JP6521449B2 - Method of manufacturing chemical container with stopper - Google Patents

Description

  The present invention relates to a method of manufacturing a stopper-equipped chemical container in which a chemical solution is stored, and more particularly to a method of manufacturing a stopper-equipped chemical container capable of effectively preventing leakage of the chemical solution.

  The mouth part which extracts a medical fluid with a syringe etc. is formed in the medical fluid container for storing a single-use type medicine, and a separate rubber stopper is provided in this mouth. When the liquid medicine inside is sucked by inserting the needle of the syringe into the plug provided at the mouth, if the sealed state between the plug and the mouth is not sufficient, there is a possibility that the liquid medicine may leak.

  Patent Document 1 describes a molding method in which a hard material is molded in such a manner that a soft material is injected in primary molding and laminated on the soft material in secondary molding. In Patent Document 2, one molded body is molded with a first mold and the other molded body is molded with a second mold, and then both molds are slid and combined, and a resin is injected into the joint portion A manufacturing method is described in which both moldings are integrated.

  In Patent Document 3, a resin is injection-molded on a primary molded product obtained by primary molding in secondary molding, the contact portion of the primary molded product is melted, and the entire first molded product is softened. The second molded resin is integrated with the first molded product. Patent Document 4 describes a molding method in which a primary molded product is molded in a primary injection process, and a resin is injected and integrated in a secondary injection process to a seal portion of the primary molded product.

Unexamined-Japanese-Patent No. 2000-52377 JP 2001-278320 A JP 2005-178097 A JP, 2009-61739, A

  In the molding method of each of the above patent documents, a resin molded by injection molding, which is secondary molding, is adhered to a molded product obtained by primary molding. For example, it is conceivable to form a drug solution container by blow molding as primary molding, and to closely attach a resin stopper to the mouth of the drug solution container by injection molding. However, simply adhering the resin plug to the mouth by injection molding does not have sufficient adhesion, and there is a risk of causing liquid leakage. In addition, when an operation of squeezing out the drug solution which is the contents is performed, the force applied to the plug increases due to the high internal pressure, and liquid leakage is likely to occur.

  Therefore, in view of the problems of the prior art, an object of the present invention is to provide a method of manufacturing a stoppered chemical container capable of reliably preventing liquid leakage.

  The method for producing a stopper-equipped drug solution container according to the present invention comprises a first forming step for forming a thermoplastic resin drug solution container having a mouth for extracting a drug solution and having a closed film for closing the mouth, The drug solution container is loaded in a molding die provided with a cavity for molding a resin plug in a state where the closed film is abutted against the cavity, a thermoplastic resin is filled in the cavity by injection molding, and the closed film is filled. And a second forming step of welding the resin plug, wherein a part of the resin plug is inserted into the container in the second forming step, and welding is performed in a state where the closure film of the chemical solution container is bent. It is characterized in that

  In the method of manufacturing a stoppered chemical liquid container according to the present invention, when welding a resin stopper by injection molding to the closing film of the opening of the liquid container, a part of the resin stopper is inserted into the container inner side. The welding is performed in a state where the closing film of the drug solution container is bent. Therefore, the resin plug is firmly welded and integrated to the closing film of the chemical solution container, and the adhesion of the resin plug can be significantly improved. Thereby, it is possible to prevent liquid leakage in various usage environments.

  It is preferable that the said chemical | medical solution container consists of resin whose fall of the visible light transmittance | permeability is 5% or less after 115-150 degreeC heat processing. Linear low density polyethylene is mentioned as such resin. By using linear low density polyethylene, high permeability can be maintained even after heat sterilization.

A recess may be formed in the mouth of the chemical solution container and may be recessed toward the inner side of the container, and the opening side portion of the resin plug may be formed in the recess. In this case, the mouth side portion of the resin plug body is tightened in the concave portion of the mouth portion, and the adhesion between the closure film of the drug solution container and the resin plug body can be further improved.

  The thickness of the occlusive membrane is preferably 200 to 1100 μm. By setting the thickness of the occlusive membrane to 200 to 1100 μm, the occlusive membrane of the drug solution container is softened and easily bent by the heat during injection molding, and the resin stopper can be more effectively welded to the occlusive membrane. .

  By molding the chemical liquid container by blow molding, a low cost and high quality chemical liquid container can be obtained.

  The drug solution container may be configured as an ampoule container, and a plurality of ampoule containers may be connected to each other. By using for medical use, the surrounding contamination at the time of extraction of a medical fluid can be reduced.

  According to the present invention, the resin stopper is inserted into the closure film of the chemical liquid container because the resin stopper is inserted into the inner side of the container and welded while the closure film of the chemical container is bent. By firmly welding and integrating, it is possible to dramatically improve the adhesion of the resin plug. Thereby, liquid leakage can be reliably prevented.

It is the top view and side view of the molded article shape | molded at the 1st shaping | molding process in the manufacturing method of the chemical | medical solution container with stopper body which concerns on one Embodiment of this invention. It is the front view seen from the opening | mouth part side of the molded article of FIG. It is a front view of a stopper equipped drug solution container provided with a resin stopper. It is an explanatory view explaining a 2nd forming process. It is an explanatory view explaining a 2nd forming process. It is principal part sectional drawing of a chemical | medical solution container before providing a stopper, and a chemical | medical solution container with a stopper. It is a principal part sectional view of a medical fluid container before providing a stopper in other forms, and a medical fluid container with a stopper.

  Embodiments of the present invention will be described. FIG. 1 is a plan view and a side view of a molded article 2 molded in a first molding step in a method of manufacturing a stopper-equipped chemical liquid container according to an embodiment of the present invention. FIG. 2 is a front view of the molded article 2 of FIG. 1 as viewed from the mouth 3 side. The molded article 2 is composed of a plurality of drug solution containers 4 formed as a plurality of ampoule containers, and a connecting portion 5 connecting the plurality of drug solution containers 4.

  The drug solution container 4 includes a cylindrical main body 6 and an opening 3 formed at one end of the main body 6 for extracting the drug solution. The main body portion 6 is constituted by a trunk portion 6a at the center in the longitudinal direction and large diameter portions 6b on both sides thereof. The connection portion 5 connects a plurality of chemical solution containers 4 to one another, and has a plurality of injection ports 5a. The other end of the main body 6 of the drug solution container 4 is in communication with the injection port 5a, and the drug solution poured from the injection port 5a is accommodated in the drug solution container 4. After the drug solution is stored in the drug solution container 4, it is cut in the vicinity of the other end on the drug solution container 4 side, and the cut portion is sealed to seal the drug solution container 4 in a sterile state.

  As shown in FIG. 2, the opening 3 of the drug solution container 4 is formed with a closing film 10 for closing the opening 3. The thickness of the drug solution container 4 is 100 to 500 μm, and the thickness of the occlusive film 10 is preferably 200 to 1100 μm. FIG. 3 is a front view of the stoppered drug solution container 1 provided with the resin stopper 11. As shown in the figure, a stoppered chemical solution container 1 is constituted of a chemical solution container 4 and a resin stopper 11 provided at the mouth 3 of the chemical solution container 4. The substantially cylindrical resin plug 11 is welded to the blocking film 10 so as to close the opening 3 of the drug solution container 4.

  A method of manufacturing the stoppered chemical solution container 1 will be described. The stoppered chemical solution container 1 forms the chemical solution container 4 by blow molding, which is a first forming step, and welds the resin stopper 11 to the opening 3 of the chemical solution container 4 by injection molding, which is the next second forming step. Manufacture by doing. The blow molding used in the first molding step for molding the drug solution container 4 can use a known method. More specifically, the air is blown into a preform molded by direct blow molding in which air is blown by sandwiching a parison made of molten resin continuously extruded in a mold, or by injection molding while the storage rod is advanced. Stretch blow molding and the like can be mentioned. By molding the drug solution container 4 by blow molding, it is possible to obtain the drug solution container 4 with low cost and high quality.

  After the drug solution container 4 is formed by blow molding, the resin plug 11 is welded so as to close the opening 3 of the drug solution container 4 by injection molding in the next second forming process. FIG.4 and FIG.5 is explanatory drawing explaining a 2nd shaping | molding process, respectively. The injection molding die (molding die) 12 is composed of two halves, and a cavity 14 for molding the resin plug body 11 is constituted by one die 13 shown in the drawing and the other die not shown. . FIG. 4 shows the state before the chemical solution container 4 is loaded into the injection mold 12, and FIG. 5 shows the state after loading.

  The mold 13 is provided with a loading mold 15 configured in the form of the opening 3 of the chemical solution container 4 so as to communicate with the cavity 14. As shown in FIG. 5, the mouth 3 of the medicine container 4 is aligned with the loading mold 15 of the mold 13, and the medicine container 4 is loaded with the closed film 10 of the mouth 3 butted against the cavity 14. Thereafter, the injection mold 12 is closed, and the cavity 14 is filled with the molten thermoplastic resin. By filling the cavity 14 with the melted thermoplastic resin, the resin plug 11 is welded to the blocking film 10 at the same time as the resin plug 11 is formed.

  FIG. 6 is a cross-sectional view of main parts of the drug solution container 4 and the drug solution container 1 with a plug before the resin plug 11 is provided. In a state in which the part 11a of the resin plug 11 is inserted into the container inward at the time of injection molding which is the second molding step, and the closure film 10 of the drug solution container 4 is bent inward as shown in FIG. It is welded. At the same time as the melted thermoplastic resin is filled in the cavity 14, the closing film 10 of the drug solution container 4 is pressed and hardened so that the part 11 a of the resin plug 11 is the outer end 3 a of the opening 3 Rather, it slightly enters the inner side of the container, and the closure film 10 of the drug solution container 4 is bent to the inner side of the container. The maximum deflection dimension of the occlusive membrane 10, which is the penetration dimension of the part 11a of the resin plug 11 into the container inner side, is about 100 to 2000 μm.

  That is, the following method for manufacturing a stoppered chemical container is carried out. A first forming step of forming a liquid medicine container 4 made of thermoplastic resin having a mouth 3 for extracting a medicine and a closure film 10 for closing the mouth 3 and a cavity for molding a resin stopper 11 The medical fluid container 4 is loaded in a state in which the closed film 10 is in contact with the cavity 14 in the injection molding die 12 having the injection mold 14, and the cavity 14 is filled with a thermoplastic resin by injection molding. 11 includes a second forming step of welding 11, and in the second forming step, a part 11a of the resin stopper 11 is introduced into the container inward side, and the closure film 10 of the drug solution container 4 is welded in a bent state It is a manufacturing method of a medical fluid container with a stopper.

  The part 11 a of the resin plug 11 can be introduced into the inside of the container because the cavity 14 is filled with the molten thermoplastic resin and the pressure on the occlusive membrane 10 is exerted or the occlusive membrane 10 is It is due to the action of both the pressing force and the expansion and contraction of the occlusive membrane 10. The expansion of the occlusive membrane 10 is due to the expansion of the occlusive membrane 10 itself due to the influence of heat at the time of injection molding and the radial outward expansion of the opening 3, and the contraction of the occlusive membrane 10 at the time of mold release of injection molding. The contraction of the occlusive membrane 10 itself and the contraction of the mouth 3 in the radial direction due to the influence of the temperature change.

  It is sufficient that the part 11a of the resin-made plug body 11 enters the container inward side more than the outer end 3a of the opening 3 and the closure film 10 of the drug solution container 4 is in a bent state. The occlusive membrane 10 is in a state of gripping the part 11 a of the resin plug 11 that has entered the inside of the container. Since the resin plug 11 is welded to the closure film 10 of the drug solution container 4 in such a state, the resin plug 11 is firmly welded to the closure film 10 and completely integrated, and the resin plug The adhesion of 11 can be significantly improved.

  When the thickness of the occlusive film 10 is smaller than 200 μm, it becomes difficult to maintain the strength. When the thickness of the occlusive film 10 exceeds 1100 μm, the occlusive film 10 becomes difficult to soften by heat, and the welding strength decreases. By setting the thickness of the occlusive film 10 to 200 to 1100 μm, the film can be softened and easily bent by heat during injection molding, and the resin plug 11 can be welded more effectively.

  The material constituting the resin stopper 11 is not limited, and specifically, thermoplastic resin such as polypropylene, polyolefin such as polyethylene, polyethylene naphthalate, polyester such as polyethylene terephthalate, polyamide such as nylon 6, ABS resin, etc. Can be mentioned. The most preferable materials for forming the resin-made plug body 11 include styrene-based elastomers that are thermoplastic resin elastic bodies, olefin-based elastomers, urethane-based elastomers, polyester-based elastomers, nitrile-based elastomers, polyamide-based elastomers, fluorine-based elastomers, There may be mentioned vinyl chloride-based elastomers, silicone-based elastomers, polymers of isobutene and isoprene (polyisobutylene), and these may be used alone or in combination of two or more.

  Among them, styrenic elastomers are preferred. Styrene-based elastomers include SBS-based (styrene-butadiene-styrene), SIS-based (styrene-isoprene-styrene), SEBS-based (styrene-ethylene-butylene-styrene), and SEPS-based (styrene-ethylene-propylene-styrene). It is representative, and may be one kind of these, or it may be a compound material which added various additives to these.

  The material constituting the chemical solution container 4 is not particularly limited, and specifically, thermoplastic resin such as polypropylene, polyolefin such as polyethylene, polyethylene naphthalate, polyester such as polyethylene terephthalate, polyamide such as nylon 6, ABS resin, etc. Be Among them, linear low density polyethylene is mentioned as the most suitable material. As a specific example of linear low density polyethylene, materials disclosed in publicly known documents such as JP-A-2015-74917 and JP-A-2015-96190 can be mentioned. By using the linear low density polyethylene disclosed in the same publication for the chemical solution container 4, the reduction of the visible light (wavelength 380 nm to 780 nm) transmittance after the heat treatment at 115 to 150 ° C. is 5% or less It can be suppressed. In particular, by using the above-mentioned linear low density polyethylene, it is possible to maintain, for example, a transmittance of 55% or more for light of 450 nm, and it is possible to conform to the Japanese Pharmacopoeia.

  The medical fluid container 4 is subjected to a sterilization process (heat process) by heating. By heating the chemical solution container 4, the degree of crystallization of the constituent resin is increased, and the transparency is reduced. When the above linear low density polyethylene is used, an increase in crystallization can be suppressed due to its molecular structure even if heat is applied, and the highly transparent drug solution container 4 can be obtained. By using the linear low density polyethylene disclosed in the same publication for the drug solution container 4, it is possible to suppress the shape change after sterilization.

  As a further advantage of using the above-mentioned linear low density polyethylene for the drug solution container 4, the improvement of the squeeze property in the operation of squeezing out the drug solution which is the contents is mentioned. Thereby, it can be set as the medical fluid container 4 with high drainage nature.

  Three ampoule containers as the drug solution container 4 were manufactured, and the visible light transmittances of the ampoule containers A and B before sterilization treatment and the ampoule container C after sterilization treatment at 121 ° C. for 15 minutes were measured. The thickness of three different portions of each sample and the transmittance for visible light having a wavelength of 450 nm were measured. The unit of thickness is μm, and the unit of visible light transmittance is%. The thickness of the ampoule container A before sterilization treatment was 320, 280, 300, and the visible light transmittance of each was 63.1, 71.7, 69.2. The thickness of ampoule container B before sterilization treatment was 330, 290, 330, and the visible light transmittance of each was 62.3, 68.7, 62.9.

  The thickness of ampoule container C after sterilization treatment was 340, 390, 320, and the visible light transmittance of each was 57.1, 53.5, 58.6. The visible light transmittance of the ampoule container C after sterilization was 53.5 to 58.6%. For example, in the 320 μm thick portion, the visible light transmittance of the ampoule container A before sterilization is 63.1, and the visible light transmittance of the ampoule container C after sterilization is 58.6%, and the visible light transmission is The rate was reduced to 4.5%.

  In the method of manufacturing the stopper-equipped drug solution container of the present embodiment, the part 11 a of the resin-made plug member 11 is welded to the closure film 10 of the opening 3 of the drug solution container 4 by injection molding. It is made to enter inside the container, and welding is performed in a state where the closure film 10 of the drug solution container 4 is bent. Therefore, the resin plug 11 is firmly welded and integrated to the occlusive film 10, and an air layer does not exist, and the adhesion of the resin plug 11 can be remarkably improved. As a result, liquid leakage can be reliably prevented in various usage environments.

  For example, at the medical site, when the needle of the syringe is pierced through the resin plug 11 and the occlusive membrane 10 is penetrated to extract the drug solution, the resin plug 11 is firmly welded to the occlusive membrane 10, so It is possible to reduce surrounding pollution without leaking. Therefore, aseptic operation outside the clean booth becomes possible, and the workability at the medical site is improved.

  In the molded article 2 of the present embodiment, a plurality of chemical solution containers 4 are connected to each other, and after manufacturing the plurality of stopper-equipped chemical solution containers 1, the chemical solution is accommodated in each stopper-equipped chemical solution container 1. Thereafter, the bonding introduction portion 5 is cut off, and the cut portion is sealed to provide a product in which a plurality of ampoules are connected. A blow fill seal is known as a method for producing a drug product containing a drug solution. When using this method of production, it is not possible to accommodate protein preparations that are disgusting to heat. In the stopper-equipped drug solution container 1 of the present embodiment, heat is not applied after the drug solution is stored, and therefore, it is suitable for storing a drug solution that does not like heat, such as a protein preparation.

  FIG. 7 is a cross-sectional view of main parts of the drug solution container 22 and the drug solution container 20 with a plug, before providing the resin plug 21 in another embodiment. A recessed portion 23 a is formed in the mouth 23 of the chemical solution container 22 so as to be recessed toward the inside of the container. The mouth side portion 21a of the resin plug 21 is formed in the concave portion 23a. The opening-side portion 21a of the resin plug 21 is formed in the recess 23a of the opening 23 of the drug solution container 22 in a state of being softened at the temperature during injection molding, and then the recess 23a is cooled and contracted. Do. By this action, the mouth side portion 21a of the resin plug 21 is crimped in the concave portion 23a.

  As in the above embodiment, the part 21 b of the resin plug 21 is inward of the container, and welding is performed in a state in which the blocking film 24 of the drug solution container 22 is bent. The occlusive membrane 24 is in a state of gripping the part 21b of the resin plug 21 which has entered the inside of the container. Since the resin plug 21 is welded to the closure film 24 of the drug solution container 22 in such a state, the resin plug 21 is firmly welded to the closure film 24 and completely integrated, and the resin plug The adhesion of 21 can be significantly improved.

  Furthermore, since the mouth side portion 21 a of the resin plug 21 is crimped by the mouth 23, the mouth side portion 21 a of the resin stopper 21 is tightened with the mouth 23. In addition, the contact area between the resin plug 21 and the opening 23 is increased. Thus, the adhesion between the blocking film 24 of the drug solution container 22 and the resin plug 21 can be further improved.

  The method for producing a stopper-equipped drug solution container of the present embodiment exemplifies the method for producing a stopper-equipped drug solution container according to the present invention. The shape and dimensions of the drug solution container and the resin stopper are not limited. Other steps may be included in the method for producing a stopper-equipped drug solution container of the present invention as required. The stopper-equipped drug solution container manufactured by the method for manufacturing a plug-equipped drug solution container of the present invention is not limited to an ampoule container, and any container may be used as long as it can store a drug solution.

1, 20 stoppered chemical liquid container 2 molded article 3, 23 mouth 4, 22 chemical liquid container 10, 24 closed film 11, 21 resin plug 11a, 21b part of resin plug 21a of resin plug Part side part 23a concave part 12 injection molding die 13 die 14 cavity 15 loaded die part

Claims (7)

A first forming step of forming a thermoplastic resin drug solution container having a mouth for extracting a drug solution and a closed film for closing the mouth formed thereon;
The drug solution container is loaded in a molding die provided with a cavity for molding a resin plug in a state where the closed film is abutted against the cavity, a thermoplastic resin is filled in the cavity by injection molding, and the closed film is filled. A second forming step of welding the resin plug body;
A method of manufacturing a stopper-equipped drug solution container, wherein a part of the resin plug is inserted into the container in the second forming step, and welding is performed in a state where the closure film of the drug solution container is bent.   The method according to claim 1, wherein the chemical solution container is made of a resin having a visible light transmittance of 5% or less after the heat treatment at 115 to 150 ° C.   The method for manufacturing a stoppered chemical container according to claim 2, wherein the chemical container is made of linear low density polyethylene. The concave portion recessed toward the inner side of the container is formed at the mouth of the chemical solution container, and the mouth side portion of the resin plug is formed in the concave portion. The manufacturing method of the chemical | medical solution container with stopper body in any one of-.   The thickness of the said occlusion film is 200-1100 micrometers, The manufacturing method of the chemical | medical solution container with a stopper as described in any one of the Claims 1-4 characterized by the above-mentioned.   The method for manufacturing a stopper-equipped liquid drug container according to any one of claims 1 to 5, wherein the liquid drug container is formed by blow molding.   The method according to any one of claims 1 to 6, wherein the drug solution container is an ampoule container, and a plurality of ampoule containers are connected to each other.

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