CN109692126B

CN109692126B - Method for preparing high-uniformity dropping pills and equipment used by same

Info

Publication number: CN109692126B
Application number: CN201910157396.3A
Authority: CN
Inventors: 黄维佳; 陈志涛; 马俊
Original assignee: SHENZHEN WANHE PHARMACEUTICAL CO Ltd
Current assignee: SHENZHEN WANHE PHARMACEUTICAL CO Ltd
Priority date: 2019-03-01
Filing date: 2019-03-01
Publication date: 2021-10-22
Anticipated expiration: 2039-03-01
Also published as: CN109692126A

Abstract

The application relates to a method for preparing dropping pills with high uniformity and equipment used by the method. In particular to multilayer dripping pill equipment, which comprises a dripper, a material supply pipeline connected with the dripper, a material supply tank, a temperature control system for providing temperature control for the material supply tank, the material supply pipeline and the dripper, and a dripping pill receiving device; the pill receiving device comprises a cylindrical pill cooling part and an inverted cone-shaped pill recovery part connected to the lower part of the cylindrical pill cooling part, and is filled with cooling liquid when the multilayer pill equipment works; the dropping nozzle is positioned below the liquid level, an isolation circular plate comprising a central circular hole and a small hole is coaxially arranged in the middle of the barrel-shaped dropping pill cooling part, the dropping pills dropping from the dropping nozzle pass through the central circular hole to descend to enter the dropping pill recovery part in the sinking process, and a stirring paddle is also arranged to stir the cooling liquid and enable the dropping pills to be dispersed and settled respectively after entering the lower part of the isolation circular plate. The pills obtained by the method have very high roundness and uniformity.

Description

Method for preparing high-uniformity dropping pills and equipment used by same

Technical Field

The application relates to the field of mechanical equipment, in particular to the field of pharmaceutical mechanical equipment, more particularly to equipment for preparing multilayer dripping pills and key parts thereof, and even more particularly to equipment capable of preparing two-layer or three-layer dripping pills and key parts thereof, wherein two or three layers of the two-layer or three-layer dripping pills can be substances with different characteristics, and the dripping pills in multiple layers have excellent and uniform structures. In particular, the present application relates to a method of dropping pills with high uniformity and an apparatus used for the method.

Background

The dripping pill is a high-end preparation formulation in the field of pharmacy, and can endow the medicament with special performance due to the special structure of the dripping pill. The drop pill is a pellet preparation prepared by heating, melting and mixing solid or liquid medicine and proper substances (generally called as matrix), dropping into immiscible condensate, and shrinking and condensing, and is mainly used for oral administration. From the composition and preparation method of the dripping pill, the dripping pill has the following characteristics: 1. the equipment is simple, the operation is convenient, the labor protection is facilitated, the process period is short, and the productivity is high; 2. the process conditions are easy to control, the quality is stable, the dosage is accurate, the heating time is short, and the stability of the medicine can be improved after the medicine which is easy to oxidize and has volatility is dissolved in a matrix; 3. the matrix has large amount of liquid medicine, so that the liquid medicine can be solidified, such as Ruta graveolens oil dripping pill with oil content of 83.5%; 4. the dripping pill prepared by solid dispersion technology has the characteristics of rapid absorption and high bioavailability, such as the griseofulvin dripping pill has effective dose of 1/4 of 100 mesh fine powder and 1/2 of micro powder (the particle size is less than 5 microns); 5. new formulations for ear and eye administration are developed, and the five sense organs preparation is mostly liquid or semisolid, has short action time, and can be prepared into dripping pills to achieve the effect of prolonging.

The dripping pill has the advantages of three effects, namely quick effect, high efficiency and long effect. Most of the dripping pills are sublingual buccal, and the medicine is directly absorbed through sublingual mucosa and enters blood circulation, so that the first pass effect of liver caused by swallowing and the degradation loss of the medicine in stomach are avoided, so that the medicine reaches a target organ at high concentration and takes effect rapidly. Generally, the medicine can take effect after being taken for 5 to 15 minutes, and the maximum time is not more than 30 minutes. And a slow release agent is also added, so that the half-life period of the medicament can be obviously prolonged, and the aim of long acting is fulfilled. When needed, the medicine is taken orally.

The current dropping pills mainly have the following types: quick-acting high-efficiency dripping pills: the dripping pill is prepared by using a solid dispersion technology. When the matrix is dissolved, the medicine in vivo is released in the form of fine crystal, amorphous particle or molecule, so the dissolution is fast, the absorption is fast, the effect is fast, and the bioavailability is high. Typical examples of such products are fast acting heartburn drop pills. Sustained-release controlled-release dropping pills: the slow release is to ensure that the medicine in the dropping pill is slowly dissolved out in a longer time to achieve long-acting effect; controlled release is to dissolve the drug in the drop pills at a constant rate, and the effect can reach more than several days, such as chloramphenicol controlled release eye pills. Solution dropping pill: since many of the lubricants and disintegrants used in tablets are water-insoluble, it is not usually possible to prepare a clear solution in a tablet. The dripping pill can be prepared with water soluble matrix, and can be disintegrated into clear solution in water, such as chlorhexidine dripping pill for drinking water disinfection. Suppository dropping pills: the dripping pill can be dissolved by body fluid when used in cavity, and can be used as water soluble matrix such as polyethylene glycol like water soluble suppository. Such as dripping pills for norfloxacin ear, dripping pills for metronidazole tooth, etc. The dripping pill can be applied to rectum, can be absorbed by rectum to directly act on whole body, and has the advantages of high bioavailability and quick action. Hard capsule dropping pills: the hard capsule can be filled with dripping pills with different dissolution rates to form sustained-release pellet capsules with the required dissolution rates, such as bifendate hard capsule dripping pills. Coating the dripping pills: the tablet and pill can be coated with sugar or film, such as bifendate dripping pill. Liposome dropping pill: the liposome is suspension liquid, and can be made into solid dosage form with polyethylene glycol by adding liposome into molten polyethylene glycol 4000 under stirring to form suspension, pouring into a mold, and condensing to form. Enteric-coated dripping pills: a matrix insoluble in stomach, such as AlK pill, is prepared by making pill with gelatin solution, treating with formaldehyde to make the amino group of gelatin insoluble in gastric juice and soluble in intestine. Dry pressing the coated dripping pills: the dripping pill is used as the center, and a coating layer consisting of other medicines is pressed on the dripping pill, so that the advantages of two dosage forms, such as cough relieving and phlegm eliminating potassium chloride dry-pressed coated tablets, are combined. The former is dripping pill and the latter is coating layer.

However, in some cases, some substances are absorbed in a specific part of the digestive tract, for example, in the small intestine, but cannot contact with the acidic gastric juice in the stomach when being prepared into a dripping pill. The dripping pill process can realize the production of dripping pills with uniform components and high roundness, can ensure that the medicine is uniformly released, has long release time and is convenient to carry and store. At present, most of the domestic dripping pill processes are single-component preparations, and effective components cannot be coated by substances with protective effect, so that the aim of multilayer coating is fulfilled. In particular, it is possible to use,

if the multilayer dripping pill equipment and the process thereof are successfully researched, the effective components can be completely wrapped and protected by gastric acid resistant substances and directly reach the small intestine or even the large intestine to be released, so that the maximization of the effect is realized. For example, probiotics go directly to the large intestine. Has obvious effects of improving the intestinal function and promoting the balance of intestinal flora. The technology can also be used for developing a novel medicinal preparation, so that the acid-afraid medicament is sent into the large intestine by avoiding gastric acid and is absorbed by the human body, and the treatment effect of the medicament is improved. Or a plurality of layers of sustained-release medicines are developed to ensure that the medicines in each layer exert effects in turn, and the like, thereby providing a practical and feasible way for the newly prepared medicines or foods.

The classic dropping pills are not layered, the dropping pills are uniform mixtures from inside to outside, and the development of multilayer dropping pills (such as double-layer dropping pills or three-layer dropping pills) presents strong requirements along with the development requirement of preparations. The process for preparing these multi-layered dripping pills, e.g., bilayer dripping pills, is distinguished from soft capsules produced by the dripping method in that their contents are liquid, whereas the inner components of the multi-layered dripping pills, e.g., bilayer dripping pills, are substantially solid at ordinary temperature. Therefore, the soft capsule production equipment/process cannot be applied to multi-layer dropping pills (e.g. double-layer dropping pills or triple-layer dropping pills).

The applicant has long dedicated the development and mechanical design of multilayer dripping pills, for example, the design of Chinese patent No. ZL2016202539660 developed by the applicant, and has provided an apparatus and/or components thereof capable of dripping into multilayer, especially three-layer dripping pills, and the apparatus can provide excellent production efficiency. However, as described above, since each layer of the multi-layered dripping pill is different in material, the physical state of each layer after dripping is substantially the same, i.e., each layer of the multi-layered dripping pill is substantially in a solid or semi-solid state after dripping, as distinguished from the soft capsule. In this state, if the thickness distribution of each layer is not uniform during the dripping process, the phenomenon of non-concentricity of the multi-layer dripping pill may occur, for example, in the case of a double-layer dripping pill, if the outer layer is spherical with very good roundness but the inner layer is ellipsoidal with poor roundness, or if the inner layer is spherical but not perfectly centered, the pellets may be non-uniform, which may cause the centers of the layers of the whole dripping pill to be different from each other, i.e., poor concentricity. In order to solve such problems, the present applicant has devised a new solution based on the aforementioned work and described in chinese patent No. ZL 2016210586095, which enables to obtain pellets having very excellent property indexes such as concentricity by reciprocating a dropper up and down. However, it has been found that pellets obtained with this protocol are not ideal in terms of pellet weight uniformity, i.e. the weight difference between each pellet is large.

Therefore, it is still desired by those skilled in the art to provide a multilayered dripping pill having excellent properties and a uniform weight and size of the pill.

Disclosure of Invention

The object of the present application is to provide an apparatus capable of being dripped into multilayer, in particular trilayer, dripping pills. It has been unexpectedly found that the apparatus and/or components thereof having three-layered pills having the structural features of the present application can achieve unexpected technical results. The present application has thus been completed.

For this reason, this application first aspect provides a multilayer dripping pill equipment, and it includes:

(i) a dripper (particularly, for example, the dripper of any of the embodiments of the second aspect of the present application) with its nozzle facing downward and its upper part connected to a vibrating device that allows the dripper to vibrate up and down;

(ii) the material supply pipeline is connected with the dripper;

(iii) material supply tank;

(iv) a temperature control system for providing temperature control for the material supply tank, the material supply pipeline and the dripper; and

(v) the pill receiving device comprises a cylindrical pill cooling part and an inverted cone-shaped pill recovery part connected to the lower part of the cylindrical pill cooling part, and is filled with cooling liquid when the multilayer pill equipment works;

it is characterized in that the preparation method is characterized in that,

the drip nozzle of the dripper extends below the liquid level of the cooling liquid, so that the drip nozzle is at least positioned at a position 10-20 mm (such as 13-17 mm, such as 15mm) below the liquid level in the up-and-down reciprocating process of the dripper,

an isolation circular plate is coaxially arranged in the middle of the cooling part of the barrel-shaped dropping pill, when the dripper is positioned at the bottommost part in the up-and-down reciprocating process, the vertical height of the dripping nozzle from the isolation circular plate is 10-30 mm (such as 15-25 mm, such as 20mm),

a central round hole with the diameter of 8-15 mm (such as 10mm) is arranged at the right center of the isolation circular plate, the drip nozzle is positioned right above the central round hole, so that a small pill dropping from the drip nozzle passes through the central round hole to descend into the pill recovery part in the sinking process,

the isolation circular plate is uniformly distributed with a plurality of small holes with the diameter of 2-5 mm (such as 3mm) on the periphery of the central circular hole, so that the cooling liquid can be exchanged up and down on the isolation circular plate,

a stirring paddle is arranged right below the central circular hole of the cooling part isolation circular plate and is used for stirring the cooling liquid and enabling the pellets to be dispersed and settled after entering the lower part of the isolation circular plate.

It has been surprisingly found that by immersing the mouth of the dripper below the liquid level and providing isolating disks in the dripping pill receiving apparatus, excellent weight uniformity of the dripping pills with respect to each other can be obtained with significantly reduced weight variation.

In addition, by applying up-and-down reciprocating vibration to the dripper, the dripped multilayer dripping pill has excellent roundness between each layer core and excellent concentricity between each layer core, so that the multilayer dripping pill has an excellent uniform structure.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein the total area of the aperture that evenly distributed set up on the isolation plectane accounts for the peripheral 5~15% of isolating plectane area of center round hole, for example 10%.

A multi-layer drop pill apparatus according to any one of the embodiments of the first aspect of the present application, wherein said dripper nozzle is located on the axis of the drum-like drop pill cooling section.

Multilayer dripping pill equipment according to any embodiment of the first aspect of the present application, wherein the dripper nozzle, the isolation circular plate and its central circular hole, the stirring paddle are coaxial with the axis of the cooling part of the barrel-shaped dripping pill.

The multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein the stirring rake sets up 10~30mm (for example 15~25mm, for example 20mm) below keeping apart the plectane.

According to the multilayer dripping pill device of any one of the embodiments of the first aspect of the application, the material supply pipeline is fixed in a frame box at the tail end connected with the dripping head and at the both ends of the dripping head; the top of the frame box is connected with a vibration device, so that the frame box and the drippers in the frame box can vibrate up and down in a reciprocating manner. Therefore, the dripper can be directly connected with the vibration device or indirectly connected with the vibration device in a frame box mode.

The frame box aims to conveniently fix the dripper and the material supply pipeline thereof together, the frame box can be a box enclosed by the upper surface and the four peripheral surfaces, and the bottom surface is open so as to extend downwards from the dripper and further ensure that the drip nozzle extends below the liquid level of the cooling liquid, so the design of the frame box does not need special requirements.

In addition, because one layer of the dripper is connected with a set of material supply pipeline and a set of material supply tank, a set of temperature control system can control a set of dripper, material supply pipeline and material supply tank. Of course, a set of temperature control system can be used to control multiple sets of drippers, material supply pipelines and material supply tanks simultaneously.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein vibrating device is for the dripper provides the amplitude of 2~ 50mm from top to bottom.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein vibrating device is for the dripper provides the amplitude of 3~ 30mm from top to bottom.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein vibrating device is for the dripper provides 4~20 mm's amplitude from top to bottom.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein vibrating device is for the dripper provides 5~15 mm's amplitude from top to bottom.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein the vibrating device for the time that the dripper provides a complete up-and-down vibrating motion is 0.1 ~5 seconds.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein the vibrating device for the time that the dripper provides a complete up-and-down vibrating motion is 0.2~4 seconds.

According to the multilayer dripping pill equipment of any embodiment of first aspect of this application, wherein the vibrating device for the time that the dripper provides a complete up-and-down vibrating motion is 0.25~2.5 seconds.

A multilayer dripping pill device according to any one of the embodiments of the first aspect of the present application, wherein the vibrating means comprises:

a motor;

the eccentric wheel comprises a central hole and at least one eccentric hole, the central hole is driven by the motor and drives the eccentric wheel to rotate to move circularly, the at least one eccentric hole deviates from the wheel center, and the distances from the central hole to the eccentric holes are different;

the first end part of the first transmission rod is connected with one eccentric hole; and

a second drive rod, the first end of which is connected to the second end of the first drive rod, the second end of which is connected to the dripper (or, optionally, the frame box);

the first transmission rod converts the circular motion of the eccentric wheel into the up-and-down reciprocating motion of the second transmission rod.

The amplitude requirement of up-and-down movement of the dripper can be realized by designing different distances between the eccentric hole and the central hole.

A multilayer drop pill apparatus according to any one of the embodiments of the first aspect of the present application, wherein said set of temperature control systems individually controls a set of drippers, material supply lines and material supply tanks. In this way, independent temperature control of the materials of the different layers can be easily achieved.

A multilayer drop pill device according to any one of the embodiments of the first aspect of the present application, wherein said temperature control system is a circulating hot air control system.

A multi-layer drop pill apparatus according to any one of the embodiments of the first aspect of the present application, wherein said drop pill receiving means comprises a drop pill cooling section and a drop pill recovery section. The cooling part of the dropping pill usually adopts liquid paraffin, dimeticone, soybean oil and the like, and preferably adopts liquid paraffin (the cooling liquid used in the specific test is liquid paraffin if the application is not particularly stated). As is also well known to those skilled in the art.

Further, in a second aspect of this application, this application provides a dripper for preparing multilayer dripping pills, it is removable and integrated structure of equipment, and it includes:

i) the inner layer material guiding part is generally in a nail shape, a first interface used for being connected with the connecting part is arranged at the expanded part at the upper end of the nail-shaped inner layer material guiding part, a through inner layer through hole is arranged from the top to the bottom of the nail-shaped inner layer material guiding part, and the inner layer through hole is used for enabling the inner layer material to flow from the upper end to the bottom end of the inner layer material guiding part and flow out;

ii) an intermediate material introduction member, which is generally nail-shaped, the enlarged upper end of which is provided with a second port for connection with the connecting member, the nail-shaped intermediate material introduction member being provided with a through intermediate through-hole from the top to the bottom; the middle through hole has a larger aperture than the outer diameter of the lower end needle part of the inner material introduction member, and the lower end needle part of the inner material introduction member is inserted into the middle through hole;

iii) the outer layer material leading-in part is in an inverted hollow cone shape as a whole, and a third interface used for being connected with the connecting part is arranged at the expanded part at the upper end of the conical outer layer material leading-in part; the hollow part in the conical outer material leading-in member is thicker than the outer diameter of the lower needle part of the middle material leading-in member, and the lower needle part of the middle material leading-in member can be inserted into the hollow part in the outer material leading-in member;

iv) a connecting part which is generally in a barrel shape and is internally provided with a first interface, a second interface and a third interface from top to bottom in sequence for being respectively connected with the inner layer material leading-in part, the middle material leading-in part and the outer layer material leading-in part, so that the three material leading-in parts are connected into a coaxial integrated form inside the connecting part,

the water dropper is characterized in that a water dropper nozzle of the water dropper faces downwards, the upper part of the water dropper is connected with a vibration device, and the vibration device enables the water dropper to vibrate up and down in a reciprocating mode.

In the production of dripping pills, it is important that the drippers can be easily disassembled and assembled, which work has a considerable impact on the time cost of production, since in many cases the cleaning of the mass of the dripping pills is very time-consuming and laborious. The applicant has not found that the prior art has a design that is more convenient to disassemble and assemble than the present application.

It has been surprisingly found that by applying such up-and-down reciprocating vibrations, excellent roundness between the cores of the layers of the multi-layer dropping pill being dropped and excellent concentricity between the cores of the layers can be achieved, resulting in an excellent uniform structure of the multi-layer dropping pill of the present application.

The dripper for use in the production of a multilayer dripping pill according to any one of the second aspect of the present application, wherein the vibration device comprises:

a motor;

the first end of the second transmission rod is connected with the second end of the first transmission rod, and the second end of the second transmission rod is connected with the dripper;

The amplitude requirement of up-and-down movement of the dripper can be realized by designing different distances between the eccentric hole and the central hole. For example, the vibration amplitude provided by the vibration device for the dripper is 2-50 mm, 3-30 mm, 4-20 mm, or 5-15 mm, and/or the time for the vibration device to provide a complete up-and-down vibration motion for the dripper is 0.1-5 seconds, 0.2-4 seconds, or 0.25-2.5 seconds.

The dripper according to any of the embodiments of the second aspect of the present application, for use in the manufacture of a multilayer dripping pill, wherein the first port, the second port and the third port are each independently in a structure selected from: screw structure, plug-in connection structure. The interfaces are generally configured to achieve the desired seal.

The dripper for manufacturing a multilayer dripping pill according to any one of the second aspect of the present application, wherein after the assembly of the inner-layer material inlet, the intermediate material inlet, the outer-layer material inlet and the connecting part, there is a gap, referred to as a first gap, between the lower edge of the upper expanded portion of the nail-like inner-layer material inlet and the upper edge of the upper expanded portion of the nail-like intermediate material inlet.

The dripper for use in the manufacture of multilayer dripping pills according to any one of the first aspect of the present application, in which the wall of the connecting cylindrical part is provided, directly opposite the first interspace, with one or more holes for the introduction of an intermediate material, this/these hole/holes being called intermediate material introduction hole/s. The intermediate material is introduced into the first gap through the intermediate material introduction hole of the connecting member, and then flows down to the outlet of the dripper through a gap formed by the intermediate through hole having a diameter larger than the outer diameter of the lower end needle portion of the inner layer material introduction member.

The dripper for manufacturing a multilayer dripping pill according to any one of the second aspect of the present application, wherein after the assembly of the inner-layer material inlet, the intermediate-layer material inlet, the outer-layer material inlet and the connecting part, there is a gap between the lower edge of the expanded upper end portion of the nail-like intermediate material inlet and the upper edge of the expanded upper end portion of the conical outer-layer material inlet, which is called the second gap.

The dripper for use in the manufacture of multilayer dripping pills according to any of the second aspects of the present application, wherein the wall of the connecting cylindrical part opposite the second interspace is provided with one or more holes for the introduction of the outer layer material, this/these hole/holes being called outer layer material introduction hole/holes. The outer material is introduced into the second gap through the outer material introducing hole of the connecting member and then flows down to the outlet of the dripper through a gap formed by the hollow part inside the outer material introducing member being larger than the outer diameter of the lower needle part of the intermediate material introducing member.

The dripper for manufacturing a multilayer dripping pill according to any one of the second aspect of the present application, wherein the lower edges of the inner material inlet, the intermediate material inlet and the outer material inlet are flush with each other. Therefore, when the inner layer material flowing out of the inner layer through hole in the inner layer material guide part flows out from the outlet at the lower end of the inner layer through hole, the inner layer material is wrapped by the middle material flowing out through the first gap to form a double-layer pellet; and the double layered pellets are in turn wrapped with the outer layer material flowing out through the second gap to form three layered pellets.

The dripper for manufacturing the multilayer dripping pill according to any one of the second aspect of the present application, wherein the upper end of the inner through hole is connected to an inner material supply device to provide uninterrupted inner material.

The dripper according to any of the second aspect of the present application, for use in the manufacture of multilayer dripping pills, wherein one or more of the intermediate material introduction holes is connected to an intermediate material supply means to provide an uninterrupted intermediate material.

The dripper according to any of the second aspect of the present application, for use in the manufacture of multilayer dripping pills, wherein one or more of the outer layer material introduction ports is connected to an outer layer material supply means to provide an uninterrupted outer layer material.

A dripper for use in the preparation of a multilayer dripping pill according to any of the second aspect of the application, comprises an intermediate material inlet and is used to prepare three layers of dripping pills.

The dripper for the preparation of a multilayer dripping pill according to any of the embodiments of the second aspect of the present application, comprises two intermediate material introductions and is used for the preparation of four layers of dripping pills. Preferably, the two intermediate material introduction pieces are basically the same in shape and are different in thickness and length; wherein the elongated intermediate material introduction member is connected to the inner layer material introduction member, the short and thick intermediate material introduction member is connected to the outer layer material introduction member, and the needle-shaped portion at the lower end of the elongated intermediate material introduction member is inserted into the intermediate through hole in the short and thick intermediate material introduction member. Similarly, when three intermediate material introduction members are included and arranged in a similar manner as described above, they may be used to prepare five-layer pills.

The dripper for preparing the multilayer dripping pill according to any one of the second aspect of the application comprises 1-4 intermediate material leading-in parts. Preferentially, the device comprises 1-3 intermediate material introduction pieces. Preferentially, the device comprises 1-2 intermediate material introduction pieces. Preferably, it comprises 1 intermediate material inlet.

The dripper for preparing the multilayer dripping pill according to any one of the second aspect of the application, wherein the wall of the cylindrical connecting part is provided with 1-3 intermediate material introducing holes at the position opposite to the first gap. Preferably, 2 intermediate material introducing holes are arranged, wherein one hole is used for introducing intermediate materials, and the other hole is reserved and can be blocked by a plug when not in use; or 2 intermediate material leading-in holes are used for leading in the intermediate material; alternatively, one opening is used for introducing the intermediate material (which is provided at its front end with a pressure pump for forcing the intermediate material to flow in a pressurized manner in the direction of the drippers), the other opening is used for discharging the intermediate material (which is not pressurized at its rear end and which can discharge excess material or for regulating the pressure of the intermediate material in the drippers) and the material discharged at this time is returned to the intermediate material tank via a circuit. It has been found, surprisingly, that when the wall of the drum-shaped connecting part is provided with 2 intermediate material feed openings facing the first gap, and one opening is used for feeding in intermediate material and the other opening is used for discharging intermediate material, the rounding of the dripping pill thus obtained is significantly higher than in the design with only one intermediate material feed opening (the rounding of the dripping pill is the ratio of the shortest to longest diameter of the dripping pill, the mean rounding of the dripping pill is in the range from 0.89 to 0.92 when one intermediate material feed opening is provided, and in the range from 0.96 to 0.99 when 2 intermediate material feed openings are provided one in and one out as described above (both values being 6 different material test values), these values being obtained in the outer layer material feed opening and also in the dripping head provided in the manner of the 2 intermediate material feed openings one in and one out as described above).

The dripper for preparing the multilayer dripping pill according to any one of the second aspect of the application, wherein the wall of the cylindrical connecting part is provided with 1-3 outer layer material introducing holes at the position opposite to the second gap. Preferably, 2 outer layer material leading-in holes are arranged, wherein one hole is used for leading in the outer layer material, and the other hole is reserved and can be blocked by a plug when not used; or 2 outer layer material leading-in holes are used for leading in the outer layer material; alternatively, one hole is used for introducing the outer material (the front end of the hole is provided with a pressure pump to enable the outer material to flow towards the dripper in a pressure mode), the other hole is used for discharging the outer material (the rear end of the hole is not provided with pressure, the hole can discharge redundant material or can be used for adjusting the pressure of the inner material and the outer material of the dripper), and the discharged material flows back to the outer material pool through the loop. It has been found that, surprisingly, when the wall of the connecting part in the form of a drum is provided with 2 outer material inlet openings facing the second gap, and one opening is used for introducing the outer material and the other opening is used for discharging the outer material, the pill roundness obtained in this way is significantly higher than in the design with only one outer material inlet opening (average pill roundness in the range from 0.88 to 0.92 when one outer material inlet opening is provided, and pill roundness in the range from 0.97 to 0.99 when one inlet and one outlet 2 outer material inlet openings are provided as described above (both values being 6 different material test values), which are obtained with a dripper arranged in the manner of the 2 outer material inlet openings also one inlet and one outlet as described above).

The dripper for use in the preparation of a multilayer dripping pill according to any one of the embodiments of the second aspect of the present application is a dripper for use in the preparation of three-layer dripping pills. There is only one intermediate material inlet.

According to the dripper for manufacturing the multilayer dripping pill of any embodiment of the second aspect of the present application, the inner material introduction part, the intermediate material introduction part and the outer material introduction part all gradually decrease in diameter at the bottom to form the dripping nozzle.

According to the dripper for preparing the multilayer dripping pill in any embodiment of the second aspect of the application, the lower edge of the dripper seen from the lower part of the dripper is in three concentric circles, and the dripper sequentially consists of the bottom end of an inner layer material introduction part, the bottom end of an intermediate material introduction part and the bottom end of an outer layer material introduction part from inside to outside, wherein the innermost layer is used for flowing out of the inner layer material, the intermediate layer is used for flowing out of the intermediate material, and the outermost layer is used for flowing out of the outer layer material.

According to the dripper for preparing the multilayer dripping pill of any embodiment of the second aspect of the application, the lower edge of the dripper seen from the bottom is in three concentric circles to form an innermost layer area, an intermediate layer area and an outermost layer area. When tested using 6 different materials, it has been found that the area of the innermost zone: area of the intermediate layer region: outermost region area 1: when the ratio is selected within a wide range of 0.5-5: 1-10, the method can prepare the dropping pill with the rounding degree of more than 0.95 (the test result obtained by adopting the design mode of one-in-one-out-2 holes for both the middle material introduction hole and the outer material introduction hole), unfortunately, the same materials are tested by adopting a three-layer design scheme (for example, FIG. 4 of CN 100506093C-200480028272.1, FIG. 1 of CN 201750916U-201020224428.1 and FIG. 3 of CN 104219951A-201280067210.1) of some documents, and the area of the innermost layer area in the schemes of the documents is adjusted: area of the intermediate layer region: the outermost region area is also 1: when the ratio is selected within a large variation range of 0.5-5: 1-10, the roundness of the obtained dropping pills is within a range of 0.67-0.84, and the dropping effect of the dropping pills is obviously inferior to that of the scheme of the application.

According to the dripper for preparing the multilayer dripping pill of any embodiment of the second aspect of the application, the lower edge of the dripper seen from the bottom is in three concentric circles to form an innermost layer area, a middle layer area and an outermost layer area, and the area ratios of the three areas are that the area of the innermost layer area: area of the intermediate layer region: outermost region area 1: 0.5-5: 1-10.

Drippers according to any of the embodiments of the second aspect of the present application for the preparation of multilayer dripping pills may be used in conventional multilayer dripping pill equipment, e.g. as described in CN 100506093C-200480028272.1, CN 201750916U-201020224428.1, CN 104219951A-201280067210.1. In one example, the dripper of the present application is used in a multilayer dripping pill apparatus. These multi-level drop pill devices typically include a material supply system connected to the drippers, and a temperature control system that controls the temperature of the material and drippers.

Further, a third aspect of the present application provides a method for preparing a multilayer dripping pill (e.g., a three-layer dripping pill), which comprises the following steps:

1) respectively preparing materials of each layer of the dripping pill;

2) adding the materials of each layer into corresponding material supply tanks respectively, wherein each material supply tank is connected with a material inlet of a material introducing part of a corresponding layer of a dripper (particularly, for example, the dripper of any one of the embodiments of the second aspect of the application) which vibrates up and down in the process of dripping pills;

3) starting a temperature control system to control the temperature of the materials in the material supply tank, the material supply pipeline and the dripper to be within a specified value or range of the materials; and

4) after the temperature of each layer of materials is balanced, starting a dripping pill process to drip the dripping pills into a dripping pill receiving device;

it is characterized in that the preparation method is characterized in that,

the pill receiving device is filled with cooling liquid and comprises a cylindrical pill cooling part and a pill recovery part which is connected with the lower part of the cylindrical pill cooling part and is in an inverted cone shape;

In addition, by applying the up-and-down reciprocating vibration to the dripper, the layers of cores of the dripped multilayer dripping pill have excellent roundness, and the layers of cores have excellent concentricity, so that the multilayer dripping pill has an excellent uniform structure.

The method according to any embodiment of the third aspect of the present application, wherein the total area of the small holes uniformly distributed on the isolation circular plate accounts for 5 to 15%, for example 10%, of the area of the isolation circular plate at the periphery of the central circular hole.

A method according to any of the embodiments of the third aspect of the present application, wherein said dripper nozzle is located on the axis of the cooling portion of the barrel-shaped dripping pill.

The method according to any embodiment of the third aspect of the present application, wherein the dripper nozzle, the insulating circular plate and its central circular hole, and the stirring paddle are coaxial with the axis of the cooling part of the cylindrical dripping pill.

The method according to any embodiment of the third aspect of the present application, wherein the stirring paddle is disposed 10 to 30mm (e.g. 15 to 25mm, e.g. 20mm) below the insulating circular plate.

The method according to any embodiment of the third aspect of the present application, wherein the amplitude of the up-and-down reciprocating vibration of the dripper is 2 to 50 mm.

The method according to any embodiment of the third aspect of the present application, wherein the amplitude of the up-and-down reciprocating vibration of the dripper is 3 to 30 mm.

The method according to any embodiment of the third aspect of the present application, wherein the amplitude of the up-and-down reciprocating vibration of the dripper is 4 to 20 mm.

The method according to any embodiment of the third aspect of the present application, wherein the amplitude of the up-and-down reciprocating vibration of the dripper is 5 to 15 mm.

The method according to any of the embodiments of the third aspect of the present application, wherein the dripper completes one complete up-and-down oscillating movement in 0.1 to 5 seconds.

The method according to any embodiment of the third aspect of the present application, wherein the dripper completes one complete up-and-down oscillating movement in 0.2 to 4 seconds.

The method according to any of the embodiments of the third aspect of the present application, wherein the dripper completes one complete up-and-down oscillating movement in 0.25 to 2.5 seconds.

The method according to any of the embodiments of the third aspect of the present application, wherein said up and down reciprocating vibration of the dripper is achieved by a vibration device attached to the dripper.

A method according to any embodiment of the third aspect of the present application, wherein the vibration device is as described in any embodiment of the second aspect of the present application.

This application fourth aspect provides a vibrating device for preparing multilayer dripping pill, and this vibrating device makes the dripper of preparation dripping pill can make reciprocating vibration from top to bottom when dripping the system dripping pill, and this vibrating device includes:

a motor;

The vibration device according to any one of the embodiments of the fourth aspect of the present application, which provides the dripper with an amplitude of 2 to 50mm up and down.

The vibration device according to any one of the embodiments of the fourth aspect of the present application, which provides the dripper with an amplitude of 3 to 30mm up and down.

The vibration device according to any one of the embodiments of the fourth aspect of the present application, which provides the dripper with an amplitude of 4 to 20mm up and down.

The vibration device according to any one of the embodiments of the fourth aspect of the present application, which provides the dripper with an amplitude of 5 to 15mm up and down.

The vibrating device according to any one of the embodiments of the fourth aspect of the present application, wherein the time for providing the dripper with a complete up-and-down vibrating motion is 0.1 to 5 seconds.

The vibrating device according to any one of the embodiments of the fourth aspect of the present application, wherein the time for providing the dripper with a complete up-and-down vibrating motion is 0.2 to 4 seconds.

The vibrating device according to any one of the embodiments of the fourth aspect of the present application, wherein the time for providing the dripper with a complete up-and-down vibrating motion is 0.25 to 2.5 seconds.

Further, the fifth aspect of the present application provides a pill receiving device used in cooperation with a multilayer pill device, where the multilayer pill device includes:

(ii) the material supply pipeline is connected with the dripper;

(iii) material supply tank;

(v) a pill receiving device which comprises a cylindrical pill cooling part and a reverse-cone-shaped pill recovery part connected to the lower part of the cylindrical pill cooling part, wherein the pill receiving device is filled with cooling liquid when the multilayer pill equipment works;

it is characterized in that the preparation method is characterized in that,

the drip nozzle of the dripper extends below the liquid level of the cooling liquid, so that the drip nozzle is at least positioned at a position 10-20 mm (13-17 mm, for example, 15mm) below the liquid level in the up-and-down reciprocating process of the dripper;

an isolation circular plate is coaxially arranged in the middle of the cooling part of the barrel-shaped dropping pill, and when the dripper is positioned at the bottommost part in the up-and-down reciprocating process, the vertical height of the dripping nozzle from the isolation circular plate is 10-30 mm (for example, 15-25 mm, for example, 20 mm);

a central circular hole with the diameter of 8-15 mm (such as 10mm) is arranged at the right center of the isolation circular plate, and the drip nozzle is positioned right above the central circular hole, so that a small pill dropping from the drip nozzle passes through the central circular hole to descend into the pill recovery part in the sinking process;

a plurality of small holes with the diameter of 2-5 mm (such as 3mm) are uniformly distributed on the periphery of the central circular hole of the isolation circular plate, so that cooling liquid can be exchanged up and down on the isolation circular plate;

a stirring paddle is arranged right below the central circular hole of the isolation circular plate of the pill cooling part for stirring the cooling liquid and enabling the pills to be dispersed and settled after entering the lower part of the isolation circular plate.

The pill receiving device according to any embodiment of the fifth aspect of the present application, wherein the total area of the small holes uniformly distributed on the isolation circular plate accounts for 5-15%, for example, 10% of the area of the isolation circular plate at the periphery of the central circular hole.

A pill receiving apparatus according to any one of the embodiments of the fifth aspect of the present application, wherein the dripper nozzle is located on the axis of the drum-like pill cooling section.

The pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the dripper nozzle, the isolation circular plate and its central circular hole, and the stirring paddle are coaxial with the axis of the cooling part of the barrel-shaped pill.

A pill receiving device according to any embodiment of the fifth aspect of the present application, wherein the stirring paddle is disposed 10-30 mm (e.g. 15-25 mm, e.g. 20mm) below the isolation circular plate.

A pill receiving apparatus according to any one of the embodiments of the fifth aspect of the present application, wherein the material supply line is fixed within a frame both at the end connected to the dripper and at the dripper; the top of the frame box is connected with a vibration device, so that the frame box and the drippers in the frame box can vibrate up and down in a reciprocating manner. Therefore, the dripper can be directly connected with the vibration device or indirectly connected with the vibration device in a frame box mode.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibration device provides the dripper with an amplitude of 2-50 mm up and down.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibration device provides an amplitude of 3-30 mm up and down to the dripper.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibration device provides the dripper with an amplitude of 4-20 mm up and down.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibration device provides an amplitude of 5 to 15mm up and down to the dripper.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibrating device provides the dripper with a complete up-and-down vibrating motion for 0.1 to 5 seconds.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibrating device provides the dripper with a complete up-and-down vibrating motion for 0.2 to 4 seconds.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the vibrating device provides the dripper with a complete up-and-down vibrating motion for 0.25 to 2.5 seconds.

A pill receiving device according to any one of the embodiments of the fifth aspect of the present application, wherein said vibrating device comprises:

a motor;

A pill receiving apparatus according to any one of the embodiments of the fifth aspect of the present application, wherein the set of temperature control systems individually controls a set of drippers, material supply lines and material supply tanks. In this way, independent temperature control of the materials of the different layers can be easily achieved.

A drop pill receiving apparatus according to any one of the embodiments of the fifth aspect of the present application, wherein the temperature control system is a circulating hot air control system.

A drop pill receiving apparatus according to any one of the embodiments of the fifth aspect of the present application, wherein the drop pill receiving apparatus comprises a drop pill cooling section and a drop pill recovery section. The cooling part of the dripping pill is usually liquid paraffin, dimethicone, soybean oil, etc., preferably liquid paraffin. As is also well known to those skilled in the art.

A pill receiving device according to any of the embodiments of the fifth aspect of the present application, wherein the stirring paddle may be disposed at the bottom, top, side walls, etc. of the pill receiving device.

In the above-described steps of the preparation method of the present application, although the specific steps described therein are distinguished in some detail or in language description from the steps described in the preparation examples of the detailed description section below, the above-described method steps can be fully summarized by those skilled in the art in light of the detailed disclosure throughout the present application.

Any embodiment of any aspect of the present application may be combined with other embodiments, as long as they do not contradict. Furthermore, in any embodiment of any aspect of the present application, any feature may be applicable to that feature in other embodiments, as long as they do not contradict.

The present application is further described below.

All documents cited in this application are incorporated herein by reference in their entirety and to the extent that the meaning of such documents is inconsistent with this application, the express disclosure of this application controls. Further, the various terms and phrases used herein have the ordinary meaning as is known to those skilled in the art, and even so, it is intended that the present application be more fully described and interpreted herein, to the extent that such terms and phrases are not inconsistent with this known meaning and from the context in which such terms and phrases are expressed.

The equipment and the process provide a more advanced and reliable medicine wrapping technology, compared with capsule filling and coating technologies, the multi-layer dropping pill has better sealing performance and more comprehensive and reliable wrapping. It is believed that economic and social benefits will be significant after industrialization. Researchers of the present application have been devoted to studying the principle of the multilayer dropping pill process and the implementation method thereof; the researchers designed and manufactured three-layer pill dropping equipment which can be used for industrialization.

The multilayer dripping pill device and the process thereof can industrially produce spherical multilayer medicaments or food preparations with different components, and can be dripped into two layers, three layers and four layers as far as the required layers. A schematic representation of a trilayer pill is depicted, for example, in figure 1 of chinese patent No. ZL2016202539660 or, for example, in figure 1 of chinese patent No. ZL 2016210586095, wherein the outer and intermediate layers are thicker than the outer layer of the current conventional softgel pellicle, as described herein, which prior art processing equipment is not capable of dropping pills of such thickness.

Drawings

Fig. 1 is a schematic cross-sectional view of a dripper of the present application (three-layer).

Fig. 2 is a bottom caliber of the dripper (three layers) of the present application, which is gradually reduced to form a drip nozzle, and the drip nozzle is schematically illustrated from the bottom of the dripper in a look-up manner, and the lower edge of the drip nozzle is three concentric circles, and sequentially comprises an inner layer material introduction part bottom end, an intermediate material introduction part bottom end and an outer layer material introduction part bottom end from inside to outside, wherein the innermost layer is used for flowing out of the inner layer material, the intermediate layer is used for flowing out of the intermediate material, and the outermost layer is used for flowing out of the outer layer material.

Fig. 3 is a schematic view of multilayer dripping pill equipment, parts thereof and a preparation process of multilayer dripping pills, wherein only one set of material flow is shown in the view, and a cooling system is not shown.

Fig. 4 is a schematic structural diagram of a vibration device according to the present application. Fig. 5 is a schematic cross-sectional view of a three-layer drop pill.

Fig. 6 is a schematic view of a pill receiving device of the present application. Fig. 7 is a schematic view of an isolation circular plate disposed inside a pill receiving device according to the present application.

Detailed Description

The present application can be further described by the following examples, however, the scope of the present application is not limited to the following examples. Those skilled in the art will appreciate that various changes and modifications can be made to the present application without departing from the spirit and scope of the application. The materials used in the tests and the test methods are generally and/or specifically described herein. Although many materials and methods of operation are known in the art for the purposes of this application, this application is nevertheless described herein in detail as far as possible. The following examples further illustrate the present application without limiting the same.

A drop pill as shown in the schematic stereomodel diagram depicted in fig. 1, see chinese patent No. ZL2016202539660, for example, is obtainable by the multi-layer (three-layer) dripper of the present application.

According to an example of the dripper used for manufacturing the multilayer dripping pill of the present application, schematically shown in fig. 1, the dripper is a combined structure that can be disassembled and assembled, and comprises:

i) the inner layer material introducing part 1 is generally in a shape of a nail, the upper expanded part 12 of the nail-shaped inner layer material introducing part 1 is provided with a first port 14 for connecting with the connecting part 4, the nail-shaped inner layer material introducing part 1 is provided with a through inner layer through hole 11 from the top to the bottom, and the inner layer through hole 11 is used for enabling the inner layer material to flow from the upper end to the bottom end of the inner layer material introducing part 1 and flow out;

ii) an intermediate material introduction member 2, which is generally nail-shaped, the upper enlarged portion 22 of the nail-shaped intermediate material introduction member 2 being provided with a second port 24 for connection with the connecting member 4, the nail-shaped intermediate material introduction member 2 being provided with a through-going intermediate through-hole 21 from top to bottom; the middle through hole 21 has a larger aperture than the outer diameter of the lower end needle portion of the inner material inlet 1, and the lower end needle portion of the inner material inlet 1 is inserted into the middle through hole 21;

iii) an outer layer material introduction part 3 which is in the shape of an inverted hollow cone overall, the upper end expansion 32 of the conical outer layer material introduction part 3 being provided with a third connection 34 for connection to the connecting part 4; the hollow part 31 inside the conical outer material introduction member 3 is thicker than the outer diameter of the lower end needle part of the intermediate material introduction member 2, and the lower end needle part of the intermediate material introduction member 2 can be inserted into the hollow part 31 inside the outer material introduction member 3;

iv) a connecting part 4, which is generally cylindrical, and which is provided with a first port 14, a second port 24 and a third port 34 in sequence from top to bottom inside thereof for connecting with the inner layer material inlet 1, the middle material inlet 2 and the outer layer material inlet 3, respectively, so that the three material inlets are connected in a coaxial and integral manner inside the connecting part 4.

According to an example of the dripper used in the present application for preparing multilayer dripping pills, as shown in fig. 1, the dripper is described with its nozzle facing downward, and in fact, the dripper is also in the same direction during operation, and the upper part of the dripper is provided with an interface 51 that can be connected to a vibration device (described later) that enables the dripper to vibrate up and down reciprocally when dripping pills. Other ways of connecting the dripper to the vibration unit are also suitable and both may be designed in one piece, although due to the need for cleaning it is preferred that the dripper (itself and inside) is connected to the vibration unit in a way that it can be easily disassembled and assembled.

An example of a dripper for use in the manufacture of multilayer dripping pills according to the present application, wherein the first junction 14, the second junction 24 and the third junction 34 are each independently in a structure selected from: screw structure, plug-in connection structure. The interfaces are generally configured to achieve the desired seal. The threaded configuration is preferred because it is easier to seal and is durable.

According to an example of the dripper of the present application for manufacturing multilayer dripping pills, there is a gap, called the first gap 13, between the lower edge of the upper end bulge 12 of the nail-like inner material inlet 1 and the upper edge of the upper end bulge 22 of the nail-like intermediate material inlet 2 after the assembly of the inner material inlet 1, the intermediate material inlet 2, the outer material inlet 3 and the connecting part 4.

According to an example of the dripper for the production of multilayer dripping pills according to the present application, the wall of the connecting part 4 in the form of a drum is provided, facing the first interspace 13, with one or more holes for the introduction of an intermediate material, called intermediate material introduction hole(s) 41. Thus, the intermediate material passes through the intermediate material introduction hole 41 of the connection member 4, enters the first gap 13, and flows down to the outlet of the dripper through a gap formed by the diameter of the intermediate through hole 21 being larger than the outer diameter of the needle-like portion at the lower end of the inner layer material introduction member 1. Two intermediate feed introduction holes 41 are shown in fig. 1.

According to an example of the dripper of the present application for the production of multilayer dripping pills, after the assembly of the inner layer material inlet 1, the intermediate material inlet 2, the outer layer material inlet 3 and the connecting part 4, there is a gap between the lower edge of the upper end bulge 22 of the nail-like intermediate material inlet 2 and the upper edge of the upper end bulge 32 of the conical outer layer material inlet 3, this gap being referred to as the second gap 23.

According to an example of the dripper for the manufacture of multilayer dripping pills of the present application, the wall of the connecting part 4 in the form of a drum is provided, in correspondence of the second interspace 23, with one or more holes for the introduction of the external layer material, called external layer material introduction hole(s) 42. Thereby, the outer material passes through the outer material introducing hole 42 of the connecting member 4, enters the second gap 23, and flows down to the outlet of the dripper through the gap formed by the inner hollow portion 31 of the outer material introducing member 3 being thicker than the outer diameter of the lower end needle portion of the intermediate material introducing member 2. Two outer layer material introduction holes 42 are shown in fig. 1.

According to an example of the dripper of the present application for the production of multilayer dripping pills, the lower edges of the inner material inlet 1, of the intermediate material inlet 2 and of the outer material inlet 3 are flush. Therefore, when the inner layer material flowing out of the inner layer through hole 11 in the inner layer material introducing member 1 flows out from the lower end outlet of the inner layer through hole 11, the inner layer material is wrapped by the intermediate material flowing out through the first gap 13 to form a double-layer pellet; which in turn are coated with the outer material flowing out through the second gap 23 to form three-layer pellets.

According to the embodiment of the dripper for producing the multilayer dripping pill, the upper end of the inner through hole 11 is connected with an inner material supply device to provide uninterrupted inner material.

According to one example of a dripper for the production of multilayer dripping pills according to the present application, one or more of the intermediate feed introduction holes 41 are connected to an intermediate feed supply means, providing an uninterrupted intermediate feed.

According to one embodiment of the dripper for the preparation of multilayer dripping pills according to the present application, one or more of the outer layer material introduction holes 42 is connected to an outer layer material supply means to provide an uninterrupted outer layer material.

According to one example of a dripper for the preparation of multilayer dripping pills according to the present application, it comprises an intermediate material inlet 2 and is intended for the preparation of three layers of dripping pills. The exemplary dripper of figure 1 is the design used to prepare three-layered dripping pills.

According to one example of a dripper for the preparation of multilayer dripping pills according to the present application, it comprises two intermediate material introducers (2) and is intended to prepare four-layer pills. Preferentially, the two intermediate material introducing parts 2 are basically the same in shape and are different in thickness and length; wherein the elongated intermediate material introduction member 2 is connected to the inner layer material introduction member 1, the short and thick intermediate material introduction member 2 is connected to the outer layer material introduction member 3, and the needle-shaped portion of the lower end of the elongated intermediate material introduction member 2 is inserted into the intermediate through hole 21 in the short and thick intermediate material introduction member 2. Similarly, when three intermediate material introduction members 2 are included and arranged in a similar manner as described above, they can be used to prepare five-layer dropping pills.

An example of a dripper for producing a multilayer dripping pill according to the present application comprises 1-4 intermediate material introducers 2. Preferentially, the device comprises 1-3 intermediate material introduction pieces 2. Preferentially, the device comprises 1-2 intermediate material introduction pieces 2. Preferably, it comprises 1 intermediate material inlet 2. The exemplary dripper of fig. 1 is a design for preparing three-layered dripping pills, using 1 intermediate material introduction part 2.

According to the embodiment of the dripper for preparing the multilayer dripping pill, the wall of the cylindrical connecting part 4 is provided with 1-3 intermediate material introducing holes 41 at the position opposite to the first gap 13. Preferably, 2 intermediate material introducing holes 41 are arranged, wherein one hole is used for introducing the intermediate material, and the other hole is reserved and can be blocked by a plug when not used; or 2 intermediate material introduction holes 41 are used for introducing intermediate materials; alternatively, one opening is used for introducing the intermediate material (which is provided at its front end with a pressure pump for forcing the intermediate material to flow in a pressurized manner in the direction of the drippers), the other opening is used for discharging the intermediate material (which is not pressurized at its rear end and which can discharge excess material or for regulating the pressure of the intermediate material in the drippers) and the material discharged at this time is returned to the intermediate material tank via a circuit. It has been surprisingly found that when the wall of the connecting part 4, which is in the form of a drum, is provided with 2 intermediate material introduction holes 41 facing the first gap 13, and one hole is used for introducing the intermediate material and the other hole is used for leading out the intermediate material, the roundness of the dropping pill obtained in this way is significantly higher than that of a design scheme with only one intermediate material leading-in hole 41 (the roundness of the dropping pill is the ratio of the shortest diameter to the longest diameter of the dropping pill, the average roundness of the dropping pill is in the range of 0.89-0.92 when one intermediate material leading-in hole is arranged, and when 2 intermediate material leading-out holes are arranged as described above, the roundness of the dropping pill is in the range of 0.96-0.99 (the two numerical ranges are 6 different material test values), and the numerical values are obtained by the dropping head arranged in the manner that the 2 intermediate material leading-in holes 41 are arranged in one inlet and one outlet as described above at the outer layer material leading-in hole 42).

According to an example of the dripper for preparing the multilayer dripping pill, the wall of the connecting part 4 in the shape of a circular barrel is provided with 1-3 outer layer material leading-in holes 42 at the position opposite to the second gap 23. Preferably, 2 outer layer material introducing holes 42 are provided, wherein one hole is used for introducing the outer layer material, and the other hole is reserved and can be blocked by a plug when not in use; or 2 outer layer material leading-in holes 42 are used for leading in the outer layer material; alternatively, one hole is used for introducing the outer material (the front end of the hole is provided with a pressure pump to enable the outer material to flow towards the dripper in a pressure mode), the other hole is used for discharging the outer material (the rear end of the hole is not provided with pressure, the hole can discharge redundant material or can be used for adjusting the pressure of the inner material and the outer material of the dripper), and the discharged material flows back to the outer material pool through the loop. It has been found that, surprisingly, when the wall of the connecting part 4 in the form of a drum is provided with 2 outer material feed openings 42 facing the second gap 23, and one opening is used for feeding in the outer material and the other opening is used for discharging the outer material, the pill roundness obtained in this way is significantly higher than in the design with only one outer material feed opening 42 (the average pill roundness is in the range from 0.88 to 0.92 when one outer material feed opening is provided, whereas the pill roundness is in the range from 0.97 to 0.99 when 2 outer material feed openings are provided one in one out as described above (both values being 6 different material test values), which are obtained in the case of a dripper with an intermediate material feed opening 41 also provided in one out 2 outer material feed openings 42 as described above).

An example of a dripper for use in the preparation of multilayer dripping pills according to the present application is a dripper for use in the preparation of three-layer dripping pills. Only one intermediate material feed 2 is present.

According to an example of the dripper for producing multilayer dripping pills, the inner material inlet 1, the intermediate material inlet 2 and the outer material inlet 3 are all reduced in diameter at the bottom to form a nozzle 5.

As shown in fig. 2, according to an example of the dripper for preparing the multilayer dripping pill of the present application, the lower edge of the dripper 5 seen from the bottom of the dripper is in three concentric circles, and the lower edge is sequentially composed of the bottom end of the inner material lead-in 1, the bottom end of the intermediate material lead-in 2 and the bottom end of the outer material lead-in 3 from inside to outside, wherein the innermost layer is used for the outflow of the inner material, the intermediate layer is used for the outflow of the intermediate material, and the outermost layer is used for the outflow of the outer material.

According to an example of the dripper used in the present application for the preparation of a multilayer dripping pill, as shown in fig. 2, the lower edge of the dripper as seen from the bottom thereof is in three concentric circles to form an innermost region 15, an intermediate region 25, and an outermost region 35. When tested using 6 different materials, it has been found that the area of the innermost zone 15: interlayer region 25 area: outermost region 35 area is 1: when the ratio is selected within a wide range of 0.5-5: 1-10, the method can prepare the dropping pill with the rounding degree of more than 0.95 (the test result obtained by adopting the design mode of one in one out of 2 holes for the middle material introducing hole 41 and the outer material introducing hole 42), unfortunately, the same materials are tested by adopting a three-layer design scheme (for example, figure 4 of CN 100506093C-200480028272.1, figure 1 of CN 201750916U-201020224428.1 and figure 3 of CN 104219951A-201280067210.1) of some documents, and the area of the innermost layer area in the schemes of the documents is adjusted: area of the intermediate layer region: the outermost region area is also 1: when the ratio is selected within a large variation range of 0.5-5: 1-10, the roundness of the obtained dropping pills is within a range of 0.67-0.84, and the dropping effect of the dropping pills is obviously inferior to that of the scheme of the application.

According to an example of a dripper for preparing multilayer dripping pill of this application, the dripper that sees from its lower part when looking up is followed and is appeared and be three concentric circles, forms inlayer region, intermediate layer region, outermost layer region, and these three's area ratio is inlayer regional area promptly: area of the intermediate layer region: outermost region area 1: 0.5-5: 1-10.

According to one example of a dripper for use in the preparation of multilayer dripping pills according to the present application, it may be used in conventional multilayer dripping pill equipment, for example as described in CN 100506093C-200480028272.1, CN 201750916U-201020224428.1, CN 104219951A-201280067210.1. In one example, the dripper of the present application is used in a multilayer dripping pill apparatus. These multi-level drop pill devices typically include a material supply system connected to the drippers, and a temperature control system that controls the temperature of the material and drippers.

As illustrated in fig. 3, the present application further provides a multilayer dripping pill device, which includes: drippers (in particular, for example, drippers of the first aspect of the present application) 101; a material supply line 102 connected to the dripper; a material supply tank 103; a temperature control system (for example, comprising a fan 104, a hot air pipeline 105, a heater 106, a temperature probe 107 and an air volume adjusting valve 108) for providing temperature control for the material supply tank 103, the material supply pipeline 102 and the dripper 101; and a pill receiving means 109.

In the multilayer dripping pill device, the dripping nozzle 5 of the dripping head 101 faces downwards, the upper part of the dripping head 101 is connected with a vibrating device 110, and the vibrating device 110 enables the dripping head 101 to vibrate up and down in a reciprocating mode.

In the multi-layer pill making apparatus of the present application, the pill receiving device 109 comprises a cylindrical pill cooling portion 1091 and a reverse conical pill recovery portion 1092 connected to a lower portion thereof, and the pill receiving device 109 is filled with a cooling liquid when the multi-layer pill making apparatus is in operation.

In this application multilayer dripping pill equipment, the drip mouth 5 of dripper 101 stretches into below the liquid level of coolant liquid for dripper 101 reciprocates the in-process drip mouth 5 and is located 10~20mm (for example 13~17mm, for example 15mm) below the liquid level at least.

In the multi-layer pill making device, an isolation circular plate 1093 is coaxially arranged in the middle of a barrel-shaped pill cooling part 1091, and when the dripper 101 is located at the bottommost part in the up-and-down reciprocating process, the vertical height of the drip nozzle 5 from the isolation circular plate 1093 is 10-30 mm (e.g., 15-25 mm, e.g., 20 mm).

In the multi-layer pill making device of the present application, a central circular hole 10931 with a diameter of 8-15 mm (e.g. 10mm) is disposed at the center of the isolation circular plate, and the drip nozzle 5 is located right above the central circular hole 10931, so that the pills dropping from the drip nozzle 5 pass through the central circular hole 10931 and enter the pill recovery portion 1092 in the sinking process.

In this application multilayer dripping pill equipment, the peripheral evenly distributed that keeps apart the plectane 1093 and be located central round hole 10931 is provided with a plurality of diameters 2~5mm (for example 3mm) aperture 10932 and makes the coolant liquid can exchange from top to bottom at isolation plectane 1093.

In the multi-layer pill making device of the present application, a stirring paddle 1094 is disposed under the central circular hole 10931 of the isolation circular plate 1093 of the cooling portion 1091 to stir the cooling liquid and make the pellets disperse and settle after entering under the isolation circular plate 1093.

In this application multilayer dripping pill equipment, the aperture 10932 total area that evenly distributed set up on isolating circular plate 1093 accounts for 5~15%, for example 10% of the peripheral isolated circular plate area of center round hole 10931.

In the multi-layer drop pill apparatus of the present application, the dripper nozzle 5 is located on the axis of the cylindrical drop pill cooling section 1091.

In the multi-layer pill making device of the present application, the dripper nozzle 5, the isolation circular plate 1093 and its central circular hole 10931, and the stirring paddle 1094 are coaxial with the axis of the cylindrical pill cooling portion 1091.

In the multilayer dripping pill equipment of this application, stirring rake 1094 sets up 10~30mm (for example 15~25mm, for example 20mm) department below keeping apart plectane 1093.

In the multilayer dripping pill device, the material supply pipeline is fixed in a frame box at the tail end connected with the dripper and the dripper; the top of the frame box is connected with a vibration device, so that the frame box and the drippers in the frame box can vibrate up and down in a reciprocating manner. Therefore, the dripper can be directly connected with the vibration device or indirectly connected with the vibration device in a frame box mode. The frame box aims to conveniently fix the dripper and the material supply pipeline thereof together, the frame box can be a box enclosed by the upper surface and the four peripheral surfaces, and the bottom surface is open so as to extend downwards from the dripper and further ensure that the drip nozzle extends below the liquid level of the cooling liquid, so the design of the frame box does not need special requirements.

In this application multilayer dripping pill equipment, the drip mouth 5 of dripper 101 is down, and dripper upper portion is connected with a vibrating device 110, and this vibrating device 110 makes this dripper 101 can make the vibration of reciprocating from top to bottom. In an exemplary embodiment, as shown in fig. 3, the material supply line 102 is fixed in a box (an exemplary box with an opening at the bottom of the outside of the dripper 101 as shown in fig. 3) at both the end connected to the dripper 101 and the dripper 101; the top of the frame box is connected with a vibration device 110, so that the frame box and the dripper 101 inside the frame box can vibrate up and down in a reciprocating manner. Therefore, the dripper can be directly connected with the vibration device or indirectly connected with the vibration device in a frame box mode. The frame box aims to conveniently fix the dripper and the material supply pipeline thereof together, the frame box can be a box enclosed by the upper surface and the four peripheral surfaces, and the bottom surface is open so as to extend downwards from the dripper 101 and further ensure that the dripper 5 extends below the liquid level of the cooling liquid, so the design of the frame box can be free from special requirements.

Because one layer of the dripper is connected with a set of material supply pipeline and a set of material supply tank, a set of temperature control system can control a set of dripper, material supply pipeline and material supply tank. Of course, a set of temperature control system can be used to control multiple sets of drippers, material supply pipelines and material supply tanks simultaneously. FIG. 3 illustrates the use of a set of temperature control systems to control a set of drippers, material supply lines and material supply tanks.

According to an example of the multilayer dripping pill apparatus of the present application, wherein the temperature control system is a circulating hot air control system.

Further, this application provides a supporting dripping pill receiving arrangement who uses in multilayer dripping pill equipment, multilayer dripping pill equipment is as described above in this application. Fig. 6 and 7 illustrate the pill receiving device 109 and the isolation circular plate 1093 disposed therein, respectively, and will now be described with reference to fig. 6 and 7.

According to one embodiment of the present application, wherein the pill receiving mechanism 109 includes a cylindrical pill cooling portion 1091 and a reverse-tapered pill retrieving portion 1092 connected to a lower portion thereof, the pill receiving mechanism 109 is filled with a cooling fluid when the multi-level pill making apparatus is in operation. The cooling liquid of the dripping pill is liquid paraffin, dimethicone, soybean oil, etc., preferably liquid paraffin. As is also well known to those skilled in the art.

In accordance with one embodiment of any aspect of the present application, the upper portion of the pill receiving device 109, preferably below the surface of the cooling fluid, is provided with a cooling fluid inlet 1095. According to one embodiment of any aspect of the present application, the bottom of the pill receiving device 109, preferably the bottom of the inverted cone-shaped pill recovery portion 1092, is provided with a coolant outlet 1096, which also serves as a pill collection port. It is known that a cooling liquid enters from the upper part of the pill receiving device, cools the prepared pills at a higher temperature, and the pills sink to a pill recovery part at the bottom in the cooling process and flow out of the receiving device along with the cooling liquid which flows out circularly.

The classical dropping process includes two types, i.e. (1) downward and (2) upward, as depicted in pages 9-22 of 286 of the classic textbook pharmacy (edited by xi thought of the Zhu president, 3 rd edition 1994) in the art, wherein the downward dropping process is such that the nozzle is above the surface of the coolant and the drop drops from above into the coolant. The applicant's other patents assigned ZL2016202539660 and ZL 2016210586095 disclose a top-down dispensing process. The present inventors have found that although the above-described schemes ZL2016202539660 and ZL 2016210586095 can provide dripping pills with excellent roundness and concentricity structural characteristics, unfortunately, these processes result in dripping pills with uneven weight and size among the pills, which can cause problems with uniformity of the drug among each pill, and thus inaccurate administration. The present inventors have surprisingly found that by extending the nozzle below the surface of the cooling liquid and agitating the cooling liquid with the provision of the isolation disks, the resulting drop pills not only retain the structural features of excellent roundness and concentricity, but also have a significant increase in weight and size uniformity between the pellets. This design is described in detail below.

According to an example of any aspect of the present application, the drip nozzle 5 of the dripper 101 extends below the liquid level of the cooling liquid 1099, so that the drip nozzle 5 is located at least 10-20 mm (e.g., 13-17 mm, e.g., 15mm, as not specifically mentioned, the test results obtained in the present application are obtained with this 15mm setting) below the liquid level during the up-and-down reciprocating of the dripper 101.

According to an embodiment of any aspect of the present application, an isolation circular plate 1093 is coaxially disposed at the middle of the cooling portion 1091, and when the dripper 101 is at the bottom during the up-and-down reciprocating process, the vertical height of the nozzle 5 from the isolation circular plate 1093 is 10 to 30mm (e.g., 15 to 25mm, e.g., 20mm, and the test results obtained by the present application are obtained with this 20mm disposition, if not specifically mentioned).

According to an example of any aspect of the present application, a central circular hole 10931 with a diameter of 8-15 mm (e.g. 10mm, as not specifically mentioned, the test results obtained in the present application are obtained with this 10mm setting) is provided at the very center of the isolation circular plate 1093, and the nozzle 5 is located directly above the central circular hole 10931, so that pellets dropping from the nozzle 5 during sinking pass through the central circular hole 10931 to descend into the pill recovery portion 1092.

According to an example of any aspect of the present application, the isolation circular plate 1093 is uniformly distributed on the periphery of the central circular hole 10931 and is provided with a plurality of small holes 10932 with diameters of 2-5 mm (e.g., 3mm, as not specifically mentioned, the test result obtained by the present application is obtained with such 3mm arrangement) so that the cooling liquid can be exchanged up and down on the isolation circular plate 1093.

According to an example of any aspect of the present application, a stirring paddle 1094 is provided just below the central circular hole 10931 of the separation disk 1093 of the pill cooling part 1091 to stir the cooling liquid and make the pellets disperse individually to settle after entering below the separation disk 1093.

Use multilayer dripping pill equipment of this application to prepare multilayer dripping pill (for example three-layer dripping pill) is easy to realize, combine figure 3 to explain this application about the method of using multilayer dripping pill equipment to prepare multilayer dripping pill, this method can include following step usually: 1) respectively preparing materials of each layer of the dripping pill; 2) adding each layer of material to a respective material supply tank 103, each material supply tank 103 being connected to a respective material inlet of a respective layer of drippers 101 (in particular, for example, drippers according to the first aspect of the present application); 3) starting a temperature control system (for example, comprising a fan 104, a hot air pipeline 105, a heater 106, a temperature probe 107 and an air volume adjusting valve 108) to control the temperature of the materials in the material supply tank 103, the material supply pipeline 102 and the dripper 101 to be within a specified value or range of the materials; 4) after the temperature of each layer of materials is balanced, starting a dripping pill process to drip the dripping pills into the dripping pill receiving device 109; in the process of dropping pills, the dripper 101 is vibrated up and down by the operation of the vibration device 110.

Apparatus, components and devices in accordance with the present method for producing drop pills are as described herein, such as drop pill receiving device 109, and exhibits the characteristics including a drop pill cooling section and a drop pill recovery section as described herein.

In accordance with the method for manufacturing a drop pill of the present application, when all the equipment/devices are operated, the drop pill receiving device 109 is filled with a cooling liquid, and the drop pill receiving device 109 includes a cylindrical drop pill cooling portion 1091 and a drop pill recovery portion 1092 connected to a lower portion thereof and having an inverted cone shape.

According to the method for preparing the dropping pill, the drip nozzle 5 of the dripper 101 extends below the liquid level of the cooling liquid, so that the drip nozzle 5 is at least positioned 10-20 mm (13-17 mm, for example, 15mm) below the liquid level in the up-and-down reciprocating process of the dripper 101.

According to the method for preparing the dripping pill, an isolation circular plate 1093 is coaxially arranged in the middle of a barrel-shaped dripping pill cooling part 1091, and when the dripping head 101 is positioned at the bottommost part in the up-and-down reciprocating process, the vertical height of the dripping nozzle from the isolation circular plate is 10-30 mm (for example, 15-25 mm, for example, 20 mm).

According to the method for preparing the dropping pill of the present application, a central circular hole 10931 with a diameter of 8-15 mm (for example, 10mm) is disposed at the center of the isolation circular plate 1093, and the dropping nozzle 5 is located right above the central circular hole 10931, so that the dropping pill from the dropping nozzle 5 passes through the central circular hole 10931 and enters the dropping pill recovery portion 1092 in the sinking process.

According to the method for preparing the dripping pill, the isolation circular plate 1093 is uniformly distributed on the periphery of the central circular hole 10931 and is provided with a plurality of small holes 10932 with diameters of 2-5 mm (for example, 3mm), so that cooling liquid can be exchanged up and down on the isolation circular plate 1093.

According to the method for preparing the dripping pill of the present application, a stirring paddle 1094 is provided right under the center circular hole 10931 of the isolation circular plate 1093 of the cooling part to stir the cooling liquid and make the pellets disperse and settle after entering under the isolation circular plate 1093.

It has been surprisingly found that by immersing the mouth of the dripper below the liquid level and providing isolating disks in the dripping pill receiving apparatus, excellent weight uniformity of the dripping pills with respect to each other can be obtained with significantly reduced weight variation. Weight uniformity determination and evaluation methods: according to the specification of the method loaded by 0941 content uniformity inspection method in the four parts of the Chinese pharmacopoeia of the 2015 edition, 30 pills are taken for each batch of prepared pills, the pills are weighed one by one, the arithmetic mean X and the standard deviation SD of the weights of the pills are calculated, and the relative standard deviation RSD of the weights of the pills in the batch is further calculated. Generally speaking, the smaller the RSD, the better the uniformity of the detected product; in the field of pharmaceutical formulation manufacture, RSD values between the smallest unit doses of less than 1% indicate a desirable uniformity of the product, RSD values of less than 0.5% indicate a highly desirable uniformity of the product, and values of greater than 5% are generally considered unacceptable. The effect of the present application will be illustrated by taking the three-layer dropping pill prepared by the apparatus, device and method of the present application as an example. Exemplary materials used in the preparation of three-layer pills herein, as not otherwise specified, are as follows: CN106821998A, example 1, wherein the oily liquid containing vitamin a, vitamin D2, edible vegetable oil, and sorbitan fatty acid ester obtained when preparing vitamin AD pellet is used as the inner layer material of the three-layer pill, the aqueous solution containing 15% gelatin and 5% glycerin is used as the middle layer material of the three-layer pill, and the aqueous solution containing 15% gelatin, 5% glycerin and 2% sucrose is used as the middle layer material of the three-layer pill; when the formula of the materials needs to be changed, all the materials are adjusted within the range of 80-120% of the proportion range. The dripper for preparing the three-layer dripping pill is characterized in that 2 middle material inlet holes which are arranged in one inlet and one outlet are arranged on the wall of the cylindrical connecting part at the position opposite to the first gap, 2 outer material inlet holes which are arranged in one inlet and one outlet are arranged on the wall of the cylindrical connecting part at the position opposite to the second gap, and the area ratio of the outermost three-layer region of the innermost middle layer formed by the three concentric circles on the lower edge of the dripper is 1: 0.5-5: 1-10, and dripping pills from a dripping nozzle suspended above a cooling liquid by a method disclosed in patent ZL 2016210586095 and combined with an equipment device shown in figures 1, 3 and 4 (namely, a dripping pill receiving device shown in figures 6 and 7 is not used) by using a dripping pill head with the frequency of 0.25-2.5 seconds and the amplitude of 5-15 mm in a reciprocating manner, wherein the roundness and deviation P values of the obtained dripping pills are respectively in an ideal range of 0.96-0.99 and 0.002-0.03, but the weight uniformity measurement result shows that RSD is in an unacceptable range of 4.3-6.7%. In addition, the dripper for preparing the three-layer dripping pill described in the application is used, 2 middle material inlet holes which are arranged in a way of being aligned with a first gap are formed in the wall of the cylindrical connecting part, 2 outer material inlet holes which are arranged in a way of being aligned with a second gap are formed in the wall of the cylindrical connecting part, the area ratio of the outermost three-layer region of the middle layer of the innermost layer formed by the three concentric circles on the lower edge of the dripper is 1: 0.5-5: 1-10, vibrating the dripper up and down in a reciprocating manner with a frequency of 0.25-2.5 seconds and an amplitude of 5-15 mm, and simultaneously using the dripping pill receiving device disclosed by the application, namely the design of the dripping pill receiving device disclosed by the application and shown in detail in figures 6 and 7 (specifically, the dripper nozzle extends below the liquid level of the cooling liquid so that the dripper is at least positioned 15mm below the liquid level in the up-and-down reciprocating process, the dripper is positioned at the position where the vertical height of the bottommost dripper from the isolation circular plate is 20mm, the diameter of the central circular hole is 10mm, the diameter of the small hole is 3mm, the total area of the small hole accounts for 10% of the area of the peripheral isolation circular plate of the central circular hole, and the deviation P values are respectively in ideal ranges of 0.97-0.99 and 0.003-0.02, and the weight uniformity measurement result shows that the RSD is in a very ideal range of 0.36-0.51%; however, as shown in FIG. 6, when only the isolation circular plate is removed or only the stirring paddle is removed, the RSD is increased to an unacceptable range of 3.8 to 5.3% although the roundness and deviation P of the dropping pill are in the ideal ranges of 0.98 to 0.99 and 0.003 to 0.03, respectively.

In addition, according to the method for preparing the dripping pill of the present application, by applying such up-and-down reciprocating vibration to the dripper, excellent roundness between the cores of the layers of the dripped multilayer dripping pill and excellent concentricity between the cores of the layers can be achieved, so that the multilayer dripping pill of the present application has an excellent uniform structure.

According to the method for preparing the dripping pill, the total area of the small holes 10932 uniformly distributed on the isolation circular plate 1093 accounts for 5-15%, for example 10%, of the area of the isolation circular plate at the periphery of the central circular hole 10931.

According to the method for preparing the dripping pill of the present application, the dripper nozzle 5 is located on the axis of the cooling part 1091 of the cylindrical dripping pill.

According to the method for preparing the dropping pill, the dropping nozzle 5, the isolation circular plate 1093 and the central circular hole 10931 thereof, and the stirring paddle 1094 are coaxial with the axis of the cooling part 1091 of the cylindrical dropping pill.

According to the method for preparing the dripping pill, the stirring paddle 1094 is disposed 10-30 mm (e.g., 15-25 mm, e.g., 20mm) below the isolation circular plate 1093.

According to the method for preparing the dripping pill, the up-and-down reciprocating vibration of the dripping head 101 is realized by a vibration device 110 connected to the dripping head 101.

A method of manufacturing a dripping pill according to the present application, the vibrating device 101 is as described in any of the embodiments of the present application, for example in any of the embodiments of the second aspect of the present application.

The amplitude of the up-and-down reciprocating vibration of the dripper can be 2-50 mm, 3-30 mm, 4-20 mm or 5-15 mm; the time for the dripper to complete a complete up-and-down vibration motion is 0.1-5 seconds, 0.2-4 seconds, or 0.25-2.5 seconds.

According to the present application, the vibration device 110 is exemplarily shown in fig. 4, and includes: a motor 111; an eccentric wheel 112, which includes a central hole 113 and at least one eccentric hole 114, wherein the central hole 113 is driven by the motor 111 and drives the eccentric wheel 112 to rotate to make a circular motion, the eccentric hole 114 is deviated from the wheel center, and the distances from the central hole are different; a first driving rod 115 having a first end connected to one eccentric hole 114; and a second transmission rod 116, the first end of which is connected with the second end of the first transmission rod 115, and the second end of which is connected with the dripper 101; the first driving lever 115 converts the circular motion of the eccentric wheel 112 into the up-and-down reciprocating motion of the second driving lever 116. By designing different distances between the eccentric hole 114 and the central hole 113, the requirement of amplitude of up-and-down movement of the dripper 101 can be met.

The vibration device 110 can provide an amplitude of 2-50 mm, 3-30 mm, 4-20 mm and 5-15 mm for the dripper 101, and the time for completing a complete up-and-down vibration motion is 0.1-5 seconds, 0.2-4 seconds or 0.25-2.5 seconds. These amplitudes can be easily adjusted by the distance of the central hole 113 and the eccentric hole 114, and thus providing a plurality of eccentric holes 114 having different distances can achieve different process requirements. In addition, the vibration period can be easily controlled by the rotation speed of the motor. It has been found that the deviation P value of the two-layer dropping pill or the three-layer dropping pill obtained by applying a reciprocating up and down vibration to the dropper in the range of 2 to 50mm, particularly 3 to 30mm, particularly 4 to 20mm, particularly 5 to 15mm, and a vibration cycle in the range of 0.1 to 5 seconds, particularly 0.2 to 4 seconds, particularly 0.25 to 2.5 seconds is less than 0.05, and that the deviation P value is in the range of 0.002 to 0.03 in all tests conducted using different materials, and in the range of 0.13 to 0.24 in the absence of such reciprocating up and down vibration, it is shown that the concentricity of the multi-layer dropping pill can be improved by the up and down vibration. In addition, it has been found that the roundness of the dripping pill can be satisfactorily 0.96 to 0.98 in all the dripping pills even when the vertical reciprocating vibration is performed.

Fig. 5 schematically depicts a cross-sectional view of a three-layered drop pill (extending from two calculated center points and being sectioned at the maximum outline of the outer layer, and being sectioned at the three center points for the three-layered drop pill), wherein the center points of the layers from the inside to the outside are respectively 1, 2 and 3, and if the center of the innermost layer is taken as a reference, i.e., the center point is 1, the centers of the middle layer and the outermost layer are deviated from the center of the innermost layer. The degree of deviation P is calculated as follows: p-1/2 (P2+ P3); where P2 represents the degree of deviation of the innermost layer of the intermediate layer deviation, calculated as: p2 ═ x2/r2, where x2 is the distance between the center of the middle layer and the center of the innermost layer, and r2 is the radius of the middle layer, with the average of the major and minor diameters as half if the cross-section is not circular; the same can be calculated for the deviation P3 of the innermost layer of the deviation of the outermost layer: p3 ═ x3/r3, where x3 is the distance between the center of the outermost layer and the center of the innermost layer, and r3 is the radius of the outermost layer. When two layers of pills are prepared, the deviation P is P2. By the deviation index capable of reflecting the concentricity of the layers, whether the distributed space among the layers of the multilayer dropping pill, such as a three-layer dropping pill, is uniform can be evaluated, and when the deviation P value is closer to 0, the deviation is smaller, and the concentricity is better.

The above-described embodiments are merely preferred embodiments for fully illustrating the present application, and the scope of the present application is not limited thereto. The equivalent substitution or change made by the person skilled in the art on the basis of the present application is within the protection scope of the present application. The protection scope of this application is subject to the claims.

Claims

1. The utility model provides a multilayer dripping pill equipment which characterized in that includes:

(i) the dripper has a downward dripper mouth, the upper part of the dripper is connected with a vibration device, and the vibration device enables the dripper to vibrate up and down in a reciprocating manner;

(ii) the material supply pipeline is connected with the dripper;

(iii) material supply tank;

it is characterized in that the preparation method is characterized in that,

the drip nozzle of the dripper extends below the liquid level of the cooling liquid, so that the drip nozzle is at least positioned 10-20 mm below the liquid level in the up-and-down reciprocating process of the dripper,

an isolation circular plate is coaxially arranged in the middle of the cooling part of the barrel-shaped dropping pill, when the dripper is positioned at the bottommost part in the up-and-down reciprocating process, the vertical height of the dripping nozzle from the isolation circular plate is 10-30 mm,

a central round hole with the diameter of 8-15 mm is arranged at the right center of the isolation circular plate, the drip nozzle is positioned right above the central round hole, so that a small pill dropping from the drip nozzle passes through the central round hole to enter the pill recovery part in the sinking process,

the periphery of the central circular hole of the isolation circular plate is uniformly distributed with a plurality of small holes with the diameter of 2-5 mm, so that the cooling liquid can be exchanged up and down on the isolation circular plate, the total area of the small holes uniformly distributed on the isolation circular plate accounts for 5-15% of the area of the isolation circular plate at the periphery of the central circular hole,

a stirring paddle is arranged at a position 10-30 mm under the central circular hole of the isolation circular plate of the cooling part for stirring the cooling liquid and enabling the pellets to be dispersed and settled respectively after entering the lower part of the isolation circular plate,

the material supply pipeline is fixed in a frame box at the tail end connected with the dripper and the dripper; the top of the frame box is connected with a vibration device so that the frame box and the drippers inside the frame box can vibrate up and down in a reciprocating manner,

the vibrating device provides an up-and-down amplitude of 4-20 mm for the dripper, and the time of a complete up-and-down vibrating motion is 0.2-4 seconds.

2. The multilayer dripping pill device according to claim 1 wherein the nozzle of the dripper extends below the liquid level of the coolant so that the nozzle is at least 13-17 mm below the liquid level during the up-and-down reciprocation of the dripper.

3. The multi-layer dripping pill device according to claim 1, wherein an isolation circular plate is coaxially disposed in the middle of the cooling part of the barrel-shaped dripping pill, and when the dripper is at the bottommost position in the up-and-down reciprocating process, the vertical height of the dripping nozzle from the isolation circular plate is 15-25 mm.

4. Multilayer dripping pill device according to claim 1, characterized in that the centre of the isolating circular plate is provided with a central circular hole with a diameter of 10mm, and the nozzle is located directly above the central circular hole, so that pellets dripping from the nozzle during sinking pass down the central circular hole into the pill recovery section.

5. The multilayer dripping pill device of claim 1, wherein the isolation circular plate is provided with a plurality of small holes with a diameter of 3mm uniformly distributed around the central circular hole, so that the cooling liquid can be exchanged up and down on the isolation circular plate.

6. The multilayer dripping pill device according to claim 1, wherein the total area of the small holes evenly distributed on the isolation circular plate accounts for 10% of the area of the isolation circular plate at the periphery of the central circular hole.

7. Multilayer dripping pill device according to claim 1, characterized in that the dripper nozzle is located on the axis of the drum-like cooling portion of the dripping pill.

8. The multilayer dripping pill device as claimed in claim 1, wherein said dripper nozzle, the isolating circular plate and its central circular hole, and the stirring paddle are coaxial with the axis of said cylindrical dripping pill cooling section.

9. The multilayer dripping pill device according to claim 1, wherein the stirring paddles are arranged 15-25 mm below the isolation circular plate.

10. The multilayer dripping pill device of claim 1, wherein the paddles are positioned 20mm below the isolation disks.

11. The multilayer dripping pill device according to claim 1 wherein said vibrating means provides said dripper with an amplitude of 5-15 mm up and down.

12. The multilayer dripping pill device according to claim 1 wherein the vibrating means provides a complete up and down vibrating movement of the dripper for a period of 0.25 to 2.5 seconds.