KR101494641B1 - Manufacturing method of cellulose aerogel membrane - Google Patents

Abstract

The present invention relates to a method for manufacturing a cellulose-based aerogel membrane which comprises the steps of: mixing lithium hydroxide (LiOH), urea, and cellulose with a first solvent; obtaining a transparent solution in which cellulose is peptized by cooling and thawing the mixed product; coating a substrate with the transparent solution with the targeted thickness, soaking in a second solvent, and solidifying; cleaning the solidified product; and obtaining a cellulose-based aerogel membrane by super critically drying or freeze-drying the cleaned product. The cellulose-based aerogel membrane manufactured according to the present invention has flexibility and performs as a drug delivery system with a drug material loaded on it.

Description

[0001] The present invention relates to a manufacturing method of cellulose aerogel membrane,

The present invention relates to a method for producing an aerogel membrane, and more particularly, to a method for producing a cellulose-based aerogel membrane having flexibility and being loaded with a drug and acting as a drug delivery system using cellulose.

Airgel is a new material that has been attracting attention as a heat insulation material and a soundproofing material of dream because of strong heat, electricity, impact, but it is difficult to put into practical use due to its difficult construction workability and easy disintegration. However, in March 2003, Aspen Aerogel succeeded in commercialization for the first time in the world, and it has been used in various fields such as wintering and space suits by developing new aerogel technology that can be easily broken and can be mass-produced in a short time. Companies are focusing on aerogels.

In addition, the drug delivery system technology that improves the drug delivery system to enhance the drug efficacy has attracted attention of the medical community. In the US and Japan, since the late 1980s, companies such as pharmaceutical companies have focused on the development of drug delivery systems along with the development of new drug delivery technologies, in combination with nanotechnology. Korea has also achieved comprehensive achievements in the development of drug delivery system technology while establishing comprehensive research systems such as pharmaceutical companies, academia and research institutes in order to advance into the global market and create pharmaceutical fields. Generally, medicines are used to treat diseases or damaged parts of the human body. Drug delivery systems are being used for maximizing the therapeutic effect and minimizing the side effects of the human body. Drug delivery systems are commonly referred to as simple formulations of medicines and formulations with high functionality. They are applied to patients through various routes of the body including oral, injection, transdermal, mucosal, and transplant. Drugs are shown to have a therapeutic effect by binding to receptors distributed in disease sites. The ideal method of administration is that the drug appears immediately upon application of the drug, maintains a constant blood concentration during the treatment period, is immediately withdrawn from the body after the drug is discontinued at the end of treatment. Therefore, new drug delivery methods have been actively studied for improving the bioavailability of the administered drug, improving the therapeutic effect, and increasing the adherence of the drug.

Korea Patent Registration No. 10-1064869

The object of the present invention is to provide a method for manufacturing a cellulose-based aerogel membrane, which is manufactured using cellulose and has flexibility and can be loaded with a drug to act as a drug delivery system.

(A) mixing lithium hydroxide (LiOH), urea, and cellulose in a first solvent, (b) thawing the resultant after mixing to obtain a clear solution in which the cellulose has been degraded, (C) coating the transparent solution to a desired thickness on a substrate and immersing the second solution in a second solvent; (d) washing the coagulated product; and (e) washing the washed product with supercritical drying Or lyophilization to obtain a cellulosic aerogel membrane. The present invention also provides a method for producing a cellulosic aerogel membrane.

The lithium hydroxide (LiOH) is mixed in an amount of 0.1 to 20 parts by weight with respect to 100 parts by weight of the first solvent, and the urea is mixed with 1 to 35 parts by weight with respect to 100 parts by weight of the first solvent.

The cellulose is preferably mixed with 0.1 to 20 parts by weight per 100 parts by weight of the total content of the lithium hydroxide (LiOH), the urea and the first solvent.

The first solvent may be distilled water, and the second solvent may be methanol.

The method of manufacturing the cellulosic aerogel membrane may further include removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature before the step (c).

The method may further include, after step (e), immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulose-based aerogel membrane loaded with the drug. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

The method may further include, after the step (e), immersing the cellulosic aerogel membrane in a polyurethane solution to obtain a cellulose-based aerogel membrane having a polyurethane complexed with the cellulosic aerogel membrane. The polyurethane solution may be a solution in which polyurethane is dissolved in a solvent in which N, N-dimethylformamide and tetrahydrofuran are mixed in a volume ratio of 1: 0.1 to 10, and the polyurethane is added to the polyurethane solution It is preferably contained in an amount of 0.1 to 30 parts by weight based on 100 parts by weight of the mixed solvent of N, N-dimethylformamide and tetrahydrofuran. The polyurethane solution may comprise a drug solution. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

The method may further include, after the step (e), immersing the cellulose-based aerogel membrane in a silicon solution to obtain a cellulose-based aerogel membrane in which silicone is complexed with the cellulosic aerogel membrane. The silicone solution may comprise a drug solution. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

(A) mixing calcium thiocyanate tetrahydrate and cellulose in a first solvent; (b) heating the resultant mixture to obtain a clear solution in which the cellulose has been degraded; and (c) (D) washing the coagulated product, and (e) drying the washed product by supercritical drying with carbon dioxide or lyophilization Thereby obtaining a cellulose-based aerogel membrane. The present invention also provides a method for producing a cellulosic aerogel membrane.

The calcium thiocyanate tetrahydrate is preferably mixed in an amount of 10 to 200 parts by weight based on 100 parts by weight of the first solvent.

Preferably, the cellulose is mixed with the calcium thiocyanate tetrahydrate in an amount of 0.1 to 20 parts by weight based on 100 parts by weight of the total amount of the first solvent.

The first solvent may be distilled water, and the second solvent may be methanol.

The method of manufacturing the cellulosic aerogel membrane may further include removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature before the step (c).

The method may further include, after step (e), immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulose-based aerogel membrane loaded with the drug. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

The method may further include, after the step (e), immersing the cellulosic aerogel membrane in a polyurethane solution to obtain a cellulose-based aerogel membrane having a polyurethane complexed with the cellulosic aerogel membrane. The polyurethane solution may be a solution in which polyurethane is dissolved in a solvent in which N, N-dimethylformamide and tetrahydrofuran are mixed in a volume ratio of 1: 0.1 to 10, and the polyurethane is added to the polyurethane solution It is preferably contained in an amount of 0.1 to 30 parts by weight based on 100 parts by weight of the mixed solvent of N, N-dimethylformamide and tetrahydrofuran. The polyurethane solution may comprise a drug solution. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

The method may further include, after the step (e), immersing the cellulose-based aerogel membrane in a silicon solution to obtain a cellulose-based aerogel membrane in which silicone is complexed with the cellulosic aerogel membrane. The silicone solution may comprise a drug solution. The drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicyl sulphoxide.

According to the present invention, the cellulosic aerogel membrane produced by the present invention has flexibility and can be loaded with drugs to act as a drug delivery system.

Typical aerogel membranes are flexible but not elastic and easily tearable and wrinkled. Polyurethane and silicone are polymers that are water-soluble, moisture-resistant, and both flexible and resilient. Cellulosic aerogels, In the case of membranes, the properties of the membrane may not change even if immersed in buffer solution for a long time. In the case of a cellulosic aerogel membrane in which polyurethane or silicone is compounded, since the drug is contained not only between the pores of the airgel but also between the polymers, it can contain a large amount of drug and release over a long period of time. In the case of cellulosic aerogel membranes composed of polyurethane or silicone, it is possible to slowly release small amounts of drug contained in pores of the aerogels, and to release the drug in a sustained and sustained manner over a long period of time .

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a diagram showing the molecular structure of cellulose.
2 is a view schematically showing the supercritical drying process.
3 is a photograph showing a cellulose-based aerogel membrane prepared using LiOH according to an experimental example.
4 is a photograph showing a cellulose-based aerogel membrane prepared using calcium thiocyanate according to an experimental example.
5A is a scanning electron microscope (SEM) image of a LiOH cellulosic aerogel membrane (L-1) having a thickness of 20 μm, FIG. 5B is a scanning electron microscopic photograph of a LiOH cellulosic aeroge membrane (L-2) 5 is a scanning electron microscope (SEM) image of a LiOH cellulosic aerogel membrane (L-3) having a diameter of 90 mu m and a LiOH cellulosic aeroge membrane (L-3) having a diameter of 190 mu m.
6A is a scanning electron micrograph of a calcium thiocyanate cellulose-based aerogel membrane (C-1) having a thickness of 21 μm, and FIG. 6B is a scanning electron microscope photograph of a calcium thiocyanate cellulosic aerogel membrane (C-2) 6C is a scanning electron microscope (SEM) image of a calcium thiocyanate cellulose-based aerogel membrane (C-3) having a size of 260 μm and FIG. 6D is a scanning electron microscopic photograph of a calcium thiocyanate cellulose- It is a scanning electron microscope photograph.
7 is a graph showing adsorption (a) and desorption (b) curves of the nitrogen gas of the LiOH cellulose-based aerogel membrane prepared according to the experimental example.
8 is a graph showing adsorption (a) and desorption (b) curves of nitrogen gas of a calcium thiocyanate cellulose-based aerogel membrane prepared according to Experimental Example.
9A to 9C show a composite membrane (LDD) composed of LiOH cellulose-based aerogel membrane (LD), a composite membrane (LPD) composed of a composite of polyurethane and LiOH cellulosic aerogel membrane (LD) and a LiOH cellulosic aerogel membrane (LSD). ≪ / RTI >
FIGS. 10A to 10C are cross-sectional views of a composite membrane (CPD) composed of a calcium thiocyanate cellulose-based airgel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD) complexed with polyurethane, a calcium thiocyanate cellulosic aerogel membrane CD) with a silicon composite membrane (CSD).
11A and 11B show a composite membrane (LD) composed of a LiOH cellulosic airgel membrane (LD), a composite membrane (LPD) complexed with a polyurethane to a LiOH cellulose-based aerogel membrane (LD) and a LiOH cellulosic aerogel membrane (LSD). ≪ / RTI >
12A and 12B show a composite membrane (LD) composed of a LiOH cellulosic airgel membrane (LD), a composite membrane (LPD) complexed with a polyurethane to a LiOH cellulosic aerogel membrane (LD) Lt; / RTI > is a graph showing the drug elution rate of LSD.
FIGS. 13A and 13B are graphs showing the results of measurement of a calcium thiocyanate cellulose-based aerogel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD), a polyurethane composite membrane (CPD) and a calcium thiocyanate cellulose- CD) of the complex membrane (CSD) complexed with silicon.
FIGS. 14A and 14B are graphs showing the results of measurement of a calcium thiocyanate cellulosic aerogel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD), a polyurethane composite membrane (CPD) and a calcium thiocyanate cellulose- CD) of the composite membrane (CSD) complexed with silicone.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, it should be understood that the following embodiments are provided so that those skilled in the art will be able to fully understand the present invention, and that various modifications may be made without departing from the scope of the present invention. It is not.

Hereinafter, the term " nano " refers to a size in nanometers (nm), which means a size of 1 to 1,000 nm.

According to the definition of IUPAC (International Union of Pure and Applied Chemistry), the pore size of the porous body is divided into three types according to the pore diameter of the porous material. The micropore has a pore diameter of 2 nm or less, the mesopore has a pore diameter And macropores of 50 nm or more are defined. Hereinafter, the term "nano pores" means micro pores, mesopores and macropores, and means pores having a pore diameter of 1 to 1,000 nm.

In the following, silicon means silicon, which is an organic compound containing silicon.

In the present invention, a flexible airgel membrane is produced by using cellulose, which is cellulose, and a method of composing the airgel membrane with a polymer in order to secure disadvantages of weak airgel is proposed.

The aerogels are composed of colloidal particles or fibrous particles formed by forming a network three-dimensionally and have nano pores (for example, pores having a diameter of about 10 nm) of about 95% Can be used as a mediator. Cellulosic aerogels are porous materials that are harmless to the human body and can be used as a good biomaterial to deliver drugs.

Cellulosic aerogel membranes are nanoporous, lightweight and have a low density.

In the experimental example of the present invention, the drug release rate can be controlled by using a nanoporous membrane using cellulose or a composite membrane prepared by compounding polyurethane or silicone as a polymer in a nanoporous membrane using cellulose And analyzing the amount and time of drug release using High Performance Liquid Chromatography (hereinafter referred to as 'HPLC').

Dietary fiber is a major nutrient in herbivorous animals, but has been considered non-nutrient in humans. It has also been noted that it plays an important role as an energy source for intestinal fermentation, and various lifestyle diseases are induced by the lack of dietary fiber. Dietary fiber is divided into water-soluble dietary fiber and insoluble dietary fiber. Water-soluble dietary fiber is related to metabolic diabetes and hypertension. Insoluble dietary fiber is related to digestive diseases such as constipation, colon cancer and gastric ulcer.

Cellulose is insoluble dietary fiber, either cellulose or fiber. Β-1,4-D-glucan distributed in most plants, bacteria and animals. The fiber that constitutes the cell wall of the higher plant is the main component of cellulose, but it becomes the skeleton of the plant together with lignin and hemicellulose. Cellulase is an enzyme that hydrolyzes cellulose. It is present in bacteria, plant tissues, snail digests, etc., and is not present in human digestive juices. Therefore, cellulose is an indigestible insoluble fiber.

The molecular formula of cellulose is represented by (C ₆ H ₁₀ O ₅ ) _n , and the average polymerization degree is about 3000 to 10,000 in a natural state. As shown in FIG. 1, the chemical structure of D-glucose is largely polymerized with? -1,4 linkages and connected in a chain. Since it is a white solid without odor and is insoluble in water, LiOH or calcium thiocyanate is used as a peptizer in the experimental examples of the present invention. Cellulose which is insoluble in 17 to 18% NaOH solution by chemical properties and? -Cellulose which is precipitated by acid among soluble ones is called? -Cellulose, and the part which is not precipitated by acid is called? -Cellulose. Many molecules are gathered to form fibers. The smallest unit is called micelles. Some of these molecules form a regularly stable crystal structure, and micelles and micelles are irregularly amorphous regions.

Cellulose is contained in higher plants, bacterium, jackal shells, mucus of shellfish, extracellular secretions of acetic acid bacteria, and the like. As such, cellulose is an industrially important resource with a large amount of organic compounds present in the natural world.

Cellulose is widely used as paper and textile fibers in the paper industry. It is also developed as a processed food as a functional dietary fiber such as a formal action by stimulating the intestine without being digested or absorbed in a person's field. It is also used as a food stabilizer such as ice cream or jam or as an expandable laxative. In addition, cellulose derivatives are used in various applications such as adhesives, films, explosives, and plastics.

Aerogels are a mixture of 'aero' for air and 'gel' for solidified liquids. Aerogels are the lightest and lowest density nano-pore solids in solids. And dried with supercritical fluid in the state of a wet gel containing a solvent to remove the solvent without deforming the structure to produce an airgel. In the case of silica airgel, silica nanoparticles are three-dimensionally connected in methanol to form a gel. In order to strengthen the three-dimensional network of the solid particles in a gel state, aging is performed in a solvent, If the pores are removed without destroying them by supercritical or solvent substitution and surface modification, aerogels having nano pores generally occupying 95% or more can be formed. Nanopores are structures that resist heat flow by holding air molecules, and long molecular chains reduce heat conduction.

Aerogels are new materials that can be used for future insulation, soundproofing, etc. because they are strong against heat, electricity, shock and so on. The airgel is a material made of silicon oxide and has a structure in which a silicon oxide thread having a thickness of 1/100 of hair is extremely shiny. Air molecules are present between the yarn and yarn chambers, and air accounts for 98% of the total volume. Aerogels have high insulation and environmental friendliness and can be used in various fields. In addition to clothing for aerospace use, it can be used as a catalyst or adsorbent due to its wide surface area in the fields of home appliances, refractories, shipbuilding, liquefied natural gas, gas storage, chemical, environment and energy. , The weight of the fighter can be reduced, and it can be used as a shockproof film that has no impact on torpedoes.

A supercritical egg is a state in which the number of neutrons generated by nuclear fission in the reactor exceeds the critical number of neutrons that are absorbed and fission. At normal temperature and pressure, gas and liquid substances are called critical points. When the temperature exceeds a certain high temperature and high pressure limit, the state in which vaporization does not occur and gas and liquid can not be distinguished is called critical state. Supercritical fluid (SCF). The critical temperature is called the critical temperature (Tc) and the pressure is called the critical pressure (Pc). Supercritical fluids are characterized by large changes in density of molecules, density of molecules close to the liquid, but low viscosity, close to the gas. In addition, since the thermal conductivity is as high as that of water due to its rapid diffusion, it is very easy to perform a chemical reaction, and when used as a solvent, the solvent concentration around the solute becomes extremely high. Ideal supercritical fluids should be chemically stable and non-corrosive to the apparatus, with critical temperatures near room temperature or near extraction temperature, low interstitial pressure, high solubility and no toxicity to the human body. Critical points of the supercritical fluid solvent are shown in Table 1. Among the supercritical fluids, in the experimental example of the present invention, a cellulose-based aerogel membrane was prepared using CO ₂ having a critical temperature of 31.1 ° C and a critical pressure of 72.8atm.

menstruum Critical temperature
(° C) Critical pressure
(ATM) density
(g / cm3) Molecular Weight
(g / mol) carbon dioxide 31.1 73.8 0.469 44.01 water 373.1 220.5 0.348 18.02 methane -87.75 46 0.162 16.04 ethane 32.4 48.8 0.203 30.07 Propane 96.8 42.5 0.217 44.09 Ethylene 9.4 50.4 0.215 28.05 Propylene 91.75 46 0.232 42.08 Methanol 239.45 80.9 0.272 32.04 ethanol 240.95 61.4 0.276 46.07 Acetone 235.1 47.0 0.278 58.08

Freeze drying and supercritical drying can be used to remove the solvent without breaking the pore structure. The supercritical drying is a method of drying the solvent used in the preparation of the gel under supercritical conditions above the critical temperature and the critical pressure of the solvent. In the supercritical state, the liquid phase and the vapor phase The density is reduced. The gel dried in this way is called an airgel, and the airgel has a very low density and a high porosity.

In the experimental example of the present invention, as shown in FIG. 2, a prepared sample is placed in a high-pressure reactor to obtain an aerogel membrane, liquid carbon dioxide is injected into the reactor to replace the internal solvent with carbon dioxide, , The temperature of the reactor is raised to set the carbon dioxide to a supercritical state, the pressure of the reactor is gradually lowered to remove the carbon dioxide, and then the carbon dioxide is removed and the temperature is lowered and dried.

On the other hand, a urethane bond is formed when an alcohol having an active hydroxyl group and an isocyanate having an isocyanate group generate reaction heat by an addition polymerization reaction. Polyurethane refers to a polymer substance containing a urethane bond formed by using polyol and isocyanate as main materials. It is produced by the reaction of a polyisocyanate (-NCO) with a polyol (-OH). Here, polyol refers to a compound having active hydrogens such as -OH and -NH _{2 in the} molecule, and initially polyester polyol was mainly used. However, due to development of petrochemical industry, propylene oxide (PO), ethylene oxide Oxide (EO) has been mass-produced and supplied, more than 90% of polyester polyols are currently used. Urethane bond was shown in Reaction Formula 1 below, and polyurethane formation reaction was shown in Reaction Formula 2. In order to obtain an industrially useful polyurethane, many kinds of raw materials and additives are used in addition to the main polyisocyanate and polyol to form urethane.

[Reaction Scheme 1]

[Reaction Scheme 2]

Due to its excellent properties, polyurethane is used in various applications to manufacture products that can be always encountered in our daily lives such as shoes, sofas, beds, cars, refrigerators, building materials, flooring,

Drug delivery system is defined as technology to optimize drug treatment by designing dosage form to efficiently deliver the necessary amount of drug to minimize the side effect of existing drug and maximize efficacy for treatment of body disease . The blood concentration is the most important factor for manifesting the therapeutic effect, and it is a field to design formulations for drug delivery such as tablets, capsules, injections, patches, mucosal agents, inhalants, Core technologies include drug release rate control techniques, poorly soluble drug solubilization techniques, nanoparticle carrier technology, targeting technology, peptide and protein drug delivery technology, and gene delivery technology. The action of the administered drug should first be such that the drug can maintain a reasonable amount of concentration in our body, and second, since our body is an automatic system of stimulus-response that only reacts when necessary, do. Finally, drugs should only be delivered to the affected tissues or cells to minimize side effects.

Drug delivery systems are divided into a sustained drug release system, a controlled release system, and a targeted drug delivery system. The sustained drug release system is a formulation designed to reduce the bioavailability by slowing the release rate of the drug or to reduce the problems of drug absorption too slowly or too quickly in vitro and the controlled release system controls the concentration of the target site The actual treatment effect is controlled. Targeted drug delivery systems are formulations developed to selectively deliver the drug to the site of need and then maintain the required concentration for the required period of time. It is possible to suppress the distribution to unnecessary parts and to reduce side effects. Targeted drug-carrier complexes should be delivered in a stable form to the target site containing sufficient quantities of drug, and the drug should be released according to the planned rate pattern after reaching the target site. After administration, they must selectively reach the target site and accumulate. The carrier should be biodegradable or at least not bioaccumulative, antigenic and toxic. Drug carriers include molecular carriers, microporous carriers, carriers using biological cognition, and external inductive carriers (magnetic carriers, external release controlled carriers).

(A) mixing lithium hydroxide (LiOH), urea, and cellulose in a first solvent; and (b) mixing the resultant mixture with a solution of the lithium hydroxide (C) coating the transparent solution on the substrate to a desired thickness and solidifying it in a second solvent; and (d) cleaning the coagulated product And (e) supercritically drying or lyophilizing the washed product with carbon dioxide to obtain a cellulosic aerogel membrane.

The lithium hydroxide (LiOH) is mixed in an amount of 0.1 to 20 parts by weight with respect to 100 parts by weight of the first solvent, and the urea is mixed with 1 to 35 parts by weight with respect to 100 parts by weight of the first solvent.

The cellulose is preferably mixed with 0.1 to 20 parts by weight per 100 parts by weight of the total content of the lithium hydroxide (LiOH), the urea and the first solvent.

The first solvent may be distilled water, and the second solvent may be methanol.

The method of manufacturing the cellulosic aerogel membrane may further include removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature before the step (c).

The method may further include, after step (e), immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulose-based aerogel membrane loaded with the drug. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm.

The method may further include, after the step (e), immersing the cellulosic aerogel membrane in a polyurethane solution to obtain a cellulose-based aerogel membrane having a polyurethane complexed with the cellulosic aerogel membrane. The polyurethane solution may be a solution in which polyurethane is dissolved in a solvent in which N, N-dimethylformamide and tetrahydrofuran are mixed in a volume ratio of 1: 0.1 to 10, and the polyurethane is added to the polyurethane solution It is preferably contained in an amount of 0.1 to 30 parts by weight based on 100 parts by weight of the mixed solvent of N, N-dimethylformamide and tetrahydrofuran. The polyurethane solution may comprise a drug solution. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm. The content of the drug solution may be set in accordance with the intended use and the desired release time, and the drug solution may be contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the polyurethane solution.

The method may further include, after the step (e), immersing the cellulose-based aerogel membrane in a silicon solution to obtain a cellulose-based aerogel membrane in which silicone is complexed with the cellulosic aerogel membrane. The silicon solution may be a solution containing silicon and xylene, and the silicon and the xylene may be mixed in a volume ratio of 1: 0.1 to 20. The silicone solution may comprise a drug solution. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm. The content of the drug solution may be set in accordance with the intended use and the desired release time. For example, the drug solution may be contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the silicone solution.

The cellulosic aerogel membrane is preferably formed to a thickness of 5 to 300 mu m.

A method for preparing a cellulose-based aerogel membrane according to another preferred embodiment of the present invention comprises the steps of: (a) mixing calcium thiocyanate tetrahydrate and cellulose in a first solvent; and (b) (C) coating the transparent solution to a desired thickness on the substrate and solidifying it in a second solvent; (d) cleaning the coagulated product; and (e) And subjecting the resultant to supercritical drying with carbon dioxide or lyophilization to obtain a cellulose-based aerogel membrane.

The calcium thiocyanate tetrahydrate is preferably mixed in an amount of 10 to 200 parts by weight based on 100 parts by weight of the first solvent.

Preferably, the cellulose is mixed with the calcium thiocyanate tetrahydrate in an amount of 0.1 to 20 parts by weight based on 100 parts by weight of the total amount of the first solvent.

The first solvent may be distilled water, and the second solvent may be methanol.

The method of manufacturing the cellulosic aerogel membrane may further include removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature before the step (c).

The method may further include, after step (e), immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulose-based aerogel membrane loaded with the drug. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm.

The method may further include, after the step (e), immersing the cellulosic aerogel membrane in a polyurethane solution to obtain a cellulose-based aerogel membrane having a polyurethane complexed with the cellulosic aerogel membrane. The polyurethane solution may be a solution in which polyurethane is dissolved in a solvent in which N, N-dimethylformamide and tetrahydrofuran are mixed in a volume ratio of 1: 0.1 to 10, and the polyurethane is added to the polyurethane solution It is preferably contained in an amount of 0.1 to 30 parts by weight based on 100 parts by weight of the mixed solvent of N, N-dimethylformamide and tetrahydrofuran. The polyurethane solution may comprise a drug solution. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm. The content of the drug solution may be set in accordance with the intended use and the desired release time, and the drug solution may be contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the polyurethane solution.

The method may further include, after the step (e), immersing the cellulose-based aerogel membrane in a silicon solution to obtain a cellulose-based aerogel membrane in which silicon is complexed with the cellulosic aerogel membrane. The silicon solution may be a solution containing silicon and xylene, and the silicon and the xylene may be mixed in a volume ratio of 1: 0.1 to 20. The silicone solution may comprise a drug solution. The drug solution is set for the intended use of the drug, for example, the drug solution may be an anticancer drug solution in which docetaxel is dissolved in dimethicylsoxide. The docetaxel may be contained in the drug solution at a concentration of 0.1 to 100,000 ppm. The content of the drug solution may be set in accordance with the intended use and the desired release time, and the drug solution may be contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the silicone solution.

The cellulosic aerogel membrane is preferably formed to a thickness of 5 to 300 mu m.

Hereinafter, experimental examples according to the present invention will be specifically shown, and the present invention is not limited by the following experimental examples.

1. Manufacture of cellulosic aerogel membrane

(1) Preparation of cellulose-based aerogel membrane using LiOH

The preparation of the cellulose-based aerogel membrane using LiOH proceeded as follows.

Lithium hydroxide (LiOH), sigma aldrich and urea (sigma aldrich) were dissolved in distilled water and cellulose powder (CF11-whatman International Ltd.) was mixed. Cellular powder (CF11-whatman International Ltd.) was mixed with lithium hydroxide (LiOH), urea and distilled water at a weight ratio of 4.6: 15: 80.4, and the total content of lithium hydroxide (LiOH) 0.5 part by weight to 7 parts by weight. The solution thus prepared was frozen and thawed, where the opaque solution became clear, which meant that the cellulose had been peeled off.

The cellulosic mixture thus obtained was centrifuged to remove bubbles. The centrifugation was carried out at -500C for 15 minutes at 5000 rpm.

The cellulosic aerogels solution from which the foam was removed was bar-coated on a glass plate to prepare a membrane, and the mixture was immersed in a bath (20 ° C) containing methanol for 2 hours to solidify the mixture. Residual chemical reagents from the coagulated cellulose membrane were removed using distilled water.

Supercritical drying with supercritical carbon dioxide was performed to remove the methanol and replace with carbon dioxide. After maintaining the temperature at 10 ° C at 5.3 MPa for 6 hours, the cellulosic aerogel membrane was prepared by drying at 40 ° C and 10 MPa for 30 minutes.

A cellulose-based aerogel membrane (hereinafter referred to as " LiOH cellulose-based aerogel membrane ") prepared using LiOH is shown in Fig. In FIG. 3, 'A' is a cellulose-based aerogel membrane having a thickness of about 40 μm and 'B' is a cellulose-based aerogel membrane having a thickness of about 70 μm.

(2) Production of cellulosic aerogel membrane using calcium thiocyanate

Preparation of a cellulose-based aerogel membrane using calcium thiocyanate proceeded as follows.

Calcium thiocyanate tetrahydrate (Sigma Aldrich) was dissolved in distilled water, and then cellulose powder (CF11-whatman International Ltd.) was mixed. The distilled water and the calcium thiocyanate tetrahydrate were mixed at a weight ratio of 41:59, and the cellulose powder (CF11-whatman International Ltd.) was mixed with 100 parts by weight of distilled water and calcium thiocyanate tetrahydrate in an amount of 0.5 to 7 Were mixed. The solution thus prepared was peeled by heating in an oil bath at a temperature of 120 to 140 占 폚 and maintained at this temperature for 10 to 20 minutes to make the opaque solution transparent.

The cellulosic aerogel solution thus obtained was bar-coated on a glass plate to form a membrane. The temperature of the solution was maintained at 80 ° C. or higher to prevent the solution from solidifying. The solution was immersed in a methanol bath (20 ° C.) for 1 hour to solidify the mixture.

The remaining chemicals (chemical reagents) were removed using distilled water, followed by supercritical drying (CO ₂ supercritical drying) with carbon dioxide. The methanol was removed and replaced with carbon dioxide. The mixture was then heated at 10 ° C. and 7.0 MPa for 7 hours and 30 minutes Followed by heating to 40 캜 and drying to complete a cellulose-based aerogel membrane.

FIG. 4 shows a cellulose-based aerogel membrane (hereinafter referred to as a calcium thiocyanate cellulose-based aerogel membrane) prepared using calcium thiocyanate.

2. Manufacture of Cellulose-based Aerogel Composite Membrane Complexed with Polymer

(1) Production of cellulosic aerogel composite membrane using polyurethane

The preparation of a cellulose-based airgel composite membrane using polyurethane proceeded as follows.

A LiOH cellulosic aerogel membrane and a calcium thiocyanate cellulosic aerogel membrane were each dip-coated on a polyurethane solution to prepare a cellulose-based airgel composite membrane. (N, N-dimethylformamide, DMF, sigma aldrich) and tetrahydrofuran (THF, sigma aldrich) were used as the solvent of the polyurethane solution. The polymer (polyurethane) C 80A (ChronoFlex C 80A, advansource biomaterials). After mixing N, N-dimethylformamide (DMF) and tetrahydrofuran (THF) in a volume ratio of 1: 1, 10% by weight of ChronoFlex C 80A (Advansource biomaterials) (total content of DMF and THF 90% by weight and Chronoflex C 80A 10% by weight). The melting time of the polymer depends on the temperature, which takes about 2 days at room temperature, about 10 hours at 100 ° C, and about 2 hours at 200 ° C.

(2) Manufacture of cellulose-based airgel composite membrane using silicone

Preparation of a cellulose-based airgel composite membrane using silicone, which is an organic compound containing silicon, proceeded as follows.

LiOH cellulosic aerogel membrane and calcium thiocyanate cellulose aerogel membrane were each dip-coated on a silicone solution to prepare a cellulose-based airgel composite membrane. The silicone solution was a mixture of MED-6640 (nusil) Part A and Part B. Part A and Part B were mixed at a volume ratio of 1: 1 for 2 hours, and then the viscosity was lowered by adding xylene (sigma aldrich) to the mixture. The silicon solution mixed with Part A and Part B and xylene were mixed in a volume ratio of 1: 2.

3. Drug injection and release method

(1) Drug loading method

The drug injection method was carried out differently in a composite membrane composed of a cellulose-based aerogel membrane and a polymer. In the case of a cellulose-based aerogel membrane, a cellulose-based aerogel membrane prepared by immersing the cellulosic aerogel membrane in a drug solution was injected to inject a drug. In the composite membrane having a polymer composite, drug was injected into the polyurethane solution and the silicone solution before the dip- . The drug was docetaxel (D-1000, LC Lab.), Which is mainly used for the treatment of breast, ovarian, prostate, etc. Since docetaxel has a strong lipophilic property and is almost insoluble in water, it is dissolved in dimethyl sulfoxide (DMSO, Sigma aldrich) when the drug is injected into the cellulosic aerogel membrane, and a drug having a concentration of 5000 ppm To obtain the solution, 50 mg of docetaxel was dissolved in 10 ml of dimethylsulfoxide. In the case of composite membranes with complex polymers, the drug was dissolved at the same concentration in the polyurethane solution and the silicon solution itself.

(2) Standard drug preparation method

A standard solution was made to compare the solution released from the prepared membrane and to determine the peak of the drug on HPLC. Standard solutions were made to be loaded with 50 ppm and 25 ppm, respectively, in buffer (PBS, Sigma aldrich). Since docetaxel does not dissolve in PBS (phosphate buffer solution), it dissolves 0.001 g in 0.5 ml of dimethlysulfoxide, and 19.5 ml of PBS is prepared. 1 ml of 25 ppm is taken from 50 ppm solution and 1 ml of buffer solution is prepared .

(3) Drug release method

Drug release is an experiment that can confirm how much drug is released in a drug-injected membrane for a given time.

10 ml of a buffer solution having a pH of 7.2 was added to the vial, and the drug-injected membrane was immersed and placed in a shaker. At this time, the condition was set at 36.5 ± 5 ° C, which is the same temperature as the body (body), and set at 100 rpm. The measurement time (10 to 120 minutes, 3 to 20 hours, 2 to 90 days / total about 90 days) was measured at intervals of 10 minutes between the first 10 and 120 minutes and every hour between 3 and 20 hours, Between 2 and 90 days were measured every day.

After the drug release measurement was completed, 10 ml of the release solution was all taken, transferred to another vial, and stored frozen. For each of the other effluent samples, 10 mL of buffered solution and buffer were injected into a new vial and placed in a shaker to measure drug release.

These freeze-thawed vials were then measured and compared with the standard sample using HPLC to determine the calculated drug loading and actual drug release.

4. Physical properties of cellulosic aerogel membranes

(1) Physical properties of LiOH cellulosic aerogel membrane

The LiOH cellulosic aerogel membrane had a thickness of 35 to 190 탆, a density of 0.1 to 0.6 g / cm ³ and a porosity of 60 to 80% when supercritical drying was performed. L-1 had a thickness of 20 탆 and L- , L-3 is 90 μm, and L-4 is 190 μm. Table 2 shows the density according to the thickness. FIGS. 5A to 5D show scanning electron microscope (SEM) photographs according to the comparison. 5A is a scanning electron microscope (SEM) image of a LiOH cellulosic aerogel membrane (L-1) having a thickness of 20 μm, FIG. 5B is a scanning electron microscopic photograph of a LiOH cellulosic aeroge membrane (L-2) 5 is a scanning electron microscope (SEM) image of a LiOH cellulosic aerogel membrane (L-3) having a diameter of 90 mu m and a LiOH cellulosic aeroge membrane (L-3) having a diameter of 190 mu m.

5A to 5D, it can be seen that as the thickness increases, the pores become denser and the density increases. The LiOH cellulosic aerogel membrane prepared according to the Experimental Example was flexible and transparent when the thickness was 40 탆 or less as shown in Fig. 3, and opaque when it was made 70 탆 or more.

Sample thickness
(mm) weight
(g) area
(cm ² ) volume
(cm ³ ) density
(g / cm ³⁾ L-1 0.020 0.0004 One 0.002 0.200 L-2 0.065 0.0020 One 0.007 0.308 L-3 0.090 0.0039 One 0.009 0.433 L-4 0.190 0.0123 One 0.019 0.647

The LiOH cellulosic aerogel membrane used for drug release had a thickness of 20 mu m, density of 0.2 g / cm < ³ > and porosity of 87%, and the amount of drug injected was 120.39 mu g, Figures 11A-12B show drug release results via HPLC.

(2) Physical properties of calcium thiocyanate cellulose-based aerogel membrane

In the case of the calcium thiocyanate cellulose-based aerogel membrane, the thickness was 33 to 470 탆, the density was 0.1 to 0.4 g / cm ³ and the porosity was 70 to 90%. The C-1 had a thickness of 21 탆, C-2 The density of C-3 is 260 μm, the density of C-4 is 470 μm, and the density of C-3 is 470 μm. Table 3 shows the density according to the thickness. FIGS. 6A to 6D show scanning electron microscope (SEM) 6A is a scanning electron micrograph of a calcium thiocyanate cellulose-based aerogel membrane (C-1) having a thickness of 21 μm, and FIG. 6B is a scanning electron microscope photograph of a calcium thiocyanate cellulosic aerogel membrane (C-2) 6C is a scanning electron microscope (SEM) image of a calcium thiocyanate cellulose-based aerogel membrane (C-3) having a size of 260 μm and FIG. 6D is a scanning electron microscopic photograph of a calcium thiocyanate cellulose- It is a scanning electron microscope photograph.

6A to 6D, it can be seen that as the thickness of the LiOH cellulose-based aerogel membrane becomes thicker, the pores become denser and the density increases. The calcium thiocyanate cellulose-based aerogel membrane prepared according to the Experimental Example was flexible and opaque regardless of its thickness as shown in Fig.

Sample thickness
(mm) weight
(g) area
(cm ² ) volume
(cm ³ ) density
(g / cm ³⁾ C-1 0.021 0.0004 One 0.0021 0.1905 C-2 0.090 0.0018 One 0.0090 0.2000 C-3 0.260 0.0053 One 0.0260 0.2038 C-4 0.470 0.0200 One 0.0470 0.4255

The calcium thiocyanate membrane used for drug release had a thickness of 21 탆, density of 0.2 g / cm ³ , porosity of 87%, loaded drug amount of 121.33 ㎍, and total drug release for one day. 13A to 14B show drug release results through HPLC.

(3) Specific surface area (BET) characteristic of cellulose-based aerogel membrane

The specific surface area was calculated by the following equation (1) at the P / Po = 0.05 to 0.995, and the sample was pretreated at 40 ° C for 24 hours.

[Equation 1]

V: adsorption amount

V _m : adsorption amount in mono-layer

C: constant

P: adsorbate equilibrium pressure

P _o : adsorbate saturation equilibrium vapor pressure (adosrbate saturated equilibrium vapor pressure)

The LiOH cellulosic aerogel membrane used for the measurement had a thickness of 20 탆, a density of 0.2 g / cm ³ , a porosity of 87.2%, a specific surface area of 324.797 m ² g ^-1 , (A) and desorption (b) curves of the gas.

The thickness of the calcium thiocyanate cellulose-based aerogel membrane was 21 탆, the density was 0.2 g / cm ³ , the porosity was 87.5%, and the specific surface area measured was 187.346 m ² g ^-1 . FIG. 8 is a graph showing adsorption (a) and desorption (b) curves of nitrogen gas of a calcium thiocyanate cellulose-based aerogel membrane.

5. Characteristics of polymer composite membranes

(1) Physical properties of LiOH polymer composite membrane

Composite membranes composed of polymers (polyurethane, silicone) in LiOH cellulosic aerogel membranes were more flexible and transparent than cellulose-based aerogels membranes weak in moisture.

The density measurement results are shown in Table 2. The LiOH cellulose-based aerogel membrane used for the composite membrane had a thickness of 20 탆, a density of 0.2 g / cm ³ and a porosity of 87%. In the case of a membrane composed of polyurethane, , The density was increased to 0.445 g / cm ³ , and the porosity was reduced to 57%. It was confirmed that the porosity was reduced and the density was increased because the pores were filled with the polymer.

The membrane complexed with silicon has a thickness of 38 μm and a density of 0.38 g / cm ³ and a porosity of 59%. It was confirmed that the porosity was reduced and the density was increased because the pores were filled with the polymer.

(2) Physical properties of calcium thiocyanate polymer composite membrane

Calcium thiocyanate Composite membranes composed of polymer (polyurethane, silicone) complexes on cellulosic aerogel membranes are more flexible, transparent and resistant to moisture than cellulose-based aerogel membranes. The calcium thiocyanate cellulosic aerogel membrane used in the composite membrane had a thickness of 21 탆, a density of 0.2 g / cm ³ and a porosity of 88%. In the case of a membrane composed of polyurethane, the thickness was 49 탆, the density was 0.438 g / cm ³ , and the porosity was reduced to 58%.

The membrane complexed with silicon had a thickness of 40 탆, a density of 0.37 g / cm ³ , and a porosity of 60%. It was confirmed that the porosity was reduced and the density was increased because the pores were filled with the polymer.

Deep-coating was used when the polymer was coated on a cellulosic aerogel membrane, and the coating condition was 0.5 mm / sec.

6. Morphological characteristics of cellulosic aerogels and composite membranes

Composite membranes composed of cellulosic aerogel membrane and polymer (polyurethane, silicone) were compared and confirmed by scanning electron microscope (SEM).

9A to 9C show a composite membrane (LDD) composed of LiOH cellulose-based aerogel membrane (LD), a composite membrane (LPD) composed of polyurethane mixed with LiOH cellulose-based aerogel membrane (LD) (LSD), which shows how pores are filled when polyurethane and silicon are combined.

FIGS. 10A to 10C are cross-sectional views of a composite membrane (CPD) composed of a calcium thiocyanate cellulose-based airgel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD) complexed with polyurethane, a calcium thiocyanate cellulosic aerogel membrane CD) with a silicon composite membrane (CSD).

Referring to FIGS. 9A to 10C, it is impossible to observe pores because the surface of the composite membrane is coated with a polymer (polyurethane or silicone), compared with a cellulosic aerogel membrane having a large number of pores, The porosity was measured, and the difference of the coated surface according to the kind of polymer can be confirmed by scanning electron microscope (SEM).

7. Drug Release Control Characteristics of Cellulosic Aerogels and Composite Membranes

The column used for the HPLC was YMC-pack ODS-A, which was 4.6 × 250 mm in size. The solvent was acetonitrile (Sigma aldrich) and water (Sigma aldrich) 4: 6 ratio, and flow rate was 1 ml / min. The detector was a UV detector with 210 nm, the most prominent of which was docetaxel, and the dose was 50.0 μL, since the amount of drug was very small.

The results of analysis of buffer solutions and standard solutions of 50ppm and 25ppm showed that the peaks of 50ppm and 25ppm were not detectable in the buffer solution, The solvent used for the release was a buffer solution. The buffer solution was detected at about 2.1 seconds, and the peak was detected at about 2.6 seconds for dimethicyl sulphoxide and about 6.6 seconds for drug.

(1) Control of Drug Release Characteristics of LiOH Cellulose-based Aerogels and Composite Membranes

The LiOH cellulosic aerogel membrane had a thickness of 20 탆, a density of 0.2 g / cm ³ and a porosity of 87%. The drug was loaded by immersing the LiOH cellulose-based aerogel membrane in dimethyl sulfoxide dissolved in the drug. The amount of loaded drug was 120.39 ㎍, and drug release was performed according to the designated drug release time, resulting in 2 hours of drug release and 63% of the total loaded drug was released.

For the composite membranes complexed with polyurethane, the thickness was increased to 51 μm, the density was 0.445 g / cm ³ , and the porosity was reduced to 57%. The polyurethane solution was loaded on the cellulosic aerogel membrane at 5000 ppm, and the amount of drug loaded was 657.14 μg. The drug release period lasted for a total of 85 days. After 60 days, a large amount of drug was released I did.

The composite membrane complexed with silicon had a thickness of 38 탆, a density of 0.38 g / cm ³ , and a porosity of 59%. As with the polyurethane, the silicone solution was coated with the drug, and the amount of loaded drug was 380.95 μg, and the amount of the drug was gradually released and released over 85 days compared with the other membranes.

11A and 11B show a composite membrane (LD) composed of a LiOH cellulosic airgel membrane (LD), a composite membrane (LPD) complexed with polyurethane to LiOH cellulose-based aerogel membrane (LD) and a LiOH cellulosic aerogel membrane (LSD). ≪ / RTI > 11A, the peak of the buffer solution, dimethysulfoxide, and docetaxel was confirmed. In FIG. 11B, the drug peak was amplified.

12A and 12B show the result of calculating the drug release amount and time. 12A and 12B show a composite membrane (LD) composed of a LiOH cellulosic airgel membrane (LD), a composite membrane (LPD) complexed with a polyurethane to a LiOH cellulosic aerogel membrane (LD) (■: LD, ●: LPD, ▲: LSD) showing the drug elution rate of the drug (LSD).

(2) Control of Drug Release Characteristics of Calcium Thiocyanate Cellulose-Based Aerogels and Composite Membranes

The calcium thiocyanate cellulosic aerogel membrane had a thickness of 21 탆, a density of 0.2 g / cm ³ , and a porosity of 88%. The calcium thiocyanate membrane was immersed in the drug-loaded dimethylsulfoxide solution to load the drug. The amount of loaded drug was 121.33 이. As a result of drug release according to the designated drug release time (10 minutes to 85 days), it became drug for 1 day and 65% of the total loaded drug was released .

For composite membranes complexed with polyurethane, the thickness was increased to 49 μm, the density was 0.438 g / cm ³ , and the porosity was reduced to 58%. Cellulosic aerogel membrane was coated on the polyurethane solution mixed with the drug. The amount of loaded drug was 619.05 g, and the drug was released for 85 days as a result of the drug release. However, no significant amount was released after 75 days, Thereafter, the drug was not released.

The composite membrane complexed with silicon had a thickness of 40 탆, a density of 0.37 g / cm ³ , and a porosity of 60%. The amount of loaded drug was 385.71 μg, and a small amount of drug was gradually released and released over 85 days compared with the cellulosic aerogel membrane or polyurethane composite membrane.

FIGS. 13A and 13B are graphs showing the results of measurement of a calcium thiocyanate cellulose-based aerogel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD), a polyurethane composite membrane (CPD) and a calcium thiocyanate cellulose- CD) of the complex membrane (CSD) complexed with silicon. 13A, the peak of the buffer solution, dimethysulfoxide, and docetaxel was confirmed, and in FIG. 13B, the drug peak was broadened.

14A and 14B show the results of calculating the drug release amount and time. FIGS. 14A and 14B are graphs showing the results of measurement of a calcium thiocyanate cellulosic aerogel membrane (CD), a calcium thiocyanate cellulose-based aerogel membrane (CD), a polyurethane composite membrane (CPD) and a calcium thiocyanate cellulose- (CD: ●: CPD, ■: CSD) showing the drug elution rate of the composite membrane (CSD) complexed with silicon in the presence of water.

In the experimental example of the present invention, the nanoporous cellulosic aerogel membrane with supercritical drying was prepared, and the amount and time of the drug release was determined by injecting the drug. In order to control the drug release time, the polymer (polyurethane, silicone) The composite membranes were fabricated and the changes of drug loading amount and time according to polymer type were investigated.

One of the important factors affecting drug release time is the complexing of suitable polymers to hygroscopic aerogel membranes. Aerogel membranes are flexible but not elastic and have the disadvantage of being easily torn and wrinkled. However, polyurethane and silicone are water-soluble and resistant to moisture, and both are flexible and resilient. Therefore, the characteristics of the membrane may not be changed even when immersed in a buffer solution for a long time.

As a drug used in the experimental example of the present invention, docetaxel was dissolved in a polymer solution because it was not soluble in water and complexed. DMF and THF were used as the polyurethane solvent, and xylene was used for the silicone solution. As a result, the drug was contained not only between the pores of the aerogels but also between the polymers, so that it could contain a large amount of the drug and released for a long time.

In order to achieve gradual release of the drug over a long period of time, the polymer must adequately fill the pores of the aerogels. In the case of silicon, it was confirmed that the drug contained in the pores of the airgel was slowly released in a small amount, while the polyurethane exhibited a porosity characteristic similar to that of silicone, but the drug had a sustained release characteristic It was confirmed that it emits a suitable amount for a long time. In the experimental example of the present invention, the thickness of all the membranes to be used in the drug release experiment was adjusted to 20 탆 in order to adjust the conditions constantly, but it is expected that the efficiency will be further improved by adjusting the thickness of the polymer in order to release the drug for a desired time.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, This is possible.

Claims (17)

delete Mixing calcium thiocyanate tetrahydrate and cellulose in a first solvent;
Heating the mixed resultant to obtain a transparent solution in which the cellulose is peptized;
Removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature;
Coating the transparent solution to a desired thickness on a substrate, immersing the second solution in a second solvent, and solidifying the second solution;
Cleaning the coagulated product;
Subjecting the washed resultant to supercritical drying with carbon dioxide or lyophilization to obtain a cellulose-based aerogel membrane;
Immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulosic aerogel membrane on which the drug is loaded; And
Immersing the cellulose-based aerogel membrane in a polyurethane solution containing a drug solution to obtain a cellulose-based aerogel membrane complexed with polyurethane,
The calcium thiocyanate tetrahydrate is mixed in an amount of 10 to 200 parts by weight based on 100 parts by weight of the first solvent,
The cellulose is mixed with the calcium thiocyanate tetrahydrate in an amount of 0.1 to 20 parts by weight based on 100 parts by weight of the total amount of the first solvent,
Wherein the drug solution is an anticancer drug solution in which docetaxel is dissolved in dimethylsulfoxide,
The polyurethane solution is a solution in which polyurethane is dissolved in a solvent in which N, N-dimethylformamide and tetrahydrofuran are mixed in a volume ratio of 1: 0.1 to 10,
The polyurethane is contained in the polyurethane solution in an amount of 0.1 to 30 parts by weight based on 100 parts by weight of the mixed solvent of N, N-dimethylformamide and tetrahydrofuran,
The drug solution is contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the polyurethane solution,
Wherein the cellulose-based aerogel membrane is formed to a thickness of 5 to 300 탆.
delete delete delete delete 3. The method of claim 2, wherein the first solvent is distilled water and the second solvent is methanol.
delete delete delete delete delete delete delete Mixing calcium thiocyanate tetrahydrate and cellulose in a first solvent;
Heating the mixed resultant to obtain a transparent solution in which the cellulose is peptized;
Removing a bubble formed in the transparent solution using a centrifuge at a temperature lower than room temperature;
Coating the transparent solution to a desired thickness on a substrate, immersing the second solution in a second solvent, and solidifying the second solution;
Cleaning the coagulated product;
Subjecting the washed resultant to supercritical drying with carbon dioxide or lyophilization to obtain a cellulose-based aerogel membrane;
Immersing the cellulosic aerogel membrane in a drug solution to obtain a cellulosic aerogel membrane on which the drug is loaded; And
And immersing the cellulose-based aerogel membrane in a silicon solution to obtain a cellulose-based aerogel membrane complexed with silicon,
The calcium thiocyanate tetrahydrate is mixed in an amount of 10 to 200 parts by weight based on 100 parts by weight of the first solvent,
The cellulose is mixed with the calcium thiocyanate tetrahydrate in an amount of 0.1 to 20 parts by weight based on 100 parts by weight of the total amount of the first solvent,
Wherein the drug solution is an anticancer drug solution in which docetaxel is dissolved in dimethylsulfoxide,
The silicon solution is a solution containing silicon and xylene,
The silicon and the xylene are mixed in a volume ratio of 1: 0.1 to 20,
The drug solution is contained in an amount of 0.0001 to 10 parts by weight based on 100 parts by weight of the silicone solution,
Wherein the cellulose-based aerogel membrane is formed to a thickness of 5 to 300 탆. delete delete

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