposited is 0.66 kg of CMC solids per kilogram of dry extract of densified microgranulated powder to be coated.
- the powder obtained at this stage has an average particle size of 350 ⁇ m and has a humidity of 7% and a water activity of less than 0.2 in order to stabilize the bacteria at heart.
- the stable powdery composition obtained as final product then has the following composition: 10% dry extract of the pure bacteria fermentation medium, 50% dry solids of starch (40% being used as a support and 10% as an impregnating agent ) and finally 40% dry extract of CMC used as a binder.
- the pulverulent composition also has a water content of 7% and a density of 450 g / l.
- the experimental protocol below describes a process for preparing a stable powdery composition in which the sensitive substance is an antibiotic, which is tylosin, already in powder form, the support is flour and the impregnating agent and the sticking agent consist of CMC.
- the distribution of the dry extract is therefore as follows: 44% dry extract of pure antibiotic and 56% of flour.
- the average particle size of the powder obtained in D (v, 0.5) is 40 ⁇ m and the moisture is 4.7%.
- the impregnation is carried out in a rapid mixer in a controlled and conditioned atmosphere and comprises the following steps: o 90 seconds of premixing of the ingredients (0.4 kg of CMC solids per kilogram of intermediate powder solids) o 60 seconds of water addition, at a rate of 0.1 kg of water per kilogram of dry powder of intermediate powder, with stirring, and 60 seconds of terminal mixing.
- the product is dried on a fluid bed dryer with inlet air at less than 2 g of water per kilogram of air, an inlet temperature of 60 ° C and an outlet temperature of 50 ° C maximum.
- the densified micro granulated powder obtained has 7% moisture
- An aqueous solution of 7% CMC is heated to a temperature of 60 ° C to 70 ° C.
- the quantity of CMC deposited is 0.14 kg of CMC solids per kilogram of dry extract of densified microgranulated powder to be coated.
- the powder obtained at this stage has an average particle size of 500 ⁇ m and has a humidity of 5.6% and a water activity of less than 0.2 in order to stabilize the antibiotic in the mixtures during application.
- the stable powdery composition obtained as final product then has the following composition: 27.5% dry extract of antibiotic, 35% dry extract of support, 37.5% dry extract of CMC (25% being used for the impregnation step and 12.5% being used for the coating step).
- the stable powdery composition also has a density of 450 g / l.
- the experimental protocol below describes a process for the preparation of a stable powdery composition in which the sensitive substance is a mixture of carotenoids containing in particular 55% of astaxanthin, the support is calcium carbonate and the impregnating and sticking agents are constituted by the CMC.
- the distribution of the dry extract is therefore as follows: 75% dry matter of the solution of carotenoids and 25% of calcium carbonate support.
- the average particle size of the powder obtained in D (v, 0.5) is 105 ⁇ m and the humidity is 5%.
- This step makes it possible to obtain a pre-stabilized dry intermediate homogeneous powder.
- the impregnation is carried out in a rapid mixer for wet and pasty products (cutter) and comprises the following steps: o 90 seconds of premixing of the ingredients (0.5 kg of CMC solids per kilogram of powder solids) intermediate), 90 seconds of addition of water, at a rate of 1 kg of water per kilogram of dry powder of intermediate powder, with stirring, and 180 seconds of terminal mixing.
- the product is dried on a fluid bed dryer with an inlet temperature of 70 ° C. and an outlet temperature of 50 ° C.
- the densified microgranulated powder obtained has 8% moisture. 3. Coating step with the binder
- An aqueous solution of 7% of CMC is heated to a temperature of 60 ° C. to 70 ° C.
- the quantity of CMC deposited is 0.25 kg of CMC solids per kilogram of densified microgranulated powder solids. to coat.
- the powder obtained at this stage has a mean particle size of 300 ⁇ m and has a humidity of 8%.
- the stable powdery composition obtained as final product then has the following composition: 40% solids content of the carotenoid solution, 13% solids content of calcium carbonate as carrier, 47% solids content of CMC (27% being used for the impregnation stage and 20% being used for the coating step).
- the stable powdery composition also has a water content of 8% and a density of 510 g / l.
- the experimental protocol below describes a process for preparing a stable powdery composition in which the sensitive substance is an essential oil, the support is wheat flour, the impregnating agent and the sticking agent are constituted by the CMC.
- the distribution of the dry extract is therefore as follows: 50% dry matter of the essential oil of garlic and 50% of wheat flour support.
- the average particle size of the powder obtained in D (v, 0.5) is 50 ⁇ m and the moisture is 7%. This step makes it possible to obtain a pre-stabilized intermediate homogeneous powder.
- the impregnation is carried out in a rapid mixer for wet and pasty products (cutter) and comprises the following steps: o 120 seconds of premixing of the ingredients (0.15 kg of dry extract of
- the product is dried on a fluid bed dryer with an inlet temperature of 50 ° C. and an outlet temperature of 40 ° C.
- the densified microgranulated powder obtained has 7% moisture.
- An aqueous solution of 7% CMC is heated to a temperature of 60 0 C to 70 ° C.
- the quantity of CMC deposited is 0.18 kg of CMC solids per kilogram of densified microgranulated powder solids to be coated.
- the powder obtained at this stage has an average particle size of 450 ⁇ m and has a humidity of 8%.
- the stable powdery composition obtained as final product then has the following composition: 37.5% dry extract of garlic essential oil, 37.5% dry extract of wheat flour as a support, 25% dry extract of CMC (10% being used for the impregnation stage and 15% being used for the coating stage).
- the stable powdery composition also has a water content of 8% and a density of 550 g / l.
- EXAMPLE 7 Microscopic Characterization of the Stable Powder Composition Containing a Mixture of Enzymes
- the conventional coating method consists of covering a solid support with a layer of product by suspending the material to be coated in a stream of air and spraying the coating liquid in the fluidized bed formed.
- the coating method using innovative systems consists, in turn, in spraying the masticating agent, to form a protective film, continuously with a mono dispersed aerosol, thus allowing better efficiency and obtaining homogeneous particles to improve the density of the particles and to limit the amount of deposited binder.
- This system allows homogeneity of the passage of the particles in front of the nozzle with a high flow rate.
- the protective film (or coating) covering the heart of the particles is visible under a scanning electron microscope.
- a conventional coating process there is a heterogeneity of the particles with the presence of partial voids, which makes it difficult to deposit the masticating agent in the voids created (see FIGS. 2, 3 and 4). .
- Example 8 Resistance to temperature and pressure of the enzymes contained in the stable powdery composition
- the objective is to test the enzymatic activity of preparations consisting of powder compositions containing enzymes added to a poultry flour food base growth after a granulation step.
- Three conditioning conditioner treatment temperatures (80, 85 and 90 ° C) are applied for each mixture according to a protocol described below.
- Test 1 A mixture of 60 kg made with 59.998 kg of poultry meal flour food and 3 g of a powdery composition is prepared using a horizontal-axis blade mixer rotating at 60 rpm. The mixing time is 2 minutes.
- Test 2 A premix of 500 g is made with 2 g of a pulverulent composition and 498 g of poultry meal flour food.
- the previous premix is prepared using a horizontal-axis blade mixer running at 60 rpm.
- the mixing time is 2 minutes.
- the pulverulent composition used then consists of: a standard composition without protection for the products A and C corresponding to the product ROVABIO EXCEL AP marketed by ADISSEO France SAS 3 which contains 80% of wheat flour and 20% of a sensitive substance, and a composition according to the invention with protection containing 20% of a sensitive substance, 25% of wheat flour support and 55% of CMC (used as an agent impregnating agent and binder) for product B or 35% CMC for products D and E, the rate of incorporation of said powdery composition into the poultry flour feed being 50 g / T.
- compositions were produced from the same batch of sensitive substance, namely a concentrated filtered fermentation mash obtained from Penicillium fimiculosum (IMI 378536), containing 19 enzymatic activities, the main ones being xylanase, ⁇ -glucanase and cellulase, which is behind the commercial product ROVABIO EXCEL AP.
- IMI 378536 Penicillium fimiculosum
- test 1 The previous mixture (test 1 or 2) is drained into a rectangular tank before bagging.
- a representative sample of the mixture of about 1 kg is taken by grouping 20 samples obtained by quartering in the rectangular tray.
- the granulation tests are carried out on a flat-die laboratory press (KAHL 14-175 press of 3 kW).
- the press die used has channels 4 mm in diameter and 24 mm thick (compression ratio: 6).
- Cooling drying time is at least 5 minutes to a load in hot pellets of about 3 , 5 kg per cooler.
- Measurements of humidity and die residence time are made from samples taken during the stabilized phase of each test.
- the opening of the steam control valve is manually raised on the control unit.
- the temperatures are recorded every second by acquisition software.
- the temperature of the die corresponds to the temperature of the granules.
- Moisture measurements are performed after oven drying of a 5 g sample at 103 ° C for 4 hours. All measurements are done in duplicate.
- the flow rate of the press is measured by weighing a sample of 30 seconds at the outlet of the die.
- This measurement calculated by a power converter is recorded every second by acquisition software.
- this parameter allows us to calculate net specific production (kg / kWh) and net specific consumption (kWh / T).
- Measurement of the residence time of the granules in the die This measurement is calculated with respect to the flow rate of the press. The calculation takes into account the weighing of 20 cm of granules.
- the regulation instructions of the press are as follows: Flow rate: approximately 41 kg / h,
- the test is based on the enzymatic hydrolysis of ⁇ -glucan in barley, a ⁇ -1,3 (4) -glucan.
- the products of the reaction are colorimetrically determined by measuring the increase of the reducing groups with 3,5-dinitrosalicylic acid (DNS).
- DNS 3,5-dinitrosalicylic acid
- the reducing sugar concentration available after enzymatic hydrolysis is determined using a standard glucose curve whose absorbance is measured at 540 nm. The enzymatic activity calculated is then expressed in glucose equivalents.
- DNS 1% (w / v) 3,5-dinitrosalicylic acid, 1.6% (w / v) NaOH, 30% ( m /
- the absorbance is corrected with that obtained for a reference solution to which the DNS is added before the enzymatic solution.
- the results are converted into ⁇ moles of reducing sugar compared to a range of standard solutions ranging from 0.00 to 0.04% (m / V) glucose treated in the DNS as in the case of the tests.
- a unit of endo-1,3 (4) - ⁇ -glucanase activity is defined as the amount of enzyme which produces 1 ⁇ mol of glucose equivalents per minute per gram of product, under the conditions of the test (pH 5.0 and 50 ° C).
- the test is based on the enzymatic hydrolysis of birch xylan, a xylose polymer containing ⁇ -D-1,4 bridges.
- the products of the reaction are colorimetrically determined by measuring the increase of the reducing groups with 3,5-dinitrosalicylic acid.
- the reducing sugar concentration available after enzymatic hydrolysis is determined using a standard xylose curve whose absorbance is measured at 540 nm. The calculated enzymatic activity is then expressed in xylose equivalents.
- a solution containing 1 ml of 1% (w / v) birch xylan solution in 0.1 M sodium acetate buffer at pH 5.0 and 1 ml of the appropriate dilution solution of the enzyme is incubated at 50 0 C for 10 minutes.
- the enzymatic reaction is stopped by the addition of 2 ml of a solution of DNS (1% (w / v) 3,5-dinitrosalicylic acid, 1.6% (w / v) NaOH, 30% ( m / V) of potassium tartrate and sodium (+) in distilled water).
- DNS 1% (w / v) 3,5-dinitrosalicylic acid, 1.6% (w / v) NaOH, 30% ( m / V) of potassium tartrate and sodium (+) in distilled water.
- the solution is homogenized and then placed in a water bath boiling at 95 ° C minimum and then cooled in a bath at room temperature (for 5 minutes).
- Ten milliliters of ultrapure water are added to the
- the absorbance is corrected with that obtained for a reference solution to which the DNS is added before the enzymatic solution.
- results are converted into ⁇ moles of reducing sugar by comparison with a range of standard solutions ranging from 0.00 to 0.04% (m / V) of xylose, treated with DNS as in the case of the tests.
- a unit of endo-1,4- ⁇ -xylanase activity is defined as the amount of enzyme which produces 1 ⁇ mol of xylose equivalent per minute per gram of product, under the conditions of the test (pH 5). , 0 and 50 0 C).
- Endo-1,4- ⁇ -xylanase hydrolyzes the xyloside bridges of xylan.
- the assay is based on the enzymatic hydrolysis of the xylose bridges of a wheat arabinose solution, substituted ⁇ -1,4-xylan polysaccharide with arabinose.
- the enzymatic activity is proportional to the viscosity reduction of a wheat arabinoxylan solution in the presence of the enzyme to be assayed.
- a unit of endo-1,4- ⁇ -xylanase activity is defined as the amount of enzyme that will hydrolyze the substrate, reducing the viscosity of the solution, to give a change in the relative fluidity of 1 unit without dimensions. minute under the conditions of the analysis: pH 5.5 and 30 0 C.
- the enzyme retains 100% of its activity, while the unprotected enzyme has lost 1/4 of its activity (test 1). At temperatures above 85 ° C, the enzyme retains more than 80% of its activity.
- test 1 or 2 correspond to powder compositions containing 55% and 35% CMC, respectively.
- the greater compaction and densification of the particles obtained with 35% CMC thus makes it possible to maintain the stability of the enzyme even with a lesser amount of CMC.
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Abstract
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Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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BRPI0814531-8A BRPI0814531B1 (pt) | 2007-07-20 | 2008-07-18 | Processo de preparo de composições pulverulentas estáveis |
EP08836060.7A EP2173189B1 (fr) | 2007-07-20 | 2008-07-18 | Compositions pulverulentes stables et leur procédé de préparation |
JP2010517443A JP5645660B2 (ja) | 2007-07-20 | 2008-07-18 | 安定な粉末組成物の製造方法 |
CA2708316A CA2708316C (fr) | 2007-07-20 | 2008-07-18 | Procede de preparation de compositions pulverulentes stables |
US12/669,868 US20100196493A1 (en) | 2007-07-20 | 2008-07-18 | Method for producing stable powder compositions |
CN200880107868.4A CN101801211B (zh) | 2007-07-20 | 2008-07-18 | 用于制备稳定的粉末状组合物的方法 |
MX2010000798A MX2010000798A (es) | 2007-07-20 | 2008-07-18 | Metodos de preparacion de composiciones pulverulentas estables. |
ES08836060T ES2733873T3 (es) | 2007-07-20 | 2008-07-18 | Composiciones pulverulentas estables y procedimiento de preparación de las mismas |
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FR0705307 | 2007-07-20 | ||
FR0705307A FR2918990B1 (fr) | 2007-07-20 | 2007-07-20 | Procede de preparation de compositions pulverulentes stables |
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WO2009043988A2 true WO2009043988A2 (fr) | 2009-04-09 |
WO2009043988A3 WO2009043988A3 (fr) | 2009-07-23 |
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PCT/FR2008/001069 WO2009043988A2 (fr) | 2007-07-20 | 2008-07-18 | Procede de preparation de compositions pulverulentes stables |
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US (1) | US20100196493A1 (fr) |
EP (1) | EP2173189B1 (fr) |
JP (1) | JP5645660B2 (fr) |
KR (1) | KR101616132B1 (fr) |
CN (1) | CN101801211B (fr) |
BR (1) | BRPI0814531B1 (fr) |
CA (1) | CA2708316C (fr) |
ES (1) | ES2733873T3 (fr) |
FR (1) | FR2918990B1 (fr) |
MX (1) | MX2010000798A (fr) |
WO (1) | WO2009043988A2 (fr) |
Cited By (1)
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JP2010534067A (ja) * | 2007-07-20 | 2010-11-04 | アディッソ・フランス・エス.エー.エス. | 酵素混合物を含む、動物向けの耐熱性配合物 |
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US9332776B1 (en) | 2010-09-27 | 2016-05-10 | ZoomEssence, Inc. | Methods and apparatus for low heat spray drying |
US8939388B1 (en) | 2010-09-27 | 2015-01-27 | ZoomEssence, Inc. | Methods and apparatus for low heat spray drying |
CN103012855B (zh) * | 2012-12-14 | 2015-10-21 | 湖北中烟工业有限责任公司 | 烟用香精微丸的薄膜包衣剂及其制备方法 |
US9585841B2 (en) * | 2013-10-22 | 2017-03-07 | Tyme, Inc. | Tyrosine derivatives and compositions comprising them |
FR3042387B1 (fr) * | 2015-10-20 | 2019-05-24 | Ynsect | Preservation de vitamines hydrosolubles |
KR101876505B1 (ko) * | 2016-11-04 | 2018-07-09 | 한국과학기술연구원 | 베타 사이클로덱스트린 기반의 푸코잔틴 미세분말 및 이의 제조방법 |
US9993787B1 (en) | 2017-08-04 | 2018-06-12 | ZoomEssence, Inc. | Ultrahigh efficiency spray drying apparatus and process |
US10252181B2 (en) | 2017-08-04 | 2019-04-09 | ZoomEssence, Inc. | Ultrahigh efficiency spray drying apparatus and process |
US10155234B1 (en) | 2017-08-04 | 2018-12-18 | ZoomEssence, Inc. | Ultrahigh efficiency spray drying apparatus and process |
US9861945B1 (en) | 2017-08-04 | 2018-01-09 | ZoomEssence, Inc. | Ultrahigh efficiency spray drying apparatus and process |
US10486173B2 (en) | 2017-08-04 | 2019-11-26 | ZoomEssence, Inc. | Ultrahigh efficiency spray drying apparatus and process |
US10569244B2 (en) | 2018-04-28 | 2020-02-25 | ZoomEssence, Inc. | Low temperature spray drying of carrier-free compositions |
KR102172273B1 (ko) * | 2019-10-31 | 2020-10-30 | 주식회사 삼양사 | 점성 저감화 환 제조용 조성물 |
CN114748436B (zh) * | 2022-05-30 | 2023-05-16 | 迪沙药业集团有限公司 | 一种硝苯地平组合物及其制备方法 |
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DE69111287T2 (de) * | 1990-04-18 | 1995-12-21 | Asahi Chemical Ind | Kugelförmige Keimkerne, kugelförmige Granulate sowie Verfahren zu deren Herstellung. |
FR2698560B1 (fr) * | 1992-11-30 | 1995-02-03 | Virbac Laboratoires | Principes actifs pulvérulents stabilisés, compositions les contenant, leur procédé d'obtention et leurs applications. |
US6156340A (en) * | 1996-03-29 | 2000-12-05 | Duquesne University Of The Holy Ghost | Orally administrable time release drug containing products |
TW409035B (en) * | 1997-06-04 | 2000-10-21 | Gist Brocades Bv | Starch-based enzyme granulates |
US6667050B1 (en) * | 1999-04-06 | 2003-12-23 | Galen (Chemicals) Limited | Chewable oral contraceptive |
CN1125638C (zh) * | 1999-05-20 | 2003-10-29 | 杭州阳光文化用品有限公司 | 稳定型缓释维生素c制剂及其生产方法 |
JP2005514049A (ja) * | 2002-01-15 | 2005-05-19 | ビーエーエスエフ アクチェンゲゼルシャフト | 飼料用酵素含有顆粒 |
ES2306079T3 (es) * | 2004-01-30 | 2008-11-01 | Basf Se | Granulados que contienen formulaciones de fitasa estabilizantes. |
ZA200803025B (en) * | 2005-10-12 | 2010-07-28 | Genencor Int | Stable, durable granules with active agents |
-
2007
- 2007-07-20 FR FR0705307A patent/FR2918990B1/fr not_active Expired - Fee Related
-
2008
- 2008-07-18 US US12/669,868 patent/US20100196493A1/en not_active Abandoned
- 2008-07-18 BR BRPI0814531-8A patent/BRPI0814531B1/pt not_active IP Right Cessation
- 2008-07-18 CA CA2708316A patent/CA2708316C/fr not_active Expired - Fee Related
- 2008-07-18 MX MX2010000798A patent/MX2010000798A/es active IP Right Grant
- 2008-07-18 JP JP2010517443A patent/JP5645660B2/ja not_active Expired - Fee Related
- 2008-07-18 CN CN200880107868.4A patent/CN101801211B/zh not_active Expired - Fee Related
- 2008-07-18 WO PCT/FR2008/001069 patent/WO2009043988A2/fr active Application Filing
- 2008-07-18 KR KR1020107003710A patent/KR101616132B1/ko active IP Right Grant
- 2008-07-18 ES ES08836060T patent/ES2733873T3/es active Active
- 2008-07-18 EP EP08836060.7A patent/EP2173189B1/fr not_active Not-in-force
Non-Patent Citations (1)
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010534067A (ja) * | 2007-07-20 | 2010-11-04 | アディッソ・フランス・エス.エー.エス. | 酵素混合物を含む、動物向けの耐熱性配合物 |
Also Published As
Publication number | Publication date |
---|---|
BRPI0814531B1 (pt) | 2018-06-05 |
WO2009043988A3 (fr) | 2009-07-23 |
JP2010534226A (ja) | 2010-11-04 |
CN101801211A (zh) | 2010-08-11 |
KR101616132B1 (ko) | 2016-05-12 |
EP2173189A2 (fr) | 2010-04-14 |
KR20100047267A (ko) | 2010-05-07 |
EP2173189B1 (fr) | 2019-03-06 |
CN101801211B (zh) | 2015-04-15 |
ES2733873T3 (es) | 2019-12-03 |
MX2010000798A (es) | 2010-05-17 |
FR2918990B1 (fr) | 2012-12-21 |
US20100196493A1 (en) | 2010-08-05 |
FR2918990A1 (fr) | 2009-01-23 |
BRPI0814531A2 (pt) | 2015-08-04 |
CA2708316C (fr) | 2016-05-03 |
JP5645660B2 (ja) | 2014-12-24 |
CA2708316A1 (fr) | 2009-04-09 |
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