In clinical infusion treatment, 1 to 3 drugs are usually added to the basic infusion. During the preparation process, the physical and chemical properties of the infusion are changed due to puncture and mixing, resulting in a large number of insoluble particles. The particles will be blocked after entering the human body. Capillary blood clots and granulomas; mismatches and bacterial contamination may occur during the preparation process, increase the labor intensity of nursing staff, increase the incidence of needle stick injuries with potential infection risks, and be detrimental to the occupational safety of medical staff; and the preparation process Time consuming, not conducive to emergency medication for patients.
Against the background of higher requirements for infusion quality, a new type of infusion package meeting the demanding requirements came into being-liquid-liquid, powder-liquid multi-chamber infusion packaging bags (hereinafter referred to as multi-chamber bags).
First, the characteristics of multi-cavity bags
Multi-chamber bag technology is very advanced for the current packaging industry and has the following characteristics:
1. Medication safety
The multi-cavity bag technology realizes closed environment preparation by opening the virtual welding between the chambers, completely eliminating possible microbial contamination and dispensing errors during preparation, preventing nosocomial infections, and at the same time, it has low environmental requirements, and does not require a special sterile dispensing room when dispensing.
Without the aid of pumps, syringes, pipelines and other auxiliary facilities, the mixing and mixing time can be greatly reduced, and the rationality of medication is highly reflected.
The bag body material is non-PVC film and does not contain phthalates such as DEHP [di (ethylhexyl) phthalate] plasticizers, which reduces the environmental pollution of medical waste.
It can reduce the storage space of medicines in circulation and medical units.
5. Emergency needs
Particularly suitable for emergency, disaster relief, emergency, field rescue, war and other characteristics.
Types and formulas of non-PVC multi-chamber bag infusion packaging films
1.Packing film type
From the state of packaged drugs, it can be divided into two types: liquid-liquid and powder-liquid. These two types have different requirements for the welding strength of the packaging film. The solubility of packaged drugs can be divided into two types: The two types have a big difference in the selection of the inner material of the packaging film. From the sensitivity of the packaged drugs to oxygen and hygroscopicity, it can be divided into low barrier and high barrier. These two types have great barriers to water and gas. difference.
2. Packaging film structure and formula
At present, there are two common structures. The first type is a five-layer structure represented by Sealed Air products in the United States. Its main composition is: modified ethylene-propylene copolymer / polyethylene / polyethylene / ethylene methyl methacrylate. Polymer / ester copolymer, the five-layer layer thickness ratio is: 15% / 5% / 65% / 5% / 10%, the inner layer is a polypropylene binary copolymer and an elastomer SEBS (styrene-ethylene-butylene -styrene block copolymer (styrene-ethylene-butene-styrene block copolymer) blend, and the heat seal window range is adjusted by adjusting the ethylene monomer content in the copolymer and the elastomer SEBS ratio to achieve solid welding and virtual Welding, and good cooking resistance; polyethylene in the middle to improve the flexibility of the film ; the outer layer of the ester copolymer is good in heat resistance and printing coloration.
The second type is a three-layer structure represented by the products of German Polysini and Baxter. Its main composition is: a mixture of PP, PE, PB copolymer and SEBS / a mixture of PP, PE copolymer and SEBS / PP and SEBS mixture, the three layer thickness ratio is: 15% / 70% / 15%, the inner layer is a mixture of polypropylene terpolymer and SEBS, by adjusting the ethylene butene monomer in the terpolymer The content and the proportion of SEBS change the range of the heat-sealing window, realizing welding and virtual welding, and excellent retort resistance and water resistance; the intermediate layer is a polypropylene binary copolymer blended with SEBS to increase its flexibility, improve film toughness and improve Low temperature resistance of the film; the outer layer provides heat resistance and printability for blending of homopolypropylene and SEBS. The three-layer materials are all improved by adding a certain proportion of SEBS (styrene-ethylene-butene-styrene) to improve the softness and crystallinity of the entire film, avoiding the increase in crystallinity caused by heat during the cooking of the film, which affects the transparency and hardening , Becomes brittle.
The inner layers of the above two formulas are non-polar polymers, which are not suitable for high-frequency welding. When the inner layer material melts and crystallizes during high-temperature hot pressing, it easily embrittles, resulting in a high leakage rate of the finished bag, and the poor gas barrier properties of these two films are not suitable for direct Packaging of fat-sensitive milk, amino acids, and other oxygen-sensitive drugs requires the addition of expensive high-barrier outer bag films for vacuum packaging. The production and sterilization process is very complicated, the quality of drugs is unstable, and the scope of application is narrow.
To this end, Hubei Hengtai Rubber & Plastic Co., Ltd. has developed a new five-layer structure after research and development. Its main composition is: EVA / COC (cyclic olefin copolymer) / polyethylene / ethylene acrylate polymer / Ester copolymer, the inner layer of EVA is copolymerized with ethylene and vinyl acetate. It does not need to add any plasticizers and stabilizers during processing. It has high transparency and excellent flexibility, low temperature resistance and aging resistance. , Heat sealing and other aspects are better than PVC. EVA is a polar polymer. It can be used for hot welding and high frequency welding to achieve real welding and virtual welding. It can reduce the leakage rate of the finished bag. It is especially important to package fat-soluble drugs. The COC is used as the secondary inner layer instead. In traditional polyolefins, COC materials do not have unsaturated double, triple or aromatic ring structures. Therefore, COC materials have better heat resistance and oxidation resistance, and their thermal cracking temperature can be higher than 400 ° C. In addition, COC materials use non-toxic monomers as raw materials (cycloolefin monomers), and the polymer is extremely pure, with transparency, very low water permeability, no cytotoxicity, no induced organism mutations, no irritation, and FDA compliance Standard and other characteristics, which greatly improve the barrier properties, temperature resistance and safety of the film, and solve the barrier problems of ordinary packaging films.
The non-PVC multi-cavity bag infusion packaging films currently used in China are all produced by blow molding. There are two main categories: one is produced by Sealed Air in the United States using a five-layer co-extrusion upper-air cooling process; the other is This type is produced by the German company Polysini, which adopts a three-layer co-extrusion bottom-blowing water cooling process.
As far as is currently known, only Fresenius and Baxter in the world use the casting method to produce non-PVC multi-cavity bag infusion packaging films, and they are mainly used to support their own pharmaceutical factories. .
Low-melting polymers such as polyethylene and ethylene-vinyl acetate copolymers are included in the other five-layer formula. In order to meet the high-temperature (115-121 ° C, 12-30min) sterilization requirements in infusion production, they must be crosslinked by electron beam radiation to The temperature resistance of the packaging film is improved. The electron beam also sterilizes the packaging film at the same time, which is more suitable for packaging sterile medicine powder.
Fourth, the main production equipment
1.Five-layer co-extruded film production equipment (manufactured by Penton, Canada)
Extrusion system: five extruders (inner and outer screw φ45mm, secondary inner and secondary outer screw φ40mm, intermediate screw φ75mm), five-layer coextrusion plane superimposed die
Top-blowing film bubble forming system: double-lip air ring, film bubble internal cooling (IBC), film bubble external cooling, film bubble diameter control device, and first traction device.
Rotary winding device: 360. Rotary traction device, second and third traction device, tension control device, surface and center winding device.
Radiation crosslinking device: linear electron accelerator (0.8Mev, 50mA)
2.Three-layer co-extruded film production equipment (manufactured by Guangdong Jinming Plastic Equipment Co., Ltd.)
Extrusion system: three extruder (inner and outer screw φ45mm, intermediate screw φ75mm), three-layer co-extrusion inclined plane superimposed die.
Blowing film bubble forming system: single-lip air ring, film bubble stabilizing device, cooling and sizing water ring, herringbone plate, first traction device, water collecting tank.
Rotary winding device: 360. Rotary traction device, second and third traction device, tension control device, surface and center winding device.
V. Production process and processing temperature
The material is melted and plasticized into the die through the extruder, passes through the film bubble forming system, and then enters the rotary winding device to be rolled into a film roll. The process is as follows:
Five-layer co-extruded film production process flow chart
Three-layer co-extruded film production process flow chart
During the processing of raw materials, the processing temperature curves of the five-layer co-extruded film inner (outer) layer extruder, sub-inner (outer) layer extruder, middle layer extruder, and die head are shown in Table 1; three layers The processing temperature curves of the inner (outer) layer extruder, middle layer extruder, and die of the coextruded film are shown in Table 2. When changing the formula or the amount of extrusion, the processing temperature needs to be adjusted.
Table 1 Five-layer co-extruded film processing temperature
Table 2 Processing temperature of three-layer co-extruded film
Product specifications and main performance
Products with different specifications can be produced according to different purposes. The general thickness ranges from 150 to 250um, and the commonly used thicknesses are 190um, 200um, and 250um. The width of the product can be cut to 170mm, 220mm, 320mm and other specifications according to needs.
2. Low-resistance diaphragm physical properties
3.Physical properties of high resistance diaphragm
5. Biological performance
Seven, multi-chamber bag infusion production process
Production process flow chart of powder and liquid multi-chamber bag infusion
Production process flow chart of liquid-liquid multi-chamber bag infusion
Application and Development Prospects
Non-PVC multi-cavity bag infusion packaging film has a wide range of uses and a broad market. With its advantages such as safety, environmental protection and energy saving, it has been widely recognized by developed countries in the world. Multi-chamber bags have been developed in foreign countries for nearly thirty years. There are many types of products, mainly packaging nutrient solutions, biological products, anti-tumor drugs, etc. At present, domestic multi-chamber bags are mainly used in the following areas:
(1) "All-in-one" nutrition infusion, mainly including: fat milk, amino acids, glucose, electrolytes and trace elements;
(2) Renal dialysate and peritoneal dialysate, mainly including: electrolytes, glucose, bicarbonate and lactate;
(3) powder-liquid double-chamber bag, mainly including: cephalosporins sterile powder, glucose or sodium chloride.
The production of non-PVC infusion films in China began in the early 21st century. At present, there are more than 10 non-PVC infusion film production lines in China. There are few domestic companies that can produce non-PVC multi-chamber bag infusion packaging films, and the quality stability of packaging films is poor. The packaging film still relies on imports, is expensive, and the production cost of pharmaceutical factories is extremely high, which seriously hinders the development of the multi-chamber bag infusion market.
At present, the multi-chamber bags used in China are basically imported, foreign-funded or joint-venture pharmaceutical products. The domestic market only has a nutrition infusion scale close to 6 billion yuan, which is less than one-third of the size of the US market. The prospect is very promising. With the improvement of people's living standards in our country, the requirements for the safety and convenience of medication are getting higher and higher. The country will definitely increase the development of multi-chamber bags. Multi-chamber bags will emerge in the future in the infusion packaging market . There will be great room for development in terms of clinical and drug safety.
 Cheng Kaisheng, Yin Lifang, Zhou Jianping. Overview of the development of double-chamber bag infusion [J]. Advances in Pharmacy, 2006, 30 (11): 448-501.
 Zhang Jihong. Application of non-PVC multilayer co-extruded film in pharmaceutical infusion package [J] .China Packaging Industry, 2002,92 (2): 23-24.
 Cheng Lianfang, Liu Ziming. Processing and application of non-PVC film infusion film [J]. Guangdong Packaging , 2011, 7 (2): 23-25.
 Edited by China Food and Drug Inspection and Research Institute. Technical requirements for on-site assessment of pharmaceutical packaging materials production [S]. April 2014.
 Yang Zemin, Chen Jisheng, Feng Ruizhi, Wang Jing. Development and quality standard of non-PVC multilayer co-extruded film infusion bag [J]. China Pharmacy, 2003, 14 (7): 395-397.
 Compiled by the State Food and Drug Administration. Compilation of standards for packaging materials and containers in direct contact with drugs (sixth series) [S]. 2005: 19-32.
 Ding Enfeng, Gao Haiyan. Brief introduction to the production process and equipment of double chamber bag injection and discussion of quality problems [J]. Medical Engineering Design, 2007, 28 (2): 39-41.