CN109096517B - Medicine packaging film and preparation method thereof - Google Patents
Medicine packaging film and preparation method thereof Download PDFInfo
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- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
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- C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
- C08J5/18—Manufacture of films or sheets
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- C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
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- C08J2327/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment containing chlorine atoms
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- C08K3/042—Graphene or derivatives, e.g. graphene oxides
Abstract
The invention discloses a medicine packaging film and a preparation method thereof, wherein the medicine packaging film comprises a polymer film and a graphene coating coated on the polymer film, the graphene coating comprises graphene and a light-cured adhesive, the light-cured adhesive comprises a hyperbranched cationic mussel-like polymer, and the hyperbranched cationic mussel-like polymer comprises a poly-o-phenolic hydroxyl benzophenone enamide monomer, a cationic monomer and a photoresponse monomer. The light-cured adhesive prepared from the hyperbranched cationic mussel-like polymer obviously increases the adhesive strength between the light-cured adhesive and the polymer film, so that the graphene coating formed by the light-cured adhesive and the graphene is combined on the polymer film more firmly, the coating effect is better, and meanwhile, the coating effect is obviously improved, so that the preparation process of the medicine packaging film is simplified to a certain extent.
Description
Technical Field
The invention relates to the field of packaging materials, in particular to a medicine packaging film and a preparation method thereof.
Background
Polymer film packaging materials have become increasingly important in daily life as the primary packaging material for pharmaceuticals. However, due to the influence of the production process of plastic films and the physical and chemical properties of the plastic films, the barrier properties of the plastic to oxygen, water vapor, liquid substances and other low molecular weight substances are difficult to meet the requirements of most drug packages. The permeation of oxygen, water vapor and other small molecular gases to the packaging material can cause the oxidative deterioration of active ingredients in the medicine, further cause the reproduction of microorganisms and other phenomena, and the shelf life of the medicine is greatly shortened as a direct consequence. Therefore, the improvement of the barrier property of the plastic film packaging material to small molecule gases such as oxygen and water vapor and the endowment of the plastic film packaging material with antibacterial performance have important significance for the improvement of the quality of the plastic film packaging material.
Graphene is a two-dimensional carbon nanomaterialEach carbon atom is represented by sp2The hybridization forms covalent bonds with 3 other carbon atoms, and then the bonds are arranged into a honeycomb hexagonal lattice. The remaining single electron 2P orbitals on each carbon atom are mutually overlapped to form delocalized conjugated large pi-bond. The pore size of the graphene six-membered ring is only 0.15nm, the diameter of the graphene six-membered ring is smaller than that of helium which is a known minimum gas molecule, and the graphene six-membered ring has natural gas barrier property. Meanwhile, the transmittance of the single-layer graphene to visible light is as high as 97%, and a high-light-transmittance film material can be easily prepared under appropriate preparation conditions. Moreover, the thickness of the single-layer graphene is only 0.34nm, and the width of the single-layer graphene can reach several micrometers to tens of centimeters. These make graphene an ideal nano-barrier material.
At present, one of the methods for preparing a graphene composite film is to prepare a graphene coating solution of a graphene solution and a binder solution, and coat the graphene coating solution on the surface of a polymer film to form the graphene composite film. However, the contact area of the existing adhesive with graphene and a polymer film is small, and reaction sites are few, so that the adhesive strength of the adhesive with the polymer film and the graphene is low, the coating effect is poor, and the coating process is complex; meanwhile, the water vapor permeability and the oxygen permeability of the existing graphene composite membrane are still high, and the requirements of most of medicine packages are difficult to meet.
Disclosure of Invention
The invention aims to provide a medicine packaging film and a preparation method thereof, and aims to solve the problems that the existing packaging film is poor in barrier property, the graphene coating is poor in coating effect, and the coating process is complex.
The invention is realized by the following technical scheme:
a pharmaceutical packaging film comprising a polymeric film, and a graphene coating coated on the polymeric film, the graphene coating comprising graphene and a photo-curable adhesive, the photo-curable adhesive comprising a hyperbranched cationic mussel-like polymer comprising a polyparaphenol hydroxybenzophenone enamide monomer, a cationic monomer, and a photo-responsive monomer.
In the prior art, chinese patent publication No. CN108165120A discloses a high thermal conductivity graphene coating for a heat dissipation device and a preparation method thereof, and the adhesive used in the method has low adhesive strength with a polymer film and graphene, resulting in poor coating effect and complex coating process. Moreover, in order to enable the bonding strength in the graphene coating to meet the requirement of a medicine packaging film, the proportion of the bonding agent in the graphene coating is improved, and the light transmittance of a final finished product is reduced by the high-proportion bonding agent; moreover, the water vapor permeability and the oxygen permeability of the existing graphene composite membrane are still high, and the requirements of most of medicine packages are difficult to meet.
In order to solve the above problems, the present invention provides a pharmaceutical packaging film, which comprises a polymer film, and a graphene coating layer coated on the polymer film, as in the prior art. Preferably, the polymer film layer can be a polymer film for drug packaging, such as polypropylene (PP), Polyethylene (PE), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polybutylene terephthalate (PBT), and the like; the graphene coating includes graphene and a light-curable binder.
Unlike the prior art, the photocurable adhesive used in the present invention comprises a hyperbranched cationic mussel-like polymer comprising a poly-o-phenolic hydroxybenzophenone enamide monomer and a cationic monomer. Preferably, the poly-o-phenol hydroxybenzophenone enamide monomer is 2,3, 4-trihydroxybenzoyl p-benzoyl- (2-aminoethyl) acrylamide, 2, 3-dihydroxybenzoyl p-benzoyl- (2-aminoethyl) acrylamide or 2,3, 4-trihydroxybenzoyl m-benzoyl- (2-aminoethyl) acrylamide, which can be synthesized by esterification reactions commonly used in the art or commercially available; the cationic monomer is any one of N- (2-aminoethyl) (meth) acrylamide hydrochloride, N- (3-aminopropyl) (meth) acrylamide hydrochloride, N- (4-aminobutyl) (meth) acrylamide hydrochloride, N- (6-aminohexyl) (meth) acrylamide hydrochloride, and 2-aminoethyl) (meth) acrylate hydrochloride.
The poly-o-phenol hydroxy benzophenone alkene amide monomer has a large number of free catechol radicals, and the catechol radicals can improve the binding force of the catechol radicals to the polymer film layer through a synergistic effect in the presence of a cationic end group. In addition, the large number of free catechol groups and cationic groups can enable the hyperbranched cationic mussel-like polymer to have good adhesion properties to a variety of polymer film layers through a series of intermolecular interactions of different strengths, such as van der waals forces, hydrogen bonds, and cation-pi interactions. Therefore, the adhesive fastness between the adhesive and the polymer film is obviously improved by the hyperbranched cationic mussel-like polymer containing the poly-o-phenolic hydroxybenzophenone enamide monomer and the cationic monomer.
The hyperbranched cationic mussel-like polymer also comprises a photo-responsive monomer. Preferably, the photo-responsive monomer may be any one of 4-azido-2, 3,5, 6-tetrafluorobenzoyl- (2-aminoethyl) acrylamide, 4-azido-2, 3, 5-trifluorobenzoyl- (2-aminoethyl) acrylamide, 4-azido-2, 3-tetrafluorobenzoyl- (2-aminoethyl) acrylamide, and 4-azido-benzoyl- (2-aminoethyl) acrylamide.
Besides intermolecular force, the photoresponse monomer generates benzene ring free radicals under the action of illumination, and the benzene ring free radicals can attack C-H bonds on graphene molecules to generate chemical reaction to form covalent bonds, so that the bonding strength between the polymer and the graphene molecules is greatly improved.
Therefore, the light-cured adhesive prepared from the hyperbranched cationic mussel-like polymer obviously increases the adhesive strength between the light-cured adhesive and the polymer film, so that the graphene coating formed by the light-cured adhesive and the graphene is combined on the polymer film more firmly, the coating effect is better, and meanwhile, the coating effect is obviously improved, so that the preparation process of the medicine packaging film is simplified to a certain extent. In addition, the adhesive strength between the light-cured adhesive and the graphene is also remarkably increased, so that the occupation ratio of the light-cured adhesive in the graphene coating can be reduced, and the light transmittance of the medicine packaging film is further improved. Moreover, compared with the existing graphene composite film, the medicine packaging film prepared by the invention obviously reduces the water vapor permeability and the oxygen permeability, and can meet the requirements of most medicine packaging.
As a preferred structure of the hyperbranched cationic mussel-like polymer of the invention, the hyperbranched cationic mussel-like polymer has a structure of formula i:
in the formula I, x is 2-10, y is 10-30, z is 40-100, w is 1-15, u is 10-40, K is 0-7, n is 10-80, and m is 5-45;
in the formula I, R1Any one selected from the group shown in formula II,
in the formula I, R2Any one selected from the group represented by formula III,
under the illumination condition, the covalent bond between the fluorine substituent in the photoresponse monomer and the graphene can be broken or combined, so that the bonding strength between the polymer and the graphene can be changed according to the illumination strength, the bonding strength of the adhesive can be adjusted according to specific requirements, and the method is more suitable for graphene film packaging materials. Preferably, the polymerization degree of the hyperbranched cationic mussel-like polymer is 100-400. Preferably, in formula I, K is 1-3, n is 10-30, and m is 20-45.
Compared with the traditional small-molecule adhesive and the common polymer adhesive, the hyperbranched cationic mussel-like polymer disclosed by the invention has excellent mussel-like non-selective adhesion performance, good biocompatibility and bonding strength adjustability.
Further, the mass ratio of graphene to the photo-curing adhesive in the graphene coating is 1: 0.01-1: 0.2. according to the invention, the bonding strength of the photo-curing adhesive and the graphene can reduce the proportion of the photo-curing adhesive in the graphene coating, so that the light transmittance of the medicine packaging film is improved. Compared with the mass ratio of 1: 0.2-1: 0.8 of graphene to the binder in the prior art, the mass ratio of graphene to the photo-curing binder is 1: 0.01-1: 0.2.
Further, the thickness of the graphene coating is 20-500 nm, and preferably, the thickness of the graphene coating is 20-60 nm. The thickness is not higher than the average value of the conventional graphene coating, but has high barrier properties against water vapor transmission and oxygen transmission.
Further, the polymer film is any one of polypropylene, polyethylene terephthalate, polyvinyl chloride and polybutylene terephthalate.
The invention also provides a preparation method of the medicine packaging film, which comprises the following steps:
(A) preparing a hyperbranched cationic mussel-like polymer by adopting a reversible addition-fragmentation chain transfer polymerization method, and preparing the prepared hyperbranched cationic mussel-like polymer into an adhesive aqueous solution;
(B) preparing a reduced graphene oxide solution;
(C) adding the adhesive aqueous solution prepared in the step (A) into the reduced graphene oxide solution prepared in the step (B), and uniformly stirring to prepare a graphene coating solution;
(D) and coating the graphene coating solution on a polymer film, and drying to form the graphene coating.
In the step (A), a hyperbranched cationic mussel-like polymer is prepared by a reversible addition-fragmentation chain transfer polymerization (RAFT polymerization) method, and comprises a poly-o-phenolic hydroxyl benzophenone enamide monomer, a cationic monomer and a photoresponsive monomer, and then the prepared hyperbranched cationic mussel-like polymer is prepared into an adhesive aqueous solution for later use.
In the step (B), commercially available graphene oxide may be used, or a graphene oxide solution may be prepared by a Hummers method, and then the graphene oxide is reduced with a reducing agent to obtain a reduced graphene oxide solution with stable dispersion. Preferably, the reducing agent is one of sodium ascorbate, hydroiodic acid, hydrazine hydrate and sodium borohydride.
In the step (C), adding the adhesive aqueous solution into the reduced graphene oxide solution and uniformly stirring, preferably, the stirring time is 5-60 min, the stirring speed is 200-500 rpm, and after the stirring is finished, forming a uniform and stable graphene coating solution for later use. Before step (C), the surface of the polymer film may be cleaned with clean water to remove contaminants from the surface and improve adhesion of the surface of the polymer film.
In the prior art, before the graphene coating solution is coated on the polymer film, the polymer film is usually required to be subjected to corona treatment. In the application, the poly-o-phenolic hydroxybenzophenone enamide monomer contains a large amount of catechol groups, and can form various intermolecular acting forces such as hydrogen bonds, van der waals forces, cation pi acting forces and the like with the surface of the polymer film, so that the poly-o-phenolic hydroxybenzophenone enamide monomer can be well combined with the surface of the polymer film, and even if no corona step is carried out, the adhesive aqueous solution can be well coated on the polymer film, so that the corona step is omitted, the process cost is reduced, the process steps are simplified, the working hours are shortened, and the poly-o-phenolic hydroxybenzophenone enamide monomer has wide popularization.
In the step (D), after the graphene coating is coated on the polymer film, drying the graphene coating solution at 40 ℃ for 8 hours to form the graphene coating adhered on the polymer film after drying.
In the process, the graphene coating solution coated on the polymer film enables the drug packaging film to have high barrier property; meanwhile, the coating process is simple, and only one-time coating of the graphene coating solution is needed; moreover, the preparation process omits a corona step adopted in the prior art on the premise of ensuring a better coating effect, so that the process cost is reduced, the process steps are simplified, the working hours are shortened, and the preparation process has wide popularization value.
Further, the step (a) includes the steps of:
(A1) adding an initiator, a RAFT agent and the first reaction mixture to a vessel containing DMF to form a second reaction mixture;
(A2) stirring the second reaction mixture until the second reaction mixture is uniform, and introducing argon to remove oxygen in the reaction system;
(A3) heating and stirring the second reaction mixture for reaction;
(A4) after the desired molecular weight of the product was reached, the reaction was exposed to air and rapidly cooled in a cold water bath to terminate the reaction;
(A5) purifying to obtain a hyperbranched cationic mussel-like polymer;
(A6) preparing the hyperbranched cationic mussel-like polymer into an adhesive aqueous solution with the concentration of 0.1-5 mg/mL;
in the above step, the first reaction mixture includes a poly-o-phenolic hydroxybenzophenone enamide monomer, a cationic monomer, a photoresponsive monomer, a polyethylene glycol diacrylate and a polyethylene glycol diacrylate.
In the above step, the first reaction mixture includes a poly-o-phenolic hydroxybenzophenone enamide monomer, a cationic monomer, a photoresponsive monomer, a polyethylene glycol diacrylate and a polyethylene glycol diacrylate.
Firstly, adding an initiator, a RAFT reagent, a poly-o-phenol hydroxy benzophenone enamide monomer, a cationic monomer, a photoresponsive monomer, polyethylene glycol diacrylate and polyethylene glycol diacrylate into a round-bottom flask filled with DMF (N, N-dimethylformamide) and uniformly stirring, preferably, the concentration of the initiator is 0.012M, and then introducing argon to remove oxygen in a reaction system, preferably, the introducing time of the argon is 20-25 minutes. And then putting the round-bottom flask into an oil bath for heating and stirring, wherein the oil bath temperature is preferably 60-90 ℃, and the stirring speed is 600-800 rpm. After the reaction was carried out until the desired conversion was achieved and the desired molecular weight of the product was obtained, the reaction system was exposed to air and the round-bottom flask was placed in a cold water bath to allow the reaction system to cool rapidly. The product is then purified to give a light brown hyperbranched cationic mussel-like polymer, preferably using dichloromethane and diethyl ether as solvents. After purification, preparing the hyperbranched cationic mussel-like polymer into an adhesive aqueous solution with the concentration of 0.1-5 mg/mL.
Preferably, the polyethylene glycol dienoate is polyethylene glycol diacrylate or polyethylene glycol dimethacrylate, and the polyethylene glycol dienoate is used for adjusting the esterification degree of the polymer; the polyethylene glycol enoate is polyethylene glycol methyl ether acrylate or polyethylene glycol methyl ether methacrylate, the polyethylene glycol enoate is used for adjusting the solubility of the polymer, and preferably, the molecular weight of polyethylene glycol is 200-6000.
Further, the mol percentages of the poly-o-phenol hydroxybenzophenone enamide monomer, the cationic monomer, the photoresponsive monomer, the polyethylene glycol enoate and the polyethylene glycol enoate are as follows in sequence: 20-40%, 30-40%, 1-5%, 20-40% and 5-10%.
Further, in step (a1), the molar ratio of the initiator, the RAFT agent and the first reaction mixture is 1:2: 100; the reaction temperature in the step (A3) is 60-90 ℃, and the stirring speed is 600-800 rmp.
Further, in the step (D), the coating process of the graphene coating solution is a roll coating process, a spin coating process or a blade coating process. The graphene coating solution can be quickly and conveniently coated on the polymer film through a roll coating process, a spin coating process or a blade coating process. The graphene coating solution process is not suitable for a spray coating process or a dip coating process.
The invention improves the existing preparation method of the reduced graphene oxide solution.
The step (B) of the preparation process of the medicine packaging film specifically comprises the following steps:
(B1) adding graphite powder into concentrated sulfuric acid, uniformly stirring in an ice-water bath, adding potassium permanganate, controlling the temperature of the water bath to be 10-15 ℃, and reacting for 2 hours;
(B2) transferring the reaction solution into a 35 ℃ water bath for constant temperature reaction for 30min, continuously stirring, adding distilled water into the reaction solution, and then controlling the temperature at 80 ℃ for reaction for 15 min;
(B3) adding a certain amount of 15% hydrogen peroxide into the reaction solution until bubbles are generated, filtering while hot, and washing a filter cake with hydrochloric acid and deionized water until the filtrate is neutral to prepare a graphene oxide aqueous solution;
(B4) before using the graphene oxide aqueous solution, diluting the graphene oxide aqueous solution with deionized water and carrying out ultrasonic treatment for 1 hour to obtain the graphene oxide solution with the concentration of 0.1-5.0 mg/mL;
(B5) mixing the prepared graphene oxide solution with a reducing agent according to the mass ratio of 1:3, reacting at normal temperature for 2 minutes, and then diluting to reduced graphene oxide solutions with different concentrations.
According to the technical scheme, the existing Hummers method for preparing graphene oxide is improved, on one hand, the total reaction time is less than 3 hours, the total reaction time of the Hummers method is greatly shortened, the steps of standing, drying and the like are not needed, and the production efficiency is effectively improved; on the other hand, water is used as a solvent in the whole reaction process, the preparation conditions are environment-friendly, the post-treatment process is simpler, and the production cost is reduced.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the light-cured adhesive prepared from the hyperbranched cationic mussel-like polymer obviously increases the adhesive strength between the light-cured adhesive and the polymer film, so that the graphene coating formed by the light-cured adhesive and the graphene is more firmly combined on the polymer film, the coating effect is better, and meanwhile, the coating effect is obviously improved, so that the preparation process of the medicine packaging film is simplified to a certain extent;
2. according to the invention, the bonding strength of the photo-curing adhesive and the graphene is also obviously increased, so that the proportion of the photo-curing adhesive in the graphene coating can be reduced, and the light transmittance of the medicine packaging film is further improved;
3. compared with the existing graphene composite film, the medicine packaging film prepared by the invention obviously reduces the water vapor permeability and the oxygen permeability, and can meet the requirements of most medicine packaging;
4. the coating process is simple, and only one-time coating of the graphene coating solution is needed; moreover, the preparation process omits a corona step adopted in the prior art on the premise of ensuring a better coating effect, so that the process cost is reduced, the process steps are simplified, the working hours are shortened, and the preparation process has a wide popularization value;
5. the method improves the existing Hummers method for preparing graphene oxide, on one hand, the total reaction time is less than 3 hours, the total reaction time of the Hummers method is greatly shortened, the steps of standing, drying and the like are not needed, and the production efficiency is effectively improved; on the other hand, water is used as a solvent in the whole reaction process, the preparation conditions are environment-friendly, the post-treatment process is simpler, and the production cost is reduced.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not used as limitations of the present invention.
All of the starting materials of the present invention, the sources of which are not particularly limited, are commercially available or can be prepared according to conventional methods well known to those skilled in the art, for example, the photoresponsive monomer can be synthesized by esterification, and the polyphthalin hydroxybenzophenone enamide monomer can be synthesized in the manner disclosed in [ J ] Polymer Bulletin,2012,68, 441-.
All the raw materials of the present invention are not particularly limited in their purity, and the present invention preferably employs purity requirements that are conventional in the field of analytical purification or binder preparation.
The expression of the substituent in the present invention is not particularly limited, and the expression known to those skilled in the art is used, and the meaning of the substituent can be correctly understood by the skilled in the art based on the general knowledge.
All the raw materials, the marks and the acronyms thereof belong to the conventional marks and the acronyms in the field, each mark and acronym is clear and definite in the field of related application, and the raw materials can be purchased from the market or prepared by the conventional method by the technical staff in the field according to the marks, the acronyms and the corresponding application.
Example 1:
preparing a hyperbranched cationic mussel-like polymer P1:
2,3, 4-Trihydroxybenzoyl-M-benzoyl- (2-aminoethyl) acrylamide, N- (2-aminoethyl) (meth) acrylamide hydrochloride, 4-azido-2, 3,5, 6-tetrafluorobenzoylethylamine (meth) acrylamide, polyethylene glycol methyl ether acrylate (PEGMEA), polyethylene glycol diacrylate (PEGDEA, degree of polymerization of ethylene glycol 22) and RAFT reagent were added to a 0.012M solution of initiator 4,4' -azobis (4-cyanovaleric acid) in N, N-dimethylformamide. Wherein the molar ratio of the first reaction mixture consisting of PEGMEA with a polymerization degree of ethylene glycol of 15, PEGDEA with a polymerization degree of ethylene glycol of 22, 4,4' -azobis (4-cyanovaleric acid), RAFT agent and all monomers involved in the polymerization is 1:2: 100. 2,3, 4-trihydroxybenzoyl-m-benzoyl- (2-aminoethyl) acrylamide: n- (2-aminoethyl) (meth) acrylamide hydrochloride: 4-azido-2, 3,5, 6-tetrafluorobenzoylethylamine (meth) acrylamide: PEGDMEA: mole percent of PEGEA is 40%: 30%: 5%: 15%: 10 percent. And (3) uniformly stirring the obtained second reaction mixture, and introducing argon for 20-25 min to remove oxygen in the second reaction mixture. The mixed system is placed at 70 ℃ and 700rmp and stirred for reaction until the expected conversion rate is reached, and the product with the required molecular weight is obtained. At the end of the reaction, the reaction system was exposed to air and quenched in cold water. After further purification of the product with dichloromethane and diethyl ether, a light brown adhesive hyperbranched cationic mussel-like polymer P1 was obtained. The hyperbranched cationic mussel-like polymer P1 was then dissolved in ethanol and water (1: 1 by volume) to obtain an aqueous binder solution S1 with a concentration of 15 wt%.
The hyperbranched cationic mussel-like polymer P1 has the structure:
the map detection results of the structure are as follows:
1H NMR(400MHz,DMSO-D6)δ(ppm)：7.90-8.2(-NHCOC6H4CO-)6.6-7.2(C6H2(OH)3),5.35(-C6H3(OH)2),4.32(CH2OOC-),3.50-3.8(-CH2CH2O-,-OCNHCH2CH2-),3.22(CH3O-),3.03(-OCNHCH2CH2NH3Cl),2.16(-CH2CHCO-),1.25-1.96(-CH2CHCO-)；
19F NMR(188MHz,DMSO-D6)δ(ppm)：-134.69～-134.88(2F),-147.58～-147.71(2F)。
example 2:
preparing a hyperbranched cationic mussel-like polymer P2:
2,3, 4-Trihydroxybenzoyl-p-benzamide ethyl (meth) acrylamide hydrochloride, N- (3-aminopropyl) (meth) acrylamide hydrochloride, 4-azido-2, 3,5, 6-tetrafluorobenzamide ethyl amine (meth) acrylamide, polyethylene glycol methyl ether acrylate (PEGMEA), polyethylene glycol diacrylate (PEGDEA) and RAFT reagent were added to a solution of 2,2' -azobis (2-methylpropionitrile) in N, N-dimethylformamide as an initiator at a concentration of 0.012M. Wherein the molar ratio of the first reaction mixture consisting of PEGMEA with a glycol polymerization degree of 45, PEGDEA with a glycol polymerization degree of 10, 2,2' -azobis (2-methylpropanenitrile), RAFT reagent and all monomers participating in polymerization is 1:2: 100. 2,3, 4-trihydroxybenzoylbenzamide ethyl (meth) acrylamide hydrochloride: n- (3-aminopropyl) (meth) acrylamide hydrochloride: 4-azido-2, 3,5, 6-tetrafluorobenzoylethylamine (meth) acrylamide: PEGDEA: the mole percentage of PEGMEA is 20%: 33%: 2%: 35%: 10 percent. And (3) uniformly stirring the obtained second reaction mixture, and introducing argon for 20-25 min to remove oxygen in the second reaction mixture. The mixed system is placed at 70 ℃ and 700rmp and stirred for reaction until the expected conversion rate is reached, and the product with the required molecular weight is obtained. At the end of the reaction, the reaction system was exposed to air and quenched in cold water. After further purification of the product with dichloromethane and diethyl ether, a light brown adhesive hyperbranched cationic mussel-like polymer P2 was obtained. The hyperbranched cationic mussel-like polymer P2 was then dissolved in ethanol and water (1: 1 by volume) to obtain an aqueous binder solution S2 with a concentration of 15 wt%.
The hyperbranched cationic mussel-like polymer P2 has the structure:
the map detection results of the structure are as follows:
1H NMR(400MHz,DMSO-D6)δ(ppm)：
7.90-8.2(-NHCOC6H4CO-)6.6-7.2(C6H2(OH)3),5.35(C6H2(OH)3),4.32(CH2OOC-),3.50-3.8(-CH2CH2O-,-OCNHCH2CH2-),3.22(CH3O-),3.03(-OCNHCH2CH2NH3Cl),2.16(-CH2CHCO-),1.25-1.96(-CH2CHCO-)；
19F NMR(188MHz,DMSO-D6)δ(ppm)：-134.69～-134.88(2F),-147.58～-147.71(2F)。
example 3:
preparing a hyperbranched cationic mussel-like polymer P3:
2, 3-Dihydroxybenzoylbenzoate aminoethyl (meth) acrylamide hydrochloride, N- (4-aminobutyl) (meth) acrylamide hydrochloride, 4-azido-benzoylethylamine (meth) acrylamide, polyethylene glycol methyl ether acrylate (PEGMEA), polyethylene glycol diacrylate (PEGDEA) and RAFT reagent 2- (dodecyltrithiocarbonate) -2-methylpropionic acid were added to a solution of initiator 2,2' -azobis (2-methylpropionitrile) in N, N-dimethylformamide at a concentration of 0.012M. Wherein the molar ratio of the first reaction mixture consisting of PEGMEA with a degree of polymerization of ethylene glycol of 5, PEGDEA with a degree of polymerization of ethylene glycol of 8, 2,2' -azobis (2-methylpropanenitrile), RAFT agent and all monomers involved in the polymerization is 1:2: 100. 2, 3-dihydroxybenzoylbenzoic acid ester aminoethyl (meth) acrylamide hydrochloride: n- (4-aminobutyl) (meth) acrylamide hydrochloride: 4-azido-benzoylethylamine (meth) acrylamide: PEGDEA: the mole percentage of PEGMEA is 25%: 35%: 5%: 30%: 5 percent. And (3) uniformly stirring the obtained mixed solution, and introducing argon for 20-25 min to remove oxygen in the mixed solution. The mixed system is placed at 70 ℃ and 700rmp and stirred for reaction until the expected conversion rate is reached, and the product with the required molecular weight is obtained. At the end of the reaction, the reaction system was exposed to air and quenched in cold water. After further purification of the product with dichloromethane and diethyl ether, a light brown adhesive hyperbranched cationic mussel-like polymer P3 was obtained. The hyperbranched cationic mussel-like polymer P3 was then dissolved in ethanol and water (1: 1 by volume) to obtain an aqueous binder solution S3 with a concentration of 15 wt%.
The hyperbranched cationic mussel-like polymer P3 has the structure:
the map detection results of the structure are as follows:
1H NMR(400MHz,DMSO-D6)δ(ppm)：7.90-8.2(-NHCOC6H4CO-)6.6-7.5(N3C6H4CO-,-C6H3(OH)2),5.35(-C6H3(OH)3),4.32(CH2OOC-),3.50-3.8(-CH2CH2O-,-OCNHCH2CH2-),3.22(CH3O-),3.03(-OCNHCH2CH2NH3Cl),2.16(-CH2CHCO-),1.25-1.96(-CH2CHCO-)。
example 4:
preparation of films for pharmaceutical packaging M1, M2 and M3:
firstly, preparing a graphene oxide solution with the concentration of 15mg/mL by using the conventional Hummers method, mixing the prepared graphene oxide solution with a 98 wt% hydrazine hydrate solution in a mass ratio of 1:3, reacting at normal temperature for 2 minutes, and diluting to reduced graphene oxide solutions with different concentrations;
subsequently, cleaning three PET films, and carrying out ultrasonic treatment to remove pollutants on the surfaces of the PET films;
the aqueous binder solutions S1 to S3 prepared in examples 1 to 3 were added to the reduced graphene oxide solution, and the mixture was uniformly stirred to prepare graphene coating solutions L1, L2, and L3. Wherein, in L1, L2 and L3, the ratio of the graphene to the adhesive is 1: 0.06-1: 0.08.
And respectively roll-coating, spin-coating and blade-coating the graphene coating solutions L1-L3 on three PET films, and drying at 40 ℃ for 8 hours to form the graphene coating. Finally, drug packaging films M1, M2 and M3 with the graphene coating thickness of 40nm are formed.
Example 5:
the hard PVC solid medicinal tablet is adopted in comparative example 1, and the hard PVDC solid medicinal tablet is adopted in comparative example 2.
The physical parameters of the drug packaging films M1, M2, M3, comparative example 1 and comparative example 2 with the same graphene coating thickness are tested according to national standards, and the obtained physical parameters are shown in Table 1:
TABLE 1 physical parameters of the respective drug packaging films
| Item | Unit of | M1 | M2 | M3 | Comparative example 1 | Comparative example 2 |
| Water vapor transmission capacity | g/m2.atm.day | 0.28 | 0.36 | 0.38 | 1.01 | 0.42 |
| Oxygen permeability | cc/m2.atm.day | 0.23 | 0.29 | 0.33 | 12.27 | 0.523 |
| Tensile Strength (longitudinal/horizontal) | MPa | 65.3/64.7 | 63.9/62.7 | 64.1/63.4 | 66.2/65.3 | 56.7/55.7 |
| Heat seal strength | N/15mm | 10.9 | 11.1 | 10.8 | 11.5 | 10.8 |
| Heavy metals | ％ | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
| Easily oxidized substance | ml | <1.5 | <1.5 | <1.5 | <1.5 | <2 |
| Non-volatile matter | mg | <25 | <30 | <30 | <30 | <30 |
| Total number of bacteria | Per cm2 | <1000 | <1000 | <1000 | <1000 | <1000 |
| Total number of moulds | Per cm2 | <100 | <100 | <100 | <100 | <100 |
| Escherichia coli | Per cm2 | 0 | 0 | 0 | 0 | 0 |
As can be seen from table 1, under the same quality and thickness, compared with comparative example 1 and comparative example 2, the water vapor permeability and the oxygen permeability of the films M1, M2 and M3 for packaging medicines prepared in examples 1 to 3 are significantly reduced, so that small molecule gases such as oxygen and water vapor are effectively prevented from permeating into a packaging material, the active ingredients in the medicines are prevented from being oxidized and deteriorated, the phenomena such as microbial propagation and the like are prevented, and the shelf life of the medicines is prolonged.
Example 6
On the basis of the embodiment 4, the preparation method of the reduced graphene oxide solution is improved.
Adding 1 g of graphite powder into 23ml of concentrated sulfuric acid, placing the mixture in an ice-water bath, fully and uniformly stirring, adding 2.5g of potassium permanganate, controlling the temperature of the water bath to be 10-15 ℃ for reaction for 2 hours, then moving the reaction solution into a 35 ℃ water bath for constant-temperature reaction for 30min, continuously stirring the reaction solution, then adding 80ml of distilled water into the reaction solution, controlling the temperature to be 80 ℃ for reaction for 15min, adding a certain amount of 15% hydrogen peroxide into the reaction solution until bubbles are generated, filtering while hot, and washing a filter cake with hydrochloric acid and deionized water until the filtrate is neutral to prepare a graphene oxide aqueous dispersion for later use; before using the graphene oxide aqueous solution, diluting the graphene oxide solution with deionized water and performing ultrasonic treatment for 1 hour to obtain the graphene oxide solution with the concentration of 0.1-5 mg/mL.
And then mixing the prepared graphene oxide solution with the concentration of 15mg/mL and a 98 wt% hydrazine hydrate solution in a mass ratio of 1:3, reacting for 2 minutes at normal temperature, and then diluting to a reduced graphene oxide solution with the required concentration.
In the technical scheme, the total reaction time is less than 3 hours, the total reaction time of the Hummers method is greatly shortened, the steps of standing, drying and the like are not needed, and the production efficiency is effectively improved; on the other hand, water is used as a solvent in the whole reaction process, the preparation conditions are environment-friendly, the post-treatment process is simpler, and the production cost is reduced.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (8)
1. A pharmaceutical packaging film comprising a polymeric film, and a graphene coating coated on the polymeric film, the graphene coating comprising graphene and a light-curable adhesive, wherein the light-curable adhesive comprises a hyperbranched cationic mussel-like polymer comprising a polyphenol hydroxybenzophenone enamide monomer, a cationic monomer, and a light-responsive monomer;
the hyperbranched cationic mussel-like polymer has a structure shown in a formula I:
in the formula I, x is 2-10, y is 10-30, z is 40-100, w is 1-15, u is 10-40, K is 0-7, n is 10-80, and m is 5-45;
in the formula I, R1Any one selected from the group shown in formula II,
in the formula I, R2Any one selected from the group represented by formula III,
2. the drug packaging film of claim 1, wherein the mass ratio of the graphene to the photo-curable binder in the graphene coating is 1: 0.01-1: 0.2.
3. the drug packaging film of claim 1, wherein the graphene coating has a thickness of 20-500 nm.
4. A pharmaceutical packaging film according to claim 1, wherein said polymer film is any one of polypropylene, polyethylene terephthalate, polyvinyl chloride, polybutylene terephthalate.
5. The method for preparing a pharmaceutical packaging film according to any one of claims 1 to 4, comprising the steps of:
(A) preparing a hyperbranched cationic mussel-like polymer by adopting a reversible addition-fragmentation chain transfer polymerization method, and preparing the prepared hyperbranched cationic mussel-like polymer into an adhesive aqueous solution;
(B) preparing a reduced graphene oxide solution;
(C) adding the adhesive aqueous solution prepared in the step (A) into the reduced graphene oxide solution prepared in the step (B), and uniformly stirring to prepare a graphene coating solution;
(D) coating the graphene coating solution on a polymer film, and drying to form a graphene coating;
the step (A) includes the steps of:
(A1) adding an initiator, a RAFT agent and the first reaction mixture to a vessel containing DMF to form a second reaction mixture;
(A2) stirring the second reaction mixture until the second reaction mixture is uniform, and introducing argon to remove oxygen in the reaction system;
(A3) heating and stirring the second reaction mixture for reaction;
(A4) after the desired molecular weight of the product was reached, the reaction was exposed to air and rapidly cooled in a cold water bath to terminate the reaction;
(A5) purifying to obtain a hyperbranched cationic mussel-like polymer;
(A6) preparing the hyperbranched cationic mussel-like polymer into an adhesive aqueous solution with the concentration of 0.1-5 mg/mL;
in the above step, the first reaction mixture includes a poly-o-phenolic hydroxybenzophenone enamide monomer, a cationic monomer, a photoresponsive monomer, a polyethylene glycol diacrylate and a polyethylene glycol diacrylate.
6. The method for preparing a drug packaging film according to claim 5, wherein the molar percentages of the poly-o-phenolic hydroxybenzophenone enamide monomer, the cationic monomer, the photoresponsive monomer, the polyethylene glycol enoate and the polyethylene glycol enoate are as follows in sequence: 20-40%, 30-40%, 1-5%, 20-40% and 5-10%.
7. The method of claim 5, wherein in step (A1), the molar ratio of the initiator, RAFT agent and first reaction mixture is 1:2: 100; the reaction temperature in the step (A3) is 60-90 ℃, and the stirring speed is 600-800 rpm.
8. The method for preparing a pharmaceutical packaging film according to claim 5, wherein in the step (D), the coating process of the graphene coating solution is a roll coating process, a spin coating process or a blade coating process.
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