CN110638785A - Andrographolide dry suspension - Google Patents
Andrographolide dry suspension Download PDFInfo
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- CN110638785A CN110638785A CN201910934345.7A CN201910934345A CN110638785A CN 110638785 A CN110638785 A CN 110638785A CN 201910934345 A CN201910934345 A CN 201910934345A CN 110638785 A CN110638785 A CN 110638785A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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Abstract
The invention relates to the technical field of medicines, and in particular relates to an andrographolide dry suspension. The specific scheme is as follows: an andrographolide dry suspension comprises the following components: the traditional Chinese medicine composition comprises, by weight, 3-10 parts of andrographolide, 1-3 parts of microcrystalline cellulose, 301-3 parts of povidone K, 1-3 parts of gastric soluble materials, 1-5 parts of suspending agents, 0.01-5 parts of flavoring agents and 5-120 parts of ethanol. The andrographolide dry suspension prepared by the invention is easy to swallow, convenient to take, good in dissolution effect, free of bitter taste, and suitable for children, the old and patients with dysphagia.
Description
Technical Field
The invention relates to the technical field of medicines, and in particular relates to an andrographolide dry suspension.
Background
Andrographolide is diterpene lactone compound extracted from Andrographis paniculata Nees of Acanthaceae, is the main effective component of Andrographis paniculata Nees of natural plant, has the effects of removing heat and toxic substances, diminishing inflammation and relieving pain, has special curative effect on bacterial and viral upper respiratory tract infection and dysentery, and is known as natural antibiotic medicine. However, andrographolide is extremely bitter in taste, nausea caused by extremely bitter taste is a main adverse reaction in clinical use, tablets are generally coated, or medicines are filled into capsules, or dripping pills and other methods are used for shielding bitter taste, but the methods are not suitable for children, old people and patients with dysphagia to take the medicine. Furthermore, andrographolide is poorly soluble in water, and the general oral preparations do not improve the saturated solubility or dissolution rate of andrographolide, and cannot fully utilize the pharmacological activity of andrographolide, so that the improvement of the bioavailability of andrographolide is still limited.
Therefore, on the premise of ensuring the dissolution rate of andrographolide, it is necessary to modify andrographolide.
Disclosure of Invention
The invention aims to provide a preparation method of andrographolide dry suspension, which is easy to swallow, good in dissolving effect and free of bitter taste.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:
the invention provides an andrographolide dry suspension which comprises the following components: the traditional Chinese medicine composition comprises, by weight, 3-10 parts of andrographolide, 1-3 parts of microcrystalline cellulose, 301-3 parts of povidone K, 1-3 parts of gastric soluble materials, 1-5 parts of suspending agents, 0.01-5 parts of flavoring agents and 5-120 parts of ethanol.
Preferably, the gastric soluble material is one or more of Eudragit E, Eudragit RD 100 and acrylic resin IV; the suspending agent is one or more of xanthan gum, carrageenan, arabic gum, gelatin, sodium carboxymethylcellulose, croscarmellose sodium, polyvidone, pectin, guar gum and sodium alginate; the correctant is one or more of aspartame, sodium cyclamate, stevioside, citric acid, orange essence, and pineapple essence.
Preferably, the andrographolide dry suspension is prepared by the following steps:
(1) grinding andrographolide in a refining device, sieving, and mixing with microcrystalline cellulose to obtain mixed powder;
(2) putting the gastric-soluble material, the povidone K30 and the ethanol into a mixing device, and uniformly stirring to obtain a coating solution;
(3) adding the mixed powder obtained in the step (1) into a coating machine, spraying the coating liquid prepared in the step (2) on the mixed powder, and carrying out centrifugal granulation to obtain andrographolide particles;
(4) and (4) uniformly mixing the andrographolide particles prepared in the step (3) with a suspending agent and a flavoring agent to prepare the andrographolide dry suspension.
Preferably, in the step (1), the andrographolide is thinned and then passes through a 100-300-mesh sieve, and the grain size of the microcrystalline cellulose is 20-80 μm; in the step (2), the solid content in the coating liquid is 5-15%; in the step (3), the rotating speed of the coating machine is 100-400 r/min, the temperature is 40 +/-5 ℃, the spraying pressure of the coating liquid is 0.1-0.4 Mpa, and the spraying speed is 10-40 mL/min.
Preferably, refine the device including the grinding groove that is the bowl form and place the grinding ball at the grinding inslot, the grinding inslot portion is equipped with the round recess on week, be equipped with supporting mechanism in the recess, the grinding ball passes through the connecting rod and can dismantle the fixing on the supporting mechanism.
Preferably, the supporting mechanism comprises a circular ring frame and a shaft sleeve fixed at the axis of the circular ring frame through a plurality of connecting columns, a plurality of sliding blocks are uniformly distributed on the circumferential side wall of the circular ring frame, and the sliding blocks are matched with the grooves; the output of first motor of shaft liner connection, the top of grinding the groove is provided with the capping, the center department of capping is equipped with the messenger the hole that the axle sleeve stretches out, first motor can dismantle through a plurality of support column and fix the top of capping.
Preferably, a discharge port is formed in the bottom of the grinding groove, a discharge pipe is fixed on the discharge port, an electromagnetic valve is arranged on the discharge pipe, a screen is arranged in the discharge pipe and below the electromagnetic valve, and an electric valve and a dust concentration detector are sequentially arranged on the discharge pipe and below the screen; the dust concentration detector and the electric valve are respectively electrically connected with the controller.
Preferably, the outlet end of discharging pipe is linked together with the powder mixer, the exit of powder mixer is connected with the powder pipe, the other end of powder pipe is connected with multichannel rotary joint, be provided with the powder pump on the powder pipe, multichannel rotary joint's the other end is connected with a plurality of shunt tubes, a plurality of the shunt tubes stretch into in the capsule machine, stretch into in the capsule machine the tip of shunt tubes is provided with the powder shower nozzle.
Preferably, the capsule machine includes the capsule jar and sets up the swing mechanism on the lower position by middle part in the capsule jar, the top of capsule jar is provided with the liquid mixer, the bottom of liquid mixer is provided with the drain pipe, the other end of drain pipe is followed the top of capsule jar stretches into in the capsule jar, and stretch into in the capsule jar be provided with the atomizer on the mouth of pipe of drain pipe, be provided with the variable speed pump on the drain pipe, the atomizer is located the top of powder shower nozzle.
Preferably, the swing mechanism comprises an inward-concave material containing disc, a support column is fixed at the bottom of the outer side of the material containing disc, a rotating ball is fixed at the other end of the support column, the inner bottom of the coating tank is provided with a bearing column at a position corresponding to the rotating ball, a spherical groove matched with the rotating ball is formed in the bearing column, and the rotating ball is positioned in the spherical groove;
the coating tank is characterized in that a plurality of metal blocks are arranged on the outer side face of the material containing disc in a circle around the support, electromagnets are arranged at the inner bottom of the coating tank and at positions corresponding to the metal blocks, and the electromagnets are electrically connected with the controller respectively.
The invention has the following beneficial effects:
1. the andrographolide dry suspension prepared by the preparation method disclosed by the invention can be taken with water, is convenient to take, has a good taste-modifying effect on andrographolide, does not have bitter taste, is suitable for children, old people and patients with dysphagia to take, has a good dissolution effect, and can fully exert the drug effect of andrographolide. Specifically, the method comprises the following steps: the andrographolide is prepared by coating the mixed powder prepared from andrographolide and microcrystalline cellulose by adopting the coating solution prepared from the gastric-soluble material and povidone K30, namely, andrographolide particles are prepared by adopting a liquid and powder coating mode, and then the bitter taste of andrographolide is well covered by using the flavoring agent and the suspending agent.
2. Through the grinding groove and the grinding groove in the refining device disclosed by the invention, the grinding balls move circularly in the grinding groove to refine andrographolide as far as possible, the mixed powder is sprayed in a spray form through a powder spray head on a coating machine, and the coating liquid is sprayed after being atomized through a liquid mixer, so that the mixed powder is coated by the coating liquid, and the prepared andrographolide particles are uniform in size; the dissolution rate of the andrographolide dry suspension prepared from the refined andrographolide is greatly increased, the whole preparation process is time-saving and labor-saving, and continuous production can be realized.
Drawings
FIG. 1 is a schematic structural view of the present invention;
FIG. 2 is an enlarged view of a portion A of FIG. 1;
FIG. 3 is a view taken along line A-A of FIG. 1;
FIG. 4 is a top view of the detailing device without a slot cover;
FIG. 5 is a schematic view of a fastener structure;
in the figure: grinding groove 1, grinding ball 2, groove 3, connecting rod 4, ring frame 5, connecting column 6, shaft sleeve 7, sliding block 8, first motor 9, groove cover 10, hole 11, support column 12, fastener 13, discharge pipe 14, electromagnetic valve 15, screen 16, electric valve 17, dust concentration detector 18, powder mixer 19, powder pipe 20, multi-channel rotary joint 21, powder pump 22, shunt tube 23, powder spray head 24, coating tank 25, liquid mixer 26, atomizing spray head 27, variable speed pump 28, material containing disc 29, support column 30, rotating ball 31, bearing column 32, metal block 33, electromagnet 34 and blocking edge 35.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise indicated, the technical means used in the examples are conventional means well known to those skilled in the art.
1. The invention provides an andrographolide dry suspension which comprises the following components: the traditional Chinese medicine composition comprises, by weight, 3-10 parts of andrographolide, 1-3 parts of microcrystalline cellulose, 301-3 parts of povidone K, 1-3 parts of gastric soluble materials, 1-5 parts of suspending agents, 0.01-5 parts of flavoring agents and 5-120 parts of ethanol. Wherein: the gastric soluble material is one or more of Eudragit E, Eudragit RD 100 and acrylic resin IV; the suspending agent is one or more of xanthan gum, carrageenan, acacia, gelatin, sodium carboxymethylcellulose, croscarmellose sodium, polyvidone, pectin, guar gum and sodium alginate; the correctant is one or more of aspartame, sodium cyclamate, stevioside, citric acid, orange essence, and pineapple essence.
2. The invention also provides a method for preparing the andrographolide dry suspension, which comprises the following steps:
(1) grinding andrographolide in a refining device, sieving with a 100-300-mesh sieve, weighing 3-10 parts by weight of andrographolide after sieving with the mesh sieve, and uniformly mixing with 1-3 parts by weight of microcrystalline cellulose (MCC) with the particle size of 20-80 mu m to prepare mixed powder;
(2) putting 1-3 parts by weight of gastric soluble material, 1-3 parts by weight of povidone K30 and 5-120 parts by weight of 20-95% ethanol solution into a mixing device, and uniformly stirring to obtain a coating solution, wherein the solid content in the coating solution is 5-15%, and the preferable formula is as follows: the ethanol solution is selected to have the concentration of 85 percent; mixing a solid mixture obtained by mixing the gastric-soluble material and povidone K30 with 85% ethanol solution, and adding 10g of the solid mixture into every 100g of the ethanol solution in the 85% ethanol solution to prepare a dispersion; the solid content in the coating liquid is preferably 9-10%.
(3) Adding the mixed powder obtained in the step (1) into a coating machine, spraying the coating liquid prepared in the step (2) on the mixed powder, and carrying out centrifugal granulation to obtain andrographolide particles; the rotating speed of the coating machine is 100-400 r/min, the temperature is 40 +/-5 ℃, the spraying pressure of the coating liquid is 0.1-0.4 Mpa, and the spraying speed is 10-40 mL/min; it should be noted that: the spraying pressure of the coating liquid is the atomizing pressure of the coating liquid, and the spraying speed is the spraying speed of the coating liquid. The coating machine can be an existing centrifugal granulating coating machine on the market, and the coating machine disclosed by the invention can also be used.
(4) And (3) uniformly mixing the andrographolide particles prepared in the step (3) with 1-5 parts by weight of suspending agent and 0.01-5 parts by weight of flavoring agent to prepare the andrographolide dry suspension.
Wherein the gastric soluble material is one or more of Eudragit E, Eudragit RD 100 and acrylic resin IV; the suspending agent is one or more of xanthan gum, carrageenan, arabic gum, gelatin, sodium carboxymethylcellulose, croscarmellose sodium, polyvidone, pectin, guar gum and sodium alginate; the correctant is one or more of aspartame, sodium cyclamate, stevioside, citric acid, orange essence, and pineapple essence.
3. The invention further provides a system for preparing the andrographolide dry suspension, which comprises a refining device, a powder mixer, a liquid mixer and a coating machine; the powder mixer and the liquid mixer are existing equipment and are mainly used for mixing powdery substances and liquid substances respectively.
The concrete structure of the refining device and the coating machine is as follows:
the refining device comprises a grinding groove 1 and grinding balls 2, wherein the grinding groove 1 is of a bowl shape, the grinding balls 2 are placed in the grinding groove 1, a circle of groove 3 is circumferentially arranged in the grinding groove 1, a supporting mechanism is arranged in the groove 3, and the grinding balls 2 are detachably fixed on the supporting mechanism through a connecting rod 4. The supporting mechanism comprises a circular ring frame 5 and a shaft sleeve 7 fixed at the axis of the circular ring frame 5 through a plurality of connecting columns 6, a plurality of sliding blocks 8 are evenly distributed on the outer side wall of the circular ring frame 5, and the sliding blocks 8 are matched with the grooves 3. The shaft sleeve 7 is fixedly connected with the output end of the first motor 9, and the top of the grinding groove 1 is provided with a groove cover 10, so that dust is prevented from entering the grinding groove 1 and polluting medicines; a hole 11 for extending the shaft sleeve 7 is formed in the center of the slot cover 10, and the first motor 9 is detachably fixed on the top of the slot cover 10 through a plurality of support columns 12, that is, the support columns 12 can be fixed on the slot cover 10 through bolts. It should be noted that: recess 3 sets up in the circumference that is close to grinding groove 1 exit, slider 8 can slide in recess 3, when rotating axle sleeve 7, ring frame 5 drives grinding ball 2 through connecting rod 4 and is circular motion in grinding groove 1, first motor 9 starts promptly, drive axle sleeve 7 and with axle sleeve 7 fixed connection's spliced pole 6, ring frame 5 and slider 8 are at the 3 internal rotations of recess, and then make the medicine of grinding ball 2 pair grinding inslot 1 of fixing on ring frame 5 grind, increase the surface area of medicine powder, reduce the particle diameter of medicine.
Furthermore, there are many connection ways of the connecting rod 4 and the circular ring frame 5, such as welding, bonding, etc., and the invention is preferably fixed by means of a fastener 13, as shown in fig. 5, specifically: lean on connecting rod 4 to one side on ring frame 5, then fix connecting rod 4 on ring frame 5 with fastener 13, fastener 13 is fixed with ring frame 5 adoption bolt's mode, shape looks adaptation after fastener 13 and connecting rod 4 slope. It should be noted that: because the connecting rod 4 is in an inclined state after the connecting rod 4 and the circular ring frame 5 lean against each other, the contact surface between the fastener 13 and the connecting rod 4 is also inclined, and the two connecting lugs on the fastener 13 are fixed with the circular ring frame 5 through bolts. In order to avoid the connecting rod 4 from loosening with the fastener 13 in the operation process, a layer of rubber pad can be arranged on the inner wall of the fastener 13, and the rubber pad can be arranged in a bonding or direct placement mode. In order to further fix the connecting rod 4 and the ring frame 5, a bolt hole is arranged on the fastener 13, and a bolt hole with the same size is arranged on the connecting rod 4 and the ring frame 5 corresponding to the bolt hole, so that the bolt penetrates through the bolt holes on the fastener 13, the connecting rod 4 and the ring frame 5 to fix the connecting rod 4 and the ring frame 5 together.
Grind the bottom in groove 1 and be equipped with the discharge gate, be fixed with discharging pipe 14 on the discharge gate, be provided with solenoid valve 15 on discharging pipe 14, on solenoid valve 15, be provided with the filter screen on the position that is linked together with the discharge gate, the shape of this filter screen is inside sunken, can the circular arc transition with the bottom of grinding groove 1, and the bottom of grinding ball 2 can laminate mutually with this filter screen, the aperture of this filter screen can be the same with the aperture of screen cloth 16, also can be greater than the aperture of screen cloth 16, make the medicine at the in-process of grinding, just fall to screen cloth 16 through the filter screen, carry out twice screening with the medicine powder. The specific installation process of the electromagnetic valve 15 is as follows: the electromagnetic valve 15 is arranged in the discharge pipe 14, an inlet of the electromagnetic valve 15 is aligned with a discharge hole, and a filter screen capable of realizing arc transition with the bottom of the grinding groove 1 is fixed at the inlet of the electromagnetic valve 15.
The screen cloth 16 is arranged in the discharge pipe 14 and below the electromagnetic valve 15, different apertures of the screen cloth 16 can be replaced according to actual use requirements, and the screen cloth 16 is provided with a vibrator which can enable medicine powder falling on the screen cloth 16 to pass through meshes of the screen cloth 16 better, so that the medicine powder is prevented from blocking the screen cloth 16. An operation hole (not shown) is provided in the wall of the discharge pipe 14 above the screen 16, and an operation door (not shown) is hinged to the operation hole to clean the medicine powder staying on the screen 16. An electric valve 17 and a dust concentration detector 18 are sequentially arranged on the discharge pipe 14 and below the screen 16; dust concentration detection appearance 18 and electric valve 17 respectively with controller electric connection, dust concentration detection appearance 18 control medicine powder's weight, after reaching appointed weight, give the controller with signal transmission, the controller control electric valve 17 opens and close to carry out automatic weighing to the medicine that enters into in the powder mixer 19.
The outlet end of the discharge pipe 14 is communicated with a powder mixer 19, so that the sieved and weighed powder is added into the powder mixer 19, a feed inlet is formed in the powder mixer 19, other medicines can be added inwards, different types of substances are uniformly mixed, and the parameters of the powder mixer 19 are conventional parameters and can be set according to actual requirements. The powder mixing machine is characterized in that a powder pipe 20 is connected to an outlet of the powder mixing machine 19, the other end of the powder pipe 20 is connected with a multi-channel rotary joint 21, a powder pump 22 is arranged on the powder pipe 20, the other end of the multi-channel rotary joint 21 is connected with a plurality of shunt pipes 23, the shunt pipes 23 extend into the coating machine, powder spray heads 24 are arranged at the end parts of the shunt pipes 23 extending into the coating machine, the powder spray heads 24 incline towards the top of a coating tank 25, namely, the powder spray heads are arranged to have a certain elevation angle, the inclined angle can be adjusted according to actual conditions, so that the time of the mixed powder staying in the air is prolonged, and the coating liquid can contact the mixed powder as. It should be noted that: the powder pump 22 is provided on the powder pipe 20 between the multi-channel rotary joint 21 and the powder mixer 19 so as to apply a high pressure to the mixed powder in the powder mixer 19 and eject the mixed powder through the plurality of shunt pipes 23. The powder spray head 24 provided at the end of the bypass pipe 23 further disperses and sprays the mixed powder so that the sprayed mixed powder is in a uniform mist form. The number of the shunt tubes 23 can be set conventionally according to actual use requirements, and can be one, or a plurality of shunt tubes 23 can be set, and the 4 shunt tubes 23 provided in the invention are only used for explaining that a plurality of shunt tubes 23 can be set, and are not limited to be only 4 shunt tubes.
The coating machine comprises a coating tank 25 and a swing mechanism arranged at the lower position of the middle part in the coating tank 25, a liquid mixer 26 is arranged above the coating tank 25, a liquid outlet pipe is arranged at the bottom of the liquid mixer 26, the other end of the liquid outlet pipe extends into the coating tank 25 from the top of the coating tank 25, an atomizing nozzle 27 is arranged on the nozzle of the liquid outlet pipe extending into the coating tank 25, and the atomizing nozzle 27 can spray coating liquid as much as possible; the liquid outlet pipe is provided with a variable speed pump 28, and the atomizing nozzle 27 is positioned above the powder nozzle 24, so that the coating liquid can be better contacted with the mixed powder. The mixed powder sprayed by the powder spray head 24 can be mixed with the coating liquid sprayed by the atomizing spray head 27, so that the coating liquid can wrap the mixed powder, and andrographolide particles are finally prepared. It should be noted that: the side wall of the coating tank 25 is a cavity, and a heating wire (not shown in the figure) is arranged in the cavity and used for heating the coating tank 25 to ensure that the coating liquid and the mixed powder can be quickly dried after being mixed, so that the mixed powder is prevented from being adhered to the inner wall or the bottom wall of the coating tank 25, a relay can be connected to the heating wire, and the heating wire is controlled to work by controlling the on-off of the relay; and a temperature sensor is provided in the coating tank 25 for monitoring the temperature in the coating tank 25. When the temperature in the coating tank 25 rises to the set temperature, the heating is stopped, the heating wires and the temperature sensor are electrically connected with the controller, and the temperature in the coating tank 25 is controlled by the controller. In addition, the liquid mixer 26 may be disposed at any position as long as the liquid outlet pipe extends from the top of the coating tank 25 into the coating tank 25. The variable speed pump 28 can adjust the flow rate and pressure of the fluid, and of course, a frequency converter can be connected to the variable speed pump 28 to better adjust the flow rate and pressure of the coating solution.
The swing mechanism can further uniformly mix andrographolide particles prepared after the coating liquid and the mixed powder are contacted, and in the process of coating the mixed powder by the coating liquid, the mixed powder or the coating liquid falls on the bottom of the coating tank 25 inevitably, so that the waste of materials and the unevenness of the prepared andrographolide particles are avoided, and therefore, the bottom of the coating tank 25 is provided with a swing structure. The swing mechanism comprises an inward-concave material containing disc 29, the outer diameter of the material containing disc 29 is smaller than the inner diameter of the coating tank 25, a support column 30 is fixed at the bottom of the outer side of the material containing disc 29, a rotating ball 31 is fixed at the other end of the support column 30, a bearing column 32 is arranged at the inner bottom of the coating tank 25 and at a position corresponding to the rotating ball 31, a spherical groove matched with the rotating ball 31 is formed in the bearing column 32, and the rotating ball 31 is located in the spherical groove. It should be noted that: the rotating ball 31 can freely rotate in the spherical groove, and in order to prevent the rotating ball 31 from falling out of the spherical groove, at least 3-2 minutes of the rotating ball 31 is positioned in the spherical groove, namely the spherical groove wraps the rotating ball 31, and the top of the spherical groove exceeds the spherical center of the rotating ball 31.
In order to make the material containing tray 29 rotate freely by taking the receiving column 32 as the center, a plurality of metal blocks 33 are arranged on the outer side surface of the material containing tray 29 and around the support column 30 in a circle, namely, the plurality of metal blocks 33 are centered on the support column 30, the material containing tray 29 can rotate regularly by the arrangement mode, and if the material containing tray 29 needs to rotate irregularly, the metal blocks 33 only need to be arranged around the support column 30 by surrounding the support column 30. The metal block 33 is a metal, such as iron, that can be attracted by the electromagnet 34 when energized. Electromagnets 34 are arranged at the inner bottom of the coating tank 25 and at positions corresponding to the metal blocks 33, the electromagnets 34 are electrically connected with a controller respectively, the controller controls the sequence of the energization of the electromagnets 34 to enable the material containing tray 29 to rotate, and the rotation speed is controlled by controlling the time of energization and deenergization between adjacent electromagnets 34. The specific control process is as follows: when one electromagnet 34 is electrified, the material containing tray 29 inclines towards the electromagnet 34, the next electromagnet 34 is electrified while the electromagnet 34 is powered off, the material containing tray 29 inclines towards the next electromagnet 34, the next electromagnets 34 can be adjacent or spaced, so that the material containing tray 29 can rotate, andrographolide particles falling in the material containing tray 29 are mixed with the mixed powder and the coating liquid falling on the material containing tray and not coated by the coating liquid, and the andrographolide particles roll and collide on the material containing tray 29 in the rotating process of the material containing tray 29, so that the prepared andrographolide particles are more uniform. Those skilled in the art will appreciate that: the feeding hole is formed in the material containing disc 29, the hose is arranged on the feeding hole, the hose cannot be affected in the rotating process of the material containing disc 29, and the electric switch is arranged on the hose and extends out of the coating tank 25.
Furthermore, because the outer diameter of the material containing disc 29 is smaller than the inner diameter of the coating tank 25, the mixed powder and the coating liquid can fall in the gap between the material containing disc 29 and the coating tank 25, a circle of flange 35 is arranged on the side wall of the coating tank 25 and above the material containing disc 29, the flange 35 is obliquely arranged towards the center of the coating tank 25, the edge of the material containing disc 29 is positioned right below the flange 35, and the flange 35 can shield the gap between the material containing disc 29 and the coating tank 25; even though the andrographolide particles fall on the rib 35, the rib 35 has a certain inclination and falls into the material containing tray 29.
It should be noted that: the electronic devices in the present invention are controlled by a controller, such as the first motor 9, the electromagnetic valve 15, a vibrator, a heater wire, a temperature sensor, the start and stop of the powder pump, the start and stop of the variable speed pump, the electromagnet 34, an electric switch, a relay, the dust concentration detector 18, the electric valve 17, and the like, which are not listed. The controller controls the on/off and running time of the electrical elements to control the whole system.
When the invention is used, firstly, the required reagents and raw materials are weighed for standby use according to the method 1, wherein the weight of the andrographolide is the weight after sieving, then the andrographolide is put into the grinding groove 1, the groove cover 10 is covered, and the output end of the first motor 9 is fixed in the shaft sleeve 7. And then starting the first motor 9 to enable the grinding balls 2 to do circular motion along with the supporting mechanism, grinding and refining the andrographolide, wherein the rotating speed of the first motor 9 is 600-1000 r/min, the running time is 15-60 min, and after grinding is finished, closing the first motor 9. Opening the electromagnetic valve 15, enabling the andrographolide subjected to primary filtration after grinding to fall onto the screen 16, enabling the mesh number of the screen 16 to be 100-300 meshes, starting the vibrator to enable the andrographolide to fall into the powder mixing machine 19 through the screen 16, detecting the weight of the fallen andrographolide by the dust concentration detector 18 at the moment, and controlling the electric valve 17 to be closed by the controller when the weight of the andrographolide reaches the using amount limited in the method 1; and then adding microcrystalline cellulose with the particle size of 20-80 microns into the powder mixer 19, starting the powder mixer 19, and uniformly mixing the powder to obtain mixed powder. Meanwhile, adding the gastric-soluble material and povidone K30 into the liquid mixer 26, adding 20-95% ethanol solution, starting the liquid mixer 26, and uniformly stirring the solution to obtain coating liquid; then, simultaneously starting the powder pump 22 and the variable speed pump 28, respectively atomizing the mixed powder and the coating liquid, wherein the atomizing pressure of the coating liquid is 0.1-0.4 Mpa, the spraying speed is 10-40 mL/min, the spraying speed and the pressure of the mixed powder can be the same as those of the coating liquid, conventional setting is carried out according to actual use requirements, the mixed powder and the coating liquid are mixed in the coating tank 25, the coating tank 25 is heated to the specified temperature of 40 +/-5 ℃ in advance, and the temperature in the coating tank 25 is controlled to be kept constant through a temperature sensor, a relay and a controller; when the mixed powder and the coating liquid are mixed, the controller respectively controls the electromagnets 34 to rotate the material containing disc 29, and the rotating speed is controlled by the controller. And finally, opening an electric switch on the material containing tray 29, collecting the prepared andrographolide particles through a hose, and mixing the andrographolide particles with a suspending agent and a flavoring agent to obtain the andrographolide dry suspension.
Example 1
The andrographolide dry suspension is prepared by adopting the formula 1 and the method 2, wherein the concentration of ethanol is 85%, the grain size of microcrystalline cellulose is 20 microns, and the solid content in the coating liquid is 10%. The specific component ratios are shown in the following tables 1 and 2.
TABLE 1 raw material ratio (parts by weight)
TABLE 2 raw material ratio (parts by weight)
The raw materials of the components shown in the table 1 and the table 2 are added into the system for preparing the andrographolide dry suspension provided by the invention in the table 3, the technological parameters in the preparation process are shown in the table 3 below, and if the existing centrifugal granulation coating machine is selected, the rotating speed of the coating machine is controlled to be 100-400 r/min.
Table 3 specific Process parameters
The andrographolide dry suspensions were prepared using the process parameters of table 3 for each group of raw materials in tables 1 and 2. Performing dissolution rate determination on the prepared andrographolide dry suspension, wherein the dissolution rate determination adopts a basket method, the rotating speed is 100r/min, and the temperature is 37 ℃; the dissolution medium is artificial gastric juice, and the preparation process of the artificial gastric juice comprises the following steps: diluting 1mol/mL diluted hydrochloric acid with water, adjusting pH to 1.5, adding 1g pepsin into each 100mL liquid, mixing, and filtering with 0.2 μm sterile filter head for use. The dissolution rate of the prepared andrographolide dry suspension is shown in the following table 4. The andrographolide bulk drug was used as a comparative example, as shown in table 5 below. The results show that: by adopting the raw material proportion of group 1 in table 1 and table, the dissolution rate of the andrographolide dry suspension is gradually increased along with the increase of the mesh number of the screen under the condition that the spraying speed of the variable speed pump is the same by using the system provided by the invention, and the dissolution rate of the andrographolide dry suspension is the best when the spraying speed is 25mL/min under the condition that the mesh number of the screen is the same.
TABLE 4 dissolution of andrographolide dry suspension
TABLE 5 dissolution of andrographolide bulk drug
Time/min | |
5 | 9.23% |
10 | 18.56% |
15 | 25.37% |
20 | 28.54% |
25 | 31.26% |
Example 2
The 27 groups of dry suspension of andrographis paniculata prepared according to table 3 above were added to water separately, and the 27 groups of dry suspension of andrographis paniculata were rapidly dispersed in water to form a suspension, and the solution was dipped every 10min for human tasting, and the results showed that: the 27 groups of dried suspension of Andrographis paniculata Nees had no bitterness within 60 min.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Claims (10)
1. An andrographolide dry suspension is characterized in that: comprises the following components: the traditional Chinese medicine composition comprises, by weight, 3-10 parts of andrographolide, 1-3 parts of microcrystalline cellulose, 301-3 parts of povidone K, 1-3 parts of gastric soluble materials, 1-5 parts of suspending agents, 0.01-5 parts of flavoring agents and 5-120 parts of ethanol.
2. The andrographolide dry suspension of claim 1, wherein: the gastric-soluble material is one or more of Eudragit E, Eudragit RD 100 and acrylic resin IV; the suspending agent is one or more of xanthan gum, carrageenan, arabic gum, gelatin, sodium carboxymethylcellulose, croscarmellose sodium, polyvidone, pectin, guar gum and sodium alginate; the correctant is one or more of aspartame, sodium cyclamate, stevioside, citric acid, orange essence, and pineapple essence.
3. The andrographolide dry suspension of claim 1, wherein: the andrographolide dry suspension is prepared by the following steps:
(1) grinding andrographolide in a refining device, sieving, and mixing with microcrystalline cellulose to obtain mixed powder;
(2) putting the gastric-soluble material, the povidone K30 and the ethanol into a mixing device, and uniformly stirring to obtain a coating solution;
(3) adding the mixed powder obtained in the step (1) into a coating machine, spraying the coating liquid prepared in the step (2) on the mixed powder, and carrying out centrifugal granulation to obtain andrographolide particles;
(4) and (4) uniformly mixing the andrographolide particles prepared in the step (3) with a suspending agent and a flavoring agent to prepare the andrographolide dry suspension.
4. The andrographolide dry suspension of claim 3, wherein: in the step (1), refining andrographolide, and then sieving with a 100-300-mesh sieve, wherein the grain size of microcrystalline cellulose is 20-80 μm; in the step (2), the solid content in the coating liquid is 5-15%; in the step (3), the rotating speed of the coating machine is 100-400 r/min, the temperature is 40 +/-5 ℃, the spraying pressure of the coating liquid is 0.1-0.4 Mpa, and the spraying speed is 10-40 mL/min.
5. The andrographolide dry suspension of claim 3, wherein: the refining device comprises a grinding groove (1) in a bowl shape and grinding balls (2) placed in the grinding groove (1), a circle of groove (3) is circumferentially arranged inside the grinding groove (1), a supporting mechanism is arranged in the groove (3), and the grinding balls (2) can be detachably fixed on the supporting mechanism through a connecting rod (4).
6. The andrographolide dry suspension of claim 5, wherein: the supporting mechanism comprises a circular ring frame (5) and a shaft sleeve (7) fixed at the axis of the circular ring frame (5) through a plurality of connecting columns (6), a plurality of sliding blocks (8) are uniformly distributed on the circumferential side wall of the circular ring frame (5), and the sliding blocks (8) are matched with the grooves (3); the output of first motor (9) is connected in axle sleeve (7), the top of grinding groove (1) is provided with capping (10), the center department of capping (10) is equipped with the messenger hole (11) that axle sleeve (7) stretches out, first motor (9) can be dismantled through a plurality of support column (12) and fix the top of capping (10).
7. The andrographolide dry suspension of claim 5, wherein: a discharge hole is formed in the bottom of the grinding groove (1), a discharge pipe (14) is fixed on the discharge hole, an electromagnetic valve (15) is arranged on the discharge pipe (14), a screen (16) is arranged in the discharge pipe (14) and below the electromagnetic valve (15), and an electric valve (17) and a dust concentration detector (18) are sequentially arranged on the discharge pipe (14) and below the screen (16); the dust concentration detector (18) and the electric valve (17) are respectively electrically connected with the controller.
8. The andrographolide dry suspension of claim 7, wherein: the exit end and the powder of discharging pipe (14) mix machine (19) and be linked together, the exit that the powder mixes machine (19) is connected with powder pipe (20), the other end of powder pipe (20) is connected with multichannel rotary joint (21), be provided with powder pump (22) on powder pipe (20), the other end of multichannel rotary joint (21) is connected with a plurality of shunt tubes (23), a plurality of shunt tubes (23) stretch into in the capsule machine, stretch into in the capsule machine the tip of shunt tubes (23) is provided with powder shower nozzle (24).
9. The andrographolide dry suspension of claim 8, wherein: the capsule machine includes coating tank (25) and sets up the swing mechanism on the position by lower position in coating tank (25) middle part, the top of coating tank (25) is provided with liquid mixer (26), the bottom of liquid mixer (26) is provided with the drain pipe, the other end of drain pipe is followed the top of coating tank (25) stretches into in coating tank (25), and stretch into in coating tank (25) be provided with atomizer (27) on the mouth of pipe of drain pipe, be provided with variable speed pump (28) on the drain pipe, atomizer (27) are located the top of powder shower nozzle (24).
10. The andrographolide dry suspension of claim 9, wherein: the swing mechanism comprises an inward-concave material containing disc (29), a support column (30) is fixed at the bottom of the outer side of the material containing disc (29), a rotating ball (31) is fixed at the other end of the support column (30), a bearing column (32) is arranged at the inner bottom of the coating tank (25) and at a position corresponding to the rotating ball (31), a groove which is matched with the rotating ball (31) is formed in the bearing column (32), and the rotating ball (31) is located in the spherical groove;
the coating device is characterized in that the outer side face of the material containing disc (29) is provided with a plurality of metal blocks (33) in a circle around the support column (30), the inner bottom of the coating tank (25) is provided with an electromagnet (34) in a position corresponding to the metal blocks (33), and the electromagnet (34) is electrically connected with the controller respectively.
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