CN109589414B - Method for carrying out drug loading by using GO or CNTs as carrier through supercritical carbon dioxide extraction device - Google Patents
Method for carrying out drug loading by using GO or CNTs as carrier through supercritical carbon dioxide extraction device Download PDFInfo
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Abstract
A method for carrying out drug loading by using GO or CNTs as a carrier through a supercritical carbon dioxide extraction device relates to a method for carrying out drug loading by using GO or CNTs as a carrier. The method comprises the following steps: placing the weighed carrier in an extraction tank of a supercritical extraction device, dissolving the weighed medicine in absolute ethyl alcohol to obtain a mixed solution, transferring the mixed solution into an entrainer tank of the supercritical extraction device, conveying the mixed solution in the entrainer tank into the extraction tank containing the carrier by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out medicine loading under the conditions of certain raw material proportion and loading time to obtain a medicine-loaded product, and drying the obtained medicine-loaded product at room temperature for 22-26 h. The invention utilizes supercritical CO2The drug loading is carried out, the problem of pollution or separation of a solvent used for loading the drug by a conventional method is avoided, and the drug loading capacity is improved. The invention is suitable for carrying out drug loading by taking GO or CNTs as a carrier.
Description
Technical Field
The invention relates to a method for carrying out drug loading by using GO or CNTs as a carrier through a supercritical carbon dioxide extraction device.
Background
Graphene is the thinnest and highest-strength novel polymer material in the natural world at present, has excellent mechanical properties and biocompatibility, and is low in toxicity. However, graphene has the characteristics of hydrophobicity and easy agglomeration due to strong van der waals force, so that the wide application of graphene is limited. The problem is solved by the appearance of Graphene Oxide (GO), the Graphene Oxide (GO) is a derivative of graphene, has high specific surface energy, good hydrophilicity and mechanical properties, and has good dispersion stability in water and most polar organic solventsAnd (5) performing qualitative determination. The graphene oxide has hydroxyl, epoxy group, carbonyl, carboxyl and the like between the layers, generally, the upper surface and the lower surface of the layers are connected with the epoxy group and the hydroxyl, the edges of the layers are the carbonyl and the carboxyl, the graphene oxide has excellent composite performance due to the huge specific surface area and the abundant functional groups on the surface, and due to the structural similarity, the two surfaces of the single layer of graphene oxide both have aromatic structures, so that the graphene oxide can adsorb drug molecules with similar structures and aromatic structures and can be used as a potential drug carrier. As a novel nano material, Carbon Nanotubes (CNTs) have a high specific surface area, a one-dimensional nanostructure, and good stability, and have been widely used and studied as carriers in the fields of drugs, genes, proteins, and the like. Each carbon atom on the carbon nanotube is sp2Hybridization is carried out, one p electron which does not participate in hybridization can form conjugated pi-pi electron cloud spanning the whole carbon nano tube, most of biomolecules such as protein, DNA and anticancer drug molecules are provided with pi electron structures, and the biomolecules can be adsorbed on the surface of the carbon nano tube through pi-pi bond interaction. The conjugated structure of Pi-Pi on the surface of the carbon nano tube enables the conjugated structure to form Pi-Pi bond interaction with a plurality of drugs with aromatic rings in the molecular structure, thereby realizing the loading of the drugs.
Supercritical carbon dioxide (SC-CO)2) The extraction technique is to utilize CO under special pressure and temperature2In a supercritical state, in which SC-CO is utilized2It has special dissolving effect on some special natural products for extraction. CO 22Because the critical pressure is low, the critical temperature is close to the normal temperature, and the supercritical fluid extraction solvent has the advantages of no pollution, no combustion, safety, no toxicity, chemical inertness, wide sources, low price and the like, the supercritical fluid extraction solvent is the most widely applied. The problem of low load capacity of the existing physical load method for loading drugs on a carrier is solved, in the GO-loaded aspirin physical load method, the drug loading time is 2 hours, the drug loading temperature is 20 ℃, and the mass ratio of GO to aspirin (ASA) is 1: under the condition of 1, the medicine loading rate of GO is only 0.0349 mg/mg; in the physical loading method of the CNTs loaded aspirin, the drug loading time is 2h, the drug loading temperature is 40 ℃, and the mass ratio of the CNTs to the aspirin is 1:4Under the condition, the drug loading of the CNTs is only 0.048 mg/mg.
Disclosure of Invention
The invention provides a method for loading a drug by using GO or CNTs as a carrier by adopting a supercritical carbon dioxide extraction device, aiming at solving the problem of low loading capacity of loading the drug on the carrier by the existing physical loading method.
The method for carrying out drug loading by using GO or CNTs as a carrier by adopting a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing a carrier, and placing the weighed carrier in an extraction tank of a supercritical extraction device;
step two: weighing the medicines, dissolving the weighed medicines in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device;
the ratio of the mass of the medicine to the volume of the absolute ethyl alcohol is 1mg (3-5) mL;
the mass ratio of the medicine to the carrier is (1-4) to 1;
the carrier is GO or CNTs;
the medicine is alcohol-soluble aromatic medicine;
the alcohol-soluble aromatic medicine is aspirin, paclitaxel or adriamycin;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing a carrier by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 22-26 h to complete the process;
adjusting the pressure of the extraction tank to 10-30 MPa;
adjusting the temperature of the extraction tank to 35-50 ℃;
the time for loading the medicine is 0.25-2 h.
The invention has the following beneficial effects:
1. the invention adopts absolute ethyl alcohol as solvent and uses the absolute ethyl alcohol as solvent to perform supercritical CO reaction2Loading the medicine on GO or CNTs under the condition of supercritical CO2Carrying GO or CNTs sheets when the drug contacts with GO or CNTsThe structure contains carbonyl, hydroxyl, epoxy group and other groups which form hydrogen bond action with carboxyl or ester group in the medicine, and hydrogen bond combination can also occur among medicine molecules to realize loading;
2. due to supercritical CO2The supercritical CO has the characteristics of high diffusivity, zero surface tension and disappearance of gas-liquid interface2Is characterized in that the carrier is loaded with medicine, supercritical CO2High diffusivity for easy penetration of the drug into the carrier, supercritical CO2Supercritical CO for zero surface tension and gas-liquid interface disappearance property2The surface tension effect existing in the carrier can be eliminated, the loading is facilitated, and the drug loading capacity is improved;
3. supercritical CO2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, thereby saving energy and resources;
4. according to the method, the drug-loading amount of a drug-loaded product obtained under the conditions that the pressure in an extraction tank is 20MPa, the temperature is 40 ℃, the loading time is 1h, and the mass ratio of ASA to GO is 2:1 is 0.1210 mg/mg; the drug-loading amount of the drug-loaded product is 0.111mg/mg under the conditions that the pressure in the extraction tank is 20MPa, the temperature is 45 ℃, the loading time is 80min and the mass ratio of ASA to CNTs is 3: 1.
Drawings
FIG. 1 is a graph of ASA loading under different pressure conditions in the extraction tank of example 1;
FIG. 2 is a graph of ASA loading under different temperature conditions in the extraction tank of example 2;
FIG. 3 is a graph of ASA loading under different loading time conditions in example 3;
FIG. 4 is a graph of ASA drug loading under different material ratios in example 4;
FIG. 5 is a graph of ASA drug loading corresponding to the physical drug loading method under different material proportioning conditions in comparative example 1;
FIG. 6 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading time conditions in comparative example 2;
FIG. 7 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading temperature conditions in comparative example 3;
FIG. 8 is a graph of ASA loading under different pressure conditions for the extraction tank of example 6;
FIG. 9 is a graph of ASA loading at different temperature conditions in the extraction tank of example 7;
FIG. 10 is a graph of ASA loading under different loading time conditions in example 8;
FIG. 11 is a graph showing ASA drug loading under different material ratios in example 9;
FIG. 12 is a graph of ASA drug loading corresponding to the physical drug loading method under different material ratios in comparative example 5;
FIG. 13 is a graph of ASA loading rate corresponding to the physical loading method under different loading time conditions in comparative example 6;
fig. 14 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading temperature conditions in comparative example 7.
The specific implementation mode is as follows:
the technical scheme of the invention is not limited to the specific embodiments listed below, and any reasonable combination of the specific embodiments is included.
The first embodiment is as follows: the method for carrying out drug loading by using GO or CNTs as a carrier by adopting the supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing a carrier, and placing the weighed carrier in an extraction tank of a supercritical extraction device;
step two: weighing the medicines, dissolving the weighed medicines in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device;
step three: and (3) conveying the mixed solution in the entrainer tank into an extraction tank filled with the carrier by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 22-26 h to complete the process.
The embodiment has the following beneficial effects:
1. the embodiment adopts absolute ethyl alcohol as a solvent and adopts supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved;
2. due to supercritical CO2Has the characteristics of high diffusivity, zero surface tension and disappearance of gas-liquid interface, and the supercritical CO is utilized in the embodiment2Is characterized in that the carrier is loaded with medicine, supercritical CO2High diffusivity for easy penetration of the drug into the carrier, supercritical CO2Supercritical CO for zero surface tension and gas-liquid interface disappearance property2The surface tension effect existing in the carrier can be eliminated, and the loading is more facilitated;
3. supercritical CO2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, thereby saving energy and resources;
4. according to the method, the drug-loading amount of the drug-loaded product obtained under the conditions that the pressure in the extraction tank is 20MPa, the temperature is 40 ℃, the loading time is 1h, and the mass ratio of ASA to GO is 2:1 is 0.1210 mg/mg; the drug-loading amount of the drug-loaded product is 0.111mg/mg under the conditions that the pressure in the extraction tank is 20MPa, the temperature is 45 ℃, the loading time is 80min and the mass ratio of ASA to CNTs is 3: 1.
The second embodiment is as follows: the first difference between the present embodiment and the specific embodiment is: and step two, the carrier is GO or CNTs. Other steps and parameters are the same as in the first embodiment.
The third concrete implementation mode: the present embodiment differs from the first or second embodiment in that: the mass ratio of the medicine to the carrier is (1-4) to 1. Other steps and parameters are the same as in the first or second embodiment.
The fourth concrete implementation mode: the difference between this embodiment mode and one of the first to third embodiment modes is: step two, the medicine is alcohol-soluble aromatic medicine; the alcohol-soluble aromatic medicine is aspirin, paclitaxel or adriamycin. Other steps and parameters are the same as in one of the first to third embodiments.
The fifth concrete implementation mode: the difference between this embodiment and one of the first to fourth embodiments is: and step three, adjusting the pressure of the extraction tank to 10-30 MPa. Other steps and parameters are the same as in one of the first to fourth embodiments.
The sixth specific implementation mode: the difference between this embodiment and one of the first to fifth embodiments is: and step three, adjusting the temperature of the extraction tank to 35-50 ℃. Other steps and parameters are the same as in one of the first to fifth embodiments.
The seventh embodiment: the difference between this embodiment and one of the first to sixth embodiments is: and step three, the time for loading the medicine is 0.25-2 h. Other steps and parameters are the same as in one of the first to sixth embodiments.
The beneficial effects of the invention are verified by adopting the following experiments:
example 1: the method for carrying out aspirin loading by using a GO carrier by using a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing 10mg of GO, and placing the weighed GO in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing GO by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 10 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for carrying out drug loading is 1 h.
The other conditions are unchanged, the pressure of the extraction tank is respectively adjusted to be 15MPa, 20MPa, 25MPa and 30MPa, the loading is carried out, the drug loading capacity under different extraction tank pressure conditions is tested, and the test result is shown in figure 1; FIG. 1 is a graph of ASA loading under different pressure conditions in an extraction tank. As can be seen from FIG. 1, the highest drug loading was achieved at 20MPa of extraction tank pressure.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 2: the method for carrying out aspirin loading by using a GO carrier by using a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing 10mg of GO, and placing the weighed GO in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing GO by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 15 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for carrying out drug loading is 1 h.
The temperature of the extraction tank was adjusted to 40 ℃ and 45 ℃ respectively, and the ASA drug-loading rate was measured under different temperature conditions of the extraction tank, with the other conditions being unchanged, the test results being shown in fig. 2, where fig. 2 is a graph of ASA drug-loading rate under different temperature conditions of the extraction tank in example 2. As can be seen in fig. 2, the extraction tank temperature was 40 ℃, with the highest drug loading.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 3: the method for carrying out aspirin loading by using a GO carrier by using a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing 10mg of GO, and placing the weighed GO in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing GO by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 20 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for carrying out drug loading is 1 h.
The other conditions are unchanged, the ASA loading time is respectively adjusted to be 0.25h, 0.5h, 1.5h and 2h, the loading is carried out, the ASA loading amount under different loading time conditions is tested, and the test result is shown in figure 3; fig. 3 is a graph of ASA drug loading under different loading time conditions in example 3, and fig. 3 shows that the drug loading is highest when the loading time is 1 h.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 4: the method for carrying out aspirin loading by using a GO carrier by using a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing 10mg of GO, and placing the weighed GO in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing GO by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 15 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for carrying out drug loading is 1 h.
Adjusting the ASA weighing amounts to be 20mg and 30mg under the condition that other conditions are unchanged, carrying out loading, and testing the ASA drug loading amount under the conditions of different material ratios, wherein the test results are shown in FIG. 4; fig. 4 is a graph of ASA drug loading under different material proportioning conditions in example 4, and fig. 4 shows that the drug loading is highest when the mass ratio of GO to ASA is 1: 2.
This example uses absolute ethanol as solvent in supercritical CO2Under the condition thatMedicine loaded on GO or CNTs, supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Comparative example 1:
weighing GO, placing the GO in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain ethanol dispersion liquid of GO; weighing ASA, adding the weighed ASA into ethanol dispersion liquid of GO, carrying out ultrasonic treatment for 2min to fully dissolve the ASA to obtain mixed dispersion liquid, stirring the mixed dispersion liquid, filtering the stirred mixed dispersion liquid through a microporous filter membrane, and drying the obtained filter cake for 24h at room temperature to obtain a physical drug-loaded product; the temperature of the mixed dispersion liquid is 20 ℃ when the mixed dispersion liquid is stirred, and the stirring time is 0.5 h; weighing GO by 10 mg; ASA was weighed at 5mg, 8mg, 10mg, 12mg, 15mg and 20mg, respectively. Testing ASA drug loading amount corresponding to the physical drug loading method under different material proportioning conditions, wherein the test result is shown in FIG. 5; fig. 5 is a graph of ASA drug loading rate corresponding to a physical drug loading method under different material proportioning conditions, and fig. 5 shows that the drug loading is highest when the mass ratio of GO to ASA is 1: 1.
Comparative example 2:
weighing GO, placing the GO in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain ethanol dispersion liquid of GO; weighing ASA, adding the weighed ASA into ethanol dispersion liquid of GO, carrying out ultrasonic treatment for 2min to fully dissolve the ASA to obtain mixed dispersion liquid, stirring the mixed dispersion liquid, filtering the stirred mixed dispersion liquid through a microporous filter membrane, and drying the obtained filter cake for 24h at room temperature to obtain a physical drug-loaded product; the temperature of the mixed dispersion liquid is 20 ℃ while stirring, and the stirring time is 0.5h, 1h, 2h, 3h, 6h, 10h and 16h respectively; weighing GO by 10 mg; ASA weighed 10 mg. Testing ASA drug loading amount corresponding to the physical drug loading method under different drug loading time conditions, wherein the test result is shown in FIG. 6; fig. 6 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading time conditions, and fig. 6 shows that the drug loading capacity is the highest when the loading time is 2 hours.
Comparative example 3:
weighing GO, placing the GO in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain ethanol dispersion liquid of GO; weighing ASA, adding the weighed ASA into ethanol dispersion liquid of GO, carrying out ultrasonic treatment for 2min to fully dissolve the ASA to obtain mixed dispersion liquid, stirring the mixed dispersion liquid, filtering the stirred mixed dispersion liquid through a microporous filter membrane, and drying the obtained filter cake for 24h at room temperature to obtain a physical drug-loaded product; the temperature of the mixed dispersion liquid is 0 ℃, 10 ℃, 20 ℃, 30 ℃ and 40 ℃ respectively when the mixed dispersion liquid is stirred, and the stirring time is 0.5 h; weighing GO by 10 mg; ASA weighed 10 mg. ASA drug loading corresponding to the physical drug loading method under different drug loading temperature conditions is tested, and the test result is shown in FIG. 7; fig. 7 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading temperature conditions, and fig. 7 shows that the drug loading rate is the highest at a loading temperature of 20 ℃.
In comparative examples 1 to 3 and examples 1 to 4, the method for testing the drug loading of ASA was: weighing the prepared drug-loaded product, dispersing the weighed drug-loaded product in absolute ethyl alcohol, releasing the drug for 2 hours by ultrasonic waves, filtering by a microporous filter membrane, fixing the volume of the filtrate in a volumetric flask, respectively measuring the absorbance value of the filtrate of the drug-loaded product by adopting an ultraviolet spectrophotometer at 275nm, and calculating the drug-loaded amount of the drug-loaded product under different conditions according to an aspirin standard curve.
Example 5: the method for carrying out aspirin loading by using a GO carrier by using a supercritical carbon dioxide extraction device is carried out according to the following steps:
the method comprises the following steps: weighing 10mg of GO, and placing the weighed GO in an extraction tank of a supercritical extraction device;
step two: weighing 20mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing GO by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 20 MPa; the temperature of the extraction tank is adjusted to 40 ℃; the time for carrying out drug loading is 1 h. The drug loading on GO of this example was 0.1210 mg/mg.
Comparative example 4:
weighing GO, placing the GO in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain ethanol dispersion liquid of GO; weighing ASA, adding the weighed ASA into ethanol dispersion liquid of GO, carrying out ultrasonic treatment for 2min to fully dissolve the ASA to obtain mixed dispersion liquid, stirring the mixed dispersion liquid, filtering the stirred mixed dispersion liquid through a microporous filter membrane, and drying the obtained filter cake for 24h at room temperature to obtain a physical drug-loaded product; the temperature of the mixed dispersion liquid is 20 ℃ while stirring, and the stirring time is 2 hours; weighing GO by 10 mg; ASA weighed 10 mg.
Comparative example 4 drug loading on GO was 0.0349 mg/mg. The GO loading in example 5 is 3.5 times the loading in the physical method of comparative example 4.
Example 6: in this embodiment, the method for loading aspirin by using CNTs as a carrier in a supercritical carbon dioxide extraction apparatus is performed according to the following steps:
the method comprises the following steps: weighing 10mg of CNTs, and placing the weighed CNTs in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing CNTs by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 10 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for drug loading was 20 min.
The other conditions were not changed, the pressure of the extraction tank was adjusted to 15MPa, 20MPa and 25MPa respectively to carry out drug loading, fig. 8 is a graph of ASA drug loading under different extraction tank pressure conditions in example 6, and fig. 8 shows that the highest drug loading was achieved when the extraction tank pressure was 20 MPa.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 7: in this embodiment, the method for loading aspirin by using CNTs as a carrier in a supercritical carbon dioxide extraction apparatus is performed according to the following steps:
the method comprises the following steps: weighing 10mg of CNTs, and placing the weighed CNTs in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing CNTs by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 15 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for drug loading was 20 min. The temperature of the extraction tank was adjusted to 40 ℃, 45 ℃ and 50 ℃ for drug loading without changing other conditions, fig. 9 is a graph of ASA drug loading amount under different temperature conditions of the extraction tank in example 7, and fig. 9 shows that the highest drug loading amount is achieved when the temperature of the extraction tank is 45 ℃.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 8: in this embodiment, the method for loading aspirin by using CNTs as a carrier in a supercritical carbon dioxide extraction apparatus is performed according to the following steps:
the method comprises the following steps: weighing 10mg of CNTs, and placing the weighed CNTs in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing CNTs by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 15 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for drug loading was 20 min.
The other conditions were not changed, the time for loading the drug was adjusted to 40min, 60min, and 80min, and the drug loading was performed, fig. 10 is a graph of ASA drug loading in the example 8 under different loading time conditions, and fig. 10 shows that the highest drug loading was achieved when the loading time was 80 min.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the conditionSupercritical CO2When the carried medicine is contacted with GO or CNTs, groups such as carbonyl, hydroxyl, epoxy and the like contained on a GO or CNTs lamellar structure form a hydrogen bond effect with carboxyl or ester groups in the medicine, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Example 9: in this embodiment, the method for loading aspirin by using CNTs as a carrier in a supercritical carbon dioxide extraction apparatus is performed according to the following steps:
the method comprises the following steps: weighing 10mg of CNTs, and placing the weighed CNTs in an extraction tank of a supercritical extraction device;
step two: weighing 10mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, transferring the mixed solution into an entrainer tank of a supercritical extraction device, and conveying the mixed solution in the entrainer tank into an extraction tank by a pump; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing CNTs by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 15 MPa; the temperature of the extraction tank is adjusted to 35 ℃; the time for drug loading was 20 min.
Under other conditions, the addition amounts of ASA are respectively adjusted to be 20mg, 30mg and 40mg for drug loading, fig. 11 is a graph of ASA drug loading amount under different material proportioning conditions in the example 9, and fig. 11 shows that the drug loading amount is the highest when the mass ratio of CNTs to ASA is 1: 3.
This example uses absolute ethanol as solvent in supercritical CO2Loading the medicine on GO or CNTs under the condition of supercritical CO2When the carried medicine contacts with GO or CNTs, the GO or CNTs lamellar structure contains carbonyl, hydroxyl, epoxy and other groupsThe clusters and carboxyl groups or ester groups in the medicine form hydrogen bond action, and hydrogen bond combination can also occur among medicine molecules, so that loading is realized, and the medicine loading capacity is improved; supercritical CO of this example2Can completely separate the drug and the carrier without solvent residue, and can avoid the pollution or separation problem of the solvent used for loading the drug by the conventional method, CO2Not only provides an inert environment for the load, but also can be recycled, and saves energy and resources.
Comparative example 5: physical method CNTs loaded aspirin: weighing 10mg of Carbon Nanotubes (CNTs), placing the CNTs in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain a CNTs ethanol dispersion liquid; adding the weighed ASA into the CNTs ethanol dispersion, carrying out ultrasonic treatment for 2min to fully dissolve the ASA to obtain mixed dispersion, stirring the mixed dispersion, filtering the stirred mixed dispersion by a microporous filter membrane, and drying the obtained filter cake for 24h at room temperature to obtain a physical drug-loaded product. The temperature of the mixed dispersion liquid is 35 ℃ respectively when the mixed dispersion liquid is stirred, and the stirring time is 60 min; the addition amounts of aspirin were 10mg, 20mg, 30mg, and 40mg, respectively. Fig. 12 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different material proportioning conditions in comparative example 5, and fig. 12 shows that the drug loading rate is the highest when the mass ratio of CNTs to ASA is 1: 4.
Comparative example 6: the present embodiment differs from comparative example 5 in that: the stirring time is 30min, 60min, 90min and 120min respectively. Fig. 13 is a graph of ASA drug loading rate corresponding to the physical drug loading method under different drug loading time conditions in comparative example 6, and fig. 13 shows that the drug loading rate is the highest when the loading time is 120 min.
Comparative example 7: the present embodiment differs from comparative example 5 in that: respectively carrying the medicine at 35 deg.C, 40 deg.C, 45 deg.C and 50 deg.C under stirring for 60min, filtering the dispersion with microporous membrane, and drying the filter cake for 24 hr to obtain the product. Fig. 14 is a graph of ASA drug loading amount corresponding to the physical drug loading method under different drug loading temperature conditions in comparative example 7, and fig. 14 shows that the drug loading amount is the highest when the loading temperature is 40 ℃.
Example 10: in this embodiment, the method for loading aspirin by using CNTs as a carrier in a supercritical carbon dioxide extraction apparatus is performed according to the following steps:
the method comprises the following steps: weighing 10mg of CNTs, and placing the weighed CNTs in an extraction tank of a supercritical extraction device;
step two: weighing 30mg of ASA, dissolving the weighed ASA in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device; the volume ratio of the mass of the ASA to the absolute ethyl alcohol is 1mg:4 mL;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing CNTs by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 24 hours to finish the process; adjusting the pressure of the extraction tank to 20 MPa; the temperature of the extraction tank is adjusted to 45 ℃; the time for loading the drug is 80 min.
The drug loading on CNTs of example 10 was 0.111 mg/mg.
Comparative example 8: the physical method utilizes CNTs to load aspirin: weighing 10mg of Carbon Nanotubes (CNTs), placing the CNTs in 30mL of absolute ethanol, and performing ultrasonic dispersion for 40min to obtain a CNTs ethanol dispersion liquid. 40mg of ASA is added into the ethanol dispersion of CNTs, and ultrasonic treatment is carried out for 2min to ensure that the ASA is fully dissolved. Stirring and loading for 2h at the temperature of 40 ℃, filtering the dispersion liquid through a microporous filter membrane, and drying a filter cake for 24h to obtain a physical drug-loaded product.
Comparative example 8 the drug loading on the CNTs was 0.048 mg/mg. The drug loading of CNTs in example 10 is 2.3 times that of the drug loading of the physical method in comparative example 8.
Claims (5)
1. A method for carrying out drug loading by using GO or CNTs as a carrier by adopting a supercritical carbon dioxide extraction device is characterized by comprising the following steps: the method comprises the following steps:
the method comprises the following steps: weighing a carrier, and placing the weighed carrier in an extraction tank of a supercritical extraction device;
step two: weighing the medicines, dissolving the weighed medicines in absolute ethyl alcohol to obtain a mixed solution, and transferring the mixed solution into an entrainer tank of a supercritical extraction device;
step three: conveying the mixed solution in the entrainer tank into an extraction tank containing a carrier by using a conveying pump, adjusting the pressure and the temperature of the extraction tank, carrying out drug loading to obtain a drug-loaded product, and drying the obtained drug-loaded product at room temperature for 22-26 h to complete the process;
wherein, the medicine in the second step is aspirin, paclitaxel or adriamycin.
2. The method for carrying out drug loading by using GO or CNTs as carriers by adopting the supercritical carbon dioxide extraction device as claimed in claim 1, wherein: the mass ratio of the medicine to the carrier is (1-4) to 1.
3. The method for carrying out drug loading by using GO or CNTs as carriers by adopting the supercritical carbon dioxide extraction device as claimed in claim 1, wherein: and step three, adjusting the pressure of the extraction tank to 10-30 MPa.
4. The method for carrying out drug loading by using GO or CNTs as carriers by adopting the supercritical carbon dioxide extraction device as claimed in claim 1, wherein: and step three, adjusting the temperature of the extraction tank to 35-50 ℃.
5. The method for carrying out drug loading by using GO or CNTs as carriers by adopting the supercritical carbon dioxide extraction device as claimed in claim 1, wherein: and step three, the time for loading the medicine is 0.25-2 h.
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