WO2015003660A1 - 气冷滴丸生产线 - Google Patents

气冷滴丸生产线 Download PDF

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Publication number
WO2015003660A1
WO2015003660A1 PCT/CN2014/082103 CN2014082103W WO2015003660A1 WO 2015003660 A1 WO2015003660 A1 WO 2015003660A1 CN 2014082103 W CN2014082103 W CN 2014082103W WO 2015003660 A1 WO2015003660 A1 WO 2015003660A1
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WO
WIPO (PCT)
Prior art keywords
air
pipe
cooling
unit
cleaning
Prior art date
Application number
PCT/CN2014/082103
Other languages
English (en)
French (fr)
Inventor
闫希军
孙小兵
郑永锋
范立君
付艳
Original Assignee
天士力制药集团股份有限公司
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 天士力制药集团股份有限公司 filed Critical 天士力制药集团股份有限公司
Priority to EP14822215.1A priority Critical patent/EP3020387B1/en
Priority to US14/903,789 priority patent/US10111811B2/en
Priority to JP2016524677A priority patent/JP6426166B2/ja
Publication of WO2015003660A1 publication Critical patent/WO2015003660A1/zh
Priority to HK16109618.5A priority patent/HK1221396A1/zh

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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
    • A61J3/005—Coating of tablets or the like
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B9/00—Cleaning hollow articles by methods or apparatus specially adapted thereto 
    • B08B9/02—Cleaning pipes or tubes or systems of pipes or tubes
    • B08B9/027—Cleaning the internal surfaces; Removal of blockages
    • B08B9/04—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes
    • B08B9/043—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes
    • B08B9/0433—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes provided exclusively with fluid jets as cleaning tools
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/18—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic using a vibrating apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B13/00—Accessories or details of general applicability for machines or apparatus for cleaning
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B9/00—Cleaning hollow articles by methods or apparatus specially adapted thereto 
    • B08B9/02—Cleaning pipes or tubes or systems of pipes or tubes
    • B08B9/027—Cleaning the internal surfaces; Removal of blockages
    • B08B9/04—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes
    • B08B9/043—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes
    • B08B9/0436—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes provided with mechanical cleaning tools, e.g. scrapers, with or without additional fluid jets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B9/00—Cleaning hollow articles by methods or apparatus specially adapted thereto 
    • B08B9/02—Cleaning pipes or tubes or systems of pipes or tubes
    • B08B9/027—Cleaning the internal surfaces; Removal of blockages
    • B08B9/04—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes
    • B08B9/043—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes
    • B08B9/047—Cleaning the internal surfaces; Removal of blockages using cleaning devices introduced into and moved along the pipes moved by externally powered mechanical linkage, e.g. pushed or drawn through the pipes the cleaning devices having internal motors, e.g. turbines for powering cleaning tools
    • 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
    • A61J2200/40—Heating or cooling means; Combinations thereof
    • A61J2200/42—Heating means
    • 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
    • A61J2200/40—Heating or cooling means; Combinations thereof
    • A61J2200/44—Cooling means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B08—CLEANING
    • B08B—CLEANING IN GENERAL; PREVENTION OF FOULING IN GENERAL
    • B08B2209/00—Details of machines or methods for cleaning hollow articles
    • B08B2209/02—Details of apparatuses or methods for cleaning pipes or tubes
    • B08B2209/027—Details of apparatuses or methods for cleaning pipes or tubes for cleaning the internal surfaces
    • B08B2209/04—Details of apparatuses or methods for cleaning pipes or tubes for cleaning the internal surfaces using cleaning devices introduced into and moved along the pipes

Definitions

  • the invention relates to a gas-cooled dropping pill production line, and belongs to the technical field of manufacturing a dropping pill machine. Background technique
  • Dropping pills are a traditional dosage form in traditional Chinese medicine preparations. They are widely recognized for their short production cycle, rapid onset of action, high drug stability and ease of carrying and storage.
  • the existing dropping pill production method is basically natural dripping and combined with liquid cooling, or a pressurized dripping method improved by natural dripping method combined with liquid cooling.
  • the defects of the existing equipment are as follows: 1. Based on liquid cooling The characteristics of the medium, the dropping weight of the dropping method by this cooling method, the weight range of the pellet is limited, usually between 20-30 mg, and the pellet or the pellet cannot be dripped. 2. At the same time, in order to ensure the effect of dripping, a large amount of matrix should be added to the raw material liquid, resulting in a small amount of drug in the unit and a corresponding increase in the dose. 3. In addition, liquid cooling is required to separate the liquid and solid of the dropping pill and the cooling liquid. It is difficult to completely separate the two.
  • the traditional drip equipment can only be adjusted by changing the dripper and pressure, the dropping frequency is lower, and the larger paraffin heat exchange surface area is required, the cycle efficiency is low, and the energy consumption is large. , resulting in a large volume of equipment, easy to clean corners, and a high risk of cross-contamination.
  • Pill preparation and dropping pill capsule preparation meet the requirements of high-speed dropping, preparation of pellets and increasing drug loading in the preparation of dropping pills, multiplying the dosage of dropping pills, greatly reducing the dosage and dosage of excipients;
  • the process is simplified, completely free of organic solvent residues; meets different process requirements including slow release coating, film coating and sugar coating. Really achieve low energy consumption, high speed, high efficiency, high drug loading, and a wider range of drip.
  • An air-cooled dropping pill production line including a dropping pill system, an air cooling circulation system and a control system
  • the dropping pill system includes a chemical tank and a dripper connected thereto, wherein a vibrating device is arranged between the chemical tank and the dripper, the vibrating device drives the dripper to vibrate up and down, and the generated vibration shearing force shears the liquid flowing out of the dripper Dropping, falling into the air-cooling circulation system to form a dropping pill
  • the dripper is provided with an on-line monitoring device, the device comprising a pulse signal transmitting mechanism, a transmitting frequency of the pulse signal transmitting mechanism and a vibration of the vibrating device The frequency is the same, and the control system controls the adjustment of the drip parameters according to the monitoring results of the online monitoring device.
  • the on-line monitoring device is disposed on a side below the dripper according to the need;
  • the pulse signal transmitting mechanism is a strobe light, and the stroboscopic lamp and the vibration device have the same vibration frequency, both being 50-300HZ;
  • the online monitoring device further comprises a camera corresponding to the strobe light, the camera and the strobe light are on the same horizontal plane, and are at an angle of 15 ° -145 ° with the strobe light irradiation route.
  • the dripping parameters mainly include: a vibration frequency of the strobe light and the vibration device: 50-300HZ, preferably 90-200 Hz, optimal 130-140HZ; a dropping speed: 10-40 Kg/hr, preferably 12-30 Kg /hr, optimal; 15-25 Kg/hr; drop acceleration: 1-20G, preferably 3-10G, optimal 3.5-4.5G; drip pressure: 0.5-4.0Bar, preferably 1.0-3.0Bar, optimal 1.8 Bar; dripper temperature: 70-200 ° C, preferably 70-100 ° C, optimal 75-85 ° C.
  • the air-cooling circulation system includes: a cooling duct, and a refrigerating device connected to the cooling duct and cooling the cooling duct, wherein the cooling duct is provided with an interlayer, and the lower portion of the interlayer is connected to the inside of the cooling duct;
  • the utility model comprises: a cold air refrigeration device and a cold trap refrigeration device, wherein: the cold air refrigeration device comprises: a cold storage, the air outlet of the cold storage is connected with a cold air inlet of the cooling pipeline, so that the cold air is circulated and rises in the inner cavity of the cooling pipeline;
  • the cold trap refrigeration device includes: a refrigerant storage tank equipped with a refrigerant, and a refrigerator and a heat exchanger for cooling the refrigerant in the refrigerant storage tank, a refrigerant outlet of the refrigerant storage tank and a refrigerant inlet disposed at an upper portion of the interlayer Connected, the refrigerant enters the interlayer through the refrigerant inlet,
  • the drip pellet air circulation circulation device further includes: a gas recovery device, comprising: a first valve, a second valve, a gas recovery machine and a separator, wherein the first valve is controlled One end of the pipe is connected to the cooling pipe, and the other end is connected to the atmosphere; one end of the pipe controlled by the second valve is connected to the cooling pipe, and the other end is connected to the separator through a gas recovery machine; the gas recovery machine further comprises: a gas discharge pipe and a vortex fan a gas recovery pipe, a gas recovery tank, when the second valve is opened, the vortex fan works to extract gas in the cooling pipe through the gas discharge pipe, and discharges the collected gas through the gas recovery pipe Go to the gas recovery tank.
  • the cooling duct is a straight barrel or spiral type pipe having a length of 5 to 10 m; preferably 6 m.
  • the cooling pipe is provided with an online cleaning device, comprising: a cleaning unit, a control unit, a lifting drive unit and a lifting unit, wherein the control unit drives the lifting unit to drive the lifting unit to lift and lower by the lifting driving unit, the lifting unit
  • the lifting unit comprises: a cleaning unit support frame, a cleaning pipe support, a cleaning pipe support frame, a cleaning pipe storage tray and a sealing pipe; the cleaning pipe support frame extends the cleaning pipe to the cooling pipe
  • the cleaning unit bracket includes a plurality of support wheels, each of which supports the inner side wall of the cooling duct, and the cleaning unit is connected to one end of the cleaning duct extending to the inside of the cooling duct, and is supported by the cleaning unit.
  • the lifting unit extends to the center of the cooling pipe; one end of the sealing pipe is connected to the other end of the cleaning pipe for introducing the cleaning liquid into the cleaning pipe; the lifting unit further comprises: an online monitoring device, the online Monitoring devices include: a unit and a calculation unit, the image acquisition unit is disposed on the cleaning unit, configured to collect a real-time image in the cooling pipeline, and send the image signal to the calculation unit, and the calculation unit converts the value into a value according to the image signal and the threshold value For comparison, if the value is greater than the threshold, a drive signal is sent to the control unit to drive the cleaning unit for cleaning.
  • an online monitoring devices include: a unit and a calculation unit, the image acquisition unit is disposed on the cleaning unit, configured to collect a real-time image in the cooling pipeline, and send the image signal to the calculation unit, and the calculation unit converts the value into a value according to the image signal and the threshold value For comparison, if the value is greater than the threshold, a drive signal is sent to the control unit to drive the
  • the gas-cooled dropping pill production line further comprises a fluidized dry coating system
  • the system mainly comprises a fluidized bed
  • the end of the cooling pipe is connected to the inlet of the fluidized bed through a vacuum pipe
  • the air-cooled shaped dropping pill is The fluidized bed of the prime pill is fed into the fluidized bed;
  • the fluidized bed comprises a furnace body, a material inlet is arranged below the furnace body, and a gas distribution plate is arranged below the feed port.
  • the bottom of the airflow distribution plate is connected with an air outlet pipe of a normal temperature and low humidity air supply system, and the normal temperature and low humidity air supply system sends the normal temperature and low humidity gas into the fluidized bed furnace through the air outlet pipe, and is built in the inside of the furnace body.
  • the normal temperature and low humidity air supply system comprises a casing and a low-humidity unit disposed in the casing, and the casing is provided with an air inlet duct and an air outlet duct, and the air enters the casing from the air inlet duct and is low-humidity
  • the furnace body is input through an air outlet duct
  • the low-humidity unit is formed by connecting a plurality of devices in series, and includes a dust removing device, a dehumidifying device, a blowing device, and the like in the flow direction of the airflow.
  • the heating device, the filtering device and the high-efficiency filtering device; the normal temperature and low-humidity air supply system further comprises a return air duct for airflow recovery, and the two ends are respectively connected to the furnace body and the casing.
  • the drying bed has a drying temperature of -20 ° C - 100 ° C and a drying time of 1-4 hours.
  • the fluidized bed is preferably a gradient heating method, -20-30 ° C. Forming a fluidized state, drying at 15-35 °C for 10-120 minutes, drying at 35-55 °C for 10-60 minutes, drying at 55-100 °C for 0-60 minutes; further, most preferably 0-20 °C Fluidized state, dried at 25 °C for 60 minutes, dried at 45 °C for 30 minutes, and dried at 55 °C for 0-30 minutes.
  • the fluidized bed is further provided with an on-line detecting device for monitoring the water content and particle size distribution of the pellets.
  • the invention combines vibration dripping, air cooling and fluidized drying coating into one body, and is applied to the dropping pill preparation and the dropping pill capsule preparation, which satisfies the high-speed dropping and preparing the micro-pill in the preparation of the dropping pill.
  • the ability and the requirement of increasing the drug loading amount double the drug loading amount of the dropping pills, greatly reduce the dosage and dosage of the auxiliary materials; the operation process is simplified, and there is no residual organic solvent; the content includes the sustained release coating, the film coating and the sugar coating. Different process requirements within. Really achieve low energy consumption, high speed, high efficiency, high drug loading, and a wider range of drip.
  • Figure 1 is a schematic view showing the overall structure of the present invention
  • Figure 2 is a cross-sectional view of the drip tray of the present invention.
  • Figure 3 is an enlarged view of a partial structure of Figure 2;
  • Figure 4 is a schematic structural view of a refrigeration apparatus of the present invention.
  • Figure 5 is a schematic structural view of a gas recovery device of the present invention.
  • FIG. 6 is a schematic view showing the overall structure of an online cleaning device of the present invention.
  • Figure 7 is a control block diagram of the online cleaning device of the present invention.
  • Figure 8 is a schematic view showing the overall structure of a fluidized bed of the present invention. detailed description
  • the present invention provides an air-cooled dropping pill production line comprising a dropping pill system, an air cooling circulation system and a control system, the dropping pill system comprising a chemical tank 100 and a dripper 200 connected thereto, the chemical material
  • a vibrating device 300 is disposed between the tank 100 and the dripper 200. The vibrating device drives the dripper to vibrate up and down, and the generated vibrating shear force shears the liquid medicine flowing out of the dripper into drops, and falls into the air-cooling circulation system after cooling.
  • the dripper is provided with an on-line monitoring device, the device comprises a pulse signal transmitting mechanism, the transmitting frequency of the pulse signal transmitting mechanism is the same as the vibration frequency of the vibration device, and the control system is monitored according to the online monitoring device As a result, the control adjusts the drip parameters.
  • the dripping parameters include: a vibration frequency of the strobe light and the vibration device: 50-300HZ, preferably 90-200 Hz, optimal 130-140HZ; a dropping speed: 10-40 Kg/hr, preferably 12-30 Kg/ Hr, optimal; 15-25 Kg/hr; drop acceleration: 1-20G, preferably 3-10G, optimal 3.5-4.5G; drip pressure: 0.5-4.0Bar, preferably 1.0-3.0Bar, optimal 1.8 Bar; dripper temperature: 70-200 ° C, preferably 70-100 ° C, optimal 75-85 ° C.
  • the on-line monitoring device is disposed on a side below the dripper according to requirements; the pulse signal transmitting mechanism is a strobe lamp 201, and the stroboscopic lamp and the vibrating device have the same vibration frequency.
  • the online monitoring device may further comprise a camera (not shown) corresponding to the strobe light, the camera and the strobe light being on the same horizontal plane and at an angle of 15 ° -145 ° with the strobe light irradiation route.
  • the vibration dripping method used in the present invention mainly applies the pressurized liquid medicine to the dripper, and uses the principle of magnetic/electric or pneumatic vibration to make the dripper vibrate up and down at a set frequency, waveform and amplitude.
  • the vibration shear force is applied to the liquid column to form droplets.
  • the vibration frequency is between 50 and 300 Hz. It can be magnetic or electric vibration according to the need, with high vibration frequency and small amplitude, suitable for high-speed drop of low-viscosity materials.
  • the way of pneumatic vibration, vibration frequency, and amplitude When the material viscosity exceeds 800 cp (centipoise), the electric method cannot cut the material effectively. The dripper is blocked, and when the drop pellet is prepared, pneumatic vibration can be used.
  • the buffer tank 500 is further disposed between the chemical tank 100 and the dripper 200.
  • the buffer tank 500 is provided with a compressed air inlet, which is connected to the air pump through a pressure pipe, and a pressure regulating valve is arranged on the pressure pipe to keep the liquid medicine in the buffer tank constant pressure supply.
  • the buffer tank is provided with a liquid level gauge for controlling the feed rate; the buffer tank is further provided with an insulation layer, which is heated by a water bath, an oil bath and an electric heating; and a temperature sensor is used to monitor the temperature of the liquid; Agitating paddles with adjustable agitation speed.
  • the in-can sensor can be configured for contact or non-contact.
  • the tank material may be 304, 316L or other heat resistant material that can be directly in contact with the product.
  • FIG. 2 is a cross-sectional view of the drip tray of the present invention
  • Figure 3 is an enlarged view of a portion of the structure of Figure 2;
  • the dripper 200 of the present invention mainly includes a drip tray 210.
  • the drip tray 210 is provided with a plurality of drip holes 220, and the drip holes 220 are equally spaced in the circumferential direction of the drip pan 210.
  • the drip hole 220 is composed of a cylindrical cavity 221, a conical cavity 222, and a straight lumen 223, and droplets are dropped from the end of the straight lumen 223.
  • the diameter d of the cylindrical cavity 221 is 0.5-lmm
  • the taper of the conical cavity 222 is 20°-170°
  • the total thickness A of the drip tray 210 is 6 mm
  • the concave ring groove 230 is formed at the periphery of the drip hole 220 to prevent residual chemical liquid from accumulating around the drip hole 220 when the viscous liquid is ejected at a high speed, which eventually causes clogging of the drip hole 220 or affects the dripping.
  • the dripper 200 can be directly exposed.
  • the outside of the dripper can also be selected to set the holding chamber so that the temperature of the dripper is maintained at about 70-20 CTC.
  • the outer layer of the heat preservation chamber is provided with a heat insulating material, and the inner layer is provided with a steam heating device or an infrared heating device to avoid the viscosity change of the liquid medicine caused by the temperature change, thereby affecting the dripping effect.
  • An opening is arranged below the holding chamber, and the position of the opening is corresponding to the outlet position of the dripper, and the size of the opening is corresponding to the width of the dripper.
  • the inside of the holding chamber can be designed with a certain arc angle, which can be compared with the square cavity. Less angles, easier to clean; open the lower end of the holding chamber to ensure the normal drop of the dropping pills.
  • a strobe light 201 is arranged for monitoring the dripping of the dropping pills.
  • the operator can observe the high-speed drop state in real time only by visual observation.
  • the image can be monitored in real time through the camera.
  • a certain vibration frequency such as: the dropping speed of 50Hz or more, real-time monitoring and accurate adjustment of the dropping state can be realized by the appearance shape of the dropping pills.
  • the vibration waveform as a monitoring index of PAT
  • the particle size distribution of the dropping pills can be measured, and the fluidization state of the dropping pills can be monitored in real time by the stroboscopic device.
  • the vibration parameters By adjusting the vibration parameters, the drug loading can be increased to more than 50%, and the excipients can be greatly reduced.
  • the vibration parameters By adjusting the vibration parameters, the diameter of the dropping pills can be adjusted from 0.2mm to 3mm, and small Chinese medicine dropping pellets which can better meet the capsule filling requirements can be produced.
  • the stroboscopic real-time inspection and online monitoring technology adopted by the invention increase the yield of the dropping pills product from the traditional 70% to over 95%.
  • the air-cooled circulation system of the present invention comprises: a cooling duct 600, and a refrigerating apparatus connected to the cooling duct 600 and cooling the cooling duct.
  • the cooling duct 600 is disposed directly under the dripper 200 of the dropping device, and the cooling duct 600 may be a straight barrel type or a spiral type pipeline.
  • the length of the cooling duct 600 is 5m - 10m, preferably according to requirements. The length is 6m.
  • An outer layer 610 is disposed outside the cooling duct 600, and a lower portion of the interlayer 610 communicates with the inside of the cooling duct 600 through the communication port 601.
  • the cold air refrigeration device includes: a cold air refrigeration device 4, wherein the cold air refrigeration device includes a cold storage 41, and an air outlet of the cold storage 41 communicates with a cold air inlet of the cooling duct 600 to cool the cold air.
  • the inner circumference of the duct 600 rises cyclically, and the angle between the cold air inlet of the cooling duct 600 and the plane of the crucible is 0° - 90 °.
  • the refrigeration apparatus further includes a cold trap refrigeration unit 5, and the cold trap refrigeration apparatus 5 includes: a refrigerant storage tank 51 equipped with a refrigerant, and refrigeration for cooling the refrigerant in the refrigerant storage tank 51.
  • the machine 52 and the heat exchanger 53, the refrigerant outlet of the refrigerant storage tank 51 is connected to the refrigerant inlet provided in the upper portion of the interlayer 610 via a pump 54, and the refrigerant is introduced into the interlayer 610 through the refrigerant inlet, and is transported from the upper portion of the interlayer 610 to the lower portion of the interlayer 610.
  • the refrigerant circulates in the inner cavity of the cooling duct 600 simultaneously with the cold air, and discharges or recovers the refrigerant and the cold air with the gas recovery device 6 connected through the top of the cooling duct 600.
  • the refrigerant is usually used: nitrogen, argon or carbon dioxide.
  • FIG. 5 is a schematic view showing the structure of a gas recovery device of the present invention.
  • the gas recovery device 6 includes: a gas recovery machine 61, a first valve 62, a second valve 63, and a separator 64, and the first valve 62 controls one end of the pipe and
  • the cooling pipe 600 is in communication, and the other end is in communication with the atmosphere;
  • the second valve 63 controls one end of the pipe to communicate with the cooling pipe 600, and the other end is connected to the separator 64 through the gas recovery machine 61.
  • FIG. 5 is a schematic view showing the structure of a gas recovery device of the present invention.
  • the gas recovery device 6 includes: a gas recovery machine 61, a first valve 62, a second valve 63, and a separator 64, and the first valve 62 controls one end of the pipe and
  • the cooling pipe 600 is in communication, and the other end is in communication with the atmosphere;
  • the second valve 63 controls one end of the pipe to communicate with the cooling pipe 600, and the other
  • the gas recovery machine 61 The utility model comprises: a gas discharge pipe 611, a vortex fan 612, a gas recovery pipe 613, a gas recovery tank 614, when the second valve 63 is opened, the vortex fan 612 works to extract the gas in the cooling duct 600 through the gas discharge pipe 611, and collects the collected gas through the gas recovery pipe. 613 is discharged into the gas recovery tank 614; the separator 64 is coupled to the gas recovery tank 614.
  • the first valve 62 When the refrigerant is harmless gas, the first valve 62 is opened and the second valve 63 is closed, so that the refrigerant in the inner cavity of the cooling pipe 600 and the cold air are simultaneously circulated to the top of the cooling pipe 600 and communicated through the first valve 62.
  • the pipe is discharged into the atmosphere; when the refrigerant is a harmful gas, the second valve 63 is opened while the first valve 62 is closed, so that the refrigerant in the inner cavity of the cooling pipe 600 and the cold air are simultaneously circulated to the top of the cooling pipe 600 and pass through
  • the pipe in which the two valves 63 are connected is recovered in the gas recovery machine 61, separated by the separator 64, and the separated cold air is separately sent to the cold storage 41, and the refrigerant is sent to the refrigerant storage tank 51.
  • the dropping air-cooling production line further includes: an online cleaning device, the device comprising: a cleaning unit 10, a cleaning monitoring control unit 11, a lifting drive unit 12, and a lifting unit 13, the cleaning Unit 10 is a showerhead or a showerhead with a cleaning cloth.
  • the cleaning monitoring control unit drives the lifting unit to raise and lower the cleaning unit 10 in the cooling duct 600 by the lifting driving unit, and the lifting unit is disposed outside the top of the cooling duct 600.
  • the lifting unit comprises: a cleaning unit support frame 131, a cleaning pipe 132, a cleaning pipe support frame 133, a cleaning pipe storage tray 134, a sealing pipe and an online cleaning monitoring device, such as: a camera.
  • the cleaning duct support 133 extends the cleaning duct 132 to the inside of the cooling duct 600.
  • the cleaning unit bracket 131 includes a plurality of supporting wheels 1311, each of the supporting wheels 1311 abutting against an inner side wall of the cooling duct 600, and the cleaning unit 10 is connected to an end of the cleaning duct 132 extending to the inside of the cooling duct 600.
  • the cleaning unit 10 is extended by the cleaning unit support frame 131 to the center of the cooling duct 600.
  • One end of the sealing joint 135 is connected to the other end of the cleaning duct 132 for introducing a cleaning liquid into the cleaning duct 132.
  • the lifting drive unit of the online cleaning device includes: a motor 121, a driving wheel 122, a sprocket 123, a belt 124, and a tensioning wheel 125, and the motor 121 is coupled to the driving wheel 122,
  • the driving wheel 122 is connected to the sprocket 123 via a belt 124
  • the sprocket 123 is connected to the cleaning duct storage tray 134
  • the cleaning monitoring control unit 11 is connected to the motor 121
  • the tensioning wheel 125 is located at the sprocket 123 and the driving wheel Between 122, and connected to the sprocket 123 and the drive wheel 122 via a belt 124.
  • those skilled in the art can also perform the driving lifting operation by using the lifting drive unit of other structures according to actual needs.
  • FIG. 7 is a control block diagram of the online cleaning device of the present invention.
  • the online cleaning monitoring device 136 includes: an image collecting unit 1361 and a calculating unit 1362.
  • the image collecting unit 1361 is disposed on the cleaning unit 10, and the image collecting unit 1361 is a camera for Collecting real-time images in the cooling duct 600,
  • the image signal is sent to the calculation unit 1362, and the calculation unit 1362 converts the value into a numerical value according to the image signal and compares it with the threshold value. If the value is greater than the threshold value, the driving signal is sent to the cleaning monitoring control unit 11 to drive the cleaning unit 10 to perform cleaning. .
  • the working process of the online cleaning device of the present invention is as follows: First, the image capturing unit 1361 collects the image in the cooling pipe 600 in real time, and sends the collected image to the computing unit 1362. Secondly, the calculating unit 1362 converts the collected image into a numerical value according to the collected image, and compares it with the threshold stored in the calculating unit 1362. If the value is greater than the threshold, the cleaning program is entered, otherwise the image collecting unit 1361 continues.
  • the acquisition image is implemented; again, the calculation unit 1362 calculates the type of cleaning liquid required to clean the cooling duct 600 and transmits a driving signal to the cleaning monitoring control unit 11; in addition, the calculation unit passes the acquired value and the pollutant stored in the calculation unit 1362. Threshold comparison, the type of the pollutant is obtained, and the type of the cleaning liquid for cleaning the corresponding pollutant is calculated; then, the cleaning monitoring control unit 11 sends a stop signal to the dropping system according to the signal sent by the calculating unit 1362, stopping the dropping of the pills.
  • drive the lifting drive unit 12 and The door 142 is configured to extend the cleaning unit 10 from the top to the bottom of the cooling duct 600 and spray the cleaning liquid; when the cleaning unit 10 moves to the lower portion of the cooling duct 600, the cleaning operation ends, and the cleaning monitoring control unit 11 controls the lifting driving unit respectively. 12 and the valve 142, the cleaning unit 10 is controlled to stop spraying and return to the top of the cooling pipe 600, and the cleaning operation is repeated until the cleaning is completed.
  • FIG. 8 is a schematic view showing the overall structure of a fluidized bed of the present invention.
  • the gas-cooled dropping pill production line further includes a fluidized dry coating system 700, the system mainly includes a fluidized bed 710, the fluidized bed 710 includes a furnace body, and the furnace body is provided below the furnace body.
  • the material inlet port 711, the end of the cooling pipe 600 is connected to the feed port 711 of the fluidized bed 710 through a vacuum pipe, and the gas-cooled shaped drop pills are vacuum-loaded and input from the feed port 711. Fluidized and dry coating in the bed.
  • An air distribution plate 712 is disposed below the feed port 711.
  • the air flow distribution plate 712 is provided with a through hole.
  • the normal temperature and low humidity air supply system 720 communicates with the furnace body through a pipe, and the air inlet position is located below the air flow distribution plate 712. , blow up.
  • the through holes provided in the air distribution plate 712 can pass the air flow and effectively prevent the material from falling out of the furnace body.
  • the normal temperature low humidity air supply system 720 includes a housing 721 and a low humidity unit 722 disposed in the housing, and the housing is provided with an air inlet 723 and an air outlet duct 724. After entering the casing from the air inlet 723, the air is processed by the low-humidity unit 722, and then introduced into the furnace body through the air outlet 725 through the air outlet duct 724, and the material built in the furnace body is fluidized and dried.
  • the normal temperature low humidity air supply system 720 further includes a return air duct 726 for airflow recovery, and the two ends are respectively connected to the furnace body and the casing.
  • the low-humidity unit 722 is a combination of a plurality of processing devices, and includes a dust removing device, a dehumidifying device, a blowing device, a heating device, a filtering device, and a high-efficiency filtering device in order according to the airflow direction indicated by the arrow in FIG.
  • a dust removing device When the fluidized bed is working, it is firstly vacuumed through the feed port 711 above the furnace body, and then introduced into the gas through the low-humidity unit 722 by the low-humidity unit 722 by the furnace air inlet 725, and the treated gas is treated.
  • the humidity is 5 g/kg
  • the injection pressure is 1-4 bar
  • the temperature is -20-100 ° C, preferably 20-60 ° C.
  • the material is fluidized and dried to a humidity of 4% for coating, and then the fluidized and dried coated product is discharged by discharging the unloading device, and the exhaust gas is discharged from the exhaust duct
  • the fluidized bed is usually dried at a temperature of from -20 ° C to 100 ° C and a drying time of from 1 to 4 hours, as needed.
  • the fluidized bed is preferably subjected to a gradient heating method, forming a fluidized state at -20-30 ° C, and drying at 15-35 ° C. -120 minutes, drying at 35-55 ° C for 10-60 minutes, drying at 55-100 ° C for 0-60 minutes; most preferably at 0-20 ° C to form a fluidized state, drying at 25 ° C for 60 minutes, drying at 45 ° C 30 Minutes, dry at 55 ° C for 0-30 minutes.
  • the fluidized bed is further provided with an on-line detecting device 800 for monitoring the water content and the particle size distribution of the pellet, and the online moisture detecting device can adopt a moisture sensor or a probe or the like.
  • the existing detecting components are not described herein because they are prior art.
  • the increased fluidized drying solves the problems of adhesion and analysis during the storage process of the dropping pills prepared by the air cooling equipment, and also ensures the dropping pills.
  • the moisture can reach a stable value, which improves the uniformity of the drug loading and coating of the device.
  • Spraying the hot melt liquid to carry the drug-loaded package can further increase the drug loading amount of the dropping pills; it can also be sprayed with the device to make the dropping pills coating to meet different process requirements, such as: slow release coating, film coating, sugar coating Wait.
  • the working process of the present invention is as follows: the liquid medicine is pushed by the buffer tank 500, and the molten chemical liquid is delivered to the dripper 200 with the heat insulating chamber, The dripper has an outlet in the same direction as the bottom opening of the holding chamber 210, ensuring that the liquid can drip from the bottom of the dripper.
  • the mixed liquid is discharged from the bottom outlet of the dripper 200 by the pressure.
  • adjust the pressure or vibration parameters of the pneumatic or electro-vibrating dripper so that the pour from the dripper is cut into drops of the desired diameter.
  • vibration acceleration 0-llOg sinusoidal
  • vibration amplitude (0-25.4mm
  • the upper port of the cooling duct 600 is in sealing communication with the opening of the lower end of the holding chamber of the dripper 200, and the lower end of the cooling duct 600 is an opening structure corresponding to the dropping barrel.
  • the cold storage 41 circulates the cold air that has been produced into the inner space of the cooling duct 600 through the cold air inlet, and the refrigerant storage tank 51 inputs the refrigerant into the interlayer 610 through the refrigerant inlet. At this time, the flow of the refrigerant in the interlayer 610 is upward.
  • the communication port 601 that communicates with the cooling duct 600 through the interlayer 610 enters the inner cavity of the cooling duct 600, mixes with the cold air in the inner cavity of the cooling duct 600, and rises cyclically, when the refrigerant and the cold air
  • the mixed gas rises to the top of the cooling pipe, the cold air and the refrigerant are respectively recovered into the cold storage 41 or the refrigerant storage tank 51 by the gas recovery device 6, or the mixed gas is discharged to the atmosphere through the gas recovery device 6, and the specific discharge process is required. See the previous section.
  • the cooling air is directly blown into the cooling duct 600 at an angle, the cold air and the refrigerant form a laminar flow in the cooling duct 600, so that the continuously dripped medicine droplets are purged with a small amount of lower temperature gas to maintain a certain distance. , to avoid the adhesion of the dropping pills in this area, affecting the subsequent molding.
  • the end of the cooling pipe 600 is connected to the fluidized drying coating system 700 through a pipe, the air volume and the exhaust air volume are adjusted, and the temperature range is controlled, and the dried pellets are discharged by vacuum negative pressure, sieved, and then re-injected into the fluidized state.
  • Bed adjust the air intake and exhaust air volume, according to the process requirements for drug loading or film coating; after coating, the device can also be connected to the capsule filling machine for perfusion, and the capsule check weighing machine for grain-by-grain inspection. Therefore, according to the actual application requirements, based on the overall structure shown in Fig. 1, the gas-cooled dropping pill production line provided by the present invention can also be equipped with a capsule filling machine and a capsule weighing device.
  • the above devices are all prior art and will not be described herein.
  • the apparatus of the present invention will be further described in detail below by way of a preferred embodiment. This example is merely illustrative of the invention and is not intended to limit the invention.
  • PEG-6000 polyethylene glycol 6000
  • the air pump supplies air to the chemical tank through the pipeline, so that the melted liquid flows into the dripper and drops from the bottom of the dripper into the cooling duct, and the cooling duct is perpendicular to the ground; the cold air is started to cool The temperature reaches -120 ° C, the angle between the inlet of the cooling air and the horizontal plane is 30 °, and the cold air circulates in the cooling duct, so that the droplets of the dripping liquid are cooled and solidified into solid pellets in the cooling duct, from cooling
  • the pipe at the lower end of the pipe can be connected to the fluidized bed portion for fluidized drying and drug loading coating.
  • Drying step then the dropping pills are fluidized and dried, and the drug-loading coating is carried out. After the material is in a good fluid state at -20 ° C -30 ° C in the bed, drying at 50 ° C for 2 hours and drying for 120 minutes. The water content of the pill is controlled at 5.0%, and the intermediate pill is obtained.
  • Coating step Calculate the amount of coating powder according to the amount of coating and the dosage of the coating, the concentration of the coating liquid is 10%, prepare the coating liquid, and stir for 45 minutes. After the inlet air temperature is set to 40 ° C and the qualified dropping pills are put into the fluidized bed, the set inlet air temperature is raised to 48 ° C, and after the material temperature reaches 38 ° C, the coating is started.
  • Coating step Calculate the amount of coating powder according to the amount of coating and the dosage of the coating.
  • the concentration of the coating liquid is 18%, prepare the coating liquid, and stir for 45 minutes.
  • the temperature of the material is controlled at 35-45 ° C.
  • the temperature is lowered to below 30 ° C.
  • the sieve is pelleted and the particle size is 1.0-2.0 mm.
  • the intermediate material liquid is vibrated by a dripper with a vibration frequency of 200 Hz, a dropping pressure of 4.0 Bar, a dripper temperature of 100 ° C, and a dropping speed matching the step (1) material speed. 15kg/hr;
  • the pipe from the lower end of the cooling pipe can be connected to the fluidized bed portion for fluidized drying and drug loading coating. Specifically, a fluidized state was formed at 0 ° C, dried at 25 ° C for 60 minutes, dried at 45 ° C for 30 minutes, and dried at 55 ° C for 30 minutes.
  • Example 5 Preparation of Compound Danshen Dripping Pills
  • Drying step Drying is carried out by fluidized drying equipment, and dried at -20 ° C for 4 hours to obtain dried pills.
  • Coating step the dried pill is coated in a fluidized bed, and the weight ratio of the coating material to the pill is 1 :
  • the compound salvia miltiorrhiza extract and polyethylene glycol 8000 were put into a homogenizer and homogenized at 2500 rpm for a time of 100 min, then homogenized at 6000 rpm, time 50 min, temperature 80 ° C, to obtain an intermediate liquid;
  • the intermediate solution is vibrated by a dripper with a vibration frequency of 140 Hz, a drop pressure of 0.5 Bar, a dripper temperature of 100 ° C, and a drip speed matching the step (1) material speed. Is 30kg/hr;
  • Drying is carried out by fluidized drying equipment, and dried at 100 ° C for 1 hour to obtain dried pills.
  • Coating step the dried pill is coated in a fluidized bed, the weight ratio of the coating material to the pill is 1:25, the concentration of the coating liquid is 10%, and the coating at 40°C is obtained. Coating drops pills.
  • Example 7 Preparation of Compound Danshen Dripping Pills
  • the dropping speed is matched with the step (1) the material speed
  • Drying is carried out by a gradient heating method, a fluidized state is formed at -20 ° C, dried at 15 ° C for 10 minutes, and dried at 35 ° C for 10 minutes to obtain a dried dropping pills.
  • Coating step The dried pill is coated in a fluidized bed, and the weight ratio of the coating material to the pill is 1: 25, the coating liquid concentration is 10%, the temperature of 40 ° C coating will be coated with pills.
  • Example 8 Preparation of Compound Danshen Dripping Pills
  • the intermediate material liquid is vibrated by a dripper with a vibration frequency of 200HZ, an acceleration of 20G, a dropping speed of 40Kg/hr, a dropping pressure of 3.0Bar, and a dripper temperature of 85 °C.
  • the dropping speed is matched with the step (1) the material speed
  • Drying is carried out by gradient heating method, forming a fluidized state at 30 ° C, drying at 35 ° C for 120 minutes, drying at 55 ° C for 60 minutes, and drying at 100 ° C for 60 minutes to obtain dried pills.
  • Coating step the dried pill is coated in a fluidized bed, the weight ratio of the coating material to the pill is 1:25, the concentration of the coating liquid is 10%, and the coating is obtained at a temperature of 40 ° C.
  • Coating drops pills.
  • the invention adopts vibration shearing and dropping, improves the forming speed of the dropping pills and the roundness of the dropping pills, and reduces the difference in weight of the dropping pills; real-time monitoring while dropping, and adjusting the droplets through adjustment of various parameters Pill product yield; using air-cooling method to achieve the preparation of dropping pills, high-speed dropping of pellets while increasing the drug loading amount, greatly reducing the amount of auxiliary materials and dosage; avoiding the organic solvent residue in the traditional liquid cooling mode.
  • the invention effectively avoids the disadvantages of the traditional dropping device, and truly achieves low energy consumption, high speed, high efficiency, high drug loading, and has a wider range of dripping, greatly improving the production speed and the dripping effect.

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Abstract

一种气冷滴丸生产线，包括滴丸系统、气冷循环系统和控制系统。所述滴丸系统包括化料罐和滴头，两者之间设有振动装置，振动装置带动滴头上下振动，振动剪切力将滴头中流出的药液剪切成滴，落入气冷循环系统冷却后形成滴丸，滴头上设有在线监测装置，该装置包括脉冲信号发射机构，脉冲信号发射机构的发射频率与所述振动装置的振动频率相同，控制系统根据在线监测装置的监测结果，控制调节滴制参数。将振动滴制及在线监测控制、空气冷却与流化干燥包衣结合为一体，满足高速滴制、制备微丸以及提高载药量的要求，成倍提高滴丸载药量，大幅度降低辅料用量和服用剂量，完全无有机溶剂残留，满足包括缓释包衣、薄膜包衣和包糖衣在内的不同工艺要求。

Description

气冷滴丸生产线 技术领域
本发明涉及一种气冷滴丸生产线， 属于滴丸机制造技术领域。 背景技术
滴丸是中药制剂中的一种传统剂型， 以其生产周期短、 起效迅速、 药物稳定性高 且便于携带贮存的诸多优点而获得普遍认可。
现有的滴丸生产方法基本上为自然滴制并结合液体冷却， 或由自然滴制法改进而 来的加压滴制法并结合液体冷却，现有设备的缺陷在于： 1、基于液体冷却介质的特性， 采用该种冷却方式滴制的滴丸， 丸重范围会受到一定的限制， 通常在 20-30mg之间， 微丸或大丸都无法滴制。 2、 同时， 为保证滴制效果， 需在原料药液中加入大量基质， 导致单位载药量小， 服药量相应增大。 3、 另外， 采用液体冷却的方式， 需要进行滴丸 和冷却液的液固分离， 两者的彻底分离操作起来比较困难， 因此， 冷却液难免会在滴 丸上存在残留， 导致滴丸污染。 4、 当需要调整产量时， 传统的滴制设备一般仅能通过 改变滴头及压力进行调节， 滴制频率较低， 再加上需要较大的石蜡热交换表面积， 循 环效率低， 能耗大， 导致设备体积大， 易存在清洁死角， 交叉污染风险大。
如何对现有的滴制设备进行改进， 包括滴制过程中的稳定性、 有效增加滴丸成形 质量及提高生产速度、 提高载药量， 并扩大滴丸可滴制尺寸范围， 同时降低能耗及冷 却液用量， 防止滴丸污染， 是目前滴丸设备改进的发展趋势和研究方向。 发明内容
本发明所要解决的技术问题在于针对现有技术的不足，提供一种气冷滴丸生产线， 首次将振动滴制及在线监测控制、 空气冷却与流化干燥包衣结合为一体， 并应用于滴 丸制剂及滴丸胶囊制剂， 满足了滴丸制备中对高速滴制、 制备微丸能力以及提高载药 量的要求， 成倍提高滴丸载药量， 大幅度降低辅料用量和服用剂量； 操作工序简化， 完全无有机溶剂残留； 满足包括缓释包衣、 薄膜包衣和包糖衣在内的不同工艺要求。 真正达到低能耗、 高速、 高效、 高载药量， 具备更广泛的可滴制范围。
本发明的所要解决的技术问题是通过如下技术方案实现的：
一种气冷滴丸生产线， 包括滴丸系统、 气冷循环系统和控制系统， 滴丸系统包括 化料罐和与其相连的滴头， 所述化料罐与滴头之间设有振动装置， 振动装置带动滴头 上下振动， 产生的振动剪切力， 将滴头中流出的药液剪切成滴， 落入气冷循环系统冷 却后形成滴丸， 所述滴头上设有在线监测装置， 该装置包括脉冲信号发射机构， 所述 脉冲信号发射机构的发射频率与所述振动装置的振动频率相同， 控制系统根据在线监 测装置的监测结果， 控制调节滴制参数。
根据需要， 所述在线监测装置设置在所述滴头下方的侧面； 所述脉冲信号发射机 构为频闪灯， 所述频闪灯和振动装置的振动频率相同， 均为 50-300HZ; 为了便于观察 和记录， 所述在线监测装置还包括与频闪灯对应设置的摄像头， 摄像头与频闪灯处于 同一水平面上， 并与频闪灯照射路线呈 15 ° -145 ° 夹角。
为了防止在滴制过程中造成堵塞， 所述滴头主要包括滴盘， 滴盘上设有多个滴孔， 滴孔的外围开设有凹形环槽； 所述凹形环槽的内径 =滴孔内径 +0.4毫米， 外径 1.5毫 米， 槽深为 0.5-5毫米。
所述滴制参数主要包括： 所述频闪灯和振动装置的振动频率： 50-300HZ, 优选 90-200Hz, 最优 130-140HZ; 滴制速度： 10-40Kg/hr， 优选 12-30 Kg/hr， 最优； 15-25 Kg/hr; 滴制加速度： 1-20G, 优选 3-10G, 最优 3.5-4.5G; 滴制压力： 0.5-4.0Bar, 优 选 1.0-3.0Bar， 最优 1.8Bar; 滴头温度： 70-200°C， 优选 70-100°C， 最优 75-85 °C。
所述气冷循环系统包括： 冷却管道， 以及与所述冷却管道连接并对冷却管道制冷 的制冷装置， 所述冷却管道外设有夹层， 所述夹层下部与冷却管道内部连通； 所述制 冷装置包括： 冷风制冷装置和冷阱制冷装置， 其中： 所述冷风制冷装置包括： 冷库， 所述冷库的出风口与冷却管道的冷风进风口相连通， 使冷风在冷却管道内腔中循环上 升； 所述冷阱制冷装置包括： 装有冷媒的冷媒储罐， 以及对冷媒储罐内的冷媒进行制 冷的制冷机和换热器，所述冷媒储罐的冷媒出口与所述夹层上部设置的冷媒入口相连， 冷媒通过冷媒入口输入夹层内，从夹层上部传输至夹层下部并传输到冷却管道内腔中； 所述冷媒在冷却管道的内腔中与冷风同时循环上升，并通过冷却管道顶部排放或回收。
为了节约能源又防止有毒冷媒造成污染， 所述滴丸气冷循环装置还包括： 气体回 收装置， 其包括： 第一阀门、 第二阀门、 气体回收机和分离机， 所述第一阀门控制的 管道一端与冷却管道连通， 另一端与大气连通； 第二阀门控制的管道一端与冷却管道 连通， 另一端通过气体回收机与分离机连接； 所述气体回收机进一步包括： 气体排放 管、 涡流风机、 气体回收管、 气体回收箱， 当所述第二阀门打开时， 所述涡流风机工 作通过所述气体排放管抽取冷却管道中的气体， 并将收取收集的气体通过所述气体回 收管排入到所述气体回收箱中。 为了保证良好的冷却效果， 所述冷却管道为直桶型或螺旋型管道， 其长度为 5- 10 米； 优选为 6米。
为了保持清洁， 所述冷却管道上设有在线清洗设备， 包括： 清洗单元、 控制单元、 升降驱动单元和升降单元， 所述控制单元通过升降驱动单元驱动升降单元带动清洁单 元升降， 所述升降单元设置在冷却装置的冷却管道顶部外侧； 所述升降单元包括： 清 洁单元支撑架、 清洁管道、 清洁管道支撑架、 清洁管道收纳盘和密封接管； 所述清洁 管道支撑架使清洁管道延伸到冷却管道内部； 所述清洁单元支架包括多个支撑轮， 每 一个所述支撑轮与冷却管道内侧壁抵顶， 所述清洁单元与所述清洁管道延伸到冷却管 道内部的一端连接， 并通过清洁单元支撑架使清洁单元延冷却管道中心升降； 所述密 封接管的一端与清洁管道的另一端连接， 用于将清洁液导入所述清洁管道内； 所述升 降单元还包括： 在线监测装置， 所述在线监测装置包括： 图像采集单元和计算单元， 所述图像采集单元设置于所述清洁单元上， 用于采集冷却管道中的实时图像， 将图像 信号发送到计算单元， 所述计算单元根据该图像信号转换为数值并与阈值比较， 若该 数值大于阈值， 则向控制单元发送驱动信号驱动所述清洁单元进行清洗。
另外， 该气冷滴丸生产线还包括流化干燥包衣系统， 该系统主要包括流化床， 所 述冷却管道的末端通过真空管道与流化床的入口相连， 将经过气冷定型的滴丸素丸真 空上料输入流化床内流化干燥包衣； 所述流化床包括炉体， 炉体下方设有物料进料口， 在所述进料口的下方设有气流分布板， 所述气流分布板的底部与常温低湿送风系统的 出风管道相连通， 所述常温低湿送风系统将常温低湿气体经过出风管道送入流化床炉 体内， 并对内置于炉体内部的物料进行流化干燥处理； 所述常温低湿送风系统包括壳 体和设置在壳体内的低湿机组， 壳体上设有进风管道和出风管道， 空气从进风管道进 入壳体后经低湿机组处理后经出风管道输入所述炉体； 所述低湿机组由多个装置串联 而成， 沿气流的流入方向依次包括除尘装置、 除湿装置、 送风装置、 加热装置、 过滤 装置和高效过滤装置； 所述的常温低湿送风系统还包括用于气流回收的回风管道， 两 端分别与所述炉体和壳体相连。
根据需要， 所述流化床的干燥温度为 -20°C - 100°C， 干燥时间为 1-4小时； 进一步 地， 所述流化床优选采用梯度升温干燥法， -20-30°C形成流化态， 15-35 °C干燥 10- 120 分钟， 35-55 °C干燥 10-60分钟， 55- 100 °C干燥 0-60分钟； 更进一步地， 最优选 0-20 °C 形成流化态， 25 °C干燥 60分钟， 45 °C干燥 30分钟， 55 °C干燥 0-30分钟。
为了有效检测含水量， 所述的流化床内还设有用于监测微丸含水量及粒径分布情 况的在线检测装置。 综上所述， 本发明将振动滴制、 空气冷却与流化干燥包衣结合为一体， 并应用于 滴丸制剂及滴丸胶囊制剂， 满足了滴丸制备中对高速滴制、 制备微丸能力以及提高载 药量的要求， 成倍提高滴丸载药量， 大幅度降低辅料用量和服用剂量； 操作工序简化， 完全无有机溶剂残留； 满足包括缓释包衣、 薄膜包衣和包糖衣在内的不同工艺要求。 真正达到低能耗、 高速、 高效、 高载药量， 具备更广泛的可滴制范围。
下面结合附图和具体实施例， 对本发明的技术方案进行详细地说明。 附图说明
图 1为本发明整体结构示意图；
图 2为本发明滴盘剖视图；
图 3为图 2的 A局部结构放大图；
图 4为本发明制冷装置结构示意图；
图 5为本发明气体回收装置的结构示意图；
图 6为本发明在线清洗设备的整体结构示意图；
图 7为本发明在线清洗设备的控制框图；
图 8为本发明流化床的整体结构示意图。 具体实施方式
图 1是本发明整体结构示意图。 如图 1所示， 本发明提供一种气冷滴丸生产线， 包括滴丸系统、 气冷循环系统和控制系统， 滴丸系统包括化料罐 100和与其相连的滴 头 200， 所述化料罐 100与滴头 200之间设有振动装置 300， 振动装置带动滴头上下振 动， 产生的振动剪切力， 将滴头中流出的药液剪切成滴， 落入气冷循环系统冷却后形 成滴丸， 所述滴头上设有在线监测装置， 该装置包括脉冲信号发射机构， 所述脉冲信 号发射机构的发射频率与所述振动装置的振动频率相同， 控制系统根据在线监测装置 的监测结果， 控制调节滴制参数。 所述滴制参数包括： 所述频闪灯和振动装置的振动 频率： 50-300HZ,优选 90-200Hz， 最优 130-140HZ; 滴制速度： 10-40Kg/hr,优选 12-30 Kg/hr, 最优； 15-25 Kg/hr; 滴制加速度： 1-20G, 优选 3-10G, 最优 3.5-4.5G; 滴制压 力: 0.5-4.0Bar， 优选 1.0-3.0Bar， 最优 1.8Bar; 滴头温度： 70-200 °C , 优选 70-100°C， 最优 75-85 °C。
根据需要， 所述在线监测装置设置在所述滴头下方的侧面； 所述脉冲信号发射机 构为频闪灯 201， 所述频闪灯和振动装置的振动频率相同。 为了便于观察和记录， 所 述在线监测装置还可以包括与频闪灯对应设置的摄像头（图中未示出）， 摄像头与频闪 灯处于同一水平面上， 并与频闪灯照射路线呈 15 ° -145 ° 夹角。
也就是说， 本发明所采用的振动滴制， 主要是将熔融药液加压输送至滴头， 利用 磁力 /电动或气动振动原理， 使滴头以设定频率、 波形及振幅上、 下振动， 使振动剪切 力作用于液柱， 使其形成液滴， 通常情况下， 振动频率在 50-300HZ之间。 可以根据需 要采用磁力或电动振动的方式， 具有振动频率高， 振幅小的特点， 适合低黏度物料的 高速滴制。 一般情况下， 气动振动的方式， 振动频率， 振幅大。 当物料黏度超过 800cp (厘泊） 时， 电动方式则无法将物料有效切割。 造成滴头堵塞， 影响滴丸制备时， 可 采用气动振动方式。
为了消除料液输送过程中，由于料液涌动产生的压力脉冲对滴制过程产生的影响， 保证送料平稳， 所述的化料罐 100和滴头 200之间还设有缓冲罐 500。 缓冲罐 500设 有压缩空气进口， 通过压力管道与气泵相连， 压力管道上设有压力调节阀， 使缓冲罐 内药液保持恒压供给。 所述缓冲罐设有液位计， 用于控制进料速度； 缓冲罐还设有保 温层， 采用水浴、 油浴及电伴热保温； 并有温度传感器监测料液温度； 缓冲罐内设有 可调节搅拌速度的搅拌桨。 罐内传感器均可配置为接触或非接触式。 罐体材料可采用 304， 316L或其它可直接与产品接触的耐热材料。
图 2为本发明滴盘剖视图； 图 3为图 2的 A局部结构放大图。 如图 2并结合图 3 所示， 本发明的滴头 200主要包括有滴盘 210， 滴盘 210上设有多个滴孔 220， 滴孔 220在滴盘 210的圆周方向上等距离间隔设置。 如图 4所示， 滴孔 220由圆柱腔 221、 圆锥腔 222和直管腔 223组成， 液滴从直管腔 223的末端滴下。 在所述滴盘 210朝向 冷却罐 600的侧面上， 在直管腔 223出口的外围开设有凹形环槽 230。 由于直管腔 223 出口的孔径 DO通常为 0.1-5mm， 所述凹形环槽 230的内径 Dl=D0+0.4mm， 外径 D2 1.5毫米， 槽深 h为 0.5-5mm。 另外， 圆柱腔 221的直径 d为 0.5-lmm， 圆锥腔 222 的锥度为 20° -170° ， 滴盘 210的总厚度 A为 6mm， 直管腔 223的高度 H= ( 0.5-6) DOo 通过在滴孔 220的外围开设凹形环槽 230， 可以防止在黏稠液体高速喷出时， 滴 孔 220的周围有残余的药液堆积， 最终导致滴孔 220的堵塞或影响滴制。
滴头 200可以选择直接暴露， 为了保持药液温度恒定， 滴头外部也可以选择设置 保温腔， 使滴头的温度保持在 70-20CTC左右。 保温腔的外层设有隔热材料， 内层设有 蒸汽加热装置或红外加热装置， 以避免温度变化导致的药液粘稠度变化从而影响滴制 效果。 保温腔的下方设有开口， 开口的位置与滴头的出口位置对应设置， 开口的大小 与滴头的宽度对应设置。 保温腔内部可设计为带有一定的圆弧角度， 可比方形内腔死 角更少， 更易于清洁； 保温腔下端开口， 以保证滴丸的正常下落。
同时在滴头 200的侧下方， 配置了频闪灯 201， 以用于监测滴丸的滴制情况。 通 过同步频闪原理， 操作者可以仅需目视， 即可实时观察出高速下落状态下， 当然， 为 了观察记录方便， 也可以通过摄像头对图像进行实时监测。 通过在某一振动频率下， 如： 50Hz以上的滴制速度时， 对滴丸的外观形状， 实现滴制状态的实时监控及准确调 节。 也就是说， 在滴制过程的同时， 利用振动波形作为 PAT的监测指标， 可测定滴丸 的粒径分布情况， 并可通过频闪装置对滴丸的流化状态进行实时监控。 通过调节振动 参数， 可提高载药量至 50%以上， 辅料大幅度减少。 通过调节振动参数， 可在 0.2mm-3mm间调整滴丸直径，并可生产出能更好地满足胶囊灌装要求的小型中药滴制 微丸。 本发明采用的频闪实时检査和在线监控技术， 使得滴丸产品收率由传统的 70% 提高到 95%以上。
结合图 1所示， 本发明的气冷循环系统包括： 冷却管道 600， 以及与所述冷却管 道 600连接并对冷却管道制冷的制冷装置。 所述的冷却管道 600设置在滴丸装置的滴 头 200的正下方， 所述冷却管道 600可以为直桶型或螺旋型管道， 根据需要， 所述冷 却管道 600的长度为 5m- 10m， 优选的长度为 6m。 所述冷却管道 600外设有夹层 610， 所述夹层 610下部通过连通口 601与冷却管道 600内部连通。
图 4为本发明制冷装置结构示意图。 如图 4所示， 所述冷风制冷装置包括： 冷风 制冷装置 4， 所述的冷风制冷装置包括冷库 41， 所述冷库 41的出风口与冷却管道 600 的冷风进风口相连通， 使冷风在冷却管道 600内腔中循环上升， 所述冷却管道 600的 冷风进风口与遂平面夹角 a为 0° -90 ° 。 为了进一步实现快速冷却， 所述的制冷装置 还包括冷阱制冷装置 5， 所述冷阱制冷装置 5包括： 装有冷媒的冷媒储罐 51， 以及对 冷媒储罐 51 内的冷媒进行制冷的制冷机 52和换热器 53， 所述冷媒储罐 51的冷媒出 口通过泵 54与所述夹层 610上部设置的冷媒入口相连， 冷媒通过冷媒入口输入夹层 610内， 从夹层 610上部传输至夹层 610下部并传输到冷却管道 600内腔中； 所述冷 媒在冷却管道 600的内腔中与冷风同时循环上升， 并与通过冷却管道 600顶部连接的 气体回收装置 6排放或回收冷媒和冷风。 冷媒通常采用： 氮气、 氩气或二氧化碳等。
图 5为本发明气体回收装置的结构示意图。 如图 5并结合图 4所示， 具体地说， 气体回收装置 6包括： 气体回收机 61、 第一阀门 62、 第二阀门 63和分离机 64， 所述 第一阀门 62控制的管道一端与冷却管道 600连通， 另一端与大气连通； 第二阀门 63 控制的管道一端与冷却管道 600连通， 另一端通过气体回收机 61与分离机 64连接， 如图 5所示， 所述气体回收机 61包括： 气体排放管 611、 涡流风机 612、 气体回收管 613、 气体回收箱 614， 当所述第二阀门 63打开时， 所述涡流风机 612工作通过所述 气体排放管 611抽取冷却管道 600中的气体， 并将收取收集的气体通过所述气体回收 管 613排入到所述气体回收箱 614中； 所述分离机 64与所述气体回收箱 614连接。
当冷媒为无害气体时， 打开第一阀门 62同时关闭第二阀门 63， 使在冷却管道 600 的内腔中的冷媒与冷风同时循环上升之冷却管道 600的顶部并通过第一阀门 62连通的 管道排放到大气中； 当冷媒为有害气体时， 关闭第一阀门 62的同时打开第二阀门 63， 使在冷却管道 600内腔中的冷媒与冷风同时循环上升至冷却管道 600的顶部并通过第 二阀门 63连通的管道回收到气体回收机 61中， 通过分离机 64进行分离， 并且分别将 分离后的冷风输送到冷库 41中， 冷媒输送到冷媒储罐 51中。
图 6为本发明在线清洗设备的整体结构示意图。 如图 6所示， 为了保持清洁， 所 述滴丸气冷生产线还包括： 在线清洗设备， 该设备包括： 清洗单元 10、 清洁监测控制 单元 11、升降驱动单元 12和升降单元 13， 所述清洁单元 10为喷淋头或带有清洁布的 喷淋头。所述清洁监测控制单元通过升降驱动单元驱动升降单元带动清洁单元 10在冷 却管道 600内升降， 所述升降单元设置在冷却管道 600顶部的外侧。 其中， 所述升降 单元包括： 清洁单元支撑架 131、 清洁管道 132、 清洁管道支撑架 133、 清洁管道收纳 盘 134、 密封接管和在线清洁监测装置， 如： 摄像头。 所述清洁管道支撑架 133使清 洁管道 132延伸到冷却管道 600内部。 所述清洁单元支架 131包括多个支撑轮 1311， 每一个所述支撑轮 1311与冷却管道 600内侧壁抵顶， 所述清洁单元 10与所述清洁管 道 132延伸到冷却管道 600内部的一端连接， 并通过清洁单元支撑架 131使清洁单元 10延冷却管道 600中心升降。所述密封接管 135的一端与清洁管道 132的另一端连接， 用于将清洁液导入所述清洁管道 132内。
更具体地， 如图 6所示， 在线清洗设备的升降驱动单元包括： 电机 121、 驱动轮 122、 链轮 123、 皮带 124和张紧轮 125， 所述电机 121与驱动轮 122连接， 所述驱动 轮 122通过皮带 124与链轮 123连接，所述链轮 123与所述清洁管道收纳盘 134连接， 所述清洁监测控制单元 11与电机 121连接；张紧轮 125位于链轮 123与驱动轮 122之 间， 并且通过皮带 124与链轮 123和驱动轮 122连接。 当然除了本发明的升降驱动单 元所记载的具体结构外， 本领域技术人员还可以根据实际需要利用其它结构的升降驱 动单元完成驱动升降工作。
图 7为本发明在线清洗设备的控制框图。如图 7所示，所述在线清洁监测装置 136 包括： 图像采集单元 1361和计算单元 1362， 所述图像采集单元 1361设置于所述清洁 单元 10上， 所述图像采集单元 1361为摄像头， 用于采集冷却管道 600中的实时图像， 将图像信号发送到计算单元 1362， 所述计算单元 1362根据该图像信号转换为数值并 与阈值比较， 若该数值大于阈值， 则向清洁监测控制单元 11发送驱动信号驱动所述清 洁单元 10进行清洗。
综上所述并结合图 6和图 7， 本发明在线清洗设备的工作过程是这样的： 首先， 图像采集单元 1361实时采集冷却管道 600中的图像，并将采集到的图像发送的计算单 元 1362; 其次， 所述计算单元 1362根据采集到的图像将其转换为数值， 并且与存储 在计算单元 1362中的阈值进行比较， 若该数值大于阈值则进入清洗程序中， 否则图像 采集单元 1361继续进行实施采集图像；再次，计算单元 1362计算出清洗冷却管道 600 所需要清洗液的类型并向清洁监测控制单元 11发送驱动信号； 另外， 计算单元通过所 取得数值与存储在计算单元 1362中的污染物阈值比较，得出污染物的种类同时计算出 清洗相应污染物的清洗液的类型；而后，所述清洁监测控制单元 11根据计算单元 1362 发出的信号， 向滴制系统发出停止信号， 停止滴丸工作后， 分别驱动升降驱动单元 12 和阀门 142， 使清洁单元 10延冷却管道 600中心轴自上而下运行并喷淋清洗液； 当清 洁单元 10移动至冷却管道 600下部时， 清洁工作结束， 清洁监测控制单元 11分别控 制升降驱动单元 12和阀门 142， 控制清洁单元 10停止喷淋并返回冷却管道 600顶端 后反复执行清洗工作， 直到清洗干净为止。
图 8为本发明流化床的整体结构示意图。 如图 8并结合图 1所示， 该气冷滴丸生 产线还包括流化干燥包衣系统 700， 该系统主要包括流化床 710， 所述流化床 710包括 炉体， 炉体下方设有物料进料口 711， 所述冷却管道 600 的末端通过真空管道与流化 床 710的进料口 711相连， 将经过气冷定型的滴丸素丸从进料口 711处真空上料输入 流化床内流化干燥包衣。 在所述进料口 711 的下方设有气流分布板 712， 气流分布板 712上设有通孔， 常温低湿送风系统 720通过管道与炉体相互连通， 进风位置位于气 流分布板 712的下方， 向上吹送。 通过设置在气流分布板 712上的通孔， 既可以使气 流通过， 又可以有效防止炉体内的物料下落遗漏。
常温低湿送风系统 720包括壳体 721和设置在壳体内的低湿机组 722， 壳体上设 有进风口 723和出风管道 724。 空气从进风口 723进入壳体后经低湿机组 722处理后 经出风管道 724从炉体进风口 725输入炉体内部， 并对内置于炉体内部的物料进行流 化干燥处理。 另外， 常温低湿送风系统 720还包括用于气流回收的回风管道 726， 两 端分别与所述炉体和壳体相连。 所述低湿机组 722为多种处理装置的组合， 按照图 8 中箭头所示的气流方向依次包括除尘装置、 除湿装置、 送风装置、 加热装置、 过滤装 置和高效过滤装置。 当流化床工作时， 先通过炉体上方的进料口 711 真空上料， 再由炉体进风口 725 通入经低湿机组 722干燥加热过滤压缩等工艺处理过的气体， 被处理后的气体湿度 5g/kg, 喷射压力为 1一 4bar， 温度为 -20-100 °C， 优选 20-60 °C。 使物料流化干燥至湿度 为 4%时进行包衣， 然后通过卸料装置卸料将流化干燥包衣后的成品输出，废气从排风 管道 727排出。
根据需要， 通常情况下， 所述流化床的干燥温度为 -20°C-100°C， 干燥时间为 1-4 小时。 为了保持滴丸处于流化状态， 解决滴丸粘连的问题同时提高生产效率， 所述流 化床优选采用梯度升温干燥法， -20-30°C形成流化态， 15-35 °C干燥 10-120分钟， 35-55°C 干燥 10-60分钟， 55-100°C干燥 0-60分钟； 最优选 0-20°C形成流化态， 25 °C干燥 60 分钟， 45°C干燥 30分钟， 55°C干燥 0-30分钟。 为了有效检测滴丸水分便于控制， 所 述的流化床内还设有用于监测微丸含水量及粒径分布情况的在线检测装置 800， 该在 线水份检测装置可以采用水分传感器或者探头之类的现有检测部件，由于为现有技术， 因此在此不再赘述。
作为滴制冷却及流化干燥包衣的一体机， 增加的流化干燥， 解决了空气冷却设备 制备的滴丸在存放过程中， 可能出现的粘连及成分析出的问题， 也保证了滴丸水分可 达到稳定值， 提高了设备载药及包衣的均匀性。 喷射热熔药液进行载药包裹， 可进一 步提高滴丸载药量； 也可使用该设备喷射进行滴丸包衣， 以满足不同工艺要求， 如： 缓释包衣， 薄膜包衣， 包糖衣等。
结合图 1和图 4所示， 具体来说， 本发明的工作过程是这样的： 利用缓冲罐 500 推送药液， 将已熔化的药液输送到带有保温腔的滴头 200中， 所述的滴头具有与保温 腔 210底部开口相同方向的出口， 确保药液能够从滴头底部滴出。 利用压力， 使混合 药液从滴头 200的底部出口流出。 根据所需滴丸的大小， 调节压力或气动或电动振动 滴头的振动参数， 使从滴头流出的药柱被切割成所需直径的药滴。 其中振动加速度 0-llOg (正弦）， 振动幅度 ( 0-25.4mm
同时启动气体制冷， 利用低温使滴出的药滴在冷却管道 600内冷却凝固成固态颗 粒， 并在冷却管道下端进行收集。 冷却管道 600的上端口与滴头 200的保温腔下端的 开口密封连通， 冷却管道 600的下端为与滴丸收集桶相对应的开口结构。
冷库 41 将制造出来的冷风通过冷风进风口进入到冷却管道 600 的内腔中循环上 升， 同时冷媒储罐 51将冷媒通过冷媒入口输入到夹层 610中， 此时夹层 610中冷媒的 流向为由上而下， 并且通过该夹层 610与冷却管道 600连通的连通口 601进入到冷却 管道 600的内腔， 与冷却管道 600内腔中的冷风混合并且循环上升， 当冷媒与冷风的 混合气体上升至冷却管道顶端时， 通过气体回收装置 6分别将冷风和冷媒回收至冷库 41或冷媒储罐 51 中， 或者通过气体回收装置 6将该混合气体排放至大气中， 具体的 排放过程请参见前述内容。
由于冷却空气与冷却管道 600之间呈一定角度直接吹入， 冷风和冷媒在冷却管道 600 中形成层流， 使连续滴出的药滴获得少量较低温度的气体的吹扫， 保持一定的距 离， 避免滴丸在此区域黏连， 影响后续的成型。
随后， 冷却管道 600末端通过管道连接至流化干燥包衣系统 700， 调节进风及排 风风量， 并控制温度范围， 干燥后的小丸通过真空负压出料， 进行筛分后重新加入流 化床， 调节进风及排风风量， 按工艺要求进行载药或薄膜包衣； 包衣后设备还可连接 胶囊填充机进行灌注， 胶囊检重机进行逐粒检重。 因此， 根据实际应用需要， 在图 1 所示整体结构的基础上， 本发明所提供的气冷滴丸生产线还可以配置胶囊填充机及胶 囊检重装置。 上述装置均为现有技术， 在此不再赘述。 以下通过最佳实施示例， 对本发明的设备进一步加以详细说明。 该实例仅用于说 明本发明， 而对本发明没有限制。
实施例一 制备复方丹参滴丸
( 1 )化料步骤：取丹参三七提取物 600g，冰片 5g，以及聚乙二醇 6000 ( PEG-6000) 辅料 2000g。 先将 PEG-6000加入化料罐中， 加热至 90°C， 预先熔融， 再加入丹参三 七提取物到均质机中 5000rpm均质混合， 时间 200min， 然后 lOOOOrpm均质化料， 时 间 lOOmin, 温度 100°C， 得混合均匀成液体。
( 2)滴制步骤： 调节气动振动滴头的振动频率为 300Hz， 保温室采用蒸汽夹套保 温， 温度控制 200°C， 滴制速度与步骤 （1 ) 化料速度匹配， 滴制压力为 3Bar， 滴制速 度 10kg/hr， 滴制加速度 1G。
( 3 )冷凝步骤： 由气泵通过管路向化料罐中送气， 使已熔化的上述液体向滴头流 入并从滴头底部滴出到冷却管道内， 冷却管道与地面垂直； 启动冷气， 使冷却温度达 到 - 120°C， 冷却空气进口与水平面的夹角为 30 ° ， 并使冷气在冷却管道内循环流动， 使从滴出的药液滴在冷却管道内冷却凝固成固态滴丸， 从冷却管道下端的管道可连接 至流化床部分进行流化干燥及载药包衣。
( 4 )干燥步骤：然后将滴丸进行流化干燥及载药包衣，待物料在床体内 -20°C -30°C 形成较好的流态后， 50°C干燥 2小时干燥 120分钟， 素丸水分控制在 5.0%， 得到中间 体素丸。 ( 5 ) 包衣步骤： 按照包衣投料量和处方计算包衣粉用量， 包衣液的浓度为 10%， 配制包衣液， 搅拌 45分钟。 设定进风温度为 40°C将合格滴丸投入流化床后， 提高设 定进风温度至 48°C， 待物料温度达到 38 °C后， 开始包衣。 包衣过程中物料温度控制在 35-45°C， 包衣完成后降温至 30°C以下出料， 筛丸， 粒径为 2.0mm滴丸。 实施例二 制备丹参滴丸
( 1 ) 化料步骤： 取丹参提取物 600g， 加水 60g， 加聚乙二醇 6000辅料 1500g， 放入化料罐中加热至 90°C， 采用低速均质 （3200rpm) 混合物料， 混合完成后， 提高 均质速度至 5000rpm进行化料， 时间 6分钟。 使其完全融化混合均匀成液体。
( 2) 滴制步骤： 调节气动振动滴头的振动频率为 50Hz， 保温室采用红外加热保 温， 温度控制 70°C， 滴制压力为 4Bar， 滴制速度 40kg/hr， 滴制加速度 3G。
( 3 )冷凝步骤： 由气泵通过管路向化料罐中送气， 使已熔化均匀的上述液体向滴 头流入并从滴头底部滴出到冷却管道内， 滴制压力 0.18MPa， 在上述液体滴出的同时 启动冷气， 使冷却温度达到 -10°C， 并使冷气在冷却管道内循环流动， 冷却空气进口与 水平面的夹角为 45 ° ， 使从滴头滴出的药液滴在冷却管道内冷却凝固成固态滴丸， 并 从冷却管道下端的管道连接至流化床部分。
( 4)流化步骤： 然后将滴丸进行流化干燥及载药包衣， 待物料在床体内形成较好 的流态后， 升温至 25°C干燥 60分钟， 再升温至 45°C干燥 30分钟， 继续升温至 55°C 干燥 30分钟， 然后降温至 30°C以下出料。 素丸水分控制在 3.0-7.0%， 得到中间体素 丸。
( 5 ) 包衣步骤： 按照包衣投料量和处方计算包衣粉用量， 包衣液的浓度为 18%， 配制包衣液， 搅拌 45分钟。 设定进风温度为 25 °C将合格滴丸投入流化床后， 提高设 定进风温度至 48°C， 待物料温度达到 38 °C后， 开始包衣。 包衣过程中物料温度控制在 35-45°C， 包衣完成后降温至 30°C以下出料， 筛丸， 粒径为 1.0-2.0mm滴丸。 实施例三 制备复方丹参滴丸
( 1 )化料步骤：取丹参三七提取物 600g，冰片 5g，以及聚乙二醇 6000辅料 2000g。 先将聚乙二醇加入化料罐中， 加热至 80°C， 预先熔融， 再加入丹参三七提取物， 投入 到均质机中 2500rpm均质混合， 时间 1 OOmin， 然后 6000rpm均质化料， 时间 20min， 温度 100 °C， 混合均匀成液体。
( 2) 滴制步骤： 调节气动振动滴头的振动频率为 90HZ, 加速度 3.5G, 滴制速度 12Kg/hr， 滴制压力 1.0Bar。 保温室采用蒸汽夹套保温， 温度控制 70°C，
( 3 )冷凝步骤： 由气泵通过管路向化料罐中送气， 使已熔化的上述液体向滴头流 入并从滴头底部滴出到冷却管道内， 冷却管道与地面垂直； 启动冷气， 使冷却温度达 到 -100°C， 冷却空气进口与水平面的夹角为 90° ， 并使冷气在冷却管道内循环流动， 使从滴出的药液滴在冷却管道内冷却凝固成固态滴丸， 从冷却管道下端的管道可连接 至流化床部分进行流化干燥及载药包衣。 具体来说， 20°C形成流化态， 25 °C干燥 60 分钟， 45 °C干燥 30分钟， 55 °C干燥 30分钟。 实施例四 制备复方丹参滴丸
( 1 ) 化料步骤： 将复方丹参提取物与阿拉伯胶和乳糖 =1: 1 的混合物投入到均质 机中 5000rpm均质混合， 时间 200min， 然后 lOOOOrpm均质化料， 时间 lOOmin, 温度 100 °C， 得中间体料液；
( 2) 滴制步骤： 中间体料液经滴头振动滴制， 振动频率为 200Hz， 滴制压力为 4.0Bar， 滴头温度 100°C， 滴制速度与步骤 （1 ) 化料速度匹配， 为 15kg/hr;
( 3 ) 冷凝步骤： 滴出的药滴在冷却气体中快速冷却凝固成直径为 4.0mm的滴丸 素丸， 所述的冷却气体温度为 -300°C。
从冷却管道下端的管道可连接至流化床部分进行流化干燥及载药包衣。具体来说， 0°C形成流化态， 25 °C干燥 60分钟， 45 °C干燥 30分钟， 55 °C干燥 30分钟。 实施例五 制备复方丹参滴丸
取复方丹参提取物 75g， 冰片 7.5g， 乳糖醇 165g， 制备成复方丹参微滴丸， 制备 方法如下：
( 1 ) 化料步骤： 将复方丹参提取物与乳糖醇投入到均质机中 2500rpm均质混合， 时间 lOOmin, 然后 6000rpm均质化料， 时间 50min， 温度 80°C， 得中间体料液； ( 2) 滴制步骤： 中间体料液经滴头振动滴制， 振动频率为 130Hz， 滴制压力为
1.8Bar， 滴头温度 140°C， 滴制速度与步骤 （1 ) 化料速度匹配， 为 25kg/hr;
( 3 ) 冷凝步骤： 滴出的药滴在冷却气体中快速冷却凝固成直径为 lmm的滴丸素 丸， 所述的冷却气体温度为 -100°C。
( 4) 干燥步骤： 采用流化干燥设备干燥， -20°C干燥 4小时， 得干燥滴丸素丸。 ( 5 ) 包衣步骤： 所述的干燥素丸在流化床中包衣， 包衣材料与素丸重量比为 1 :
25， 包衣液浓度为 10%， 温度 40°C包衣即得包衣滴丸。 实施例六 制备复方丹参滴丸
取复方丹参提取物 75g， 冰片 7.5g， 聚乙二醇 8000165g， 制备成复方丹参微滴丸， 制备方法如下：
将复方丹参提取物粉末加水后， 于 60°C搅拌 10分钟以上， 得到药物预混料。
(1) 化料步骤：
将复方丹参提取物与聚乙二醇 8000 投入到均质机中 2500rpm 均质混合， 时间 lOOmin, 然后 6000rpm均质化料， 时间 50min， 温度 80°C， 得中间体料液；
(2) 滴制步骤： 中间体料液经滴头振动滴制， 振动频率为 140Hz， 滴制压力为 0.5Bar， 滴头温度 100°C， 滴制速度与步骤 （1) 化料速度匹配， 为 30kg/hr;
(3) 冷凝步骤： 滴出的药滴在冷却气体中快速冷却凝固成直径为 2mm的滴丸素 丸， 所述的冷却气体温度为 -100°C。
(4) 干燥步骤： 采用流化干燥设备干燥， 100°C干燥 1小时， 得干燥滴丸素丸。
(5) 包衣步骤： 所述的干燥素丸在流化床中包衣， 包衣材料与素丸重量比为 1: 25， 包衣液浓度为 10%， 温度 40°C包衣即得包衣滴丸。 实施例七 制备复方丹参滴丸
取复方丹参提取物 90g， 冰片 2g， 聚乙二醇 1000270g， 制备成复方丹参微滴丸， 制备方法如下：
将复方丹参活性成分粉末加水后， 于 30°C搅拌 10分钟以上， 得到药物预混料。
(1) 化料步骤： 将复方丹参提取物与聚乙二醇 1000投入到均质机中 2500rpm均 质混合， 时间 lOOmin, 然后 6000rpm均质化料， 时间 20min， 温度 100°C， 得中间体 料液；
(2) 滴制步骤： 中间体料液经滴头振动滴制， 振动频率 100HZ, 加速度 1G， 滴 制速度 10Kg/hr， 滴制压力 l.OBar, 滴头温度 75°C。
滴制速度与步骤 （1) 化料速度匹配；
(3) 冷凝步骤： 滴出的药滴在冷却气体中快速冷却凝固成直径为 1.5mm的滴丸 素丸， 所述的冷却气体温度为 -80°C。
(4)干燥步骤： 干燥采用梯度升温干燥法， -20°C形成流化态， 15°C干燥 10分钟， 35°C干燥 10分钟， 得干燥滴丸素丸。
(5) 包衣步骤： 所述的干燥素丸在流化床中包衣， 包衣材料与素丸重量比为 1: 25， 包衣液浓度为 10%， 温度 40°C包衣即得包衣滴丸。 实施例八 制备复方丹参滴丸
取复方丹参提取物 100g， 冰片 5g， 聚乙二醇 4000和聚乙二醇 6000=1: 1 的组合 35g， 制备成复方丹参微滴丸， 制备方法如下：
将复方丹参提取物粉末加水后， 于 80°C搅拌 10分钟以上， 得到药物预混料。 ( 1 )化料步骤： 将复方丹参提取物与聚乙二醇 4000和聚乙二醇 6000=1: 1的组合 投入到均质机中 2500rpm均质混合，时间 lOOmin,然后 6000rpm均质化料，时间 80min， 温度 80°C， 得中间体料液；
( 2)滴制步骤： 中间体料液经滴头振动滴制， 振动频率 200HZ, 加速度 20G， 滴 制速度 40Kg/hr， 滴制压力 3.0Bar， 滴头温度 85 °C。
滴制速度与步骤 （1 ) 化料速度匹配；
( 3 ) 冷凝步骤： 滴出的药滴在冷却气体中快速冷却凝固成直径为 0.5mm的滴丸 素丸， 所述的冷却气体温度为 120°C。
( 4 ) 干燥步骤： 干燥采用梯度升温干燥法， 30°C形成流化态， 35 °C干燥 120 分钟， 55°C干燥 60分钟， 100°C干燥 60分钟， 得干燥滴丸素丸。
( 5 ) 包衣步骤： 所述的干燥素丸在流化床中包衣， 包衣材料与素丸重量比为 1 : 25， 包衣液浓度为 10%， 温度 40°C包衣即得包衣滴丸。 综上所述， 本发明采用振动剪切滴制， 提高滴丸成形速度及滴丸圆度， 并降低滴 丸重量差异； 在滴制的同时进行实时监控， 通过各项参数的调节， 提高滴丸产品 收率； 利用气冷方式实现了滴丸制备在高速滴制微丸的同时提高载药量， 大幅 度降低辅料用量和服用剂量； 避免传统液冷方式的有机溶剂残留。 本发明有效 避免传统滴丸设备存在的弊端， 真正达到低能耗、 高速、 高效、 高载药量， 具 备更广泛的可滴制范围， 极大提高生产速度和滴制效果。

Claims

权利要求书
1、 一种气冷滴丸生产线， 包括滴丸系统、 气冷循环系统和控制系统， 滴丸系统包 括化料罐和与其相连的滴头， 所述化料罐与滴头之间设有振动装置， 振动装置带动滴 头上下振动， 产生的振动剪切力， 将滴头中流出的药液剪切成滴， 落入气冷循环系统 冷却后形成滴丸， 其特征在于， 所述滴头上设有在线监测装置， 该装置包括脉冲信号 发射机构， 所述脉冲信号发射机构的发射频率与所述振动装置的振动频率相同， 控制 系统根据在线监测装置的监测结果， 控制调节滴制参数。
2、 如权利要求 1所述的气冷滴丸生产线， 其特征在于， 所述在线监测装置设置在 所述滴头下方的侧面；
所述脉冲信号发射机构为频闪灯， 所述频闪灯和振动装置的振动频率相同。
3、 如权利要求 2所述的气冷滴丸生产线， 其特征在于， 所述在线监测装置还包括 与频闪灯对应设置的摄像头， 摄像头与频闪灯处于同一水平面上， 并与频闪灯照射路 线呈 15 ° -145 ° 夹角。
4、 如权利要求 3所述的气冷滴丸生产线， 其特征在于， 所述滴头主要包括滴盘， 滴盘上设有多个滴孔， 滴孔的外围开设有凹形环槽；
所述凹形环槽的内径 =滴孔内径 +0.4毫米， 外径 1.5毫米， 槽深为 0.5-5毫米。
5、 如权利要求 2所述的气冷滴丸生产线， 其特征在于， 所述滴制参数主要包括： 所述频闪灯和振动装置的振动频率： 50-300HZ,优选 90-200Hz， 最优 130-140HZ; 滴制速度： 10-40Kg/hr， 优选 12-30 Kg/hr， 最优; 15-25 Kg/hr;
滴制加速度： 1-20G, 优选 3-10G, 最优 3.5-4.5G;
滴制压力： 0.5-4.0Bar, 优选 1.0-3.0Bar， 最优 1.8Bar;
滴头温度： 70-200°C， 优选 70-100°C， 最优 75-85 °C。
6、 如权利要求 1所述的气冷滴丸生产线， 其特征在于， 所述气冷循环系统包括： 冷却管道， 以及与所述冷却管道连接并对冷却管道制冷的制冷装置， 所述冷却管道外 设有夹层， 所述夹层下部与冷却管道内部连通；
所述制冷装置包括： 冷风制冷装置和冷阱制冷装置， 其中：
所述冷风制冷装置包括： 冷库， 所述冷库的出风口与冷却管道的冷风进风口相连 通， 使冷风在冷却管道内腔中循环上升；
所述冷阱制冷装置包括： 装有冷媒的冷媒储罐， 以及对冷媒储罐内的冷媒进行制 冷的制冷机和换热器，所述冷媒储罐的冷媒出口与所述夹层上部设置的冷媒入口相连， 冷媒通过冷媒入口输入夹层内，从夹层上部传输至夹层下部并传输到冷却管道内腔中； 所述冷媒在冷却管道的内腔中与冷风同时循环上升，并通过冷却管道顶部排放或回收。
7、 如权利要求 6所述的滴丸气冷生产线， 其特征在于， 所述冷却管道为直桶型或 螺旋型管道， 其长度为 5- 10米； 优选为 6米。
8、如权利要求 6所述的滴丸气冷生产线，其特征在于，所述气冷循环系统还包括: 气体回收装置， 其包括： 第一阀门、 第二阀门、 气体回收机和分离机， 所述第一阀门 控制的管道一端与冷却管道连通， 另一端与大气连通； 第二阀门控制的管道一端与冷 却管道连通， 另一端通过气体回收机与分离机连接；
所述气体回收机进一步包括： 气体排放管、 涡流风机、 气体回收管、 气体回收箱， 当所述第二阀门打开时， 所述涡流风机工作通过所述气体排放管抽取冷却管道中的气 体， 并将收取收集的气体通过所述气体回收管排入到所述气体回收箱中。
9、 如权利要求 7所述的气冷滴丸生产线， 其特征在于， 所述冷却管道上设有在线 清洗设备， 包括： 清洗单元、 控制单元、 升降驱动单元和升降单元， 所述控制单元通 过升降驱动单元驱动升降单元带动清洁单元升降， 所述升降单元设置在冷却装置的冷 却管道顶部外侧。
10、 如权利要求 9所述的气冷滴丸生产线， 其特征在于， 所述升降单元包括： 清 洁单元支撑架、 清洁管道、 清洁管道支撑架、 清洁管道收纳盘和密封接管； 所述清洁 管道支撑架使清洁管道延伸到冷却管道内部； 所述清洁单元支架包括多个支撑轮， 每 一个所述支撑轮与冷却管道内侧壁抵顶， 所述清洁单元与所述清洁管道延伸到冷却管 道内部的一端连接， 并通过清洁单元支撑架使清洁单元延冷却管道中心升降； 所述密 封接管的一端与清洁管道的另一端连接， 用于将清洁液导入所述清洁管道内。
11、 如权利要求 10所述的气冷滴丸生产线， 其特征在于， 所述升降单元还包括： 在线监测装置， 所述在线监测装置包括： 图像采集单元和计算单元， 所述图像采集单 元设置于所述清洁单元上， 用于采集冷却管道中的实时图像， 将图像信号发送到计算 单元， 所述计算单元根据该图像信号转换为数值并与阈值比较， 若该数值大于阈值， 则向控制单元发送驱动信号驱动所述清洁单元进行清洗。
12、 如权利要求 1所述的气冷滴丸生产线， 其特征在于， 该气冷滴丸生产线还包 括流化干燥包衣系统， 该系统主要包括流化床， 所述冷却管道的末端通过真空管道与 流化床的入口相连，将经过气冷定型的滴丸素丸真空上料输入流化床内流化干燥包衣； 所述流化床包括炉体， 炉体下方设有物料进料口， 在所述进料口的下方设有气流 分布板， 所述气流分布板的底部与常温低湿送风系统的出风管道相连通， 所述常温低 湿送风系统将常温低湿气体经过出风管道送入流化床炉体内， 并对内置于炉体内部的 物料进行流化干燥处理；
所述常温低湿送风系统包括壳体和设置在壳体内的低湿机组， 壳体上设有进风管 道和出风管道， 空气从进风管道进入壳体后经低湿机组处理后经出风管道输入所述炉 体；
所述的常温低湿送风系统还包括用于气流回收的回风管道， 两端分别与所述炉体 和壳体相连。
13、 如权利要求 12所述的滴丸气冷生产线， 其特征在于， 所述低湿机组由多个装 置串联而成， 沿气流的流入方向依次包括除尘装置、 除湿装置、 送风装置、 加热装置、 过滤装置和高效过滤装置。
14、 如权利要求 13所述的气冷滴丸生产线， 其特征在于， 所述流化床的干燥温度 为 -20°C - 100°C， 干燥时间为 1-4小时。
15、 如权利要求 14所述的滴丸气冷生产线， 其特征在于， 所述流化床优选采用梯 度升温干燥法， -20-30°C形成流化态， 15-35 °C干燥 10- 120 分钟， 35-55 °C干燥 10-60 分钟， 55- 100 °C干燥 0-60分钟。
16、 如权利要求 15所述的滴丸气冷生产线， 其特征在于， 所述流化床采用梯度升 温干燥法， 最优 0-20°C形成流化态， 25 °C干燥 60分钟， 45 °C干燥 30分钟， 55 °C干燥
0-30分钟。
17、 如权利要求 10所述的气冷滴丸生产线， 其特征在于， 所述的流化床内还设有 用于监测微丸含水量及粒径分布情况的在线检测装置。
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