阅读说明：本技术 一种不可被穿刺的药品包装的顶空残氧量检测方法 (Method for detecting headspace residual oxygen of medicine package incapable of being punctured ) 是由 袁继博 于 2020-07-21 设计创作，主要内容包括：本发明涉及药品检测领域,公开了一种适用于不可被穿刺的药品包装的顶空残氧量检测方法,包括：将待检测的样品通过待熔封开口装载于预制袋中,将开口熔封后,通过注液模块向预制袋内注入排气液体,排出袋内空气并密封注液模块,在袋中开启待测样品,收集样品顶空,用残氧仪探针穿刺预制袋的穿刺取样部位(穿刺密封垫),抽取样品顶空气体,测定数值。本发明方法可适用于安瓿瓶,旋盖瓶,预灌封注射器等多种不可被穿刺的药品包装的顶空残氧量测定,具有广泛适用性。同时无需水下操作,不损伤残氧仪。本方法还可将待测样品封袋后留存,于检测时,即时开启样品即时测定,避免样品气体溶解在排气液体中而影响测定结果。(The invention relates to the field of medicine detection, and discloses a headspace residual oxygen amount detection method suitable for medicine packages which cannot be punctured, which comprises the following steps: loading a sample to be detected in a prefabricated bag through an opening to be sealed by melting, injecting exhaust liquid into the prefabricated bag through a liquid injection module after the opening is sealed by melting, exhausting air in the bag and sealing the liquid injection module, opening the sample to be detected in the bag, collecting sample headspace, puncturing a puncture sampling part (puncture sealing gasket) of the prefabricated bag by using a probe of a residual oxygen meter, extracting sample headspace gas, and determining a numerical value. The method of the invention can be applied to measuring the headspace residual oxygen content of various medicine packages which can not be punctured, such as ampoule bottles, cap-screwing bottles, pre-filled syringes and the like, and has wide applicability. Meanwhile, underwater operation is not needed, and the residual oxygen meter is not damaged. The method can also seal the bag of the sample to be measured and keep the sample, and open the sample for immediate measurement in real time during detection, thereby avoiding the influence of the sample gas dissolved in the exhaust gas on the measurement result.)

1. A headspace residual oxygen amount detection method for a medicine package which cannot be punctured is characterized by comprising the following steps: the method is suitable for packaging various medicines which cannot be punctured, and comprises the application steps of firstly placing a sample (one or more samples) to be detected in a prefabricated bag made of flexible sealing materials, then sealing a sealing opening in a melting mode, injecting exhaust liquid through a liquid injection module and completely exhausting air in the bag, opening the sample package in the bag through a puncture-proof friction gasket, collecting gas at the headspace of the sample, puncturing a probe of an oxygen residual instrument through a puncture sealing gasket, absorbing the collected sample gas, and measuring data.

2. The method of claim 1, wherein the preformed bag is made of a flexible sealing material, the material is capable of being sealed by melting, and the preformed bag is provided with an opening to be sealed by melting.

3. The method according to claim 1, wherein the liquid injection module is made of plastic material, has a structure such as a cap or a plug which is easy to open and seal repeatedly, and is connected to the preformed bag by a ship-shaped or pipe-shaped interface.

4. The method of claim 1, wherein the piercing seal is in the form of a pre-formed bag with an attached rubber or silicone patch or a plastic component with a welded rubber plug on the pre-formed bag, and is self-sealing and maintains a seal after piercing.

5. The method of claim 1, wherein the puncture-proof gasket is formed of rubber or silicone on the inner wall of the preformed bag.

6. The method of claim 1, wherein the number of samples is greater than or equal to 1.

7. The method of claim 1, wherein the area and volume of the preformed bag are selectable according to the requirement of the sample to be tested, and the method can be applied with the structure kept unchanged.

8. The method as claimed in claim 1, wherein the exhaust gas is not limited to water, but may be liquid with good fluidity such as dimethyl silicon oil, and the air dissolved in the liquid can be removed by vacuum pumping, filtration with microporous membrane, heating, ultrasonic treatment, etc., and the appropriate exhaust gas can be selected according to the other physical and chemical properties of the sample (for example, inert solution such as dimethyl silicon oil can be used for gas interference measurement when the contents in the sample and water react chemically).

Technical Field

The invention relates to the field of medicine detection, in particular to a headspace residual oxygen amount detection method for a medicine package which cannot be punctured.

Background

The headspace residual oxygen in the medicine package is related to the stability of the medicine in the period of validity, the residual oxygen in the headspace of the medicine package is generally controlled by a nitrogen filling or vacuum pumping mode in the current medicine manufacturing industry, but the measuring means of the headspace residual oxygen of the product is still not mature enough, and how to quickly, conveniently and accurately measure the headspace gas component in the medicine package in practical application, thereby providing data support for the stability of the medicine, and the method is the key point concerned by the invention.

The headspace gas analysis technology for medicine packaging actually originates from the food packaging industry, and due to the fact that foods are rich in carbohydrate, protein and fat and have high water content, the headspace gas analysis technology is beneficial to the deterioration caused by the growth of microorganisms; therefore, the food industry usually adopts a mode of filling nitrogen or carbon dioxide or a mixed gas of the nitrogen and the carbon dioxide into packages to perform modified atmosphere packaging (such as milk powder, potato chips, puffed food, some fresh foods and the like), or places a deoxidizer into the packages to perform deoxidation packaging (such as bread, cakes and the like), thereby protecting the foods from going bad.

There are three methods for headspace gas analyzers (also known in the field of drug testing as residual oxygen meters): one method is to puncture medicine packages by sampling, absorb a certain amount of sample gas by adopting a pump suction principle, and analyze the components of the sample gas by gas sensors with different principles; one is a fluorescent patch which is positioned and adhered on the inner wall of the package, and the gas components in the package are analyzed through optical irradiation and attenuation; one is to directly use a light beam, and after penetrating through transparent glass, collect the change in wavelength or energy of the light beam, thereby analyzing the gas composition inside the package.

The top air gas analyzer which adopts a way of puncturing to extract sample gas for determination has the inevitable defects that: 1, if the medicine package is a hard material package (such as a glass ampoule, a hard plastic screw cap bottle and the like), the product package design itself does not have the puncture function, and the puncture cannot be carried out; 2, if the headspace volume of the medicine unit package is too small to meet the minimum measurement sample gas volume of the headspace gas analyzer, a plurality of packages need to be opened and the sample gas needs to be collected.

The top air body analyzer adopting the optical method of an optical patch built in a package or directly adopting light beam penetration has the following inevitable defects: 1, an optical patch is arranged in a package, if the medicine needs to be sterilized by hot pressing, the optical patch is resistant to severe conditions of 116-121 ℃ for at least 15 minutes, otherwise, the headspace residual oxygen amount of the product needing hot pressing sterilization cannot be measured by the method; 2, if the direct beam penetrates the headspace, the packaging material itself must have good light transmission, otherwise it will interfere with the data and even render it undetectable (e.g., brown glass may interfere, opaque plastic is completely undetectable).

In the prior production verification, an ampoule bottle which is made of glass and cannot be punctured is generally measured manually by using a probe of an oxygen residue instrument, in the process, a medicine is immersed under water, a medicine package is opened, bubbles are collected through a funnel, and the probe is inserted into the bubbles for measurement; the method has the defects that: the operation technique and skill of the personnel are highly required, if the bubbles are not completely collected, the measurement cannot be carried out, and if the probe of the residual oxygen meter sucks liquid, the sensor of the residual oxygen meter is damaged.

The patent CN207751971U provides a simple device for measuring the residual oxygen content in air in zinc sulfate injection ampoule bottle, which is an extension and supplement to the use method in the current production verification, and aims to use a simple mechanical device to replace manual operation, so as to prevent operators from being damaged by cullet, but still has the disadvantage that the probe of the residual oxygen meter is easy to suck liquid by underwater operation.

The patent CN110118853A provides a method for detecting the headspace residual oxygen amount of an ampoule bottle, which uses a large-size penicillin bottle, places the ampoule to be detected and glass beads/steel balls for crushing together, and crushes the ampoule by shaking forcefully; but still has the following disadvantages: 1, if the top of the ampoule bottle is too much, after water is filled in the penicillin bottle, the ampoule bottle floats on the top, so that the ampoule bottle is not beneficial to being completely filled with water; 2, a depression is formed at the bottom of the rubber plug of the penicillin bottle, and a small amount of air is easy to remain when the rubber plug is added; 3, the effect of shaking and crushing the ampoule bottle is limited, and only the bottleneck of the ampoule bottle is an easily-broken part due to the design of the ampoule bottle; 4, the method can only be used for glass ampoules and can not be used for other medicine packages.

Disclosure of Invention

The invention aims to provide a universal headspace residual oxygen amount detection method suitable for various medicament packaging forms which cannot be punctured.

The specific technical scheme of the invention is as follows: a headspace residual oxygen amount detection method for a medicine package which cannot be punctured comprises the following steps: loading the pharmaceutical packaging unit to be inspected into an open preformed bag of a flexible sealing material, sealing the opening of the preformed bag; filling liquid through a liquid injection module of the prefabricated bag, and exhausting all air to ensure that only the unopened medicine packaging units and the liquid are stored in the prefabricated bag; and (3) opening the medicine packaging unit in the bag through the blocking contact of the prefabricated bag, discharging the headspace gas bubbles to a puncture sampling part of the prefabricated bag, and detecting the residual oxygen amount of the gas in the prefabricated bag by using a probe of a residual oxygen meter.

The invention limits the flexible sealing material adopted by the prefabricated bag adopted by the method to be a film made of polyvinyl chloride, polyethylene, polypropylene, polystyrene and other resins.

The flexible sealing material adopted by the invention has a hot-melting sealing function, and can meet the special requirements of medicine detection on water resistance, oxygen resistance, light resistance and the like in different degrees through the combination of film coating or film covering.

Preferably, the preformed bag made of flexible sealing material according to the present invention should be sized according to the volume of the sample to be tested and the opening mode: if the sample is opened in a rotating way, enough space is provided for completing the rotating opening action in the prefabricated bag filled with liquid; if the sample is opened by drawing, enough space is provided for completing the drawing and opening action in the prefabricated bag filled with liquid; if the sample is broken and opened, enough space is provided in the prefabricated bag filled with liquid to finish the breaking and opening actions; typically, the volume of the sample to be tested should be between 10% and 60% of the volume of the preformed bag.

The prefabricated bag comprises a liquid injection module which is sealed in a melting mode, wherein the liquid injection module is generally a ship-shaped interface and a pipe-shaped interface.

The prefabricated bag is provided with a puncture sampling part (puncture sealing gasket) and a puncture sampling gasket or a plastic component (containing a rubber plug) welded with the bag, the material of the puncture sampling part is usually rubber or silica gel, and preferably, the puncture sampling part is made of butyl rubber.

The preformed bag design of the present invention can add a gasket or coating on the inner side of the bag body to enhance friction or prevent sample corners or debris from leaking.

Preferably, when the volume of headspace gas of the sample to be measured is small, the volume of the prefabricated bag can be correspondingly enlarged so as to simultaneously accommodate a plurality of samples to be measured in the bag.

Preferably, in the technical solution of the present invention, the liquid used to remove the air in the bag can be removed by one or more of vacuum, heating, ultrasonic, or boiling and then cooling by introducing nitrogen to remove dissolved oxygen in the liquid.

In order to further increase the detection accuracy, the puncture sampling part of the prefabricated bag has self-sealing property, so that no air leakage exists between the puncture needle head and the prefabricated bag after puncture action is performed.

Compared with the prior art, the invention has the beneficial effects that: the method is simple and convenient, easy to operate, high in sensitivity, accurate in measurement and free from interference of outside air. The application range is wide (the invention is suitable for all hard material packages which can be opened manually and cannot be punctured, including but not limited to glass ampoules, screw-cap glass oral liquid bottles, pre-filled syringes made of glass or COP plastic and the like). The exhaust liquid adopted in the invention is not limited to water, and if the contents in the sample and water are subjected to chemical reaction to generate other gases, other inert liquids with good fluidity, such as dimethyl silicon oil, can be used, and the method can be used for measuring. Meanwhile, the invention can separate the sample preparation link from the sample determination link, can prepare a plurality of samples at one time, and can combine the samples to wait for inspection without instant inspection, thereby bringing great convenience to operators. The method of the invention can conveniently collect headspace gas in a plurality of samples at one time. The method of the invention can uniformly and immediately open the package of the sample to be measured before measurement because the sample to be measured is not opened after being sealed in the prefabricated bag, thereby ensuring the accuracy of the measurement result.

Drawings

Fig. 1 is a schematic diagram of a general embodiment.

FIG. 2 is a schematic diagram of the operation of example 1.

FIG. 3 is a schematic diagram showing the operation of example 2.

FIG. 4 is a schematic diagram showing the operation of example 3.

The reference signs are: a prefabricated bag sealing part-1, a prefabricated bag opening part-2 to be sealed by melting, a liquid injection module-3, a puncture sampling part (puncture sealing gasket) -4, a residual oxygen meter measuring probe-5, a sample headspace gas-6, an exhaust liquid-7 and an anti-puncture friction gasket-8.

Detailed Description

The present invention will be further described with reference to the following examples.

General examples.

A headspace residual oxygen amount detection method for a non-puncturable medicine package comprises the following steps: loading the pharmaceutical packaging unit to be inspected into an open preformed bag of a flexible sealing material, sealing the opening of the preformed bag; filling liquid through a liquid injection module of the prefabricated bag, and exhausting all air to ensure that only the unopened medicine packaging units and the liquid are stored in the prefabricated bag; and (3) opening the medicine packaging unit in the bag through the blocking contact of the prefabricated bag, discharging the headspace gas bubbles to a puncture sampling part of the prefabricated bag, and detecting the residual oxygen amount of the gas in the prefabricated bag by using a probe of a residual oxygen meter.

Fig. 1 is a schematic view of a preformed bag as described in the general example.

Preferably, the exhaust gas used in the general examples is degassed purified water after being filtered by a microporous filter membrane after sonication.

Preferably, the length and width of the prefabricated bag are determined by the package opening form of the sample to be tested, and the injection volume of the exhaust liquid is also determined by the package opening form of the sample to be tested: if the ampoule is measured, the injection volume of the exhaust liquid accounts for 70% of the total volume of the bag, so that the prefabricated bag is slightly filled, the bag body is protected from being scratched by broken glass when the ampoule is broken, and air leakage is avoided; if the screw cap oral liquid bottle is measured, the injection volume of the exhausted liquid accounts for about 50 percent of the total volume of the bag, so as to ensure that the opening action of the screw cap can be finished outside the bag; if the sample is determined to be a pre-filled syringe, the volume of the evacuated liquid injected should be about 30% to 40% of the total volume of the bag to ensure that the action of withdrawing the plunger or opening the needle can be accomplished outside the bag.

Optionally, when the volume of the gas contained in the sample to be detected cannot meet the measurement requirement of the residual oxygen meter, the number of the samples to be detected can be increased at will, and only a prefabricated bag with a reasonable volume needs to be selected correspondingly.