Sterile medicine storage bag convenient to carry and freeze and preparation method thereof

Abstract

The invention relates to the technical field of medicine packaging, and discloses a sterile medicine storage bag convenient to carry and freeze and a preparation method thereof, the sterile medicine storage bag comprises the following raw materials by mass: 80-90 parts of low density polyethylene, 15-20 parts of linear low density polyethylene, 5-10 parts of a composite additive, 3-5 parts of a plasticizer, 1-1.5 parts of a lubricant, 3-5 parts of a stabilizer, and 1-2 parts of an antioxidant. The composite additive comprises a compound and cellulose nanowhiskers, and the cellulose nanowhiskers can be inserted into a polyethylene molecular chain structure through a long-chain alkane structure in the compound to serve as a lubricating component, so that the polyethylene molecular chain is arranged in the whisker direction, finer crystals are formed through induction, and the low-temperature resistance of the polyethylene resin is improved; the polyethylene resin still has good low-temperature toughness in an environment below-80 DEG C, and the antibacterial performance, the mechanical performance, the barrier performance and the low-temperature resistance of the polyethylene-based medicine storage bag are remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical packaging, in particular to a sterile medicine storage bag convenient to carry and freeze and a preparation method thereof. BACKGROUND

[0002] With the improvement of medical level and the popularity of long-term treatment of chronic diseases, a large number of patients need to use medicine at home. The medicine needs to be stored in a low-temperature environment of minus 80 DEG C for a long time. When used, it is taken out for use. Low-temperature storage is a common means for long-term storage of many biological products and biological samples. Because low temperature can slow down the activity change or loss of these biological active substances, the medicine is usually packaged and stored in a sterile medicine storage bag.

[0003] The sterile medicine storage bag is usually made of plastic products, including polyethylene, polypropylene, polyester, etc. The sterile medicine storage bag is usually prepared by compounding polyethylene resin with additives. However, the polyethylene medicine storage bag has poor barrier property and is easily affected by moisture and oxygen in the air, cannot retain the medicinal properties of the medicine, and has poor antibacterial property and is easily contaminated. In addition, the medical packaging has poor compatibility with polyethylene resin, which affects the barrier property, antibacterial property and low-temperature toughness of the sterile medicine storage bag. SUMMARY

[0004] The present application provides a sterile medicine storage bag convenient to carry and freeze and a preparation method thereof, which solves the problem of poor barrier property, antibacterial property and low-temperature toughness of the polyethylene-based medicine storage bag.

[0005] The technical scheme of the present application is as follows:

[0006] A sterile medicine storage bag convenient to carry and freeze comprises the following raw materials by mass: low-density polyethylene 80-90 parts, linear low-density polyethylene 15-20 parts, composite additive 5-10 parts, plasticizer 3-5 parts, lubricant 1-1.5 parts, stabilizer 3-5 parts, and antioxidant 1-2 parts.

[0007] The composite additive is obtained by mixing and reacting nanosilver synthesized on the surface of carboxylated cellulose nanowhiskers with tannic acid and a composite.

[0008] The composite is obtained by mixing and reacting p-hydroxycinnamic acid and polyvinyl alcohol, and then reacting with myristic acid.

[0009] A preparation method of a sterile medicine storage bag convenient to carry and freeze comprises the following preparation steps:

[0010] S1, low-density polyethylene, linear low-density polyethylene, composite additive, plasticizer, lubricant, stabilizer and antioxidant are mixed and stirred at 400-500 r / min for 40-50 min, and then extruded and granulated to obtain medicine storage bag raw materials.

[0011] S2, the medicine storage bag raw material is formed by film blowing, and then subjected to sterilization treatment to obtain a sterile medicine storage bag.

[0012] Further, in step S1, the extrusion is performed by using a double-screw extruder, and the temperature of the extruder is: the temperature of the first zone is 100-110 DEG C, the temperature of the second zone is 145-150 DEG C, the temperature of the third zone is 156-160 DEG C, and the temperature of the fourth zone is 170-180 DEG C; the rotation speed of the screw is 200-230 r / min.

[0013] Further, in step S2, the film blowing is performed by using a single-screw extruder, wherein the feeding temperature during the film blowing is 70-75 DEG C; the compression plasticizing temperature is 100-115 DEG C; the blow ratio is 1:3; the pulling speed is 4-4.2 m / min; and the length-diameter ratio is 1:50.

[0014] Further, in step S2, the sterilization treatment is performed by using radiation sterilization, and the gamma ray dose is 20-30 kGy.

[0015] Further, the plasticizer is selected from any one of dihexyl phthalate, epoxy soybean oil, and acetyl tri-butyl citrate.

[0016] Further, the lubricant is selected from n-butyl stearate or castor oil.

[0017] Further, the antioxidant is antioxidant 1178.

[0018] Further, the stabilizer is selected from any one of barium stearate, calcium stearate, and zinc stearate.

[0019] Further, the composite additive is prepared by the following steps:

[0020] A1. p-hydroxycinnamic acid and N,N-carbonyl diimidazole are added into dimethyl sulfoxide, stirred uniformly, polyvinyl alcohol is added, and after the reaction is completed, the mixture is cooled to room temperature, left to stand, and then dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, which is washed and dried to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0021] A2. myristic acid is added into ethanol, stirred until completely dissolved, p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, and then sodium hydroxide solution is added to adjust the pH, and then the mixture is stirred and heated until the ethanol is volatilized, and then the mixture is washed and dried to obtain a composite;

[0022] A3. carboxylated cellulose nanowhiskers are added into an aqueous silver nitrate solution, stirred uniformly, 1.1 g of sodium borohydride is added, and then the mixture is continuously stirred and reacted, filtered, washed, and dried to obtain cellulose nanowhiskers loaded with nano-silver;

[0023] A4. The complex and tannic acid are added into ethanol, stirred uniformly, the cellulose nanowhisker loaded with nano-silver is added, stirred and mixed, and stirred and heated until the ethanol volatilizes, to obtain a composite additive.

[0024] Further, in the above-mentioned A1 reaction process, N,N-carbonyldiimidazole is used as a catalyst, and dimethyl sulfoxide is used as a solvent, so that the carboxyl contained in the p-hydroxycinnamic acid can be combined with the hydroxyl on the polyvinyl alcohol molecular chain through a chemical bond, so that the p-hydroxycinnamic acid is grafted on the polyvinyl alcohol, to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol.

[0025] Further, in the above-mentioned A2 reaction process, the p-hydroxycinnamic acid grafted polyvinyl alcohol and myristic acid are mixed, ethanol is used as a solvent, and hydrochloric acid is used as a catalyst, so that the carboxyl of the myristic acid can undergo an esterification reaction with the hydroxyl contained in the p-hydroxycinnamic acid grafted polyvinyl alcohol, to obtain a complex.

[0026] Further, in the above-mentioned A3 reaction process, the carboxylated cellulose nanowhisker contains a large number of carboxyl groups, which can be combined with silver ions in silver nitrate, so that the silver ions are adsorbed to the surface of the carboxylated cellulose nanowhisker, and sodium borohydride is used as a reducing agent, which can reduce the silver ions to nano-silver, so that the nano-silver is synthesized on the surface of the carboxylated cellulose nanowhisker, to obtain a cellulose nanowhisker loaded with nano-silver.

[0027] Further, in the above-mentioned A4 reaction process, the cellulose nanowhisker loaded with nano-silver, tannic acid and the complex are mixed, and the tannic acid is used as a connecting agent, so that the complex is coated on the surface of the cellulose nanowhisker loaded with nano-silver through the tannic acid, to obtain a composite additive.

[0028] Further, in step A1, the amount ratio of p-hydroxycinnamic acid, N,N-carbonyldiimidazole, dimethyl sulfoxide and polyvinyl alcohol is (3-5) g:(2-2.4) g:(35-45) mL:(3-5) g.

[0029] Further, in step A2, the amount ratio of myristic acid, ethanol and p-hydroxycinnamic acid grafted polyvinyl alcohol is (4-4.4) g:(35-45) mL:(4-5) g.

[0030] Further, in step A3, the amount ratio of carboxylated cellulose nanowhisker, silver nitrate aqueous solution and sodium borohydride is (2-3) g:(25-35) mL:(1-1.2) g.

[0031] Further, in step A4, the amount ratio of the complex, tannic acid, ethanol and cellulose nanowhisker loaded with nano-silver is (1-1.4) g:(0.4-0.6) g:(55-65) mL:(3-4) g.

[0032] The present application has the following beneficial effects:

[0033] (1) In the technical scheme of the present application, p-hydroxy cinnamic acid and polyvinyl alcohol are mixed and reacted, and then reacted with myristic acid to obtain a complex. On the one hand, as an environmentally friendly and non-toxic antibacterial substance, p-hydroxy cinnamic acid can enhance the antibacterial performance of the polyvinyl storage bag. Moreover, p-hydroxy cinnamic acid is grafted on the molecular chain of polyvinyl alcohol to increase the molecular weight of p-hydroxy cinnamic acid, avoid the easy migration and precipitation of p-hydroxy cinnamic acid in the polyvinyl storage bag, and affect the antibacterial activity. On the other hand, the grafting of p-hydroxy cinnamic acid on polyvinyl alcohol is reacted with myristic acid to introduce myristic acid containing a hydrophobic long chain into the polyvinyl storage bag, thereby providing excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the storage bag, and improve the antibacterial performance and barrier performance of the storage bag.

[0034] (2) In the technical scheme of the present application, nano-silver is synthesized on the surface of carboxylated cellulose nanowhiskers. On the one hand, cellulose nanowhiskers have excellent length-diameter ratio and low-temperature resistance, and are randomly distributed in polyethylene resin, which can absorb and disperse impact energy and prevent cracks from further expanding, thereby significantly improving the low-temperature resistance of the polyvinyl storage bag, so that the polyvinyl storage bag still has good use performance at-80℃. On the other hand, the synthesized nano-silver forms a rough surface on the surface of the cellulose nanowhiskers, which increases the surface roughness of the cellulose nanowhiskers and increases the contact area with the polyethylene resin, which is beneficial to the better dispersion of the cellulose nanowhiskers loaded with nano-silver in the polyethylene resin. Moreover, as an inorganic antibacterial material, nano-silver further enhances the antibacterial activity of the polyvinyl storage bag.

[0035] (3) In the technical scheme of the present application, the complex is coated on the surface of the cellulose nanowhiskers loaded with nano-silver by tannic acid. On the one hand, the complex contains a large amount of long-chain alkane structures, which are coated on the surface of the whiskers, which is beneficial to the uniform dispersion of the whiskers in the polyethylene resin, and improves the antibacterial performance, mechanical performance and barrier performance of the polyvinyl storage bag. On the other hand, the long-chain alkane structure in the complex can intertwine with the molecular chain of polyethylene, hinder the close packing of the polyethylene molecular chain, improve the flexibility of the material, and improve the low-temperature resistance of the polyethylene resin, so that the polyethylene resin has excellent flexibility at low temperature.

[0036] (4) In the technical scheme of the present application, the cellulose nanowhiskers can also be inserted into the polyethylene molecular chain structure through the long-chain alkane structure in the complex, as a lubricating component, so that the polyethylene molecular chain is arranged along the direction of the whiskers, inducing the formation of smaller crystals, improving the low-temperature resistance of the polyethylene resin, and making the polyethylene resin still have good low-temperature toughness in an environment below-80℃. Moreover, the whiskers are uniformly dispersed in the polyethylene resin matrix, which significantly improves the antibacterial performance, mechanical performance, barrier performance and low-temperature resistance of the polyvinyl storage bag. DETAILED DESCRIPTION

[0037] The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.

[0038] The raw materials used in the embodiments of the present application are shown as follows, and all the reagents used are analytical grade.

[0039] The low-density polyethylene has a melt index of 70 g / 10 min and a product number of L790446, and the linear low-density polyethylene has a melt index of 2 g / 10 min and a product number of L909897, both of which are purchased from Shanghai Macklin Biochemical Technology Co., Ltd.

[0040] The plasticizer is dihexyl phthalate, the lubricant is n-butyl stearate, the stabilizer is barium stearate, and the antioxidant is antioxidant 1178.

[0041] The polyvinyl alcohol has a product number of 767382 and a molecular weight of 9000, and is purchased from Shanghai Macklin Biochemical Technology Co., Ltd.

[0042] The cellulose nanocrystal whisker has a diameter of 50 nm and a length of 500 nm, and is purchased from Zhongke Leiming (Beijing) Technology Co., Ltd.

[0043] The carboxylated cellulose nanocrystal whisker is prepared by the following steps:

[0044] 3 g of cellulose nanocrystal whisker is added to 100 mL of deionized water, stirred uniformly, 0.5 g of 2,2,6,6-tetramethylpiperidine oxide and 1 g of sodium bromide are added, stirred until completely dissolved, 0.2 g of sodium hypochlorite is added, stirred uniformly, 10 mL of ethanol is added to terminate the reaction, centrifuged, washed with deionized water for 3 times, dried in a 70℃ oven for 10 min, and the carboxylated cellulose nanocrystal whisker is obtained.

[0045] Embodiment 1

[0046] A sterile medicine storage bag convenient to carry and freeze comprises the following raw materials in mass parts: 80 parts of low-density polyethylene, 15 parts of linear low-density polyethylene, 5 parts of composite additive, 3 parts of dihexyl phthalate, 1 part of n-butyl stearate, 3 parts of barium stearate, and 1 part of antioxidant 1178.

[0047] A preparation method of a sterile medicine storage bag convenient to carry and freeze comprises the following preparation steps:

[0048] S1, low density polyethylene, linear low density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 are mixed, stirred at 400 r / min for 40 min, extruded and granulated to obtain the medicine storage bag raw material; wherein the extrusion is carried out by using a double screw extruder, the extruder temperature is: the temperature of the first zone is 100 DEG C, the temperature of the second zone is 145 DEG C, the temperature of the third zone is 156 DEG C, and the temperature of the fourth zone is 170 DEG C; the screw rotation speed is 200 r / min;

[0049] S2, the medicine storage bag raw material is blown into a film, and then sterilized to obtain a sterile medicine storage bag; wherein the film blowing is carried out by using a single screw extruder, wherein the feeding temperature during film blowing is 70 DEG C; the compression plasticizing temperature is 100 DEG C; the blowing ratio is 1:3; the traction speed is 4 m / min; the length-diameter ratio is 1:50; the sterilization treatment is carried out by using radiation sterilization, and the gamma ray dose is 20 kGy.

[0050] The composite additive is prepared by the following steps:

[0051] A1. 3g of p-hydroxycinnamic acid and 2g of N,N-carbonyldiimidazole are added to 35mL of dimethyl sulfoxide, stirred at 65 DEG C for 12h, then 3g of polyvinyl alcohol is added, stirred at 95 DEG C for 4h, cooled to room temperature, and then left to stand for 10min, after which the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in a 70 DEG C oven for 10min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0052] A2. 4g of myristic acid is added to 35mL of ethanol, stirred until completely dissolved, 4g of p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, 1mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70 DEG C for 15min, heated to 85 DEG C, and stirred until the ethanol evaporates, washed with ethanol for 3 times, and dried in a 70 DEG C oven for 15min to obtain the composite;

[0053] A3. 2g of carboxylated cellulose nanowhisker is added to 25mL of 2.5mol / L silver nitrate aqueous solution, stirred at 25 DEG C and 300r / min for 30min, 1g of sodium borohydride is added, and the stirring reaction is continued for 6h, then filtered, washed with deionized water for 3 times, and dried in an 80 DEG C oven for 8min to obtain silver nanowhisker loaded cellulose nanowhisker;

[0054] A4. 1g of the composite and 0.4g of tannic acid are added to 65mL of ethanol, stirred uniformly, 3g of silver nanowhisker loaded cellulose nanowhisker is added, stirred and mixed at 70 DEG C for 30min, heated to 85 DEG C, and stirred until the ethanol evaporates to obtain the composite additive.

[0055] Example 2

[0056] A sterile medicine storage bag convenient to carry and freeze, comprising the following raw materials by mass fraction: low-density polyethylene 85 parts, linear low-density polyethylene 18 parts, composite additive 7 parts, dihexyl phthalate 4 parts, n-butyl stearate 1.3 parts, barium stearate 4 parts, antioxidant 1178 1.5 parts;

[0057] A preparation method of a sterile medicine storage bag convenient to carry and freeze, comprising the following preparation steps:

[0058] S1, low-density polyethylene, linear low-density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 are mixed, stirred at 450 r / min for 45 min, extruded and granulated to obtain medicine storage bag raw materials; wherein the extrusion adopts a double-screw extruder, the extruder temperature is: the first zone temperature is 105℃, the second zone temperature is 148℃, the third zone temperature is 158℃, and the fourth zone temperature is 175℃; the screw rotation speed is 215 r / min;

[0059] S2, the medicine storage bag raw materials are blown into a film shape, and then sterilized to obtain a sterile medicine storage bag; wherein a single-screw extruder is used for film blowing, wherein the feeding temperature during film blowing is 73℃; the compression plasticization temperature is 110℃; the blow-up ratio is 1:3; the pulling speed is 4.1 m / min; the length-diameter ratio is 1:50; the sterilization treatment adopts radiation sterilization, and the gamma ray dose is 25 kGy.

[0060] The composite additive is specifically prepared by the following steps:

[0061] A1. 4g of p-hydroxycinnamic acid and 2.2g of N,N-carbonyldiimidazole are added to 40mL of dimethyl sulfoxide, stirred at 65℃ for 12h, then 4g of polyvinyl alcohol is added, stirred at 95℃ for 4h, cooled to room temperature, and then left to stand for 10min, then the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in a 70℃ oven for 10min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0062] A2. 4.2g of myristic acid is added to 40mL of ethanol, stirred until completely dissolved, 4.5g of p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, 1mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70℃ for 15min, then heated to 85℃, and stirred until the ethanol is volatilized, washed with ethanol for 3 times, and dried in a 70℃ oven for 15min to obtain a composite;

[0063] A3. 2.5 g of carboxylated cellulose nanowhiskers were added to 30 mL of silver nitrate aqueous solution with a concentration of 2.5 mol / L, stirred at 25℃ and 300 r / min for 30 min, 1.1 g of sodium borohydride was added, and the stirring reaction was continued for 6 h, then filtered, washed with deionized water for 3 times, and dried in an oven at 80℃ for 8 min to obtain silver nanoparticle-loaded cellulose nanowhiskers;

[0064] A4. 1.2 g of the composite and 0.5 g of tannic acid were added to 60 mL of ethanol, stirred uniformly, 3.5 g of silver nanoparticle-loaded cellulose nanowhiskers were added, and the mixture was stirred at 70℃ for 30 min, then the temperature was increased to 85℃, and the stirring was continued until the ethanol was volatilized to obtain the composite additive.

[0065] Example 3

[0066] A sterile medicine storage bag convenient for carrying and freezing, comprising the following mass parts of raw materials: low-density polyethylene 90 parts, linear low-density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, and antioxidant 1178 2 parts.

[0067] A preparation method of a sterile medicine storage bag convenient for carrying and freezing, comprising the following preparation steps:

[0068] S1, low-density polyethylene, linear low-density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, and antioxidant 1178 were mixed and stirred at 500 r / min for 50 min, then extruded and granulated to obtain the medicine storage bag raw material; wherein the extrusion was performed by using a double-screw extruder, the extruder temperature was as follows: the temperature of the first zone was 110℃, the temperature of the second zone was 150℃, the temperature of the third zone was 160℃, and the temperature of the fourth zone was 180℃; and the screw rotation speed was 230 r / min;

[0069] S2, the medicine storage bag raw material was blown into a film and then subjected to sterilization treatment to obtain the sterile medicine storage bag; wherein the blowing film forming was performed by using a single-screw extruder, wherein the feeding temperature during the film blowing was 75℃; the compression plasticization temperature was 115℃; the blow-up ratio was 1:3; the traction speed was 4.2 m / min; the length-diameter ratio was 1:50; and the sterilization treatment was performed by using radiation sterilization with a γ-ray dose of 30 kGy.

[0070] The composite additive was prepared by the following steps:

[0071] A1. 5 g of p-hydroxycinnamic acid and 2.4 g of N,N-carbonyldiimidazole were added to 45 mL of dimethyl sulfoxide, stirred at 65°C for 12 h, then 5 g of polyvinyl alcohol was added, and the reaction was stirred at 95°C for 4 h, cooled to room temperature, and after standing for 10 min, the dimethyl sulfoxide was removed by distillation under reduced pressure to collect the product, which was washed with ethanol 3 times and dried in an oven at 70°C for 10 min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0072] A2. 4.4 g of myristic acid was added to 45 mL of ethanol, stirred until completely dissolved, 5 g of p-hydroxycinnamic acid grafted polyvinyl alcohol was added, stirred evenly, 1 mol / L sodium hydroxide solution was added to adjust the pH to 8.5, stirred at 70°C for 15 min, the temperature was raised to 85°C, and the ethanol was evaporated by stirring, washed with ethanol 3 times, and dried in an oven at 70°C for 15 min to obtain the composite;

[0073] A3. 3 g of carboxylated cellulose nanowhiskers were added to 35 mL of 2.5 mol / L silver nitrate aqueous solution, stirred at 25°C and 300 r / min for 30 min, 1.2 g of sodium borohydride was added, and the reaction was continued to stir for 6 h, filtered, washed with deionized water 3 times, and dried in an oven at 80°C for 8 min to obtain silver nanoparticle loaded cellulose nanowhiskers;

[0074] A4. 1.4 g of the composite and 0.6 g of tannic acid were added to 65 mL of ethanol, stirred evenly, 4 g of silver nanoparticle loaded cellulose nanowhiskers was added, and the mixture was stirred at 70°C for 30 min, and the temperature was raised to 85°C to evaporate the ethanol to obtain the composite additive.

[0075] Comparative Example 1

[0076] A sterile medicine storage bag convenient for carrying and freezing, comprising the following mass parts of raw materials: low density polyethylene 90 parts, linear low density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, antioxidant 1178 2 parts;

[0077] A preparation method of a sterile medicine storage bag convenient for carrying and freezing, comprising the following preparation steps:

[0078] S1, low density polyethylene, linear low density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 were mixed and stirred at 500 r / min for 50 min, extruded and granulated to obtain the medicine storage bag raw material; wherein the extrusion was carried out by a double screw extruder, the extruder temperature was: zone 1 temperature 110°C, zone 2 temperature 150°C, zone 3 temperature 160°C, and zone 4 temperature 180°C; the screw rotation speed was 230 r / min;

[0079] S2, the raw material of the medicine storage bag is blown into a film, and then sterilized to obtain a sterile medicine storage bag; wherein the blowing film forming adopts a single screw extruder, wherein the feeding temperature during blowing film forming is 75°C; the compression plasticizing temperature is 115°C; the blowing ratio is 1:3; the pulling speed is 4.2 m / min; the length-diameter ratio is 1:50; the sterilization treatment adopts radiation sterilization, and the gamma ray dose is 30 kGy.

[0080] The composite additive is specifically prepared by the following steps:

[0081] A1. 4.4 g of myristic acid is added to 45 mL of ethanol, stirred until completely dissolved, 5 g of polyvinyl alcohol is added, stirred uniformly, 1 mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70°C for 15 min, the temperature is raised to 85°C, and the ethanol is evaporated by stirring, washed with ethanol for 3 times, and dried in a 70°C oven for 15 min to obtain a composite;

[0082] A2. 3 g of carboxylated cellulose nanowhiskers is added to 35 mL of 2.5 mol / L silver nitrate aqueous solution, stirred at 25°C and 300 r / min for 30 min, 1.2 g of sodium borohydride is added, and the stirring reaction is continued for 6 h, filtered, washed with deionized water for 3 times, and dried in an 80°C oven for 8 min to obtain silver nanowhisker-loaded cellulose nanowhiskers;

[0083] A3. 1.4 g of the composite and 0.6 g of tannic acid are added to 65 mL of ethanol, stirred uniformly, 4 g of silver nanowhisker-loaded cellulose nanowhiskers is added, stirred and mixed at 70°C for 30 min, the temperature is raised to 85°C, and the ethanol is evaporated by stirring to obtain a composite additive.

[0084] Comparative Example 2

[0085] A sterile medicine storage bag convenient to carry and freeze, comprising the following raw materials in parts by mass: low-density polyethylene 90 parts, linear low-density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, and antioxidant 1178 2 parts.

[0086] A preparation method of a sterile medicine storage bag convenient to carry and freeze, comprising the following preparation steps:

[0087] S1, low-density polyethylene, linear low-density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, and antioxidant 1178 are mixed and stirred at 500 r / min for 50 min, extruded and granulated to obtain a medicine storage bag raw material; wherein the extrusion adopts a double-screw extruder, the extruder temperature is: the first zone temperature is 110°C, the second zone temperature is 150°C, the third zone temperature is 160°C, and the fourth zone temperature is 180°C; the screw rotation speed is 230 r / min;

[0088] S2, the medicine storage bag raw material is blow molded, and then subjected to sterilization treatment to obtain a sterile medicine storage bag; wherein the blow molding adopts a single screw extruder, wherein the feeding temperature during blow molding is 75℃; the compression plasticization temperature is 115℃; the blow-up ratio is 1:3; the pulling speed is 4.2m / min; the length-diameter ratio is 1:50; the sterilization treatment adopts radiation sterilization, and the gamma ray dose is 30kGy.

[0089] The composite additive is specifically prepared by the following steps:

[0090] A1. 5g of p-hydroxycinnamic acid and 2.4g of N,N-carbonyldiimidazole are added to 45mL of dimethyl sulfoxide, stirred at 65℃ for 12h, then 5g of polyvinyl alcohol is added, and the reaction is stirred at 95℃ for 4h, cooled to room temperature, and after standing for 10min, the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in an oven at 70℃ for 10min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0091] A2. 3g of carboxylated cellulose nanowhiskers is added to 35mL of silver nitrate aqueous solution with a concentration of 2.5mol / L, stirred at 25℃ and 300r / min for 30min, 1.2g of sodium borohydride is added, and the reaction is continuously stirred for 6h, filtered, washed with deionized water for 3 times, and dried in an oven at 80℃ for 8min to obtain silver nanowhisker-loaded cellulose nanowhiskers;

[0092] A3. 1.4g of the composite and 0.6g of tannic acid are added to 65mL of ethanol, stirred uniformly, 4g of silver nanowhisker-loaded cellulose nanowhiskers is added, and the mixture is stirred at 70℃ for 30min, and then heated to 85℃ and stirred until the ethanol volatilizes to obtain the composite additive.

[0093] Comparative Example 3

[0094] A sterile medicine storage bag convenient to carry and freeze, comprising the following raw materials in parts by mass: low-density polyethylene 90 parts, linear low-density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, and antioxidant 1178 2 parts.

[0095] A preparation method of a sterile medicine storage bag convenient to carry and freeze, comprising the following preparation steps:

[0096] S1, low density polyethylene, linear low density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 are mixed, stirred at 500 r / min for 50 min, extruded and granulated to obtain the raw material of the medicine storage bag; wherein the extrusion is carried out by using a double screw extruder, the temperature of the extruder is 110℃ for the first zone, 150℃ for the second zone, 160℃ for the third zone and 180℃ for the fourth zone, and the screw rotation speed is 230 r / min;

[0097] S2, the raw material of the medicine storage bag is blown into a film, and then sterilized to obtain a sterile medicine storage bag; wherein the film blowing is carried out by using a single screw extruder, wherein the feeding temperature during film blowing is 75℃; the compression plasticization temperature is 115℃; the blowing ratio is 1:3; the pulling speed is 4.2 m / min; the length-diameter ratio is 1:50; the sterilization treatment is carried out by using radiation sterilization, and the gamma ray dose is 30 kGy.

[0098] The composite additive is prepared by the following steps:

[0099] A1. 5 g of p-hydroxycinnamic acid and 2.4 g of N,N-carbonyldiimidazole are added to 45 mL of dimethyl sulfoxide, stirred at 65℃ for 12 h, then 5 g of polyvinyl alcohol is added, stirred at 95℃ for 4 h, cooled to room temperature, and then placed for 10 min, and then the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in an oven at 70℃ for 10 min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0100] A2. 4.4 g of myristic acid is added to 45 mL of ethanol, stirred until completely dissolved, 5 g of p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, 1 mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70℃ for 15 min, heated to 85℃, and stirred until the ethanol is volatilized, washed with ethanol for 3 times, and dried in an oven at 70℃ for 15 min to obtain the composite;

[0101] A3. 1.4 g of the composite and 0.6 g of tannic acid are added to 65 mL of ethanol, stirred uniformly, 4 g of carboxylated cellulose nanowhiskers is added, stirred and mixed at 70℃ for 30 min, heated to 85℃, and stirred until the ethanol is volatilized to obtain the composite additive.

[0102] Comparative Example 4

[0103] A sterile medicine storage bag convenient to carry and freeze, comprising the following raw materials in parts by mass: low density polyethylene 90 parts, linear low density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, antioxidant 1178 2 parts;

[0104] A method for preparing a sterile medicine storage bag convenient to carry and freeze, comprising the following preparation steps:

[0105] S1, low density polyethylene, linear low density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 are mixed, stirred at 500 r / min for 50 min, extruded and granulated to obtain medicine storage bag raw material; wherein the extrusion adopts a double screw extruder, the extruder temperature is: the first zone temperature is 110 DEG C, the second zone temperature is 150 DEG C, the third zone temperature is 160 DEG C, and the fourth zone temperature is 180 DEG C; the screw rotation speed is 230 r / min;

[0106] S2, the medicine storage bag raw material is formed by blowing film and then sterilized to obtain a sterile medicine storage bag; wherein the blowing film forming adopts a single screw extruder, wherein the feeding temperature during blowing film forming is 75 DEG C; the compression plasticizing temperature is 115 DEG C; the blowing ratio is 1:3; the traction speed is 4.2 m / min; the length-diameter ratio is 1:50; the sterilization treatment adopts radiation sterilization, and the gamma ray dose is 30 kGy.

[0107] The composite additive is prepared by the following steps:

[0108] A1. 5g of p-hydroxycinnamic acid and 2.4g of N,N-carbonyldiimidazole are added to 45mL of dimethyl sulfoxide, stirred at 65℃ for 12h, then 5g of polyvinyl alcohol is added, stirred at 95℃ for 4h, cooled to room temperature, and then placed for 10min, and then the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in a 70℃ oven for 10min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0109] A2. 4.4g of myristic acid is added to 45mL of ethanol, stirred until completely dissolved, 5g of p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, 1mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70℃ for 15min, heated to 85℃, and stirred until the ethanol evaporates, washed with ethanol for 3 times, and dried in a 70℃ oven for 15min to obtain a composite;

[0110] A3. 35mL of 2.5mol / L silver nitrate aqueous solution and 1.2g of sodium borohydride are mixed, stirred at 25℃ and 300r / min for 6h, filtered, washed with deionized water for 3 times, and dried in an 80℃ oven for 8min to obtain nano-silver;

[0111] A4. 1.4g of the composite and 0.6g of tannic acid are added to 65mL of ethanol, stirred uniformly, 4g of nano-silver is added, stirred and mixed at 70℃ for 30min, heated to 85℃, and stirred until the ethanol evaporates to obtain a composite additive.

[0112] Comparative Example 5

[0113] A sterile medicine storage bag convenient to carry and freeze, comprising the following raw materials in mass parts: low-density polyethylene 90 parts, linear low-density polyethylene 20 parts, composite additive 10 parts, dihexyl phthalate 5 parts, n-butyl stearate 1.5 parts, barium stearate 5 parts, antioxidant 1178 82 parts;

[0114] A preparation method of a sterile medicine storage bag convenient to carry and freeze, comprising the following preparation steps:

[0115] S1, low-density polyethylene, linear low-density polyethylene, composite additive, dihexyl phthalate, n-butyl stearate, barium stearate, antioxidant 1178 are mixed, stirred at 500 r / min for 50 min, extruded and granulated to obtain medicine storage bag raw materials; wherein the extrusion adopts a double-screw extruder, the extruder temperature is: the first zone temperature is 110°C, the second zone temperature is 150°C, the third zone temperature is 160°C, and the fourth zone temperature is 180°C; the screw rotation speed is 230 r / min;

[0116] S2, the medicine storage bag raw materials are blown into a film shape, and then sterilized to obtain a sterile medicine storage bag; wherein a single-screw extruder is used for film blowing, wherein the feeding temperature during film blowing is 75°C; the compression plasticization temperature is 115°C; the blow-up ratio is 1:3; the pulling speed is 4.2 m / min; the length-diameter ratio is 1:50; the sterilization treatment adopts radiation sterilization, and the gamma ray dose is 30 kGy.

[0117] The composite additive is specifically prepared by the following steps:

[0118] A1. 5g of p-hydroxycinnamic acid and 2.4g of N,N-carbonyldiimidazole are added to 45mL of dimethyl sulfoxide, stirred at 65°C for 12h, then 5g of polyvinyl alcohol is added, stirred at 95°C for 4h, cooled to room temperature, and then left to stand for 10min, then the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product, the product is washed with ethanol for 3 times, and dried in an oven at 70°C for 10min to obtain p-hydroxycinnamic acid grafted polyvinyl alcohol;

[0119] A2. 4.4g of myristic acid is added to 45mL of ethanol, stirred until completely dissolved, 5g of p-hydroxycinnamic acid grafted polyvinyl alcohol is added, stirred uniformly, 1mol / L sodium hydroxide solution is added to adjust the pH to 8.5, stirred at 70°C for 15min, then heated to 85°C, and stirred until the ethanol is volatilized, washed with ethanol for 3 times, and dried in an oven at 70°C for 15min to obtain a composite;

[0120] A3. 3 g of carboxylated cellulose nanowhiskers were added to 35 mL of silver nitrate aqueous solution with a concentration of 2.5 mol / L, stirred at 25℃ and 300 r / min for 30 min, 1.2 g of sodium borohydride was added, and the stirring reaction was continued for 6 h. After filtration, deionized water was washed for 3 times, and dried in an oven at 80℃ for 8 min to obtain silver nanoparticle loaded cellulose nanowhiskers;

[0121] A4. 1.4 g of the composite was added to 65 mL of ethanol, stirred uniformly, and 4 g of silver nanoparticle loaded cellulose nanowhiskers were added. The mixture was stirred at 70℃ for 30 min, and the temperature was raised to 85℃. Stirring was continued until the ethanol was volatilized to obtain the composite additive.

[0122] The sterile drug storage bags prepared in Examples 1-3 and Comparative Examples 1-5 were subjected to performance testing.

[0123] Mechanical property and low temperature resistance test: the tensile strength and elongation at break of the sterile drug storage bags prepared above were detected according to standard GB / T1040.1-2018, and the sterile drug storage bags were placed in a-80℃ environment to detect the tensile strength and elongation at break of the sterile drug storage bags in a low temperature environment.

[0124] Antibacterial property test: the antibacterial rate of the sterile drug storage bags prepared above was detected according to standard ISO22196:2011 "Determination of antibacterial property of plastics and other non-porous surfaces".

[0125] Barrier property test: water vapor transmission rate was determined according to GB / T1037-2021 "Determination of water vapor transmission property of plastic film and sheet"; oxygen transmission amount was determined according to GB / T19789-2021 standard.

[0126] As shown in Tables 1 and 2 below.

[0127] Table 1

[0128]

[0129]

[0130] As can be seen from the data in Table 1, the sterile drug storage bags prepared in Examples 1-3 have high mechanical properties and antibacterial properties, and still have good low temperature toughness in an environment below-80℃.

[0131] The composite additive prepared by replacing the p-hydroxycinnamic acid grafted polyvinyl alcohol with polyvinyl alcohol is added to the sterile medicine storage bag, and the antibacterial performance and barrier performance thereof are reduced, which proves that the p-hydroxycinnamic acid as an environmentally friendly and non-toxic antibacterial substance can enhance the antibacterial performance of the polyvinyl medicine storage bag, and the p-hydroxycinnamic acid grafted on the polyvinyl alcohol molecular chain is beneficial to the introduction of myristic acid containing a hydrophobic long chain, and the addition of the polyvinyl medicine storage bag can further provide excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the medicine storage bag, and improve the antibacterial performance and barrier performance of the medicine storage bag.

[0132] The composite additive prepared by replacing the p-hydroxycinnamic acid grafted polyvinyl alcohol with polyvinyl alcohol is added to the sterile medicine storage bag, and the antibacterial performance and barrier performance thereof are reduced, which proves that the p-hydroxycinnamic acid as an environmentally friendly and non-toxic antibacterial substance can enhance the antibacterial performance of the polyvinyl medicine storage bag, and the p-hydroxycinnamic acid grafted on the polyvinyl alcohol molecular chain is beneficial to the introduction of myristic acid containing a hydrophobic long chain, and the addition of the polyvinyl medicine storage bag can further provide excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the medicine storage bag, and improve the antibacterial performance and barrier performance of the medicine storage bag.

[0133] The composite additive prepared by replacing the p-hydroxycinnamic acid grafted polyvinyl alcohol with polyvinyl alcohol is added to the sterile medicine storage bag, and the antibacterial performance and barrier performance thereof are reduced, which proves that the p-hydroxycinnamic acid as an environmentally friendly and non-toxic antibacterial substance can enhance the antibacterial performance of the polyvinyl medicine storage bag, and the p-hydroxycinnamic acid grafted on the polyvinyl alcohol molecular chain is beneficial to the introduction of myristic acid containing a hydrophobic long chain, and the addition of the polyvinyl medicine storage bag can further provide excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the medicine storage bag, and improve the antibacterial performance and barrier performance of the medicine storage bag.

[0134] The composite additive prepared by replacing the p-hydroxycinnamic acid grafted polyvinyl alcohol with polyvinyl alcohol is added to the sterile medicine storage bag, and the antibacterial performance and barrier performance thereof are reduced, which proves that the p-hydroxycinnamic acid as an environmentally friendly and non-toxic antibacterial substance can enhance the antibacterial performance of the polyvinyl medicine storage bag, and the p-hydroxycinnamic acid grafted on the polyvinyl alcohol molecular chain is beneficial to the introduction of myristic acid containing a hydrophobic long chain, and the addition of the polyvinyl medicine storage bag can further provide excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the medicine storage bag, and improve the antibacterial performance and barrier performance of the medicine storage bag.

[0135] The composite additive prepared by replacing the p-hydroxycinnamic acid grafted polyvinyl alcohol with polyvinyl alcohol is added to the sterile medicine storage bag, and the antibacterial performance and barrier performance thereof are reduced, which proves that the p-hydroxycinnamic acid as an environmentally friendly and non-toxic antibacterial substance can enhance the antibacterial performance of the polyvinyl medicine storage bag, and the p-hydroxycinnamic acid grafted on the polyvinyl alcohol molecular chain is beneficial to the introduction of myristic acid containing a hydrophobic long chain, and the addition of the polyvinyl medicine storage bag can further provide excellent hydrophobic performance, which can block the penetration of water molecules and oxygen molecules in the air into the medicine storage bag, and improve the antibacterial performance and barrier performance of the medicine storage bag.

[0136] In the description, references to "one embodiment," "an example," "certain examples" etc. mean that the particular feature, structure, material, or characteristic being described is included in at least one embodiment or example of the application. The appearances of an item in various examples or embodiments is not necessarily indicative of a frequency of occurrence in the various examples or embodiments. Moreover, descriptions of well-known methods associated are omitted so as not to obscure the disclosure.

[0137] The foregoing merely illustrates the principles of the application. Various modifications and adaptations will occur to those skilled in the art after consideration of the preceding description. All such modifications and adaptations employing the principles of the application are intended to be within the scope of the claims.

Claims

1. A sterile drug storage bag for ease of carrying and freezing, characterized in that, The composite additive is obtained by mixing reaction of the tannic acid and the complex after the carboxylated cellulose nanowhisker synthesizes nanometer silver on the surface. The complex is obtained by mixing reaction of the p-hydroxycinnamic acid and polyvinyl alcohol, and then reacting with myristic acid. The composite additive is specifically prepared by the following steps:

2. A sterile storage bag according to claim 1, wherein, A1. The p-hydroxycinnamic acid and N,N-carbonyldiimidazole are added into dimethyl sulfoxide, stirred uniformly, and then the polyvinyl alcohol is added. After the reaction is completed, the mixture is cooled to room temperature, left to stand, and then the dimethyl sulfoxide is removed by reduced pressure distillation to collect the product. The product is washed and dried to obtain the p-hydroxycinnamic acid grafted polyvinyl alcohol; A2. The myristic acid is added into ethanol and stirred until completely dissolved. The p-hydroxycinnamic acid grafted polyvinyl alcohol is added and stirred uniformly. After the pH is adjusted by adding sodium hydroxide solution, the mixture is stirred and heated until the ethanol is volatilized. After washing and drying, the complex is obtained; A3. The carboxylated cellulose nanowhisker is added into silver nitrate aqueous solution and stirred uniformly. Then 1.1 g of sodium borohydride is added and the mixture is continuously stirred. After filtration, washing and drying, the cellulose nanowhisker loaded with nanometer silver is obtained; A4. The complex and tannic acid are added into ethanol and stirred uniformly. The cellulose nanowhisker loaded with nanometer silver is added and stirred. After heating and stirring until the ethanol is volatilized, the composite additive is obtained. In step A1, the amount ratio of the p-hydroxycinnamic acid, N,N-carbonyldiimidazole, dimethyl sulfoxide and polyvinyl alcohol is (3-5) g:(2-2.4) g:(35-45) mL:(3-5) g.

3. A sterile storage bag for easy portability and freezing as claimed in claim 2, wherein, In step A2, the amount ratio of the myristic acid, ethanol and p-hydroxycinnamic acid grafted polyvinyl alcohol is (4-4.4) g:(35-45) mL:(4-5) g.

4. A sterile storage bag according to claim 2, wherein, In step A3, the amount ratio of the carboxylated cellulose nanowhisker, silver nitrate aqueous solution and sodium borohydride is (2-3) g:(25-35) mL:(1-1.2) g.

5. A sterile storage bag for easy portability and freezing as claimed in claim 2, wherein, In step A4, the amount ratio of the complex, tannic acid, ethanol and cellulose nanowhisker loaded with nanometer silver is (1-1.4) g:(0.4-0.6) g:(55-65) mL:(3-4) g.

6. A sterile storage bag for easy portability and freezing as claimed in claim 2, wherein, The plasticizer is selected from any one of dihexyl phthalate, epoxy soybean oil and acetyl tri-butyl citrate.

7. The sterile, frozen, medicament storage bag of claim 1, wherein, The lubricant is selected from n-butyl stearate or castor oil; and the antioxidant is antioxidant 1178.

8. The sterile, frozen, medicament storage bag of claim 1, wherein, The stabilizer is selected from any one of barium stearate, calcium stearate and zinc stearate.

9. The sterile, frozen, medicament storage bag of claim 1, wherein, The preparation steps are as follows:

10. A method of preparing a sterile storage bag for easy handling and freezing as claimed in any one of claims 1 to 9, characterized in that, S1. The low-density polyethylene, linear low-density polyethylene, composite additive, plasticizer, lubricant, stabilizer and antioxidant are mixed and stirred at 400-500 r / min for 40-50 min. After extrusion and granulation, the raw material of the medicine storage bag is obtained; S2. The raw material of the medicine storage bag is formed into a film by blowing and then sterilized to obtain the sterile medicine storage bag. ​

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