KR100227996B1 - Filling apparatus - Google Patents

Abstract

An apparatus is provided for filling fine bonsai into long, narrow cavities or holes with relatively small openings. The device is filled to orient toward the opening of the vaginal opening but includes an outlet for floating the particulate in a gas stream spaced apart from the opening of the opening to be filled so that, in operation, the particulate is due to its inertia. It continues to fill the cavity beyond the gap, but the gas is vented through that gap.

Description

Apparatus and method for filling particulate matter

1 shows the outlet, spacing and filling cavity and inlet.

2 is a block diagram of a system control element.

3 shows an embodiment of a filling device according to the invention.

4 is a detailed view of the manifold of the nozzle assembly.

5 shows the nozzle housing in detail.

6 shows a dispenser filled with a device according to the invention.

7 is a bar graph showing the filling amount for pharmaceutical powder with a target filling amount of 4.5 mg.

8 shows one embodiment of a powder dispenser having multiple unit dose amounts of a type usable for drugs that can be administered by oral inhalation.

9 shows another embodiment of a filling device according to the invention.

* Explanation of symbols for main parts of the drawings

1: outlet 2: cavity

3, 145: injector 4: outlet orifice

5, 70 inlet 10: gas supply source

15 regulator 20 pneumatic valve

30: gas pipe 35: timer relay

40 foot switch 45 venturi nozzle assembly

50: pneumatic connector 60: powder feed pipe

65 color 75 plenum

85: orifice plate 115: nozzle housing

135: overflow conduit 140: venturi area

50: overflow collector 200: injector

210: barrel 220: plunger

230: micrometer 235: pin

900: slit G: spacing

[Field of Invention]

FIELD OF THE INVENTION The present invention relates to a filling apparatus, and more particularly to an apparatus for filling polar particulate powder into long narrow cavities or holes with fairly small open holes.

[Prior art]

Preferably, the patient is administered the active agent in the form of particulate powder. For example, anti-ashma and other agents are administered using oral inhalation dosage devices. A problem with the administration of the particulate powder is that the need for accurate and repeated filling of the powder material is often encountered in long narrow cavities or holes having a dispenser with a unit dosage.

In connection with this fact, a device and method have been invented for administering an antibiotic therapeutic consisting of particulate powder into the periodontal pocket of a patient suffering from periodontal disease in recent years (US Pat. No. 5,333,886). It is small enough to contain a narrow tip. The powdered therapeutic agent is fed into a narrow bore disposed within the tip and administered at the tip into the periodontal pocket.

Filling the narrow bore of the periodontal injector with a suitable amount of powder is a very difficult task since the therapeutic agent is introduced through a small open hole inlet and filled into a relatively long, narrow hole. In addition, since a standard amount of therapeutic agent must be administered into the periodontal pocket, the injector must be a filling device in a precise and repeatable manner.

One known method of filling a cylinder, such as a cartridge, with a material made of a powder, such as gunpowder, involves pouring the gunpowder into the funnel and feeding it using gravity into the cartridge through a funnel stem. This method cannot be used to fill the periodontal dosing device, since the filling hole is so narrow that it is difficult to supply the particulates by gravity. In addition, the therapeutic agent is hydroscopic and does not move uniformly and fluidly.

Another method of filling into a long narrow hole, such as a bore in a periodontal injector, is to collect a pile of powder and repeatedly temper the bore into a pile of powder until the required dose is added to the weight of the dispenser. There is something done by doing. However, the method is time consuming and inaccurate.

It is an object of the present invention to provide a device for precisely filling a material of fine powder into a long narrow cavity or hole with a fairly small open hole opening. Another object of the present invention is to provide a device for filling a quantitative powdered drug into a long narrow cavity or cavity of a device for administering a unit dose of the active powdered drug.

[Summary of invention]

The present invention provides a filling device for administering and filling particulate powder into a long narrow cavity or hole with a fairly small open hole inlet. The filling device located at the open hole inlet of the filled cavity is provided with an orifice spaced apart from the open hole inlet of the cavity or hole, and the mixed flow gas is transported by moving the particulate powder to the moving airflow to provide an orifice at the outlet. And a flow gas containing airflow-bound suspended powder is discharged through the orifice of the outlet, so that the powder is filled into a hole or cavity past a certain gap, while gas is discharged past that gap. will be. As a result of repeated tests, the spacing between the outlet and the inlet of the filling cavity is preferably no more than two times the outlet orifice size, specifically 0.2 or more and no more than two times the outlet orifice size. Since the density of the powder is generally higher than that of the gas, the gas is easily redirected and released through the gap, and the powder, which is denser relative to the gas, is continually directed into a long, narrow cavity or hole due to its inertia . To fill the cavity, the innermost end of the hole must be sealed off. In the case of filling with equipment such as small tubes or tubes, the inner end must be temporarily sealed until filling is complete. Once the cavity is completely filled, the excess powder will be automatically released through the gap, allowing the excess powder to be regenerated for reuse purposes as needed. In the present invention, since it is a pharmaceutical powder with sufficient reuse value, it shall be recovered and regenerated.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The filling device of the present invention is particularly suitable for filling fine powder material in long narrow holes or holes with fairly small open hole inlets. In the present invention, the narrow means a diameter of about 1 mm or smaller in width or diameter, and the long means a length longer than about 7 mm in length. Filling cavities or holes can take any cross-sectional shape, for example square, rectangular, spherical or irregular shapes. That is, the cross section of the hole does not have to be formed uniformly. The relatively small open holes in the present invention are those having a width or diameter of about 1 mm or smaller. Like cavities or holes, open holes can take many forms.

The present invention is suitable for filling a variety of doses in which the active agent substance is administered in unit doses. In this regard, the substance is filled in the cavity in such a way that administration can be made from the cavity of the administering device. The apparatus of the present invention is particularly suitable for filling powders of this type, since the powder material is carried on the air stream of the moving gas stream so that it is not filled in an overly dense state. Also in that regard, the cylindrical barrel and cylindrical plunger provide a reproducible cross section and volume for administration, which makes the cylindrical cavity particularly suitable for filling with the device of the present invention. In addition, the cylindrical plunger is suitable for the administration of the majority of the substances since it leaves no substance in the corners. If the cavity has more than one open hole, during the filling operation, all but one hole is temporarily blocked to fill, or vice versa, by discharging suspended particulates through the other open hole in the gas stream. Do not fill. Such temporary barriers should be ones that can be easily removed, so filling takes place in items such as small tubes or pipes.

The filling device of the invention is suitable for filling fine solid powders of the same type as pharmaceutical active powders. There are peptides and proteins as pharmaceutical actives which can be in the form of fine powders and thus can be filled with the devices of the invention. Specific examples of proteins include: parasitic natriuretic factor, tumor ganglia factor, oxytocin, vasopressin, corticosteroids (ACTH), epidemic growth factor, triosidine, grammarcidin, lenin, bradykinin, ENG Orensin, Entropin, Enkephalin, Calsimmonin, Salmon Calcitonin, Secretin, Calcitonin Gene Related Factors, Tissue Plasminogen Factor, Renal Plasminogen Particles, Cholecystokinin, Melanocytic Inhibitor, Melanocytic Hormone, Neuron Peptides y, nerve growth factor, muramyl dipeptides, thymopoietin, human growth hormone, porcine growth hormone, pentemedin sodium, bovine growth hormone, insulin, tyrotropin releasing hormone (TRH), arogastron, Pentagastrin, tetragastrin, gastrin, interferon, glucagon, somatostatin, prolactin, peroxide molecular dismutose, progesterone Release Hormone (LRRH), h-5-Oxo-Pro-His-Tyr-Ser-Tyr-DTrp-Leu-Arg-Pro-GlyNH ₂ , H-5-Oxo-Pro-His-Try-Ser-Tyr-3 -(2Napthyl) -D-alanyl-Leu-Arg-Pro-Gly-NH ₂ , progesterone releasing factor (pig), 6- [0- (1,1-dimethylethyl) -D-serine] -10-deglycinamide- , 2- (amincarbonyl) hydrazide (9CI), progesterone releasing factor (pig), 6- [0- (1,1-dimethylethyl) -D-serine] -9- [N-ethyl-L-prolinamide) -10 -deglycinamide- (9CI), progesterone releasing factor (pig), 6-D-leucine-9- (N-ethyl-L-prolinamide) -10-deglycinamide)-(9CI), and synthetic analogs and modifications thereof There is a pharmaceutically active side of the component and pharmaceutically acceptable salts.

Other kinds of compounds suitable for filling through the device of the present invention include; Penicillin, beta-lactamase inhibitors, cephatosporin, quinoline, aminoglycosides, antibiotics (gentamicin, tobramycin, kanamycin, amikacin), estradiol, norescirone, noresidrone, progesterone, Testosterone, Amcinonin, Acromycin, Tetracycline (Doxycycline, Minocycline, Demecrocycline, Metacycline), Clindamycin, Vitamin B-12 Anesthetics (Procaine, Tetracaine, Lidocaine, Mepivacaine, Ethidocaine) , Mitosantron, bisantrene, doxorubicin, mitomycin C, buleomycin, vinblastine, vincristine, cytosine aribinose, ARA-AC, actinomycin D, daunomycin, daunomycin benzolhai Dragon, Nitrogen Mustard, 5-Azaquidine, Calcium Leuucolin, Cis-Platinum Compound, 5-Fluorouracil, Methotrexate, Aminoprerin, Maytansine , Melhalan, mecapropurin, methyl CCNU, hexamethylmelamine, etoposide, urea hydroxide, levamisol, mitertozone, mysonidazole, pentosterine, teniposide, thioginine, dichloromet-trexate, clopro Lysene, molybdenum, roxapine, haloperidol, chlorpromazine, triple lupromazine, mesodazine, thiolidazine, flufenazine, perphenazine, trifluoroperazine, thiocytene, and the pharmaceutical Acceptable salts, hydromorphones, oxymorphones, levorphenol, hydrocodenes, oxcodone, narroxine, naroxone, naltrexone, buprenorphine, butorphenol, nalbuphine, mepridine, alphaproyne, anieri Dine, diphenosylate, fentanyl and pharmaceutically acceptable salts of these compounds.

The compound is one that is available in the form of fine powders of about 0.5 micron or larger in size. However, the material may not be large in size as described above in order to prevent it from being floated in the air stream of the moving flow gas. Useful materials also include medicaments packaged in microcapsules of the type disclosed in US Pat. No. 5,000,886. The diameter of the material packaged into the microcapsules is generally on the order of 20 to 120 microns suitable for filling with the device of the present invention.

The gas used to suspend the solid particulate material must be compatible with the material and, if the material is a medicament, meet the hygienic requirements. In this regard, various types of gases can be used, including air, nitrogen, dry air, carbon dioxide, argon and other inert gases, taking into account the requirements of compatibility and hygiene. Dry air or nitrogen is preferably used in connection with hydroscopic or hydrophillic particulates.

FIG. 1 shows the outlet 1 having an orifice 4 of width or diameter 'D' spaced apart from the inlet 5 of the injector 3 with the cavity 2. The width or diameter of the inlet 5 is 'X'. The outlet 1 is spaced apart from the inlet 5 of the cavity 2 by a gap G. The width or diameter D of the outlet orifice 4 should be equal to or smaller than the width or diameter X of the inlet 5 of the filled cavity 2. If the orifice or cavity inlet of the outlet is irregular or otherwise shaped, it is preferable that the outlet corresponds snugly within the cavity inlet. If the width or diameter of the outlet orifice 4 is larger than the width or diameter X of the cavity 2, a large amount of particulate material piggybacked and floating in the flow gas airflow will flow to the side of the injector 3 so that the cavity It is not desirable because it will not flow into (2). The dispenser inlet 5 to the outlet orifice 4 is spaced apart at regular intervals G. In general, the spacing is suitably no greater than twice the width or diameter D of the orifice 4. The interval G is preferably 0.2 to 2 times the width or diameter D of the orifice 4. The size of the gap G should be such that it is large enough to allow the gas to escape and that the particulate material can move along the gas flow.

In the embodiment of the dosing device shown in FIGS. 2-4, the outlet orifice diameter is 0.9652 mm (0.038 inches) and the spacing is 0.254 mm (0.010 inches).

Combination configuration of various devices such as a venturi device or a fluidized bed or a device that floats and floats in a gas stream air stream for moving particulate matter, as described in detail herein, whereby the powdered material is suspended in a flow gas stream air stream and suspended in flow. It can be. However, the device must be able to piggyback and move a sufficient amount of particulate to allow for rapid and sufficient filling in the destination cavity, but not too many particulates to be carried on a piggybacked suspension to block the particulates or outlets. In this connection, for example, by adjusting the flow amount of the gas through an apparatus such as Venturi, the amount of fine particles suspended on the gas stream can be properly maintained.

In one embodiment, the filling device comprises a vessel holding a packed powder, a source of gas (preferably dry air or nitrogen), a regulator providing a flow rate of the required volume, the discharge of the gas and aspiration of the discharged powder into the gas stream. A Venturi nozzle assembly. It also optionally includes a vortex collector that blocks the powder in excess of the amount needed to fill the narrow bore holes.

Referring to FIG. 2, the gas supply source 10 is regulated by the regulator 15 before being supplied to the solenoid controlled pneumatic valve 20. When power is supplied to the pneumatic valve 20 from a 115 V rated voltage source 25, the solenoid control valve opens, causing gas to travel through the tube 30 to the filling system. Since only a small amount of gas flow is required for the operation of the present invention, an adjustable timer relay 35 is set to limit the opening time of the solenoid controlled pneumatic valve to 1 second or less. It is not necessary to supply the gas in a pulsating manner, but it is preferable to supply the pulsating in order to prevent the packing of the fine powder. By closing the foot switch 40, the timer relay 35 starts to close.

3 shows the filling system in detail. The gas source to the system is as shown in FIGS. 1 and 2. The gas source is connected to the venturi nozzle assembly 45 using a standard pneumatic connector 50. In the venturi nozzle assembly 45, gas enters the manifold 55 shown in FIGS. 3 and 4. Referring to FIG. 4, the powder feed canal 60 extends through the manifold, acting as a strut of the manifold assembly. The collar 65 allows gas to enter the manifold assembly through the inlet 70 and pass through the plenum 75 to exit through the orifice 80 of the orifice plate 85. In this way, the gas is discharged through a plurality of orifices and surrounds the powder feed canal 60.

In FIG. 3 the gas supply line 30 branches off at the T-shaped connection 90 towards the nozzle assembly 45 and the powder source 95, in particular the space 100 above the powder. In the pulsatile mode of operation, the powder begins to be administered very quickly by compacting the powder source. Without this "bias pressure" it takes a few seconds to generate the venturi effect to develop into a useful powder flow. A sipper tube 110 is inserted into the powder 105 and directed through the manifold assembly to the nozzle assembly 45.

5 illustrates the nozzle housing 115. Feed gas enters through the cylindrical bore 120 and a manifold by the bore 125 is provided. A narrow cylinder to be filled is disposed in the cylindrical holder 130, and if the powder flows excessively, discharge through the overflow tube 135 is achieved.

In use, the gas exiting the nozzle 80 flows through the downstream necked down venturi region 140 formed between the manifold and the powder feed canal 60. As the gas velocity becomes faster as it passes through the venturi region 140, the pressure in this region will be greatly reduced.

At low pressure in the venturi region, the powder 105 is sucked through the siffer tube 110 to mix the powder and gas, and the gas / powder mixture is discharged through the outlet 131. In use, an dispenser 145 having a cavity filled as shown in FIG. 3 is secured within the retainer 130 of the nozzle housing 115.

An important factor in the operation of this device is the spacing G. Excess gas and powder are discharged through the overflow conduit 135 during the filling process. In operation, the powder is filled into the cavity of the injector 145 at the gas / powder mixture rate, but the low density gas diverts the flow and releases through the overflow conduit 135 during the gap G.

A small amount of powder is mixed with the overflow gas and moved into the overflow collector 150. In order to prevent the mixture from pressurizing the overflow collector 150, the collector is provided with a discharge port 155 for releasing the overflow to the atmosphere. If the collector 150 storing the overflow does not release the overflow into the atmosphere, pressure will build up in the collector. As this pressure increases, there will come a time when the pressure used to blow off the gas equals the pressure of the overflow collector, at which point there will be no pressure difference, and thus the driving force will also be lost. In order to prevent the surrounding environment from being contaminated by the filled powder, a filter 160 is installed in the overflow collector 150 to prevent the powder from leaking out, and when the powder is reused, the powder is reused. To play back.

FIG. 6 is a diagram showing the dispenser 200 composed of two parts, a barrel 210 and a plunger 220. In a preferred embodiment, exactly 4.5 mg of active pharmaceutical agent is metered and fed into the doser 200. When the micrometer 230, which has been modified in depth, is installed into the block 240 and the micrometer barrel is rotated, the pin 235 attached to the barrel moves inward or outward depending on the direction of rotation of the micrometer barrel. do. The pin 235 is sized to be easily inserted into the dispenser barrel 210. In use, the dispenser assembly is inserted onto the pin 235 so that when the plunger 220 is pressed, the plunger 220 in the barrel 210 is set in a repeatable fixed position. If the amount of metered material is always constant, then micrometer adjustment is unnecessary and can be replaced with a pin of fixed length.

The embodiments shown in FIGS. 1-6 are also contemplated to determine whether cavity 250 in dispenser 200 is accurately and precisely filled. 7 shows a fill amount or approximately 5400 fills bar graph.

The x-axis of the bar graph represents the fill volume of the 5400 periodontal injector filled with the antibiotic minocycline. The resultant filling amount is shown in 14 bins in 0.1 mg increments from 3.9 mg to 5.2 mg for display purposes. The y-axis of the bar graph represents the number of dosers with the indicated fill amount.

It is clear that the filling volume is narrowly distributed. In particular, the average fill amount is 4.5 mg (packaging target amount) with a standard deviation of 0.19 mg. This 4.22% standard deviation is an allowable deviation in pharmaceutical applications.

The device described herein can also be used to fill other drug administration devices that administer a powder absorbent to the lungs. In particular, some drugs are most effective when administered directly to the lungs of a patient. Examples of such drugs include medications for switchable airway obstruction such as asthma, drugs to suppress lung disease or lung infection, and timely combating infections of the lungs that can infect patients with antibodies to the HIV virus (AIDS). Contains drugs. Examples also include polypeptide products of biotechnology.

Lyophilized polypeptides can be administered along the route of administration of the lungs. Since this rDNA product is very potent, the dosage required is also small. In the present invention, a small amount of the drug in powder can be accurately metered into the injector for later use.

8 is a view showing the device used in the drug administration equipment for storing the drug substance to be administered several times to administer the drug to the lung. The device is preferably made of plastic or paper, with an installation portion 810, which is shown as a hole but which may be a de facto fixing means, and one or more long thin tubular shapes capable of holding one or several doses of the drug. It consists of the support plate 800 containing the containers 820a-820n. The present invention can be used to fill a drug in a tubular container. The tubular container is made of a material that can be destroyed or broken immediately, so that the contents in one container can be used completely for treatment. The number of such containers is chosen according to the design, but may easily include from 1 to 30 doses. The apparatus of the present invention can be used to fill one container at a time by sealing the filled container and then directing the support plate 800 to the filling device at the next location, such as 820b.

Alternatively, the filling device according to the present invention can be filled simultaneously with all the containers on the support plate 800 by providing a plurality of venturis, and a plurality of sources and a predetermined interval.

FIG. 9 shows a filling device adapted to fill the dispenser 810a instead of filling a small diameter cylinder as a modification of FIG. 2. The nozzle housing 115 was modified to replace the outlet 130 shown in FIG. 4 with a slit 900. The support plate 800 may be rotated about the axis 910 such that the dispensers 810a, 810b, 810c are directed toward the outlet.

Claims (18)

A housing 115 holding a structure consisting of a particulate cavity powder source 95, a gas source 10 and a filling cavity 2 having an inlet 5 correspondingly spaced from the orifice 4 of the outlet 1. A device for filling particulate material into a long narrow cavity (2) having a small open hole inlet (5), comprising: means for flowing a flowing gas and communicating with a particulate material source; ; A region for discharging the floating gas containing the suspended particulate matter, which floats the particulate matter on the flow gas flow moving part and communicates with the discharge port 1; An outlet (1) installed at a position separated from the inlet (5) at a predetermined interval (G) and having an orifice (4) of a shape corresponding to the filled cavity inlet (5) of the dispensers (3, 145); ; A space G spaced apart at a distance to a space communicating with the overflow collector 150; When releasing a flowing gas containing particulate matter piggybacking in the flow gas flow through the orifice 4 of the outlet 1, the gap-filled particulate matter fills the cavity 2 at a constant interval ( Filling device characterized in that the gas is introduced into the cavity (2) across G) and the gas is discharged to the overflow collector (150) via a gap (G). 2. Filling device according to claim 1, characterized in that the orifice (4) has a diameter equal to or smaller than the open hole inlet (5) of the filling cavity. Filling device according to claim 1, characterized in that the gap (G) is no more than twice the diameter of the orifice (4) of the outlet. 2. The filling apparatus of claim 1, comprising a venturi region for drawing particulate material to create a low pressure zone to mix gas and particulate material so that particulate material floats in the flow gas stream. A filling apparatus according to claim 1, wherein the means for suspending the particulate material comprises a fluidized bed. The system of claim 1, wherein the particulate material recycling system includes a collection vessel that is pneumatically connected to the overflow collector 150, the collection vessel having a filter 160 that does not penetrate certain materials and an outlet opening to the atmosphere. 155). A filling device according to claim 1, wherein the gas comprises air. The filling device of claim 1, wherein the particulate material comprises a pharmaceutical component. The filling device according to claim 8, wherein the pharmaceutical component comprises minocycline. 2. The filling apparatus as claimed in claim 1, wherein the means for providing the filling apparatus comprises timer means for pulsating the gas at a time interval sufficient to fill the cavity. CLAIMS 1. A method of filling a cavity of a pharmaceutical dispenser with a cavity having a pharmaceutically active powder and having an open hole, the method comprising: a) supplying a powder and a pharmaceutically acceptable gas; b) positioning the inlet of the cavity of the filling injector spaced apart from the orifice at regular intervals, facing the orifice through which the flowing gas containing suspended powder is discharged; c) successively piggybacking the continuous flow of the flowing gas to float the powder, thereby discharging the flowing gas through spaced apart orifices towards the inlet of the cavity to be filled; Upon exiting the flowing gas through the orifice, the powdered ash is pushed across the gap into the filling cavity until it fills the cavity and the gas is released to the atmosphere via the gap. 12. The method of claim 11, wherein the cavity is contained in a device comprising a moving face to adjust the capacity of the cavity. The filling apparatus according to claim 1, wherein the material source contains a feed consisting of fine particulate pharmaceticyl compound. The filling device of claim 1, wherein the filling device comprises a pharmaceutical dispenser. 2. The filling apparatus of claim 1, wherein the gas comprises nitrogen. 2. The filling apparatus of claim 1, wherein the gas comprises carbon dioxide. An apparatus for filling minocycline powder packed in a small bore diameter pharmaceutical dispenser having an inlet through which the powder is filled, the filling device comprising: a) supply means containing a large amount of packaged minocycline powder; b) an acceptable source of dry gas for pharmaceutical use; c) flow flow providing means for moving gas to communicate with the supply means; d) venturi means for piggybacking powder on said flow gas moving flow part, communicating with an outlet, and having an outlet orifice for discharging a flowing gas containing suspended powder; e) a hole for holding the outlet orifice, a gap, and a housing for holding the pharmaceutical dispenser and the overflow means; f) the outlet comprises an orifice spaced apart at a distance G in communication with the overflow means and positioned in the housing in accordance with the inlet of the dispenser; Upon exiting the flowing gas containing suspended powder piggybacking suspended in the flowing gas flow through the orifice, the powder is driven to fill the inlet of the dispenser across the interval until filled in the cavity of the dispenser, and And the gas is discharged to the overflow means through a gap. 18. The particulate matter regeneration system of claim 17, wherein the particulate material regeneration system comprises a collection vessel pneumatically connected to the overflow means, the collection vessel having a filter that does not penetrate the minocycline powder and a discharge port through which it is released into the atmosphere. Filling device.