JP2006182430A - Rubber cap and its production method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical rubber cap which is provided with a superior sealing characteristic and which maintains superior coring resistance and re-sealing characteristics even if a syringe needle is applied to the rubber cap multiple times, and to provide its production method. <P>SOLUTION: The surface layer part of a rubber cap is provided with a layer containing fluorine atoms. The composite proportion of the layer containing fluorine atoms is continuously decreased from the surface to the inside of the cap. Preferably, a method of impregnation uses a method for bringing the rubber cap whose surface is purged into contact with an atmosphere containing a fluorine gas. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a rubber plug and a method for producing the same.

  As is well known, a rubber stopper is used to seal a container for storing a medicine such as an injection. The medicines stored in the medicine container may be used all at once, but in most cases, they are used in several parts. When removing, remove the rubber stopper, and after removal, the container is sealed by being pushed into the neck of the container again. Therefore, it is important that the rubber plug does not deteriorate in sealing performance no matter how many times it is removed.

  When the drug is a drug solution, an injection needle is inserted into a rubber stopper pushed into the mouth of the storage container, and the drug solution is taken out into the syringe or dosing circuit via the injection needle. It is said that it is important for a medical rubber stopper to fulfill such a role that the resealability and the coring resistance are good.

  Resealability means the property of instantly closing the puncture hole by the elasticity of the rubber material after puncturing and removing the needle from the rubber stopper. Therefore, if the elasticity of the rubber material is insufficient or deteriorates over time, the resealability is insufficient, i.e. the outside air enters the container without blocking the puncture hole, or the chemical solution It will leak to the outside.

  The coring means a phenomenon in which a fine rubber piece having a diameter equal to or smaller than the hole diameter of an injection needle called a fragment is generated when the injection needle is inserted into a rubber stopper. When such a coring occurs every time the injection needle is inserted into and removed from the rubber stopper, the chemical solution in the container is contaminated by the generated fragments. The cause of this coring is caused by the injection needle and the rubber stopper, respectively. In the injection needle, the surface state mainly affects the shape of the injection needle and the accuracy of the finishing process of the injection needle. One rubber plug is caused by its thickness, hardness, surface slipperiness, and the like.

  The thickness, hardness, surface slipperiness, etc. of the rubber plug are greatly affected by the characteristics of the rubber material itself. For example, examples of the rubber material rich in rubber elasticity include natural rubber, polybutadiene rubber, polyisoprene rubber, and blends thereof. In a rubber stopper obtained from a rubber material rich in rubber elasticity, the frequency of occurrence of coring is very low. However, such a rubber material rich in rubber elasticity has a problem of high gas permeability. This large gas permeability is a major drawback for the application of rubber plugs. This is because if the gas easily permeates into the container sealed with the rubber stopper, the chemical solution in the container is easily contaminated by the atmosphere in which the container is placed. If the chemical in the container is easily oxidized, oxygen easily enters the container through the rubber stopper, so the chemical in the container will oxidize within a relatively short time even if sealed. Will be.

  For this reason, butyl rubber having excellent gas barrier properties is used for a rubber plug for pharmaceuticals. However, this butyl rubber has a problem that it is inferior in rubber elasticity and easily causes a coring phenomenon as compared with a rubber material rich in rubber elasticity such as the natural rubber.

  As described above, the rubber stopper made of butyl rubber is currently used as a rubber stopper for pharmaceuticals because, in normal use, the insertion of the injection needle into the rubber stopper is completed in about five times. . This is because, even with a rubber plug made of butyl rubber having relatively low resistance to coring (hereinafter referred to as coring resistance), coring does not occur when the number of repeated punctures is about five.

  However, in practice, some of the various types of medicines have needles that far exceed the number of five needles. For example, in the case of drug solutions such as insulin preparations and heparin preparations, sampling is performed more than 100 times from their storage containers. In such a rubber stopper that has been pierced many times, there is a risk of coring, and countermeasures have been demanded.

  On the other hand, conventionally, a rubber plug for pharmaceuticals has been proposed in which the coring resistance is improved by laminating a fluororesin film on the surface of the rubber plug (see, for example, Patent Document 1). This rubber plug is characterized by a rubber material (butyl rubber) with excellent gas barrier properties and a porous polytetrafluoroethylene (PTFE) thin film (film) with low rigidity, excellent lubricity, high elongation and tear resistance It is said that the coring resistance of the rubber plug can be improved by such a configuration.

JP-A-11-29160

  However, the rubber plug laminated on the surface with the PTFE film has insufficient adhesion at the interface between the rubber plug main body and the PTFE film on the surface, and the sealing performance of the container is significantly deteriorated due to peeling at the interface. There is a risk of it. Further, in this rubber plug, the slipperiness with respect to the injection needle is only good only on the surface PTFE film layer, and the coring resistance of the rubber plug main body is not changed. Therefore, the effect of reducing the frequency of occurrence of coring when the puncture needle is performed many times remains insufficient. Further, since the PTFE film on the surface has poor elasticity, the rubber plug as a whole has a resealability comparable to that of a conventional rubber plug made of butyl rubber, and the resealability is not improved.

  The present invention has been made in view of the above circumstances, and its problem is that it has excellent sealing performance and excellent coring resistance and re-use even when the needle is used for multiple punctures. It is an object of the present invention to provide a rubber plug for pharmaceuticals capable of maintaining sealing performance and a method for producing the same.

  In order to solve the above-described problems, the rubber plug according to the present invention has a layer containing a fluorine atom in a surface layer portion, and the fluorine atom-containing layer has a composition ratio of fluorine atoms from the surface toward the inside. Is characterized by a continuous decrease.

  The rubber plug manufacturing method according to the present invention includes a first purging step in which the rubber plug is left in an inert gas atmosphere or under reduced pressure, and the surface of the rubber plug after the first purging step is subjected to fluorine treatment. A fluorine atom contacting step for contacting with a gas-containing atmosphere; and a second purge step for leaving the rubber stopper after the fluorine atom contacting step in an inert gas atmosphere or under reduced pressure.

  According to the rubber plug and the manufacturing method thereof according to the present invention, a rubber plug that is excellent in sealing performance and that exhibits high resealability and coring resistance in the case of performing many times of puncture with an injection needle is easily provided. can do.

Embodiments of the present invention will be described below.
As described above, the rubber plug according to the present invention has a layer containing fluorine atoms in the surface layer portion, and the fluorine atom-containing layer has a continuous composition ratio of fluorine atoms from the surface to the inside. It is characterized by a decrease. In the rubber plug manufacturing method according to the present invention, the rubber plug is allowed to stand in an inert gas atmosphere or under reduced pressure, and the surface of the rubber plug after the first purge process is subjected to fluorine treatment. A fluorine atom contact step for contacting with a gas-containing atmosphere; and a second purge step for leaving the rubber stopper after the fluorine atom contact step in an inert gas atmosphere or under reduced pressure. It is.

  When the injection needle is inserted, the needle is inserted from the top surface of the rubber stopper, and when it is extracted, the bottom surface located in the container of the rubber stopper is first deformed. That is, when the needle is pierced, the slipperiness of the surface of the rubber stopper has a major influence on the ease of piercing. Therefore, if the fluorine atom content on the surface is large, a good needle operation of the injection needle is provided. On the other hand, since the content of fluorine atoms in the interior is small, the adhesion between the rubber members is sufficiently maintained, and both the sealing performance at the time of puncture and the sealing performance after removal (resealability) are deteriorated. There is nothing to do.

  The rubber plug of the present invention has a layer having a higher fluorine atom content in the surface layer portion than the inner layer portion of the rubber plug, and the fluorine atom-containing layer has a continuous composition ratio of fluorine atoms from the surface to the inside. is decreasing. In the rubber plug of the present invention, at least the surface into which the injection needle is inserted has a layer having a high fluorine atom content, and the fluorine atom-containing layer has a continuous composition ratio of fluorine atoms from the surface to the inside. In some cases, the fluorine-containing layer may be present on the entire surface.

  The fluorine atom content can be confirmed by an analyzer such as X-ray electron spectroscopy (ESCA). The fluorine atom content may have a distribution that gradually decreases from the surface layer portion toward the inner layer portion, or a distribution that decreases stepwise from the surface layer portion toward the inner layer portion. Also good.

  The rubber plug of the present invention having such characteristics is optimally applied to a pharmaceutical rubber plug used for a container for storing a pharmaceutical product.

  The aforementioned fluorine atom is preferably chemically bonded to the rubber compound by substituting the terminal hydrogen atom of the rubber material compound.

  Moreover, it can confirm that the above-mentioned fluorine atom has couple | bonded with the rubber compound chemically by measuring the film | membrane surface by FTIR-ATR method.

  As the raw rubber used in the production of the rubber plug of the present invention, any rubber material conventionally used in the production of various rubber plugs can be used, and is not particularly limited. It is appropriately selected according to the drug, solvent, etc. in the container. For example, isoprene rubber, butadiene rubber, styrene butadiene rubber, ethylene propylene rubber, ethylene-propylene-diene monomer terpolymer rubber, butyl rubber (isoprene-isobutylene rubber), epichlorohydrin rubber, nitrile rubber and other synthetic rubber, natural rubber , Thermoplastic elastomers and the like, which are blended with fillers, crosslinking agents and the like. Of these, butyl rubbers such as butyl rubber, chlorinated butyl rubber, brominated butyl rubber, divinylbenzene copolymer micro-crosslinked butyl rubber and epichlorohydrin rubber, which have excellent gas barrier properties, are preferably used.

  The manufacturing method of the rubber plug of the present invention is not particularly limited, and can be manufactured by compression molding similar to a normal rubber plug. The above raw rubber is mixed and kneaded by mixing and kneading various compounding agents used in the production of ordinary rubber stoppers such as vulcanization systems, fillers, and colorants suitable for each raw rubber. A vulcanizable rubber composition is prepared. The obtained unvulcanized sheet-like vulcanizable rubber composition is placed in upper and lower molds, and compression-formed at a predetermined temperature and pressure, and at the same time vulcanizes the rubber composition. The desired rubber stopper is obtained by releasing the pressure after a predetermined time and taking out the molded product from the mold. The molding conditions (pressure, heating temperature, pressurization time, etc.) are not particularly limited, and as in the production of conventional rubber plugs, the type of rubber composition used, that is, the type of raw rubber component, the vulcanizing agent The molding conditions satisfying the required quality are determined by preliminary experiments depending on the type and amount of the material.

  In the present invention, the shape of the rubber plug is not particularly limited, and may be any shape such as a rubber plug having a leg portion (including those having a flange portion) and a disk type rubber plug.

  More specifically, the rubber plug manufacturing method of the present invention includes a first purging step in which the rubber plug is left in an inert gas atmosphere or under reduced pressure, and the rubber plug that has completed the first purging step. A fluorine atom contact step of bringing the surface into contact with a fluorine gas-containing atmosphere; and a second purge step of leaving the rubber stopper after the fluorine atom contact step in an inert gas atmosphere or under reduced pressure. It is what.

  The production method of the present invention will be described with reference to the drawings. FIG. 1 shows an example of a reaction apparatus used in the production method of the present invention. This reaction apparatus includes a chamber 1 and a heating device 5 for controlling the temperature of the chamber, and a fluorine gas supply line 2 and an inert gas supply line 3 for introducing fluorine gas and inert gas into the chamber. Are connected. An exhaust line 4 for extracting unnecessary gas is connected to another position of the chamber. The chamber has a space where the above-mentioned molded body can be placed, and various shaped molded bodies can be placed there. The gas extracted from the exhaust line 4 can be recycled as it is or can be separated and purified and returned to each gas supply line.

(1) First purge step in which the rubber plug is left in an inert gas atmosphere or under reduced pressure By passing through the step (1), a phase having a large fluorine atom content is present in the surface portion of the rubber plug without in-plane distribution. To be able to.

  In this step (1), first, the rubber stopper 6 is placed in the chamber 1, the chamber is closed, the valve of the inert gas supply line 3 is opened, and the inert gas flows into the chamber. Examples of the inert gas include argon, nitrogen, helium, neon, krypton, and xenon. In the present invention, argon is preferably used. The chamber used is preferably made of stainless steel or aluminum.

  It is preferable that the rubber plug in the chamber is heated by a heating device in an inert gas atmosphere. By this heating, water, oxygen and volatile components contained in the rubber plug can be efficiently removed. The heating temperature is the surface temperature of the rubber plug, and is usually 60 to 180 ° C, preferably 80 to 130 ° C. The heating time is usually 1 to 360 minutes, preferably 1 to 200 minutes.

  Instead of leaving in an inert gas atmosphere, the rubber stopper may be left under reduced pressure. When left under reduced pressure, the pressure is usually 500 mmHg or less, preferably 100 mmHg or less. The lower limit of the pressure is 1 mmHg. If the pressure is extremely reduced, contaminants such as oil and moisture may reversely diffuse from the exhaust system. Heating is also preferred when left under reduced pressure. The heating temperature is usually 15 to 100 ° C. In addition, it is preferable to inject a high-purity inert gas simultaneously with decompression because the amount of oxygen and water can be efficiently removed. The decompression time is usually 1 to 360 minutes, preferably 1 to 200 minutes.

  If a large amount of oxygen or moisture is present in the rubber stopper, the surface of the rubber stopper is easily hydrophilized in the next step (2). Therefore, it is preferable to reduce the amount of oxygen or moisture in the step (1). The amounts of oxygen and water in the rubber plug are usually 1% by weight or less, preferably 100 ppm by weight or less, and more preferably 10 ppm by weight or less.

(2) The step of bringing the surface of the rubber stopper that has finished the first purge step into contact with an atmosphere containing fluorine gas After the step (1), the valve of the inert gas supply line is closed, and if necessary Cool the chamber, then open the fluorine gas supply line 2 valve and the inert gas supply line 3 valve to adjust the concentration of fluorine gas, mix fluorine gas and inert gas in the line and dilute The fluorine gas is obtained and flows into the chamber, and the inside of the chamber is filled with an atmosphere containing fluorine gas. The atmosphere containing fluorine gas may be an atmosphere composed of only fluorine gas, but is preferably composed of fluorine gas diluted with an inert gas as described above in order to moderate the reaction. The atmosphere containing fluorine gas is preferably free of oxygen and water. Specifically, the amount of oxygen and water is preferably 100 ppm by weight or less, more preferably 10 ppm by weight or less, and particularly preferably 1 ppm by weight or less.

  By bringing the surface of the rubber plug into contact with an atmosphere containing fluorine gas, fluorine gas gradually introduces fluorine atoms into the molecule from the surface of the rubber plug toward the surface layer portion and further to the inner layer portion. The fluorine atom content in the constituent material increases. The penetration depth of fluorine atoms from the rubber plug surface and the fluorine atom content vary depending on the concentration, temperature, and time of the fluorine gas.

  The concentration of the fluorine gas diluted with an inert gas is usually 0.1 to 50% by weight, preferably 0.1 to 30% by weight, more preferably 0.1 to 20% by weight. The surface temperature of the rubber plug when contacting the fluorine gas is not particularly limited, but is usually 50 to 150 ° C, preferably 20 to 80 ° C, and particularly preferably 0 to 50 ° C. The contact time is usually 0.1 second to 600 minutes, preferably 0.5 seconds to 500 minutes, more preferably 1 second to 400 minutes. When the fluorine gas concentration is high, the temperature is high, or the time is long, the penetration depth of fluorine atoms becomes deep and the fluorine atom content increases. When the fluorine gas concentration is extremely high, or when the temperature is extremely high for a long time, the material constituting the rubber plug is deteriorated. Therefore, it is preferable to contact the fluorine gas within the above range.

(3) A second purge step in which the rubber stopper in contact with the fluorine gas is left in an inert gas atmosphere or under reduced pressure. After contacting the fluorine gas and a predetermined time has elapsed, the inert gas supply line 3 is opened, The valve of the fluorine gas supply line 2 is closed to bring the chamber into an inert gas atmosphere. Examples of the inert gas are the same as those described in the step (1). And it is preferable to heat a rubber stopper with a heating apparatus. This heating can remove fluorine gas that could not be introduced into the rubber plug. The heating temperature is the surface temperature of the rubber plug, and is usually 60 to 180 ° C, preferably 80 to 130 ° C. The heating time is 1 to 360 minutes, preferably 1 to 200 minutes.

  Instead of leaving in an inert gas atmosphere, the rubber stopper may be left under reduced pressure. When left under reduced pressure, the pressure is usually 500 mmHg or less, preferably 100 mmHg or less. The lower limit of the pressure is 1 mmHg. This is because if the pressure is extremely reduced, contaminants such as oil and moisture may diffuse back from the exhaust system. Heating is also preferred when left under reduced pressure. The heating temperature is usually 15 to 100 ° C. In addition, it is preferable to inject a high-purity inert gas simultaneously with the decompression because the fluorine gas can be efficiently removed. The decompression time is 1 to 360 minutes, preferably 1 to 200 minutes.

  In addition, it is preferable that the thickness of the layer containing a fluorine atom is in the range of 0.01 to 100 μm, more preferably in the range of 0.01 to 50 μm, and in the range of 0.01 to 10 μm. Is particularly preferred. Moreover, as a ratio with respect to the total number of atoms of the fluorine atom in the surface, 10 to 70% is preferable, and it is preferable that the ratio of a fluorine atom changes to less than 5% continuously or stepwise toward the inside.

  Examples of the present invention will be described below. The following examples are illustrations for suitably explaining the present invention, and do not limit the present invention.

Example 1
(Process 1)
Using the following commercially available butyl rubber, a butyl rubber and each compounding agent were mixed and kneaded on a roll with the following compounding formulation to prepare a compounded rubber composition. This was put into a mold and compression molded under conditions of a pressure of 50 kg / cm ² and 145 ° C. for 7 minutes to produce a rubber plug A1.

(Combination prescription)
Butyl rubber (JSR Butyl 365, manufactured by Nippon Butyl Co., Ltd.) 100 parts Silica (Nippsil ER-100, manufactured by Nippon Silica Industry Co., Ltd.) 4 parts Bis (t-butylperoxy-3,3,5-trimethylcyclohexane)
(Nippon Yushi Co., Ltd. Perhexa 3M-100) 1.5 parts

(Process 2)
The rubber stopper A1 obtained in the above step 1 is put in a stainless steel container and heated at 100 ° C. for 3 hours in a high purity argon stream having an oxygen and water content of 1 weight ppb or less to remove oxygen and water from the rubber stopper A1. (First purge step). The amount of oxygen and water in the rubber stopper A1 after the treatment was less than 10 ppm by weight. This rubber stopper A1 is cooled to room temperature, and the valve is switched while taking care not to mix oxygen and moisture from the outside air, and 1 wt% fluorine gas diluted with argon gas (content of oxygen and water is 1 weight) less than ppm) was introduced at 20 ° C. (fluorine atom contact step). After 20 minutes from the introduction of the fluorine gas, the valve was switched to introduce high-purity argon having an oxygen and moisture content of 1 weight ppb or less and heated at 100 ° C. for 1 hour to remove excess fluorine gas (second Purge step). The rubber stopper after this treatment is referred to as a rubber stopper A2.

(Example 2)
(Process 1)
Using the following commercially available chlorinated butyl rubber, a compounded rubber composition was prepared by mixing and kneading chlorinated butyl rubber with each compounding agent on a roll with the following formulation. This was put into a mold and compression molded under the conditions of a pressure of 50 kg / cm ² and 145 ° C. for 7 minutes to produce a rubber plug B1.

(Compound formulation 2)
Chlorinated butyl rubber (Exxon Chemical Co., Essobutyl HT1066) 100 parts Silica (Nippon Silica Industry Co., Ltd. Nipsil ER-100) 40 parts Active zinc oxide (Shodo Chemical Industry Co., Ltd., Active Zinc Hana AZO) 4 parts Stearic acid (Kao) Lunac S # 98) 3 parts 2-di-n-butylamino-4,6-dimercapto-s-triazine 1.5 parts

(Process 2)
A rubber plug B2 was obtained in the same manner as in Example 1 except that the rubber plug B1 was used instead of the rubber plug A1.

(Comparative Example 1)
The rubber plug A1 obtained in Step 1 of Example 1 was left as it was without being subjected to Step 2, and was referred to as Comparative Example 1.

(Comparative Example 2)
Comparative Example 2 was prepared by leaving the rubber plug B1 obtained in Step 1 of Example 2 as it was without being subjected to Step 2.

(Comparative Example 3)
The butyl rubber shown in the formulation of Example 1 and each compounding agent were mixed and kneaded on a roll to prepare a compounded rubber composition, and this was sheeted with a roll to obtain a rubber sheet I of about 10 mm. . This rubber sheet I was cut into an appropriate size.

A commercially available PTFE sheet (polyflon TFE (PTFE, thickness: 0.50 mm) manufactured by Daikin Industries, Ltd.) and the rubber sheet I were stacked. This laminated sheet is placed so that the rubber surface faces the lower mold, and the upper mold for rubber plug molding is placed on the PTFE sheet surface of this laminated sheet, and the pressure is 50 kg / cm ² and the condition is 175 ° C. for 10 minutes. Then, a rubber plug laminated with a PTFE sheet was manufactured by compression molding using a mold. This rubber stopper is referred to as a rubber stopper a.

(Comparative Example 4)
Comparative Example 3 except that the compounded rubber composition used for the rubber sheet was changed to a compounded rubber composition prepared by mixing and kneading the chlorinated butyl rubber shown in the compounding formulation of Example 2 and each compounding agent on a roll. Similarly, a rubber sheet II was obtained, and this rubber sheet II and a commercially available PTFE sheet were overlapped to obtain a rubber stopper. This rubber stopper is referred to as a rubber stopper b.

  For each rubber plug (rubber plugs A2, B2, A1, B1, a, and b) obtained in Example 1 and Comparative Examples 1 and 2, the following sealing test, coring resistance test, and liquid leakage resistance A test was conducted to measure each characteristic. The measurement results are shown in Table 1.

(1) Sealability test Each of the 100 rubber stoppers was stoppered into vials having a vial mouth inner diameter (center value) of 12.5 mm, and the following airtightness confirmation test (vacuum holding test) was performed. The average value of 100 measurement results was used as a representative value.

    (Airtightness confirmation test (vacuum holding test)): A zero adjustment button of the electronic manometer is put in a state of +0 Torr. Place the test rubber stopper at the end of an empty vial in a semi-plugged state (with the legs fitted into the vial opening to the extent that the air in the vial can flow out) into the vacuum chamber and vacuum pump Then, the chamber is evacuated and held for 3 seconds, and when the inside of the vial is evacuated, the rubber stopper is completely stoppered (completely stoppered). A 22G injection needle connected to an electronic manometer is pierced into the needle puncture portion of the rubber stopper that has been completely stoppered, and the degree of vacuum in the container is measured. The degree of vacuum was compared immediately after the plugging and after 24 hours to evaluate the vacuum retention. In this test, it was determined that there was no leak (good vacuum retention) when the difference in the degree of vacuum was less than 200 Torr immediately after the plugging and after 24 hours.

(2) Coring resistance 10 mL of water is put into a vial, a rubber stopper is plugged, an aluminum cap (commercially available, plastic is acceptable) is covered, and it is wound with a hand crimper (manual clamp). Seal. After removing the upper lid of the aluminum cap (which may be made of plastic), aspirate 2 mL of water into a disposable syringe, and then attach an 18G injection needle, and randomly penetrate through the rubber stopper 100 times vertically (puncture needle). Thereafter, water inside the syringe is injected into the vial, and the injection needle is pulled out. Then, after shaking the vial up and down several times, the number of pieces of the rubber stopper in the vial is counted. As a general allowable value, the number of samples c (medical rubber plugs) dropped is 5 or less for 100 puncture needles at random.

(3) Liquid Leakage Test Put 10 mL of water into the vial, plug a rubber stopper, cover with an aluminum cap (commercially available, plastic), and tighten with a hand crimper (manual clamp) Seal. Remove the upper lid of the aluminum cap (which may be made of plastic), attach an 18G injection needle to the disposable syringe, aspirate 2 mL of air, pierce the rubber stopper vertically (puncture needle), and then insert the air into the vial. Inject 2 mL. Immediately after air injection, the vial is turned upside down, 2 mL of water is sucked, the needle is gently pulled out, and then the weight of the leaked liquid is measured. As a general allowable value, the total leakage amount is 0.1 ml (0.1 g) or less.

(4) Fluorine atom impregnation amount The fluorine concentration in the depth direction was measured for each rubber plug (rubber plug A2 and rubber plug B) obtained in Example 1 and Comparative Example 3. The measurement is a method of measuring the weight ratio of fluorine atoms to the total weight of carbon atoms, oxygen atoms, and fluorine atoms using XPS (X-ray photoelectron spectrometer) while sputtering Ar ions in the depth direction of the rubber plug. I did. The results are shown in FIG.

For Example 1, the thickness of the layer containing fluorine atoms was estimated to be 0.2 μm from the Ar sputtering time.
Further, when the film surface was measured by the FTIR-ATR method for Example 1, a broad peak derived from C—F stretching vibration was observed at 1400 to 1000 cm ⁻¹ .

  As is clear from Examples 1 and 2 and Comparative Examples 1 to 4, the rubber plug is not made into a multilayer structure, but fluorine atoms are brought into contact with the rubber material of the rubber plug, and fluorine atoms are applied from the surface of the rubber plug to the inside. It was confirmed that a significant improvement effect was obtained for all of adhesion, coring resistance and resealability by inclining the content.

  According to the rubber plug and the manufacturing method thereof according to the present invention, a rubber plug that is excellent in sealing performance and that exhibits high resealability and coring resistance in the case of performing many times of puncture with an injection needle is easily provided. can do. Accordingly, the rubber plug of the present invention is particularly important for sealing properties during storage, and provides excellent quality as a rubber plug for pharmaceuticals that uses an injection needle when collecting a drug solution from a container.

It is a figure which shows an example of the reaction apparatus used for the manufacturing method of the rubber stopper of this invention. It is the figure which showed the result of having measured the fluorine density | concentration of the depth direction with respect to each rubber stopper (rubber stopper A2 and rubber stopper B) obtained in Example 1 and the comparative example 3 by the graph.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Chamber 2 Fluorine gas supply line 3 Inert gas supply line 4 Exhaust line 5 Heating device 6 Rubber stopper

Claims (3)

  A rubber plug having a layer containing a fluorine atom in a surface layer part, wherein the fluorine atom-containing layer has a composition ratio of fluorine atoms continuously decreasing from the surface toward the inside.   2. The rubber stopper according to claim 1, wherein the rubber stopper is used for a container for storing a medicine. A first purge step of leaving the rubber plug in an inert gas atmosphere or under reduced pressure;
A fluorine atom impregnation step of bringing the surface of the rubber stopper after the first purge step into contact with a fluorine gas-containing atmosphere;
A second purge step of leaving the rubber stopper after the fluorine atom impregnation step in an inert gas atmosphere or under reduced pressure;
The method for producing a rubber plug according to claim 1, wherein:

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