CN112760347A - Process and device for preparing heparin sodium by utilizing enzyme method combined membrane - Google Patents
Process and device for preparing heparin sodium by utilizing enzyme method combined membrane Download PDFInfo
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- CN112760347A CN112760347A CN202011475773.7A CN202011475773A CN112760347A CN 112760347 A CN112760347 A CN 112760347A CN 202011475773 A CN202011475773 A CN 202011475773A CN 112760347 A CN112760347 A CN 112760347A
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- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
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- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
- C12M33/10—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by centrifugation ; Cyclones
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Abstract
The invention discloses a process and a device for preparing heparin sodium by utilizing an enzyme method binding membrane. Put into raw and other materials in the stirring shell and stir the enzymolysis, then send into centrifugal shell, centrifugal motor driving pulley makes and changes the relative centrifugal shell rotation of shell, carries out centrifugal filtration to the raw and other materials that change in the shell, and the toper shell increases and external area of contact to can increase the radiating effect, make centrifugal separation's effect better, reduced transition structure, make the preparation process simpler, improve the integrated level of equipment, reduced area.
Description
Technical Field
The invention relates to the technical field of heparin sodium preparation, in particular to a process and a device for preparing heparin sodium by utilizing an enzyme method combined membrane.
Background
Heparin is widely present in various organ tissues of mammals and is a type of mucopolysaccharide substance produced by mast cells of connective tissues. Is widely distributed in the internal organs and intestinal mucosa of mammals such as pigs, cows, dogs and the like in nature. The heparin is mainly mucopolysaccharide sulfate consisting of D-glucosamine, L-iduronic acid, N-acetyl glucosamine and D-glucuronic acid in an alternating manner, and the molecular weight distribution of the heparin is 6000-20000. Is white or white-like powder, and has no toxicity, odor or moisture absorption. Heparin is usually present in the form of a Sodium salt, called Heparin Sodium (Heparin Sodium) or Heparin calcium, and in use Heparin Sodium is the main component. Heparin and sodium salt thereof are easily soluble in water and insoluble in organic solvents such as ethanol, acetone, dioxane and the like, molecular structural units contain 5 sulfate groups and 2 hydroxyl groups, are strongly acidic, are polyanions, and can react with cations to generate salts. The free acid has a certain solubility in ether. Heparin sodium is extracted from heparin in the form of sodium salt, and is made into medicinal preparation. Heparin actually has a medicinal effect, has an anticoagulant effect, and is an anticoagulant with long application.
The existing equipment used in the preparation process of heparin sodium is complex, and the occupied area is large, so that the production cost is increased.
Disclosure of Invention
The invention aims to provide a process and a device for preparing heparin sodium by utilizing an enzyme method combined membrane, and aims to solve the problems of complicated equipment and large occupied area in the existing preparation process of heparin sodium, so that the production cost is increased.
In order to achieve the above object, in a first aspect, the present invention provides an apparatus for preparing heparin sodium by using an enzymatic binding membrane, comprising a support assembly, a stirring assembly and a centrifugal assembly, wherein the support assembly comprises a base and a support frame, the support frame is fixedly connected with the base and positioned at one side of the base, the stirring assembly comprises a stirring shell, a stirring motor and a stirring blade, the stirring shell is fixedly connected with the support frame and positioned at one side of the support frame, the stirring motor is fixedly connected with the stirring shell and positioned at one side of the stirring shell, the stirring blade is fixedly connected with an output end of the stirring motor and positioned in the stirring shell, the centrifugal assembly comprises a cover plate, a centrifugal shell, a rotating rod, a centrifugal motor and a belt wheel, the centrifugal shell is fixedly connected with the support frame and positioned between the stirring shell and the base, the apron with centrifugation shell sliding connection, and with stirring shell intercommunication, it has the toper shell to change the shell, the toper shell is located change the shell center, change the shell with the centrifugation shell rotates to be connected, and is located in the centrifugation shell, the bull stick with the centrifugation shell rotates to be connected, and with toper shell fixed connection, centrifugal motor with support frame fixed connection, and be located one side of support frame, the band pulley with centrifugal motor's output with the bull stick rotates to be connected, and is located one side of centrifugation shell.
The stirring assembly further comprises a heating coil, and the heating coil is fixedly connected with the stirring shell and is positioned on the outer side of the stirring shell.
Wherein, stirring vane includes blade body, extension rod and swash plate, the extension rod with blade body fixed connection to be located the blade body is kept away from agitator motor's one side, the swash plate with extension rod fixed connection, and be located the agitator housing bottom.
The cover plate comprises a plate body, a transmission gear, a rack and a telescopic pipe, wherein the plate body is connected with the centrifugal shell in a sliding mode and is located on one side of the centrifugal shell, the telescopic pipe is connected with the stirring shell in a sliding mode and is located on one side of the plate body, the rack is fixedly connected with the telescopic pipe and is located on one side of the telescopic pipe, and the transmission gear is connected with the centrifugal shell in a rotating mode and is meshed with the plate body and the rack.
The centrifugal assembly further comprises a radiating blade, and the radiating blade is fixedly connected with the rotating rod and is positioned on one side of the rotating rod.
Wherein, centrifugal component still includes the cooling shell, the cooling shell with centrifugal shell fixed connection to be located the centrifugal shell outside.
Wherein the cooling shell is provided with a plurality of cooling fins which are distributed on the cooling shell.
In a second aspect, the present invention also provides a process for preparing heparin sodium by using an enzymatic binding membrane, comprising: adding porcine small intestine mucosa and water into the stirring shell and adjusting the pH value; adding a proteolytic complex enzyme into the stirring shell, stirring and carrying out enzymolysis to obtain an enzymolysis liquid; the cover plate is slid to enable the enzymolysis liquid to enter the rotary shell; starting a centrifugal motor to drive a rotating shell to rotate for centrifugation, and discharging clear liquid; removing impurities from the clear liquid by a filter membrane, adding ethanol, and collecting filtrate; standing the filtrate, collecting the precipitate, and freeze-drying to obtain the heparin sodium.
According to the process and the device for preparing the heparin sodium by using the enzyme method combined membrane, the support frame is fixedly connected with the base, the base is used for supporting the support frame, the stirring shell is fixedly connected with the support frame and serves as a stirring enzymolysis place, the stirring motor is fixedly connected with the stirring shell, the stirring blade is fixedly connected with the output end of the stirring motor, and the stirring motor can drive the stirring blade to rotate, so that the raw materials in the stirring shell can be stirred, and the reaction can be more sufficient; the centrifugal shell is fixedly connected with the supporting frame, the cover plate is connected with the centrifugal shell in a sliding manner, the centrifugal shell is communicated with the stirring shell through the cover plate, so that substances stirred in the stirring shell can downwards enter the centrifugal shell, the rotating shell is provided with a conical shell which is positioned at the center of the rotating shell and is rotatably connected with the centrifugal shell, the rotating rod is rotatably connected with the centrifugal shell, the centrifugal motor is fixedly connected with the supporting frame, the belt wheel is rotatably connected with the output end of the centrifugal motor and the rotating rod, the belt wheel is driven by the centrifugal motor to drive the rotating rod to rotate, so that the rotating shell rotates relative to the centrifugal shell, raw materials in the rotating shell are centrifugally filtered, and the contact area between the rotating shell and the outside can be increased through the conical shell, thereby can increase the radiating effect for centrifugal separation's effect is better, through inciting somebody to action the stirring shell with the centrifugation shell is installed on same support frame to reduce transition structure, make the preparation process simpler, improved the integrated level of equipment, reduced area, thereby solve current heparin sodium preparation in-process equipment complicacy, area makes the problem that manufacturing cost increases greatly.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a top structural view of an apparatus for preparing heparin sodium using an enzymatic binding membrane according to the present invention;
FIG. 2 is a bottom structural view of an apparatus for preparing heparin sodium using an enzymatic binding membrane according to the present invention;
FIG. 3 is a schematic sectional view of an apparatus for preparing heparin sodium using an enzymatic binding membrane according to the present invention;
FIG. 4 is a flow chart of a process for preparing heparin sodium using an enzymatic binding membrane according to the present invention.
1-supporting component, 2-stirring component, 3-centrifugal component, 11-base, 12-supporting frame, 13-vibration damping pad, 21-stirring shell, 22-stirring motor, 23-stirring blade, 24-heating coil, 31-cover plate, 32-centrifugal shell, 33-rotating shell, 34-rotating rod, 35-centrifugal motor, 36-belt wheel, 37-radiating blade, 38-cooling shell, 39-cooling pipe, 40-cooling pump, 41-cooling fence, 231-blade body, 232-extension rod, 233-inclined plate, 311-plate body, 312-transmission gear, 313-rack, 314-telescopic pipe, 331-conical shell and 381-radiating fin.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.
In the description of the present invention, it is to be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships illustrated in the drawings, and are used merely for convenience in describing the present invention and for simplicity in description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed in a particular orientation, and be operated, and thus, are not to be construed as limiting the present invention. Further, in the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
In a first aspect, referring to fig. 1 to 3, the present invention provides an apparatus for preparing heparin sodium using an enzymatic binding membrane, comprising:
supporting component 1, stirring subassembly 2 and centrifugal subassembly 3, supporting component 1 includes base 11 and support frame 12, support frame 12 with base 11 fixed connection to be located one side of base 11, stirring subassembly 2 includes stirring shell 21, agitator motor 22 and stirring vane 23, stirring shell 21 with support frame 12 fixed connection, and be located one side of support frame 12, agitator motor 22 with stirring shell 21 fixed connection, and be located one side of stirring shell 21, agitator vane 23 with agitator motor 22's output fixed connection, and be located in stirring shell 21, centrifugal subassembly 3 includes apron 31, centrifugal shell 32, commentaries on classics shell 33, bull stick 34, centrifugal motor 35 and band pulley 36, centrifugal shell 32 with support frame 12 fixed connection, and be located stirring shell 21 with between the base 11, the apron 31 with centrifugation shell 32 sliding connection, and with stirring shell 21 intercommunication, it has toper shell 331 to change shell 33, toper shell 331 is located change shell 33 center, change shell 33 with centrifugation shell 32 rotates and is connected, and is located in centrifugation shell 32, bull stick 34 with centrifugation shell 32 rotates and is connected, and with toper shell 331 fixed connection, centrifugal motor 35 with support frame 12 fixed connection, and be located one side of support frame 12, band pulley 36 with centrifugal motor 35's output with bull stick 34 rotates and is connected, and is located one side of centrifugation shell 32.
In the present embodiment, the supporting component 1 includes a base 11 and a supporting frame 12, the supporting frame 12 is fixedly connected with the base 11, and is located at one side of the base 11, the base 11 is used for supporting the supporting frame 12, the stirring component 2 comprises a stirring shell 21, a stirring motor 22 and a stirring blade 23, the stirring shell 21 is fixedly connected with the supporting frame 12, and is positioned at one side of the supporting frame 12, the stirring shell 21 is used as a place for stirring and enzymolysis, the stirring motor 22 is fixedly connected with the stirring shell 21, and is positioned at one side of the stirring shell 21, the stirring blade 23 is fixedly connected with the output end of the stirring motor 22, and is positioned in the stirring shell 21, the stirring blade 23 can be driven to rotate by the stirring motor 22, so that the raw materials in the stirring shell 21 can be stirred, and the reaction can be more sufficient; the centrifugal component 3 comprises a cover plate 31, a centrifugal shell 32, a rotating shell 33, a rotating rod 34, a centrifugal motor 35 and a belt wheel 36, the centrifugal shell 32 is fixedly connected with the support frame 12 and is positioned between the stirring shell 21 and the base 11, the cover plate 31 is connected with the centrifugal shell 32 in a sliding manner and is communicated with the stirring shell 21, the centrifugal shell 32 is communicated with the stirring shell 21 through the cover plate 31, so that substances stirred in the stirring shell 21 can enter the centrifugal shell 32 downwards, the rotating shell 33 is provided with a conical shell 331, the conical shell 331 is positioned at the center of the rotating shell 33, the rotating shell 33 is rotatably connected with the centrifugal shell 32 and is positioned in the centrifugal shell 32, the rotating rod 34 is rotatably connected with the centrifugal shell 32 and is fixedly connected with the conical shell 331, the centrifugal motor 35 is fixedly connected with the support frame 12, and is positioned at one side of the supporting frame 12, the belt wheel 36 is rotatably connected with the output end of the centrifugal motor 35 and the rotating rod 34, and is positioned at one side of the centrifugal shell 32, the centrifugal motor 35 drives the belt wheel 36 to drive the rotating rod 34 to rotate, thereby rotating the rotary housing 33 with respect to the centrifugal housing 32, thereby centrifugally filtering the raw material in the rotary housing 33, increasing the contact area of the rotary housing 33 with the outside through the conical housing 331, so that the heat radiation effect can be increased, and the centrifugal separation effect can be improved, by mounting the agitating case 21 and the centrifugal case 32 on the same supporting frame 12, and the transition structure is reduced, so that the preparation process is simpler, the integration level of the equipment is improved, the occupied area is reduced, thereby solving the problems of complicated equipment and large occupied area in the prior heparin sodium preparation process, which increases the production cost.
Further, the stirring assembly 2 further comprises a heating coil 24, and the heating coil 24 is fixedly connected with the stirring shell 21 and is located outside the stirring shell 21.
In the present embodiment, the heating coil 24 is disposed outside the stirring shell 21, and can heat the raw material in the stirring shell 21, thereby increasing the enzymolysis efficiency.
Further, the stirring vane 23 includes a vane body 231, an extension rod 232 and an inclined plate 233, the extension rod 232 is fixedly connected to the vane body 231 and is located on a side of the vane body 231 away from the stirring motor 22, and the inclined plate 233 is fixedly connected to the extension rod 232 and is located at the bottom of the stirring shell 21.
In this embodiment, the extension rod 232 supports the inclined plate 233 at the bottom of the stirring shell 21, and when the blade body 231 rotates, the inclined plate 233 rotates, so that the substance settled at the bottom of the stirring shell 21 can be pushed up, and thus the stirring can be more sufficient.
Further, the cover plate 31 includes a plate body 311, a transmission gear 312, a rack 313 and an extension tube 314, the plate body 311 is slidably connected to the centrifugal shell 32 and is located at one side of the centrifugal shell 32, the extension tube 314 is slidably connected to the stirring shell 21 and is located at one side of the plate body 311, the rack 313 is fixedly connected to the extension tube 314 and is located at one side of the extension tube 314, and the transmission gear 312 is rotatably connected to the centrifugal shell 32 and is engaged with the plate body 311 and the rack 313.
In this embodiment, the plate body 311 is slidably connected to the centrifugal shell 32, so that sliding the plate body 311 can drive the transmission gear 312 to move, the transmission gear 312 drives the extension tube 314 fixedly connected to the rack 313 to move up and down, so that when feeding into the centrifugal shell 32 is required, the extension tube 314 moves down to contact the centrifugal shell 32, and after feeding is completed, sliding the plate body 311 and lifting the extension tube 314 to block the through hole, so that a centrifugal process can be started.
Further, the centrifugal assembly 3 further includes a heat dissipating blade 37, and the heat dissipating blade 37 is fixedly connected to the rotating rod 34 and is located at one side of the rotating rod 34.
In this embodiment, the rotating rod 34 is provided with the heat dissipating blades 37, so that the heat dissipating blades 37 can be driven to rotate in the centrifugal process, and the conical shell 331 is cooled, thereby accelerating the sedimentation and filtration efficiency.
Further, the centrifugal assembly 3 further comprises a cooling shell 38, wherein the cooling shell 38 is fixedly connected with the centrifugal shell 32 and is located outside the centrifugal shell 32.
In the present embodiment, the cooling case 38 is provided on one side of the centrifugal case 32, and the cooling liquid is placed in the cooling case 38 to cool the centrifugal case 32, thereby improving cooling efficiency.
Further, the cooling shell 38 has a plurality of cooling fins 381, and the plurality of cooling fins 381 are distributed on the cooling shell 38.
In this embodiment, the provision of the plurality of cooling fins 381 on the cooling case 38 can enhance the heat radiation efficiency of the cooling liquid in the cooling pipe 39.
Further, the centrifugal assembly 3 further includes a cooling pipe 39, a cooling pump 40 and a cooling fence 41, the cooling pipe 39 is communicated with the cooling shell 38 and is located at one side of the cooling shell 38, the cooling pump 40 is communicated with the cooling pipe 39 and the cooling shell 38 and is located between the cooling pipe 39 and the cooling shell 38, and the cooling fence 41 is fixedly connected with the cooling pipe 39 and is close to the heat dissipating blades 37.
In this embodiment, the cooling pump 40 drives the cooling liquid to circulate in the cooling pipe 39, so that the cooling fence 41 can be cooled, the cooling fence 41 can dissipate heat of the air near the cooling fins 37, and then the cooling fins 37 can drive the air cooled by the cooling fence 41 to cool the conical shell 331, thereby improving the heat dissipation efficiency.
Further, the support assembly 1 further comprises a vibration damping pad 13, and the vibration damping pad 13 is fixedly connected with the base 11 and is located on one side of the base 11.
In the present embodiment, the vibration damping pad 13 is disposed at one side of the base 11 to reduce vibration generated during operation.
In a second aspect, referring to fig. 4, the present invention further provides a process for preparing heparin sodium by using an enzymatic binding membrane, comprising:
s101, putting pig small intestine mucosa and water into the stirring shell 21 and adjusting the pH value;
fresh intestinal mucosa was put into the stirring shell 21, and pure water was added to adjust the pH to 7.2.
S102, adding a proteolytic complex enzyme into the stirring shell 21, stirring and carrying out enzymolysis to obtain an enzymolysis liquid;
and adding complex enzyme into the stirring shell 21, and stirring for enzymolysis for 3.5 hours to ensure that the enzymolysis can be fully performed.
S103, sliding the cover plate 31 to enable the enzymolysis liquid to enter the rotary shell 33;
the sufficiently dissolved enzymatic hydrolysate is fed into the rotary shell 33, and the enzymatic hydrolysate is cooled to room temperature.
S104, starting the centrifugal motor 35 to drive the rotating shell 33 to rotate for centrifugation, and discharging clear liquid;
the centrifugal motor 35 is started at the rotation speed of 3500 plus 3800r/min for centrifugation, so that large-particle impurities can be removed, and then the clear liquid is discharged for the next treatment.
S105, removing impurities from the clear liquid by using a filter membrane, adding ethanol, and collecting filtrate;
impurities are further removed through a filter membrane with small pores, and other components are extracted through ethanol, so that the heparin sodium is precipitated.
S106 standing the filtrate, collecting the precipitate and freeze-drying to obtain the heparin sodium.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (8)
1. A device for preparing heparin sodium by utilizing an enzyme method combined membrane is characterized in that,
comprises a supporting component, a stirring component and a centrifugal component, wherein the supporting component comprises a base and a supporting frame, the supporting frame is fixedly connected with the base and is positioned on one side of the base, the stirring component comprises a stirring shell, a stirring motor and stirring blades, the stirring shell is fixedly connected with the supporting frame and is positioned on one side of the supporting frame, the stirring motor is fixedly connected with the stirring shell and is positioned on one side of the stirring shell, the stirring blades are fixedly connected with the output end of the stirring motor and are positioned in the stirring shell, the centrifugal component comprises a cover plate, a centrifugal shell, a rotating rod, a centrifugal motor and a belt wheel, the centrifugal shell is fixedly connected with the supporting frame and is positioned between the stirring shell and the base, the cover plate is slidably connected with the centrifugal shell and is communicated with the stirring shell, and the rotating shell is provided with a conical shell, the toper shell is located change shell center, change the shell with the centrifugation shell rotates to be connected, and is located in the centrifugation shell, the bull stick with the centrifugation shell rotates to be connected, and with toper shell fixed connection, centrifugal motor with support frame fixed connection, and be located one side of support frame, the band pulley with centrifugal motor's output with the bull stick rotates to be connected, and is located one side of centrifugation shell.
2. The device for preparing heparin sodium by using an enzymatic binding membrane according to claim 1,
the stirring assembly further comprises a heating coil, and the heating coil is fixedly connected with the stirring shell and is positioned on the outer side of the stirring shell.
3. The device for preparing heparin sodium by using the enzyme method combined membrane as claimed in claim 2,
the stirring vane comprises a vane body, an extension rod and an inclined plate, the extension rod is fixedly connected with the vane body and is positioned on one side of the vane body far away from the stirring motor, and the inclined plate is fixedly connected with the extension rod and is positioned at the bottom of the stirring shell.
4. The device for preparing heparin sodium by using an enzymatic binding membrane according to claim 1,
the apron includes plate body, drive gear, rack and flexible pipe, the plate body with centrifugation shell sliding connection, and be located one side of centrifugation shell, flexible pipe with stirring shell sliding connection, and be located one side of plate body, the rack with flexible pipe fixed connection, and be located one side of flexible pipe, drive gear with the centrifugation shell rotates to be connected, and with the plate body with rack toothing.
5. The device for preparing heparin sodium by using an enzymatic binding membrane according to claim 1,
the centrifugal assembly further comprises a radiating blade, and the radiating blade is fixedly connected with the rotating rod and is positioned on one side of the rotating rod.
6. The device for preparing heparin sodium by using the enzyme method combined membrane as claimed in claim 5,
the centrifugal assembly further comprises a cooling shell, wherein the cooling shell is fixedly connected with the centrifugal shell and is positioned on the outer side of the centrifugal shell.
7. The device for preparing heparin sodium by using the enzyme method combined membrane as claimed in claim 6,
the cooling shell is provided with a plurality of cooling fins which are distributed on the cooling shell.
8. A process for preparing heparin sodium by utilizing an enzyme method combined membrane is characterized in that,
the method comprises the following steps: adding porcine small intestine mucosa and water into the stirring shell and adjusting the pH value;
adding a proteolytic complex enzyme into the stirring shell, stirring and carrying out enzymolysis to obtain an enzymolysis liquid;
the cover plate is slid to enable the enzymolysis liquid to enter the rotary shell;
starting a centrifugal motor to drive a rotating shell to rotate for centrifugation, and discharging clear liquid;
removing impurities from the clear liquid by a filter membrane, adding ethanol, and collecting filtrate;
standing the filtrate, collecting the precipitate, and freeze-drying to obtain the heparin sodium.
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CN116376693A (en) * | 2023-05-23 | 2023-07-04 | 南京南大药业有限责任公司 | Low-residue low-molecular-weight heparin sodium production method and equipment |
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