JP2009268836A - Inverse opal structure, processes for producing and using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inverse opal structure having a high structural regularity together with excellent weatherability, heat resistance and chemical resistance. <P>SOLUTION: The inverse opal structure including polysaccharides is produced by a template method using as a casting mold a colloidal crystalline, i.e., a self-assembly of monodispersed colloidal particles. Processes for producing and methods of using the structure are also provided. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an inverse opal structure mainly used in the field of medical biomaterials, a method for producing and using the same, and a medical material comprising the inverse opal structure. Specifically, the present invention relates to a polysaccharide inverse opal structure produced by a template method using a colloidal crystal that is a self-assembly of monodispersed colloidal particles as a template, and a method for producing the same.

  Conventionally, as medical materials used in the field of medical biomaterials, for example, many inventions relating to implants for carrying drugs have been created. Such an implant has a merit that the side effect of the drug can be reduced because the drug can be released at a specific in-vivo site by embedding in the living body after the drug is loaded. Have.

Polysaccharides are used as the composition constituting the medical material, and porous structures have been adopted as the structure thereof.
For example, Patent Document 1 discloses a chitin nonwoven fabric that has a protective effect on wound skin and is manufactured by spinning.
Patent Document 2 discloses a regenerated granular porous chitosan carrying an immobilized enzyme characterized by the performance in organic synthesis of various peptides and lipids in a polar solvent such as water.
Patent Document 3 discloses a porous cellulose membrane produced by spinning using a copper ammonia method regenerated cellulose as a separation membrane filter for virus removal when producing blood products and biopharmaceuticals.
Patent Document 4 discloses a transparent porous membrane produced by a dry phase separation method and formed of cellulose acetate.

  In any of the inventions described in Patent Documents 1 to 4, it is not easy to control the hole form such as hole diameter, hole arrangement, porosity, and mutual penetration between holes.

  On the other hand, an inverse opal structure whose pore shape is precisely controlled can be produced by a template method using a colloidal crystal that is a self-assembled body of monodispersed colloidal particles as a template. This structure is a porous material that utilizes the process of reversing the particle occupation space and interparticle voids of the colloidal crystal in the manufacturing process, and reflects the monodispersity of the colloidal particles and the three-dimensional regular arrangement of the colloidal crystals. It is characterized by having pores with a uniform pore size and an ordered porous structure. Further, the porosity of the structure and the mutual penetration between the holes can be controlled in accordance with the crystal structure of the colloidal crystal serving as a template and the bonding property between the colloidal particles.

  This structure selectively Bragg diffracts light of a specific wavelength by interference of light reflected from the hole arrangement surface when the arrangement period of the holes is about a half wavelength of visible light. For example, Patent Documents 5 and 6 disclose that a structure having such optical characteristics is applied to an optical element, a coloring material, and the like. However, these documents do not mention any use in the medical bio field.

Patent Document 7 discloses the use of an inverse opal structure in the medical field. The inverse opal structure described in this document is made from an aliphatic polyester. Such an aliphatic polyester is generally very degradable depending on its composition. Therefore, the inverse opal structure of aliphatic polyester has a problem that it is difficult to use it as a separation membrane or an adsorption medium.
Furthermore, since the aliphatic polyester used in the inverse opal structure described in Patent Document 7 has low chemical stability, the aliphatic polyester is physically deformed by an etching solution used as a mold in the production stage. there's a possibility that. Thereby, the obtained inverse opal structure has a problem that it is inferior in structural regularity.

JP-A-10-52481 JP-A-11-164687 JP 2005-40756 A Japanese Patent Laid-Open No. 11-71476 JP 2007-44598 A JP 2007-197305 A International Publication No. 2007-086306

The present invention has been made in view of the problems of the prior art.
That is, an object of the present invention is to provide an inverted opal structure having high structural regularity and having excellent weather resistance, heat resistance and chemical resistance, and a method for using the same.
Another object of the present invention is to provide a production method for easily producing an inverted opal structure having high structural regularity and having excellent weather resistance, heat resistance and chemical resistance.

The invention according to claim 1 relates to an inverse opal structure characterized in that it contains a polysaccharide.
The invention according to claim 2 relates to the inverted opal structure according to claim 1, wherein the polysaccharide is a cellulose derivative and / or cellulose.
The invention according to claim 3 relates to the inverted opal structure according to claim 1 or 2, wherein the polysaccharide is cellulose acetate.
The invention according to claim 4 relates to the inverted opal structure according to claim 1, wherein the polysaccharide is a cross-linked product of a polysaccharide cross-linked by deacetylated chitin and / or any cross-linking molecule. .
The invention according to claim 5 relates to the inverse opal structure according to any one of claims 1 to 4, characterized by having three-dimensional regular array of holes that selectively reflect light in the visible and near infrared regions.

The invention according to claim 6 relates to the inverted opal structure according to claim 5, wherein the light in the visible and near-infrared region has a wavelength of 400 to 1500 nm.
The invention according to claim 7 relates to the inverse opal structure according to claim 5 or 6, characterized in that a diameter of the hole is 10 to 1000 nm.
The invention according to claim 8 is a medical implant, a separation membrane, a wound dressing, a cell culture medium, or an adsorption medium, and the reverse according to any one of claims 1 to 7 It relates to an opal structure.
The invention according to claim 9 relates to a polysaccharide-coated colloidal crystal composition produced by a production method comprising the following steps (1) to (3).
(1) Step of obtaining a colloidal crystal containing silica particles or polystyrene particles (2) Step of impregnating the colloidal crystal with a solution containing polysaccharide (3) Solidifying the colloidal crystal obtained in the step (2) The composition according to claim 10, wherein the weight fraction of the silica particles or polystyrene particles is 0.01 to 90% by weight. To a composition of polysaccharide-coated colloidal crystals.

The invention according to claim 11 relates to a method of manufacturing an inverted opal structure, comprising the following steps (1) to (4).
(1) Step of obtaining a colloidal crystal containing silica particles or polystyrene particles (2) Step of impregnating the colloidal crystal with a solution containing polysaccharide (3) Solidifying the colloidal crystal obtained in the step (2) 13. A step of obtaining a composition of a polysaccharide-coated colloidal crystal by (4) a step of removing a silica particle from the composition by etching, or a step of obtaining a reverse opal structure by eluting and removing polystyrene particles in an organic solvent. The invention according to the present invention relates to a method for using an inverse opal structure containing a polysaccharide, wherein the inverse opal structure carrying a drug is released in vivo by biodegradation and / or enzymatic degradation. About.
The invention according to claim 13 relates to a method for measuring a drug release amount from an inverted opal structure containing a polysaccharide in vivo, comprising the following steps (a) and (b).
(A) A step of releasing the drug by biodegrading and / or degrading the inverse opal structure carrying the drug with an enzyme (b) Injecting light in the visible and near infrared region into the inverse opal structure And measuring the change in wavelength and intensity of the reflected light. The invention according to claim 14 further includes the following steps (a) and (b): The present invention relates to a method for measuring the amount of drug released from an inverse opal structure.
(B) A step of releasing a drug by carrying a pseudo-drug that absorbs visible light on the inverse opal structure and decomposing the inverse opal structure by biodegradation and / or enzyme (b) the inverse opal Visible or near-infrared light is incident on the structure, and the change (A) in the wavelength and / or intensity of the reflected light is measured, and the amount of the pseudo drug released (B) by quantitative analysis of the visible absorption spectrum The step of correlating (A) and (B) after the measurement of the invention is as follows. The invention according to claim 15 is directed to the inverse opal containing polysaccharide by enzymatic degradation of the pore inner wall of the inverse opal structure containing polysaccharide. The present invention relates to a method for expanding the pore diameter of a structure.

Since the polysaccharide constituting the inverse opal structure of the present invention has high chemical stability, it is not chemically deteriorated by the solution used in the etching process of the manufacturing process. Therefore, the obtained inverse opal structure has high regularity in structure. With the improved regularity, the inverse opal structure of the present invention can accurately measure or adjust the loading amount, release amount, release rate, and the like of the drug carried on the structure.
The polysaccharide constituting the inverse opal structure of the present invention is a biodegradable polymer that is degraded by an enzyme such as cellulase, but has high biodegradation resistance in a non-enzymatic environment. Moreover, the inverse opal structure of the present invention has high hydrophilicity, weather resistance, heat resistance, and chemical resistance.

The inverse opal structure of the present invention is made of a polysaccharide having three-dimensional regular pores therein. The inverse opal structure of the present invention has unique light reflection characteristics due to the three-dimensional regular holes.
Polysaccharides are natural fiber materials extracted from the cell walls of plant cells and the exoskeleton of arthropods, and have an overwhelmingly higher annual output on earth than synthetic polymers made from fossil fuels. , The resources are inexhaustible, the natural environment has a low load, and the adaptability to the living environment is excellent.
The polysaccharide constituting the inverse opal structure of the present invention itself has biodegradability, but physical properties can be controlled by chemically modifying the polysaccharide. Examples of physical properties that can be imparted include heat resistance, transparency, insulation, and pH responsiveness.
Since the inverse opal structure of the present invention has high structural regularity, it has reflection characteristics that accurately reflect the inverse opal structure.

  The medical implant, separation membrane, wound dressing material, cell culture medium and adsorption medium of the present invention are produced by the inverse opal structure of the present invention. That is, the implant or the like is a biodegradable polymer that is degraded by an enzyme, but has high biodegradability in a non-enzymatic environment. In addition, the medical implant, separation membrane, wound dressing material, cell culture medium, and adsorption medium of the present invention have high hydrophilicity, weather resistance, heat resistance, and chemical resistance.

Since the inverse opal structure of the present invention has a porous structure in which pores having a diameter of several tens to several hundreds of nm are closely packed, the surface area is increased. Thereby, the inverse opal structure of the present invention has an improved decomposition rate and an increased amount of adsorbed material.
In the inverted opal structure of the present invention, the porosity and the mutual penetration between the holes can be precisely controlled. Moreover, the movement efficiency of the substance in the structure is improved by the mutual penetration between the holes.

The method for producing an inverse opal structure of the present invention can easily produce an inverse opal structure having the above effects.
The method for measuring the amount of drug released from the inverse opal structure of the present invention can be easily measured while suppressing the burden on the patient. Furthermore, since the value of the drug release amount obtained by the measurement method is accurate, it is preferably used in the medical field.

Hereinafter, the inverse opal structure of the present invention will be described.
The inverted opal structure having three-dimensional regular pores of the present invention is composed of a polysaccharide having pores regularly arranged three-dimensionally inside. That is, the structure reflects the three-dimensional regular structure of the colloidal crystal serving as a template, and has three-dimensionally regularly arranged vacancies, which are preferably about the diameter of the wavelength of light. .
Such an inverse opal structure is known to selectively reflect light of a specific wavelength and exhibit a structural color as seen in natural opal. In addition, the large specific surface area derived from the porous structure is characterized in that the mechanical response speed to external stimuli is 3 to 4 orders of magnitude higher than that of the non-porous polymer.

The polysaccharide is not particularly limited. For example, cellulose, cellulose derivatives (cellulose acetate (cellulose acetate), cellulose propionate, cellulose butyrate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose nitrate, Cellulose sulfate, cellulose phosphate, cellulose nitrate acetate, methyl cellulose, ethyl cellulose, isopropyl cellulose, butyl cellulose, benzyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, cyanoethyl cellulose), chitin, deacetylated chitin, chitin derivatives , Chitosan, chitosan derivatives, carrageenan (κ, λ, ι, μ, ν, θ xi], [pi), alginic acid, hyaluronic acid, glycosaminoglycans, such as chondroitin sulfate.
Alternatively, the polysaccharide may be a cross-linked polysaccharide cross-linked by an arbitrary cross-linking molecule. Examples of the crosslinking molecule include glutaraldehyde, succinaldehyde, malonaldehyde, and glyoxal.

  The polysaccharide used in the present invention is not particularly limited to the above as long as the monomer includes all polymers composed of monosaccharides and can form the polymer. Moreover, the blend polymer containing 2 or more types of said polysaccharide also corresponds, The combination and composition ratio are not specifically limited, The thing of various compositions is obtained by adjusting these.

Next, the shape of the inverted opal structure of the present invention will be described.
The inverted opal structure of the present invention reflects a three-dimensional regular structure of a colloidal crystal serving as a template, and is composed of a polysaccharide having pores regularly arranged three-dimensionally.
The diameter of the holes is preferably 10 to 1000 nm, and more desirably 200 to 600 nm. Since the inverse opal structure of the present invention has such holes, it exhibits the property of selectively reflecting light of a specific wavelength. The wavelength of the reflected light varies depending on the incident angle of light, the hole diameter, the volume fraction of the inverse opal structure and the substance existing in the hole, and the refractive index based on the Braggsnell law. Examples of the light having the specific wavelength include visible light and near infrared light having a wavelength of 400 to 1500 nm.

  The inverse opal structure of the present invention has a high tissue permeability and can selectively reflect light in the visible and near-infrared regions with less hindrance than the non-porous polymer due to its wide specific surface area. Moreover, the inverse opal structure of the present invention can respond to pH change at high speed. For example, when chitin is used as a polysaccharide, it itself has pH responsiveness, or when cellulose sesulose is used as a polysaccharide, chemically modify the cellulose acetate with amino groups, sulfate groups, etc. Enables a pH response.

Next, the manufacturing method of the inverse opal structure of this invention is demonstrated.
The manufacturing method of the inverse opal structure of the present invention includes the following steps (1) to (4).
(1) A step of obtaining a colloidal crystal containing silica particles or polystyrene particles (2) A step of impregnating the colloidal crystal with a solution containing a polysaccharide (3) A polysaccharide-coated colloid by solidifying the solution containing the polysaccharide Step (4) of obtaining a crystal composition (4) Step of removing colloidal particles from the composition by etching, or eluting polystyrene particles into an organic solvent to remove them, thereby obtaining an inverse opal structure.

In the step (1), colloidal crystals are obtained from silica particles or polystyrene particles.
The inverse opal structure of the present invention is preferably produced by a replica method using a colloidal crystal as a template.
In order to produce colloidal crystals, preferably silica particles and / or polystyrene particles can be used. Silica particles may be synthesized by, for example, a sol-gel method. The silica particles used in the present invention are preferably those having a particle size of 200 to 500 nm. Polystyrene particles can be obtained, for example, by an emulsion polymerization method. As the polystyrene particles used in the present invention, those having a particle size of 200 to 500 nm are preferably used.
Alternatively, as colloidal particles having a uniform particle size, for example, particles having a particle size ranging from 3 nm to 90 nm are commercially available at a relatively low cost.

  As a simple method for producing a colloidal crystal, there is a gravity sedimentation method. This method utilizes the property that when a solvent gradually evaporates from a colloidal suspension dropped on a substrate, a lateral capillary force acts between colloidal particles and self-assembles. According to this method, a low crystalline colloidal crystal can be obtained. However, a relatively large area colloidal crystal film can be produced by covering the surface of the solvent with a non-volatile substance. In addition to this method, colloidal crystals with high three-dimensional regularity can also be produced using an electrochemical self-assembly method or a hydrodynamic integration method.

  The colloidal crystal is used as a template when producing the inverse opal structure of the present invention. Although the colloidal crystal depends on the synthesis conditions, it usually forms a cubic close-packed structure, and the lattice constant can be controlled by the particle size of the colloidal particles. In order to selectively reflect light in the visible to near-infrared region, the particle size of the colloidal particles is preferably 200 to 600 nm, more preferably 300 to 500 nm, but is not particularly limited to this range. . The appearance of the colloidal crystal according to the present invention is shown in FIG.

In the step (2), the colloidal crystal produced in the step (1) is impregnated with a solution containing a polysaccharide (hereinafter sometimes referred to as a polysaccharide solution). The impregnation may be performed, for example, by dropping a solution containing the polysaccharide onto a colloidal crystal.
Specifically, in the step (3), the dropped solution is filled in the particle gaps of the colloidal crystal, and a process in which all or most of the gaps are occupied by the solution is performed.

The polysaccharide has been described above. For example, cellulose, cellulose derivatives (cellulose acetate (cellulose acetate), cellulose propionate, cellulose butyrate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose nitrate, Cellulose sulfate, cellulose phosphate, cellulose nitrate acetate, methyl cellulose, ethyl cellulose, isopropyl cellulose, butyl cellulose, benzyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, cyanoethyl cellulose), chitin, deacetylated chitin, chitin derivatives , Chitosan, chitosan derivatives, carrageenan (κ, λ, ι, μ, ν, θ, ξ, π ), Glycosaminoglycans such as alginic acid, hyaluronic acid, and chondroitin sulfate.
Alternatively, the polysaccharide may be a cross-linked polysaccharide cross-linked by an arbitrary cross-linking molecule. Examples of the crosslinking molecule include glutaraldehyde, succinaldehyde, malonaldehyde, and glyoxal.

The polysaccharide solution is a solution obtained by dissolving the polysaccharide according to the present invention in an appropriate solvent.
The concentration of the polysaccharide in the polysaccharide solution is preferably about 0.01 wt% to 50 wt%, although it depends on the type of polysaccharide and solvent and the combination thereof. If it is less than 0.01% by weight, the amount of the polysaccharide substance filled in the gaps between the particles of the colloidal crystal becomes small, and the skeleton part of the porous body does not have sufficient strength, which is not preferable. Alternatively, if it exceeds 50% by weight, the viscosity of the solution increases, and therefore the polysaccharide solution does not reach the fine gaps between the colloidal crystal particles, which is not preferable.

When the polysaccharide is chitin, the solvent may be determined according to the degree of deacetylation, and preferably a calcium chloride dihydrate-saturated methanol solution, a lithium chloride-dimethylacetamide solution, an acidic solution ( Acetic acid, formic acid, phosphoric acid, hydrochloric acid, sulfuric acid, etc.).
In particular, considering the solubility in acidic solutions (acetic acid, formic acid, phosphoric acid, hydrochloric acid, sulfuric acid, etc.), it is desirable to use deacetylated chitin obtained by deacetylation of chitin as the polysaccharide. This is because a part of the acetyl group is substituted with an amino group, so that the solubility in an acidic solution (acetic acid, formic acid, phosphoric acid, hydrochloric acid, sulfuric acid, etc.) is improved. In addition, the deacetylation degree of the deacetylated chitin used suitably in this invention is 20 to 80%.

When the polysaccharide is cellulose, Schweizer reagent, ethers (dioxane, tetrahydrofuran, etc.), ketones (acetone, methyl ethyl ketone, etc.), esters (methyl acetate, ethyl acetate, etc.), halides (chloroform, methylene chloride, etc.) ), Nitrides (acetonitrile, dimethylformamide and the like), dimethyl sulfoxide, methyl glycol and the like are preferably used. Of the solvents, acetone, ethyl acetate, and dimethylformamide are particularly preferable.
In particular, considering the solubility in a solvent (organic solvent), it is desirable to use cellulose acetate as the polysaccharide. The reason for this is that cellulose acetate is obtained by esterification of cellulose, and part of the hydroxyl groups are substituted with acetyl groups (acetylation), thereby weakening the interaction between molecules, thereby making it soluble in organic solvents. It is because it improves.

A preferred combination of the solvent and the polysaccharide is a combination of at least one solvent selected from acetone, ethyl acetate, and dimethylformamide and cellulose acetate. In this case, the cellulose acetate is preferably contained in 1 to 30% by weight in acetone, 1 to 30% by weight in ethyl acetate, and 1 to 30% by weight in dimethylformamide.
Another suitable combination of the solvent and polysaccharide is a combination of hydrochloric acid solution and chitin. In this case, chitin is desirably contained in the hydrochloric acid solution in an amount of 1 to 10% by weight.

  When the colloidal crystal has a face-centered cubic structure, since the colloidal crystal occupies 74% of the volume fraction, the polysaccharide solution occupies the remaining 26% of the voids. Further, when the structure of the colloidal crystal is different from the above, and when the colloidal crystal is produced from a mixed solution of the colloidal suspension and the polysaccharide solution, the volume fraction is not limited to the above.

Next, in the step (3), the polysaccharide-containing colloidal crystal composition is obtained by solidifying the solution containing the polysaccharide.
The method for solidifying the solution containing the polysaccharide is not particularly limited, and, for example, a method of drying under reduced pressure, heat drying, freeze drying, conductive drying, infrared drying, microwave drying, or ultrasonic drying is employed.

The weight fraction of silica particles or polystyrene particles in the composition of the polysaccharide-coated colloidal crystal according to the present invention is preferably 0.01 to 90% by weight, more preferably 0.1 to 50% by weight. This is because when the weight of silica particles or polystyrene particles is in the range of 0.01 to 90% by weight in the composition, the three-dimensional periodicity of the colloidal crystal is excellent.
The composition of the aliphatic polyester-coated colloidal crystal obtained by the step (3) is shown in (2) of FIG.

Next, in the step (4), the inverse opal structure can be obtained by removing the silica particles used as a template in the polysaccharide-coated colloidal crystal by etching. The etching is preferably performed using hydrofluoric acid or the like (for example, hydrofluoric acid aqueous solution).
Alternatively, in step (4), the inverse opal structure can be obtained by removing the polystyrene particles in the polysaccharide-coated colloidal crystal by eluting them in an organic solvent such as toluene. The inverted opal structure obtained by the step (4) is shown in (3) of FIG.

  The shape of the obtained inverse opal structure is preferably a thin film, but a colloidal crystal is prepared using silica particles or polystyrene particles having an appropriate particle diameter and an appropriately shaped container, and this is used as a template. Thus, inverted opal structures having various shapes such as a needle shape, a wafer shape, and a pellet shape can be obtained.

  The pore diameter of the inverse opal structure of the present invention obtained in the step (4) depends on the particle diameter of colloidal particles of the colloidal crystal serving as a template, and can be controlled to a pore diameter of about 200 nm to 500 nm, for example. Alternatively, the pore diameter of the inverse opal structure can be adjusted after the creation of the inverse opal structure. For example, the pore diameter can be expanded by hydrolyzing the pore inner wall using a buffer solution or an enzyme, or by immersing in an aqueous solution adjusted to an arbitrary pH. Further, the pore diameter can be reduced by immersing the structure in a monomer solution diluted to an appropriate concentration and performing thermal polymerization.

  In addition, since colloidal crystals usually have a face-centered cubic close-packed structure, the inverse opal structure obtained in step (4) has an ordered porous structure reflecting its periodicity (lattice constant). In a colloidal crystal, 74% of the volume fraction is particles and the remaining 26% is voids between the particles. Therefore, in the inverse opal structure, 74% of the volume fraction is vacant, and the remaining 26% is approximately It becomes a skeleton formed by a polysaccharide.

In addition, the vacancies of the inverted opal structure formed in the step (4) are mutually penetrating. This is because, in the step (2), an operation of immersing the colloidal crystal in the polysaccharide solution is performed, but the polysaccharide solution does not penetrate into the site where the colloidal particles are in contact with each other.
As described above, according to the manufacturing method of the inverted opal structure of the present invention, a porous structure in which pore diameter, pore arrangement, porosity, and mutual penetration of pores are controlled by a template method using a colloidal crystal. It is possible to form.
Alternatively, as another embodiment, the above-described pore shape can be controlled by using a colloidal crystal composed of two or more types of colloidal particles having different particle diameters as a template.

Next, a method for using the inverse opal structure of the present invention will be described.
The inverse opal structure of the present invention can be used as a medical material. For example, it can be used as a medical implant. In this case, after the drug is supported in the pores of the inverse opal structure, the drug can be released by embedding it in a living tissue and decomposing the polysaccharide with an enzyme or the like.
Although it does not specifically limit as said drug, It can carry | support suitably the drug with low solubility to a solvent, and the drug decomposed | disassembled easily in the living body. Specifically, alkylating agents such as ACNU and BCNU, platinum preparations, antibiotics, and hormonal agents can be mentioned. Alternatively, a DNA drug or the like can be used as the drug. Further, since the degree of hydrophilicity can be adjusted, it is also suitable for loading a drug having high hydrophilicity.
In addition, in order to carry | support a drug, the method by immersing an inverse opal structure in the solution containing a drug is mentioned, However It is not limited to this.

  Examples of a method for embedding an inverted opal structure carrying a drug in a pore into a living tissue include a method using a trocar used in laparoscopic surgery.

As a method for releasing a drug from the inverse opal structure of the present invention, there is a method using an enzyme that degrades the polysaccharide used as described above. This enzyme can be appropriately selected according to the type of polysaccharide constituting the inverse opal structure of the present invention. For example, when the polysaccharide constituting the inverse opal structure is chitin, such as chitinase Enzymes are preferably used. Further, when the polysaccharide is cellulose or a cellulose derivative, cellulase or the like is preferably used as the enzyme.
Evaluation of degradability by the enzyme is performed by a known method such as a turbidimetric method, a viscosity method, a radioactivity measurement method, a produced reducing sugar quantification method, and HPLC.

  Another method of drug release according to the present invention is a method using ion-exchanged water or a buffer solution whose pH is adjusted to acidic or basic. Evaluation of drug release by the solution or the like is performed by a known method such as absorption spectroscopy, fluorescence spectroscopy, fluorescence microscope observation, or HPLC. With these solutions, the biodegradability based on the hydrolysis reaction is evaluated, and the decomposition reaction rate can be adjusted. Therefore, the release rate of the drug can be adjusted by the solution.

  When the enzyme or solution is administered separately, a buffer solution in which the enzyme is dissolved or a droplet of the solution is dropped on the surface of the inverted opal structure and permeated into the pores.

  Considering that the inverse opal structure of the present invention is used as a medical implant and the drug carried on the implant is released in vivo, the time until the inverse opal structure is completely decomposed is from several weeks. It is desirable to be about one year.

Next, a method for detecting the amount of medicine released from the inverse opal structure of the present invention will be described.
As described above, the inverse opal structure of the present invention is gradually decomposed by the action of a buffer solution or an enzyme. In addition, the pore diameter and the three-dimensional regularity of the pores change due to a mechanical response to biodegradation and the like. The amount of drug released can be detected by measuring this structural change. For this measurement, a reflection measuring device including a spectroscope, a light source, and a detection probe may be used. Since the reflection measuring apparatus is small unlike X-ray CT and MRI, real-time measurement can be performed quickly and easily at the bedside, and the burden on the patient is small.

  In order to detect a change in the pore diameter, it is desirable to use visible light and near infrared light having a wavelength of about 600-1100 nm, which has high permeability to living tissue, as the incident light source. In particular, near-infrared light having a wavelength of 700 to 1000 nm called a spectroscopic window is excellent in tissue permeability. For example, near-infrared light of 830 nm has a penetration depth of 1300 nm. Since the inverse opal structure of the present invention can easily control the pore diameter, light in a desired region can be selected.

  The reflection spectrum can be measured using an ordinary spectrophotometer. To measure the biodegradation process in real time, it consists of a fiber optic compact spectrophotometer, an optical microscope, and a CCD camera. It is desirable to use a reflection measurement system. In this apparatus, a white light source such as a halogen light source or a xenon light source, or a monochromatic light source such as a solid laser or a laser diode is used as an incident light source.

Furthermore, the method for measuring the amount of drug released will be described more specifically.
Drug release can be performed using the action of a buffer solution or an enzyme as described above. For example, when a drug is released by biodegradation, the adsorbed or absorbed drug is gradually released in the process of collapse of the inverse opal structure. Alternatively, the drug can be released also by volume swelling / contraction of the structure accompanying the pH response.
In order to measure the release amount, a pseudo-drug such as methylene blue that absorbs visible light is used, and the release amount of the pseudo-drug is measured from the absorbance of the visible absorption spectrum, and the wavelength and intensity of the reflected light accompanying biodegradation. Measure changes. By correlating both measurement results, the amount of emission can be determined from changes in the wavelength and intensity of the reflected light.

  Other uses of the inverse opal structure of the present invention include biological material and virus separation membranes (for example, separation membranes for hemodialysis using artificial kidneys) and artificial organ separation membranes. Alternatively, the inverted opal structure of the present invention may be used as a cell culture medium, such as a wound dressing (or artificial skin). Other applications include, for example, purification of water such as ultrapure water, drinking water and industrial water, treatment of industrial and municipal wastewater, chemical separation, purification in each process of the chemical industry, pharmaceutical industry and food industry. It is done.

The method for using the inverse opal structure of the present invention will be further described.
The inverted opal structure of the present invention can be used as a separation membrane for biological materials and viruses. When used in this way, it can be used as a separation membrane for separation of biological materials such as proteins and nucleic acids using a porous structure with a size of several hundred nanometers. It can be measured from. This separation membrane is a multilayer film in which a plurality of thin films are stacked, or fine powder by pulverization, and then filled in a container such as a column, and then a fluid (gas or liquid) containing a substance to be separated is filled. When continuously supplied, molecules and particles having a particle size smaller than the pore size are permeated mainly by a sieving effect (filtration). At this time, the refractive index and volume fraction of the pores change due to adsorption of the separation target substance on the inner wall of the pores, and as a result, the reflection wavelength and reflection intensity of the inverse opal structure are considered to be modulated. .

Alternatively, when the inverse opal structure of the present invention is used as a culture medium for cell culture, cells can be grown or proliferated on the inverse opal structure of the present invention. At this time, the growth and proliferation of cells can be measured from the change in the reflection characteristics of the inverse opal structure. As a specific method of use, serum, antibiotics, glucose, and the like are infiltrated into a sterilized inverted opal structure, and then cells are introduced to the surface and cultured at 37 ° C. in a 5% carbon dioxide atmosphere. Do. At that time, a reflection measurement probe is attached to the upper part of the culture vessel, and the change over time of the reflection characteristic of the inverse opal structure is measured. Since the surface of the inverse opal structure is gradually covered with the grown and proliferated cultured cells, it is considered that the reflected light intensity continuously decreases.
When the polysaccharide constituting the inverse opal structure of the present invention is chitin, it is suitably used as a wound dressing (or artificial skin). In this case, gas and moisture can be exchanged by the porous structure of the inverse opal structure, and the state of absorption into the living body can be measured from the change in reflection characteristics.
Alternatively, the inverse opal structure of the present invention may be used as an adsorption medium. Specifically, the adsorption medium may be used as an adsorption medium for proteins, sugars, biomolecules such as nucleic acids, and viruses. This adsorption medium is a multilayer film in which a plurality of thin films are stacked, or is made into fine powder by pulverization, and then filled and held in a container such as a column, and then a fluid (gas or liquid) containing an adsorbate is filled. Used by continuous supply and adsorption (stationary phase adsorption). Or it is used also by operation (fluidized bed adsorption | suction) which makes it adsorb | suck by distribute | circulating the fluid containing an adsorbate continuously to the container filled with the powder of adsorption medium.

  The inverse opal structure of the present invention is highly biodegradable in a non-enzymatic environment, and also has the characteristics of polysaccharides such as high weather resistance, heat resistance, and chemical resistance, and a pore size and high regularity. The membrane separation performance can be stably maintained over a long period of time due to both the pore arrangement and the structural feature of having a large specific surface area, so that it can be suitably used as a separation membrane. Further, the combination of the two features makes it possible to stably maintain the adsorption performance over a long period of time, and therefore can be suitably used as an adsorption medium.

Hereinafter, the effects of the present invention will be made clearer by describing examples of the present invention.
In addition, this invention is not limited at all by the following examples.

(Synthesis of inverted opal structure 1)
After dropping 4 to 5 drops of silica particle suspension with an average particle size of 200 nm onto a glass substrate with a Pasteur pipette, the silica colloidal crystal thin film is obtained by leaving it in a dark room at room temperature and humidity for 2 days. Obtained.
Cellulose acetate (manufactured by Daicel Chemical Industries, Ltd.) was dissolved in ethyl acetate at room temperature to obtain a 6 wt% solution. 40 μm of this solution was dropped onto the silica colloidal crystal thin film produced as described above with a Pasteur pipette, and then refrigerated for 1 day to obtain a composite thin film containing silica colloidal crystals inside. The composite thin film was dried with a vacuum desiccator for 1 day, and then immersed in a 2.3 wt% hydrofluoric acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) for 2 days to remove silica particles. The obtained thin film was sufficiently washed with ion-exchanged water while performing suction filtration, and dried and stored in a vacuum desiccator to obtain an inverse opal structure 1.

(Electron microscope observation)
Scanning electron microscope observation was performed to confirm the porous structure of the structure obtained by the above operation (measuring device: ultra-high resolution field emission scanning electron microscope S-4800 manufactured by Hitachi High-Technologies Corporation). . As the observation sample, one obtained by sputtering PtPd was used.
FIG. 2 is an electron micrograph of the inverse opal structure 1, and it can be confirmed that holes having uniform pore diameters are periodically arranged. Since the hexagonal lattice of vacancies can be confirmed on the sample observation surface, it is considered that the vacancy array layer is three-dimensionally laminated to form a face-centered cubic structure. From this, it can be said that an inverse opal structure was produced by using a silica colloid crystal and a polystyrene colloid crystal as a template.

(Reflectance spectrum measurement)
The reflection characteristics of the structure obtained by the above operation were examined. For the measurement, film-like samples of structure 1 were used, and these were placed on the stage of an optical microscope (industrial microscope ECLIPSE LV100D manufactured by Nikon Corporation) and irradiated with white light from the vertical direction of the sample surface. A reflection spectrum in a wavelength region of 200 to 1100 nm was measured (measuring device: high-resolution fiber multichannel spectroscopic system for reflection measurement manufactured by Ocean Optics, Inc.). As shown in FIG. 3, each of the structures 1 exhibited a reflection peak at 486 nm. This is considered to be caused by the fact that the hole array observed in FIG. 2 forms a layer in the sample, and the light reflected from each layer interferes.

(Synthesis of inverted opal structure 2)
After dropping 4 to 5 drops of silica particle suspension with an average particle size of 200 nm onto a glass substrate with a Pasteur pipette, the silica colloidal crystal thin film is obtained by leaving it in a dark room at room temperature and humidity for 2 days. Obtained.
Cellulose acetate (manufactured by Daicel Chemical Industries, Ltd.) was dissolved in dimethylformamide at room temperature to obtain a 20 wt% solution. 40 μm of this solution was dropped onto the silica colloidal crystal thin film produced as described above with a Pasteur pipette, and then refrigerated for 1 day to obtain a composite thin film containing silica colloidal crystals inside. The composite thin film was dried with a vacuum desiccator for 1 day, and then immersed in a 2.3 wt% hydrofluoric acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) for 2 days to remove silica particles. The obtained thin film was sufficiently washed with ion-exchanged water while performing suction filtration, and dried and stored in a vacuum desiccator to obtain an inverse opal structure 2.

(Electron microscope observation)
Scanning electron microscope observation was performed to confirm the porous structure of the structure 2 (measuring device: ultra-high resolution field emission scanning electron microscope S-4800 manufactured by Hitachi High-Technologies Corporation). As the observation sample, one obtained by sputtering PtPd was used.
FIG. 4 (a) is a colloidal crystal of silica particles, (b) is a composition of a polysaccharide-coated colloidal crystal (a composite thin film containing silica colloid crystals inside), and (c) is obtained by removing the silica particles by etching. The microscope picture of the inverse opal structure 2 is shown.

(Reflectance spectrum measurement)
The reflection characteristics of the structure obtained by the above operation were examined. That is, by using the structure 2 and placing them on the stage of an optical microscope (industrial microscope ECLIPSE LV100D manufactured by Nikon Corporation) and irradiating white light from the vertical direction of the sample surface, a wavelength of 200 to 1100 nm The reflection spectrum in the region was measured (measuring device: high-resolution fiber multichannel spectroscopic system for reflection measurement manufactured by Ocean Optics, Inc.). In FIG. 5, (a) shows a colloidal crystal of silica particles, (b) a composition of a polysaccharide-coated colloidal crystal, and (c) shows a reflection spectrum of the inverse opal structure 2. As FIG. 5 shows, it turns out that the structure 2 shows the reflection derived from a regular porous structure in the visible light region of 450-550 nm.

(Synthesis of inverse opal structures 3 and 4)
After dropping 40 μm onto a glass substrate with a suspension of polystyrene particles having an average particle size of 200 nm (manufactured by polysciences) on a glass substrate, the polystyrene colloidal crystals are allowed to stand in an incubator at 30 ° C. and RH 100% for 2 days. A thin film was obtained.
Chitin having a deacetylation rate of 45 to 55% (manufactured by Koyo Chemical Co., Ltd.) was mixed in a 0.1 M hydrochloric acid aqueous solution and stirred at room temperature for 1 day to completely dissolve it to obtain a 4 wt% solution. This solution was dropped and immersed in the polystyrene colloidal crystal thin film prepared as described above with a Pasteur pipette, and then refrigerated for 5 days to obtain a composite thin film containing polystyrene colloidal crystals inside. The composite thin film was immersed in toluene (manufactured by Wako Pure Chemical Industries, Ltd.) for 24 hours to remove polystyrene particles. The obtained thin film was washed with ethanol, and then stored in a desiccator under reduced pressure to obtain an inverse opal structure 3.
Further, the composite thin film was immersed in a mixed solution of 1% v / v of 25% aqueous glutaraldehyde and ethanol for 1 hour, and then immersed in toluene for 24 hours to remove polystyrene particles. The obtained crosslinked thin film was washed with ethanol and then stored in a desiccator under reduced pressure to obtain an inverse opal structure 4.

(Electron microscope observation)
Scanning electron microscope observation was performed to confirm the porous structures of the structures 3 and 4 and the composition of colloidal crystals of polystyrene particles and polysaccharide-coated colloidal crystals obtained during production (measuring apparatus: Hitachi, Ltd.). Ultra-high resolution field emission scanning electron microscope S-4800 manufactured by High Technologies. As the observation sample, one obtained by sputtering PtPd was used.
FIG. 6 relates to inverse opal structures 3 and 4 manufactured using polystyrene colloid having a particle size of 200 nm. (A) is a microscopic (SEM) photograph of colloidal crystals of polystyrene particles (a-1: 25,000 magnification). And optical micrographs (a-2) and (b) are microscopic (SEM) photographs (b-1: 25,000 magnifications) and optical micrographs (b-2) and (c) of the composition of polysaccharide-coated colloidal crystals. ) Is a microscopic (SEM) photograph of the inverse opal structure 3 (c-1: 22,000 magnification) (c-2: 40,000 magnification), and (d) is an inverse opal structure 4 manufactured using a crosslinking agent. The microscope (SEM) photograph (d-1: 20,000 magnification) (d-2: 40,000 magnification) is shown.

(Synthesis of inverse opal structures 5 and 6)
Inverse opal structures 5 and 6 were obtained by the same method as the manufacturing method of the inverse opal structures 3 and 4 described above except that the average particle diameter of the polystyrene particles was 400 nm. That is, a polystyrene particle suspension (manufactured by polysciences) having an average particle diameter of 400 nm was dropped onto a glass substrate by 40 μm, and then allowed to stand in an incubator at 30 ° C. in an RH 100% atmosphere for 2 days. A colloidal crystal thin film was obtained.
Chitin having a deacetylation rate of 45 to 55% (manufactured by Koyo Chemical Co., Ltd.) was mixed in a 0.1 M hydrochloric acid aqueous solution and stirred at room temperature for 1 day to completely dissolve it to obtain a 4 wt% solution. This solution was dropped and immersed in the polystyrene colloidal crystal thin film prepared as described above with a Pasteur pipette, and then refrigerated for 5 days to obtain a composite thin film containing polystyrene colloidal crystals inside. The composite thin film was immersed in toluene (manufactured by Wako Pure Chemical Industries, Ltd.) for 24 hours to remove polystyrene particles. The obtained thin film was washed with ethanol, and then stored in a desiccator under reduced pressure to obtain inverse opal structure 5.
Moreover, after immersing the composite thin film in a mixed solution (1/9 v / v) of 25% glutaraldehyde aqueous solution and ethanol for 1 hour, it was immersed in toluene for 24 hours to remove polystyrene particles. The obtained crosslinked thin film was washed with ethanol and then stored in a desiccator under reduced pressure to obtain an inverse opal structure 6.

(Electron microscope observation)
Scanning electron microscope observation was performed to confirm the porous structures of the structures 5 and 6 and the composition of colloidal crystals of polystyrene particles and polysaccharide-coated colloidal crystals obtained during production (measuring apparatus: Hitachi, Ltd.). Ultra-high resolution field emission scanning electron microscope S-4800 manufactured by High Technologies. As the observation sample, one obtained by sputtering PtPd was used.
FIG. 7 shows an inverse opal structure 5 manufactured using a polystyrene colloid having a particle size of 400 nm. (A) is a microscopic (SEM) photograph (a-1: 50,000 magnification) and optical of a colloidal crystal of polystyrene particles. Micrographs (a-2) and (b) are microscopic (SEM) photographs (b-1: 20,000 magnifications) and optical micrographs (b-2) and (c) of the composition of polysaccharide-coated colloidal crystals. Microscopic (SEM) photograph (c-1: 10,000 magnification) (c-2: 20,000 magnification) and optical micrographs (c-3) and (d) of the inverted opal structure 5 are obtained using a crosslinking agent. The microscope (SEM) photograph (d-1: 10,000 magnification) (d-2: 20,000 magnification) and optical microscope photograph (d-3) of the manufactured reverse opal structure 6 are shown.
From the microscope (SEM) photograph, it can be confirmed that holes having a uniform hole diameter are periodically arranged. Since the hexagonal lattice of vacancies can be confirmed on the sample observation surface, it is considered that the vacancy array layer is three-dimensionally laminated to form a face-centered cubic structure. From this, it can be said that an inverted opal structure was produced by using a colloidal polystyrene crystal as a template.
In addition, since (c-3) and (d-3) structural colors were observed, it is considered that a highly ordered porous structure was formed in the inverted opal structure.
FIG. 8 shows another electron micrograph of the inverted opal structure 5.

(Reflectance spectrum measurement)
The reflection characteristics of the structure obtained by the above operation were examined. That is, a colloidal crystal of polystyrene particles, a composition of a polysaccharide-coated colloidal crystal, a structure 5 and a structure 6 obtained in the course of production are used, and this is used as a stage of an optical microscope (an industrial microscope ECLIPSE LV100D manufactured by Nikon Corporation) The reflection spectrum in the wavelength range of 200 to 1100 nm was measured by irradiating white light from the vertical direction of the sample surface (measuring device: high-resolution fiber multichannel for reflection measurement manufactured by Ocean Optics, Inc.) Spectroscopy system).
In FIG. 9, (a) is a colloidal crystal, (b) is a composition of a polysaccharide-coated colloidal crystal, (c) is a structure 5, (d) is a structure 6, and (e) is a structure 6 (underwater). ) Shows the reflection spectrum. As shown in FIG. 9, it can be seen that the structure 5 shows reflection in the visible / near infrared light region of 600 to 700 nm in a dry state in an air atmosphere. This is considered to be caused by the fact that the hole array observed in FIG. 8 forms a layer in the sample, and the light reflected from each layer interferes. Similarly, it can be seen that the structure 6 shows a reflection derived from the ordered porous structure at 700 to 900 nm. On the other hand, under immersion in water, the structure 5 collapsed due to elution of chitin, and the reflection spectrum could not be measured. As shown in FIG. 9 (e), with respect to the structure 6, a reflection peak could be observed in substantially the same wavelength region. From this, it is considered that the water resistance of the structure was improved by crosslinking of chitin with glutaraldehyde.

(Evaluation of structural regularity of inverse opal structure of the present invention)
In order to evaluate the structural regularity of the inverse opal structure of the present invention, an inverse opal structure of aliphatic polyester was produced by the following production method as a comparative example. The structural regularity was evaluated by comparing micrographs of the obtained inverse opal structure of the comparative example and the above-described inverse opal structures 1 and 5 of the present invention.

(Manufacturing method of comparative example)
After 4-5 drops of silica particle suspension with an average particle size of 400 nm is dropped onto a glass substrate with a Pasteur pipette, the mixture is allowed to stand at room temperature in an RH 100% atmosphere for 2 weeks to obtain a silica colloidal crystal thin film. It was.
DL-polylactic acid (manufactured by Taki Chemical Co., Ltd., average molecular weight 11,000) was dissolved in acetone at room temperature to obtain a 20 wt% solution. A few drops of this solution were dropped onto the silica colloidal crystal thin film produced as described above with a Pasteur pipette, and then allowed to stand at room temperature for 1 day to obtain a composite thin film containing silica colloidal crystals inside. The composite thin film was dried at room temperature for 1 day, and then immersed in a 1.15 wt% hydrofluoric acid aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) for 2 days in a refrigerator to remove silica particles. The obtained thin film was sufficiently washed with ion-exchanged water, and dried and stored in a vacuum desiccator to produce an inverse opal structure as a comparative example.

(Electron microscope observation)
A photomicrograph of the inverse opal structure 1 of the present invention is shown in FIG. 10, a photomicrograph of the inverse opal structure 5 of the present invention is shown in FIG. 11, and a photomicrograph of the aliphatic polyester (comparative example) is shown in FIG.
As shown in FIGS. 10 to 12, the inverse opal structure of the present invention has improved structural regularity as compared with the inverse opal structure made of aliphatic polyester.
Furthermore, the two-dimensional Fourier transform image of FIGS. In the figure, (A) is the inverse opal structure 1, (B) is the inverse opal structure 5, and (C) is a two-dimensional Fourier transform image of the inverse opal structure made of aliphatic polyester. In FIGS. 13A and 13B, clear scattered images are seen, confirming the existence of high regularity. On the other hand, in FIG. 13C, a scattered image is not seen, suggesting that there is no regularity.

The process for producing an inverse opal structure according to the present invention represents a process of producing an inverse opal structure from a colloidal crystal. (1) is a colloidal crystal, (2) is a polysaccharide-coated colloidal crystal composition, and (3) is an inverse opal structure. It is an electron micrograph which shows an example of the porous structure of the structure concerning this invention. (Inverse opal structure 1) It is a graph which shows an example of the reflection spectrum of the structure concerning the present invention. (Inverse opal structure 1) (A) Colloidal crystals of silica particles, (b) a composition of polysaccharide-coated colloidal crystals (composite thin film containing silica colloidal crystals inside), and (c) an inverted opal structure obtained by removing silica particles by etching. A photomicrograph of body 2 is shown. (A) shows a colloidal crystal of silica particles, (b) a composition of a polysaccharide-coated colloidal crystal, and (c) shows a reflection spectrum of the inverse opal structure 2. (A) is a microscopic (SEM) photograph of a colloidal crystal of polystyrene particles (a-1: 25,000 magnification) and an optical micrograph (a-2), and (b) is a microscope of a composition of a polysaccharide-coated colloidal crystal ( (SEM) photograph (b-1: 25,000 magnification) and optical microscope photograph (b-2), (c) is a microscope (SEM) photograph of inverted opal structure 3 (c-1: 22,000 magnification) (c -2: 40,000 magnification), (d) is a microscope (SEM) photograph (d-1: 20,000 magnification) (d-2: 40,000 magnification) of the inverted opal structure 4 produced using a crosslinking agent. ). (A) is a microscopic (SEM) photograph of colloidal crystals of polystyrene particles (a-1: 50,000 magnifications) and optical micrograph (a-2), (b) is a microscope of the composition of polysaccharide-coated colloidal crystals ( (SEM) photograph (b-1: 20,000 magnification) and optical microscope photograph (b-2), (c) is a microscope (SEM) photograph of inverted opal structure 5 (c-1: 10,000 magnification) (c -2: 20,000 magnification) and optical micrographs (c-3), (d) are microscopic (SEM) photographs of the inverse opal structure 6 produced using a crosslinking agent (d-1: 10,000 magnifications). (D-2: 20,000 magnifications) and an optical micrograph (d-3) are shown. It is an electron micrograph which shows an example of the porous structure of the structure concerning this invention. (Inverse opal structure 5) (A) is a colloidal crystal, (b) is a composition of a polysaccharide-coated colloidal crystal, (c) is a structure 5, (d) is a structure 6 and (e) is a reflection spectrum of the structure 6 (in water). Show. The microscope picture of the inverse opal structure 1 of this invention is shown. The microscope picture of the reverse opal structure 5 of this invention is shown. The microscope picture of the reverse opal structure (comparative example) which consists of aliphatic polyester is shown. The two-dimensional Fourier-transform image of the microscope picture of the inverse opal structure 1 (A) of this invention, the inverse opal structure 5 (B), and the inverse opal structure (comparative example) (C) which consists of aliphatic polyester is shown.

Claims (15)

An inverted opal structure comprising a polysaccharide. The inverted opal structure according to claim 1, wherein the polysaccharide is a cellulose derivative and / or cellulose. The inverted opal structure according to claim 1 or 2, wherein the polysaccharide is cellulose acetate. The inverted opal structure according to claim 1, wherein the polysaccharide is a cross-linked product of a polysaccharide cross-linked by deacetylated chitin and / or an arbitrary cross-linking molecule. The inverse opal structure according to any one of claims 1 to 4, further comprising a three-dimensional regular array of holes that selectively reflect light in the visible and near infrared regions. 6. The inverted opal structure according to claim 5, wherein the light in the visible and near infrared region has a wavelength of 400 to 1500 nm. The inverse opal structure according to claim 5 or 6, wherein the hole has a diameter of 10 to 1000 nm. The inverted opal structure according to any one of claims 1 to 7, which is any one of a medical implant, a separation membrane, a wound dressing, a cell culture medium, and an adsorption medium. A polysaccharide-coated colloidal crystal composition produced by a production method comprising the following steps (1) to (3).
(1) Step of obtaining a colloidal crystal containing silica particles or polystyrene particles (2) Step of impregnating the colloidal crystal with a solution containing polysaccharide (3) Solidifying the colloidal crystal obtained in the step (2) For obtaining a composition of polysaccharide-coated colloidal crystals The composition of polysaccharide-coated colloidal crystals according to claim 9, wherein a weight fraction of the silica particles or polystyrene particles is 0.01 to 90% by weight. A method for producing an inverse opal structure, comprising the following steps (1) to (4):
(1) Step of obtaining a colloidal crystal containing silica particles or polystyrene particles (2) Step of impregnating the colloidal crystal with a solution containing polysaccharide (3) Solidifying the colloidal crystal obtained in the step (2) (4) A step of obtaining a reverse opal structure by removing silica particles from the composition by etching or removing polystyrene particles by eluting them in an organic solvent. A method for using an inverted opal structure containing a polysaccharide, wherein the drug is released from the inverted opal structure carrying a drug in vivo by biodegradation and / or enzymatic degradation. A method for measuring a drug release amount from an inverted opal structure containing a polysaccharide in vivo, comprising the following steps (a) and (b):
(A) A step of releasing the drug by biodegrading and / or degrading the inverse opal structure carrying the drug with an enzyme (b) Injecting light in the visible and near infrared region into the inverse opal structure And measuring the change in wavelength and intensity of the reflected light. 14. The method for measuring the amount of drug released from an inverted opal structure in vivo according to claim 13, further comprising the following steps (a) and (b).
(B) A step of releasing a drug by carrying a pseudo-drug that absorbs visible light on the inverse opal structure and decomposing the inverse opal structure by biodegradation and / or enzyme (b) the inverse opal Visible or near-infrared light is incident on the structure, and the change (A) in the wavelength and / or intensity of the reflected light is measured, and the amount of the pseudo drug released (B) by quantitative analysis of the visible absorption spectrum Correlating (A) and (B) after measuring A method for enlarging the pore diameter of a reverse opal structure containing a polysaccharide by enzymatic decomposition of the pore inner wall of the reverse opal structure containing a polysaccharide.

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