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EP2173781A1 - Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution - Google Patents

Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution

Info

Publication number
EP2173781A1
EP2173781A1 EP08786188A EP08786188A EP2173781A1 EP 2173781 A1 EP2173781 A1 EP 2173781A1 EP 08786188 A EP08786188 A EP 08786188A EP 08786188 A EP08786188 A EP 08786188A EP 2173781 A1 EP2173781 A1 EP 2173781A1
Authority
EP
European Patent Office
Prior art keywords
extruder
solvent
copolymers
water
polymer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08786188A
Other languages
German (de)
English (en)
Inventor
Murat Mertoglu
Rainer Dobrawa
Kathrin MEYER-BÖHM
Norbert Güntherberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Priority to EP08786188A priority Critical patent/EP2173781A1/fr
Publication of EP2173781A1 publication Critical patent/EP2173781A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
    • C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C48/00—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor
    • B29C48/03—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor characterised by the shape of the extruded material at extrusion
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C48/00—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor
    • B29C48/25—Component parts, details or accessories; Auxiliary operations
    • B29C48/36—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die
    • B29C48/395—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die using screws surrounded by a cooperating barrel, e.g. single screw extruders
    • B29C48/40—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die using screws surrounded by a cooperating barrel, e.g. single screw extruders using two or more parallel screws or at least two parallel non-intermeshing screws, e.g. twin screw extruders
    • B29C48/405—Intermeshing co-rotating screws
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C48/00—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor
    • B29C48/25—Component parts, details or accessories; Auxiliary operations
    • B29C48/36—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die
    • B29C48/395—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die using screws surrounded by a cooperating barrel, e.g. single screw extruders
    • B29C48/40—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die using screws surrounded by a cooperating barrel, e.g. single screw extruders using two or more parallel screws or at least two parallel non-intermeshing screws, e.g. twin screw extruders
    • B29C48/41—Intermeshing counter-rotating screws
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C48/00—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor
    • B29C48/25—Component parts, details or accessories; Auxiliary operations
    • B29C48/36—Means for plasticising or homogenising the moulding material or forcing it through the nozzle or die
    • B29C48/50—Details of extruders
    • B29C48/76—Venting, drying means; Degassing means

Definitions

  • the present invention relates to a process for producing solid copolymers for use as solubilizers for sparingly water-soluble substances obtained by polymerizing vinyl acetate and N-vinyl lactams in the presence of a polyether as solutions. Furthermore, the invention relates to a process for the preparation of solid solutions of said copolymers and poorly water-soluble substances.
  • the corresponding copolymers are, as stated, suitable for use as solubilizers for substances sparingly soluble in water.
  • Solubilization is understood to mean the solubilization of substances which are soluble or insoluble in a particular solvent, in particular water, by surface-active compounds, the solubilizers. Such solubilizers are able to convert poorly water-soluble or water-insoluble substances into clear, at most opalescent aqueous solutions without the chemical structure of these substances undergoing any change (see Römpp Chemie Lexikon, 9th edition, Bd.5. 4203, Thieme Verlag, Stuttgart, 1992).
  • solubilizates prepared are characterized in that the sparingly water-soluble or water-insoluble substance is colloidally dissolved in the molecular associates of the surface-active compounds which form in aqueous solution, for example hydrophobic domains or micelles.
  • the resulting solutions are stable or metastable single-phase systems that appear optically clear to opalescent.
  • Solubilizers can, for example, the appearance of cosmetic
  • Formulations and food preparations by making the formulations more transparent.
  • the bioavailability and thus the effect of drugs can be increased by the use of solubilizers.
  • solubilizers for pharmaceutical drugs and cosmetic agents are mainly surfactants such as ethoxylated castor oil or ethoxylated hydrogenated Castor oil, ethoxylated sorbitan fatty acid esters or ethoxylated hydroxystearic acid.
  • solubilizers have, for some sparingly soluble drugs, e.g. Clotrimazole only a small solubilizing effect.
  • EP-A 876 819 describes the use of copolymers of at least 60% by weight of N-vinylpyrrolidone and amides or esters with long-chain alkyl groups.
  • EP-A 948 957 describes the use of copolymers of monoethylenically unsaturated carboxylic acids such as acrylic acid and hydrophobically modified comonomers such as, for example, N-alkyl or N, N-dialkylamides of unsaturated carboxylic acids with Cs-Cso-alkyl radicals.
  • DE-A 199 350 63 discloses polyalkylene oxide-containing graft polymers based on vinyllactams and vinyl acetate and their use as gas hydrate inhibitors.
  • solid solution refers to a state in which a substance is dispersed in a microdispersed or, ideally, molecularly dispersed form in a solid matrix, such as a polymer matrix .
  • solid solutions for example, when used in solid pharmaceutical dosage forms of a poorly soluble drug to an improved release of the drug.
  • An important requirement of such solid solutions is that they are stable even over long periods of storage, that is, that the active ingredient does not crystallize out.
  • the capacity of the solid solution in other words the ability to form stable solid solutions with the highest possible active ingredient contents, is of importance.
  • the hygroscopicity of the solubilizers also plays an important role. Solubilizers coming from the ambient air To absorb too much water, lead to a flow of the solid solution and the unwanted crystallization of the active ingredients. Even when processed into dosage forms too great hygroscopicity can cause problems.
  • solubilizers have the disadvantages that they do not form stable solid solutions. In addition, they leave room for improvement in terms of solubilization in aqueous systems. Also in terms of processability, some of the known solubilizers have disadvantages due to their tendency to stick, since they do not constitute sufficiently flowable powders.
  • WO 2007/051743 discloses the use of water-soluble or water-dispersible copolymers which are obtained by free-radically initiated polymerization, in particular solution polymerization, of a mixture
  • solubilizers for pharmaceutical, cosmetic, food-processing, agrotechnical or other technical applications.
  • solubilizers for pharmaceutical, cosmetic, food-processing, agrotechnical or other technical applications.
  • the object of the present invention was an improved process for converting the graft copolymers described above from the solutions obtained after the polymerization into the solid form. Task was further to allow the incorporation of other components, in particular heavy water-soluble active substances. Accordingly, a process for the preparation of copolymers in solid form has been found, wherein the copolymers are obtained by free-radically initiated polymerization of a mixture
  • At least one further component preferably an active substance, is added before or during the removal of the solvent.
  • preferred polymers are obtained from:
  • Suitable N-vinyllactam are N-vinylcaprolactam or N-vinylpyrrolidone or mixtures thereof. Preference is given to using N-vinylcaprolactam.
  • the graft is polyether.
  • Suitable polyethers are preferably polyalkylene glycols. The polyalkylene glycols may have molecular weights of from 1000 to 100,000 D [daltons], preferably from 1500 to 35,000 D, more preferably from 1,500 to 10,000 D. The molecular weights are determined on the basis of the measured according to DIN 53240 OH number.
  • polyalkylene glycols are polyethylene glycols. Also suitable are polypropylene glycols, polytetrahydrofurans or polybutylene glycols which are obtained from 2-ethyloxirane or 2,3-dimethyloxirane.
  • Suitable polyethers are also random or block copolymers of polyalkylene glycols derived from ethylene oxide, propylene oxide and butylene oxides such as polyethylene glycol-polypropylene glycol block copolymers.
  • the block copolymers may be of the AB or ABA type.
  • the preferred polyalkylene glycols also include those which are alkylated at one or both OH end groups.
  • Suitable alkyl radicals are branched or unbranched C 1 -C 22 -alkyl radicals, preferably C 1 -C -alkyl radicals, for example methyl, ethyl, n-butyl, isobutyl, pentyl, hexyl, octyl, nonyl, decyl , Dodecyl, tridecyl or octadecyl radicals.
  • the preparation is carried out by free-radically initiated polymerization, preferably in solution, in nonaqueous, organic solvents or in mixed nonaqueous / aqueous solvents.
  • Suitable non-aqueous organic solvents are, for example, alcohols, such as methanol, ethanol, n-propanol, and isopropanol, and also glycols, such as ethylene glycol and glycerol.
  • esters such as, for example, ethyl acetate, n-propyl acetate, isopropyl acetate, isobutyl acetate or butyl acetate, ethyl acetate being preferred.
  • the polymerization is preferably carried out at temperatures of 60 to 100 0 C.
  • Radical initiators are used to initiate the polymerization.
  • the amounts of initiator or initiator mixtures used based on the monomer used are between 0.01 and 10 wt .-%, preferably between 0.3 and 5 wt .-%.
  • organic and inorganic peroxides such as sodium persulfate or azo initiators such as azo-bis-isobutyronitrile, azobis (2-amidopropane) dihydrochloride or 2,2'-azobis (2-methyl) butyronitrile).
  • Peroxidic initiators are, for example, dibenzoyl peroxide, diacetyl peroxide, succinic peroxide, tert-butyl perpivalate, tert-butyl perethyl hexanoate, tert-butyl pernodecanoate, tert-butyl permalate, bis (tert-butyl per) cyclohexane, tert-butyl per-isopropyl carbonate.
  • tert-butyl peracetate 2,2-bis (tert-butylper) butane, dicumyl peroxide, di-tert-amyl peroxide, di-tert-butyl peroxide, p-menthane hydroperoxide, pinane hydroperoxide, cumene hydroperoxide, tert-butyl hydroperoxide, hydrogen peroxide and mixtures of the initiators mentioned.
  • the initiators mentioned can also be used in combination with redox components such as ascorbic acid.
  • Particularly suitable initiators are tert-butyl perneodecanoate, tert-butyl perpivalate or tert-butyl perethyl hexanoate.
  • the free-radical polymerization can take place in the presence of emulsifiers, optionally further protective colloids, optionally molecular weight regulators, optionally buffer systems and, if appropriate, subsequent pH adjustment by means of bases or acids.
  • Suitable molecular weight regulators are hydrogen sulfide compounds such as alkyl mercaptans, e.g. n-dodecylmercaptan, tert-dodecylmercaptan, thioglycolic acid and its esters, mercaptoalkanols such as mercaptoethanol.
  • alkyl mercaptans e.g. n-dodecylmercaptan, tert-dodecylmercaptan, thioglycolic acid and its esters, mercaptoalkanols such as mercaptoethanol.
  • Other suitable regulators are e.g. in DE 197 12 247 A1, page 4, called.
  • the required amount of molecular weight regulator is in the range of 0 to 5 wt .-% based on the (co) monomer to be polymerized.
  • the amount used is in particular in the range of 0.05 to 2 wt .-%, particularly preferably 0.1 to 1, 5 wt .-%.
  • the polymerization in the absence of a regulator.
  • emulsifiers may also be used, for example ionic or nonionic surfactants, the HLB value of which is usually in the range of 3 to 13.
  • HLB value the HLB value of which is usually in the range of 3 to 13.
  • the amount of surfactants based on the polymer can be from 0 to 10% by weight, preferably from 0 to 5% by weight.
  • the monomer or monomer mixture or the monomer (s) emulsion are introduced together with the initiator, which is generally in solution, in a stirred reactor at the polymerization temperature (batch process), or optionally continuously or in several successive stages in the polymerization reactor metered (Feed process).
  • the initiator which is generally in solution, in a stirred reactor at the polymerization temperature (batch process), or optionally continuously or in several successive stages in the polymerization reactor metered (Feed process).
  • the reactor before the actual polymerization in addition to the solvent (to allow stirring of the reaction mixture) already with subsets, rarely the entire intended amount for the polymerization, the starting materials such as emulsifiers, protective colloids, monomers, regulators, etc ., or subsets of the feeds (ia monomer or emulsion feed and initiator feed) is filled.
  • the polymerization can be carried out both at atmospheric pressure and in a closed reactor at elevated pressure. In this case, it is possible to polymerize either at the pressure which occurs during the reaction, or the pressure can be adjusted by pressing on a gas or evacuating. Furthermore, the pressure can also be controlled by temporarily releasing the reactor into the cooler.
  • a nonaqueous solvent used for the polymerization may then be removed by steam distillation and exchanged for water.
  • the non-aqueous solvent is distilled off as far as possible pure and then completely replaced by introducing steam into water.
  • the polymerization mixtures may be treated by well-known residual monomer lowering techniques. Such methods are, for example, the further addition of initiator at the end of the polymerization, the hydrolysis of vinyl lactam monomers by addition of acids, treatment of the polymer solution with solid phases such as ion exchangers, feed of a good copolymerizing monomer, membrane filtration and other conventional methods.
  • the solids content of the resulting polymerization in the form of polymer dispersions or solutions may be 10 to 80 wt .-%.
  • the dispersions or solutions of the polymer are converted into solid form by removal of the dispersing agent or solvent by means of an extruder, preferably in the molten state and cooling the melt.
  • the process according to the invention is preferably carried out with solutions of the active ingredient in an organic solvent. In this case, preference is given to using solutions having solids contents of 50-80% by weight, more preferably 60-70% by weight.
  • the polymer solution or polymer dispersion is introduced into an extruder, wherein the solvent evaporates with heating and kneading and forms a substantially solvent-free melt with continuous transport through the extruder.
  • the solvent evaporates with heating and kneading and forms a substantially solvent-free melt with continuous transport through the extruder.
  • Variant is this melt by introducing small amounts of water even from residual amounts of solvent and residual monomer and other volatile Substances released.
  • the thus isolated polymer melts and can then be cooled and granulated. Since the polymer is generally water-soluble, the usual methods of granulation of thermoplastic melts by cooling with water are less suitable. Rather, a so-called H depictabschlag or cooling takes place under air or inert gas, for example, a Teflon or chain belt and subsequent granulation of the cooled melt strand.
  • the molten polymer may be further processed in a further step.
  • this melt can be introduced into a suitable mixing device and provided with active ingredients and additives. Suitable mixing devices are, for example, a second extruder, kneaders, dynamic and static mixers, and combinations thereof.
  • a common process variant is the melting of the above-described isolated and solidified polymers and mixing with powdered or liquid active ingredients or additives.
  • Liquid additives can also be pumped well into the extruder by means of a suitable pump (piston pump, membrane pump, gear pump,
  • the extruder screw should be suitably provided with suitable mixing elements.
  • suitable mixing elements can be, for example, conveying and non-conveying kneading blocks, tooth mixing elements, elements with perforated webs, turbine mixing elements, hedgehogs, tooth blocks etc.
  • all commercially available mixing elements are suitable, in particular those which are intended for the mixing of liquids.
  • polymer melt and active substance are mixed with each other before granulation.
  • the recovery of the dry polymer takes place in the presence of an active substance and optionally further components.
  • the active substance and the further components can either be added immediately to the solution or dispersion of the polymer or into the molten polymer and the resultant mixture fed to an extruder, or the active substance and the optional further components are introduced separately into the extruder.
  • the extruder can cold submit the active substance as a solid, slurry or dispersion in the extruder and pump the polymer solution, and degas both together, or you put the polymer solution, ie pumps them into the heated extruder and first vaporizes a certain proportion of the solvent (for example, 50-95%) and then at a later stage, the active ingredient or as a slurry and evaporates together solvent and suspending agent, or you clean the polymer melt even further by stripping with water and only then add the active ingredient as a solid. Or one adds a slurry of the active ingredient in water and at the same time takes this water as a stripping agent.
  • the extruder must be constructed differently and the worm shafts and peripherals must be differently equipped. This will be explained below using selected examples.
  • the extruder consists of several sections, each of which can be assigned to specific process units. Each of these sections consists of one or more cylinders (shots) as the smallest independent unit - and the associated screw sections with the process elements corresponding screw elements.
  • the process can be carried out in a single-screw extruder, a twin-screw extruder or in multi-screw extruders, for example a twelve-screw extruder, but preferably in a twin-screw extruder.
  • Several screws can be made in the same direction or in opposite directions, rotating, meshing or tightly meshing.
  • the extruder is preferably designed in the same direction rotating tightly combing.
  • the individual cylinders should be heated.
  • the cylinders can also be designed for cooling, for example for cooling with water.
  • the individual extruder sections can preferably be heated and cooled independently of each other, so that different temperature zones can also be set along the extrusion direction
  • the screws can be made up of all the usual elements in the extrusion.
  • extruder used according to the invention is divided essentially into the following sections:
  • the extruder is divided into the following sections by way of example:
  • a first zone with an open-top shot which can serve on the one hand the degassing or gassing with inert gas, or else the feeding of active ingredient or additives or a neutral polymer to shut off the
  • the worm is equipped in this area with normal conveying elements and a blocking and melting zone of a kneading block and a recirculating screw element. This first zone is followed by the feed zone for the polymer solution. This consists of several shots with overhead opening, which are closed by entfrenbare cover. Depending on the task and degassing of the solution, a cover provided with an injection valve is placed on one of these openings, through which the polymer solution is injected by means of a pump.
  • the screw has in this area pure conveying elements or mixing and kneading elements to promote the surface renewal to promote evaporation.
  • the solvent evaporates in this case and is removed in the following first degassing section over 1 to 2, for example open top shots with low vacuum, (for example, atm to 400 mbar)
  • shots with side openings are suitable, if the product properties allow this (product leakage).
  • Aus In a particular Aus completelyungsform it may also be useful and conducive to provide a vent backwards to the injector to improve the driving safety of the process.
  • the metering of the polymer solution into the extruder takes place by means of pumps via a heatable line.
  • the polymer solution can be metered in cold, or heated to better flowability, or be overheated to a temperature well above the boiling point of the solvent of the solution, so that the solvent at Entry into the extruder evaporates more or less abruptly.
  • the vapors (solvent vapors) removed from the first degassing zone are withdrawn, condensed and sent for recycling. Following this first degassing zone is followed by an area with closed
  • Housing units which in addition to conveying screw elements also have accumulating and recirculating elements to the extruder chamber against the following second
  • Shut off degassing zone This consists of several shots with one or more vent openings, which are operated under vacuum. Usually, the pressure in this range is between 600 and 20 mbar.
  • the screw has in this area preferably conveying elements, but can also kneading or
  • degassing sections which are designed similarly in their construction. This may be necessary, for example, if the temperature and vacuum can only be increased slowly because of the degassing properties of the solutions.
  • the screw here has mixing and kneading elements.
  • the appropriate screw elements are promotional and non-promotional
  • Knetblöcke various embodiments, as well as combinations of promotional and recirculating screw elements and special mixing elements such
  • Tooth mixing elements turbine mixing elements, tooth blocks and special kneading blocks, as offered by the trade.
  • the degassing of the polymer solution / polymer dispersion is already better than 99%, but still not sufficient.
  • a suitable pump preferably pump, membrane pump
  • a stripping agent preferably water
  • the screw elements in this area allow intensive mixing.
  • Suitable screw elements are, for example, tooth mixing elements, narrow conveying and non-conveying kneading disks, SME, turbine mixing elements, so-called hedgehogs and others which must be thawed in a suitable manner in order to ensure a high degree of filling in this area.
  • At least one final degassing zone adjoins this mixing zone, in which the stripping agent and the remaining volatile substances are removed.
  • the Vacuum in this area should be particularly good and ranges from 50 mbar to 2 mbar, accessible for example by means of a steam jet. After this last degassing the discharge takes place from the extruder, for example through a nozzle bar. In principle, it is also possible to incorporate at this point active ingredients and additives in the melt, if the extruder here still has a feed opening and corresponding mixing elements on the screw.
  • the temperature control is ideally for the extruder so that a sufficient temperature for the evaporation of the solvent is present that a thermal
  • the temperature is 100-220 0 C, preferably 110 to 180 0 C, particularly preferably 120 to 160 ° C.
  • the ideal temperature range depends on the polymer.
  • the polymer is either alone or already mixed with the additives or simultaneously metered (coldfeed) into the feed opening of an extruder with the additives, then conveyed by conveying elements into the melting zone provided with kneading blocks and here plasticized and mixed by intensive kneading.
  • the pure polymer is melted and metered the additive, for example via a side feed as powder or in another form firmly into the hot melt and intimately mixed here with the polymer flow while also homogeneously mixed.
  • the dosage of the active ingredients and additives after the metering of the polymer is still cold in the extruder before the melting zone. This approach avoids certain types of collection problems.
  • the throughput depends on the polymer-solvent system, the amount of solvent to be removed, the desired degassing performance and the type of extruder used and can be determined by the skilled person by a few experiments.
  • the still plastic mixture is preferably extruded through a die, cooled and comminuted.
  • For comminution are in principle all the usual known techniques such as hot or cold deduction.
  • the extrudate is cut off, for example, with a rotating knife or with an air jet and then cooled with air or under protective gas. It is also possible to deposit the extrudate as a melt strand on a cooled belt (stainless steel, Teflon, chain belt) and granulate after solidification.
  • a cooled belt stainless steel, Teflon, chain belt
  • the extrudate can optionally be ground.
  • the copolymers are obtained as free-flowing and flowable water-soluble powders. Particle sizes of 20 to 250 ⁇ m are preferably set.
  • the polymers have Fikentscher K values in the range from 10 to 60, preferably 15 to 40, measured in a 1% strength by weight ethanolic solution. applications:
  • the copolymers obtained according to the invention can be used in all fields in which only sparingly soluble or insoluble substances in water are to be used either in aqueous preparations or to have their effect in an aqueous medium.
  • the copolymers accordingly find use as solubilizers of water-sparingly soluble substances, in particular biologically active substances.
  • the term "poorly water-soluble” also encompasses practically insoluble substances and means that at least 30 to 100 g of water per g of substance is required for a solution of the substance in water at 20 ° C. In the case of practically insoluble substances, at least 10,000 g of water per g substance needed.
  • sparingly soluble active substances in water are, for example, biologically active substances such as pharmaceutical active substances for humans and animals, cosmetic or agrochemical active substances or dietary supplements or dietary active substances.
  • dyes such as inorganic or organic pigments.
  • active ingredients are also referred to as active ingredients.
  • amphiphilic compounds for use as solubilizers for pharmaceutical and cosmetic preparations and food preparations are provided. They have the property of poorly soluble active ingredients in the field of pharmacy and cosmetics, sparingly soluble dietary supplements, such as vitamins and carotenoids, but also poorly soluble drugs for use in
  • the copolymers can be used as solubilizers in cosmetic formulations.
  • they are suitable as solubilizers for cosmetic oils. They have a good solubility for fats and oils such as peanut oil, jojoba oil, coconut oil, almond oil, olive oil, palm oil, castor oil, soybean oil or wheat germ oil or for essential oils such as mountain pine oil, lavender oil, rosemary oil, pine needle oil, pine needle oil, eucalyptus oil, peppermint oil, sage oil, bergamot oil, Turpentine oil, lemon balm oil, juniper oil, lemon oil, aniseed oil, cardamom oil; Camphor oil etc. or for mixtures of these oils.
  • fats and oils such as peanut oil, jojoba oil, coconut oil, almond oil, olive oil, palm oil, castor oil, soybean oil or wheat germ oil or for essential oils such as mountain pine oil, lavender oil, rosemary oil, pine needle oil, pine needle oil, eucalyptus oil, peppermint oil, sage oil,
  • the polymers may be used as solubilizers for water-insoluble or insoluble UV absorbers such as 2-hydroxy-4-methoxybenzophenone (Uvinul® M 40, BASF), 2,2 ', 4,4'-tetrahydroxybenzophenone (Uvinul® D 50), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (Uvinul® D49), 2,4-dihydroxybenzophenone (Uvinul® 400), 2-cyano-3,3-diphenylacrylic acid 2-ethylhexyl ester (Uvinul® N 539), 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1, 3,5-triazine (Uvinul ® T 150), 3- (4-methoxybenzylidene) camphor (Eusolex ® 6300, Merck), N, N-dimethyl-4-aminobenzoic acid 2-ethylhexyl ester
  • Methoxycinnamic acid 2-ethylhexylester and p-Methoxycinntklareisoamylester and mixtures thereof can be used.
  • camphor derivatives marketed by L'Oreal under the brand names Mexoryl® SX, SL, SO and SW or Mexoryl XL (drometrizoltrisiloxane).
  • formulations are water or water / alcohol based solubilisates.
  • the solubilizers according to the invention are used in a ratio of 0.2: 1 to 20: 1, preferably 1: 1 to 15: 1, more preferably 2: 1 to 12: 1 to the sparingly soluble cosmetic active ingredient.
  • the content of solubilizer according to the invention in the cosmetic preparation is, depending on the active ingredient, in the range of 1 to 50 wt .-%, preferably 3 to 40 wt .-%, particularly preferably 5 to 30 wt .-%.
  • auxiliaries may be added to this formulation, for example nonionic, cationic or anionic surfactants such as alkylpolyglycosides, fatty alcohol sulfates, fatty alcohol ether sulfates, alkanesulfonates, fatty alcohol ethoxylates, fatty alcohol phosphates, alkylbetaines, sorbitan esters, POE sorbitan esters, sugar fatty acid esters, fatty acid polyglycerol esters, fatty acid partial glycerides, fatty acid carboxylates, fatty alcohol sulfosuccinates,
  • nonionic, cationic or anionic surfactants such as alkylpolyglycosides, fatty alcohol sulfates, fatty alcohol ether sulfates, alkanesulfonates, fatty alcohol ethoxylates, fatty alcohol phosphates, alkylbetaines, sorbitan esters, POE sorbitan esters
  • Fatty acid sarcosinates Fatty acid sarcosinates, fatty acid isethionates, fatty acid taurinates, citric acid esters, silicone copolymers, fatty acid polyglycol esters, fatty acid amides, fatty acid alkanolamides, Quaternary ammonium compounds, Alkylphenoloxethylate, Fettaminoxethylate, Cosolvenzien such as ethylene glycol, propylene glycol, glycerin and others.
  • natural or synthetic compounds e.g. Lanolin derivatives, cholesterol derivatives, isopropyl myristate, isopropyl palmitate, electrolytes, dyes, preservatives, acids (e.g., lactic acid, citric acid).
  • formulations are used, for example, in bath-supplement preparations such as bath oils, shaving waters, face lotions, hair lotions, colognes, toilet water and in sunscreens.
  • bath-supplement preparations such as bath oils, shaving waters, face lotions, hair lotions, colognes, toilet water and in sunscreens.
  • Another field of application is the field of oral care, for example in mouthwashes, toothpastes, denture detersive creams and the like.
  • copolymers are also suitable for industrial applications, for example for preparations of poorly soluble colorants, in toners, preparations of magnetic pigments and the like.
  • the copolymers of the invention can be used as a 100% substance or preferably as an aqueous solution.
  • solubilizer is dissolved in water and mixed intensively with the sparingly soluble cosmetic active ingredient to be used in each case.
  • solubilizer it is also possible for the solubilizer to be intensively mixed with the sparingly soluble cosmetic active ingredient to be used in each case and then mixed with demineralized water with constant stirring.
  • copolymers are also suitable for use as solubilizers in pharmaceutical preparations of any kind, which are characterized in that they may contain one or more sparingly soluble in water or insoluble in water drugs and vitamins and / or carotenoids.
  • these are aqueous solutions or solubilisates for oral administration.
  • the claimed copolymers are suitable for use in oral dosage forms such as tablets, capsules, powders, solutions.
  • oral dosage forms such as tablets, capsules, powders, solutions.
  • solid solutions of active ingredient and solubilizer find use.
  • emulsions for example fat emulsions
  • the claimed copolymers are suitable for processing a sparingly soluble drug.
  • compositions of the above type may be obtained by processing the claimed copolymers with pharmaceutically active agents by conventional methods and using known and novel drugs.
  • the formulation may additionally contain pharmaceutical excipients and / or diluents.
  • Cosolvents, stabilizers, preservatives are especially listed as auxiliaries.
  • the pharmaceutical active ingredients used are water-insoluble or sparingly soluble substances. According to DAB 9 (German Pharmacopoeia), the
  • Examples include benzodiazepines, antihypertensives, vitamins, cytostatic drugs - especially taxol, anesthetics, neuroleptics, antidepressants, antiviral agents such as anti-HIV agents, antibiotics, antimycotics, anti-dementia, fungicides, chemotherapeutics, urologics, antiplatelet agents, sulfonamides, anticonvulsants, Hormones, immunoglobulins, serums, thyroid therapeutics, psychotropic drugs, Parkinson's and other antihyperkinetics, ophthalmics, neuropathy preparations, calcium metabolism regulators, muscle relaxants, anesthetics, lipid lowering agents, liver therapeutics, coronary agents, cardiakats, immunotherapeutics, regulatory peptides and their inhibitors, hypnotics, sedatives, gynecologics, gout, fibrinolytics , Enzyme preparations and transport proteins, enzyme inhibitors, emetics, circulation-promoting
  • a possible preparation variant is the dissolution of the solubilizer in the aqueous phase, optionally with gentle heating, and the subsequent dissolution of the active ingredient in the aqueous solubilizer solution.
  • the simultaneous dissolution of solubilizer and active ingredient in the aqueous phase is also possible.
  • copolymers according to the invention as a solubilizer can also be carried out, for example, by dispersing the active ingredient in the solubilizer, if appropriate with heating, and mixing it with water while stirring.
  • solid solubilizers obtained by the process according to the invention can also be processed in a subsequent extrusion step in the melt with the active ingredients.
  • solid solutions can be obtained in this way.
  • Another possibility for the preparation of solid solutions is also solutions of solubilizer and active ingredient in suitable organic
  • the invention therefore also relates generally to pharmaceutical preparations obtained by the process according to the invention which contain at least one of the copolymers according to the invention as a solubilizer. Preference is given to those preparations which, in addition to the solubilizer, contain a sparingly soluble or water-insoluble pharmaceutical active substance, for example from the above-mentioned indications.
  • Particularly preferred of the abovementioned pharmaceutical preparations are those which are orally administrable formulations.
  • the content of solubilizer according to the invention in the pharmaceutical preparation is, depending on the active ingredient, in the range of 1 to 75 wt .-%, preferably 5 to 60 wt .-%, particularly preferably 5 to 50 wt .-%.
  • Another particularly preferred embodiment relates to pharmaceutical preparations in which the active ingredients and the solubilizer are in the form of a solid solution, the removal of the solvent and the incorporation of the active substance taking place in one process step.
  • the weight ratio of solubilizer to active ingredient is preferably from 1: 1 to 4: 1, but may be up to 100: 1, in particular to 15: 1. It is only important that when used in the finished dosage form on the one hand, an effective amount of active ingredient is contained in the drug form, and on the other hand, in oral dosage forms, the forms are not too large.
  • copolymers according to the invention are also suitable as solubilizers in the food industry for nutrients, auxiliaries or additives which are sparingly soluble in water or insoluble in water, for example.
  • fat-soluble vitamins or carotenoids examples include drinks colored with carotenoids.
  • compositions containing pesticides, herbicides, fungicides or insecticides include, in particular, those preparations of pesticides used as spraying or pouring broths.
  • copolymers obtained in this way are distinguished by a particularly good solubilizing effect. They are also able to form so-called solid solutions with sparingly soluble substances.
  • solid solutions according to the invention systems are referred to, in which no crystalline components of the poorly soluble substance can be recognized by visual inspection. Furthermore, no visual inspection of the stable solid solutions, no amorphous constituents can be seen. The visual inspection is carried out with a light microscope at 40x magnification.
  • the inventive method allows in a simple way the removal of
  • Solvent of the polymerization and conversion of the graft copolymer into solid form Furthermore, the method allows the simultaneous incorporation of an active substance to obtain a solid solution.
  • VCap N-vinylcaprolactam
  • VP N-vinylpyrrolidone
  • VAc vinyl acetate
  • PEG polyethylene glycol
  • the template without the subset of feed 2 was heated to 77 ° C under an N 2 atmosphere. When the internal temperature reached 77 ° C, addition of the feeds was started. Feed 1 was in 5 h, feed 2 in 2 h and feed 3 added in 5.5 h. After all feeds had been metered in, the reaction mixture was postpolymerized for a further 3 hours. After postpolymerization, the solution was adjusted to a solids content of 50% by weight.
  • Feed 2 456 g vinylcaprolactam 240 g ethyl acetate
  • Feed 3 10.44 g of tert-butyl perpivalate (75% strength by weight in aliphatic mixture) 67.90 g of ethyl acetate
  • Method I Polymer solution with water or ethyl acetate with active ingredient dispersed therein
  • the treatment took place in a twin-screw extruder ZSK 30 from Coperion Werner & Pfleiderer.
  • the screw diameter was 30 mm at a l / d ratio of 42.
  • the extruder consisted of a total of 12 shots and 6
  • Shot 1 housing open at the top, screw conveyor thread and neutral kneading block shut off on the left
  • shot 2 housing open at the side, possibility for powder dosing via ZSB
  • Shot 3 housing open at the top, closed with plate and injection nozzle, connection of a gear pump; Housing to open laterally for connection of a
  • the worm was designed to be promotional in this area, with narrow promotional kneading blocks.
  • Shots 4 and 5 open at the top, with pure screw conveyor; Degassing zone 1
  • Shot 6 and an intermediate plate 1 D closed; Snail promoting and neutral
  • Shot 8 Open case, closed with pierced lid, injection for
  • Method II Feeding the drug through a separate side dosing in the molten
  • Shot 1 housing open at the top, screw conveyor thread and neutral kneading block shut off on the left,
  • Shot 2 housing open on the side, possibility of powder dosing via ZSB,
  • Shot 3 housing open at the top, closed with plate and injection nozzle, connection of a gear pump; Housing to open laterally for connection of an eccentric screw pump.
  • Shots 4 and 5 open at the top, with pure screw conveyor; Degassing zone 1
  • Shot 8 closed housing intermediate plate with hole, sealed; Snail left jammed KB
  • Shot 9 Open case, closed with lid, open at the side
  • Shot 10 closed, snail ZSB, dammed
  • Shot 1 1 and 12 Degassing zone, nozzle head and discharge

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
  • Medicinal Preparation (AREA)
  • Graft Or Block Polymers (AREA)

Abstract

L'invention concerne un procédé de fabrication de copolymères sous forme solide. Selon l'invention, les copolymères sont obtenus par polymérisation radicalaire d'un mélange de 30 à 80 % en poids de N-vinyl-lactame, 10 à 50 % en poids d'acétate de vinyle et 10 à 50 % en poids d'un polyéther, en présence d'au moins un solvant, à condition que la somme de i), ii) et iii) représente 100 % en poids. Le procédé est caractérisé en ce que le solvant est éliminé du mélange de polymérisation à l'aide d'une extrudeuse.
EP08786188A 2007-07-26 2008-07-16 Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution Withdrawn EP2173781A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08786188A EP2173781A1 (fr) 2007-07-26 2008-07-16 Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07113228 2007-07-26
PCT/EP2008/059299 WO2009013202A1 (fr) 2007-07-26 2008-07-16 Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution
EP08786188A EP2173781A1 (fr) 2007-07-26 2008-07-16 Procédé de fabrication de copolymères à base de polyéthers sous forme solide pouvant être obtenus par polymérisation-greffage en solution

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Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10026698A1 (de) 2000-05-30 2001-12-06 Basf Ag Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
US8377952B2 (en) 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
DE102005053066A1 (de) 2005-11-04 2007-05-10 Basf Ag Verwendung von Copolymeren als Solubilisatoren für in Wasser schwerlöslichen Verbindungen
WO2007065846A2 (fr) * 2005-12-09 2007-06-14 Basf Se Utilisation de copolymeres blocs de lactame polyvinylique et d'oxyde de polyalkylene comme solubilisants dans des composes peu solubles dans l'eau
US20110178183A1 (en) * 2008-09-25 2011-07-21 Meyer-Boehm Kathrin Use Of Polyether-Based And Vinyl Monomer-Based Copolymers As Binders For Dosing Forms Comprising Solid Active Ingredients
JP2012522029A (ja) * 2009-03-31 2012-09-20 ビーエーエスエフ ソシエタス・ヨーロピア 水に難溶性の物質の製剤を製造する方法
WO2010130728A2 (fr) * 2009-05-13 2010-11-18 Basf Se Préparations pharmaceutiques solides contenant des copolymères à base de polyéthers en association avec des polymères peu solubles dans l'eau
CN102549029B (zh) * 2009-09-17 2015-03-04 巴斯夫欧洲公司 涂覆有含有活性物质的涂层的丸剂
CN102655857A (zh) * 2009-09-18 2012-09-05 巴斯夫欧洲公司 含有基于聚醚的两亲性共聚物与亲水聚合物组合的速溶性固体药物制剂
CN102573755A (zh) * 2009-09-18 2012-07-11 巴斯夫欧洲公司 制备具有低水溶性的物质的制剂的方法
EP2477605A1 (fr) * 2009-09-18 2012-07-25 Basf Se Préparations pharmaceutiques solides à dissolution rapide contenant des copolymères amphiphiles à base de polyéthers en combinaison avec des tensioactifs
JP2013511565A (ja) 2009-11-24 2013-04-04 ビーエーエスエフ ソシエタス・ヨーロピア フィルム様医薬剤形
CN102781429A (zh) 2010-03-05 2012-11-14 巴斯夫欧洲公司 经熔体涂覆的药物剂型
RU2558542C2 (ru) * 2010-03-30 2015-08-10 Басф Се Применение сополимера для повышения активности пестицида
CN102906169A (zh) 2010-05-21 2013-01-30 巴斯夫欧洲公司 基于药学上可接受热塑性可加工聚合物的含活性成分的纳米多孔发泡制剂
CN102905695A (zh) * 2010-05-21 2013-01-30 巴斯夫欧洲公司 基于两亲共聚物的具有增大表面积的生物活性物质制剂
US8636929B2 (en) * 2010-05-21 2014-01-28 Basf Se Nanoporous foamed active compound-containing preparations based on pharmaceutically acceptable thermoplastically workable polymers
EP2463327A3 (fr) * 2010-12-10 2015-06-03 Basf Se Procédé de fabrication de granulés comprenant au moins un composant soluble dans l'eau
BR112013027812A2 (pt) * 2011-04-29 2017-03-14 Resilux Nv método para produzir um produto polimérico de componentes agregados multidimensionais como barreira ou carreadores de células microbianas vivas e barreias biológicas em materiais plásticos e texteis
EP2572731A1 (fr) 2011-09-26 2013-03-27 Abbott GmbH & Co. KG Formulations à base de dispersions solides
ES2587787T3 (es) 2012-03-09 2016-10-26 Basf Se Procedimiento continuo de síntesis de polímeros de injerto en base a poliéteres
US9068023B2 (en) 2012-03-09 2015-06-30 Basf Se Continuous process for the synthesis of graft polymers based on polyethers
JP6113613B2 (ja) * 2013-09-18 2017-04-12 第一工業製薬株式会社 ポリビニルピロリドン水溶液の製造方法
MX388812B (es) 2015-10-23 2025-03-20 Basf Se Soluciones solidas de sustancias odoriferas y agentes aromatizantes con polimeros de vinillactama.
MX380617B (es) 2016-09-13 2025-03-12 Procter & Gamble Proceso para elaborar una composicion que comprende particulas de suministro de agente benefico
CN108623744B (zh) * 2018-06-01 2020-12-15 辽宁奥克医药辅料股份有限公司 共聚物、增溶剂及制备方法
EP3741355A1 (fr) 2019-05-22 2020-11-25 The Procter & Gamble Company Compositions liquides comprenant des particules d'administration
JP2021093979A (ja) * 2019-12-18 2021-06-24 太陽化学株式会社 難水溶性物質含有組成物
CN112029048A (zh) * 2020-09-14 2020-12-04 安徽瑞和新材料有限公司 一种超缓释型固体聚羧酸系减水剂的反应性挤出制备方法
US20240327615A1 (en) 2023-03-31 2024-10-03 Evonik Operations Gmbh Solutions of amines in polymeric phenols in combination with other resins
US20240327567A1 (en) 2023-03-31 2024-10-03 Evonik Operations Gmbh Low Temperature Curable One Component Epoxy Compositions containing Resin-Blocked Urea Curatives
US20240327610A1 (en) 2023-03-31 2024-10-03 Evonik Operations Gmbh Solutions of amines in functional and non-functional resins

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2016470C3 (de) * 1970-04-07 1973-12-13 Bayer Ag, 5090 Leverkusen Verfahren zur Herstellung stabiler wäßriger Dispersionen von in Wasser schwerlöslichen optischen Aufhellern
US3767578A (en) * 1971-06-10 1973-10-23 Xerox Corp Carrier material for electrostatographic developer
NZ193221A (en) * 1979-03-21 1984-08-24 M P Embrey Controlled release composition
DE3711318A1 (de) * 1987-04-03 1988-10-20 Basf Ag Verwendung von pfropfpolymerisaten auf basis von polyalkylenoxiden als vergrauungsinhibitoren beim waschen und nachbehandeln von synthesefasern enthaltendem textilgut
US5013556A (en) * 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
TW203065B (fr) * 1990-10-24 1993-04-01 Hoechst Ag
DE4138513A1 (de) * 1991-11-23 1993-05-27 Basf Ag Feste pharmazeutische retardform
US5395619A (en) * 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
US6107397A (en) * 1997-03-24 2000-08-22 Basf Aktiengesellschaft Aqueous copolymer dispersions of water-soluble monomers with N-vinyl groups and hydrophobic monomers
DE19719187A1 (de) * 1997-05-07 1998-11-12 Basf Ag Verwendung von Copolymerisaten des N-Vinyl-pyrrolidons in Zubereitungen wasserunlöslicher Stoffe
US6271301B1 (en) * 1997-08-15 2001-08-07 Teknor Apex Company Polyvinyl chloride elastomers
DE19811919A1 (de) * 1998-03-18 1999-09-23 Basf Ag Verwendung von Copolymerisaten monoethylenisch ungesättigter Carbonsäuren als Solubilisatoren
DE19814739A1 (de) * 1998-04-02 1999-10-07 Basf Ag Verwendung von Polyalkylenoxid-haltigen Pfropfpolymerisaten als Solubilisatoren
DE19840256A1 (de) * 1998-09-03 2000-03-09 Basf Ag Verfahren zur Herstellung von beschichteten festen Dosierungsformen
DE19935063A1 (de) * 1999-07-28 2001-02-01 Basf Ag Pfropfpolymerisate als Gashydratinhibitoren
DE10012063A1 (de) * 2000-03-14 2001-09-20 Basf Ag Weichkapseln enthaltend Polymerisate von Vinylestern und Polyethern, deren Verwendung und Herstellung
DE10015468A1 (de) * 2000-03-29 2001-10-11 Basf Ag Hartkapseln, enthaltend Polymerisate und Vinylestern und Polyethern, deren Verwendung und Herstellung
DE10041220A1 (de) * 2000-08-22 2002-03-07 Basf Ag Hautkosmetische Formulierungen
DE102004062200A1 (de) * 2004-12-23 2006-07-13 Basf Ag Verfahren zur Herstellung von Polyvinylalkohol-Polyether-Pfropfcopolymeren durch Extrusion
US7915350B2 (en) * 2005-04-15 2011-03-29 Ticona Gmbh Polyoxymethylene compositions, their preparation and use
DE102005053066A1 (de) * 2005-11-04 2007-05-10 Basf Ag Verwendung von Copolymeren als Solubilisatoren für in Wasser schwerlöslichen Verbindungen
CN101325975A (zh) * 2005-12-09 2008-12-17 巴斯夫欧洲公司 基于聚氧化烯-改性的n-乙烯基内酰胺共聚物的共聚物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009013202A1 *

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