The packaging of fully enclosed infusions needs to exclude air pollution during the infusion process, completely eliminate the risk of cross infection, and make clinical applications safer. Therefore, high barrier properties are required for infusion packaging. Non-PVC flexible packaging infusion bags have the characteristics of light weight, environmental protection and convenient transportation. They have advantages over traditional glass bottles, plastic bottles and PVC bags in product composition, production process, quality control, clinical application and environmental protection. At present, the share of infusion products in non-PVC soft bags is increasing year by year, which is the future development trend.
Amino acid is a common infusion compound preparation. It is generally composed of tryptophan, leucine, isoleucine, methionine, valine, phenylalanine and other amino acid components. It is colorless or almost Colorless clear liquid. Tryptophan and other ingredients in the formula are easily oxidatively decomposed, and the stability in the production and storage process is greatly affected by the oxygen content in the medicinal solution. The higher the oxygen content in the medicinal solution, the more oxidative degradation during production and storage, the worse the stability, the darker the medicinal solution, and the lower the product quality.
Therefore, for amino acid non-PVC infusion packaging, the technical problem of reducing the oxidation content of the packaging bag during industrial production needs to be solved.
First, the shortage of non-PVC soft bags
Non-PVC soft bags show insufficient barrier properties compared to glass bottles. According to YBB00102005 three-layer coextrusion film (Ⅰ), bag and YBB00112005 five-layer coextrusion film (Ⅰ), bag standard, oxygen transmission rate is 1200cc / m2.24h.0.1Mpa, nitrogen transmission rate is 600cc /m2.24h.0.1Mpa is qualified.
The five-layer membrane currently used in the market has an oxygen transmission rate of about 200cc / m2.24h.0.1Mpa, and the three-layer membrane has an oxygen transmission rate of about 700cc / m2.24h.0.1Mpa, which is a standard product. However, in the amino acid production process, even if measures such as thinning the production workshop and nitrogen protection during the filling process are taken, there is still 3% residual oxygen in the non-PVC soft bag after filling, and the non-PVC soft bag is highly transparent. The excess rate causes oxygen in the outside air to continuously penetrate into the soft bag during sterilization and storage. As the oxygen content in the bag continues to increase, under the action of oxygen, the product is oxidized in a short time, and the effective ingredients are reduced. , Which affects the efficacy.
In order to ensure that the product can effectively block the penetration of external oxygen during the shelf life, the oxygen transmission rate of the package is required to be lower than 5cc / m2.24h.0.1Mpa. At present, a common practice is to add a transparent outer packaging bag (referred to as a barrier outer bag) with a high barrier performance to a non-PVC soft bag (referred to as an inner bag) to achieve an oxygen transmission rate lower than 5cc / m2.24h. The requirement of 0.1Mpa, so as to ensure the stability of the quality of amino acids during the shelf life.
Factors affecting the oxygen content in non-PVC soft bags
Generally, there are three sources of oxygen that affect the environment of the bag during the storage and transportation of the product after packaging: one is the residual oxygen in the non-PVC soft bag, the other is the penetration of the packaging material and the leakage of oxygen from the outside, and the external oxygen Residual oxygen in the bag.
Residual oxygen in non-PVC soft bags can be reduced by adopting reasonable processes. For example, high-barrier packaging materials are used in outer bags to prevent outside oxygen from entering the non-PVC soft bags. Select reasonable packaging to reduce the residual oxygen between the inner and outer bags. These measures reduce the oxidation reaction and extend the shelf life of the product. However, to ensure that the amino acid does not deteriorate during the shelf life and the content does not decrease, it is necessary to continuously control the oxygen content in the non-PVC soft bag and reduce the oxidation reaction. This requires the use of a deoxidizer.
Application of deoxidizer on non-PVC infusion soft bag outer bag
1. Non-PVC infusion soft bag outer bag packaging sterilization method
Generally, the sterilization of infusion products adopts the moist heat sterilization method, and the sterilization conditions are 115 ° C, 30min or 121 ° C, 20min. Generally, first sterilization and then packaging. Practice verification: As an amino acid infusion product, under normal sterilization conditions, the sterilization process has a large effect on the content of amino acids. A sterilization cabinet containing a nitrogen protection device must be used. Sterilization under nitrogen protection conditions can ensure sterilization. During the process, the amino acid content is stable.
In order to ensure the stability of the sterilized amino acid infusion content during the sterilization under the existing conditions, the outer bag is mostly used for sterilization, light inspection, and boxing, so as not to affect the effect of heat and humidity sterilization. The outer packaging uses vacuum packaging, that is, first packaging and then sterilization.
2. Use of deoxidizer
When using, take a 250ml (assuming) non-PVC infusion bag into the high-barrier outer bag, and then put a selected type of deoxidizer into the high-barrier outer bag for heat-sealing and sealing. Pay attention to the quality of the seal to prevent air leakage.
Because the deoxidizer will inevitably come into contact with air during packaging, and the deoxidizer can remain effective in the air for 4 hours. According to the packaging speed, choose a suitable large package. When using, you need to open one bag with one bag to ensure that each opened A large bag is used up within 1 ~ 2 hours; if it is not used up under special circumstances, the air in the original packaging bag should be removed in time and resealed to avoid failure.
3.Requirements for high-barrier packaging materials
According to the purpose of the packaging, the outer bag composite material is required to have the following properties:
(1) The outer bag composite material has transparency, high gas barrier properties, good barrier properties to N2, O2, and CO2, oxygen transmission rate ≤5cm3 / m2.24h.0.1MPa, water The vapor transmission rate is ≤3g / m2.24h, which prevents the penetration of oxygen. Different amino acid content, different sensitivity to oxygen, need different packaging properties of outer packaging.
(2) The composite material of the outer packaging bag must have sufficient mechanical strength, puncture resistance, certain stiffness, and good drop resistance and pressure resistance. It can withstand the pressure change during vacuuming and sterilization, and ensure that the 100% to 1000ml non-PVC infusion products have the lowest damage rate during transportation and storage.
(3) The outer bag composite material needs to be sterilized and must have high temperature resistance.
(4) It has good sealing performance to ensure product sealing.
Therefore, the outer packaging bag composite material is usually a three-side sealed packaging bag or a composite film made of a double-layer composite film or a three-layer composite film or a multilayer co-extruded film. High barrier PVDC or EVOH co-extruded film, K coating film, modified PVA coating film and transparent evaporation film are commonly used as the barrier layer.
4.Vacuum packaging with oxygen absorbent
Vacuum packaging is a packaging technology in which the air in the packaging container is evacuated before the container is sealed so that the air in the sealed container reaches a predetermined degree of vacuum, and the sealing is completed. It uses packaging materials with excellent barrier properties (air tightness) and strict The sealing technology keeps the bag in a highly decompressed state, and the air is scarce, which is equivalent to the effect of low oxygen, to achieve a packaging method that extends the shelf life of the product. The vacuum degree in the container packed with vacuum packaging technology is usually 80 ~ 150KPa. Vacuum packaging is equipped with oxygen absorber, which has the following characteristics:
(1) The vacuum reduces the oxygen content between the non-PVC soft bag and the outer bag, and the oxygen absorbent further reduces the oxygen content between the inner and outer bag, which can effectively prevent the oxygen in the outer bag from penetrating into the non-PVC soft bag. Slow down the oxidation of amino acids in non-PVC soft bags and extend the shelf life of the product.
(2) The outer bag with excellent barrier properties (air tightness) and strict sealing technology can effectively prevent the external environment oxygen from penetrating into the outer bag and entering the non-PVC soft bag, which can avoid amino acid oxidation and prevent Secondary pollution, at the same time, the oxygen absorber can continuously consume the oxygen infiltrating into the outer bag, and keep the low oxygen content between the inner and outer bags.
(3) The gas inside the vacuum packaging container has been eliminated, and the inner and outer bags are close together, which accelerates the heat transfer, can improve the heat sterilization efficiency, and does not affect the effect of moist heat sterilization. At present, most of the amino acid infusion production plants in our country generally adopt this packaging first and then sterilization process based on technical reasons and equipment conditions.
(4) Because the air between the inner and outer bags is removed, the outer bag will collapse and adhere to it according to the shape of the non-PVC soft bag. There will be a lot of wrinkles on the shape, which will affect the appearance. The layer has poor folding resistance, pinholes appear in the wrinkles, and increase in moisture and oxygen permeability during high temperature sterilization will reduce the barrier performance. Therefore, the puncture resistance of the outer bag is required, and the transportation and storage conditions are required to prevent During the storage and transportation, the outer bag ruptured or the contents were damaged.
(5) Adopting the sterilization process after packaging, it is required that the high-barrier transparent outer bag must be able to withstand sterilization at 121 ° C, 20min, or 115 ° C for 30min. After sterilization, the outer bag contains a small amount of water vapor and sometimes requires subsequent processing.
(6) Filling and sealing of packaging materials must be performed in the same vacuum, which greatly reduces the efficiency of packaging. And packaging and sealing equipment with vacuum chambers is expensive.
(7) The oxygen absorbing agent needs to select a sterilizing oxygen absorbing agent, which has a high cost.
5. Atmospheric packaging with oxygen absorbent
Atmospheric pressure packaging is the most common packaging method. It means that under normal pressure and normal temperature conditions, the bag is opened to fill the contents or sealed automatically after filling. The bag contains a certain amount of air. Its characteristics are:
(1) Simple operation and high efficiency. It is only necessary to put the deoxidizer between the inner and outer packaging bags, without adding other complicated procedures, and the technical level of the staff is not high, eliminating the original step of extracting oxygen in the package, and the overall packaging speed Faster and more efficient; automatic packaging can be achieved by selecting suitable packaging materials.
(2) The space between the inner and outer bags is large, and the function of the oxygen absorber is fully exerted. Selecting a suitable oxygen absorber can make the oxygen concentration between the inner and outer bags reach below 0.1% over a day and night, or even close to the anaerobic state. (0.01%); At the same time, the continuous oxygen absorption ability can eliminate the oxygen infiltrating from the outer bag to the inner and outer bags from the outside air, and continue to maintain a near anaerobic state, which makes up the weakness of the membrane material and reduces the non-PVC softness. The amount of residual oxygen in the bag eliminates or reduces the adverse effects of oxygen.
(3) Because the air in the outer bag affects the heat transfer, reduces the heat sterilization efficiency, and affects the sterilization effect, it is not suitable for the first packaging and then sterilization process. It is more suitable for the first sterilization and then packaging process to improve the non-PVC softness. Requirements for bag sterilization.
(4) The appearance of the package is flat, and no wrinkles are formed due to vacuuming, which reduces the puncture resistance requirements of the high-barrier packaging material. At the same time, the packaging material does not need to be sterilized at 121 ° C, 20min or 115 ° C, 30min to make the outer packaging composite material. The range of choice is wider.
6. Nitrogen-filled packaging with oxygen absorber
Nitrogen-filled packaging is also called vacuum nitrogen-filled packaging and gas replacement packaging. The product is packed into a packaging container. After the air in the packaging container has reached a predetermined vacuum degree, it is filled with nitrogen and then the sealing process is completed. The gas replacement rate is required to reach More than 99.5% of a kind of packaging.
(1) In addition to the oxygen and quality assurance functions of vacuum packaging, nitrogen-filled packaging mainly has a pressure-resistant effect. Nitrogen is a cheap and ideal inert gas. Injecting an appropriate amount of nitrogen can not only effectively expel the oxygen in the outer bag, reduce the amount of residual oxygen in the outer bag, but also act as a supplementary gas or a buffer gas to reduce the pressure difference between the two sides of the outer bag and maintain The geometry of the product does not affect the appearance of the outer bag and the printing and decoration.
(2) The space between the inner and outer bags is large, and the function of the oxygen absorber can be fully exerted, which can further reduce the oxygen content between the inner and outer bags; at the same time, the outer bags with excellent barrier properties (air tightness) and strict Under the condition of sealing technology, the continuous oxygen absorption capacity of the oxygen absorber can eliminate the oxygen infiltrating from the outer bag to the inner and outer bags from the outside air, and continuously maintain a near-anaerobic state, slowing the oxidation of products in non-PVC soft bags process.
(3) The buffer gas reduces the damage rate of the product during transportation.
(4) Due to the nitrogen in the outer bag, it affects the heat transfer, reduces the heat sterilization efficiency, and affects the sterilization effect. It is also not suitable for the first packaging and then sterilization process. It is more suitable for the first sterilization and then packaging process and improves non-PVC. Requirements for sterilization of soft bags.
(5) The packaging material does not need to be sterilized at 121 ° C, 20min or 115 ° C, 30min, which makes the selection of outer packaging composites wider, but because of nitrogen, the barrier properties of outer bags are higher.
(6) Similar to vacuum packaging, although it has a good effect on reducing the oxygen content, the equipment cost is high and the packaging efficiency is low.