JPH0634806B2 - Method of filling and sealing container having non-locking type fitting structure - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION It is known that injection molding techniques can be used to produce compression moldings from natural starch or hydrophilic substances such as gelatin. Containers of this nature are manufactured because they are preferred vehicles for filling with medical supplies, consumables, chemicals, etc., especially in the form of medical capsules for the proper administration of medicaments. These containers consist of a container part and a closure part, to ensure that at least one or sometimes both parts together ensure a snap effect and thereby a good closure between them. , With fitting projections and grooves. The size of medical capsules is relatively small.
The snap effect is particularly important when the container is filled with the drug, because the container must be prevented from being opened even if it is accidentally or intentionally opened. According to currently known methods, the snap closure has a depth of approximately 0.03-0.1 in the container part and / or the closure part.
This is done by providing a very tight undercut of 5mm. If the undercut is too small, the closure will be incomplete, while if it is too large, cracks will occur especially in the container.

Even if it is manufactured accurately, various disadvantages and inconveniences cannot be avoided. The wall thickness of the medical capsule should be as thin as possible. Therefore, the wall thickness of the container part will be different from that of the closure part. Due to their different thicknesses, these two parts behave dimensionally under unstable conditions, which makes them geometrically dissimilar, especially in air. Generates stress when the humidity is changing.
Under certain circumstances this will cause the containers to rupture and if they are filled with powder or liquid, their contents will leak. In particular, difficulties can also occur in the filling machine, especially during the closing operation of the two parts.

Furthermore, the production of such a snap closure structure is technically complicated. In particular, slide molds or split-follower molds are required, the movable mold part leaving spots, which then appear as bumps on the molding surface. Because of the need for a sliding carriage or follower, the mold optionally has more sliding parts, wears more, and operates at higher pressures or higher locking forces. , And more vulnerable, which manifests itself in longer downtime and increased equipment costs. In addition, the slide makes the mold somewhat unstable. Also, in particular, since there are fewer cavities that can be installed per available area, the production volume is significantly reduced.

All of the above disadvantages and inconveniences can be eliminated by utilizing a compression molded part having a non-locking mating structure and sealing the molded part according to the method of the present invention described later in this specification. Was found.

The present invention is a method of filling and sealing a container having a non-locking mating structure, wherein the container is compression molded, preferably at least one of starch or other hydrophilic substance or a mixture of such compounds. A method for filling and sealing a container, which is manufactured by injection molding and has a non-locking mating structure, preferably consisting of a container part and a closure part, preferably in the form of a medical capsule, comprising: a) filling The product comprising is introduced into a container of the type described above, the container is not snap-locked, and b) the sealing liquid contacts the mating part of the container part when the container is in the closed state. A container that contacts the mating part of the closure part and / or part of the mating part of the closure part and / or the mating part of the closure part when the container is closed. The whole fitting part of the container part or a part of the fitting part of the container part, and further, c) the container part and the closure part are fitted together and sealed in an irreversible state. The present invention relates to a method for filling and sealing a container having a non-locking fitting structure, which comprises forming a closed container.

The term “starch” is to be understood as meaning a naturally occurring plant-derived carbohydrate consisting mainly of amylose and amylopectin. It is extracted from various plants, such as potato, rice, tapioca, corn, and cereals such as rye, oats and wheat. By heating at the same time as pressurizing, such starch is molded into a dense molded product having high precision. Manufacturing techniques for compression molding operations, particularly injection molding operations performed under pressure and at elevated temperature, are described in European Patent Application No. 84300940.8 (published 118240).
No.) specification, and also applies to the present invention.
This published description details working conditions and contains information on suitable additives such as extenders, mold release agents, plasticizers and / or colorants and is therefore incorporated by reference (preferred temperature, The same applies to pressure and water content).

The expression "other hydrophilic substances" is understood to mean hydrophilic substances which are suitable for producing the containers according to the invention and which are particularly suitable for producing containers in the form of medical capsules. Should.

"Other hydrophilic substances" include, for example, gelatin; sunflower protein, soybean protein, cottonseed protein, fallen protein, rapeseed protein and other vegetable proteins; blood protein; egg protein; acrylated protein; alginate, carrageenan, guar gum. , Agar, gum arabic and related gums (gatch gum,
Karaya gum, tragacanth gum), water-soluble polysaccharides such as pectin; alkylcellulose such as methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, hydroxyalkylcellulose and hydroxyalkylalkylcellulose; Cellulose acetyl phthalate (CA
P), cellulose esters such as hydroxypropylmethyl cellulose phthalate (HPMCP) and hydroxyalkyl cellulose esters; water-soluble cellulose comprising carboxyalkyl cellulose such as carboxymethyl hecellulose, carboxyalkylalkyl cellulose, carboxyalkyl cellulose ester and alkali metal salts thereof. Derivatives: polyacrylic acid and polyacrylic acid ester, polymethacrylic acid and polymethacrylic acid ester, polyvinyl acetate, polyvinyl alcohol, polyvinyl acetate phthalate (PVA
P), polyvinylpyrrolidone, water-soluble synthetic polymers such as polycrotonic acid; preferably phthalated gelatin, gelatin succinate, cross-linked gelatin, shellac, water-soluble chemical derivatives of starch, and optionally quaternization Polymers such as cationically modified acrylates and methacrylates having tertiary or quaternary amino groups such as optionally diethylaminoethyl groups and other similar polymers. Gelatin is preferred.

Manufacturing techniques for compression molding of other hydrophilic substances of the type mentioned above, and in particular for injection molding operations under pressure and at elevated temperature, are described in European patent application No. 83301643.9 (publication No. 090600).
Described in the specification, it details working conditions and contains information on suitable additives such as extenders, mold release agents, plasticizers and / or colorants. The application is also incorporated by reference (including preferred temperature, pressure and water content). Such a hydrophilic substance is, for example, “Robert LD
avidson, Water Soluble Gums and Resins Guide, McGraw-Hill B
ook Company ”.

The two European patent applications 84300940.8 and 83
The details described in 301643.9 relate to the production of compression-molded containers of that type, in particular to medical capsules molded by compression molding, preferably injection molding, which also applies in the case of the present invention, It forms part of the invention.

The invention utilizes the compression-molded, preferably injection-molded, container thus produced, which container preferably takes the form of a medical capsule.

It is within the scope of the present invention to combine or combine the various hydrophilic substances listed. Inorganic fillers, for example oxides of magnesium, aluminum, silicon, titanium, etc., may be added to the substances mentioned above. The concentration of the bulking agent is preferably 50% or less, more preferably 3 to 10%, based on the weight of all the components forming the container wall.

Examples of plasticizers that may be added are polyalkylene oxides such as polyethylene glycol, polypropylene glycol, polyethylene-propylene glycol; low molecular weight organic plasticizers such as glycerol, glycerol monoacetate, diacetate or triacetate;
Propylene glycol, sorbitol, diethyl sodium sulfosuccinate, triethyl citrate, tributyl citrate and the like can be mentioned, and these have a concentration of 0.5 to 15%, preferably 0.5 to 5% with respect to the weight of all components. Added in.

Examples of colorants include known azo dyes, organic or inorganic pigments or colorants of natural origin. Inorganic pigments such as iron or titanium oxides are preferred, and these oxides known per se are 0.001 to 10%, preferably 0.5 to 3%, based on the weight of all components forming the container wall. Added at a concentration of.

The water content of a container formed from starch and / or other hydrophilic material is 1 with respect to the weight of all components forming the container wall.
It is 0 to 20%, preferably 12 to 19%, more preferably 14 to 18%.

The total content of plasticizer and water is preferably less than 25%, most preferably less than 20%, based on the weight of all components forming the vessel wall.

Although the present invention has been described in terms of capsule form, it is essentially hollow and includes all containers that can be made from the hydrophilic materials to form disposable sealed containers. Furthermore, the container is preferably characterized as having an essentially continuous outer surface.

Compared to European Patent Applications Nos. 84300940.8 (Publication 118240) and 83301643.9 (Publication No. 090600), a feature of the container of the present invention is that the container closure part and the container part are snap-lock type protrusions or grooves. Not shown,
And therefore, it does not have any snap closure structure. A preferred type of container is one in which the container part and closure part are mated together without deformation. This type of container is new and is the object of the present invention. After closure, the container according to the invention preferably has the same wall thickness virtually everywhere, thus avoiding the development of stress as a result of dimensionally different behavior under instability.

The container of the present invention is easy to manufacture and easy to fill and close. However, since it is not snap-closed,
Easily cleaved, or especially because the container and closure parts are mated without deformation, even if this mating operation is done in a very precise manner, it will be spontaneous during subsequent handling. Will cleave. The respective parts of the region pressed one inside the other are generally only 0.5 to 2 mm wide, the latter value being a maximum.

Therefore, the sealing liquid and / or the container portion in contact with each other are
Or found that the container does not tear if it is brought into contact with at least one of those areas of the closure part, thus enabling a high speed filling operation and if this filling operation is carried out before the capsule is irreversibly closed. Is amazing.

This sealing liquid preferably contains water. The sealing liquid is preferably a mixture of water and alcohol, which is preferably an alcohol having 1 to 4 carbon atoms, preferably ethanol, propyl alcohol or butyl alcohol, more preferably ethanol or isopropyl alcohol, most preferably Is ethanol and the water / alcohol ratio is 95: 5 to 40:60, preferably about 80:20 to 60:40, most preferably about 70:30.
Is.

Furthermore, the sealing liquids may be, for example, sucrose, starch, monosaccharides, oligosaccharides and polysaccharides, glycerol and other polyols, glycols, polyethylene glycols and / or polypropylene glycols, anionic, cationic or known agents known per se. 0.5 to 1 with respect to the total weight of the sealing liquid, of an amphoteric surfactant, gelatin, polyvinyl alcohol, or an anionic or cationic water-soluble acrylic polymer.
It contains an aqueous solution with a concentration of 0% by weight, preferably 1 to 4% by weight.

The mixtures of water and alcohols mentioned are preferred.

Water alone, for example, results in excessive wetting and inaccurately dispensed wetting, which damages the capsule and causes decomposition of its contents. Since the outer wall of the capsule is susceptible to water, the sealing liquid must be wettable with precise control both with regard to its alignment and the amount of liquid used.

Of course, it takes a certain amount of time before the sealing effect begins to occur. It is therefore surprising to find that the closed containers of the present invention can be further processed and packaged without any phenomenon indicating that they are torn or damaged. Was that.

The application of the sealing liquid was carried out in a precisely controlled manner with regard to its position adjustment and usage, resulting in a liquid tightly closed container. Once sealed, the container cannot be cleaved unless destroyed.

If appropriate, it is also possible to heat the closed container or its mating area in order to expedite the sealing process. Any heat source that does not harm the container or its contents may be utilized, examples of such heat sources include heat conduction, eg by hot air; electromagnetic waves of suitable frequency, eg microwave or infrared; and ultrasonic energy. Named
The temperature thus generated is not limited as long as the capsule or its contents are not damaged. However, it is usually not necessary to accelerate the sealing process by such additional treatment. Generally, heating to 30 to 50 ° C is sufficient. Moreover, you may heat all or one part using the sealing liquid maintained at the temperature of 30-100 degreeC.

The products that make up the fill may be solids, pastes or liquids. The substances to be dispensed in medical containers are known per se and, according to the invention, are compatible with the container wall,
Hard gelatine A substance normally distributed in medical containers.

Besides removing the disadvantages and inconveniences mentioned in the introduction,
Further unexpected benefits result from the use of the container according to the invention and the means by which it is sealed. Since the mechanical stress caused by the snap closure is reduced, the thickness of the container wall can be significantly reduced. This manifests itself as a significant reduction in the time it takes to cleave and dissolve in gastric or intestinal fluid, material savings and improved container volume utilization.

The present invention can be more easily understood with reference to the following drawings.

1 is a side view of the container of the present invention.

2 is a vertical cross-sectional view of the container of the present invention along the line II-II of FIG.

FIGS. 3a to 3t are cross-sectional views corresponding to the display symbol (III) in FIG. 2 and showing various aspects of the joint portion where no stress remains in the closure portion of the container portion.

4 is a plan view of a filling and sealing machine for the container of the present invention.

Fig. 5 Wetting / sealing mechanism connected to the filling / sealing machine
FIG. 5 is a sectional view taken along line VV of FIG. 4.

6 is a perspective view of a filling machine with a wetting mechanism, ie a machine of the design shown in FIG.

The container (20) containing the powder filling component (19), consisting of the container (22) and the closure (21), is shown in FIG.
And the post-filling state having the stress-free shape shown in FIGS. As can be seen, the container mating part (24) has adjacent closure mating parts (2
After being positioned in 3), an essentially continuous surface is formed on the outer surface of the capsule. 3a to 3t show a fitting unit (II
I) shows different shapes. From each of these figures,
It can be seen that a smooth, essentially continuous outer surface of the container (20) is formed on the mating unit part (III). FIG. 4 is a cross-sectional view of the design of a filling machine with a sealing mechanism.
In this machine, the magazine (1) is connected to a continuously vibrating transport path (2), which guides the container part to the container part supply mechanism part (3).

In this container part supply mechanism part (3), the container part is pushed into the container part holder (5) by the ram (3a) with its open finished surface facing upward. The container holder (5) is fixedly attached to the turntable (4). The container parts are then transported to the filling mechanism part (6) in successive regular steps defined by the stepwise rotation of the turntable, where each container part is metered from a storage container (6a). Receive a quantity of powder (19) or paste or liquid.

The container part filled in this way is then transferred to the closing mechanism part (7) in a likewise continuous periodical stage. In this closing mechanism part (7), the closure part supplied from the closure part magazine (10) through the transfer path (9) by vibration is transferred onto one sheet of felt (21a) for wetting them, and then the container. Can be placed on the department. These operations are performed by the star rotor (8) and the closure part holder (8a). After further transport, the closed container, which also takes the form of the medical capsule according to the present application, is likewise discharged from the container holder (5) when it reaches the discharge mechanism (11) in a continuous regular stage. It FIG. 5 is a vertical cross-sectional view of the sealing mechanism section. The closure part (21) is placed in the transport path (9), and from there, it is caught by the closure part holder (8a) by the decompression means, and then the rotary movement and the vertical movement are performed together to position and wet the device (12). Moved to. Vertical movement of the closure part holder (8a) presses the closure part (21) onto the felt (12a) impregnated with the sealing liquid (13).

At the same time, the closure parts (21) are aligned, and the overlapping part is wetted with the sealing liquid. The sealing liquid is stored in a container (1
4) to supply the liquid amount in the container (14) with a dropper (1
The felt (12a) is impregnated by capillarity while being kept constant by 5) and the overflow (16). Subsequently, the closure part holder (8a) is rotated together with the vertical movement to bring the closure part (21) to the sealing mechanism part (7), where the vertical movement of the closure part holder (8a) causes the container part (22) to move. Press up. Of course, any other suitable wetting technique may be used.

At the same time, the decompression holding the closure part (21) in the closure part holder (8a) is released. After that, the closure part holder (8a) performs both rotational movement and vertical movement, advances to the vibrating conveyance path (9), and receives a new closure part (21).

Both the closing machine and the sealing mechanism are novel and are the constituent elements of the present invention. Although hard gelatin capsules for medical use are usually pre-closed before being fed to the closure machine, the present invention provides a closure part (21) and a container part (22) in separate magazines (10) and (1). And can be transported to the closure mechanism (7) separately from each other. Therefore, both parts can be separately wetted prior to the closing operation.

Hereinafter, the present invention will be described with reference to examples.

Example 1 The closure part (2 of the container having the form shown in FIG.
Pressing the lip of 1) (the fitting part in FIG. 3a) to a depth of 1.5 mm on one fine felt impregnated with a sealing solution containing 70% by volume of water and 30% by volume of ethanol,
The thin lip on the closure was completely wetted. The container is described in European Patent Application No. 84300940.8 (published 1182).
No. 40) injection molded from wheat starch according to the conditions detailed in Example 8 (water content: 12.7%) of the description. The closure was then fitted to a matching container and no stress was produced as a result of the closing operation.

After 10 minutes, the container could no longer be cleaved. Similar results were obtained when the container was pre-filled with the solid, paste or liquid pharmaceutical composition and the contents did not leak from the sealed container.

Example 2 The procedure described in Example 1 was repeated, except that the operation of exposing the container to one of the following heat sources was added without delay.

(I) Air heated to 35 ° C .: 3 minutes (ii) Infrared: 2.5 minutes (iii) Ultrasonic energy: 2 seconds After that, the container was no longer cleaved and could withstand liquid.

Example 3 The lip of the closure part (21) of the gelatin capsule having the morphology shown in FIG. 1 according to the present invention (the fitting part in FIG. 3k) was made to a depth of 1.0 mm consisting of an 80:20 mixture of water and ethanol. Placed on a plate with a thin liquid layer of. The capsule itself is the European patent application No. 83301643.9
No. (Publication No. 090600) specification, Example 2 B-2 (water content: 14.6%). Then, when the closure part was fitted to the container part, no deformation occurred during the closing operation.

After holding at room temperature for 15 minutes, the container could no longer be cleaved. After that, when one of the heat sources described in Example 2 was used, the welding time required was shorter than indicated there.

After the sealing process was completed, the container could never be cleaved without breaking it at the same time.

Example 4 Examples 1, 2 and 3 were prepared using a sealing liquid having the composition shown below.
The procedure described in 1. was repeated.

[Brief description of drawings]

FIG. 1 is a side view of the container of the present invention. FIG. 2 corresponds to FIG.
It is a longitudinal cross-sectional view of the container of the present invention along the line II-II. Figure 3
FIGS. 3A to 3T are cross-sectional views corresponding to the display symbol (III) in FIG. 2 and showing various aspects of the joint portion where no stress remains in the closure portion of the container portion. FIG. 4 is a plan view of a filling and sealing machine for the container of the present invention. Figure 5
Fig. 4 shows the wetting / sealing mechanism connected to the filling / sealing machine.
5 is a sectional view taken along line VV of FIG. FIG. 6 is a perspective view of a filling machine with a wetting mechanism, ie a machine of the design shown in FIG.

Claims (16)

[Claims] 1. A non-locking mating structural part (24,2) made by molding at least one of starch or other hydrophilic substance or a mixture of such compounds.
3) each having a container part (22) and a closure part (21), which can be put into a closed relationship by fitting both parts, and the closed relationship is at least one of the fitting structure parts. A container characterized in that it is fixed by interposing a sealing liquid in (24, 23), and the two parts can be separated again when the sealing liquid is not interposed. 2. When the container portion and the closure portion are fitted to each other to form one container, the outer surface of the fitted portion is in a substantially stepless continuous state. The container according to claim 1. 3. When the container portion and the closure portion are fitted to each other to form one container, the height of the fitting structure portion is 0.5 to 2 mm, respectively. The container according to claim 1 or 2. 4. A method for filling and sealing a container comprising a container part and a closure part having a non-locking mating structure part, which is produced by molding starch, at least one hydrophilic substance or a mixture thereof. The container can be placed in a closed relationship by fitting both parts together, and the closed relationship is fixed by interposing a sealing liquid in the fitting structure portion, and the sealing liquid intervenes. A method of filling and sealing a container that can be reseparated from both parts when not performed, a) introducing the material constituting the filling into the container part of the container, and b) when the container is in a closed relationship , All or part of the fitting structure part of the closure part that contacts the fitting part of the container part, and / or the whole or one part of the fitting structure part of the container part that contacts the fitting structure part of the closure part A container having a non-locking mating structure part, characterized in that a sealing liquid is brought into contact with and c) and then the container part and the closure part are fitted to each other to form a sealed container. Filling and sealing method. 5. The method according to claim 4, wherein the starch is a natural plant-derived carbohydrate consisting mainly of amylose and amylopectin. 6. The starch comprises potato, rice, tapioca,
The method according to claim 4 or 5, which is a product extracted from corn, rye, oats and / or wheat. 7. The other hydrophilic substance is gelatin; vegetable protein such as sunflower protein, soybean protein, cottonseed protein, fallen protein, rapeseed protein; blood protein; egg protein; acrylated protein; or alginate, carrageenin. A guar gum, agar, gum arabic and a homologous gum (gatch gum, karaya gum, or tragacanth gum), or a water-soluble polysaccharide such as pectin.
Item 5. The method according to Item 5 or Item 6. 8. The other hydrophilic substance is alkyl cellulose such as methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxybutyl methyl cellulose, hydroxyalkyl cellulose and hydroxyalkyl alkyl cellulose; cellulose. Cellulose ester such as acetyl phthalate (CAP), hydroxypropylmethyl cellulose phthalate (HPMCP) and hydroxyalkyl cellulose ester; consisting of carboxyalkyl cellulose such as carboxymethyl cellulose, carboxyalkylalkyl cellulose, carboxyalkyl cellulose ester and their alkali metal salts Soluble cellulose derivatives; polyacrylic acid and polyacrylic acid esters, polymethacrylic acid and polymethacrylic acid esters, polyvinyl acetate,
Water-soluble synthetic polymers such as polyvinyl alcohol, polyvinyl acetate phthalate (PVAP), polyvinylpyrrolidone, and polycrotonic acid; phthalated gelatin, gelatin succinate, crosslinked gelatin, shellac, water-soluble chemical derivatives of starch, and cation-modified acrylates. The method according to claim 4, which is a hydrophilic polymer substance selected from the group consisting of: and a methacrylate. 9. In addition to starch and / or other hydrophilic substances, additives such as extenders, plasticizers and / or colorants are present, and any one of claims 4-8. The method described in. 10. The water content of a container formed from starch and / or other hydrophilic substances is 10 to 20%, preferably 12 to 19%, based on the weight of all components forming the container wall.
More preferably, it is 14 to 18%.
Item 10. A method according to any one of items 9 to 9. 11. As a sealing liquid, sucrose, starch, monosaccharides, oligosaccharides and polysaccharides, glycerol and other polyols, glycol, polyethylene glycol and / or polypropylene glycol, anionic, cationic or amphoteric. Concentration of surface active agent, gelatin, polyvinyl alcohol, or anionic or cationic water-soluble acrylic polymer of 0.5 to 10% by weight, preferably 1 to 4% by weight, based on the total weight of the sealing liquid. The method according to any one of claims 4 to 10, wherein the aqueous solution is used. 12. A sealing liquid having a water / alcohol ratio of 95: 5 to 40:60, preferably about 80:20 to 6.
Claims 4 to 1 with a mixture of water and alcohol of 0:40, most preferably about 70:30.
The method according to any one of item 1. 13. The sealing liquid according to claim 12, wherein an alcohol having 1 to 4 carbon atoms, preferably ethanol, propyl alcohol or butyl alcohol, more preferably ethanol or isopropyl alcohol, most preferably ethanol is used. the method of. 14. The closure area after the closing operation,
5. The method according to claim 4, wherein the heating is carried out by heat conduction, electromagnetic waves of suitable frequency, preferably microwave or infrared or ultrasonic energy. 15. The method according to any one of claims 4 to 14, wherein the product constituting the filling is a solid, paste or liquid. 16. A device for filling and sealing a compression-molded container in the form of a medical capsule, comprising a container section magazine (1) and a container section supply mechanism section (3). ), A member (3a) for storing the container part in a container part holder (5) fixedly attached to the rotary table (4), a filling mechanism part (6), and a closing mechanism. (7), a closure magazine (10), a conveying path (9) for supplying the closure to the closure holder (8a), and a discharge mechanism (11) following the closing mechanism (7). And the device.