CN1016673B - Method for producing pharmaceutical hard-shell capsule - Google Patents

Abstract

The present invention relates to a method for producing a capsule. Solution of heat gel is coagulated at a time, and then the heat gel is dried. Therefore, the influence on the method for producing a capsule from drying conditions is little so that a capsule with the even wall thickness can be obtained, and the capsule can not be corrugated. In a device of the present invention, a capsule core rod which is cyclically used is immersed into the solution of the heat gel, the solution adheres on the core rod, the core rod is turned over by 180DEG so that the thickness of the solution which adheres on the core rod is even, the core rod is then kept in a container of which the temperature is higher than that of the solution gel for a certain period so that the gel can be accelerated, the formed capsule is dried by a drying device, and then, the dried capsule is taken off from the core rod.

Description

Method for producing pharmaceutical hard-shell capsule

The invention relates to a kind of method that is applicable to the mass production hard capsules for medicament use.

Gelatin once was used as the employed thermal coagulation material of hard capsules for medicament use.But the shortcoming of gelatin is that it may react with pharmaceutical compositions, and from the angle of storage and transportation, the water content in the control capsule is the thing of a trouble simultaneously.

In order to overcome the capsular above-mentioned shortcoming that gelatin is manufactured, the someone has proposed the method that some of the recommendations adopt: a kind of method is to replace carrying out molding after the cellulose ether heat fused with alkyl or hydroxyalkyl; Another kind method is that the shaping core bar is immersed in organic solvent or a kind of aqueous solution, and solution is coated in and forms capsule on the core bar.

With the existing problem of the way of heating means fusing-shaping is that capsular uniformity is difficult to accomplish, also can make the capsule variable color sometimes simultaneously when heating is shaped, becomes yellow or brown.The method of soaking in organic solution has a shortcoming, and that might remain in the capsule the deleterious solvent of human body exactly, and in addition, transporting solvent also is a trouble.As for the manufacturing process that immerses in the aqueous solution, after core bar took out from solution, therefore the solution that sticks on the core bar can be difficult to obtain the uniform capsule of wall thickness toward dirty.In order to improve this method, there is the people once to advise in advance core bar being heated, stick to the lip-deep solution of shaping core bar like this and can be gelatinized.But, this method is difficult to put into practice, because if heating-up temperature is too low.This effect is insufficient, if preheat temperature too Gao Ze in dry run usually wrinkle can appear again.

At United States Patent (USP) NO.3,493,407, United States Patent (USP) NO.4,001,211; United States Patent (USP) NO.2,810,659, United States Patent (USP) NO.2, these materials and the method for production said above can finding in 526,683 and United States Patent (USP) NO.3,617,588.

Manufacturing capsular equipment also can be at United States Patent (USP) № .1, finds in 787,777.

For the shortcoming of being said above overcoming, we study, result of study makes us finally find a kind of manufacturing process of hard capsules for medicament use, and this method can obtain the uniform capsule of wall thickness, can be not wrinkling with this capsule that the aqueous solution of cellulose ether is manufactured.

So, the objective of the invention is to provide a kind of improved new method of manufacturing hard capsules for medicament use, the capsule of being manufactured has homogeneous thickness, can be not wrinkling and have an extraordinary performance.

The top purpose of saying of the present invention and other purposes with and distinctive performance characteristics in the reference accompanying drawing, can further obtain detailed explanation.But, must clearly realize that these accompanying drawings just for the present invention is described, and be not limitation of the present invention.

It shown in Figure 1A and Figure 1B the partial cross-sectional front view of manufacturing capsule device of the present invention.

Be the partial side, cross-sectional view of the said equipment shown in Fig. 2 A and Fig. 2 B.

Shown in Figure 3 is the partial rear side viewing sectional drawing of the said equipment.

Shown in Figure 4 be among Figure 1A and Fig. 3 along IV-IV hatching, the sectional drawing of getting in the direction of arrow.

Shown in Figure 5 is the operation sequence chart of hard-shell capsule method for production.

Shown in Figure 6 is the perspective view of capsule core bar.

Shown in Figure 7 is along hatching VII-VII, the sectional drawing of getting in the direction of arrow.

Shown in Figure 8 is the working condition sketch map of the part of the said equipment.

Shown in Figure 9 be among Fig. 8 along hatching IX-IX, the sectional drawing of getting in the direction of arrow.

Shown in Figure 10 is the perspective view of pneumatic gripping.

Shown in Figure 11 is the top view of pneumatic gripping.

Shown in Figure 12 be among Fig. 9 along hatching XII-XII, the sectional drawing of getting in the direction of arrow.

Shown in Figure 13 is the working condition sketch map of the part of the said equipment.

Shown in Figure 14 is the sketch map of a pair of capsule pairing of explanation process.

Shown in Figure 15 is the sectional drawing of lubricating arrangement.

Shown in Figure 16 is the block diagram of control system in the said equipment.

Figure 17 A is the flow diagram of control system shown in Figure 17 B and Figure 17 C.

Below with reference to operation sequence chart among Fig. 5 the method for manufacturing hard-shell capsule with equipment of the present invention is described.

Produce line comprises following operation: (1) capsule core bar is lubricated; (2) capsule core bar is immersed in a kind of solution of thermal coagulation material, and then from solution, mention; (3) rotation of capsule core bar is in order to stick to equably on the capsule core bar gelling soln; (4) capsule core bar is immersed in the hot water, from hot water, put forward then; (5) drying; (6) capsule is taken off; (7) finishing and (8) pairing. Capsule core bar turns back to (1) operation after by (1)-(6) operation, recycles between these operations. Producing equipment configuration has two lines, and every all comprises these operations of (1)-(7), and this two lines is used for respectively manufacturing the capsule of different-diameter. One pair of capsule of different-diameter is worked in coordination.

The top thermal coagulation material of saying should be can pass through heating and the aqueous solution of gel, this material comprises alkylcellulose, hydroxylated cellulose and hydroxy alkyl cellulose, such as methylcellulose propoxyl cellulose hydroxy ethoxy-methylcellulose, propoxyl-methylcellulose hydroxy butoxy-methylcellulose, hydroxy ethoxy cellulose, hydroxy ethoxy-propoxyl-methylcellulose and other similar materials.These cellulose ethers must be water-soluble, therefore wishes usually to use a certain amount of substituent group, promptly adopts the material of alkyl and hydroxyalkyl, has 1.4 moles at least in one mole of glucose unit.The viscosity in aqueous solution of manufacturing does not like this have any special restriction.The present invention uses cellulose ether usually, uses 2% aqueous solution, and its viscosity in the time of 20 ℃ is 2～20 centipoises.If the cellulose ether that is adopted makes viscosity in aqueous solution be higher than above-mentioned numerical value, when implementing the inventive method, will meet difficulty so, unless reduced the concentration of soaking solution.

Cellulose ether is non-ionic, does not react with ingredient, and is fool proof.As the Ionized substitution material of derivatives, just might react as hydroxyalkyl and similar material, thereby cause degeneration, so this class derivatives can not be used for method of the present invention with medicine.

In manufacturing capsular practical methods, cellulose ether is to be dissolved in earlier in the water, reaches predetermined concentration.Zhi Bei aqueous solution preferably has 10～30% concentration like this, and its viscosity is 1000～15,000 centipoise.If the concentration of solution or viscosity are too low, resulting capsule thickness just may be too little.Otherwise,, then can bring operational difficulty if the concentration of solution or viscosity are too high.Then, aqueous solution will remove contained air bubble by the way that reduces pressure, with this aqueous solution, after promptly soaking solution suitably heats, a period of time of the capsule core bar being soaked into and keeping being scheduled in solution, mentions from solution then.The capsule core bar generally is at room temperature, can certainly carry out preheating so that reach the purpose of accurate adjustment capsule wall thickness.Then, the capsule core bar is dipped in the hot water, water temperature is higher than the thermal gel temperature of soaking solution so that impel condensing of cellulose ether aqueous solution.After hot water soaked, capsule core bar band cellulose ether gel attached to it and carry out drying together in furnace chamber.

After super-dry, the capsule of shaping takes off from core bar, repairs the preliminary dimension that obtains the capsule body then.In addition, capsule lid has the diameter more slightly bigger than capsule body, will form in the same way, and a pair of capsule lid and capsule body are supporting mutually, and lumping together becomes medicinal complete capsule.In capsular stock, can add some other additive as required, in additive, comprise regulator (as polyvinyl alcohol), plasticizer is (as glycerol, sorbitol, mannitol, sucrose and Polyethylene Glycol), brightener (as titanium dioxide, barium sulfate and winnofil) and last toner (as water-soluble dye and color lake).For the capsule that makes shaping takes off from core bar easily, can on core bar, be coated with a kind of remover, such as Oleum Gossypii semen; Liquid paraffin and so on.

The preferred embodiment of present device is shown in Figure 1A, 1B, and 2A, 2B is in 3 and 4.These accompanying drawings have only been represented in the two lines, with the situation of explanation practical operation.The difference of this two lines is that structurally the two is mutually the other side's a mirror image, in addition, the capsule core bar size that two lines adopted is slightly different, thereby the capsule that a lines is produced can match with the capsule of another lines production, forms a complete capsule.Therefore, introduce in detail after the lines, another lines has also just been understood.

Shown in Figure 1A (I A-I A) and Figure 1B (I B-I B) is the elevation cross-sectional view of present device, and these two figure are connected with each other, and is I A I B-I A I B hatching in Fig. 2 A and Fig. 4, the profile of getting in the direction of arrow.Fig. 2 A(II A-II A) and Fig. 2 B(II B-II B) shown in be II A II B-II A II B hatching in Figure 1B and Fig. 3, at the profile that the direction of arrow is got, these two figure also should couple together.Shown in Fig. 3 (III-III) III-III hatching in Fig. 2 B and Fig. 4, the profile of getting in the direction of arrow.Shown in Fig. 4 (IV-IV) IV-IV hatching in Figure 1A and Fig. 3, the profile of getting in the direction of arrow.Form a tetragon roughly at the plane graph shown in these figure, each limit and Figure 1A and Figure 1B accordingly, Fig. 2 A and Fig. 2 B, Fig. 3 is corresponding with the device shown in Fig. 4.When the capsule core bar has just formed capsule product along the cycling of each limit of this tetragon the time.

On each chassis 50, arrange and fixed two or several capsule core bars 2, as shown in Figure 6.Each capsule core bar 2 all has slick surface and semicircular termination.These core bars can carry out coating to obtain slick surface.Chassis 50 is the erosion resistant material with magnetic, manufactures as rustless steel or coated steel.

In process of production, capsule core bar 2 does not have certain starting point and terminating point, produces capsule 1 because capsule core bar 2 always recycles, and following introduction just comes from this operation that gelling soln is immersed in the lubricated back of core bar.

Shown in Figure 1A, there is a pair of guide plate 51 to hold the lower surface on chassis 50, promptly chassis 50 to be held at two places, front and back of Figure 1A, the capsule core bar 2 on the base plate all is upside down.There is the piston 10 of a cylinder to be used for pushing away forward with being in this locational chassis 50.A pick off 102 is housed on a guide plate 51 is used for surveying chassis 50.

Near guide plate 51, disposed an elevator 5.This elevator 5 is by linear electric motors 12 transmissions, and these linear electric motors are installed on the top framework 48, and the power transmission shaft 55 of motor links to each other with elevator 5.The body of elevator 5 is box-shaped, its left side, right side and bottom side all be open wide and have following projecting plate 56, there is gusset the both sides, front and back of following projecting plate, these down projecting plates supporting chassis 50 from the front and back of Figure 1A.Elevator 5 can be mentioned five chassis 50.When elevator 5 is in the position shown in Figure 1A, promptly during the home position, the push rod 53 of cylinder 10 can promote chassis 50 and be with core bar 2 to move on to down on the projecting plate 56.Below elevator, have a trough 4, fill the aqueous solution 3 of immersion in the groove, be i.e. the non-ionic cellulose ether gel rubber material of the sort of thermal coagulation.58, one these thermocouples of thermocouple 59(of an electric heater are housed in this solution tank to be connected with a temperature controller 200) and a magnetic stirring apparatus 60 be used for agitating solution 3, make solution keep stationary temperature.The control system that temperature controller 200 can use everybody to be familiar with is such as the PID control system.A pick off 104 is housed in solution tank 4 is used for surveying elevator 5.Under this condition, capsule core bar 2 is immersed in this solution 3, then from solution, put forward again.

Linear electric motors 14 have been installed on the framework 48 in the above, on the power transmission shaft 62 of linear electric motors 14, push rod 62a and 62b have been housed.These two push rod 62a and 62b match with a block 63 respectively, and like this, push rod just can only be swung and can not counterclockwise be swung by clockwise direction.The home position of power transmission shaft 62 is shown in the solid line among Figure 1A, and the termination of power transmission shaft is near the center of elevator 5.The end of push rod 62a contacts with a chassis 50, this be in elevator 5 apart from a nearest chassis of guide plate 51.

Be provided with a revolving drum 11 near on the position of elevator 5.Shown in Fig. 7 (section VII-VII), two groove 11a and 11b are arranged on this revolving drum, these two grooves are used for supporting the chassis 50 that core bar 2 is housed on the relative position of tube inboard.The outer surface of this revolving drum 11 is by rotating bearing arrangement 65 supportings, and the circumference gear 66 of revolving drum is meshed with the travelling gear 67 of motor 16.Shown in Figure 1A in this case, the upper surface of the following projecting plate 56 when the groove 11a of support chassis 50 and the groove face of 11b and elevator 5 are in the home position is on same height.When push rod 62a pushes chassis 50 when going in the elevator 5, chassis 50 is being slided and is being entered in the revolving drum 11.By with the rotation of capsule core bar 2 in revolving drum 11, gel solution is coated on the core bar 2 equably.

Shown in Figure 1B, an elevator 7 is also arranged near revolving drum 11, elevator is connected with the power transmission shaft 69 of linear electric motors 18 on being installed in framework 48.The shape of elevator 7 is the same with the elevator 5 that the front had been said.Shown in Figure 1B, when elevator 7 is on the home position, the groove 11a of the upper surface of following projecting plate 70 and revolving drum 11 and the groove face of 11b are on same height, this revolving drum 11 is supporting the chassis 50 that core bar 2 is housed, like this, the impetus of push rod 62b just can make chassis 50 slip in the elevator 7.At an end of elevator 7 pick off 106 is housed and is used for surveying push rod 62b, below elevator 7, be provided with a hot water storgae 6.An electric heater 72 is housed in hot water storgae, a thermocouple 73 and a magnetic stirring apparatus 75, thermocouple links to each other with a temperature controller 199, and magnetic stirring apparatus is used for making the hot water in the hot water storgae to keep stationary temperature, a pick off 108 also is housed in hot water storgae 6 is used for surveying elevator 7.In this part, the capsule core bar immerses in the hot water storgae, mentions from hot water then, and that can quicken the adherent solution of institute on the capsule core bar like this condenses the formation capsule.

Be provided with a ribbon conveyer 77 on elevator 7 next doors, bracing frame 78 can be placed on above the transporter.The end face of the following projecting plate 70 of the supporting surface of bracing frame 78 and elevator 7 is on same height, like this, just can be transplanted on the bracing frame 78 from elevator 7, and hooked rod 81 is connected with the axle 80 of linear electric motors 20 with the chassis 50 that hooked rod 81 will be equipped with core bar 2.Maintaining static on the part of ribbon conveyer 77 position that a pick off 112 is used for surveying bracing frame 78 is housed.

Shown in Fig. 2 A and Fig. 2 B, bracing frame 78 is being with chassis 50 to pass through a hothouse 8 on ribbon conveyer.The pipe 82 that there are some apertures a side is housed in hothouse, in hothouse, blows the hot-air that is about 50 ℃ so that carry out drying by these apertures on the pipe.Move to some Fig. 2 B on bracing frame 78 from the P point on Fig. 2 A by the ribbon conveyer 77 of motor 22 transmissions.There is a pick off 114 to be used for surveying chassis 50 and arrives the Q point.In case chassis 50 has been transplanted on the Q point from the P point, will unload the chassis down from bracing frame 78 with the device that the back will be talked about, bracing frame 78 then turns back on the position that P orders from the Q point.The mode of returning as bracing frame, also can consider to be provided with another kind of transporter, bracing frame 78 is fixed on the ribbon conveyer 77, allows bracing frame 78 pass through, or adopt the way of manually bracing frame 78 being transported back and below ribbon conveyer 77, reserve enough big place.

As shown in Figure 3, by axle 83 the impetus of linear electric motors 24, the chassis that core bar 2 is housed 50 that is placed on the bracing frame 78 just slides on the roller conveyer 84 of inclination singly.Under situation shown in Figure 3, there is an electric magnet 26 that a chassis 50 is held, stop it to move forward.After electric magnet 26 had been with chassis 50 to be gone back to by a device (back will be introduced), next chassis 50 just was placed on that hold-down support 85 and by a block 86 and locatees.A pick off 116 is housed on this hold-down support 85 is used for surveying chassis 50, above hold-down support 85, be provided with two rotating disks 88, these two rotating disks are coaxial, and distance therebetween approximates the length on chassis 50 greatly.Rotating disk 88 comes transmission by a motor 28.Between these two rotating disks, there is an electric magnet 26 good as if ride over two intermediary bridges of rotating disk.When rotating disk 88 rotations made electric magnet 26 drop to its extreme lower position, the chassis 50 that electric magnet just will be placed on the hold-down support 85 held, and the horse back turn-off.In addition, the extreme lower position that pick off 128,118 and 126 is used for surveying electric magnet 26 respectively is housed also, extreme higher position (1/2 changes) and the centre position (3/4 changes) that is in the right.When electric magnet 26 dropped to extreme lower position, it picked up a chassis 50.When electric magnet rotated with rotating disk 88, electric magnet 26 took the chassis to extreme higher position, and on this position, the capsule that has been shaped just takes off from core bar.

The device that capsule is taken off from core bar, the paired device of trimming device and capsule all is arranged in the top of rotating disk 88.

The device that capsule is taken off from core bar comprises a hydraulic piston bar 30 and pneumatic gripping 32.When piston rod 30 is drawn among the cylinder body 30a, piston rod 30 just passes through a spring 90 with swing arm 91 pull-ups, and that connecting rod 93 with swing arm 91 swing just contacts with baffle plate 92, and at this moment, swing arm 91 just is in the position perpendicular with piston rod 30.When piston rod 30 was released from cylinder body 30a, it moved down.The retroaction that swing arm 91 is connected bar 93 promotes to come on the baffle plate 92, and swing arm 91 also begins to overcome the power that spring 90 pulls back, swing in the counterclockwise direction.In case swing when having surpassed extreme position with respect to swinging axle 95, swing arm 91 is just swung by the pulling force of spring 90 suddenly when swing arm 91, thus connecting rod 93 strike on the baffle plate 96 and be parked in piston rod 30 same lines on.There is a pick off 120 to be used for surveying connecting rod 93 and whether piston rod 30 aligns.After this pick off detects them and aligns, piston rod 30 just by Zhejiang move downward, and be parked on certain position.When piston rod 30 stopped, the chassis that core bar 2 is housed 50 that rotating disk 88 carries was just in time come on the extreme higher position of rotating disk 88.This situation as shown in Figure 8.Detect piston rod 30 by a pick off 122 and be moved down into certain position.

Among the Fig. 8 of being shown in Figure 9 along profile that IX-the IX hatching is got in the direction of arrow.Shown in this accompanying drawing, swing arm 91 is connected with the support 98 that pneumatic gripping 32 is housed.As shown in figure 10, the jaw plate 32a and the 32b of pneumatic gripping 32 have semicircular cross-section, and the external diameter of its internal diameter and capsule core bar 2 adapts.Shown in Figure 4 is to reduce when air pressure, the jaw plate 32a of pneumatic gripping 32 and the open state of 32b, the just state that leaves of jaw plate.When piston rod 30 is in certain certain position, after compressed air fed in the pneumatic gripping 32, two jaw plate 32a and 32b closure were being clamped core bar near on the position of core bar 2 roots.Shown in Figure 11 is partial vertical view, comprises pneumatic gripping 32, the part that capsule core bar 2 is relevant with some.As shown in Figure 9, an oil hydraulic cylinder 34a and a former 38 are housed on the support 98.On the hydraulic piston bar 34 of oil hydraulic cylinder 34a jumper bar 40 is housed, the spacing of jumper bar is identical with the spacing that capsule core bar 2 is arranged on chassis 50.Above a former 38 is arranged some apertures are arranged, the spacing of the aperture also spacing with capsule core bar 2 is identical.The cross-section illustration of getting along hatching XII-XII is in Figure 12.The diameter of former 38 endoporus changes in the middle part of its degree of depth, the diameter of one side is big, and the diameter of another side is less, bigger its diameter of endoporus 38a just in time adds that with capsule core bar 2 outside adherent capsule exsiccant size matches, and the diameter of less endoporus 38b can make jumper bar 40 than loose ground by going.As shown in figure 12, jaw plate 32a and 32b are clipped in core bar 2 does not slidably have the adherent position of dry capsule (near the position on chassis 50).Therefore, if support 98 is carried vertically upward from situation shown in Figure 12, capsule 1 will keep closely cooperating in former 38 so, and takes off from core bar 2, thereby has finished the operation sequence that capsule takes off from core bar.

Now begin from state shown in Figure 8, hydraulic piston bar 30 moves up, thereby swing arm 91 is vertically risen, the capsule 1 that is in the former 38 is deviate from from core bar 2, then pneumatic gripping 32 is opened, along with the rise of swing arm 91, an inclined-plane 93a of connecting rod 93 contacts with a guide finger 41 and is promoted by this guide finger, and the pulling force backward that makes connecting rod 93 overcome spring 90 is swung in the clockwise direction.When connecting rod 93 swing surpassed extreme position with respect to swinging axle 95, swing arm 91 was just swung by the pulling force of spring 90 suddenly, thereby made connecting rod 93 run on the baffle plate 92 and be in on the perpendicular position of piston rod 30.Shown in Figure 13 is exactly the part sectioned view of this state.Survey this state with a pick off 124.Because a cutting knife 43 is housed near the swinging track of former 38 end faces, so the termination 1a of capsule 1 just is cut off in former 38 swings, like this, capsule 1 has just obtained finishing and has had uniform length.

Swing at former 38, as shown in Figure 13, just have one the pairing mould 44 be configured in former 38 near.This pairing mould 44 has an endoporus that runs through, and the diameter of each endoporus changes on the centre position in hole to some extent, is step-like.The diameter of endoporus small diameter portion 44a can make capsule 1 slide in the hole, and endoporus matches with the diameter of capsule 100 than the diameter of major diameter part 44b, the external diameter of capsule 100 is slightly greater than the external diameter of capsule 1, manufacture by another lines, this lines is and that lines of producing capsule 1 mirror image each other, as previously mentioned.The capsule 100 of packing into and manufacturing in the pairing mould 44 with above-mentioned same method.Whether in pairing a pick off 130 has been installed on the mould 44 is used for detecting capsule 100 and correctly is in the endoporus of mould 44.In this case, promote piston rod 34 by cylinder body 34a and by jumper bar 40 capsule 1 is pushed in, each capsule 1 is matched with capsule 100, the capsule that is formed by these two capsule pairings is released from pairing mould 44 then, as shown in figure 14.

Meanwhile, as shown in Figure 3, the position above the electric magnet 26 on being installed in rotating disk 88 is in, after capsule 1 takes off from the core bar 2 on the chassis 50, rotating disk 88 is being with chassis 50 to rotate 1/4 again to be changeed, thereby makes electric magnet 26 towards the right side, and chassis 50 is in the face of clamper 45.The clamping face of clamper 45 is only just having with chassis corresponding that section of 50 two end portions, so just can not hinder the rotation (referring to Fig. 4) of capsule core bar 2.During this time electric magnet 26 stops to attract the chassis.Therefore just can promote these chassis 50 with linear electric motors 36.By the impetus of linear electric motors 36, chassis 50 is pushed out from clamper 45, and chassis 50 is through slide rail 46, lubricating arrangement 47 and another one slide rail 49.Be provided with one in the end of slide rail 49 and fall road 54, landslide, and thereunder be provided with a pair of leading truck 51() referring to Figure 1A.As shown in figure 15, lubricating arrangement 47 has soft hairbrush 57 on the position that capsule core bar 2 passes through, and has the circulation that pipeline 61a and 61b are used for being lubricated agent, and the purpose that is coated with lubricant is that capsule 1 is taken off from core bar 2 easily.Used lubricant is liquid paraffin, edible oil or silicone oil preferably.

The operation control system of the said equipment comprises the content shown in the block diagram among Figure 16, and this control system is operated each corresponding actuating device 10 to 30, and is surveyed and timing by pick off 102 to 130.Figure 17 A, the program that the flow diagram shown in 17B and the 17C comprises all is stored in read-only storage (ROM) part of the control circuit of block diagram.The operation control of from 201 to 250 these operations is all carried out according to operation listed the flow diagram.

The work of control system detects chassis 50(201 by pick off 102) begin to carry out.If pick off does not detect the chassis, then control system is in waiting state.If detected chassis 50, then cylinder rod 10 promptly enters reciprocating motion (202).Whenever cylinder rod 10 reciprocating actions once, just have a chassis 50 to be sent in the elevator 5 and go.When cylinder rod 10 reciprocating action during five cycles (203), linear electric motors 12 are promptly moved (204) by transmission, after pick off 104 detects capsule core bar 2 to have finished the action of soaking in gel solution 3 (205), linear electric motors 12 are counteragent (206) just.Then, linear electric motors 14 actions (207).(208) occurred if pick off 106 detects push rod 62b, this explanation is because the promotion of push rod 62a has had five chassis 50 to be sent to that revolving drum 11.Detect after the push rod 62b, linear electric motors 14 are promptly by transmission counteragent (209), and will confirm that linear electric motors 14 have been counteragents, and push rod 62b just can not hinder next operating process like this.

In next operation, motor 16 rotates certain revolution (211) makes revolving drum 11 can only rotate a week.Because linear electric motors 14 are to move forward in operation 207, push rod 62b pushes elevator 7 to the chassis 50 that places revolving drum 11, and at this moment, linear electric motors 18 move forward capsule core bar 2 is immersed in the hot water storgae 6 (212).Immerse in the hot water storgaes after (213) when pick off 108 detects capsule core bar 2, linear electric motors 18 stop immediately, make capsule core bar 2 stop one section preset time " a " (214) in hot water storgae, have enough heats to pass on the capsule core bar with assurance.(215) (216) after the time T on the clock in the control system has reached predetermined value " a ", linear electric motors 18 counteragent (217) are immediately risen elevator 7.On the other hand, when pick off 112 detects bracing frame 78 after on the position of ribbon conveyer 77 (218), just reciprocating action of linear electric motors 20 (219) is transplanted on chassis 50 bracing frame 78 from elevator 7 with hooked rod 81.

Then motor 22 actions (220) are transferred forward with the bracing frame 78 that ribbon conveyer 77 will be equipped with chassis 50, by hothouse 8, shown in Figure 17 B.After pick off 114 detects chassis 50 (221), motor 22 stops, so belt transportation 77 shuts down (222).At this moment, linear electric motors 24 reciprocating actions are transported to (223) on the cross roll road 84 with chassis 50.Then, detect from the chassis 50(224 that roller-way 84 ships by pick off 116) and chassis 50 has been attracted (225) by electric magnet 26.In this case, motor 28 rotates (226) in its normal direction, and after pick off 118 detects electric magnet 26 (227), motor 28 just stops (228).At this moment, chassis 50 is in the top position of rotating disk 88.Then, hydraulic piston bar 30 promotes (229), and swing arm 91 begins swing, and last and piston rod 30 is on the same straight line.After pick off 120 detects piston rod and swing arm and aligns (230), pneumatic gripping 32 is just opened (231).After pick off 122 detects (232), hydraulic piston bar 30 just stops (233).At this moment, pneumatic gripping 32 closures (234).Then, piston rod 30 begins to be pulled (235), and capsule takes off from core bar 2.When piston rod 30 is not detected by pick off 122 (236), pneumatic gripping 32 is opened (237) at once.Swung 90 ° of arrival its home positions (238) when pick off 124 detects swing arm 91, control system just forwards the operation shown in Figure 17 C to, and piston rod 30 stops action (239).

At this moment, motor 28 is in its normal direction action, and when pick off 126 detects chassis 50 (241), motor 28 promptly stops (242), makes chassis 50 in the face of clamper 45.Then, electric magnet 26 stops to attract (243) and linear electric motors 36 counteragents (244), chassis 50 is being with capsule core bar 2 to turn back to (this position is detected) on its home position by lubricating arrangement 47 in operation 201, at linear electric motors 36 in operation (244) after the reciprocating action one-period, motor 28 is in counter-rotation (245), after pick off 128 detects electric magnet 26 (246), operation 224 is got back in operation.These operations are carried out repeatedly.

, be on the tram of pairing in the mould 44 (247) if pick off 130 detects capsule 100 after operation 239 quits work at hydraulic piston bar 30, hydraulic piston bar 34 will promote (248) so.When capsule 100 with capsule 1 is worked good and decline from pairing mould 44, this point can be confirmed (249) by pick off 130 signal interruption.Then, hydraulic piston bar 34 is pulled (250).Like this, operation 227 is got back in operating process again.These operations repeat.

For the ease of understanding the operating process of each operation, above what said all is to introduce according to the mode of Serial Control.But, control system of the present invention also can be carried out parallel control.Such as, the action of the elevator 7 that the downward action of the elevator 5 that linear electric motors 12 drive and linear electric motors 18 drive just can parallel control.

Can a clearer understanding be arranged to the present invention with reference to the example of enumerating below:

Example 1

Hydroxypropyl-methyl-the cellulose that uses contains propoxyl (hydroxypropoxyly) 10%(by weight), methoxyl group (methoxyl) 29%(by weight), its viscosity in aqueous solution is 6 centipoises in the time of 20 ℃, with this propoxyl-methyl-cellulose dissolution in water, concentration is 22%, then solution is placed a night, under vacuum, remove the bubble in the solution, be used for ^#3 capsular core bars are coated with liquid paraffin earlier, immerse in the soaking solution that has been heated to 40 ℃ again, mention from solution then.After under the vertical drips of solution of core bar, with 180 ° of core bar upsets and kept for 25 seconds.Then in the hot water with 85 ℃ of core bar immersions, stopped for 10 seconds, be transplanted on then in the hothouse with 55 ℃ of temperature, here stopped 30 minutes, gel solution obtains drying and has capsular shape like this.The capsule of molding takes off and is trimmed to predetermined size from core bar and just become capsular body.The capsule of manufacturing does not like this have wrinkle, has 0.12 millimeter uniform wall thickness in the end, and has 0.10～0.11 millimeter thickness at barrel portion.Capsule lid also is to manufacture after the same method.After charging into starch, a pair of capsule body and capsule lid fit together and form a capsule, the capsule that obtains like this will be according to the method that Japanese pharmacoeia the 11st edition the goes up regulation test of changing in quality, our discovery, and the transformation time during test is 6.5 minutes.

Example 2

Employing contains the soaking solution of 22% solid composition, the preparation of this solution is 100 parts 22.2% aqueous solution that example 1 is same, the dispersion of hydroxypropyl-methyl-cellulose and 2 parts of titanium dioxide (Sakai chemical company product A-110) mixes to add and calculates in the quantitative water, then solution is placed a night, and under vacuum, remove the bubble in the solution.Manufacture the capsule that contains brightener according to example 1 same method below.The capsule of being manufactured does not have wrinkle, and uniform wall thickness is arranged.According to the same method test that is adopted in the example 1, the transformation time is 6.0 minutes.

Example 3

The aqueous solution that contains 18% solid constituent is preparation like this, promptly use propoxyl-methyl-cellulose dissolution of 97 parts, this cellulose contains propoxyl (hydroxyprop-oxyl) 5%(respectively by weight) and methoxyl group (mefhoxyl) 28%(by weight) and 2% the viscosity of aqueous solution in the time of 20 ℃ be 12 centipoises, add 3 parts of polyvinyl alcohol again, its saponification degree is 88 moles of %, 4% viscosity in aqueous solution is 5 centipoises in the time of 25 ℃, these compositions are added in the entry, place a night, going down in vacuum promptly obtains desired soaking solution except that bubble.Be used for the capsular core bar of #3 and coat liquid paraffin earlier, be heated to 50 ℃, immerse then in the soaking solution at room temperature, then carry out the step identical, can obtain capsule at last with example 1.Capsule does not have wrinkle, and wall thickness is even.Transformation time during test is 9.5 minutes.

Example 4

The preparation of soaking solution is with the propoxyl cellulose dissolution, it comprises propoxyl (hydroxypropoxyl) 63%(by weight), their 2% viscosity in aqueous solution are 6 centipoises in the time of 20 ℃, and this composition is added in the entry, concentration is 21%, places a night and goes down except that bubble in vacuum.Be used for the capsular core bar of #3 and be coated with earlier, immerse then in the soaking solution with liquid paraffin, according to carry out with example 1 in those operations, the temperature of different is hot water is 70 ℃, resulting capsule does not have wrinkle, has uniform wall thickness.Transformation time during test is 6.0 minutes.

The present invention has been done special explanation above, but can make various modifications in form with on the particular problem, but do not left the spirit and scope of the present invention for the people that these technology that the front is said are proficient in art technology with reference to preferred embodiment.

Claims (3)

1, a kind of hard capsules for medicament use is made up of a capsule body and capsule lid, and its manufacture method comprises following operation:

(a) lubricating jelly capsule-core bar;

(b) the capsule core bar is immersed the solution of the hot gel material of a kind of non-ionic celluloses ether, and then from solution, mention;

(c) the capsule core bar that will be stained with above-mentioned solution overturns 180 ℃ at least;

(d) the capsule core bar that will be stained with above-mentioned solution immerses in the hot water that temperature can control, and makes the above-mentioned solution gel that sticks on the capsule core bar;

(e) agglomerative solution on the capsule core bar is carried out drying to form hard-shell capsule body and hard-shell capsule lid;

(f) take off capsule body and capsule lid from the capsule core bar;

(g) capsule body and the capsule lid finishing pairing of taking off formed hard-shell capsule.

2, method according to claim 1 is characterized in that: the solution of the hot gel rubber material of above-mentioned nonionic is aqueous solution.

3, method according to claim 2 is characterized in that: above-mentioned nonionic cellulose ether has 1.4 moles alkyl and hydroxyalkyl at least in one mole of glucose unit.

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