Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B30—PRESSES
  • B30B—PRESSES IN GENERAL
  • B30B11/00—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses
  • B30B11/16—Presses specially adapted for forming shaped articles from material in particulate or plastic state, e.g. briquetting presses, tabletting presses using pocketed rollers, e.g. two co-operating pocketed rollers
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P10/00—Shaping or working of foodstuffs characterised by the products
  • A23P10/20—Agglomerating; Granulating; Tabletting
  • A23P10/28—Tabletting; Making food bars by compression of a dry powdered mixture
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P30/00—Shaping or working of foodstuffs characterised by the process or apparatus
  • A23P30/10—Moulding
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
  • A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
• • 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
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2893—Tablet coating processes
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B30—PRESSES
  • B30B—PRESSES IN GENERAL
  • B30B5/00—Presses characterised by the use of pressing means other than those mentioned in the preceding groups
  • B30B5/04—Presses characterised by the use of pressing means other than those mentioned in the preceding groups wherein the pressing means is in the form of an endless band
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J2200/00—General characteristics or adaptations
  • A61J2200/20—Extrusion means, e.g. for producing pharmaceutical forms

Definitions

• the present invention relates to a device and a method for producing flat shapes, in particular tablets, from a product mass containing active ingredients.
• melt calendering A known method for the production of tablets is the so-called melt calendering. Such a process is described, for example, in DE-A-17 66 546 and US-A-4,880,585 b . The basis of this process is the embedding of an active ingredient in a melt from a carrier for
• Example fatty substances or water-soluble, thermoplastic polymers The melt is produced by melting the mixture of active ingredient, polymer and optionally other auxiliaries, for example in an extruder, and shaping it as a melt in a downstream calender into tablets, which harden by cooling.
• the molding calender comprises a pair of molding rollers rotating in opposite directions, the molding rollers having engravings (depressions) on their surface which correspond to the shape of half the desired tablet.
• the tablets are formed in the contact area of the two rollers by connecting the tablet masses in the depressions of one roller with those in the opposite depressions of the other roller.
• roller construction is very complex.
• the depressions are milled into the rollers and in most cases have to be polished afterwards in order to get the tablet surface as smooth as possible.
• the production of such rollers is very expensive because the recesses have to be made with great precision.
• the rollers have to be adjusted so that always two recesses face each other as exactly as possible. This condition is particularly difficult to achieve if the depressions are very small.
• Such a device is also inflexible because, for example, if you want to use the same device to produce different tablet shapes and / or sizes, this is only possible through a complete exchange of the rollers and a complex readjustment.
• devices for tablet production are becoming large
• the object of the present invention to provide a device for producing tablets which, on the one hand, is cheaper than the known devices and, on the other hand, offers greater flexibility.
• the object of the invention is also to provide a simple and flexible method for tablet production.
• a device for producing flat shapes from an active substance-containing product mass with at least one charging means for supplying the product mass, at least one pair of rollers, consisting of two counter-rotating calender rollers, the device being characterized in that it is a, preferably as Endless belt encircling forming belt, which is guided between the two rollers of a pair of rollers, the forming belt having recesses on its surface for receiving the product mass.
• the rollers are arranged so that they have a gap-like passage between their lateral surfaces.
• the smallest distance between the lateral surfaces of the pair of rollers essentially corresponds to the thickness of the forming strip.
• the product mass preferably as a wide belt
• the trough-like trough fed between the two rollers.
• the forming belt and product ends are guided further into the area between the calender rolls, which is becoming ever narrower, the product mass being pressed into the recesses in the forming belt.
• the distance between the rollers essentially determines the pressure that is exerted on the product mass and thus the density of the moldings thus produced.
• Forming tapes made of plastic, in which the cutouts can be produced by molding are particularly inexpensive. Of course, care must be taken that the plastic is dimensionally stable at the temperatures that occur during tablet production.
• the moldings formed in this way have a flat surface formed by the pressure roller, while the opposite surface is determined by the shape of the recess in the forming belt.
• the cutouts are through openings in the forming band.
• the openings are preferably produced by punching, any tablet shape being able to be produced depending on the punching tool used.
• the product mass which is pressed into the molds during tablet production comes into contact with the two lateral surfaces of the pair of calender rolls, so that here Tablets are produced that have two flat surfaces.
• cutouts or the openings in the forming belt are introduced in such a way that the product mass can be transferred into the product moldings with as little loss as possible.
• Recesses or openings are preferred which have a round, oval or hexagonal shape when viewed from above.
• the openings can also have webs on their circumferential surface, for example, which are produced by corresponding notches in the punching mold, so that tablets with broken notches can be produced.
• the forming tape can be made from any material, but preferably from metal, particularly preferably from steel, plastic or rubber. If a molding tape made of a relatively rigid material is used, the thickness of the tape corresponds essentially to the desired thickness of the tablets. Thicker tablet forms therefore require a thicker belt, which can optionally be in the form of a link belt, so that it can be guided around the deflection rollers of the device more easily. However, it is also possible to use shaped tapes made of flexible material, which can then also be thicker than the desired thickness of the tablets. In this case, in particular, the forming belt is thicker than the gap between the calender rolls. When it is drawn in between the rollers, the forming belt is pressed ever further together, so that, depending on the distance between the calender rollers, a different pressure can be exerted on the tablet tablets.
• the calender rolls preferably have smooth outer surfaces. If tablet moldings with an enlarged surface are required, then, for example, calender rolls are also conceivable, the surface of which has a certain roughness. Calender rolls which can be tempered are advantageously used. If a product mass is used that is plastic at high temperature and solidifies on cooling, it is preferred to work with cooled calender rolls. On the other hand, product masses are also known which are plastic in the moist state and solid in the dry state, so that in this case it is preferred to work with heatable calender rolls. The rollers therefore serve to cool or dry the product mass. Depending on the diameter of the rollers, the product mass has different lengths of thermal contact with these rollers.
• the pressure rollers are universal tools that are preferably thermally conductive, stable under pressure and inert to the substances used. The distance between the rollers can be adjusted to generate different contact pressures.
• the device has only one loading means for the product mass.
• the product belts can be fed to a pair of rollers at the same time.
• the distance between the pairs of rollers will preferably be set so that the contact pressure is lowest for the first pair of rollers and highest for the last pair of rollers.
• the resulting tablets are then multi-layer tablets.
• a thin protective film for example a diffusion-tight polymer in order to achieve a specific release of active ingredient.
• Protective films can be produced that only dissolve under specific ambient conditions (for example with regard to pH or temperature) and release the active ingredient.
• the coating can also serve as a taste or light protection. Should the entire tablet are covered with a protective film, this is generally carried out in a separate subsequent step using known coating processes.
• the protective films on the top and bottom do not have to be identical. In the case of multilayer tablets, the protective films can, for example, lead to a different release of active ingredient.
• Extruders and / or heatable filling wedges are used as preferred feed agents.
• the device according to the invention tablets or pellet-like moldings can be produced continuously.
• the device is extremely universal, since the basic roller device remains unchanged and only the forming belt has to be replaced. Depending on the ribbon used and the dimensions of the
• the range of products that can be produced ranges from very small pellet-like products to tablet weights of 1 gram and more.
• the moldings have edge angles of 90 ° or less, which, particularly in the case of brittle product masses, facilitates deburring of the tablets.
• the openings in the forming belt are preferably spaced from one another, so that there is no twin formation of tablets during manufacture. A subsequent separation of the tablets is therefore not necessary.
• the length of the forming belt can be varied within wide limits. It proves to be particularly advantageous that the residence time of the tablets in the molds can be extended as required, so that an ejection of not yet cooled (not yet cured) tablets is avoided.
• the products can be removed from the forming belt in a simple manner by the roller deflection or, if appropriate, by using a spiked roller. This is particularly true in the case of shaped tapes with through openings, since here the tablets are accessible from the top and bottom and can be easily pushed out of the tape.
• the flat moldings available with the forming calender are particularly suitable for use as tablets.
• IR tablets in particular tablets that release the active ingredient quickly (instant release), SR tablets, i.e. Tablets with slow release of active ingredient (SJLow Release), prolonged-release tablets, i.e. Tablets with delayed release of active ingredients, sublingual tablets, the active ingredients of which are absorbed through the oral mucosa and which are therefore intended to dissolve "under the tongue", lozenges or dissolving tablets.
• the tablets that can be produced in this way can of course not only be used in the pharmaceutical or food sector (e.g. in the form of vitamin tablets), but also applications in crop protection and in many areas of technology are conceivable.
• the present invention also relates to a process for the production of flat moldings from an active substance-containing product mass, wherein a shaped strip provided with recesses is passed between the counter-rotating rollers of a pair of calender rollers, at least one product strand consisting of the active substance-containing mass, preferably as a wide strip, forms this Feeding the product strand to the pair of rollers, the product mass being pressed into the recesses between the rollers of the pair of rollers and the shaped articles being removed from the recesses after passing through the pair of rollers.
• the desired contact pressure with which the product mass is compressed is set by the
• the distance between the rollers ie the smallest distance between their lateral surfaces, should preferably not be greater than the thickness of the forming tape used.
• the gap between the rollers can be selected to be significantly smaller than the thickness of the belt, so that a higher pressure can be exerted on the product mass.
• the product strip is passed through several successive pairs of rollers. It is also possible to form a number of different product strands which are fed simultaneously to a pair of rollers or to a plurality of pairs of rollers in succession.
• a multilayer melt can be produced by coextrusion, which already has the desired layer sequence of the later tablet in the melt.
• the product mass is hot plastic or wet plastic.
• the roller pairs will either be heated or cooled in order to obtain solid, dimensionally stable tablets.
• the tablets are produced from a mixture which contains one or more active pharmaceutical ingredients and one or more customary auxiliaries and which, by melting or softening at least one component, becomes pasty to viscous and therefore extrudable.
• mixtures which contain pharmacologically acceptable polymers for example polyvinylpyrrolidone (PVP), copolymers of N-vinylpyrrolidone (NVP) and vinyl acetate, copolymers of vinyl acetate and crotonic acid, partially saponified polyvinyl acetate, polyvinyl alcohol , Ethylene / vinyl acetate copolymers, polyhydroxyethyl methacrylate, copolymers of methyl methacrylate and acrylic acid, cellulose esters, cellulose ethers, polyethylene glycol or polyethylene.
• PVP polyvinylpyrrolidone
• NDP N-vinylpyrrolidone
• VRP N-vinylpyrrolidone
• vinyl acetate copolymers of vinyl acetate and crotonic acid
• partially saponified polyvinyl acetate polyvinyl alcohol
• Ethylene / vinyl acetate copolymers polyhydroxyethyl methacrylate
• Fikentscher, Cellulose-Chemie 13 (1932), pages 58 to 64 and 71 and 74) of the polymers are in the range from 10 to 100, preferably 12 to 70, in particular 12 to 35, for PVP preferably at 12 to 35, especially at 12 to 17.
• the polymeric binder must soften or melt in the total mixture of all components in the range from 50 to 180, preferably 60 to 130 ° C., so that the composition can be extruded.
• the glass transition temperature of the mixture must therefore be below 180, preferably below 130 ° C.
• plasticizing ancillary substances such as long chain alcohols, ethylene glycol, Propylen ⁇ , trimethylolpropane, triethylene glycol, butanediols, pentanols, hexanols, polyethylene glycols, silicones, aromatic Carbonsaureester (such as dialkyl phthalates, trimellitic esters, benzoic esters, terephthalic esters) or aliphatic dicarboxylic esters (eg Dialkyl adipates, sebacic acid esters, azelaic acid esters, citric and tartaric acid esters) or fatty acid esters.
• plasticizing ancillary substances such as long chain alcohols, ethylene glycol, Propylen ⁇ , trimethylolpropane, triethylene glycol, butanediols, pentanols, hexanols, polyethylene glycols, silicones, aromatic Carbonsaureester (such as dialkyl phthalates
• Common pharmaceutical auxiliaries the total amount of which can be up to 100% by weight, based on the polymer, are e.g.
• Extenders or fillers such as silicates or silica, magnesium oxide, aluminum oxide, titanium oxide, stearic acid or their salts, e.g. the magnesium or calcium salt, methyl cellulose, sodium carboxymethyl cellulose, talc, sucrose, lactose, corn or corn starch, potato flour, polyvinyl alcohol, in particular in a concentration of 0.02 to 50, preferably 0.20 to 20,% by weight. %, based on the total weight of the mixture, are preferred;
• Lubricants such as aluminum and calcium stearate, talc and silicone, in a concentration of 0.1 to 5, preferably 0.1 to 3% by weight, based on the total weight of the mixture, are preferred; Dyes, such as azo dyes, organic or inorganic pigments or dyes of natural origin, inorganic pigments in a concentration of 0.001 to 10, preferably 0.5 to 3% by weight, based on the total weight of the mixture;
• Plasticizers such as animal or vegetable fats, especially in hydrogenated form and those which are solid at room temperature. These fats preferably have a melting point of 50 ° C or higher. Triglycerides of C 12 , C 14 , C 16 and C 18 fatty acids are preferred. Waxes such as carnauba wax can also be used. These fats and waxes can advantageously be admixed alone or together with mono- and / or diglycerides or phosphatides, in particular lecithin. The mono- and diglycerides are preferably those mentioned above
• the total amount of fats, waxes, mono-, diglycerides and / or lecithins is 0.1 to 30, preferably 0.1 to 5% by weight, based on the total weight of the mass for the respective layer;
• Stabilizers such as antioxidants, light stabilizers, hydroperoxide killers, radical scavengers, stabilizers against microbial attack.
• wetting agents, preservatives, disintegrants, adsorbents, mold release agents and blowing agents can also be added (cf. e.g. H. Sucker et al. Pharmaceutical Technology, Thieme-Verlag, Stuttgart 1978).
• auxiliaries are, for example, pentaerythritol and pentaerythritol tetraacetate, polymers such as polyethylene or polypropylene oxides and their block copolymers (poloxamers), phosphatides such as lecithin, homo- and copolymers of vinyl pyrrolidone, surfactants such as polyoxyethylene 40 stearate as well as citric and succinic acid, bile acids, sterols and others as for example given by JL Ford, Pharm. Acta Helv. 6_1, 69-88 (1986).
• compositions in the sense of the invention are understood to mean all substances with a pharmaceutical effect and as few side effects as possible, provided that they do not decompose under the processing conditions.
• the amount of active ingredient per dose unit and the concentration can vary within wide limits depending on the effectiveness and rate of release. The only requirement is that they are sufficient to achieve the desired effect.
• the active substance concentration can be in the range from 0.1 to 95, preferably from 20 to 80, in particular 30 to 70% by weight.
• Combinations of active substances, for example ibuprofen / caffeine can also be used.
• Active substances in the sense of the invention are also vitamins and minerals, as well as plant treatment agents and insecticides.
• the vitamins include the vitamins of the A group, the B group, meaning next to B ⁇ B 2, B 6 and B 12 i e nicotinic acid and nicotinamide sow also compounds with vitamin B properties are understood, such as adenine, choline, Pantothenic acid, biotin, adenylic acid, folic acid, orotic acid,
• Active substances in the sense of the invention also include peptide therapeutic agents.
• the method according to the invention is for example for processing suitable for the following active ingredients:
• Cisplatin clarithromycin, clavulanic acid, clomibramine, clonazepam, clonidine, clotrimazole, codeine, cholestyramine, cromoglycine acid, cyanocobalamin, cyproterone, desogestrel, dexamethasone, dexpanthenol, dextrroethporphoxipod, dextro doproethoxamine, dextro dia methoxane, dextro dia methane pod
• ron dihydroergotoxin diltiazem, diphenhydramine, dipyridamole, Dipy-, disopyramide, domperidone, dopamine, Doxocyclin, enalapril, ephedrine, epinephrine, ergocalciferol, ergotamine, erythromycin, estradiol, ethinylestradiol, etoposide, Eucalyptus globulus, famotidine, felodipine, fenofibrate, fenoterol, fentanyl , Flavin mononucleotide, fluconazole, flunarizine, fluorouracil, fluoXetin, flurbiprofen, furosemide, gallopamil, gemfibrozil, gentamicin, ginkgo biloba, glibenclamide, glipizide, clozapine, gly
• Preferred active substances are ibuprofen, (as racemate, enantiomer or enriched enantiomer), ketoprofen, flurbiprofen, acetylsalicylic acid, verapamil, paracetamol, nifedipine or captopril.
• solid solutions can be formed.
• the term “solid solutions” is familiar to the person skilled in the art, for example from the literature cited at the beginning.
• the active ingredient is molecularly dispersed in the polymer.
• the pharmaceutical mixture is then melted in a conventional manner, preferably in an extruder, and fed to the forming belt calender, as is the case, for example, in US Pat. 4,880,585. If necessary, the tablets are cooled after calendering, for example in an air or cooling bath.
• a mold release agent for example a silicone oil or a silicone varnish.
• FIG. 1 shows a schematic view of the forming band calender according to the invention
• FIG. 2 shows a detailed view in longitudinal section according to a first embodiment of the forming belt of the device from FIG. 1 carried out between the calender rolls,
• Figure 3 is a view as in Figure 2 of a second embodiment of the forming belt.
• FIG. 1 shows the forming belt calender 10 according to the invention, a forming belt 12 being guided between the calender rollers 14, 16 via deflection rollers 18.
• An extruder 20 is used to produce the plastic product mass, which is preferably produced as a wide product band 22.
• the width of the calender rolls 14, 16, the forming belt 12 and the product belt 22 are preferably essentially the same.
• the direction of rotation of the forming belt 12 and the direction of rotation of the rollers 14 and 16 are indicated by arrows.
• the product belt 22 is added parallel to the direction of movement of the forming belt 12 into the trough-like recess 26 between the rollers 14 and 16.
• the forming tape 12 has depressions 24 or openings 30 on its surface, as in particular in FIGS. 2 and 3 is shown.
• FIG. 2 shows a first embodiment of the device according to the invention, in which the forming belt 12 has depressions 24. Molding tape 12 and product mass 22 are carried in the increasingly narrow gap between the two rollers 14 and 16, the product mass 22 being pressed into the recesses 24 of the molding tape 12. If it is, for example, a product mass that is supplied in a hot, plastic state, at least one of the rollers 14, 16 can be cooled, so that the product mass cools down in the recesses 24 as it passes between the rollers, thereby producing solid moldings 28 which can then be removed from the recesses.
• FIG. 3 shows the same detail as FIG. 2 of a forming band calender according to the invention according to FIG. 1, the forming band 12 in FIG. 3 according to another embodiment of the invention having through openings 30 into which the product mass 22 is pressed as it passes between the rollers 14 and 16 of the device becomes.
• the moldings 28 produced in this case have two smooth surfaces.
• the openings 30 in the forming band 12 are preferably created by punching out the forming band.
• shaped articles 28 are formed, the edge angles of which are essentially 90 °. Any protruding product mass can be easily deburred with tablets shaped in this way.

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• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Food Science & Technology (AREA)
• Pharmacology & Pharmacy (AREA)
• Polymers & Plastics (AREA)
• Mechanical Engineering (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Manufacturing & Machinery (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Medicinal Preparation (AREA)
• Casting Or Compression Moulding Of Plastics Or The Like (AREA)
• Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
• Medical Preparation Storing Or Oral Administration Devices (AREA)

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Citations (6)

• 1995
  • 1995-10-23 DE DE19539359A patent/DE19539359A1/de not_active Withdrawn
• 1996
  • 1996-10-16 TW TW085112660A patent/TW343920B/zh active
  • 1996-10-22 ZA ZA9608848A patent/ZA968848B/xx unknown
  • 1996-10-23 CA CA002232353A patent/CA2232353A1/en not_active Abandoned
  • 1996-10-23 AU AU74911/96A patent/AU705657B2/en not_active Ceased
  • 1996-10-23 CZ CZ981096A patent/CZ109698A3/cs unknown
  • 1996-10-23 BR BR9611239A patent/BR9611239A/pt not_active Application Discontinuation
  • 1996-10-23 WO PCT/EP1996/004600 patent/WO1997015268A1/de not_active Application Discontinuation
  • 1996-10-23 SI SI9620112A patent/SI9620112A/sl unknown
  • 1996-10-23 JP JP9516273A patent/JPH11514275A/ja active Pending
  • 1996-10-23 CN CN96197806A patent/CN1200663A/zh active Pending
  • 1996-10-23 SK SK506-98A patent/SK50698A3/sk unknown
  • 1996-10-23 EP EP96937213A patent/EP0957884A1/de not_active Withdrawn
  • 1996-10-23 HU HU9900734A patent/HUP9900734A3/hu unknown
  • 1996-10-23 KR KR1019980702910A patent/KR19990066977A/ko not_active Application Discontinuation
• 1998
  • 1998-04-22 NO NO981795A patent/NO981795L/no not_active Application Discontinuation

Patent Citations (6)

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